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Search Results (156)

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15 pages, 1329 KiB  
Article
Phytochemical Profile, Cytotoxicity, Anti-Inflammatory, Antioxidant, and Antiglycation Activity of Annona crassiflora Extract: An In Vitro Study
by Laura Akie Corrêa de Souza, Gislene Parreiras Costa, Júlia Amanda Rodrigues Fracasso, Luisa Taynara Silvério da Costa, Debora Barros Barbosa, Natalia Alves Zoppé, Júlia Marques Ribeiro, Valdecir Farias Ximenes, João Tadeu Ribeiro-Paes and Lucineia dos Santos
Cosmetics 2025, 12(2), 36; https://doi.org/10.3390/cosmetics12020036 - 27 Feb 2025
Viewed by 60
Abstract
Chronic inflammation and oxidative stress play significant roles in the development of various diseases like diabetes, cancer, and cardiovascular diseases. This study aimed to explore the potential therapeutic benefits of Annona crassiflora (Araticum-do-Cerrado) leaves, specifically focusing on their anti-inflammatory, antioxidant, and antiglycation properties. [...] Read more.
Chronic inflammation and oxidative stress play significant roles in the development of various diseases like diabetes, cancer, and cardiovascular diseases. This study aimed to explore the potential therapeutic benefits of Annona crassiflora (Araticum-do-Cerrado) leaves, specifically focusing on their anti-inflammatory, antioxidant, and antiglycation properties. To achieve this, a hydroethanolic extract of the plant’s leaves (EHAC) was prepared and subjected to phytochemical analysis and in vitro tests to evaluate its effects. The tests included assessing its impact on fibroblast cytotoxicity, anti-inflammatory capabilities (phagocytosis and macrophage spreading), antioxidant activity (DPPH and lipid peroxidation), and antiglycation activity. The results indicated that the EHAC contains high levels of phenolic compounds, including rutin and quercetin. The extract demonstrated strong anti-inflammatory activity by significantly inhibiting phagocytosis and macrophage spreading. Furthermore, it exhibited high antioxidant capacity by inhibiting lipid peroxidation and scavenging free radicals. Additionally, it showed notable antiglycation activity by completely inhibiting the formation of AGEs at the tested concentrations. The cell viability remained above 95% at concentrations up to 800 µg/mL. In conclusion, the EHAC has significant therapeutic potential, and further research is warranted for its development as a phytotherapeutic, with the aim of preserving the biodiversity of the Brazilian Cerrado. Full article
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Figure 1

Figure 1
<p>(<b>A</b>) Retention times of the eight flavonoid standards used in this study: quercetin (1); rutin (2); morin (3); kaempferol (4); isorhamnetin (5); fisetin (6); chrysin (7); and catechin (8); (<b>B</b>) fingerprint of the EHAC obtained by high-performance liquid chromatography according to the conditions presented in the methodology: 1—quercetin; 2—rutin.</p>
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<p>Mean ± SD of percentage values referring to the cell viability rate in NIH 3T3 fibroblasts at the evaluation time of 24 h after the following treatments: saline solution—negative control (NC); Tween 80 at 2%—positive control (PC); hydroalcoholic extract of <span class="html-italic">Annona crassiflora</span> (EHAC) at concentrations of 100, 200, 400, 800, and 1600 μg/mL. The asterisk (*) indicates a significant difference (<span class="html-italic">p</span> &lt; 0.05) compared to the PC group.</p>
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<p>Mean percentage ± standard deviation (% inhibition of phagocytosis (<b>A</b>) and % inhibition of spreading) (<b>B</b>) after the following treatments: saline solution—negative control (NC); dexamethasone 100 µg/mL; hydroalcoholic extract of <span class="html-italic">Annona crassiflora</span> (EHAC) at concentrations of 100, 200, 400, and 800 µg/mL. One-way ANOVA followed by Tukey’s post hoc test. The asterisk (*) indicates a significant difference (<span class="html-italic">p</span> &lt; 0.05) from the NC.</p>
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<p>Mean ± SD of the percentage values for antioxidant activity through DPPH (<b>A</b>) and percentage inhibition of lipid peroxidation (<b>B</b>) after the following treatments: quercetin 200 μg/mL—positive control (PC); hydroalcoholic extract of <span class="html-italic">Annona crassiflora</span> (EHAC) at concentrations of 100, 200, 400, and 800 μg/mL. One-way ANOVA followed by Tukey’s post hoc test. The asterisk (*) indicates a significant difference (<span class="html-italic">p</span> &lt; 0.05) from the negative control (NC).</p>
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<p>Mean ± SD values for antiglycation activity (%) evaluated through the BSA/GLUCOSE (<b>A</b>) and BSA/MGO (<b>B</b>) systems after the following treatments: quercetin 200 μg/mL—positive control (PC); hydroalcoholic extract of <span class="html-italic">Annona crassiflora</span> (EHAC) at concentrations of 100, 200, 400, and 800 μg/mL. One-way ANOVA followed by Tukey’s post hoc test. The asterisk (*) indicates a significant difference (<span class="html-italic">p</span> &lt; 0.05) from the NC.</p>
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37 pages, 24138 KiB  
Article
Phytotherapeutic Analysis of Chloroform-Based Fractions of Alstonia scholaris and Wrightia tinctoria Extracts Reveals Potent Anti-Psoriatic Activity: An In Vitro and In Vivo Study
by Madhavi Ojha, Nilanshu Manocha, Vinod Kumar, Ganeshan Karthikeyan and Devinder Toor
Pharmaceuticals 2025, 18(3), 304; https://doi.org/10.3390/ph18030304 - 22 Feb 2025
Viewed by 340
Abstract
Background/Objectives: Psoriasis, a prevalent dermatological disorder, poses therapeutic challenges due to limited effective treatments or adverse side-effects. Traditional medicinal plants like Alstonia scholaris and Wrightia tinctoria, historically used in Ayurvedic and Siddha practices, show potential in treating inflammatory skin diseases. This study [...] Read more.
Background/Objectives: Psoriasis, a prevalent dermatological disorder, poses therapeutic challenges due to limited effective treatments or adverse side-effects. Traditional medicinal plants like Alstonia scholaris and Wrightia tinctoria, historically used in Ayurvedic and Siddha practices, show potential in treating inflammatory skin diseases. This study aims to explore their in vitro and in vivo anti-psoriatic properties to develop safer and more effective therapies. Methods: Chloroform:methanol fractions from ethanol extracts of Alstonia scholaris and Wrightia tinctoria were evaluated for anti-psoriatic activity. In vitro assays using HaCaT cells assessed cell viability, apoptosis, and inflammatory markers. In vivo studies utilized an IMQ-induced psoriasis mouse model, evaluating skin lesions, histopathology, and cytokine profiles. Results: Chloroform fractions significantly reduced HaCaT cell viability and induced apoptosis. They also dose-dependently downregulated IL-8 and RANTES levels. In vivo, these fractions reduced skin inflammation, edema, and psoriasis scores. Histopathological analysis showed decreased epidermal thickness and dermal inflammation. Key psoriasis biomarkers IL-17 and IL-23 were significantly reduced. Conclusions: Chloroform:methanol fractions from Alstonia scholaris and Wrightia tinctoria demonstrated potent anti-psoriatic effects in vitro and in vivo. These findings support their potential as novel phytotherapeutic agents for managing psoriasis, offering promise for further development and clinical application. Full article
(This article belongs to the Special Issue Plant-Based Bioactive Products for Pharmaceutical Applications)
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Figure 1

Figure 1
<p>(<b>A</b>) Calibration curve of oxirane (marker compound) concentrations ranging from 200 to 1000 ppm. The plot shows a linear correlation (R<sup>2</sup> = 0.996) between oxirane concentration and peak area, as determined by chromatographic analysis. The linear regression equation is y = mx + c, where y represents the peak area and x represents the oxirane concentration in ppm. This calibration curve was used to quantify oxirane content in fractions ASE 1–ASE 6 of <span class="html-italic">A. scholaris</span>. (<b>B</b>) Quantification of oxirane content in fractions (ASE 1–ASE 6) of <span class="html-italic">A. scholaris</span> using chromatographic analysis. The oxirane content in each fraction was calculated based on a standard calibration curve (<b>A</b>) established with oxirane concentrations ranging from 200 to 1000 ppm. Data are represented as mean ± SD of three independent measurements.</p>
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<p>(<b>A</b>) Calibration curve of 2-hydroxypyridine (2-HP, marker compound) concentrations ranging from 200 to 1000 ppm. The plot shows a linear correlation (R<sup>2</sup> = 0.9995) between 2-hydroxypyridine concentration and peak area, as determined by chromatographic analysis. The linear regression equation is <span class="html-italic">y = mx + c</span>, where <span class="html-italic">y</span> represents the peak area and <span class="html-italic">x</span> represents the 2-hydroxypyridine concentration in ppm. This calibration curve was used to quantify 2-hydroxypyridine content in fractions of <span class="html-italic">W. tinctoria</span>. (<b>B</b>) Quantification of 2-hydroxypyridine content in fractions of <span class="html-italic">W. tinctoria</span> using chromatographic analysis. The 2-hydroxypyridine content in each fraction was calculated based on a standard calibration curve (<b>A</b>) established with 2-hydroxypyridine concentrations ranging from 200 to 1000 ppm. Data are represented as mean ± SD of three independent measurements.</p>
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<p>Anti-proliferative effects of ASE1, ASE2, ASE3, ASE4, ASE5, and ASE6 on HaCaT cells. HaCaT cells (10,000 cells/well) were treated with varying concentrations of each fraction (<b>A</b>) 0.1 µg/mL, (<b>B</b>) 1 µg/mL, (<b>C</b>) 10 µg/mL, (<b>D</b>) 100 µg/mL, and (<b>E</b>) 200 µg/mL for 24, 48, and 72 h. Cell proliferation was assessed using the MTT assay. Curcumin was used as the positive control, and DMSO-treated cells served as the vehicle control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
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<p>Anti-proliferative effects of WTE1, WTE2, WTE3, WTE4, WTE5, and WTE6 on HaCaT cells. HaCaT cells (10,000 cells/well) were treated with varying concentrations of each fraction (<b>A</b>) 0.1 µg/mL, (<b>B</b>) 1 µg/mL, (<b>C</b>) 10 µg/mL, (<b>D</b>) 100 µg/mL, and (<b>E</b>) 200 µg/mL for 24, 48, and 72 h. Cell proliferation was assessed using the MTT assay. Curcumin was used as the positive control and DMSO-treated cells served as the vehicle control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
Full article ">Figure 4 Cont.
