Process Optimization of Tinospora cordifolia Extract-Loaded Water in Oil Nanoemulsion Developed by Ultrasound-Assisted Homogenization.

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.

Anti-dengue therapeutic potential of Tinospora cordifolia and its bioactives.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue is one of the most prevalent mosquito-borne viral infections. Moreover, due to the absence of appropriate curative and preventive measures against it, the mortality rate is increasing alarmingly. However, remarkable docking and clinical advances have been achieved with plant-based natural and conventional therapeutics. Tinospora cordifolia is one of the highly explored panaceas at the local level for its effective anti-dengue formulations. AIM OF THE STUDY: The present article aims for critical assessment of the data available on the anti-dengue therapeutic use of T. cordifolia. Efforts have also been made on the clinical and in-silico anti-dengue efficacy of this plant. The phytochemistry and the antiviral machinery of the plant are also emphasized. MATERIALS AND METHODS: The present article is the outcome of the literature survey on the anti-dengue effect of T. cordifolia. A literature survey was conducted from 2011 to 2024 using different databases with appropriate keywords. RESULTS: The present study confirms the anti-dengue potential of T. cordifolia. The plant can suppress the initiation of 'cytokine storm', vascular leakage and inhibition of various structural and NS proteins to exert its anti-dengue potential. Berberine and magnoflorine phytocompounds were highly explored for their anti-dengue potential. CONCLUSIONS: The present study concluded that T. cordifolia serves as an effective therapeutic agent for treating dengue. Further in-silico and clinical studies are needed so that stable, safe and efficacious anti-dengue drug can be developed. Besides, a precise antiviral mechanism of T. cordifolia against DENV infection is still needed.

Structural Revision of Tinotufolins from Tinospora crispa Leaves Guided by Empirical Rules and DFT Calculations.

Clerodane diterpenes are a class of secondary metabolites that can be classified into four types according to the configuration of the H3-19/H-10-H3-17/H3-20 fragment, i.e., trans-cis (TC), trans-trans (TT), cis-cis (CC), and cis-trans (CT). Tinotufolins A-C and E (1a-3a and 5a), isolated from the leaves of Tinospora crispa, were previously elucidated as CT-type clerodanes; however, our established 13C NMR-based empirical rules and density functional theory calculations suggested that these clerodanes belong to the CC type. Therefore, tinotufolins A-F (1-6) were reisolated from the leaves of T. crispa, along with an undescribed compound 7 and known compounds 8-11, and their structures were established by extensive spectroscopic analyses. The structures of tinotufolins A-C and E were revised to CC-type 1-3 and 5, and undescribed compound 7 was established as a CC-type clerodane. The present study demonstrates that empirical rules and calculations can efficiently identify and revise erroneous structures in clerodane diterpenes.

Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AIM: The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. METHODS: Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. RESULTS: The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20ß-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20ß-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. CONCLUSION: T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.

Development and Validation of Novel Quality Evaluation Methods to Differentiate Two Closely Related Species of Tinospora: A Rapid HPTLC- and HPLC-Based Assessment with MS/MS Characterization.

BACKGROUND: The sympatric occurrence of the species that often resulted in different gatherings of plant material, ambiguous history on traditional use, and taxonomic flux due to similarities within the Tinospora (Menispermaceae) taxa are some of the reasons that triggered the necessity to develop robust analytical methods for efficient QC, especially to recognize dry and powder forms. OBJECTIVE: To develop novel HPTLC-based fingerprinting of two closely resembling Tinospora species followed by HPTLC-MS analysis and identification of compounds differentiating Tinospora crispa (TCP) and Tinospora cordifolia (TCR) and a rapid and quantitative assessment by HPLC with a photodiode array detector (HPLC-PDA) with MS/MS characterization of specific TCP and TCR analytical markers. METHODS: An HPTLC-based method was developed using chloroform-toluene-methanol-formic acid (7 + 4 + 2 + 0.2, by volume). The TCP compounds could be distinguished and isolated using successive column chromatography with complete characterization. Further these used in the reverse phase (RP)-HPLC-PDA coupled with LC-ESI (electrospray ionization)-MS/MS to quantify and confirmation in TCP and TCR. RESULTS: The fingerprinting showed distinct bands in TCP stems, confirmed as clerodane- furanoditerpenoids with indirect profiling by the HPTLC-MS technique. Systematic isolation confirmed these compounds as borapetosides B and E. Thus, the RP-HPLC-PDA method was developed for these borapetosides B and E, with tinosporide to differentiate these two species. The quantitation method was well validated with good linearity (r2 >0.99) with sensitive LOD (0.49-3.71 mcg/mL) and LOQ (1.48-11.23 mcg/mL) with recoveries of 92.34-96.19%. CONCLUSION: A novel, validated HPLC-PDA method showed good resolution and reliability (up to 1% adulteration) in quantification for targeted major analytical markers from TCP to differentiate TCR. Thus, HPTLC and HPLC-PDA-based techniques are helpful with MS/MS-based characterization to identify and quantify these analytical markers from TCP (borapetoside B and E) and TCR (tinosporide) in dry and powder form. HIGHLIGHTS: This article reports on the systemic use of HPTLC-MS for separating and identifying analytical markers in Tinospora species, distinguishing TCR and TCP with quantitative HPLC-PDA and MS/MS assessment.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

