Search Results (23)

The use of metal nanoparticles is gaining popularity owing to their low cost and high efficacy. We focused on green synthesis of silver nanoparticles (AgNPs) using Tinospora cordifolia (Tc) leaf extracts. The structural characteristics of Tc nanoparticles (TcAgNPs) were determined using several advanced techniques. Pharmacological activities, including antioxidant, anti-inflammatory, and antibacterial properties, were evaluated through in vitro studies. In the results, the change in sample color from yellow to brown after adding silver nitrate revealed the synthesis of TcAgNPs, and the UV–visible spectrum confirmed their formation. X-ray diffraction studies showed the presence of reducing agents and the crystalline nature of the nanoparticles. Fourier-transform infrared spectra revealed the existence of essential secondary metabolites, which act as reducing/capping agents and stabilize the nanoparticles. The size of the TcAgNPs was small (range 36–168 nm) based on the measurement method. Their negative zeta potential (−32.3 mV) ensured their stability in water suspensions. The TcAgNPs were predominantly spherical, as evidenced from scanning electron microscopy and transmission electron microscopy. Atomic absorption spectroscopy data further revealed the conversion of silver nitrate into silver nanoparticles, and thermogravimetric analysis data showed their thermal stability. The TcAgNPs showed significant DPPH/ABTS radical scavenging ability in a concentration-dependent manner (25–100 µg/mL). Membrane lysis assays showed an effective anti-inflammatory activity of the TcAgNPs. Furthermore, the TcAgNPs showed potent antibacterial effects against multidrug-resistant bacteria (Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, and Staphylococcus aureus). The TcAgNPs treatment also exhibited antibiofilm activity against bacterial strains, in a concentration-dependent manner. Our findings demonstrate the structural characteristics of green-synthesized TcAgNPs using advanced techniques. TcAgNPs can be developed as potential antioxidant, anti-inflammatory, and antibacterial drugs. Full article

Background/Objectives: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pathways. The metabolites of these pathways play a role in the biological reward system. Addictive substances have been shown to cause imbalances in the ratios of these metabolites. With current treatment and therapeutic options being suboptimal, identifying biochemical mechanisms that are impacted during the use of addictive substances can provide alternative options for treatment or drug discovery. Methods: A systematic literature search was conducted to identify studies evaluating the relationship between substance use disorder and tryptophan metabolism through the kynurenine pathway. A total of 32 articles meeting eligibility criteria were used to review the relationship between the kynurenine pathway, tryptophan breakdown, and addictive substances. Results: The use of addictive substances dysregulates tryptophan metabolism and kynurenine metabolite concentrations. This imbalance directly affects the dopamine reward system and is thought to promote continued substance use. Conclusions: Further studies are needed to fully evaluate the metabolites of the kynurenine pathway, along with other options for treatment to repair the metabolite imbalance. Several possible therapeutics have been identified; drugs that restore homeostasis, such as Ro 61-8048 and natural products like Tinospora cordifolia or Decaisnea insignis, are promising options for the treatment of substance use disorder. Full article

Nanoemulsions are gaining interest in a variety of products as a means of integrating easily degradable bioactive compounds, preserving them from oxidation, and increasing their bioavailability. However, preparing stable emulsion compositions with the desired characteristics is a difficult task. The aim of this study was to encapsulate the Tinospora cordifolia aqueous extract (TCAE) into a water in oil (W/O) nanoemulsion and identify its critical process and formulation variables, like oil (27–29.4 mL), the surfactant concentration (0.6–3 mL), and sonication amplitude (40% to 100%), using response surface methodology (RSM). The responses of this formulation were studied with an analysis of the particle size (PS), free fatty acids (FFAs), and encapsulation efficiency (EE). In between, we have studied a fishbone diagram that was used to measure risk and preliminary research. The optimized condition for the formation of a stable nanoemulsion using quality by design was surfactant (2.43 mL), oil concentration (27.61 mL), and sonication amplitude (88.6%), providing a PS of 171.62 nm, FFA content of 0.86 meq/kg oil and viscosity of 0.597 Pa.s for the blank sample compared to the enriched TCAE nanoemulsion with a PS of 243.60 nm, FFA content of 0.27 meq/kg oil and viscosity of 0.22 Pa.s. The EE increases with increasing concentrations of TCAE, from 56.88% to 85.45%. The RSM response demonstrated that both composition variables had a considerable impact on the properties of the W/O nanoemulsion. Furthermore, after the storage time, the enriched TCAE nanoemulsion showed better stability over the blank nanoemulsion, specially the FFAs, and the blank increased from 0.142 to 1.22 meq/kg oil, while TCAE showed 0.266 to 0.82 meq/kg. Full article

