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.

Humoral immune and adjuvant responses of mucosally-administered Tinospora cordifolia immunomodulatory protein in BALB/c mice

Background: Argyreia boseana Santapau and Patel commonly known as Kumbharao belongs to the familyof Convolvulaceae. The plant is rare in distribution and found chiefly in the dediapada region of Gujarat.Traditionally it is used by the tribals of south Gujarat forest region in the treatment of various diseases ofthe nervous system. In order to study the scientific basis of the plants effect we set out to investigate theeffect of the plant on ageing organisms and used Caenorhabditis elegans as a model.Objective: To evaluate the effect of crude extract of leaves, prepared from A. boseana on oxidative stress,thermal stress, longevity and in vivo gene expression of C. elegans.Material and Methods: Plant extracts was prepared by sonication based method using solvent ethanol:water. Longevity experiments were carried out in liquid S media. Oxidative stress was induced byparaquat.Result: Results indicate no increase in the normal life span of C. elegans. However, A. boseana significantlyinduces stress tolerance and increased the mean lifespan of worms during thermal and oxidative stress.Additionally A. boseana was also able to up regulate the stress associated gene gst-4.Conclusion: Thus the present study, for the first time, unravels the anti-stress and ROS modulating effectof A. boseana.

Evaluation of nephroprotective activity of Tinospora cordifolia against gentamicin induced nephrotoxicity in albino rats: an experimental study

Background: Gentamicin induced nephrotoxicity is a major contributor to Acute Kidney Injury (AKI) resulting from free radicals induced oxidative stress. Tinospora cordifolia is an Indian medicinal plant, widely used because of its antioxidant activity. Due to limited scientific literature exploring its nephroprotective potential, the present study was designed to investigate the nephroprotective effect of aqueous extract of Tinospora cordifolia against gentamicin induced nephrotoxicity in albino rats.Methods: The study was commenced following approval from Institutional Animal Ethical Committee of L.L.R.M. Medical College, Meerut (UP). Twenty four rats were randomised into four groups of six animals each. Total duration of study was 21 days. Group I received normal saline p.o., group II received normal saline along with gentamicin on last 5 days, group III and IV received Tinospora cordifolia in graded doses p.o. along with gentamicin on last 5 days. Injection gentamicin (40mg/kg) i.p. was given once daily for last 5 days to induce nephrotoxicity in rats of groups II, III and IV. The rats were sacrificed under anaesthesia, blood samples analysed for blood urea nitrogen (BUN) and serum creatinine levels and histopathological changes were studied. Statistical analysis was done using ANOVA followed by post hoc test.Results: Tinospora cordifolia pre-treated groups exhibited significant (p<0.001) limitation in rise in levels of BUN and serum creatinine in a dose dependent manner. Histolopathological observations further corroborated the biochemical findings.Conclusions: The present study concluded that aqueous extract of Tinospora cordifolia possesses nephroprotective potential against gentamicin induced nephrotoxicity.

Evaluation of the analgesic activity of the water soluble extract of stem of Tinospora cordifolia in experimentally induced pain in albino rats

Background: Pain and pyrexia are the warning signals, primarily protective in nature, that cause discomfort and suffering and may even be unbearable and incapacitating. The modern drugs (like opioids, NSAIDs, corticosteroids) currently used for the management of pain, fever and inflammatory conditions, present with many known adverse effects. Tinospora cordifolia known as Giloe, widely used in folk medicine due to its property to cure a number of diseases. Hence the present study was undertaken to explore the analgesic activity of water-soluble extract of stem of T. cordifolia in albino rats in experimentally induced pain.Methods: Present study was done in the department of pharmacology, albino rats were used to study the analgesic activity of T. cordifolia aqueous extract at the dose of 1.25g/kg,2.5g/kg and 5g/kg p.o. Various methods like Eddy’s hot plate, tail flick test and acetic acid induced writhing were used for the anti- nociceptive study.Results: In Eddy’s hot plate and tail flick test an increase in reaction time was observed with peak effect at 90min. Results were similar to the standard drug Tramadol in acetic acid induced writhing increase in time of onset, decrease in number and duration of writhing was observed.Conclusions: Aqueous extract of T. cordifolia was effective in all the three models of pain suggesting its possible action by central and peripheral mechanisms. Activity of T. cordifolia can be attributed to various phytoconstituents viz. protoberberine alkaloids, terpenoids, glycosides and polysaccharides. It can be developed as potent analgesic agent in future.