Exploration of the main active metabolites from Tinospora crispa (L.) Hook. f. & Thomson stem as insulin sensitizer in L6.C11 skeletal muscle cell by integrating in vitro, metabolomics, and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. AIM OF THE STUDY: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. MATERIALS AND METHODS: We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. RESULTS: The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. CONCLUSIONS: Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.

Unveiling Various Facades of Tinospora cordifolia Stem in Food: Medicinal and Nutraceutical Aspects.

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.

Tinospora cordifolia Miers enhances the immune response in mice immunized with JEV-vaccine: A network pharmacology and experimental approach.

BACKGROUND: Tinospora cordifolia Miers. (TC) (Giloya/Guduchi) is a native Indian herb, reported for its wide array of medicinal activities including immunomodulatory activity. However, the exact pharmacological mechanism of TC as an immunomodulatory agent remains unclear. Central to this, to the best of our knowledge, no study has explored the immunoadjuvant potential of TC in response to the Japanese encephalitis (JE) vaccines. PURPOSE: The study aims to explore the immunoadjuvant potential of TC ethanolic extract in response to the JE vaccine and illustrates its potential mechanism of immunomodulation using an integrated approach of network pharmacology and in-vivo experimental study. STUDY DESIGN AND METHODS: Initially, the extract was prepared and the components of TC were identified through high-resolution liquid chromatography mass spectrometry (HR-LC/MS). The compounds were then screened for network pharmacology analysis. Next, the drug and disease targets were identified and the network was constructed using Cytoscape 3.7.2 to obtain different signalling pathways of TC in JEV. We then evaluated the immunoadjuvant potential of TC ethanolic extract in mice immunized with inactivated JE vaccine (SA-14-14-2 strain). BALB/c mice were supplemented with TC extract (30 and 100 mg/kg, i.g.), daily for 56 days, marked with immunization on 28th day of the study, by JE vaccine. Blood was collected for flow cytometry and haematological analysis (total and differential cell counts). The surface expression of immune-cell markers (CD3+, CD4+, CD19+, CD11c+, CD40+) were evaluated on day 0 (pre-immunization), day 14 and 28 post-immunization. Additionally, inflammatory cytokines (IFN-γ+/IL-17A+) were evaluated post-14 and 28 days of immunization. RESULTS: The HR-LC/MS analysis identified the presence of glycosides, terpenoids, steroids and alkaloids in the TC extract. Through network analysis, 09 components and 166 targets were obtained, including pathways that involve toll-like receptor signalling, pattern-recognition receptor signalling, cytokine receptor and cytokine mediated signalling, etc. The in-vivo results showed that preconditioning with TC ethanolic extract significantly elevated the haematological variables (leucocyte count) as well as the surface expression of CD markers (B and T cell subsets) on day 0 (pre-immunization), day 14 and 28 post-immunization. Furthermore, preconditioning of TC demonstrated a dose-dependant augmentation of immune cells (CD3+, CD4+, CD19+, CD11c+) and inflammatory cytokines (IFN-γ+/IL-17A+) on day 14 and 28 post-immunization when compared to vaccine alone group. CONCLUSION: Results showed that preconditioning with TC extract before immunization might play a potential role in enhancing the cell-mediated as well as humoral immunity. Altogether, the combinatorial approach of network pharmacology and in-vivo animal experimentation demonstrated the immunoadjuvant potential of TC in response to JEV vaccine.