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview. Full article

Natural products with curative properties are gaining immense popularity in scientific and food research, possessing no side effects in contrast to other drugs. Guduchi, or Tinospora cordifolia, belongs to the menispermaceae family of universal drugs used to treat various diseases in traditional Indian literature. It has received attention in recent decades because of its utilization in folklore medicine for treating several disorders. Lately, the findings of active phytoconstituents present in herbal plants and their pharmacological function in disease treatment and control have stimulated interest in plants around the world. Guduchi is ethnobotanically used for jaundice, diabetes, urinary problems, stomachaches, prolonged diarrhea, skin ailments, and dysentery. The treatment with Guduchi extracts was accredited to phytochemical constituents, which include glycosides, alkaloids, steroids, and diterpenoid lactones. This review places emphasis on providing in-depth information on the budding applications of herbal medicine in the advancement of functional foods and nutraceuticals to natural product researchers. Full article

Despite the fact that there are many studies related to the adaptogenic and pro-healthy activities of plant-based compounds, there are some adaptogenic plants whose activities are not fully known, especially those coming from the wild regions of Asia, Africa, and South America. The aim of these studies was to examine the contents of non-nutritional compounds, such as polyphenols, flavonoids, and phenolic acids in ten adaptogenic species (Astragalus membranaceus (AM), Uncaria rhynchophylla (UR), Polygonum multiflorum (PM), Angelica sinensis (AS), Andrographis paniculatea (AP), Tinospora cordifolia (TC), Uncaria tomentosa (UT), Pfaffia paniculate (PP), Sutherlandia frutescens (SF), and Rhaponticum carthamoides (RC)). Considering biological activity, their antioxidant (DPPH, ABTS, FRAP, and ferrous-ion-chelating ability assays), anti-acetylcholinesterase, anti-hyaluronidase, and anti-tyrosinase activities were evaluated. The richest in polyphenols, flavonoids, and phenolic acids was UR (327.78 mg GAE/g, 230.13 mg QE/g, and 81.03 mg CA/g, respectively). The highest inhibitions of acetylcholinesterase, hyaluronidase, and tyrosinase were observed for TC, UR, and PM, respectively. In the case of antioxidant properties, extract from PM appeared to most strongly reduce DPPH, extract from UR inhibited ABTS, and extract from SF showed the best chelating properties. It should be noted that a particularly interesting plant was Ulcaria rhynchophylla. The results mean that there were compounds in UR with broad biological activities, and this species should be explored in more detail. Additionally, our results justify the traditional use of these species in the nutripharmacological or ethnopharmacological care systems of different regions. Full article