A post marketing randomized placebo controlled study to evaluate the efficacy of study product UPLAT® (Carica papaya leaf extract + Tinospora cordifolia extract) in the cancer patients with thrombocytopenia induced by chemotherapy

Background:Thrombocytopenia refers to abnormal decrease in platelet count in an individual. The condition may rise at different grades of severity in cancer patients under chemotherapy. In most of the cases, thrombocytopenic condition of cancer patient becomes a major therapy limiting factor. Generally, the treatment of thrombocytopenia lies in dose reduction and/or dose delay but this may adversely affect the treatment plan of cancer. Therefore, managing chemotherapy induced thrombocytopenia is still a challenge. This study was conducted to examine the platelet count improving effect of marketed product UPLAT® (Carica papayaleaf extract + Tinospora cordifoliaextract) in cancer patients with chemotherapy induced thrombocytopenia (CIT).Methods:Fourty (40) subjects were recruited as „case? and twenty (20) as „control?. „Cases? were cancer patients with chemotherapy induced thrombocytopenia. UPLAT® containing following active ingredients;Carica papayaleaf extract: 350mg (standardized to 2% flavonoids)and Tinospora cardifoliaextract: 150mg (standardized to 3% bitters) was given twice daily (2units each) for 10 consecutive days. Platelet count was observed at baseline and day 15 (end of the study). Then pre and post-treatment platelet counts were compared individually in both arms by statistical tests. Response was evaluated in fourty (40) „cases? and twenty „control?y.Results:Mean change for platelet count in case group (93990.00±63896.73) was much higher than control group(27600.00±29758.42).No adverse events with the treatment were observed. Conclusions: This study proves the effectiveness of platelet booster UPLAT® (combination of Carica papayaleaf extract and Tinospora cordifolia) as it significantly increased thrombocytes/platelet count in post-chemotherapy cancer patients.

Attenuation of quorum sensing-regulated behaviour by Tinospora cordifolia extract & identification of its active constituents.

Background & objectives: The pathogenicity of the nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii is regulated by their quorum sensing (QS) systems. The objective of the present study was to examine the effect of the cold ethyl acetate extract of Tinospora cordifolia stem on virulence and biofilm development in the wild type and clinical strains of P. aeruginosa and A. baumannii. The study was further aimed to identify the probable active constituents in the plant extract. Methods: P. aeruginosa virulence factors viz., LasA protease, LasB elastase and pyocyanin production were analyzed spectrophotometrically. Biofilm formation was studied using crystal violet staining-microtitre plate assay. The plant extract was fractionated using silica gel column chromatography and the most active fraction was derivatized using silylation and analyzed by gas chromatography-mass spectrometry (GC-MS). In silico testing of the molecules identified in GC-MS was performed, for binding to the P. aeruginosa LasI and LasR proteins, to predict the QS inhibitory molecules. Results: The plant extract inhibited three major virulence factors in P. aeruginosa; it exhibited enhanced biofilm formation in P. aeruginosa while decreased biofilm development in A. baumannii. The most active fraction obtained from column chromatography, exhibited suppression of virulence as well as biofilm in both the organisms. Docking scores were calculated for all the molecules identified in GC-MS, and high docking scores were obtained for 2,3,4-triacetyloxybutyl acetate, methyl 16-methyl heptadecanoate, 2-(5-ethenyl-5-methyloxolan-2-yl)propan-2-ol, methyl hexadecanoate and 2-methoxy-4-vinyl phenol. Interpretation & conclusions: The compounds showing high docking scores could probably be the QS inhibitors. These molecules can be screened further for the development of new anti-infective drugs.

Efficacy and safety of Tinospora cordifolia (Tc) as an add-on therapy in patients with type-2 diabetes.

Background: Type 2 diabetes has become a global epidemic. Tinospora cordifolia is being used in the treatment of type 2 diabetes since ancient times. It is a common misconception that Ayurvedic medicines are always safe. In fact, they also pose serious health risks either in the form of adverse reactions or in the form of drug interactions. Hence this study was undertaken to study the efficacy and safety of Tc on human subjects. Methods: We recruited 40 type 2 diabetic patients who were on oral hypoglycaemic agents. These patients were then randomly divided into two groups, A and B. Patients in group A continued with their anti-diabetic medications while in group B Tc was given at a dose of 500 mg three times daily along with their conventional medications. The fasting and post prandial blood glucose levels, renal function tests and liver function tests were recorded at baseline, 3 months and 6 months. Results: During the course of study we observed a decrease in the fasting and post prandial blood glucose levels of the patients. No significant change was observed in the renal function tests and liver function tests and no other event of any adverse drug reactions were recorded. Conclusion: Tinospora cordifolia (Tc) is effective as an add-on therapy in patients with type-2 diabetes. There is no negative impact of Tc on the renal as well as liver function tests.