Diterpenoids and Their Glycosides from the Stems of Tinospora crispa with Beta-Cell Protective Activity.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.

Therapeutic Application, Phytoactives and Pharmacology of Tinospora cordifolia: An Evocative Review.

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.

A Case Report of Acute Hepatitis Involving the Medicinal Herb Tinospora cordifolia Along with Other Variables.

This is a 54-year-old woman from Germany of central European origin who developed an acute hepatitis while orally taking Ayurvedic herbal remedies, among those was the medicinal herb Tinospora cordifolia. She took the plant powders from July 1, 2021, to October 1, 2021, with the intention of relieving the symptoms of her subjectively irritated gastrointestinal tract. The patient's main symptoms of acute hepatitis were progressively increasing general fatigue, nausea, and exhaustion. During an inpatient hospital admission from November 4, 2021, to November 9, 2021, she was under clinical observation, but no specific therapeutic measures were deemed necessary; however, blood chemistry showed an acute toxic hepatitis. There was no clinical or laboratory evidence of acute liver failure. Aminotransferase values decreased to normal values on December 14, 2021, by themselves. This case report contributes to the ongoing discussion about the potential risks of triggering an acute hepatitis due to the intake of herbal remedies from the Tinospora genus in rare cases, differentiating other involved risk factors. The case also shows that causality assignments are not trivial in the context of multivariate clinical scenarios. In the case of known hepatic metabolism-associated risk factors, T. cordifolia should be used with more caution based on available case reports. At the same time, no hasty and exaggerated prejudgments should be made about this medicinal herb, which has been very successfully used in traditional South Asian systems of medicine for many centuries.

Exploration of bioactive molecules from Tinospora cordifolia and Actinidia deliciosa as an immunity modulator via molecular docking and molecular dynamics simulation study.

Tinospora cordifolia and Actinidia deliciosa are the widely used plant in Ayurvedic systems of medicine. Both plants are well known for their immunomodulatory activity. In the current study, in silico exploration was performed using advanced computational techniques such as molecular docking and molecular dynamics simulation approach. Bioactive molecules from the Tinospora cordifolia and Actinidia deliciosa were docked against the Human IL-2. Out of all the docked bioactive molecules, Pygenic acid-B (PubChem CID:146157192) showed the highest negative binding affinity.

The combined analgesic, sedative, and anti-gastric cancer mechanisms of Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo based on integrated ethnopharmacological data.

ETHNOPHARMACOLOGY RELEVANCE: As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear. AIM OF THE STUDY: This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy. MATERIALS AND METHODS: The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses. RESULTS: Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro. CONCLUSIONS: TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.

Tinospora cordifolia (Willd.) Hook.f. & Thomson polysaccharides: A review on extraction, characterization, and bioactivities.

Human awareness of the need for health and wellness practices that enhance disease resilience has increased as a result of recent health risks. Plant-derived polysaccharides with biological activity are good candidates to fight diseases because of their low toxicity. Tinospora cordifolia (Willd.) Hook.f. & Thomson polysaccharides extract from different plant parts have been reported to possess significant biological activity such as anti-oxidant, anti-cancer, immunomodulatory, anti-diabetic, radioprotective and hepatoprotective. Several extraction and purification techniques have been used to isolate and characterize T. cordifolia polysaccharides. Along with hot-water extraction (HWE), other novel techniques like microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), pulsed electric field (PEF), supercritical-fluid extraction (SFE), and enzyme-assisted extraction (EAE) are used to extract T cordifolia polysaccharides. SFE is a revolutionary technology that gives the best yield and purity of low-molecular-weight polysaccharides. According to the findings, polysaccharides extracted and purified from T. cordifolia have a significant impact on their structure and biological activity. As a result, the methods of extraction, structural characterization, and biological activity of T. cordifolia polysaccharides are covered in this review. Research on T. cordifolia polysaccharides and their potential applications will benefit greatly from the findings presented in this review.

