Indian Herb Tinospora Cordifolia: An Insight on The Numerous Pharmacological Activities

Abstract

In Ayurvedic medicine, Guduchi, or Tinospora cordifolia, is revered as one of the three Amrit plants, symbolizing divine qualities. Its Sanskrit name, “Amritavalli,” reflects its esteemed status in healing traditions. Well-documented in Ayurvedic texts, Guduchi is integral to numerous formulations, regarded as a panacea for various ailments, from dyspepsia and diabetes to fever, urinary issues, jaundice, chronic diarrhea, cardiac diseases, and skin disorders, among others. This review highlights Guduchi's classical therapeutic properties, including its antitoxic, antidiabetic, anticancer, immunomodulatory, antioxidant, antimicrobial, and hepatoprotective activities, supported by existing literature. The plant is rich in bioactive compounds such as alkaloids, glycosides, steroids, and terpenoids. This study aims to explore and establish the phytochemistry and pharmacological efficacy of Tinospora cordifolia, reinforcing its significance in modern herbal medicine.

Keywords

Tinospora Cordifolia, Pharmacological Activities.

Introduction

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Phytochemistry

Tinospora cordifolia (Guduchi) is rich in a diverse array of phytochemicals that contribute to its therapeutic properties. The primary constituents include:

Alkaloids, glycosides, steroids, aliphatic compounds, essential oil, mixture of fatty acid, calcium, phosphorous, protein and polysaccharides.

Active Components and Therapeutic Activities of Tinospora cordifolia

Tinospora cordifolia is characterized by a rich array of active components, primarily found in its stem and root, which contribute to its diverse therapeutic activities:

1. Alkaloids

The stem and root of T. cordifolia contain several bioactive alkaloids, including:

• Tembertine

• Choline

• Magnoflorine

• Berberine

• Tinosporin

• Isocolumbin

• Palmatine

• Jatrorrhizine

• Aporphine alkaloids

• Tetrahydropalmatine

These alkaloids exhibit a range of pharmacological activities such as anti-cancer, anti-diabetic, anti- viral, anti-inflammatory, anti-psychiatric, and immunomodulatory effects.[18,19]

2. Whole Plant Constituents

The entire plant contains various other compounds, including:

• Furanolactone

• Diterpenoid lactones

• Cleodrane derivatives

• Columbin

• Jateorine

These constituents are associated with biological actions including vasorelaxant, anti-inflammatory, anti-microbial, anti-hypertensive, and anti-viral activities.[20,21]

3. Steroids

The shoot part of T. cordifolia is rich in steroids such as:

• ?-Sitosterol

• ?-Sitosterol

• 20 ?-Hydroxyecdysone

• Giloinsterol

• akisterone A

•  Ecdysterone

These steroids have shown effectiveness against glucocorticoid-induced osteoporosis and early inflammatory arthritis. They induce cell cycle arrest in the G2/M phase and inhibit pro-inflammatory cytokines such as TNF-?, IL-1?, IL-6, and COX-2.[22,23]

4. Glycosides

 The stem part also contains various glycosides, including:

• 18-Norcleodrane glucoside

• Tinocordifolioside

• Cordioside

• Cordifolioside A, B, C, D, and E

• Furanoid diterpine glucoside

• Syringin and its derivatives

 These glycosides have shown immunomodulatory effects, particularly in conditions like Parkinson’s disease, dementia, and other neurological disorders. They inhibit NF-?B, contributing to their anti- cancer properties.[24,25]

5. Aliphatic Compounds

Active constituents include:

• Octacosanol

• Nanocosan-15-one

• Heptacosanol

These compounds demonstrate anti-nociceptive and anti-inflammatory activities, protecting against neurodegeneration.[26,27]

6. Sesquiterpenoids

Tinocordifolin and other sesquiterpenoids exhibit antiseptic activities.[28]

7. Other Active Constituents

The plant contains additional compounds such as:

