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Biological Activities of Natural Products II
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Biological Activities of Natural Products II

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 66316

Special Issue Editors

Prof. Dr. Halina Ekiert

E-Mail Website
Guest Editor
Head of Chair and Department of Pharmaceutical Botany, Pharmaceutical Faculty, Jagiellonian University, Medical College, Krakow, Poland
Interests: pharmaceutical botany; plant biotechnology (plant in vitro cultures, endogenic production of bioactive products; biotransformation of egzogenic substrates); phytochemistry (quantification of natural products, isolation of natural products); medicinal plants; cosmetic plants, biotechnology of mushrooms; mycochemistry (chemistry of fruitbodies of mushrooms and mycelial cultures); natural products; bioactive compounds (especially coumarins, phenolic acids, flavonoids, schisandra lignans, nonhalucinogenic indole compounds, and polysaccharides); ethnobotany; ethnopharmacology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Agnieszka Szopa

E-Mail Website
Guest Editor
Department of Pharmaceutical Botany, Medical College, Jagiellonian University, ul. Medyczna 9, 30-688 Kraków, Poland
Interests: pharmaceutical botany; plant biotechnology; phytochemistry; medicinal plants; cosmetic plants; natural products; bioactive compounds (especially lignans, phenolic acids, flavonoids); ethnobotany; ethnopharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products originating from the plant kingdom offer an unexplored wealth of potentially valuable medicinal, health promoting and cosmetic applications.

In recent years, special attention has been given to natural products exhibiting antioxidant and antiproliferative/anticancer properties. They are of vital importance since they can be used in the treatment and prevention of different lifestyle diseases. Plant extracts and/or isolated compounds exhibiting other directions of biological activities, such as anti-inflammatory, immunostimulating or antimicrobial effects and also cardioprotective, neuroprotective, and antidiabetic activities, are also very significant.

The results of biological activity studies of to date unknown and/or uninvestigated natural products can broaden the range of professional phytotherapeutics available in different regions of the world, including Europe. The selection of plant-derived medicinal products can also be expanded through the verification of ethnobotanical and ethnopharmacological knowledge of various ethnic groups in the world.

In addition to plants, fruitbodies of mushrooms, algae and lichens are rich and still unrecognized sources of natural products.

The main aim of the Special Issue on “Biological Activities of Natural Products” is to present the newest results of investigations and findings in the above-presented area. Results presenting the correlation between chemical composition of extracts and/or isolated compounds and their biological activity are particularly welcome. Research on antioxidant and antiproliferative/anticancer activities of extracts and/or isolated products will be preferentially considered. All research on the other above-mentioned activities will also be received with much interest. The results of biological activity studies documented in vitro and in vivo, as well as results of clinical investigations, will be anticipated.

Original papers or review articles are welcome.

Prof. Dr. Halina Ekiert
Dr. Agnieszka Szopa
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bioactive natural compounds
  • Antioxidants
  • Polyphenols
  • Antioxidant activity
  • Anticancer/antiproliferative activity
  • Anti-inflammatory activity
  • Immunostimulating activity
  • Antimicrobial activity
  • Other activities
  • In vitro approach
  • In vivo approach
  • Clinical investigations
  • Ethnopharmacological indications
  • Ethnobotanical indications

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Published Papers (18 papers)

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Editorial

Jump to: Research, Review

4 pages, 187 KiB  
Editorial
Biological Activities of Natural Products II
by Halina Maria Ekiert and Agnieszka Szopa
Molecules 2022, 27(5), 1519; https://doi.org/10.3390/molecules27051519 - 24 Feb 2022
Cited by 10 | Viewed by 2095
Abstract
Natural products of different origin and their potential therapeutic activities are of unceasing widespread interest to many scientific teams from all around the world [...] Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)