<p>Anti-proliferative effects of WTE1, WTE2, WTE3, WTE4, WTE5, and WTE6 on HaCaT cells. HaCaT cells (10,000 cells/well) were treated with varying concentrations of each fraction (<b>A</b>) 0.1 µg/mL, (<b>B</b>) 1 µg/mL, (<b>C</b>) 10 µg/mL, (<b>D</b>) 100 µg/mL, and (<b>E</b>) 200 µg/mL for 24, 48, and 72 h. Cell proliferation was assessed using the MTT assay. Curcumin was used as the positive control and DMSO-treated cells served as the vehicle control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
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<p>Apoptotic effects of ASE and WTE fractions on HaCaT cells. HaCaT cells (10,000 cells/well) were treated with ASE fractions (<b>A</b>) and WTE fractions (<b>B</b>), and apoptosis was measured using the JC-1 assay. Curcumin was used as the positive control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
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<p>Inhibition of IL-8 levels in TNF-α-induced HaCaT cells by ASE and WTE fractions. HaCaT cells (10,000 cells/well) were treated with ASE fractions (<b>A</b>) and WTE fractions (<b>B</b>) to assess IL-8 levels. Methotrexate was used as the positive control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
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<p>Inhibition of RANTES levels in TNF-α-induced HaCaT cells by ASE and WTE fractions. HaCaT cells (10,000 cells/well) were treated with ASE fractions (<b>A</b>) and WTE fractions (<b>B</b>) to assess RANTES levels. Methotrexate was used as the positive control. Data are normalized and presented as Mean ± S.E.M. from three independent experiments (n = 3).</p>
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<p>Evaluation of daily body weight (<b>A</b>) and skin edema (<b>B</b>) post-treatment with the positive control, ASE2, ASE3, WTE2, and WTE3 on an imiquimod (IMQ)-induced psoriasis-like mouse model. Clobetasol was used as the positive control. Data were statistically analyzed by two-way ANOVA followed by Bonferroni’s test. Statistical significance is indicated as follows: comparison between the disease control group (G2) and the normal control group (G1): <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 (###). Comparison between treatment groups (G3–G7) and the disease control group (G2): <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 (***).</p>
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<p>Evaluation of spleen weight post-treatment with the positive control, ASE2, ASE3, WTE2, and WTE3 on imiquimod-induced psoriasis-like mouse model. Clobetasol was used as the positive control. Data were statistically analyzed by two-way ANOVA followed by Bonferroni’s test. Statistical significance is indicated as follows: comparison between the disease control group (G2) and the normal control group (G1): <span class="html-italic">p</span> &lt; 0.001 (###). Comparison between treatment groups (G3–G7) and the disease control group (G2): <span class="html-italic">p</span> &lt; 0.001 (***).</p>
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<p>Assessment of PASI scores following treatment with the positive control, ASE2, ASE3, WTE2, and WTE3 in an imiquimod-induced psoriasis-like mouse model. Clobetasol was used as the positive control. Data were statistically analyzed by two-way ANOVA followed by Bonferroni’s test. Statistical significance is indicated as follows: comparison between the disease control group (G2) and the normal control group (G1): <span class="html-italic">p</span> &lt; 0.001 (###). Comparison between treatment groups (G3–G7) and the disease control group (G2): <span class="html-italic">p</span> &lt; 0.01 (**) and <span class="html-italic">p</span> &lt; 0.001 (***).</p>
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<p>Effect of the positive control, ASE2, ASE3, WTE2, and WTE3 on ear punch biopsy weight in imiquimod-induced psoriasis-like mouse model. Clobetasol was used as the positive control. Data were statistically analyzed by two-way ANOVA followed by Bonferroni’s test. Statistical significance is indicated as follows: comparison between the disease control group (G2) and the normal control group (G1): <span class="html-italic">p</span> &lt; 0.001 (###). Comparison between treatment groups (G3–G7) and the disease control group (G2): <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 (***).</p>
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<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
Full article ">Figure 12 Cont.
<p>Representative histopathological images of dorsal skin sections (<b>A</b>) and macroscopic appearance of the dorsal skin (<b>B</b>) from BALB/c mice (n = 6 per group, represented by A1 to A6) following repeated applications of ASE2, ASE3, WTE2, and WTE3. The groups are designed as follows: (<b>G1</b>) negative control, (<b>G2</b>) disease control, (<b>G3</b>) 0.05% clobetasol (positive control), (<b>G4</b>) ASE2, (<b>G5</b>) ASE3, (<b>G6</b>) WTE2, and (<b>G7</b>) WTE3. Arrows indicate key histopathological features used to assess disease severity and treatment effects: <b>E</b> (epidermal thickening), <b>Hy</b> (hyperkeratosis), <b>P</b> (parakeratosis), <b>Pu</b> (pustule), <b>I</b> (inflammatory infiltration), and <b>Ed</b> (edema). Scale bar: 200 μm.</p>
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<p>Evaluation of IL-17 in skin homogenate (<b>A</b>) and serum (<b>B</b>) and IL-23 in skin homogenate (<b>C</b>) and serum (<b>D</b>) levels post-treatment with positive control, ASE2, ASE3, WTE2, and WTE3 on an imiquimod-induced psoriasis-like mice model. Clobetasol was used as the positive control. Data were statistically analyzed by two-way ANOVA followed by Bonferroni’s test. Statistical significance is indicated as follows: comparison between the disease control group (G2) and the normal control group (G1): <span class="html-italic">p</span> &lt; 0.01 (##), <span class="html-italic">p</span> &lt; 0.001 (###). Comparison between treatment groups (G3–G7) and the disease control group (G2): <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 (***).</p>
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20 pages, 2487 KiB  
Review
Oxidative Stress in Benign Prostatic Hyperplasia: Mechanisms, Clinical Relevance and Therapeutic Perspectives
by Aris Kaltsas, Timoleon Giannakas, Marios Stavropoulos, Zisis Kratiras and Michael Chrisofos
Diseases 2025, 13(2), 53; https://doi.org/10.3390/diseases13020053 - 11 Feb 2025
Viewed by 493
Abstract
Background/Objectives: Benign prostatic hyperplasia (BPH) is among the most common conditions affecting men as they age, resulting in lower urinary tract symptoms (LUTS) that can profoundly impact quality of life. While historically attributed primarily to androgenic imbalances, current evidence implicates additional factors—particularly oxidative [...] Read more.
Background/Objectives: Benign prostatic hyperplasia (BPH) is among the most common conditions affecting men as they age, resulting in lower urinary tract symptoms (LUTS) that can profoundly impact quality of life. While historically attributed primarily to androgenic imbalances, current evidence implicates additional factors—particularly oxidative stress (OS) and chronic inflammation—in BPH pathogenesis. This review aims to synthesize research on the interplay between OS, inflammation, and hormonal regulation in BPH, emphasizing their clinical relevance and potential therapeutic implications. Methods: A comprehensive review of peer-reviewed literature was conducted focusing on mechanistic studies, clinical trials, and observational reports. Searches included data on ROS generation, antioxidant capacity, inflammatory mediators, and their contribution to pathological prostatic overgrowth. Potential interventions targeting OS—such as antioxidant supplementation, anti-inflammatory drugs, vitamin D receptor agonists, and phytotherapeutics—were also evaluated for their efficacy and safety profiles. Results: Chronic inflammation and OS were consistently identified within hyperplastic prostate tissue. Excessive ROS production, diminished antioxidant defense, and sustained cytokine release create a proproliferative and antiapoptotic environment, accelerating disease progression. Metabolic comorbidities (e.g., obesity, insulin resistance) further exacerbate these imbalances. Standard therapies (α-blockers and 5-ARIs) effectively relieve symptoms but do not directly address the oxidative–inflammatory axis. Emerging evidence suggests that pharmacological and dietary approaches targeting OS and inflammation may reduce prostate volume expansion and alleviate LUTS. Conclusions: Findings indicate that OS and inflammation are key contributors to BPH progression. Incorporating antioxidant and anti-inflammatory strategies alongside conventional treatments holds promise for improving clinical outcomes and patient quality of life. Future research should focus on validating OS-specific biomarkers and optimizing personalized therapy regimens. Full article
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Figure 1
<p>Schematic of ROS generation and oxidative pathways leading to BPH progression. <span class="html-italic">Created in BioRender. Kaltsas, A. (2025)</span>, <a href="https://BioRender.com/e65o135" target="_blank">https://BioRender.com/e65o135</a> (accessed on 13 January 2025).</p>
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<p>Therapeutic strategies targeting oxidative stress in benign prostatic hyperplasia. <span class="html-italic">Created in BioRender. Kaltsas, A. (2025)</span>, <a href="https://BioRender.com/m32o053" target="_blank">https://BioRender.com/m32o053</a> (accessed on 13 January 2025).</p>
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20 pages, 1717 KiB  
Article
Antitumor Activity of Warbugia ugandensis: Methanolic Extracts and Gene Regulation in Colorectal Cancer
by John M. Macharia, John K. Maina, Afshin Zand, Betsy Rono Cheriro, Tímea Varjas, Dávid Sipos, Zsolt Káposztás, Ferenc Budán, Orsolya Liza Kövesdi and Bence L. Raposa
Nutrients 2025, 17(3), 471; https://doi.org/10.3390/nu17030471 - 28 Jan 2025
Viewed by 721
Abstract
A promising approach to accelerating the development of innovative anti-cancer therapies involves the evaluation of natural plant compounds. In this study, we focused on examining the effects of Warbugia ugandensis (W. ugandensis) methanolic root and stem infusions on the activity of [...] Read more.