Effect of Tinospora cordifolia as an add - on therapy on the blood glucose levels of patients with Type 2 diabetes.

Background: Type 2 diabetes is a fast growing epidemic affecting people globally. Good glycemic control helps in reducing the risk of macro and microvascular complications in diabetics. Alternative medicines have been used since ancient times in India to achieve good glycemic control. Tinospora cordifolia (Tc) is a well reported plant possessing anti-diabetic property. Therefore, we undertook this study to evaluate the effectivity of Tc in reducing the blood glucose levels of Type 2 diabetic patients in the form of add-on therapy. Methods: In the present study, we enrolled 100 Type 2 diabetic patients who met our inclusion criteria. These patients were then randomly divided into two Groups, A and B. Patients in Group A were treated as controls and they continued with their anti-diabetic medications. In Group B, Tc was added to the conventional treatment at a dose of 500 mg 3 times daily along with meals. The fasting and postprandial blood glucose levels and glycosylated hemoglobin (HbA1c) were recorded baseline and after 6 months. Results: During the course of study, we observed a decrease in the fasting, postprandial, and HbA1c levels of the patients. However, this decrease was found to be more statistically significant (p≤0.005) in Group B. Conclusion: The results obtained from the present study conclude that Tc, when given in the form of add-on therapy, was found to be synergistic and effective in the better management of Type 2 diabetes. The drug was well tolerated by the patients and no adverse drug event was recorded.

Antidiabetic claims of Tinospora cordifolia (Willd.) Miers: Critical appraisal and role in therapy

Currently, available conventional options for diabetes mellitus have certain limitations of their own, and options from medicinal plants with antihyperglycemic activities are being searched to meet the need. Antidiabetic properties of Tinospora cordifolia are highly appreciated in Ayurveda and even in recent modern researches. Several studies on its extracts (viz. immunemodulatory, anti-hyperglycemic, antioxidant, adaptogenic, hepatoprotective, hormone regulator etc.) and isolated phytoconstituents (like tinosporin, berberine, jatrorrhizine etc.) have reported that it is a preventive and curative antidiabetic herb, which are substantiated by clinical trials. Scattered information pertaining to antidiabetic potential of Tinospora is reported. Present review encompasses (i) in-depth information of reported antidiabetic activities of the plant in light of available experimental and clinical studies, and (ii) understanding on the possible mechanism of its action in combating the complex pathology of diabetes.

Effect of combination of Phyllanthus emblica, Tinospora cordifolia, and Ocimum sanctum on spatial learning and memory in rats.

Background: There has been a steady rise in number of patients suffering from dementia including dementia associated with Alzheimer’s disease. Effective treatment of Alzheimer’s disease dementia is an unmet medical need. Objective: To evaluate effects of formulation containing combination of Phyllanthus emblica (Pe) and Tinospora cordifolia (Tc) with and without Ocimum sanctum (Os) on learning and memory performance of normal and memory impaired rats in complex maze and compare with effects of Tinospora cordifolia and Phyllanthus emblica alone. Materials and Methods: Wistar rats; either sex (100–150 g) were divided in seven groups Control, Piracetam, Rivastigmine, Tc, Pe, Formulation 1 (Tc + Pe), and Formulation 2 (Tc + Pe + Os).The study was divided in four parts: In part 1 memory enhancement was tested in normal rats. In part 2, 3, and 4 the effects of drugs were tested in Scopolamine‑, Diazepam‑, and Cyclosporine‑induced amnesia. Hebb–Williams maze was used to test for learning and memory. Time required to trace food and number of errors in maze were noted. Results: In normal rats, all test drugs showed significant reduction in time required to trace the food and number of errors after 24 h compared with vehicle control. Formulations 1 and 2 reduced the time required to trace food and number of errors and the results were comparable with positive control groups and comparators Tc and Pe. Formulations 1 and 2 reversed amnesia produced by Scopolamine, Diazepam, and Cyclosporine when compared with vehicle control and showed comparable results with those of positive control groups and comparators Tc and Pe. Conclusion: Formulations 1 and 2 demonstrated nootropic activity and both the formulations showed comparable nootropic activity with that of Tc and Pe alone.

Comparative immunomodulation potential of Tinospora cordifolia (Willd.) Miers ex Hook. F., Tinospora sinensis (Lour.) Merrill and Tinospora cordifolia growing on Azadirachta indica A. Juss.