Research

Jump to: Editorial, Review

12 pages, 2556 KiB  
Article
Apigenin Isolated from Carduus crispus Protects against H2O2-Induced Oxidative Damage and Spermatogenic Expression Changes in GC-2spd Sperm Cells
by Spandana Rajendra Kopalli, Sung-Kwang Yoo, Bokyung Kim, Si-Kwan Kim and Sushruta Koppula
Molecules 2022, 27(6), 1777; https://doi.org/10.3390/molecules27061777 - 8 Mar 2022
Cited by 7 | Viewed by 2292
Abstract
Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative [...] Read more.
Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative damage induced by hydrogen peroxide (H2O2) and dysregulation in spermatogenesis associated parameters in testicular sperm cells was investigated. Cell viabilities, ROS scavenging effects, and spermatogenic associated molecular expressions were measured by MTT, DCF-DA, Western blotting and real-time RT-PCR, respectively. A single peak with 100% purity of apigenin was obtained in HPLC conditions. Apigenin treated alone (2.5, 5, 10 and 20 µM) did not exhibit cytotoxicity, but inhibited the H2O2-induced cellular damage and elevated ROS levels significantly (p < 0.05 at 5, 10 and 20 µM) and dose-dependently. Further, H2O2-induced down-regulation of antioxidant (glutathione S-transferases m5, glutathione peroxidase 4, and peroxiredoxin 3) and spermatogenesis-associated (nectin-2 and phosphorylated-cAMP response element-binding protein) molecular expression in GC-2spd cells were attenuated by apigenin at both protein and mRNA levels (p < 0.05). In conclusion, our study showed that apigenin isolated from C. crispus might be an effective agent that can protect ROS-induced testicular dysfunctions. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>HPLC fingerprint of apigenin isolated from <span class="html-italic">C. crispus</span>. (<b>a</b>) Chemical name and structure of apigenin. (<b>b</b>) HPLC fingerprint of apigenin.</p> Full article ">Figure 2
<p>Effects of apigenin on cell viability in GC-2spd sperm cells. Cell viability was evaluated using the MTT assay. (<b>a</b>) The effect of apigenin (2.5, 5, 10, 20 and 40 μM) on the viability of GC-2spd cells. (<b>b</b>) The effect of apigenin (2.5, 5, 10 and 20 μM) in GC-2spd cells exposed to 200 μM hydrogen peroxide. Data are expressed as the mean ± standard deviation. The groups of control, H<sub>2</sub>O<sub>2</sub>, and different concentrations of apigenin were compared with each other, and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA.</p> Full article ">Figure 3
<p>Effect of apigenin on the inhibition of intracellular ROS formation. DCFH-DA fluorescence assay was performed and the fluorescence intensity (fold increase) in each treated group compared with control was shown. H<sub>2</sub>O<sub>2</sub> (200 μM) treatment significantly increased the fluorescent intensity (fold increase) compared to control cells. Apigenin (2.5, 5, 10 and 20 μM) and positive control ascorbic acid (20 μM) treatment inhibited the H<sub>2</sub>O<sub>2</sub>-exposed increase in ROS generation by decreasing the florescence intensity in GC-2spd cells. Data are expressed as the mean ± standard deviation. The groups of control, H<sub>2</sub>O<sub>2</sub>, ascorbic acid, and different concentrations of apigenin were compared with each other and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA.</p> Full article ">Figure 4
<p>The effect of apigenin on the antioxidant enzyme protein expression level in H<sub>2</sub>O<sub>2</sub>-exposed cells. (<b>a</b>) The protein expression of GSTm5, GPX4 and PRX3 in H<sub>2</sub>O<sub>2</sub>-exposed GC-2spd cells was analyzed using Western blotting. Cell lysates from each groups were immunoblotted with specific antibodies. (<b>b</b>–<b>d</b>) The protein band intensity of GSTm5, GPX4 and PRX3 in H<sub>2</sub>O<sub>2</sub>-exposed GC-2spd cells, respectively, normalized to that of β-actin is shown. The data represent the mean ± standard deviation. The groups of control, H<sub>2</sub>O<sub>2</sub>, and different concentrations of apigenin were compared with each other and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA. GSTm5, glutathione S-transferase m5; GPX4, glutathione peroxidase 4; PRX3, peroxiredoxin 3.</p> Full article ">Figure 5
<p>Effects of apigenin on the antioxidant enzyme mRNA expression level in hydrogen peroxide-exposed GC-2spd cells. (<b>a</b>) The mRNA expression level of the antioxidant enzymes GSTm5, GPX4 and PRX3 in H<sub>2</sub>O<sub>2</sub>-exposed GC-2spd cells. (<b>b</b>–<b>d</b>) The polymerase chain reaction band intensity of GSTm5, GPX4 and PRX3 was analyzed using the ImageJ 1.41o software package and was normalized to that of glyceraldehyde 3-phosphate dehydrogenase. Data are expressed as the mean ± standard deviation. The groups of control, H<sub>2</sub>O<sub>2</sub>, and different concentrations of apigenin were compared with each other and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA. GSTm5, glutathione S-transferase m5; GPX4, glutathione peroxidase 4; PRX3, peroxiredoxin 3; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.</p> Full article ">Figure 6
<p>The effect of apigenin on the expression level of nectin-2 in H<sub>2</sub>O<sub>2</sub>-exposed GC-2spd cells. (<b>a</b>) The protein expression level of nectin-2 was analyzed using Western blotting. Cell lysates were immunoblotted with specific antibodies with Beta-actin as the internal control (upper panel) and the band intensity of nectin-2 normalized to β-actin is shown in corresponding lower panel. (<b>b</b>) The mRNA expression of nectin-2 (upper panel) and corresponding band intensities normalized to GAPDH (lower panel). Data are expressed as the mean ± standard deviation. The groups of control, H<sub>2</sub>O<sub>2</sub>, and different concentrations of apigenin were compared with each other and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA.</p> Full article ">Figure 7
<p>The effect of apigenin on the expression level of p-CREB in H<sub>2</sub>O<sub>2</sub>-exposed GC-2spd cells. (<b>a</b>) The protein expression level of p-CREB was analyzed using Western blotting. Cell lysates were immunoblotted with specific antibodies with Beta-actin as the internal control (upper panel) and the band intensity of p-CREB normalized to β-actin is shown in corresponding lower panel. (<b>b</b>) The mRNA expression of p-CREB was shown in upper panel and corresponding band intensities normalized to GAPDH was shown in lower panel. Data are expressed as the mean ± standard deviation (<span class="html-italic">n</span> = 6). The groups of control, H<sub>2</sub>O<sub>2</sub>, and different concentrations of apigenin were compared with each other and letters on the top of the columns that do not share the same letters are statistically significant among the groups (<span class="html-italic">p</span> &lt; 0.05) by one-way ANOVA.</p> Full article ">
16 pages, 4454 KiB  
Article
Quality Related Safety Evaluation of a South African Traditional Formulation (PHELA®) as Novel Anti-Biofilm Candidate
by Bhaskar Das, Amit Kar, Rudranil Bhowmik, Sanmoy Karmakar, Satyajit Tripathy, Motlalepula G. Matsabisa and Pulok Kumar Mukherjee
Molecules 2022, 27(4), 1219; https://doi.org/10.3390/molecules27041219 - 11 Feb 2022
Cited by 3 | Viewed by 2322
Abstract
A South African traditional formulation, PHELA®, is consumed by the traditional people for severe chest problems with coughing, diarrhea, oral ulcers etc. The present study focused on establishing the anti-infective properties of a safe and standardized poly-herbal formulation through a series [...] Read more.
A South African traditional formulation, PHELA®, is consumed by the traditional people for severe chest problems with coughing, diarrhea, oral ulcers etc. The present study focused on establishing the anti-infective properties of a safe and standardized poly-herbal formulation through a series of criteria and specifications. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>UPLC-QTOF-MS/MS total ion chromatogram for PHELA<sup>®</sup> extract in negative ionization mode (<b>a</b>) and negative ionization mode (<b>b</b>).</p> Full article ">Figure 1 Cont.
<p>UPLC-QTOF-MS/MS total ion chromatogram for PHELA<sup>®</sup> extract in negative ionization mode (<b>a</b>) and negative ionization mode (<b>b</b>).</p> Full article ">Figure 2
<p>RP-HPLC chromatograms for standard emodin (<b>a</b>) and PHELA<sup>®</sup> extract (<b>b</b>).</p> Full article ">Figure 3
<p>CYP3A4 (<b>a</b>) and CYP2D6 (<b>b</b>) inhibitory effect of PHELA<sup>®</sup> extract and standard inhibitors.</p> Full article ">Figure 4
<p>Growth curve of S. aureus against PHELA<sup>®</sup> extract.</p> Full article ">Figure 5
<p><span class="html-italic">S. aureus</span> biofilm inhibition of PHELA<sup>®</sup> extract and ciprofloxacin.</p> Full article ">Figure 6
<p>AFM image of <span class="html-italic">S. aureus</span> biofilm surface (untreated) formed on the polycarbonate membrane filter taken at the 1 × 1 μm scan area in the tapping mode. (<b>a</b>) Height topography 3D, (<b>b</b>) The structure and complete surface coverage of the biofilm, and (<b>c</b>) Height distribution pattern.</p> Full article ">Figure 7
<p>AFM image of <span class="html-italic">S. aureus</span> biofilm surface (treated with standard antimicrobial agent) formed on the polycarbonate membrane filter taken at the 1 × 1 μm scan area in the tapping mode. (<b>a</b>) Height topography 3D and (<b>b</b>) The structure and complete surface coverage of the biofilm, and (<b>c</b>) Height distribution pattern.</p> Full article ">Figure 8
<p>AFM image of <span class="html-italic">S. aureus</span> biofilm surface (treated with PHELA<sup>®</sup> extract) formed on the polycarbonate membrane filter taken at the 1 × 1 μm scan area in the tapping mode. (<b>a</b>) Height topography in three dimensions, (<b>b</b>) The structure and complete surface coverage of the biofilm, and (<b>c</b>) Height distribution pattern.</p> Full article ">Figure 8 Cont.
<p>AFM image of <span class="html-italic">S. aureus</span> biofilm surface (treated with PHELA<sup>®</sup> extract) formed on the polycarbonate membrane filter taken at the 1 × 1 μm scan area in the tapping mode. (<b>a</b>) Height topography in three dimensions, (<b>b</b>) The structure and complete surface coverage of the biofilm, and (<b>c</b>) Height distribution pattern.</p> Full article ">
24 pages, 3508 KiB  
Article
Antioxidant Potential and Enhancement of Bioactive Metabolite Production in In Vitro Cultures of Scutellaria lateriflora L. by Biotechnological Methods
by Inga Kwiecień, Natalizia Miceli, Manuela D’Arrigo, Andreana Marino and Halina Ekiert
Molecules 2022, 27(3), 1140; https://doi.org/10.3390/molecules27031140 - 8 Feb 2022
Cited by 17 | Viewed by 3004
Abstract
Studies carried out using three different in vitro assays and a biological setting (Escherichia coil) demonstrated the antioxidant activity of Scutellaria lateriflora microshoot extract. Moreover, the extract exhibited no toxicity in a brine shrimp lethality bioassay. These results indicated that microshoots [...] Read more.
Studies carried out using three different in vitro assays and a biological setting (Escherichia coil) demonstrated the antioxidant activity of Scutellaria lateriflora microshoot extract. Moreover, the extract exhibited no toxicity in a brine shrimp lethality bioassay. These results indicated that microshoots are a rich, safe source of antioxidants, which encouraged us to enhance their production in vitro. In agar and agitated cultures, two biotechnological strategies were applied: feeding the cultures with the biogenetic precursors of the phenolics—phenylalanine and tyrosine, and eliciting them with methyl jasmonate. Specific Scutellaria flavonoids and verbascoside were analysed by HPLC. Feeding with precursors (1 g/L) in agar cultures decreased the production of the metabolites. In agitated cultures, different concentrations of precursors (1.0–2.5 g/L) and the elicitor (10; 50; 100 µM) were tested. Additionally, parallel feeding with the precursor and elicitor in a concentration of 50 µM were applied. The best strategy for total flavonoid and verbascoside production was phenylalanine feeding (1.5 g/L), max. 3765 and 475 mg/100 g DW, respectively, after 7 days. This is the first report documenting the high antioxidant production in S. lateriflora microshoots after feeding with phenylalanine. Moreover, for the first time, bioreactor cultures were successfully maintained, obtaining attractive results (max. total flavonoid content 2348 and verbascoside 485 mg/100 g DW). Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>Free radical scavenging activity of the extract obtained from in vitro microshoot cultures of <span class="html-italic">S. lateriflora</span> (MS solid medium, supplemented with 1.0 mg/L BA and 0.5 mg/L NAA). Values are expressed as the mean ± SD (<span class="html-italic">n</span> = 3).</p> Full article ">Figure 2
<p>Reducing power of the extract obtained from in vitro microshoot cultures of <span class="html-italic">S. lateriflora</span> (MS solid medium, supplemented with 1.0 mg/L BA and 0.5 mg/L NAA) evaluated by spectrophotometric detection of Fe<sup>3+</sup>−Fe<sup>2+</sup> transformation method. Values are expressed as the mean ± SD (<span class="html-italic">n</span> = 3).</p> Full article ">Figure 3
<p>Chelating activity of the extract obtained from in vitro microshoot cultures of <span class="html-italic">S. lateriflora</span> (MS solid medium, supplemented with 1.0 mg/L BA and 0.5 mg/L NAA) measured by inhibition of ferrozine-Fe<sup>2+</sup> complex formation. Values are expressed as the mean ± SD (<span class="html-italic">n</span> = 3).</p> Full article ">Figure 4
<p>Protective effect of the extract obtained from in vitro microshoot cultures of <span class="html-italic">S. lateriflora</span> (MS solid medium, supplemented with 1.0 mg/L BA and 0.5 mg/L NAA) on <span class="html-italic">E. coli</span> growth under peroxide stress. Values are expressed as the mean ± SD (<span class="html-italic">n</span> = 3). Statistically significant differences compared to control group with H<sub>2</sub>O<sub>2</sub> treatment (Ctr + H<sub>2</sub>O<sub>2</sub>) are indicated with asterisks (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 5