A promising approach to accelerating the development of innovative anti-cancer therapies involves the evaluation of natural plant compounds. In this study, we focused on examining the effects of Warbugia ugandensis (W. ugandensis) methanolic root and stem infusions on the activity of five target genes—COX-2, CASPS-9, Bcl-xL, Bcl2, and 5-LOX—using colorectal cancer (CRC) cell lines (Caco-2). The plant extracts were prepared for testing by dissolving them in dimethyl sulfoxide (DMSO) after undergoing a step-by-step extraction process. Caco-2 cells were then treated with different concentrations of the extracts, and RNA was extracted and purified for analysis. Our results demonstrated a dose-dependent relationship between the phytoconstituents of W. ugandensis and the overexpression of CASP9, along with the downregulation of COX-2, 5-LOX, Bcl-xL, and Bcl2 genes. This suggests that W. ugandensis acts as a potent natural inhibitor of CRC progression. Given the potential clinical benefits, we propose the use of W. ugandensis methanolic root and stem extracts as promising organic inhibitors for CRC tumorigenesis, with more in vitro studies warranted to validate and expand on our findings. Additionally, we recommend further studies to identify and characterize the specific metabolites in W. ugandensis that contribute to the modulation of pathways responsible for inhibiting CRC growth. Full article
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<p>Alterations in <span class="html-italic">COX-2</span> gene expression subsequent to treatment with methanolic stem and root extracts. (<b>a</b>) Box plot showing the regulatory properties of the stem extracts on <span class="html-italic">COX2</span>, (<span class="html-italic">p</span> = 0.001), (<b>b</b>) Box plot showing the regulatory properties of the root extracts on <span class="html-italic">COX2</span>, (<span class="html-italic">p</span> = 0.021).</p>
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<p>Modulation of <span class="html-italic">CASP9</span> gene expression following exposure to methanolic stem and root extracts. (<b>a</b>) Box plot showing the regulatory properties of the stem extracts on <span class="html-italic">CASP9</span>, (<span class="html-italic">p</span> = 0.001), (<b>b</b>) Box plot showing the regulatory properties of the root extracts on <span class="html-italic">CASP9</span>, (<span class="html-italic">p</span> = 0.059).</p>
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<p>Modulation of <span class="html-italic">Bcl-xL</span> gene expression following exposure to methanolic stem and root extracts. (<b>a</b>) Box plot showing the regulatory properties of the stem extracts on Bcl-xL, (<span class="html-italic">p</span> = 0.001), (<b>b</b>) Box plot showing the regulatory properties of the root extracts on Bcl-xL, (<span class="html-italic">p</span> = 0.002).</p>
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<p>Alterations in <span class="html-italic">Bcl2</span> gene expression upon treatment with methanolic root and stem extracts. (<b>a</b>) Box plot showing the regulatory properties of the stem extracts on Bcl2, (<span class="html-italic">p</span> = 0.001), (<b>b</b>) Box plot showing the regulatory properties of the root extracts on Bcl2, (<span class="html-italic">p</span> = 0.002).</p>
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<p>Alterations in <span class="html-italic">5-LOX</span> gene expression subsequent to treatment with methanolic stem and root extracts. (<b>a</b>) Box plot showing the regulatory properties of the stem extracts on <span class="html-italic">5LOX</span>, (<span class="html-italic">p</span> = 0.001), (<b>b</b>) Box plot showing the regulatory properties of the root extracts on <span class="html-italic">5LOX</span>, (<span class="html-italic">p</span> = 0.048).</p>
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<p>A schematic illustration of the bioactive phytocomponents present in <span class="html-italic">W. ugandensis</span>, and their regulatory characteristics on gene targets: <span class="html-italic">Bcl2</span>, <span class="html-italic">Bcl-xL</span>, <span class="html-italic">CASP9</span>, <span class="html-italic">COX-2</span> and <span class="html-italic">5-LOX</span>.</p>
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27 pages, 2733 KiB  
Article
Simarouba berteroana Krug & Urb. Extracts and Fractions Possess Anthelmintic Activity Against Eggs and Larvae of Multidrug-Resistant Haemonchus contortus
by Marcos Javier Espino Ureña, Albert Katchborian-Neto, José Ribamar Garcez Neto, Francisco Flávio da Silva Lopes, Selene Maia de Morais, Vitor Eduardo Narciso dos Reis, Carmen Lúcia Cardoso, Lorena Mayana Beserra de Oliveira, Claudio Viegas Jr., Marcos José Marques and Wesley Lyeverton Correia Ribeiro
Vet. Sci. 2025, 12(2), 90; https://doi.org/10.3390/vetsci12020090 - 23 Jan 2025
Viewed by 1003
Abstract
Gastrointestinal nematode infections significantly impact small ruminant production, causing substantial economic losses worldwide. The rising resistance to anthelmintics has led to the search for alternative treatments, including phytotherapeutic approaches. This study investigates the chemical composition and anthelmintic activity of crude extracts and fractions [...] Read more.
Gastrointestinal nematode infections significantly impact small ruminant production, causing substantial economic losses worldwide. The rising resistance to anthelmintics has led to the search for alternative treatments, including phytotherapeutic approaches. This study investigates the chemical composition and anthelmintic activity of crude extracts and fractions from Simarouba berteroana, an endemic plant from Hispaniola, against a multidrug-resistant isolate of Haemonchus contortus. Chemical analyses revealed high contents of phenolic compounds, tannins, and flavonoids and confirmed the presence of 22 quassinoids, 5 phytosterol lipids, 3 terpenoid quinones, 3 alkaloids, and 1 naphthoquinone. The hydroalcoholic and iso-butanol fractions showed the strongest egg hatching inhibition (IC50 = 0.93 and 1.21 mg/mL, respectively), while hexane fractions were less effective (p < 0.05). Fluorescence microscopy showed that the extracts and fractions adhered to eggshells, causing evisceration and cuticle detachment in hatched larvae. All extracts, except for hexane fractions, inhibited larval exsheathment at 0.3 mg/mL, with phenolic compounds being responsible for this effect. These results provide the first evidence of the ovicidal and larval exsheathment inhibition activities of S. berteroana extracts and fractions against H. contortus, highlighting their potential in managing gastrointestinal nematodes in small ruminants. Further in vivo studies are needed to confirm these findings. Full article
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<p>LC-MS analyses of the overlapped base peak ion (BPI) chromatogram of samples (Sb1: crude extract, Sb1Halc: hydroalcoholic fraction from the 1st collection in February 2020, Sb2: crude extract, and Sb2Halc: hydroalcoholic fraction from the 2nd collection in June 2021) in the positive ionization mode with chemical structures of the putatively annotated metabolites. The numbers of the compound are shown in <a href="#vetsci-12-00090-t001" class="html-table">Table 1</a> (final ID).</p>
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<p>Eggs and 1st-stage larvae of <span class="html-italic">H. contortus</span> treated with <span class="html-italic">S. berteroana iso</span>-butanol fraction at a concentration of 0.5 mg/mL (<b>B</b>,<b>G</b>,<b>H</b>,<b>I</b>), hydroalcoholic fraction at 2.5 mg/mL (<b>C</b>) and at 1 mg/mL (<b>E</b>,<b>J</b>), hexane fraction at 8 mg/mL (<b>K</b>), and negative control with 0.5% DMSO in distilled water (<b>A</b>,<b>F</b>) and thiabendazole at 0.1 mg/mL (<b>D</b>,<b>L</b>). The black bars in the lower-right margin of the images represent a length of 50 μm.</p>
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<p>Eggs and 1st-stage larvae of <span class="html-italic">H. contortus</span> treated with <span class="html-italic">S. berteroana</span> crude extract and hydroalcoholic fraction with and without propidium iodide (<b>A</b>–<b>F</b>), while (<b>G</b>–<b>L</b>) were treated with 0.5% DMSO ((<b>G</b>,<b>H</b>) show an inviable egg and (<b>I</b>–<b>L</b>) live at the 1st-stage larvae). The white bars in the lower-right margin of the images represent a length of 100 μm.</p>
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<p>Percentage of exsheathment inhibition (mean and standard error) of 3rd-stage <span class="html-italic">H. contortus</span> larvae in contact with the crude extract and fractions of <span class="html-italic">S. berteroana</span> at 300 μg/mL. Sb1 and Sb2: <span class="html-italic">S. berteroana</span> crude extract derived from Sb1 and Sb2, respectively; the hexane fractions (Sb1-HexFr and Sb2-HexFr), ethyl acetate (Sb1-EtAcFr and Sb2-EtAcFr), <span class="html-italic">iso</span>-butanol (Sb1-isobFr and Sb2-isobFr), and hydroalcoholic fractions (Sb1-HalcFr and Sb2-HalcFr) were obtained from each crude extract of <span class="html-italic">S. berteroana</span>; PVPP: polyvinylpolypyrrolidone; and PBS: phosphate-buffered solution.</p>
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17 pages, 2168 KiB  
Article
Syntrichia laevipila Brid., a Bryophyta from Northwest Argentina as a Source of Antioxidants and Antimicrobials
by Luis Ignacio Jiménez, Florencia Maria Correa Uriburu, José Javier Martínez Chamás, Guillermo Martin Suárez, Iris Catiana Zampini, Mario J. Simirgiotis and María Inés Isla
Plants 2025, 14(2), 253; https://doi.org/10.3390/plants14020253 - 17 Jan 2025
Viewed by 544
Abstract
In recent years, numerous studies have emerged on the biological activities of bryophytes and their potential for therapeutic use. However, mosses appear to be a relatively overlooked group. The objective of this study was to conduct a phytochemical analysis of one hydroalcoholic extract [...] Read more.