Guduchi has been widely used in the traditional medicine as an immunomodulator. Description of guduchi in Ayurvedic literature resemble with T. sinensis rather than with commonly available T. cordifolia and hence this may be used as substitutes for T. sinensis. T. cordifolia growing on Azadirachta indica commonly called Neem-guduchi has more immunomodulatory potential. Thus, immunomodulatory activity of three Tinospora spp. was assessed by checking humoral and cell mediated immune responses to the antigenic challenges with sheep RBCs and by neutrophil adhesion tests on albino Wistar rats using Guduchi-Satwa, a well known dosage form. Results revealed that Neem-guduchi possesses higher immunomodulatory potential at the dose of 300 mg/kg, po and validated the traditional claim. Hence, Neem-Guduchi can be employed in immunomodulatory formulation prepared using guduchi.

Histological, Histochemical and Phytochemical Studies of The Raw Drug Amrita From Different Raw Drug Markets of Kerala.

There are two source plants for the raw drug Amrita, Chittamrita and wild amrita. The accepted source of the former is Tinospora cordifolia and Tinospora sinensis is often used as a substitute. This paper deals with the study of “Histological, Histochemical and Phytochemical studies of the Raw drug Amrita from different Raw Drug Markets of Kerala”. The present study reveals that in the raw drug market of Kerala, T. cordifolia, T. sinensis and few other menispermaceae members are obtained as source plant of Amrita and concluded that about 40% of the raw drug amrita was found to be substitution/ adulteration.

Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial.

Background: AmrutBhallatak (ABFN02), a ‘rasayana’ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and effi cacy of ABFN02 in osteoarthritis (OA) and compare it with Glucosamine sulphate (GS) Materials and Methods: This was a randomized open comparative study. Ambulant OPD patients of OA knees (n = 112) were enrolled for 24 weeks. Tablets (750mg each) of GS and ABFN02 were matched. Three groups of patients: (A) GS, one tablet × twice/day × 24 weeks. (B) ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks), two such cycles of drug and non-drug phases alternately for six weeks each (C) ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS) and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC) were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ), paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has signifi cant activity in OA; the formulation needs further investigation.

Seasonal variations in physicochemical profi les of Guduchi Satva (starchy substance from Tinospora cordifolia [Willd.] Miers).

Guduchi Satva (GS), the starchy material extracted from the Guduchi stem is well-known Ayurvedic single drug formulation having a wide range of therapeutic utility. Species of the plant, stem size, collection time, season and maturity of the plant may affect the yield and physico-chemical profi le of GS. However, published data on such variations is lacking. Considering this, present study is planned to screen seasonal variations in physico-chemical profi le of GS. 18 batches of GS were prepared in six different seasons (3 batches in each season) and fi ndings were systematically recorded. The obtained Satva was further subjected to relevant physico-chemical parameters. Principal component analysis method was adopted to analyze variations. Maximum yield of Satva was obtained in Shishira Ritu (January-February) while the minimum in Grishma (May-June). Variation in taste and color was found in Satva prepared in Varsha Ritu. All functional groups were found to be same in each season. Total alkaloidal contents found bit higher in Varsha and Vasanta. More residual x-variance in alcohol soluble extract and more leverage were observed in water soluble extract due to impact of seasonal spells.

Comparative Hepatoprotective Potential of Tinospora cordifolia, Tinospora sinensis and Neem-guduchi.

Aims: Aim of this study was to evaluate the comparative efficacy of Tinospora cordifolia (Willd.) Miers ex Hook. F., Tinospora sinensis (Lour.) Merrill and T. cordifolia growing on Neem (Azadirachta indica A. Juss.) called Neem-guduchi. Study Design: Selected species have been widely used in the traditional medicine systems in various dosage forms to treat liver disorders. They are of common occurrence and are being used as substitutes to each other. There is no comparative hepatoprotection study yet published, therefore, present study has carried out. Place and Duration of Study: Interactive Research School for Health Affairs, Pune and Amrutvahini College of Pharmacy, Sangamner, between November 2011 and August 2012. Methodology: Guduchi-Satwa, a well-known dosage form was prepared according to the traditional procedure. Hepatoprotective potential was assessed using paracetamolinduced hepatotoxicity model in rats and evaluated by using biochemical parameters viz. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (BIL). Results: Both T. cordifolia and T. sinensis Satwa significantly reduced the paracetamol induced elevated levels of serum ALT, AST, ALP and BIL at dose of 200 mg/kg, i.p. as compared to Neem-guduchi. Conclusions: Satwa preparation form of T. sinensis offers exploitable level of hepatoprotection potential.