<p>Protective effect of the extract obtained from in vitro microshoot cultures of <span class="html-italic">S. lateriflora</span> (MS solid medium, supplemented with 1.0 mg/L BA and 0.5 mg/L NAA) on <span class="html-italic">E. coli</span> survival under peroxide stress. Values are expressed as the mean ± SD (<span class="html-italic">n</span> = 3). Statistically significant differences compared to control group with H<sub>2</sub>O<sub>2</sub> treatment (Ctr + H<sub>2</sub>O<sub>2</sub>) are indicated with asterisks (**** <span class="html-italic">p</span> &lt; 0.0001).</p> Full article ">Figure 6
<p>Chemical structure of the compounds detected in the extracts from <span class="html-italic">S. lateriflora</span> in vitro cultures.</p> Full article ">Figure 7
<p>Total flavonoid contents in agitated microshoot in vitro cultures of <span class="html-italic">S. lateriflora</span> grown on LS medium supplemented with 1.0 mg/L BA and 1.0 NAA mg/L after administering different concentrations of the biosynthetic precursors—phenylalanine (Phe) and tyrosine (Tyr), and the elicitor—methyl jasmonate (MeJa), collected 3 days after supplementation. <sup>a–f</sup> Different letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 8
<p>Total flavonoid contents in agitated microshoot in vitro cultures of <span class="html-italic">S. lateriflora</span> grown on LS medium supplemented with 1.0 mg/L BA and 1.0 NAA mg/L after administering different concentrations of the biosynthetic precursors—phenylalanine (Phe) and tyrosine (Tyr), and the elicitor—methyl jasmonate (MeJa), collected 7 days after supplementation. <sup>a–f</sup> Different letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">
23 pages, 3314 KiB  
Article
Antidiarrheal and Antibacterial Activities of Monterey Cypress Phytochemicals: In Vivo and In Vitro Approach
by Elshaymaa I. Elmongy, Walaa A. Negm, Engy Elekhnawy, Thanaa A. El-Masry, Nashwah G. M. Attallah, Najla Altwaijry, Gaber El-Saber Batiha and Suzy A. El-Sherbeni
Molecules 2022, 27(2), 346; https://doi.org/10.3390/molecules27020346 - 6 Jan 2022
Cited by 31 | Viewed by 3079
Abstract
Monterey cypress (Cupressus macrocarpa) is a decorative plant; however, it possesses various pharmacological activities. Therefore, we explored the phytochemical profile of C. macrocarpa root methanol extract (CRME) for the first time. Moreover, we investigated its antidiarrheal (in vivo), antibacterial, and antibiofilm [...] Read more.
Monterey cypress (Cupressus macrocarpa) is a decorative plant; however, it possesses various pharmacological activities. Therefore, we explored the phytochemical profile of C. macrocarpa root methanol extract (CRME) for the first time. Moreover, we investigated its antidiarrheal (in vivo), antibacterial, and antibiofilm (in vitro) activities against Salmonella enterica clinical isolates. The LC-ESI-MS/MS analysis of CRME detected the presence of 39 compounds, besides isolation of 2,3,2″,3″-tetrahydro-4′-O-methyl amentoflavone, amentoflavone, and dihydrokaempferol-3-O-α-l-rhamnoside for the first time. Dihydrokaempferol-3-O-α-l-rhamnoside presented the highest antimicrobial activity and the range of values of MICs against S. enterica isolates was from 64 to 256 µg/mL. The antidiarrheal activity of CRME was investigated by induction of diarrhea using castor oil, and exhibited a significant reduction in diarrhea and defecation frequency at all doses, enteropooling (at 400 mg/kg), and gastrointestinal motility (at 200, 400 mg/kg) in mice. The antidiarrheal index of CRME increased in a dose-dependent manner. The effect of CRME on various membrane characters of S. enterica was studied after typing the isolates by ERIC-PCR. Its impact on efflux and its antibiofilm activity were inspected. The biofilm morphology was observed using light and scanning electron microscopes. The effect on efflux activity and biofilm formation was further elucidated using qRT-PCR. A significant increase in inner and outer membrane permeability and a significant decrease in integrity and depolarization (using flow cytometry) were detected with variable percentages. Furthermore, a significant reduction in efflux and biofilm formation was observed. Therefore, CRME could be a promising source for treatment of gastrointestinal tract diseases. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>Chemical structures of the isolated compounds from CRME.</p> Full article ">Figure 2
<p>Dendrogram showing the degree of relatedness of <span class="html-italic">S. enterica</span> isolates as determined by ERIC-PCR fingerprinting.</p> Full article ">Figure 3
<p>A chart showing the increase in the release of the material absorbing at 260 nm (indicating a decrease in the membrane integrity) from a representative <span class="html-italic">S. enterica</span> isolate after treatment with CRME (32 µg/mL).</p> Full article ">Figure 4
<p>A chart showing the increase in the inner membrane permeability of a representative <span class="html-italic">S. enterica</span> isolate after treatment with CRME was determined by measuring the ONP absorbance with time.</p> Full article ">Figure 5
<p>A chart showing the increase in the outer membrane permeability of a representative <span class="html-italic">S. enterica</span> isolate after treatment with CRME was detected by determining the fluorescence of NPN against time.</p> Full article ">Figure 6
<p>A representative flow cytometric chart (dot plot) showing the fluorescent gap (<b>a</b>) before (95.7%) and (<b>b</b>) after (22.8%) treatment with CRME measured by FACS verse flow cytometer.</p> Full article ">Figure 7
<p>Crystal violet assay for evaluation of the antibiofilm efficiency of CRME against <span class="html-italic">S. enterica</span> isolates showing a significant reduction (<span class="html-italic">p</span> &lt; 0.05) in biofilm formation in 8 isolates (S1, S2, S4, S6, S8, S9, S11, and S13).</p> Full article ">Figure 8
<p>A representative example of the decrease in biofilm formation by <span class="html-italic">S. enterica</span> isolates (<b>a</b>,<b>b</b>) viewed by the light microscope, and (<b>c</b>,<b>d</b>) viewed by the scanning electron microscope before (<b>a</b>,<b>c</b>) and after (<b>b</b>,<b>d</b>) treatment with CRME.</p> Full article ">
14 pages, 4443 KiB  
Article
Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells
by Wonmin Ko, Zhiming Liu, Kwan-Woo Kim, Linsha Dong, Hwan Lee, Na Young Kim, Dong-Sung Lee and Eun-Rhan Woo
Molecules 2021, 26(24), 7642; https://doi.org/10.3390/molecules26247642 - 16 Dec 2021
Cited by 9 | Viewed by 3033
Abstract
We previously investigated the methanolic extract of Morus alba bark and characterized 11 compounds from the extract: kuwanon G (1), kuwanon E (2), kuwanon T (3), sanggenon A (4), sanggenon M (5), sanggenol [...] Read more.
We previously investigated the methanolic extract of Morus alba bark and characterized 11 compounds from the extract: kuwanon G (1), kuwanon E (2), kuwanon T (3), sanggenon A (4), sanggenon M (5), sanggenol A (6), mulberofuran B (7), mulberofuran G (8), moracin M (9), moracin O (10), and norartocarpanone (11). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them, 3 and 4 markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with 3 and 4 inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with 3 and 4, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together, 3 and 4 are potential candidates for developing therapeutic and preventive agents for inflammatory diseases. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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<p>Chemical structures of compounds <b>1</b>–<b>11</b> isolated from <span class="html-italic">M. alba</span>.</p> Full article ">Figure 2
<p>Cytotoxic effects of compounds <b>1</b>–<b>11</b> isolated from <span class="html-italic">M. alba</span> on BV2 (<b>A</b>) and RAW264.7 (<b>B</b>) cells. The cells were incubated for 48 h with various concentrations of the compounds, and their viability was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Error bars represent mean ± standard deviation of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 compared with the control group.</p> Full article ">Figure 3
<p>Inhibitory effects of compounds <b>1</b>–<b>11</b> on nitrite production in BV2 (<b>A</b>) and RAW264.7 (<b>B</b>) cells. The cells were pretreated for 2 h with concentrations of compounds and stimulated for 24 h with lipopolysaccharide (LPS; 1 μg/mL). Error bars represent mean ± standard deviation of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 compared with the LPS-treated group.</p> Full article ">Figure 4
<p>Protein expression levels of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated BV2 (<b>A</b>) and RAW264.7 (<b>C</b>) cells. The cells were pretreated for 2 h with various concentrations of compounds <b>3</b> or <b>4</b> and stimulated for 24 h with LPS (1 μg/mL). Representative blots from three independent experiments are shown. Immunoblots were quantified using the ImageJ software. Band intensities are normalized to that of β-actin (<b>B</b>,<b>D</b>). Error bars represent mean ± standard deviation of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compared with the LPS-treated group.</p> Full article ">Figure 5
<p>Inhibitory effects of compounds <b>3</b> and <b>4</b> on the level of PGE<sub>2</sub> (<b>A</b>,<b>D</b>), IL-6 (<b>B</b>,<b>E</b>), and TNF-α (<b>C</b>,<b>F</b>) in BV2 and RAW264.7 cells. The cells were pretreated for 2 h with various concentrations of compounds <b>3</b> or <b>4</b> and stimulated for 24 h with lipopolysaccharide (LPS; 1 μg/mL). Error bars represent mean ± standard deviation of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 compared with the LPS-treated group.</p> Full article ">Figure 6
<p>Effects of compounds <b>3</b> and <b>4</b> on and NF-κB DNA-binding activity (<b>A</b>,<b>B</b>) and NF-κB (p65) localization (<b>C</b>–<b>F</b>) in BV2 and RAW264.7 cells. The cells were pretreated with compounds <b>3</b> or <b>4</b> for 2 h and stimulated with liposaccharide (LPS; 1 μg/mL) for 1 h. Experiments were performed using a commercially available enzyme-linked immunosorbent assay kit, as described in the Materials and Methods section. ** <span class="html-italic">p</span> and *** <span class="html-italic">p</span> &lt; 0.001 compared with the LPS-treated group.</p> Full article ">Figure 7
<p>Effects of compounds <b>3</b> and <b>4</b> on heme oxygenase (HO)-1 expression in BV2 (<b>A</b>) and RAW264.7 (<b>C</b>) cells. The cells were treated with compounds <b>3</b> or <b>4</b> or CoPP (10 μM) for 12 h. Representative blots from three independent experiments are shown. Immunoblots were quantified using the ImageJ software. Band intensity was normalized to each total form expression (<b>B</b>,<b>D</b>). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compared with the control group.</p> Full article ">Figure 8
<p>Effects of compounds <b>3</b> and <b>4</b> on Nrf2 activation in BV2 (<b>A</b>,<b>C</b>) and RAW264.7 (<b>B</b>,<b>D</b>) cells. The cells were treated with compounds <b>3</b> or <b>4</b> for 0.5, 1, and 1.5 h. Representative blots from three independent experiments are shown. Immunoblots were quantified using the ImageJ software. Band intensity was normalized to each β-actin or PCNA. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01, and ### <span class="html-italic">p</span> &lt; 0.001, compared with the control group.</p> Full article ">Figure 9
<p>Inhibitory effects of compounds <b>3</b> and <b>4</b> on nitrite production through the regulation of HO-1 activity in BV2 (<b>A</b>,<b>C</b>,<b>E</b>) and RAW264.7 (<b>B</b>,<b>D</b>,<b>F</b>) cells. The cells were treated with 50 μM of tin protoporphyrin-IX (SnPP) or compounds <b>3</b> or <b>4</b> and stimulated for 24 h with lipopolysaccharide (LPS; 1 μg/mL). Data are presented as mean ± standard deviation of three independent experiments. ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">
27 pages, 33361 KiB  
Article
Linnaea borealis L. var. borealis—In Vitro Cultures and Phytochemical Screening as a Dual Strategy for Its Ex Situ Conservation and a Source of Bioactive Compounds of the Rare Species
by Barbara Thiem, Dariusz Kruszka, Natalia Turowska, Elwira Sliwinska, Viktor Berge and Małgorzata Kikowska
Molecules 2021, 26(22), 6823; https://doi.org/10.3390/molecules26226823 - 11 Nov 2021
Cited by 4 | Viewed by 2383
Abstract
Linnaea borealis L. (Twinflower)—a dwarf shrub in the Linnaeeae tribe of Caprifoliaceae family—is distributed across the Northern Hemisphere. By means of this study, a reliable protocol for efficient micropropagation of uniform L. borealis L. var. borealis plantlets has been provided for the first [...] Read more.
Linnaea borealis L. (Twinflower)—a dwarf shrub in the Linnaeeae tribe of Caprifoliaceae family—is distributed across the Northern Hemisphere. By means of this study, a reliable protocol for efficient micropropagation of uniform L. borealis L. var. borealis plantlets has been provided for the first time; callus culture was also established. Different initial explants, types of cultures, media systems, and plant growth regulators in Murashige and Skoog (MS) media were tested. Agitated shoot cultures in the liquid media turned out to be the best system for the production of sustainable plant biomass. After stabilization of the callus lines, the highest growth index (c.a. 526%) was gained for callus maintained on MS enriched with picloram. TLC and UHPLC-HESI-HRMS analysis confirmed the presence of phenolic acids and flavonoids, and for the first time, the presence of iridoids and triterpenoid saponins in this species. Multiplication of L. borealis shoot culture provides renewable raw material, allowing for the assessment of the phytochemical profile, and, in the future, for the quantitative analyses and the studies of the biological activity of extracts, fractions, or isolated compounds. This is the first report on in vitro cultures of traditionally used L. borealis rare taxon and its biosynthetic potential. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Graphical abstract