In recent years, numerous studies have emerged on the biological activities of bryophytes and their potential for therapeutic use. However, mosses appear to be a relatively overlooked group. The objective of this study was to conduct a phytochemical analysis of one hydroalcoholic extract of Syntrichia laevipila and to evaluate its potential as an antioxidant and antimicrobial agent. The moss was collected in the Chaco Serrano region of Argentina, specifically on Jacaranda mimosifolia, and subsequently extracted by maceration in ethanol/water. UHPLC/ESI/MS/MS analysis identified 32 peaks, including phenolic compounds (phenolic acids, lignans, chalcones, and flavonoids) and non-hydrophilic compounds (terpenoids, fatty acids, and brassinosteroids). Maslinic and oleanolic acids, two triterpenoids present in S. laevipila, were also detected in J. mimosifolia, a substrate of this moss. The concentration of phenolic compounds was 19.05 ± 0.21 µg GAE/mL, while the total flavonoid concentration was 13.13 ± 0.33 µg QE/mL. The determination of reducing and total sugars yielded 0.22 ± 0.03 mg GE/mL and 1.26 ± 0.24 mg GE/mL, respectively, while the concentration of soluble proteins was 90.60 ± 4.50 µg BSAE/mL. The extract exhibited antioxidant properties by scavenging ABTS•+, H2O2, AAPH, and HO radicals. Additionally, it demonstrated antibacterial activity by inhibiting the growth of four strains of Staphylococcus aureus. The data obtained suggest that the hydroalcoholic extract of S. laevipila possesses significant potential as a natural antioxidant and antimicrobial agent, making it a promising candidate for the development of phytotherapeutic and cosmetic products. Full article
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<p><span class="html-italic">S. laevipila</span>, (<b>A</b>)—Habit of dry plant, (<b>B</b>)—Habit of wet plant, (<b>C</b>)—Specialized asexual propagule. The drawing was made by the authors.</p>
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<p>Flowchart of process of obtention of <span class="html-italic">S. laevipila</span> extracts and its characterization.</p>
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<p>UHPLC/ESI/MS/MS chromatogram of <span class="html-italic">S. laevipila</span> extract. The numbers above the peaks correspond to major components identified in the extract.</p>
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<p>Structures of some representative compounds detected in <span class="html-italic">S. laevipila</span>: peak 5, pinellic acid; peak 6, 2’,4’-Dihydroxychalcone; peak 12, hederagenin; peak 16, maslinic acid; peak 17, piperochromenoic acid; peak 21, mogroside I-A1; peak 22, recurvoside A; peak 23, oleanolic acid; and peak 27, cirsimaritin.</p>
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55 pages, 8204 KiB  
Review
Bioactive Compounds from Vegetal Organs of Taraxacum Species (Dandelion) with Biomedical Applications: A Review
by Maria-Virginia Tanasa (Acretei), Ticuta Negreanu-Pirjol, Laura Olariu, Bogdan-Stefan Negreanu-Pirjol, Anca-Cristina Lepadatu, Larisa Anghel (Cireasa) and Natalia Rosoiu
Int. J. Mol. Sci. 2025, 26(2), 450; https://doi.org/10.3390/ijms26020450 - 7 Jan 2025
Viewed by 1042
Abstract
Taraxacum officinale (dandelion) is a perennial flowering plant of the Asteraceae family that has spread globally and is well-known for its traditional uses. The aim of this work is to provide a detailed review of scientific literature on the genus Taraxacum from the [...] Read more.
Taraxacum officinale (dandelion) is a perennial flowering plant of the Asteraceae family that has spread globally and is well-known for its traditional uses. The aim of this work is to provide a detailed review of scientific literature on the genus Taraxacum from the last two decades, with particular emphasis on the biological and pharmacological characteristics of dandelions. The traditional use of Taraxacum species and their potential use in medicine are assessed. In addition, individual papers describing principal pathways and molecules modulated by Taraxacum in antitumoral, anti-inflammatory, antidiabetic, hepatoprotective, immunomodulatory, antimicrobial, and antioxidant activities are presented. This review of phytochemical studies reveals that dandelions contain a wide range of bioactive compounds, such as polyphenols, phytosterols, flavonoids, carotenoids, terpene, and coumarins, whose biological activities are actively explored in various areas of human health, some constituents having synergistic activities, including antioxidant, antimicrobial, anti-inflammatory and anticancer activities. The study provides a screening of Taraxacum sp. chemical composition, an assessment of the main pharmacological properties, and a description of relevant studies supporting the use of dandelion for its particularly valuable and diversified therapeutic potential in different diseases. Full article
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<p>Flow chart describing the selection and screening of literature for systematic reviews using preferred articles.</p>
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<p><span class="html-italic">Taraxacum officinale</span> L. vegetal organs (original photo).</p>
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<p>Key HMBC correlations of compounds 1 = taraxinositol A, 2 = taraxinositol B and 3 = taraxinol (adapted after [<a href="#B30-ijms-26-00450" class="html-bibr">30</a>]).</p>
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<p>Biosynthetic pathway of some important polyphenols in plants (adapted after [<a href="#B37-ijms-26-00450" class="html-bibr">37</a>]).</p>
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<p>The main active compounds of dandelion (original).</p>
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<p>The described anti-inflammatory, antibacterial, and antiviral mechanisms of <span class="html-italic">Taraxacum</span> extracts (adapted after [<a href="#B200-ijms-26-00450" class="html-bibr">200</a>]).</p>
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<p>The described antidiabetic, hepatoprotective, and immunomodulator mechanisms of <span class="html-italic">Taraxacum</span> extracts (adapted after [<a href="#B6-ijms-26-00450" class="html-bibr">6</a>,<a href="#B65-ijms-26-00450" class="html-bibr">65</a>,<a href="#B264-ijms-26-00450" class="html-bibr">264</a>]).</p>
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<p>The described antitumoral and antioxidant mechanisms of <span class="html-italic">Taraxacum</span> extracts (adapted after [<a href="#B65-ijms-26-00450" class="html-bibr">65</a>]).</p>
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18 pages, 2473 KiB  
Article
An Innovative Method of Improving an Extract of Andrographis paniculata from Leaves: Its Anticancer Effect Involves the Cell Endoplasmic Reticulum
by Jessica Maiuolo, Rosamaria Caminiti, Valeria Mazza, Francesca Oppedisano, Saverio Nucera, Maria Serra, Roberta Macrì, Ernesto Palma, Annie Eng, Vincenzo Mollace and Carolina Muscoli
Int. J. Mol. Sci. 2025, 26(1), 344; https://doi.org/10.3390/ijms26010344 - 2 Jan 2025
Viewed by 683
Abstract
In this manuscript, the effects of two extracts from Andrographis paniculata were tested: (a) an extract titrated to 49.7% of andrographolide and obtained from leaves of the plant: (b) the pure andrographolide titrated to 99%. The extracts were dissolved in 1-butanol and tested [...] Read more.