Evaluation of phytoconstituents of Tinospora cordifolia against K417N and N501Y mutant spike glycoprotein and main protease of SARS-CoV-2- an in silico study.

Coronavirus disease 2019 (COVID-19) caused appalling conditions over the globe, which is currently faced by the entire human population. One of the primary reasons behind the uncontrollable situation is the lack of specific therapeutics. In such conditions, drug repurposing of available drugs (viz. Chloroquine, Lopinavir, etc.) has been proposed, but various clinical and preclinical investigations indicated the toxicity and adverse side effects of these drugs. This study explores the inhibition potency of phytochemicals from Tinospora cordifolia (Giloy) against SARS CoV-2 drugable targets (spike glycoprotein and Mpro proteins) using molecular docking and MD simulation studies. ADMET, virtual screening, MD simulation, postsimulation analysis (RMSD, RMSF, Rg, SASA, PCA, FES) and MM-PBSA calculations were carried out to predict the inhibition efficacy of the phytochemicals against SARS CoV-2 targets. Tinospora compounds showed better binding affinity than the corresponding reference. Their binding affinity ranges from -9.63 to -5.68 kcal/mole with spike protein and -10.27 to -7.25 kcal/mole with main protease. Further 100 ns exhaustive simulation studies and MM-PBSA calculations supported favorable and stable binding of them. This work identifies Nine Tinospora compounds as potential inhibitors. Among those, 7-desacetoxy-6,7-dehydrogedunin was found to inhibit both spike (7NEG) and Mpro (7MGS and 6LU7) proteins, and Columbin was found to inhibit selected spike targets (7NEG and 7NX7). In all the analyses, these compounds performed well and confirms the stable binding. Hence the identified compounds, advocated as potential inhibitors can be taken for further in vitro and in vivo experimental validation to determine their anti-SARS-CoV-2 potential.Communicated by Ramaswamy H. Sarma.

Constituents of Tinospora sinensis and their nitric oxide inhibitory activities.

One new phenylpropanoid glycoside, tinosinen A (1) and 13 known compounds, tinosinen (2), citrusin B (3), picraquassioside C (4), erythro-guaiacylglycerol-ß-O-4'-coniferyl alcohol (5), erythro-guaiacylglycerol-8-O-4'-(sinapyl alcohol) ether (6), erythro-syringylglycerol-8-O-4'-(sinapyl alcohol) ether (7), seco-isolariciresinol 9-O-D-ß-glucopyranoside (8), tinosposide A (9), pinoresinol-4'-O-ß-D-glucopyranoside (10), syringaresinol-4'-O-ß-D-glucopyranoside (11), pinoresinol (12), syringaresinol (13), and lirioresino-ß-dimethyl ether (14) were isolated from the stems of Tinospora sinensis (Lour.) Merr. Their structures were established by detailed spectroscopic studies and comparisons with those reported in the literature. Compound 13 showed significant inhibitory NO production (IC50 value of 38.53 ± 1.90 µM) in RAW264.7 macrophages, LPS-stimulated. Compounds 3-7, 11, 12, and 14 inhibited NO production with IC50 values ranging from 38.53 to 99.07 µM.

Therapeutic Application, Phytoactives and Pharmacology of Tinospora cordifolia: An Evocative Review / 中国结合医学杂志

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.

Isolation, Structure Characterization, Total Synthesis and Biological Evaluation of Cinnamic Acid Derivatives from Tinospora sagittata.

Thirteen cinnamic acid derivatives (1-13), including six formerly unreported hybrids incorporating different short-chain fatty acid esters (1-6), have been obtained and structurally elucidated from an ethnological herb Tinospora sagittata. The structures of them have been established by spectroscopic data analyses and NMR comparison with known analogs, while those of 1, 2, 4 and 6 have been further supported by total synthesis, and it is the first report of this type of metabolites from the title species. All the isolates have been assessed in an array of bioassays encompassing cytotoxic, antibacterial, anti-inflammatory, antioxidant, as well as α-glucosidase and HDAC1 inhibitory models. Compound 7 showed significant inhibitory activity against α-glucosidase, and half of the isolates also displayed moderate antiradical effect.

Network pharmacology integrated molecular dynamics reveals the bioactive compounds and potential targets of Tinospora crispa Linn. as insulin sensitizer.

Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and ß sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.