Background: The plant Tinospora cordifolia (TC), traditionally known as guduchi or giloy, is used for a number of health conditions as a nutritional supplement and rejuvenation medicine. Its nutritional supplementary products are traditionally recommended for a wide range of health issues, including diabetes, menstruation discomfort, fever, obesity, inflammation, and more. Unfortunately, there has not been extensive research into its effectiveness in treating or managing insulin resistance, lipid and carbohydrate metabolism, hormonal imbalance, and metabolic syndrome-associated polycystic ovary syndrome (PCOS). Methods: Consequently, the present study was designed to induce insulin resistance, dyslipidemia, hormonal abnormality, hyperglycemia, and menstrual disturbance of PCOS using dehydroepiandrosterone (DHEA) in mice and study the effect of oral TC extracts on these factors by using ancient and modern technologies. During the 21-day study, 6 mg/100 g/day of DHEA was given to female mice. Levels of glucose, insulin, lipids, and hormones were estimated. In addition to being seen with the naked eye, the morphological and microscopic changes were also observed on histology slides. Results: The study outcomes show that pretreatment with TC preparations significantly improved biochemical and histological abnormalities in female mice. Diestrus phase was only observed in DHEA-treated animals, while cornified epithelial cells were present in TC-treated mice. Pretreatment with TC satva showed significant (p < 0.001) reductions in body weight compared to placebo. Fasting blood glucose, 1-h OGTT, and 2-h OGTT levels were all significantly lower in TC satva- and oil-treated animals in comparison to the disease control group (p < 0.001). Treatment with TC extracts resulted in a normalization of estradiol, progesterone, and testosterone levels (p < 0.05). Treatment with TC extract improved lipid profiles (p < 0.001), LH/FSH ratios (p < 0.01), fasting insulin levels (p < 0.001), HOMA-IR (p < 0.001), HOMA-Beta (p < 0.001), and QUICKI (p < 0.001). Both macroscopic and microscopic alterations were seen to be restored after TC extract treatment. After being treated with TC satva, oil, and hydroalcoholic extract, the severity of PCOS decreased by 54.86%. Conclusions: These findings lead us to the conclusion that TC extracts and satva as nutritional supplements are useful for treating PCOS and associated symptoms. It is recommended that additional research be conducted to determine the molecular mechanism of action of TC nutritional supplements on PCOS-related changes in metabolic profiles. We also recommend further clinical studies to explore the clinical efficacy and effectiveness of TC nutritional supplements in treating and/or managing PCOS. Full article

The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5′ AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms. Full article

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia—a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal—using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2. Full article

Antimicrobial resistance has posed a serious health concern worldwide, which is mainly due to the excessive use of antibiotics. In this study, gold nanoparticles synthesized from the plant Tinospora cordifolia were used against multidrug-resistant Pseudomonas aeruginosa. The active components involved in the reduction and stabilization of gold nanoparticles were revealed by gas chromatography–mass spectrophotometry(GC-MS) of the stem extract of Tinospora cordifolia. Gold nanoparticles (TG-AuNPs) were effective against P. aeruginosa at different concentrations (50,100, and 150 µg/mL). TG-AuNPs effectively reduced the pyocyanin level by 63.1% in PAO1 and by 68.7% in clinical isolates at 150 µg/mL; similarly, swarming and swimming motilities decreased by 53.1% and 53.8% for PAO1 and 66.6% and 52.8% in clinical isolates, respectively. Biofilm production was also reduced, and at a maximum concentration of 150 µg/mL of TG-AuNPs a 59.09% reduction inPAO1 and 64.7% reduction in clinical isolates were observed. Lower concentrations of TG-AuNPs (100 and 50 µg/mL) also reduced the pyocyanin, biofilm, swarming, and swimming. Phenotypically, the downregulation of exopolysaccharide secretion from P. aeruginosa due to TG-AuNPs was observed on Congo red agar plates Full article