In this manuscript, the effects of two extracts from Andrographis paniculata were tested: (a) an extract titrated to 49.7% of andrographolide and obtained from leaves of the plant: (b) the pure andrographolide titrated to 99%. The extracts were dissolved in 1-butanol and tested on tumor lines (MCF7 and SH-SY5Y) and the non-tumor line (Huvec) to understand the effects on cell proliferation. The addition of a sonication process improved their dissolution and efficacy making these extracts unique and innovative. The experiments conducted (viability measurements, solubility of the extracts, IC50 tests, measurement of oxidative potential, lipid and cytosolic calcium concentration, and mortality assessment by annexin assay) showed a different behavior of the extracts on cancer cells and not. In particular, the extracts did not cause toxic effects on the viability of the Huvec cells, while both tumor lines were damaged, demonstrating that cancer cells are more susceptible to extracts of A. paniculata than healthy cells. The mechanism of action responsible for the damage detected involved the functioning of the endoplasmic reticulum organelle and finally resulted in apoptotic death. For this reason, the extracts considered have shown a potential anti-tumor role and A. paniculata could be used and exploited in pharmacological therapy against cancer. However, further studies, obtained in clinical practice, should be conducted to increase knowledge of the effects of A. paniculata on the organism and its phytotherapeutic role. Full article
(This article belongs to the Special Issue Cell Metabolism and Small Natural Compounds (2nd Edition))
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<p>Effects of PA and ALE on cell viability. <a href="#ijms-26-00344-f001" class="html-fig">Figure 1</a> shows the effect of ALE and PA, dissolved in several solvents, on the three cell lines chosen: Huvec panels (<b>a</b>,<b>b</b>), MCF-7 panels (<b>c</b>,<b>d</b>), and SH-SY5Y panels (<b>e</b>,<b>f</b>). Three independent experiments were carried out, and the values are expressed as the mean ± SD. * denotes <span class="html-italic">p</span> &lt; 0.05 vs. the lowest concentration ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. the lowest concentration; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. the lowest concentration; A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Comparison of IC<sub>50</sub> of PA and ALE dissolved in several solvents. <a href="#ijms-26-00344-f002" class="html-fig">Figure 2</a> shows the variation of IC<sub>50</sub> when PA and ALE are dissolved in different solvents. This analysis was conducted in Huvec, MCF-7, and SH-SY5Y cells as shown in panels (<b>a</b>–<b>c</b>), respectively. Three independent experiments were carried out, and the values are expressed as the mean ± SD. * denotes <span class="html-italic">p</span> &lt; 0.05 vs. the respective PA; ° denotes <span class="html-italic">p</span> &lt; 0.05 vs. the respective PA § denotes <span class="html-italic">p</span> &lt; 0.05 vs. the respective PA; §§ denotes <span class="html-italic">p</span> &lt; 0.01 vs. the respective PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Effects of extracts following sonication. In Panel (<b>a</b>), cell lines were treated or untreated with ALE or PA, and extracts were subjected to a sonication process at different times. As can be seen in the legend of the figure, for each cell line the white histograms correspond to the viability of untreated cells, while the light pink and blue histograms correspond to the viability of cells treated with PA and ALE, respectively. Three independent experiments were carried out, and the values are expressed as the mean ± SD. * denotes <span class="html-italic">p</span> &lt; 0.05 vs. untreated cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. untreated cells; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. untreated cells. § denotes <span class="html-italic">p</span> &lt; 0.05 vs. the sonication time of 0′; §§ denotes <span class="html-italic">p</span> &lt; 0.01 vs. the sonication time of 0′. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA). In Panel (<b>b</b>), differences in cell viability, obtained before and after sonication for 10′, were summarized. White histograms indicate cell viability obtained before the sonication of the extract, while yellow ones indicate cell viability obtained after the sonication of the extract. Three independent experiments were carried out, and the values are expressed as the mean ± SD. § denotes <span class="html-italic">p</span> &lt; 0.05 vs. respective un-sonicated extract; §§ denotes <span class="html-italic">p</span> &lt; 0.01 vs. respective un-sonicated extract.</p>
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<p>Panel (<b>a</b>) shows the antioxidant activity of PA and ALE obtained by the ORAC test. The curves corresponding to PA and ALE 10 μg/mL are represented in black and red, respectively. Three independent experiments were carried out and a representative experiment was shown. Panels (<b>b</b>,<b>c</b>) highlight the chelating and reducing properties of PA and ALE at increasing concentrations (0.01–0.32 mg/mL). Three independent experiments were carried out and the values are expressed as the mean ± SD. * denotes <span class="html-italic">p</span> &lt; 0.05 vs. ALE. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Production and accumulation of ROS. Panels (<b>a</b>–<b>c</b>) show the accumulation of ROS caused by PA and ALE in Huvec, MCF-7, and SH-SY5Y cells, respectively. The results were obtained from cytofluorimetric readings, and on the right of the plots, the respective quantifications are shown. Hydrogen peroxide was used as the positive control. Each box refers to a treatment as indicated: the <span class="html-italic">x</span>-axis represents the fluorescence of the fluorochrome FITC connected to our fluorescent probe, while the <span class="html-italic">y</span>-axis is relative to the number of cells we decided to acquire (10,000). At the top of each box, there is a marker (M1), which is arbitrarily drawn in the control and kept the same for all other samples. The part of the peak included in M1 is indicated by a numerical percentage. In the respective quantification, the percentages were compared. The control percentage is arbitrarily made equal to 1 and the other values are related to it. The control is represented by the white histogram, PA and ALE are highlighted by black and red histograms respectively; finally hydrogen peroxide is shown in orange. Three independent experiments were carried out, and a representative experiment was shown. The values are expressed as the mean ± standard deviation (sd). * denotes <span class="html-italic">p</span> &lt; 0.05 vs. untreated cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. untreated cells; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. untreated cells. § denotes <span class="html-italic">p</span> &lt; 0.05 vs. PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>PA and ALE modify lipid and calcium concentrations. Panel (<b>a</b>) highlights the lipid concentrations resulting from treatment with PA and ALE in the selected cell lines. Panels (<b>b</b>–<b>d</b>) show the cytoplasmatic calcium concentration under the same experimental conditions. Thapsigargin, an endoplasmic reticulum stress inducer, has been used as a positive control. Three independent experiments were carried out. The values are expressed as the mean ± standard deviation (sd). * denotes <span class="html-italic">p</span> &lt; 0.05 vs. untreated cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. untreated cells; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. untreated cells. § denotes <span class="html-italic">p</span> &lt; 0.05 vs. PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Involvement of UPR. Panels (<b>a</b>–<b>c</b>) show whether or not UPR is involved, following treatment with PA and ALE in Huvec, MCF-7, and SH-SY5Y, respectively. The studied UPR sensor was PERK, and its possible activation was justified by the modulation of the expression of its phosphorylated form (p-PERK) and by the phosphorylation of eIF2α. The results obtained were normalized for the housekeeping protein tubulin and one representative experiment was shown. The respective quantification is shown in the lower part of <a href="#ijms-26-00344-f007" class="html-fig">Figure 7</a>. Three independent experiments were carried out. The values are expressed as the mean ± standard deviation (sd). * denotes <span class="html-italic">p</span> &lt; 0.05 vs. untreated cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. untreated cells; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. untreated cells. § denotes <span class="html-italic">p</span> &lt; 0.05 vs. PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Expression of ATF4. Panel (<b>a</b>) shows the modulation of ATF4 expression in our experimental model. In every single box, the <span class="html-italic">x</span>-axis represents the fluorescence of fluorochrome FITC linked to our fluorescent probe and measured on a logarithmic scale; the <span class="html-italic">y</span>-axis is relative to the number of cells that we have decided to acquire (20,000). Panel (<b>b</b>) highlights the respective quantifications. On the plot, control is shown in black, while PA and ALE are shown in blue and red respectively. Three independent experiments were carried out. The values are expressed as the mean ± standard deviation (sd). * denotes <span class="html-italic">p</span> &lt; 0.05 vs. untreated cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. untreated cells; *** denotes <span class="html-italic">p</span> &lt; 0.001 vs. untreated cells. §§ denotes <span class="html-italic">p</span> &lt; 0.01 vs. PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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<p>Treatment with PA and ALE: when is apoptosis present? To evaluate the effects of PA and ALE on the apoptotic process, cytofluorimetric experiments with annexin V/PI were conducted. Panels (<b>a</b>–<b>c</b>) represent these results obtained on Hucec, MCF-7, and SH-SY5Y cells, respectively. The upper part of the panels shows a representative experiment, while the lower part shows the respective quantification. Every box is divided into four quadrants (Q1, Q2, Q3, and Q4). Q1 refers to annexin V-negative/PI-negative cells (viable cells). Q2 refers to annexin V-positive/PI-negative cells (early apoptosis). Q3 refers to annexin V-positive/PI-positive cells (late apoptosis); Q4 refers to annexin V-negative/PI-positive cells (necrosis). Three independent experiments were carried out. The values are expressed as the mean ± standard deviation (sd). * denotes <span class="html-italic">p</span> &lt; 0.05 vs. Q1 of Huvec cells; ** denotes <span class="html-italic">p</span> &lt; 0.01 vs. Q1 of Huvec cells; ° denotes <span class="html-italic">p</span> &lt; 0.05 vs. Q2 of Huvec cells; ## denotes <span class="html-italic">p</span> &lt; 0.01 vs. Q3 of Huvec cells; ### denotes <span class="html-italic">p</span> &lt; 0.001 vs. Q3 of Huvec cells; ∞ denotes <span class="html-italic">p</span> &lt; 0.05 vs. Q4 of Huvec cells; § denotes <span class="html-italic">p</span> &lt; 0.05 vs. PA. A Tukey–Kramer comparison test followed the analysis of Variance (ANOVA).</p>
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56 pages, 2782 KiB  
Review
Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals
by Ghyda Murad Hashim, Mehdi Shahgolzari, Kathleen Hefferon, Afagh Yavari and Srividhya Venkataraman
Bioengineering 2025, 12(1), 7; https://doi.org/10.3390/bioengineering12010007 - 25 Dec 2024
Cited by 1 | Viewed by 1318
Abstract
In spite of significant advancements in diagnosis and treatment, cancer remains one of the major threats to human health due to its ability to cause disease with high morbidity and mortality. A multifactorial and multitargeted approach is required towards intervention of the multitude [...] Read more.