Graphical abstract
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<p>Micropropagation of <span class="html-italic">Linnaea borealis</span> var. <span class="html-italic">borealis</span> (<b>A</b>) shoots on the solidified medium; (<b>B</b>) multiplied shoots on the solidified medium; (<b>C</b>) rooted shoots; (<b>D</b>) rooted shoots before acclimatization; (<b>E</b>) micropropagated plantlets hardened in a glasshouse; (<b>F</b>) micro-shoots in the liquid media on a rotary shaker; (<b>G</b>) multiplied shoots in the liquid medium obtained from double shoots; (<b>H</b>) multiplied shoot obtained from one shoot explant from the liquid media.</p> Full article ">Figure 2
<p>Histograms of the nuclear DNA content obtained after the flow cytometric analysis of the PI-stained nuclei isolated simultaneously from leaves of <span class="html-italic">Linnaea borealis</span> var. <span class="html-italic">borealis</span> (peak 1), seedling (<b>A</b>) and a micropropagated plant (<b>B</b>), and <span class="html-italic">Petunia hybrida</span> (the internal standard; peak 2).</p> Full article ">Figure 3
<p>Leaf-derived callus of <span class="html-italic">Linnaea borealis</span> var. <span class="html-italic">borealis</span> cultured on MS medium enriched with picloram 2.0 mg/L.</p> Full article ">Figure 4
<p>The UPLC-PDA (254 nm) chromatograms of <span class="html-italic">Linnaea borealis</span> var. <span class="html-italic">borealis</span> extracts of leafy shoots from natural sites (purple, <b>D</b>); shoot cultures (red, <b>A</b>); roots from micropropagated plantlets (green, <b>B</b>); biomass from callus cultures (blue, <b>C</b>).</p> Full article ">
15 pages, 3785 KiB  
Article
Caryophyllene Oxide, the Active Compound Isolated from Leaves of Hymenaea courbaril L. (Fabaceae) with Antiproliferative and Apoptotic Effects on PC-3 Androgen-Independent Prostate Cancer Cell Line
by Claudia Delgado, Gina Mendez-Callejas and Crispin Celis
Molecules 2021, 26(20), 6142; https://doi.org/10.3390/molecules26206142 - 12 Oct 2021
Cited by 32 | Viewed by 2836
Abstract
Cancer treatment frequently carries side effects, therefore, the search for new selective and effective molecules is indispensable. Hymenaea courbaril L. has been used in traditional medicine in South America to treat several diseases, including prostate cancer. Leaves’ extracts from different polarities were evaluated [...] Read more.
Cancer treatment frequently carries side effects, therefore, the search for new selective and effective molecules is indispensable. Hymenaea courbaril L. has been used in traditional medicine in South America to treat several diseases, including prostate cancer. Leaves’ extracts from different polarities were evaluated using the 3-(4,5-methyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability assay to determine the cytotoxicity in prostate p53-null cells, followed by bio-guided fractionations to obtain the most cytotoxic fraction considering the selectivity index. The most cytotoxic fraction was analyzed by GC/MS to identify the active compounds. The majority compound, caryophyllene oxide, induced early and late apoptosis, depolarized the mitochondrial membrane, leading to several morphological changes and shifts in apoptotic proteins, and caspases were evidenced. Depolarization of the mitochondrial membrane releases the pro-apoptotic protein Bax from Bcl-xL. The apoptosis process is caspase-7 activation-dependent. Caryophyllene oxide is a safe anti-proliferative agent against PC-3 cells, inducing apoptosis with low toxicity towards normal cells. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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<p>Cytotoxic activity of the extracts, fractions, and subfractions. (<b>a</b>) IC<sub>50</sub> of the hexane, dichloromethane, and ethanol total extracts obtained from <span class="html-italic">H. courbaril</span> leaves in the PC-3 tumor cell line. (<b>b</b>(1)) Cytotoxic activity of the seven fractions with the highest activity on the PC-3 cell line. (<b>b</b>(2)) Selectivity Index of the fractions. (<b>c</b>(1)) The IC<sub>50</sub> value of the sub-fractions of the fraction-2 with the highest activity on the PC-3 cell line. (<b>c</b>(2)) Selectivity Index of the sub-fractions of the fraction-2. Somehow, throughout fraction-2 fractionation, the cytotoxic activity was diminished. It changed from IC<sub>50</sub> = 42.53 (fraction-2) to IC<sub>50</sub> = 80.41 µg/mL (SFB). (<b>d</b>(1)) The cytotoxic activity of the six sub-fractions obtained in the RP18 reverse-phase chromatography from the SFB sub-fraction. (<b>d</b>(2)) Selectivity Index of these six sub-fractions obtained in the reverse-phase chromatography. SFB.3 sub-fraction presented the highest anti-cancer potential, with a moderately cytotoxic IC<sub>50</sub> of 86.81 µg/mL and a SI of 1.71. The experiments were carried out in triplicate with two replicas.</p> Full article ">Figure 2
<p>Mass spectrum and partial fragmentation of caryophyllene oxide.</p> Full article ">Figure 3
<p>(<b>a</b>) The purified compound, OXC, evaluated by the MTT assay, wherein it obtains an IC<sub>50</sub> of 22.86 µg/mL in PC-3 and 44.78 µg/mL in MRC5 normal cells. (<b>b</b>) The positive control, Paclitaxel, 0.028 µg/mL in PC-3 and 0.020 µg/mL in MRC5 normal cells. (<b>c</b>) The Selectivity Index of OXC and Paclitaxel, being 1.96 and 0.7, respectively. The experiment was carried out in triplicate with two replicas.</p> Full article ">Figure 4
<p>Morphological changes in PC-3 after 24 h of OXC and Paclitaxel exposure. Immunofluorescence micrographs showing the nuclear (in blue) and microtubular (in green) effects in PC-3 cancer cells. Paclitaxel-treated cells displayed a moderate destabilization of the microtubules, an increase in cell size, the appearance of some apoptotic bodies (marked with a red arrow) that were not observed in the negative control cells treated with 1% DMSO, and the formation of abnormal nuclear morphologies. Otherwise, cells treated with OXC were visibly affected at the microtubules, considerably increasing the size of the cells, presenting cellular clusters, variable nuclear morphologies, and leading to the emergence of apoptotic cells (white arrow).</p> Full article ">Figure 5
<p>Quantitative detection of Annexin V/7-AAD on PC-3 cells. (<b>a</b>) Dot plots of OXC and Paclitaxel treatments in the Annexin V/7-AAD assay. (1) Negative control, cells without any treatment. (2) Negative control, cells exposed to 1% DMSO. (3) Cells exposed to Paclitaxel for 8 h. (4) Cells exposed to Paclitaxel for 24 h. (5) Cells exposed to OXC for 8 h. (6) Cells exposed to OXC for 24 h. (<b>b</b>) Bar chart representing the distribution of the PC-3 cells detected by Annexin V/7-AAD following OXC and Paclitaxel exposure. Cells located in the lower right stained with Annexin V were defined as early apoptotic (EA), and Annexin V and 7-AAD double-stained cells were defined as late apoptotic (LA), located in the upper right. In the lower left are cells negative to both dyes, defined as live cells (LC), and cells in the upper left were stained only with 7-AAD, and correspond to non-apoptotic dead cells or nuclear debris.</p> Full article ">Figure 6
<p>Loss of the membrane potential (Δψm) in PC-3 cells induced by OXC and Paclitaxel (TX). (<b>a</b>) Immunofluorescence micrographs show the distribution of JC-10 aggregates in the mitochondrial membrane (in red) or monomers in the cytoplasm (in green) on PC-3 cancer cells after 16 h of incubation at the IC<sub>50</sub> value, cells treated with 1% DMSO are considered as a negative control (NC). (<b>b</b>) Flow cytometry representative density plots evidencing the loss of mitochondrial membrane potential at 16 and 24 h after OXC treatment. Valinomycin was used as a positive control at 100 nM and evaluated at 2 h. The percentage of polarized cells are shown in the box.</p> Full article ">Figure 7
<p>Comparison between the pro-apoptotic and anti-apoptotic protein levels in PC-3 cells treated for up to 48 h with OXC and Paclitaxel. The readouts, defined as the protein levels, were normalized to the readouts of α-tubulin, which are shown below each band. After OXC treatment, the Bax protein expression level decreases until 16 h, then increases at 24 h. Bim protein is maintained without a significant increase until 48 h. Bcl-2 protein was observed to decrease in a time-dependent manner, while Bcl-xL protein remained constant until 24 h, and finally decreased at 48 h. The immunoblot images were semi-quantitated by ImageJ according to the relative densitometric units of each band.</p> Full article ">Figure 8
<p>Caspases 3 and 7 activations in PC-3 cells treated for up to 48 h with OXC and the control Paclitaxel. In cells with OXC, the activation of Caspase-3 increases at 6 h and remains until 24 h. Additionally, it leads to an increase in active Caspase-7 in a time-dependent manner. The immunoblot images were semi-quantitated by ImageJ according to the relative densitometric units of each band, and the readouts, defined as the protein complex levels, were normalized to the readouts of α-tubulin, which are shown below each band.</p> Full article ">Figure 9
<p>The Bcl-xL/Bax and Bcl-xL/Bim protein complexes’ formation in PC-3 cells exposed to OXC for up to 48 h. The Bcl-xL/Bim protein complex levels remained until 48 h, while the Bcl-xL/Bax complex decreased at 6 h. Protein levels were normalized to the readouts of α-tubulin. The immunoblot images were semi-quantitated by ImageJ according to the relative densitometric units of each band.</p> Full article ">
14 pages, 11839 KiB  
Article
Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury
by Mi-Gyeong Gwon, Hyemin Gu, Jaechan Leem and Kwan-Kyu Park
Molecules 2021, 26(19), 5931; https://doi.org/10.3390/molecules26195931 - 30 Sep 2021
Cited by 27 | Viewed by 3023
Abstract
Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol [...] Read more.
Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol is a major component of ginger and exhibits anti-oxidative and anti-inflammatory effects. Accumulating evidence suggest that 6-shogaol may serve as a potential therapeutic agent for various inflammatory diseases. However, whether 6-shogaol exerts a protective effect on cisplatin-induced renal side effect has not yet been determined. The aim of this study was to evaluate the effect of 6-shogaol on cisplatin-induced AKI and to investigate its underlying mechanisms. An administration of 6-shogaol after cisplatin treatment ameliorated renal dysfunction and tubular injury, as shown by a reduction in serum levels of creatinine and blood urea nitrogen and an improvement in histological abnormalities. Mechanistically, 6-shogaol attenuated cisplatin-induced oxidative stress and modulated the renal expression of prooxidant and antioxidant enzymes. Apoptosis and necroptosis induced by cisplatin were also suppressed by 6-shogaol. Moreover, 6-shogaol inhibited cisplatin-induced cytokine production and immune cell infiltration. These results suggest that 6-shogaol exhibits therapeutic effects against cisplatin-induced AKI via the suppression of oxidative stress, tubular cell death, and inflammation. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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<p>Effect of 6-shogaol on renal function in cisplatin-treated mice. Mice were given an intraperitoneal injection of 6-shogaol (20 mg/kg; 6-SHO) daily for 3 consecutive days, starting from 1 h after cisplatin treatment (20 mg/kg; CP). All mice were sacrificed 72 h after a single dose of cisplatin and blood samples were obtained. (<b>A</b>) Serum creatinine levels. (<b>B</b>) Blood urea nitrogen (BUN) levels. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus the control group (Con). <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus the cisplatin-treated group (CP).</p> Full article ">Figure 2