The present work aimed to biofabricate copper oxide nanoparticles (CuO NPs) using Tinospora cordifolia leaf extract. The biofabricated CuO NPs were treated against the malarial parasite of chloroquine-resistant Plasmodium falciparum (INDO) and the antilarval efficacy was evaluated against the malaria vector Anopheles stephensi and dengue vector Aedes aegypti. The prominence at 285 nm in the UV–visible spectrum helped to identify the produced CuO NPs. Based on the XRD patterns, the concentric rings correspond to reflections at 38.26° (111), 44.11° (200), 64.58° (220), and 77.34° (311). These separations are indicative of CuO’s face-centered cubic (fcc) structure. The synthesized CuO NPs have FTIR spectra with band intensities of 3427, 2925, 1629, 1387, 1096, and 600 cm⁻¹. The absorbance band at 3427 cm⁻¹ is known to be associated with the stretching O-H due to the alcoholic group. FTIR proved that the presence of the -OH group is responsible for reducing and capping agents in the synthesis of nanoparticles (NPs). The synthesized CuO NPs were found to be polymorphic (oval, elongated, and roughly spherical) in form with a size range of 11–47 nm and an average size of 16 nm when the morphology was examined using FESEM and HRTEM. The highest antiplasmodial efficacy against the chloroquine-resistant strain of P. falciparum (INDO) was found in the synthesized CuO NPs, with LC₅₀ values of 19.82 µg/mL, whilst HEK293 cells are the least toxic, with a CC₅₀ value of 265.85 µg/mL, leading to a selectivity index of 13.41. However, the antiplasmodial activity of T. cordifolia leaf extract (TCLE) and copper sulfate (CS) solution showed moderate activity, with LC₅₀ values of 52.24 and 63.88 µg/mL, respectively. The green synthesized NPs demonstrated extremely high antilarval efficacy against the larvae of An. stephensi and Ae. aegypti, with LC₅₀ values of 4.06 and 3.69 mg/L, respectively. Full article

In the present study, novel genomic-SSR (g-SSR) markers generated in our laboratory were used to characterize Tinospora cordifolia and related species. The g-SSR marker was also compared with EST-SSR and SCoT markers used earlier in our laboratory to assess the genetic diversity of T. cordifolia. A total of 26 accessions of T. cordifolia and 1 accession each of Tinospora rumphii and Tinospora sinensis were characterized using 65 novel g-SSR markers. A total of 125 alleles were detected with 49 polymorphic g-SSR markers. The number of alleles per locus varied from 1–4 with a mean value of 2.55 alleles per locus. Mean PIC, gene diversity, and heterozygosity were estimated to be 0.33, 0.41, and 0.65, respectively. The two species, namely T. rumphii and T. sinensis, showed cross-species transferability of g-SSRs developed in T. cordifolia. The success rate of cross-species transferability in T. rumphii was 95.3% and 93.8% in T. sinensis, proving the usefulness of this marker in genetic diversity studies of related species. The Tinospora accessions were also used for molecular characterization using SCoT and EST-SSR markers and compared for genetic diversity and cross-species transferability. The PIC, gene diversity, heterozygosity, and principal coordinate analysis showed that g-SSR is the better maker for a genetic diversity study of T. cordifolia. Additionally, high cross-species transferability of g-SSRs was found (95.3% and 93.8%) compared to EST-SSRs (68.8% and 67.7%) in T. rumphii and T. sinensis, respectively. Full article

Cerebral malaria (CM) is a severe manifestation of parasite infection caused by Plasmodium species. In 2018, there were approximately 228 million malaria cases worldwide, resulting in about 405,000 deaths. Survivors of CM may live with lifelong post-CM consequences apart from an increased risk of childhood neurodisability. EphA2 receptors have been linked to several neurological disorders and have a vital role in the CM-associated breakdown of the blood–brain barrier. Molecular docking (MD) studies of phytochemicals from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis, Ocimum basilicum, and the native ligand ephrin-A were conducted to identify the potential blockers of the EphA2 receptor. The software program Autodock Vina 1.1.2 in PyRx-Virtual Screening Tool and BIOVIA Discovery Studio visualizer was used for this MD study. The present work showed that blocking the EphA2 receptor by these phytochemicals prevents endothelial cell apoptosis by averting ephrin-A ligand-expressing CD8+ T cell bioadhesion. These phytochemicals showed excellent docking scores and binding affinity, demonstrating hydrogen bond, electrostatic, Pi-sigma, and pi alkyl hydrophobic binding interactions when compared with native ligands at the EphA2 receptor. The comparative MD study using two PDB IDs showed that isocolumbin, carnosol, luteolin, and taraxasterol have better binding affinities (viz. −9.3, −9.0, −9.5, and −9.2 kcal/mol, respectively). Ocimum basilicum phytochemicals showed a lower docking score but more binding interactions than native ligands at the EphA2 receptor for both PDB IDs. This suggests that these phytochemicals may serve as potential drug candidates in the management of CM. We consider that the present MD study provides leads in drug development by targeting the EphA2 receptor in managing CM. The approach is innovative because a role for EphA2 receptors in CM has never been highlighted. Full article

Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, or rigid. As cardiomyopathy worsens, the heart becomes weaker and is unable to conduct the right amount of blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or arrhythmias. Chronic diabetes is one of the instigating factors behind the etiology of this cardiac complication. Type-II diabetes is associated with impaired glucose metabolism that increases the dependence of a diabetic heart on fatty acid oxidation to meet its functional demands, resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction that finally gives way to heart failure. The increasing diabetic population with cardiac disorders and the ironically decreasing trend in newer medications to counter this complication leave us at a crossroads for pharmacological management of diabetic cardiomyopathy. Keeping this in view, the present study proclaims a newly developed polyherbal combination (PHC) with three herbs, namely Tinospora cordifolia, Withania somnifera and Boerhavia diffusa based in olive oil and administered in fixed dose (PHC-6 and PHC-10) to screen its cardioprotective potential against a well-established experimental model for diabetic cardiomyopathy. The three herbs mentioned have been known through the traditional literature for their antidiabetic and cardioprotective roles, hence they became the obvious choice. The study follows an experimental model proposed by Reed et al., where the capacity of the β-cell is unobtrusively impeded without totally compromising insulin release, bringing about a moderate disability in glucose resilience. Various sophisticated parameters, namely intraventricular septum thickness of hearts, Western blot of α/β- MHC monoclonal antibody (Ab), cardiac pyruvate dehydrogenase (PDH) activity, medium chain acyl coenzyme A dehydrogenase (MCAD) enzyme, etc. showed promising results where treatment with PHC (PHC-6 and PHC-10) significantly (*** p < 0.001 and **** p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group. Full article

Tinospora cordifolia, commonly known as “Giloe” in India, is a shrub belonging to the family Menispermaceae. It is an important medicinal plant known for its antipyretic, anti-inflammatory, antispasmodic, and antidiabetic properties and is used in the treatment of jaundice, gout, and rheumatism. Despite its economic importance, the limited information related to its genomic resources prohibits its judicious exploitation through molecular breeding or biotechnological approaches. In this study, we generated a meta-transcriptome assembly of 43,090 non-redundant transcripts by merging the RNASeq data obtained from Roche 454 GS-FLX, and Illumina platforms, and report the first transcriptome-based database for simple sequence repeats and transcription factors (“TinoTranscriptDB” (Tinospora cordifolia Transcriptome Database)). We annotated 26,716 (62%) of the total transcripts successfully from National Center for Biotechnology Information non-redundant protein (NCBI-NR), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Swiss-Prot, and Pfam databases. This database contains information of 2620 perfect simple sequence repeats (P-SSRs) with a relative abundance of 340.12 (loci/Mb), and relative density of 6309.29 (bp/Mb). Excluding mono-nucleotides, the most abundant SSR motifs were tri-nucleotides (54.31%), followed by di-nucleotides (37.51%), tetra-nucleotides (4.54%), penta-nucleotides (3.16%) and hexa-nucleotides (0.45%). Additionally, we also identified 4,311 transcription factors (TFs) and categorized them into 55 sub-families. This database is expected to fill the gap in genomic resource availability in T. cordifolia and thus accelerate molecular breeding and related functional and other applied studies aimed towards genetic improvements of T. cordifolia and related species. Full article