Study of hypoglycemic activity of Tinospora cordifolia in alloxan induced diabetic rabbits.

Background: This study was designed to investigate the hypoglycemic effect of Tinospora Cordifolia in alloxan-induced diabetic rabbits. Methods: Rabbits were divided into four experimental groups: Non-diabetic rabbits treated with normal saline, Non-diabetic rabbits treated with TCREt, Diabetic rabbits treated with Metformin, Diabetic rabbits treated with TCREt. Treatment with drugs was started on the 8th day of alloxan treatment (i.e. day 1) and was continued for 30 days. Statistical evaluation was done using student’s ‘t’ test & one way ANOVA followed by Tuckey`s post hoc test. ‘p’ value less than 0.05 was considered statistically significant. Results: TCREt showed hypoglycemic action in alloxan induced diabetes rabbits. It did not produce hypoglycemia in non diabetic rabbits. Conclusion: Hypoglycemic action of TCREt is comparable to that of standard oral hypoglycemic drug metformin.

Antimicrobial Activity and Photochemical Screening of Tinospora Cordifolia and Euphorbia Hirta.

The present study deals with the antimicrobial activity and phytochemical screening of the two medicinal plants, Tinospora cordifolia and Euphorbia hirta those are commonly available in India. Results of antimicrobial activity revealed that these medicinal plant extracts were very effective against Serratia marcescens, E. coli, Streptococcus thermophilus, Fusarium oxysporium, Aspergillus niger while these extracts showed very less inhibition against Trichoderma reesei. Phytochemical analysis of these plants confirms the presence of various phytochemical like alkaloids, flavonoids, polyphenols, steroidal terpenes in Euphorbia hirta and alkaloids, flavonoids, Saponin, tannins, steroidal terpenes, reducing sugar in Tinospora cordifolia. While other phytochemical like, glycosides, phylobatamins, xanthoproteins, phenolic compounds were found to be absent in these extracts. These plants can be a source of useful drugs but further studies are required to isolate the active component from the crude plant extract for proper drug development.

Immunomodulatory activity of guduchi ghana (aqueous extract of tinospora cordifolia miers).

In the present work, Guduchi Ghana (concentrated form of aqueous extract of Guduchi) was prepared according to the method described in classical text – Sidhdha Yoga Samgraha and the other sample of aqueous extract was purchased from the market for the assessment of the immunomodulatory activity. It was done by haemagglutination antibody titre method for humoral immunity and footpad swelling method for cell mediated immunity on wistar albino rats. Results of present studies suggest that Guduchi Ghana prepared by classically was found to possess significant immunostimulatory action on immune system but market sample of it exhibited significant immunosuppression effect in dose dependent manner when compare with control group at a dose of 50 mg/kg orally.

Polysaccharide enriched immunomodulatory fractions from Tinospora cordifolia (Willd) miers ax hook. F. & Thoms†.

Tinospora cordifolia is used in Ayurveda as "Rasayanas" to improve the immune system and the body resistance against infections. Polysaccharides are the main constituents which are considered to be responsible for immune enhancement. In this study, immunomodulatory activity of three polysaccharide enriched fractions was evaluated using the polymorphonuclear leukocyte function test. Sugar composition was determined by GC-MS analysis of the derivatised fractions. The active polysaccharide fractions mainly constitute glucose, fructose and arabinose as monomer units.

Supporting the immune system through functional modulation of carbon tetrachloride intoxicated splenic macrophages by administering Tinospora cordifolia.

The suppression of immune system leads to the development of several chronic illnesses; in replying to this the available allopathic system of medicine is provided with limited tools for treatment and prevention. In this context, the present investigation focuses on immunostimulant properties of an aqueous extract of Tinospora cordifolia in splenic macrophages isolated from carbon tetrachloride induced immunosuppressive mice. Our results suggested that carbon tetra chloride intoxication (0.5ml/Kg body weight) significantly altered the functional status like morphology, cell adhesion, phagocytosis, myeloperoxidase (MPO) release, nitric oxide (NO) release, DNA fragmentation and killing capacity of splenic macrophages. However administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo) in CCl4 intoxicated male albino mice ameliorated the effect of CCl4, as was evident from the scanning electron micrographs, percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity. Thus, it has been coclude that bioactive compounds presents in polar fractions of Tinospora cordifolia were accountable for boosting the immune system.