<p>Effect of 6-shogaol on histological abnormalities in cisplatin-treated mice. (<b>A</b>) Representative images of hematoxylin and eosin (H&amp;E) or periodic acid-Schiff (PAS) staining of renal cortex. Scale bar = 40 μm. Red arrows indicate tubular dilatation. Blue arrows indicate cast deposition in the lumens of tubules. (<b>B</b>) Tubular injury was semiquantitatively scored using PAS-stained sections. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 3
<p>Effect of 6-shogaol on expression of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in cisplatin-treated mice. (<b>A</b>) Representative images of immunohistochemistry (IHC) staining for NGAL and KIM-1. Scale bar = 40 μm. (<b>B</b>) Quantification of positive staining for NGAL. (<b>C</b>) Quantification of positive staining for KIM-1. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 4
<p>Effect of 6-shogaol on oxidative stress in cisplatin-treated mice. (<b>A</b>) Representative images of IHC staining for 4-hydroxynonenal (4-HNE). Scale bar = 40 μm. (<b>B</b>) Quantification of positive staining for 4-HNE. (<b>C</b>) Renal levels of malondialdehyde (MDA). (<b>D</b>) Ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 5
<p>Effect of 6-shogaol on expression of prooxidant and antioxidant enzymes in cisplatin-treated mice. (<b>A</b>) Relative mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). (<b>B</b>) Relative mRNA levels of catalase and manganese superoxide dismutase (MnSOD). (<b>C</b>) Western blotting of NOX4 and MnSOD. (<b>D</b>) Quantification of western blots for NOX4 and MnSOD. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was chosen as an internal control. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 6
<p>Effect of 6-shogaol on tubular cell apoptosis in cisplatin-treated mice. (<b>A</b>) TdT-mediated dUTP nick end labeling (TUNEL) assay on kidney sections. Scale bar = 10 μm. To detect nuclei, 4′, 6-diamidino-2-phenylindole (DAPI) was used. (<b>B</b>) Number of TUNEL-stained cells per field. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 7
<p>Effect of 6-shogaol on tubular cell necroptosis in cisplatin-treated mice. (<b>A</b>) Western blotting of receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, mixed-lineage kinase domain-like protein (MLKL), and p-MLKL. (<b>B</b>) Quantification of western blots for RIPK1, RIPK3, and p-MLKL. GAPDH was used as an internal control. (<b>C</b>) Representative images of IHC staining for RIPK3. Scale bar = 40 μm. (<b>D</b>) Quantification of positive staining for RIPK3. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 8
<p>Effect of 6-shogaol on production of cytokines and chemokines in cisplatin-treated mice. (<b>A</b>) Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). (<b>B</b>) Relative mRNA levels of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), and C-C motif chemokine ligand 5 (CCL5). GAPDH was chosen as an internal control. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">Figure 9
<p>Effect of 6-shogaol on immune cell infiltration in cisplatin-treated mice. (<b>A</b>) Representative images of IHC staining for F4/80 and CD4. Red arrows indicate positively stained cells. Scale bar = 20 μm. (<b>B</b>) Number of F4/80-stained cells per field. (<b>C</b>) Number of CD4-stained cells per field. <span class="html-italic">n</span> = 8 per group of mice. * <span class="html-italic">p</span> &lt; 0.05 versus Con. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 versus CP.</p> Full article ">
17 pages, 3667 KiB  
Article
Lichen-Derived Depsides and Depsidones Modulate the Nrf2, NF-κB and STAT3 Signaling Pathways in Colorectal Cancer Cells
by Katarzyna Papierska, Violetta Krajka-Kuźniak, Jarosław Paluszczak, Robert Kleszcz, Marcin Skalski, Elżbieta Studzińska-Sroka and Wanda Baer-Dubowska
Molecules 2021, 26(16), 4787; https://doi.org/10.3390/molecules26164787 - 7 Aug 2021
Cited by 11 | Viewed by 2695
Abstract
The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling [...] Read more.
The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling pathways. Attention was also paid to the effects of the compounds tested on CRC cells using anakoinosis—that is, simultaneous analysis of several signaling pathways. The effects of the tested natural compounds on the activity of selected transcriptional factors related to CRC were analyzed by Western blot and RT-PCR assays. The highest activity against CRC cells was shown by physodic and salazinic acids from the studied secondary metabolites of lichens. As a result, an increase in the activation of transcription factor Nrf2 and the expression of its selected target genes was observed. Physodic and salazinic acids induced the opposite effect in relation to the NF-κB and STAT3 pathways. These results confirmed our earlier observations that lichen-derived compounds have the ability to modulate signaling pathway networks. While caperatic acid affected Wnt/β-catenin to the most extent, salazinic acid was the most potent modulator of Nrf2, NF-κB and STAT3 pathways. Physodic acid seemed to affect all the investigated pathways. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1
<p>The chemical structure of the investigated lichen-derived compounds.</p> Full article ">Figure 2
<p>The effect of lichen-derived compounds on Nrf2 activation in DLD-1 and HCT116 cells. (<b>A</b>) The level of Nrf2 protein in the cytosolic fraction. (<b>B</b>) The level of Nrf2 protein in the nuclear fraction. (<b>C</b>) The level of p-Nrf2 protein in the nuclear fraction. Representative Western immunoblots are presented under the graphs (<b>A</b>–<b>C</b>). Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin or lamin. (<b>D</b>) The level of Nrf2 binding to DNA. Results are presented as the means ± SEM from three separate experiments percentage of control). Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 3
<p>The effect of lichen-derived compounds on the expression of <span class="html-italic">Nrf2</span> in DLD-1 and HCT116 cells. The values (fold of control) are presented as the means ± SEM from three separate experiments. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 4
<p>The effect of lichen-derived compounds on the expression of selected Nrf2 target genes: SOD and GSTP in DLD-1 and HCT116 cells. (<b>A</b>) Levels of <span class="html-italic">SOD</span> and <span class="html-italic">GSTP</span> transcripts. The values (fold of control) are presented as the means ± SEM from three separate experiments. (<b>B</b>) Level of SOD and GSTP proteins. Representative Western immunoblots are presented under the graphs. Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 5
<p>The effect of lichen-derived compounds on the expression of selected Nrf2 target genes: CAT and GPx in DLD-1 and HCT116 cells. (<b>A</b>) Levels of <span class="html-italic">CAT</span> and <span class="html-italic">GPx</span> transcripts. The values (fold of control) are presented as the means ± SEM from three separate experiments. (<b>B</b>) Levels of CAT and GPx proteins. Representative Western immunoblots are presented under the graphs. Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 6
<p>The effect of lichen-derived compounds on NF-κB activation in DLD-1 and HCT116 cells. (<b>A</b>) The levels of NF-κB p50 and p65 proteins in the cytosolic fraction. (<b>B</b>) The levels of NF-κB p50 and p65 proteins in the nuclear fraction. Representative Western immunoblots are presented under the graphs (<b>A</b>,<b>B</b>). Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin or lamin. (<b>C</b>) The levels of NF-κB p50 and p65 binding to DNA. Results are presented as the means ± SEM from three separate experiments percentage of control). Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 7
<p>The effect of lichen-derived compounds on the expression of NF-κB p50 and p65 in DLD-1 and HCT116 cells. The values (fold of control) are presented as the means ± SEM from three separate experiments. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 8
<p>The effect of lichen-derived compounds on the expression of selected NF-κB target genes: COX-2 and <span class="html-italic">iNOS</span> in DLD-1 and HCT116 cells. (<b>A</b>) Levels of COX-2 and <span class="html-italic">iNOS</span> transcripts. The values (fold of control) are presented as the means ± SEM from three separate experiments. (<b>B</b>) Levels of COX-2 and <span class="html-italic">iNOS</span> proteins. Representative Western immunoblots are presented under the graphs. Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 9
<p>The effect of lichen-derived compounds on STAT3 activation in DLD-1 and HCT116 cells. (<b>A</b>) The level of STAT3 protein in the cytosolic fraction. (<b>B</b>) The level of STAT3 protein in the nuclear fraction. Representative Western immunoblots are presented under the graphs (<b>A</b>,<b>B</b>). Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin or lamin. (<b>C</b>) The level of STAT3 binding to DNA. Results are presented as the means ± SEM from three separate experiments percentage of control). Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 10
<p>The effect of lichen-derived compounds on the level of p-STAT3 in DLD-1 and HCT116 cells. (<b>A</b>) The level of p-STAT3 protein in the nuclear fraction. Representative Western immunoblots are presented under the graphs. Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of lamin. (<b>B</b>) The ratio of nuclear p-STAT3 and nuclear STAT3 compared with the control group. <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 11
<p>The effect of lichen-derived compounds on the expression of <span class="html-italic">STAT3</span> in DLD-1 and HCT116 cells. The values (fold of control) are presented as the means ± SEM from three separate experiments. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">Figure 12