In spite of significant advancements in diagnosis and treatment, cancer remains one of the major threats to human health due to its ability to cause disease with high morbidity and mortality. A multifactorial and multitargeted approach is required towards intervention of the multitude of signaling pathways associated with carcinogenesis inclusive of angiogenesis and metastasis. In this context, plants provide an immense source of phytotherapeutics that show great promise as anticancer drugs. There is increasing epidemiological data indicating that diets rich in vegetables and fruits could decrease the risks of certain cancers. Several studies have proved that natural plant polyphenols, such as flavonoids, lignans, phenolic acids, alkaloids, phenylpropanoids, isoprenoids, terpenes, and stilbenes, could be used in anticancer prophylaxis and therapeutics by recruitment of mechanisms inclusive of antioxidant and anti-inflammatory activities and modulation of several molecular events associated with carcinogenesis. The current review discusses the anticancer activities of principal phytochemicals with focus on signaling circuits towards targeted cancer prophylaxis and therapy. Also addressed are plant-derived anti-cancer vaccines, nanoparticles, monoclonal antibodies, and immunotherapies. This review article brings to light the importance of plants and plant-based platforms as invaluable, low-cost sources of anti-cancer molecules of particular applicability in resource-poor developing countries. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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<p>The chemical structures of some prominent natural alkaloids and their semisynthetic derivatives serve as effective agents in combating cancer. Reproduced from an open-access source Dhyani et al., 2022 [<a href="#B151-bioengineering-12-00007" class="html-bibr">151</a>].</p>
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<p>The phototherapy mechanism of action. In photodynamic therapy (PDT), photosensitizers (PS) absorb light, transitioning to an excited state. This leads to two pathways: PDT Type I, where the PS reacts with biomolecules to create reactive oxygen species (ROS), and PDT Type II, where the PS transfers energy directly to oxygen, producing ROS. ROS exhibits high oxidizing power, causing cytotoxic effects primarily near their site of generation due to their short lifespan. PS* refers to the photosensitizer’s excited state. Reproduced from an open access source Pivetta et al., 2021 [<a href="#B212-bioengineering-12-00007" class="html-bibr">212</a>].</p>
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<p>PVNPs as delivery therapeutic and imaging agents in cancer. (<b>A</b>) Tobacco mosaic virus (TMV) for the targeted delivery of cisplatin in Pt-resistant ovarian cancer cells [<a href="#B312-bioengineering-12-00007" class="html-bibr">312</a>] (Reprinted/Adapted with permission from [<a href="#B272-bioengineering-12-00007" class="html-bibr">272</a>] Copyright© 2018, American Chemical Society. (<b>B</b>) The preparative process for potato virus X (PVX)-HisTRAIL by coordinating the bond between a Ni-nitrilotriacetic (NTA) group on the virus; the His-tag at the N-terminus of HisTRAIL is shown with a purple triangle. Multivalent display of HisTRAIL on the elongated PVX particle permits proper binding on death receptors DR4/5 (the trimers with blue color) for activating the caspase-dependent apoptosis in cancerous cells [<a href="#B313-bioengineering-12-00007" class="html-bibr">313</a>] (Reprinted/Adapted with permission from [<a href="#B273-bioengineering-12-00007" class="html-bibr">273</a>] Copyright© 2019, American Chemical Society). (<b>C</b>) miR-181a is an important target for ovarian cancer therapy. qPCR data and cancer cell migration assays demonstrated higher knockdown efficacy when anti-miR-181a oligonucleotides were encapsulated and delivered using the VLPs resulting in reduced cancer cell invasiveness [<a href="#B314-bioengineering-12-00007" class="html-bibr">314</a>] [Adapted from open access source: 274 Citation needed]. (<b>D</b>) Schematic illustration of Gd-Cy5.5-PhMV-mPEG NPs for cancer imaging. In vivo NIR fluorescence images of PC-3 prostate tumors in athymic nude mice after the intravenous injection of Gd-Cy5.5-PhMV-DGEA [<a href="#B315-bioengineering-12-00007" class="html-bibr">315</a>] [Adapted from open access source 275: Citation needed].</p>
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<p>PVNPs in cancer immune and combinational therapy (<b>A</b>) Intratumoral administration of plant-derived Cowpea mosaic virus (CPMV) nanoparticles as an in situ vaccine overcomes the local immunosuppression and stimulates a potent anti-tumor response in several mouse cancer models and canine patients [<a href="#B349-bioengineering-12-00007" class="html-bibr">349</a>] (Adapted from open access source: 309, Citation needed). (<b>B</b>) The PhMV-based anti-HER2 vaccine PhMV-CH401, demonstrated efficacy as an anti-HER2 cancer vaccine. Our studies highlight that VLPs derived from PhMV are a promising platform to develop cancer vaccines [<a href="#B350-bioengineering-12-00007" class="html-bibr">350</a>] (Adapted from open access source: 310, Citation needed). (<b>C</b>) Schematic diagram of preparing CCMV VLPs containing ODN 1826 (CCMV-ODN1826) for cancer therapy [<a href="#B315-bioengineering-12-00007" class="html-bibr">315</a>] (Adapted from open access source: 275, Citation needed). (<b>D</b>) Photothermal immunotherapy of melanoma using TLR-7 agonist laden TMV with polydopamine coat [<a href="#B325-bioengineering-12-00007" class="html-bibr">325</a>]. (Adapted from open access source: 285, Citation needed). Statistical significance was measured by one-way ANOVA with Tukey’s test: * <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. ns refers to not significant.</p>
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16 pages, 1937 KiB  
Article
Encapsulation of Chasteberry (Vitex agnus castus L.) Extract by Spray-Drying Followed by Spray-Chilling for Its Application in Dark Chocolate
by Mariana Alejandra Echalar Barrientos, Juliana Peralta, Fabrício Luiz Tulini, Samuel Henrique Gomes de Sá, Marcella Chalella Mazzocato, Marco Antonio Trindade, Valdecir Luccas and Carmen Silvia Favaro-Trindade
Foods 2024, 13(23), 3742; https://doi.org/10.3390/foods13233742 - 22 Nov 2024
Cited by 1 | Viewed by 882
Abstract
Chasteberry extract offers considerable phytotherapeutic benefits, particularly in alleviating premenstrual syndrome (PMS) symptoms. However, its hydroalcoholic nature leads to a bitter taste and a burning sensation, presenting challenges for direct consumption or incorporation into new food products. This study aimed to address these [...] Read more.
Chasteberry extract offers considerable phytotherapeutic benefits, particularly in alleviating premenstrual syndrome (PMS) symptoms. However, its hydroalcoholic nature leads to a bitter taste and a burning sensation, presenting challenges for direct consumption or incorporation into new food products. This study aimed to address these issues by encapsulating concentrated chasteberry extract using spray-drying with Arabic gum, followed by spray-chilling with vegetable fat as carriers. The encapsulated particles were characterized by their morphology, size, and stability, with a specific focus on phenolics and casticin stabilization. The microparticles were incorporated into dark chocolate formulations, and sensory trials conducted with dark chocolate revealed that encapsulation effectively masked undesirable flavors while safeguarding the bioactive compounds. This strategy resulted in a product that demonstrated enhanced stability and sensory appeal. This innovative formulation holds promise for delivering chasteberry phytochemicals that help alleviate PMS symptoms. Full article
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<p>Chromatographic analysis of chasteberry extract, showing the casticin peak at 17 min. Upper chromatogram was made using an external standard for casticin.</p>
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<p>The appearance of powders produced by spray-drying and coated by spray-chilling, using 5, 10, and 15 g of spray-dried chasteberry extract per 50 g of vegetable fat.</p>
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<p>Size distribution of microparticles produced by spray-drying and coated by spray-chilling, using 5, 10, and 15 g of spray-dried chasteberry extract per 50 g of vegetable fat.</p>
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<p>X-ray diffractograms of powders produced by spray-drying and coated by spray-chilling with 5, 10, and 15 g of spray-dried chasteberry extract per 50 g of vegetable fat.</p>
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<p>Scanning electronic micrographs (500× and 100× magnification) of particles produced by spray-drying and coated by spray-chilling; (<b>A</b>) particles produced with 5 g of spray-dried chasteberry extract per 50 g of vegetable fat and 500x magnification; (<b>B</b>) particles produced with 10 g of spray-dried chasteberry extract per 50 g of vegetable fat and 500× magnification; (<b>C</b>) particles produced with 15 g of spray-dried chasteberry extract per 50 g of vegetable fat and 500× magnification; (<b>D</b>) particles produced with 5 g of spray-dried chasteberry extract per 50 g of vegetable fat 100× magnification; (<b>E</b>) particles produced with 10 g of spray-dried chasteberry extract per 50 g of vegetable fat 100× magnification; (<b>F</b>) particles produced with 15 g of spray-dried chasteberry extract per 50 g of vegetable fat—100× magnification.</p>
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<p>Mass variation according to the temperature applied in samples produced with 5, 10, and 15 g of spray-dried chasteberry extract per 50 g of vegetable fat.</p>
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10 pages, 1914 KiB  
Article
Nitric Oxide and Small and Intermediate Calcium-Activated Potassium Channels Mediate the Vasodilation Induced by Apigenin in the Resistance Vessels of Hypertensive Rats
by Lislaine Maria Klider, Maria Luiza Fidelis da Silva, Gustavo Ratti da Silva, João Ricardo Cray da Costa, Marcia Alessandra Arantes Marques, Emerson Luiz Botelho Lourenço, Francislaine Aparecida dos Reis Lívero, Jane Manfron and Arquimedes Gasparotto Junior
Molecules 2024, 29(22), 5425; https://doi.org/10.3390/molecules29225425 - 18 Nov 2024
Viewed by 884
Abstract
Background: Apigenin (4′,5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). Methods: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin [...] Read more.