<p>The effect of lichen-derived compounds on the expression of selected STAT3 target gene: Bcl-xl in DLD-1 and HCT116 cells. (<b>A</b>) Level of the <span class="html-italic">Bcl-xl</span> transcript. The values (fold of control) are presented as the means ± SEM from three separate experiments. (<b>B</b>) Level of the Bcl-xl protein. Representative Western immunoblots are presented under the graphs. Results (means ± SEM from three separate experiments) are presented as a fold change to control after normalization against the level of actin. Asterisks (*) denote statistically significant changes from the control group (<span class="html-italic">p</span> ≤ 0.05). <b>DMSO</b>, vehicle control; <b>Cap50</b>, caperatic acid (50 µM); <b>Atra50</b>, atranorin (50 µM); <b>Leca50</b>, lecanoric acid (50 µM); <b>Squam50</b>, squamatic acid (50 µM); <b>Phys25</b>, physodic acid (25 µM); <b>Salaz50</b>, salazinic acid (50 µM).</p> Full article ">
24 pages, 1590 KiB  
Article
Precursor-Boosted Production of Metabolites in Nasturtium officinale Microshoots Grown in Plantform Bioreactors, and Antioxidant and Antimicrobial Activities of Biomass Extracts
by Marta Klimek-Szczykutowicz, Michał Dziurka, Ivica Blažević, Azra Đulović, Małgorzata Miazga-Karska, Katarzyna Klimek, Halina Ekiert and Agnieszka Szopa
Molecules 2021, 26(15), 4660; https://doi.org/10.3390/molecules26154660 - 31 Jul 2021
Cited by 11 | Viewed by 2604
Abstract
The study demonstrated the effects of precursor feeding on the production of glucosinolates (GSLs), flavonoids, polyphenols, saccharides, and photosynthetic pigments in Nasturtium officinale microshoot cultures grown in Plantform bioreactors. It also evaluated the antioxidant and antimicrobial activities of extracts. L-phenylalanine (Phe) and L-tryptophan [...] Read more.
The study demonstrated the effects of precursor feeding on the production of glucosinolates (GSLs), flavonoids, polyphenols, saccharides, and photosynthetic pigments in Nasturtium officinale microshoot cultures grown in Plantform bioreactors. It also evaluated the antioxidant and antimicrobial activities of extracts. L-phenylalanine (Phe) and L-tryptophan (Trp) as precursors were tested at 0.05, 0.1, 0.5, 1.0, and 3.0 mM. They were added at the beginning (day 0) or on day 10 of the culture. Microshoots were harvested after 20 days. Microshoots treated with 3.0 mM Phe (day 0) had the highest total GSL content (269.20 mg/100 g DW). The qualitative and quantitative profiles of the GSLs (UHPLC-DAD-MS/MS) were influenced by precursor feeding. Phe at 3.0 mM stimulated the best production of 4-methoxyglucobrassicin (149.99 mg/100 g DW) and gluconasturtiin (36.17 mg/100 g DW). Total flavonoids increased to a maximum of 1364.38 mg/100 g DW with 3.0 mM Phe (day 0), and polyphenols to a maximum of 1062.76 mg/100 g DW with 3.0 mM Trp (day 0). The precursors also increased the amounts of p-coumaric and ferulic acids, and rutoside, and generally increased the production of active photosynthetic pigments. Antioxidant potential increased the most with 0.1 mM Phe (day 0) (CUPRAC, FRAP), and with 0.5 mM Trp (day 10) (DPPH). The extracts of microshoots treated with 3.0 mM Phe (day 0) showed the most promising bacteriostatic activity against microaerobic Gram-positive acne strains (MIC 250–500 µg/mL, 20–21 mm inhibition zones). No extract was cytotoxic to normal human fibroblasts over the tested concentration range (up to 250 μg/mL). Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>Morphological appearance of Plantform bioreactor-grown <span class="html-italic">N. officinale</span> microshoot cultures after precursor feeding.</p> Full article ">Figure 2
<p>Principal component analysis (PCA) plot of measured bio-chemical parameters for plant material (panel <b>A</b>) and heat map of biochemical parameters of different treatments (panel <b>B</b>). Original values are ln(x)-transformed. Unit variance scaling is applied to rows; singular value decomposition (SVD) with imputation is used to calculate principal components. X and Y axis show principal component 1 (PC1) and principal component 2 (PC2) that explain 95.4 and 1.6% of the total variance, respectively. In heat map columns are centered; unit variance scaling is applied to columns. Columns are clustered using correlation distance and average linkage [<a href="#B36-molecules-26-04660" class="html-bibr">36</a>].</p> Full article ">Figure 3
<p>Zones of bacterial growth inhibition by the tested <span class="html-italic">N. officinale</span> extracts (mm).</p> Full article ">Figure 4
<p>Fibroblast viability after 48 h incubation with extract from <span class="html-italic">N. officinale</span> grown with 3.0 mM Phe (day 0). The results were obtained using MTT assay. * Significantly different data between tested groups. <span class="html-italic">p</span> &lt; 0.05; one-way ANOVA followed by Tukey’s multiple comparison test.</p> Full article ">
13 pages, 2573 KiB  
Article
Germacranolides from Carpesium divaricatum: Some New Data on Cytotoxic and Anti-Inflammatory Activity
by Natalia Kłeczek, Janusz Malarz, Barbara Gierlikowska, Łukasz Skalniak, Agnieszka Galanty, Anna K. Kiss and Anna Stojakowska
Molecules 2021, 26(15), 4644; https://doi.org/10.3390/molecules26154644 - 30 Jul 2021
Cited by 5 | Viewed by 3361
Abstract
Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro [...] Read more.
Carpesium divaricatum Sieb. & Zucc., a traditional medicinal plant used as an inflammation-relieving remedy, is a rich source of terpenoids. At least 40 germacrane-type sesquiterpene lactones, representatives of four different structural groups, were isolated from the plant. Cytotoxicity against cancer cells in vitro is the most frequently described biological activity of the compounds. However, little is known about the selectivity of the cytotoxic effect. The anti-inflammatory activity of the germacranolides is also poorly documented. The objective of the present study was to assess the cytotoxic activity of selected C. divaricatum germacranolides-derivatives of 4,5,8,9-tetrahydroxy-3-oxo-germacran-6,12-olide towards cancer and normal cell lines (including cells of different p53 status). Moreover, to assess the anti-inflammatory effect of the compounds, the release of four proinflammatory cytokines/chemokines (IL-1β, IL-8, TNF-α and CCL2) by lipopolysaccharide-stimulated human neutrophils was measured by ELISA. The investigated sesquiterpene lactones demonstrated nonselective activity towards prostate cancer (Du145 and PC3) and normal prostate epithelial cells (PNT2) as well as against melanoma cells (A375 and HTB140) and keratinocytes (HaCaT). Cytotoxic activity against osteosarcoma cells was independent of their p53 status. In sub-cytotoxic concentrations (0.5–2.5 µM) the studied compounds significantly decreased cytokine/chemokine release by lipopolysaccharide-stimulated human leukocytes. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Chemical structures of 4β,8α-dihydroxy-5β-angeloyloxy-9β-(2-methylbutyryloxy)-3-oxo-germacran-6α,12-olide (<b>1,</b> R1 = Ang, R2 = 2-MeBu), 4β,8α-dihydroxy-5β-angeloyloxy-9β-(3-methylbutyryloxy)-3-oxo-germacran-6α,12-olide (<b>2,</b> R1 = Ang, R2 = 3-MeBu) and 4β,8α-dihydroxy-5β-isobutyryloxy-9β-(3-methylbutyryloxy)-3-oxo-germacran-6α,12-olide (<b>3,</b> R1 = iBu, R2 = 3-Mebu).</p> Full article ">Figure 2
<p>Viabilities of osteosarcoma cell lines U-2 OS (wild-type p53 status) and SAOS-2 (with p53 deletion) after 24 h treatment with <b>1</b>, <b>2</b> and doxorubicin (Doxo): (<b>a</b>) U-2 OS cells; (<b>b</b>) SAOS-2 cells.</p> Full article ">Figure 3
<p>Viabilities of osteosarcoma cell lines U-2 OS (wild-type p53 status) and SAOS-2 (with p53 deletion) after 48 h treatment with <b>1</b>, <b>2</b> and doxorubicin (Doxo): (<b>a</b>) U-2 OS cells; (<b>b</b>) SAOS-2 cells.</p> Full article ">Figure 4
<p>Cytotoxic effects of <b>1</b> (4β,8α-dihydroxy-5β-angeloyloxy-9β-(2-methylbutyryloxy)-3-oxo-germacran-6α,12-olide) and <b>2</b> (cardivarolide G), at concentrations 0.5, 1.0 and 2.5 μM, on human LPS-stimulated neutrophils. Results shown as percentage of cells without diminished membrane integrity (propidium iodide negative cells). Control, untreated cells; LPS, cells stimulated with LPS (stimulated control). Statistical significance: * <span class="html-italic">p</span> &lt; 0.05, with reference to a stimulated control.</p> Full article ">Figure 5
<p>Inhibitory effects of <b>1</b> (4β,8α-dihydroxy-5β-angeloyloxy-9β-(2-methylbutyryloxy)-3-oxo-germacran-6α,12-olide) and <b>2</b> (cardivarolide G), at concentrations 0.5, 1.0 and 2.5 μM, on the ROS release from f-MLP-stimulated human neutrophils. Statistical significance: *** <span class="html-italic">p</span> &lt; 0.001, with reference to a stimulated control.</p> Full article ">Figure 6
<p>Inhibitory effects of <b>1</b> (4β,8α-dihydroxy-5β-angeloyloxy-9β-(2-methylbutyryloxy)-3-oxo-germacran-6α,12-olide) and <b>2</b> (cardivarolide G), at concentrations 0.5, 1.0 and 2.5 μM, on IL-1β (<b>a</b>), IL-8 (<b>b</b>), TNF-α (<b>c</b>) and CCL2 (<b>d</b>) secretion by LPS-stimulated human neutrophils. Statistical significance: ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, with reference to a stimulated control.</p> Full article ">
10 pages, 1734 KiB  
Communication
Phenolic Constituents from Platycodon grandiflorum Root and Their Anti-Inflammatory Activity
by Wei Li and Hye Jin Yang
Molecules 2021, 26(15), 4530; https://doi.org/10.3390/molecules26154530 - 27 Jul 2021
Cited by 17 | Viewed by 3138
Abstract
Six lignols (1–6), including two new compounds (+)-(7R,8R)-palmitoyl alatusol D (1) and (+)-(7R,8R)-linoleyl alatusol D (2), along with four phenolics (7–10), a neolignan [...] Read more.
Six lignols (1–6), including two new compounds (+)-(7R,8R)-palmitoyl alatusol D (1) and (+)-(7R,8R)-linoleyl alatusol D (2), along with four phenolics (7–10), a neolignan (11), three alkyl aryl ether-type lignans (12–14), two furofuran-type lignans (15–16), three benzofuran-type lignans (17–19), a tetrahydrofuran-type lignan (20), and a dibenzylbutane-type lignan (21) were isolated from the ethyl acetate-soluble fraction of the methanol extract of Platycodon grandiflorum (Jacq.) A. DC. root. The chemical structures of the obtained compounds were elucidated via high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy analyses. The obtained spectroscopic data agreed well with literature. Among the isolated compounds, eighteen (1–7 and 11–21) were isolated from P. grandiflorum and the Campanulaceae family for the first time. This is the first report on lignol and lignan components of P. grandiflorum. The anti-inflammatory effects of the isolated compounds were examined in terms of their ability to inhibit the production of pro-inflammatory cytokines IL-6, IL-12 p40, and TNF-α in lipopolysaccharide-stimulated murine RAW264.7 macrophage cells. Nine compounds (4–6, 12, and 15–19) exhibited inhibitory effects on IL-12 p40 production, eleven compounds (1–6, 12, 15–17, and 19) exhibited inhibitory activity on IL-6 production, and eleven compounds (1–6 and 15–19) exhibited inhibitory effects against TNF-α. These results warrant further investigation into the potential anti-inflammatory activity and general benefits of the phenolic constituents of P. grandiflorum root. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1

Figure 1
<p>Structures of compounds <b>1</b>–<b>21</b> from the root of <span class="html-italic">P. grandiflorum</span>.</p> Full article ">Figure 2
<p>Key COSY and HMBC correlations of <b>1</b> and <b>2</b> (<b>A</b>) and the ICD spectrum of <b>1a</b> (<b>B</b>).</p> Full article ">
19 pages, 6298 KiB  
Article
Rosa platyacantha Schrenk from Kazakhstan—Natural Source of Bioactive Compounds with Cosmetic Significance
by Askhat Sabitov, Katarzyna Gaweł-Bęben, Zuriyadda Sakipova, Marcelina Strzępek-Gomółka, Uliana Hoian, Elmira Satbayeva, Kazimierz Głowniak and Agnieszka Ludwiczuk
Molecules 2021, 26(9), 2578; https://doi.org/10.3390/molecules26092578 - 28 Apr 2021
Cited by 9 | Viewed by 2899
Abstract
Plants belonging to the Rosa genus are known for their high content of bioactive molecules and broad spectrum of healing and cosmetic activities. Rosa platyacantha Schrenk is a wild-type species abundant in the mountainous regions of Kazakhstan. The phytochemical composition as well as [...] Read more.
Plants belonging to the Rosa genus are known for their high content of bioactive molecules and broad spectrum of healing and cosmetic activities. Rosa platyacantha Schrenk is a wild-type species abundant in the mountainous regions of Kazakhstan. The phytochemical composition as well as the bioactivity of R. platyacantha extracts have not been fully investigated to date. In this study, various parts of R. platyacantha plant, collected in Almaty region, Kazakhstan, were used to prepare five hydroalcoholic extracts (R1–R5). The extracts were compared for the content of phytochemicals and selected biological activities, which are important for the potential cosmetic application of R. platyacantha. Extract R3, prepared from flower buds, showed the most significant antioxidant and tyrosinase inhibitory potential, decreasing the monophenolase and diphenolase activities of tyrosinase. Extract R3 showed also collagenase inhibitory activity and cytotoxicity against human melanoma cells A375, being less cytotoxic for noncancerous skin keratinocytes HaCaT. Analysis of fractions E and F, obtained from R3 extracts, revealed that quercetin, kaempferol, rutin, and their derivatives are more likely responsible for the tyrosinase inhibitory properties of R. platyacantha extracts. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Figure 1
<p>The effect of R1–R5 <span class="html-italic">R. platyacantha</span> extracts on the intracellular ROS levels in HaCaT keratinocytes treated for 60 min with 1 mM H<sub>2</sub>O<sub>2</sub>; nt—no pre-treatment, NAC—2 mM N-acetylcysteine; values on graph represent mean ± SD (<span class="html-italic">n</span> = 3), *** <span class="html-italic">p</span> &lt; 0.001, * <span class="html-italic">p</span> &lt; 0.05 in comparison with “nt + H<sub>2</sub>O<sub>2</sub>” sample.</p> Full article ">Figure 2
<p>Elastase (<b>a</b>) and collagenase (<b>b</b>) inhibitory activity of R1–R5 extracts from various parts of <span class="html-italic">R. platyacantha,</span> 1,10-phenantroline (1,10-Phe) was used as inhibitor control; values on graphs represent means ± SD (<span class="html-italic">n</span> = 3), *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05.</p> Full article ">Figure 3
<p>Inhibition of monophenolase (<b>a</b>) and diphenolase (<b>b</b>) activity of tyrosinase by R1–R5 extracts from various parts of <span class="html-italic">R. platyacantha;</span> KA- kojic acid, values on graphs represent mean ± SD (<span class="html-italic">n</span> = 3), *** <span class="html-italic">p</span> &lt; 0.001, ** <span class="html-italic">p</span> &lt; 0.01, * <span class="html-italic">p</span> &lt; 0.05.</p> Full article ">Figure 4
<p>Inhibition of monophenolase (<b>a</b>) and diphenolase (<b>b</b>) activity of tyrosinase by C-I fractions of closed flower extract (R3) of <span class="html-italic">R. platyacantha</span> KA- kojic acid, values on graphs represent mean ± SD (<span class="html-italic">n</span> = 3), *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">Figure 5
<p>Inhibition of monophenolase (<b>a</b>) and diphenolase (<b>b</b>) activity of tyrosinase by main constituents identified in fraction E from extract R3, values on graphs represent mean ± SD (<span class="html-italic">n</span> = 3), *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">
10 pages, 946 KiB  
Article
Morus alba Prevented the Cyclophosphamide Induced Somatic and Germinal Cell Damage in Male Rats by Ameliorating the Antioxidant Enzyme Levels
by Abhijit Ghosh, Syed Imam Rabbani, Syed Mohammed Basheeruddin Asdaq, Yahya Mohzari, Ahmed Alrashed, Hamdan Najib Alajami, Awad Othman Aljohani, Abdullah Ali Al Mushtawi, Majed Sultan Alenazy, Rakan Fahad Alamer and Abdulmajead Khalid Alanazi
Molecules 2021, 26(5), 1266; https://doi.org/10.3390/molecules26051266 - 26 Feb 2021
Cited by 5 | Viewed by 2126
Abstract
Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage [...] Read more.
Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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<p>Effect of pretreatment of <span class="html-italic">M. alba</span> extract on sperm motility in cyclophosphamide treated animals. (P.S: <span class="html-italic">M. alba—Morus alba</span>, CP—cyclophosphamide, α-toco—α-tocopherol); values are represented as Mean ± SD, N = 6. Statistics: one-way ANOVA followed by Bonferroni; a <span class="html-italic">p</span> &lt; 0.001 compared with control, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared with cyclophosphamide group.</p> Full article ">Figure 2
<p>Effect of pretreatment of <span class="html-italic">M. alba</span> extract on serum SOD levels in cyclophosphamide treated animals. (P.S: <span class="html-italic">M. alba</span>—<span class="html-italic">Morus alba</span>, CP—cyclophosphamide, α-toco—α-tocopherol); values are represented as Mean ± SD, N = 6. Statistics: one-way ANOVA followed by Bonferroni; a <span class="html-italic">p</span> &lt; 0.001 compared with control, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 compared with cyclophosphamide group.</p> Full article ">Figure 3
<p>Effect of pretreatment of <span class="html-italic">M.</span> <span class="html-italic">alba</span> extract on serum catalase levels in cyclophosphamide. Statistics: one-way ANOVA followed by Bonferroni; a <span class="html-italic">p</span> &lt; 0.001 compared with control, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 compared with cyclophosphamide group.</p> Full article ">