Background: Apigenin (4′,5,7-trihydroxyflavone), a flavonoid with potential cardiovascular benefits, has unclear mechanisms of action. This study investigates its effects on vascular function in Spontaneously Hypertensive Rats (SHRs). Methods: Mesenteric vascular beds (MVBs) were isolated from SHRs and perfused with increasing doses of apigenin after pre-contraction with phenylephrine. To explore the mechanisms, different MVBs were pre-perfused with antagonists and inhibitors, including indomethacin, L-NAME, and potassium channel blockers (tetraethylammonium, a non-specific potassium channel blocker; glibenclamide, an ATP-sensitive potassium channel blocker; 4-aminopyridine, a voltage-gated potassium channel blocker; charybdotoxin a selective intermediate-conductance calcium-activated potassium channel blocker; and apamin, a selective small-conductance calcium-activated potassium channel blocker). Results: Apigenin induced a dose-dependent reduction in perfusion pressure in MVBs with intact endothelium, an effect abolished by endothelium removal. L-NAME reduced apigenin-induced vasodilation by approximately 40%. The vasodilatory effect was blocked by potassium chloride and tetraethylammonium. The inhibition of small and intermediate calcium-activated potassium channels with charybdotoxin and apamin reduced apigenin-induced vasodilation by 50%, and a combination of these blockers with L-NAME completely inhibited the effect. Conclusions: Apigenin promotes vasodilation in resistance arteries through endothelial nitric oxide and calcium-activated potassium channels. These findings suggest that apigenin could have therapeutic potential in cardiovascular disease, warranting further clinical research. Full article
(This article belongs to the Special Issue Analyses and Applications of Phenolic Compounds in Food—2nd Edition)
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<p>Apigenin induces vasodilation in resistance arteries of rats. Molecular structure of apigenin (<b>A</b>). Effects of apigenin on the mesenteric vascular beds of WKY and SHRs (<b>B</b>,<b>C</b>). Typical representative record of the administration of acetylcholine (1 nmol) and apigenin (0.1, 0.3, and 1 µmol) in preparations of mesenteric vascular bed of SHRs (<b>D</b>). Values represent the mean ± standard error of the mean (<span class="html-italic">n</span> = 6 preparations). + <span class="html-italic">p</span> &lt; 0.05 compared with the previously administered dose. All experiments were performed in endothelium-intact preparations.</p>
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<p>The vasodilatory effects of apigenin are dependent on vascular endothelium and nitric oxide release. Vasodilatory action of apigenin in the presence (End+) and absence of endothelium (End-) are presented (<b>A</b>). Apigenin’s vasodilatory action was investigated in the presence of the nitric oxide synthase inhibitor (L-NAME) (<b>B</b>), regarding the formation of cGMP (<b>C</b>), or during the inhibition of the enzyme cyclooxygenase (indomethacin) (<b>D</b>). Values represent the mean ± standard error of the mean (<span class="html-italic">n</span> = 6 preparations). * <span class="html-italic">p</span> &lt; 0.05 compared with preparations in the presence of endothelium (<b>A</b>) or after treatment only with vehicle (<b>B</b>,<b>C</b>). + <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose.</p>
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<p>The vasodilatory effects of apigenin depend on potassium channels. Apigenin’s vasodilatory action was investigated in the presence of 40 mM KCl (<b>A</b>), tetraethylammonium (TEA) (<b>B</b>), glibenclamide (<b>C</b>), 4-aminopyridine (4-AP) (<b>D</b>), charybdotoxin (ChTx) (<b>E</b>), or apamin (Apm) (<b>F</b>). The results show the mean ± S.E.M. of six preparations per group. * Indicate <span class="html-italic">p</span> &lt; 0.05 compared with the effects of apigenin on the vehicle group. + indicates <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose. All experiments were performed in endothelium-intact preparations.</p>
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<p>The vasodilator effects of apigenin are dependent on the release of nitric oxide and the activation of potassium channels. Apigenin’s vasodilatory action was investigated in the presence of charybdotoxin (ChTx) plus apamin (Apm) (<b>A</b>), and charybdotoxin (ChTx) plus apamin (Apm) plus L-NAME (<b>B</b>). The results show the mean ± S.E.M. of six preparations per group. * Indicate <span class="html-italic">p</span> &lt; 0.05 compared with the effects of apigenin on the vehicle group. + indicates <span class="html-italic">p</span> &lt; 0.05 compared with the respective previous dose. All experiments were performed in endothelium-intact preparations.</p>
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16 pages, 3510 KiB  
Article
Effects of Baccharis dracunculifolia DC on an Innovative Animal Model of Cardiometabolic Syndrome
by Gustavo Ratti da Silva, Arianne Jung Kluck, Edilson Rodrigues Albuquerque, Lucas Pires Guarnier, Fernanda de Abreu Braga, Ester Pelegrini Silva, Karina Sposito Negrini, Juliana Aparecida Mendonça, Zilda Cristiani Gazim, Arquimedes Gasparotto Junior, João Tadeu Ribeiro-Paes and Francislaine Aparecida dos Reis Lívero
Pharmaceutics 2024, 16(11), 1446; https://doi.org/10.3390/pharmaceutics16111446 - 12 Nov 2024
Viewed by 1076
Abstract
Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions [...] Read more.
Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions are treated independently. This approach may be partially due to limited preclinical models to mimic the clinical conditions of CMS. Therefore, our study aims to present an innovative animal model of cardiometabolic syndrome and evaluate the effects of Baccharis dracunculifolia on the set of clinical alterations associated with the condition. Methods: Female Wistar rats were induced to develop diabetes, fed a cholesterol-enriched diet, and exposed to the smoke of 9 cigarettes/day for 6 weeks. During the last 2 weeks, the rats were treated with vehicle, B. dracunculifolia (30, 100, and 300 mg/kg), or a combination of simvastatin and insulin. At the end of the treatment, plasma lipid levels were measured, and the liver was analyzed histologically for hepatic lipid quantification and oxidative stress assessment. Results: Phytochemical analysis revealed seven phenolic acids and six flavonoids in the extract. B. dracunculifolia showed significant hepatoprotective effects, reducing AST and ALT levels and lowering both plasma and hepatic lipid levels. The extract also reversed hepatic steatosis and demonstrated antioxidant properties. Conclusions: These findings suggest that B. dracunculifolia may be a therapeutic option for the metabolic dysregulation present in CMS. Full article
(This article belongs to the Special Issue Alternative Model-Based Translational Drug Development)
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<p>The model of fatty liver disease associated with metabolism was generated by inducing diabetes, dyslipidemia, and smoking conditions in Wistar rats. The study lasted for 4 weeks and consisted of a baseline group [normoglycemic rats not exposed to risk factors and treated with vehicle (filtered water, 1 mL/kg, <span class="html-italic">n</span> = 6)] and five other groups exposed to risk factors and treated orally (gavage) in the last two experimental weeks with vehicle (filtered water, 1 mL/kg, negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> extract (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin (2.5 mg/kg) + insulin (6 IU, s.c., positive control group [SIM + INSU], <span class="html-italic">n</span> = 8). At the end of the treatment, the lipid-lowering and hepatoprotective effects of <span class="html-italic">B. dracunculifolia</span> were analyzed.</p>
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<p>Plasma levels of (<b>A</b>) glucose, (<b>B</b>) aspartate aminotransferase, and (<b>C</b>) alanine aminotransferase in normoglycemic, non-dyslipidemic, and non-smoker Wistar rats (basal group, <span class="html-italic">n</span> = 6) and diabetic, dyslipidemic, and smoker Wistar rats that were treated with vehicle (negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin (2.5 mg/kg) + insulin (6IU; SIM + INSU, <span class="html-italic">n</span> = 8). The data are expressed as mean ± SEM. <sup>a</sup> <span class="html-italic">p</span> &lt; 0.05, vs. basal; <sup>b</sup> <span class="html-italic">p</span> &lt; 0.05, vs. C−; <sup>c</sup> <span class="html-italic">p</span> &lt; 0.05, vs. SIM + INSU (one-way ANOVA followed by Bonferroni post hoc test).</p>
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<p>Plasma levels of (<b>A</b>) triglycerides and (<b>B</b>) cholesterol as well as hepatic levels of (<b>C</b>) triglycerides and (<b>D</b>) cholesterol in normoglycemic, non-dyslipidemic, and non-smoker Wistar rats (basal group, <span class="html-italic">n</span> = 6) and diabetic, dyslipidemic, and smoker Wistar rats that were treated with vehicle (negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin (2.5 mg/kg) + insulin (6IU; SIM + INSU, <span class="html-italic">n</span> = 8). n = 8/group. The data are expressed as mean ± SEM. <sup>a</sup> <span class="html-italic">p</span> &lt; 0.05, vs. basal; <sup>b</sup> <span class="html-italic">p</span> &lt; 0.05, vs. C−; <sup>c</sup> <span class="html-italic">p</span> &lt; 0.05, vs. SIM + INSU (one-way ANOVA followed by Bonferroni post hoc test).</p>
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<p>Relative (%) hepatic weight (<b>A</b>) and % of hepatic lipids (<b>B</b>). The study involved normoglycemic, non-dyslipidemic, and non-smoker Wistar rats (basal group, <span class="html-italic">n</span> = 6) as well as diabetic, dyslipidemic, and smoker Wistar rats treated with vehicle (negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin + insulin (SIM + INSU, <span class="html-italic">n</span> = 8). The data are shown as mean ± SEM. <sup>a</sup> <span class="html-italic">p</span> &lt; 0.05, vs. basal; <sup>b</sup> <span class="html-italic">p</span> &lt; 0.05, vs. C−; <sup>c</sup> <span class="html-italic">p</span> &lt; 0.05, vs. SIM + INSU (one-way ANOVA followed by Bonferroni post hoc test).</p>
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<p>Hepatic histopathological analysis with hematoxylin/eosin (<b>A</b>), Sudan Black (<b>B</b>), and grades of liver injury (<b>C</b>). The study involved normoglycemic, non-dyslipidemic, and non-smoker Wistar rats (basal group, <span class="html-italic">n</span> = 6) as well as diabetic, dyslipidemic, and smoker Wistar rats treated with vehicle (negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin + insulin (SIM + INSU, <span class="html-italic">n</span> = 8). In the histopathological analysis, black arrows indicate hepatic fatty degeneration (steatosis). The images were taken at 40× magnification.</p>
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<p>Reduced glutathione (<b>A</b>), superoxide dismutase (<b>B</b>), and lipoperoxidation (<b>C</b>). The study involved normoglycemic, non-dyslipidemic, and non-smoker Wistar rats (basal group, <span class="html-italic">n</span> = 6) as well as diabetic, dyslipidemic, and smoker Wistar rats treated with vehicle (negative control [C−], <span class="html-italic">n</span> = 8), <span class="html-italic">Baccharis dracunculifolia</span> (30, 100, and 300 mg/kg, <span class="html-italic">n</span> = 8), and simvastatin + insulin (SIM + INSU, <span class="html-italic">n</span> = 8). The data are shown as mean ± SEM. <sup>a</sup> <span class="html-italic">p</span> &lt; 0.05, vs. basal; <sup>b</sup> <span class="html-italic">p</span> &lt; 0.05, vs. C− (one-way ANOVA followed by Bonferroni post hoc test).</p>
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27 pages, 1397 KiB  
Article
Analysis of Adverse Reactions Associated with the Use of Crataegus-Containing Herbal Products
by Herman J. Woerdenbag, Melissa Ursidae, Corine Ekhart, Martina Schmidt, Annabella Vitalone and Florence P. A. M. van Hunsel
Pharmaceuticals 2024, 17(11), 1490; https://doi.org/10.3390/ph17111490 - 6 Nov 2024
Cited by 1 | Viewed by 1315
Abstract
Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. [...] Read more.
Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure. Full article
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<p>Structural formulas of typical constituents of <span class="html-italic">Crataegus</span>: vitexin (<b>left</b>), vitexin rhamnoside (<b>middle</b>) and procyanidine B2 (OPC) (<b>right</b>) [<a href="#B8-pharmaceuticals-17-01490" class="html-bibr">8</a>,<a href="#B40-pharmaceuticals-17-01490" class="html-bibr">40</a>].</p>
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<p>PRISMA flow diagram of included articles in the scoping review.</p>
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<p>The number of ICSRs (1527 in total) received by national pharmacovigilance centres included in VigiBase per year, from 1970 through 2023.</p>
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<p>Overview of the distribution of the ICSRs over the different types of <span class="html-italic">Crataegus</span> products used as included in VigiBase. The reports are first categorised into the use of a single- or multi-herb <span class="html-italic">Crataegus</span>-containing product and subsequently into the <span class="html-italic">Crataegus</span>-containing product as the only suspect or more than one product (including a <span class="html-italic">Crataegus</span>-containing product) being suspected to cause the adverse reaction.</p>
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24 pages, 1941 KiB  
Systematic Review
Effects of Arnica Phytotherapeutic and Homeopathic Formulations on Traumatic Injuries and Inflammatory Conditions: A Systematic Review
by Claudia-Crina Toma, Mariangela Marrelli, Monica Puticiu, Filomena Conforti and Giancarlo Statti
Plants 2024, 13(21), 3112; https://doi.org/10.3390/plants13213112 - 4 Nov 2024
Viewed by 3055
Abstract
Arnica L. genus (Asteraceae) comprises perennial herbs native to the temperate and boreal parts of the northern hemisphere. Arnica montana is the main species. It shows different biological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, and antitumor effects. The Arnica formulations are mainly [...] Read more.
Arnica L. genus (Asteraceae) comprises perennial herbs native to the temperate and boreal parts of the northern hemisphere. Arnica montana is the main species. It shows different biological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, and antitumor effects. The Arnica formulations are mainly used for pain management. This systematic review is aimed at summarizing the studies focusing on the use of Arnica products on pain and inflammatory signs due to traumatic injuries related to sport and surgical interventions as well as to arthritis and other inflammatory conditions. Both phytotherapeutic and homeopathic formulations are taken into account. This paper only includes manuscripts published in mainstream journals. A literature search from Scopus, Web of Science, and PubMed databases has been carried out using a combination of the keywords “Arnica”, “trauma”, “sport”, “injury”, “injuries”, and “pain”. According to the search strategy and inclusion criteria for this study, 42 eligible papers, focusing on both Arnica alone and formulations containing a mixture of plant extracts, have been finally selected. This review critically discusses the in vitro, in vivo, and clinical studies dealing with Arnica products, reporting both positive and negative outcomes, thus providing perspectives for future research on the plant pharmacological potential. Full article
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<p>Selection process of the eligible papers based on the PRISMA 2020 flow diagram.</p>
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<p>Papers included in this review distributed by year (created with MySLR).</p>
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<p>Word cloud highlighting the importance of keywords (Produced by MySLR platform).</p>
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21 pages, 5821 KiB  
Review
Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis
by Giovanni Tossetta, Sonia Fantone, Lucrezia Togni, Andrea Santarelli, Fabiola Olivieri, Daniela Marzioni and Maria Rita Rippo
Antioxidants 2024, 13(10), 1270; https://doi.org/10.3390/antiox13101270 - 18 Oct 2024
Cited by 8 | Viewed by 1714
Abstract
Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 [...] Read more.
Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis by modulating redox balance and inflammation of the periodontium. However, NRF2 expression is decreased in gingival tissues of patients with periodontitis while oxidative stress is significantly increased in this pathology. Oxidative stress and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory causing periodontal inflammation and favoring alveolar bone. In this review, we analyzed the current literature regarding the role of natural and synthetic compounds in modulating the NRF2/KEAP1 pathway in in vitro and in vivo models of periodontitis in order to evaluate new potential treatments of periodontitis that can improve the outcome of this disease. Full article
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<p>Pathogenesis of periodontitis. If gingivitis remains unresolved, there is a persistence of pathogens and inflammation that leads to different grades of periodontitis. CAL = clinical attachment loss; PD = probing depth.</p>
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<p>NRF2/KEAP1 signaling regulation. Under the basal condition, NRF2 is bound to the KEAP1/CUL3/RBX1 E3-Ub ligase complex that induces NRF2 proteasomal degradation. Under oxidant stimuli, ROS oxidate the cysteine residues of KEAP1, causing a conformational change that inhibits NRF2 ubiquitination/degradation. Since NRF2 avoids proteasomal degradation, it can migrate into the nucleus and bind ARE regions present in the upstream regulatory region (promoter) of several antioxidant genes, causing their transcription. ARE, antioxidant response element; Cul3, Cullin 3; E3, Ubiquitin ligase 3; KEAP1, Kelch Like ECH Associated Protein 1; NRF2, Nuclear Factor Erythroid 2-Related Factor 2; RBX1, RING box protein 1; Ub, Ubiquitin.</p>
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<p>Molecular structures of dehydrocostus lactone and hesperetin. The chemical structures of the compounds illustrated in this table have been taken from ChemSpider free database (<a href="https://www.chemspider.com" target="_blank">https://www.chemspider.com</a> (accessed on 30 September 2024)).</p>
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<p>Molecular structures of baicalein and magnolol. The chemical structures of the compounds illustrated in this figure have been taken from ChemSpider free database (<a href="https://www.chemspider.com" target="_blank">https://www.chemspider.com</a> (accessed on 30 September 2024)).</p>
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<p>Modulation of NRF2/KEAP1 signaling by phytotherapeutics in periodontitis. Phytotherapeutics (in light blue) increase NRF2 expression, favoring its nuclear translocation and binding to the ARE regions present in the promoter of antioxidant genes (NQO1, CAT, HO-1, SOD, etc.), inducing their transcription. The increased expression of HO-1 inhibits NF-κB activation, thus reducing inflammatory cytokines production (in green). The activation of NRF2 also increases GSH levels, reducing ROS levels and DNA damage (in blue). Moreover, the activation of NRF2 reduces cell senescence, osteoclast differentiation, and alveolar bone loss while favoring osteoblast differentiation, osteogenesis, and periodontal tissue repair (in red). ARE, antioxidant response element; CAT, catalase; GSH, glutathione; HO-1, Heme-oxygenase 1; IL, interleukin; NQO1, NAD(P)H:quinone oxidoreductase; NRF2, Nuclear Factor Erythroid 2-Related Factor 2; SOD, superoxide dismutase; TNF-α, Tumor Necrosis Factor-α.</p>
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