Review

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20 pages, 1177 KiB  
Review
The Current State of Knowledge on Salvia hispanica and Salviae hispanicae semen (Chia Seeds)
by Sara Motyka, Katarzyna Koc, Halina Ekiert, Eliza Blicharska, Katarzyna Czarnek and Agnieszka Szopa
Molecules 2022, 27(4), 1207; https://doi.org/10.3390/molecules27041207 - 11 Feb 2022
Cited by 29 | Viewed by 10784
Abstract
Chia seeds (Salviae hispanicae semen) are obtained from Salvia hispanica L. This raw material is distinguished by its rich chemical composition and valuable nutritional properties. It is currently referred to as “health food”. The purpose of the present work was to [...] Read more.
Chia seeds (Salviae hispanicae semen) are obtained from Salvia hispanica L. This raw material is distinguished by its rich chemical composition and valuable nutritional properties. It is currently referred to as “health food”. The purpose of the present work was to perform a literature review on S. hispanica and chia seeds, focusing on their chemical composition, biological properties, dietary importance, and medicinal uses. The valuable biological properties of chia seeds are related to their rich chemical composition, with particularly high content of polyunsaturated fatty acids, essential amino acids, polyphenols, as well as vitamins and bioelements. The available scientific literature indicates the cardioprotective, hypotensive, antidiabetic, and antiatherosclerotic effects of this raw material. In addition, studies based on in vitro assays and animal and human models have proven that chia seeds are characterized by neuroprotective, hepatoprotective, anti-inflammatory, and antioxidant properties. These properties indicate a valuable role of chia in the prevention of civilization diseases. Chia seeds are increasingly popular in functional food and cosmetic and pharmaceutical industries. That is attributed not only to their desirable chemical composition and biological activity but also to their high availability. Nevertheless, S. hispanica is also the object of specific biotechnological studies aimed at elaboration of micropropagation protocols of this plant species. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Morphological appearance of <span class="html-italic">S. hispanica</span> seeds.</p> Full article ">
20 pages, 3751 KiB  
Review
Overview of the Biological Activity of Anthraquinons and Flavanoids of the Plant Rumex Species
by Dmitriy Berillo, Marzhan Kozhahmetova and Lina Lebedeva
Molecules 2022, 27(4), 1204; https://doi.org/10.3390/molecules27041204 - 10 Feb 2022
Cited by 17 | Viewed by 4691
Abstract
Rumex confertus belongs to the genus Rumex and is classified as an invasive parasitic plant in agriculture. Despite other Rumex species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the [...] Read more.
Rumex confertus belongs to the genus Rumex and is classified as an invasive parasitic plant in agriculture. Despite other Rumex species being widely used in herbal medicine due to their antimicrobial, antioxidant, antitumor, and anti-inflammatory effects, there are almost no information about the potential of Rumex confertus for the treatment of various diseases. In this review we analyzed scientific articles revealing properties of Rumex plant’s substances against cancer, diabetes, pathogenic bacterial invasions, viruses, inflammation, and oxidative stress for the past 20 years. Compounds dominating in each composition of solvents for extraction were discussed, and common thin layer chromatography(TLC) and high performance liquid chromatography(HPLC) methods for efficient separation of the plant’s extract are included. Physico-chemical properties such as solubility, hydrophobicity (Log P), pKa of flavonoids, anthraquinones, and other derivatives are very important for modeling of pharmacokinetic and pharmacodynamics. An overview of clinical studies for abounded selected substances of Rumex species is presented. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Chromatogram (RP-HPLC) of methanolic extracts from the leaves of <span class="html-italic">R. confertus</span> reproduced with the permission of Smolarz [<a href="#B8-molecules-27-01204" class="html-bibr">8</a>].</p> Full article ">Figure 2
<p>Influence of different concentrations of ethanol extract and emodin of leaves of <span class="html-italic">R. confertus</span> on the viability of EAC cells in vitro, adapted from Antonyan et al. [<a href="#B35-molecules-27-01204" class="html-bibr">35</a>].</p> Full article ">Figure 3
<p>Correlation between emodin and ethanol extract of leaves of <span class="html-italic">Rumex Confertus</span> on the viability hippocampal cells, adapted from Antonyan et al. [<a href="#B35-molecules-27-01204" class="html-bibr">35</a>].</p> Full article ">
19 pages, 1459 KiB  
Review
Promising Strategies in Plant-Derived Treatments of Psoriasis-Update of In Vitro, In Vivo, and Clinical Trials Studies
by Martyna Nowak-Perlak, Krzysztof Szpadel, Izabella Jabłońska, Monika Pizon and Marta Woźniak
Molecules 2022, 27(3), 591; https://doi.org/10.3390/molecules27030591 - 18 Jan 2022
Cited by 26 | Viewed by 7814
Abstract
Psoriasis is a common, chronic systemic inflammatory disease affecting 125 million people worldwide. It is associated with several important conditions, including psoriatic arthritis, cardiometabolic syndrome, and depression, leading to a significant reduction in patients’ quality of life. Current treatments only reduce symptoms, not [...] Read more.
Psoriasis is a common, chronic systemic inflammatory disease affecting 125 million people worldwide. It is associated with several important conditions, including psoriatic arthritis, cardiometabolic syndrome, and depression, leading to a significant reduction in patients’ quality of life. Current treatments only reduce symptoms, not cure. This review discusses the mechanisms involved in the initiation and development of the disease, the role of oxidative stress in this autoimmune disease, as well as potential therapeutic options with substances of natural origin. The main aim of the study is intended to offer a review of the literature to present plants and phytochemicals that can represent potential remedies in the fight against psoriasis. We identified many in vitro, in vivo, and clinical trials studies that evaluated the relationship between chosen natural substances and immune system response in the course of psoriasis. We sought to find articles about the efficacy of potential natural-derived drugs in controlling symptoms and their ability to maintain long-term disease inactivity without side effects, and the result of our work is a review, which highlights the effectiveness of plant-derived drugs in controlling the inflammatory burden on psoriatic patients by decreasing the oxidative stress conditions. Full article
(This article belongs to the Special Issue Biological Activities of Natural Products II)
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<p>The scheme presents complicated mechanisms of the psoriasis course. Proinflammatory cytokines and other factors overproduced in psoriasis contribute to the increased proliferation of keratinocytes. Moreover, in psoriasis conditions, activation of inflammatory cells occurs and stimulates intense inflammation. These self-perpetuating loops of proinflammatory activators and effectors enhance the symptoms of this autoimmune disease.</p> Full article ">Figure 2
<p>The scheme demonstrating the chosen plants and phytochemicals that may help to reduce symptoms of psoriasis, and act as antiproliferative compounds for psoriatic keratinocytes.</p> Full article ">Figure 3
<p>Schematic figure presenting the possible mechanisms of plant-derived compounds in order to treat psoriasis disease.</p> Full article ">
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