• Jatrorrhizine

• Tinosporic acid

• N-trans-feruloyltyramine diacetate

These constituents have shown protective effects against HIV.[29,30]

Key Phytoconstituents

The principal phytoconstituents of T. cordifolia include:

• Diterpenoid furano lactones

• Cordifolide

• Heptacosanol

• Tinosporide

• ?-Sitosterol

• Tinosporine

• Clerodane furano diterpine

• Tinosporaside

• Columbin

These diverse bioactive compounds illustrate the therapeutic potential of Tinospora cordifolia, making it a significant subject of interest in both traditional and modern medicinal research.[31]

Pharmacological Aspects

Tinospora cordifolia has long been recognized in traditional medicine for its wide-ranging therapeutic properties. Key pharmacological aspects include:

• Spasmolytic Activity: T. cordifolia.

• Allergen-Free Properties:

• Anti-Diabetic Effects:

• Immune System Enhancement: T. cordifolia

• Stress Relief:

• Antimalarial Properties:

• Bitter Stomachic:

• Diuretic Activity: T. cordifolia

• Biliary Secretion Stimulation:

• Blood Enrichment and Jaundice Treatment.

Major Biological Activities

The major biological activities of T. cordifolia include:

1. Anti-inflammatory:

2. Antioxidant:

3. Antimicrobial:

4. Hepatoprotective.

5. Adaptogenic:

Anti-Cancer/Anti-Tumor Activity of Tinospora cordifolia

Tinospora cordifolia (Guduchi) has demonstrated significant anti-cancer and anti-tumor activities in various experimental models, showcasing its potential as a natural therapeutic agent in cancer treatment.

Key Findings on Anti-Cancer Activity:

1. Radioprotection: Guduchi exhibits radioprotective properties, increasing body weight and tissue weight in animal models. It protects against gamma radiation, particularly in the testes of Swiss Albino mice, suggesting its potential to mitigate radiation-induced damage.

2. Cell Death Induction: Methylene chloride extracts of T. cordifolia were tested on cultured HeLa cells at varying concentrations (0, 5, 10, 25, 50, and 100 ?g/ml), showing a dose- dependent increase in cell death compared to untreated controls. This indicates its capacity to induce apoptosis in cancer cells.[32]

3. Antioxidative Properties: Hydroalcoholic extracts from the aerial roots significantly increased glutathione (GSH) levels and other metabolizing enzymes in liver and extrahepatic organs of mice. This resulted in decreased levels of malondialdehyde (MLD), a marker of oxidative stress, thereby providing a protective antioxidative effect on cells.[33]

4. Inhibition of Tumor Proliferation: Hexane extracts showed inhibition of proliferation in Ehrlich ascites tumor cells, particularly affecting the G1 phase of the cell cycle. This was accompanied by enhanced expression of the pro-apoptotic Bax gene, leading to caspase- mediated apoptosis.[34]

5. Skin Carcinogenesis Model: In a two-stage skin carcinogenesis model, T. cordifolia reduced the incidence and weight of papillary tumors while increasing the levels of phase-II detoxifying enzymes, indicating its role in cancer prevention.[35]

6. Combined Treatment Effects: When combined with ?-radiation, Guduchi extract reduced GSH levels, causing oxidative damage to cancerous cells. It also improved outcomes in mouse models of skin cancer by reducing micronucleus formation in bone marrow cells, thereby increasing survival times.[36]

7. Synergistic Effects with Chemotherapy: T. cordifolia exhibited a cumulative effect when combined with cyclophosphamide, enhancing tumor inhibition and improving survival rates[37].

8. Active Constituents: The isolated alkaloid palmatine demonstrated anti-cancer effects in a dimethylbenzanthracene (DMBA)-induced skin cancer model. Other metabolites like magnoflorine, yangambin, and jatrorrhizine have also shown effectiveness against various tumor cells, including KB cells (oral cancer) and colon cancer cells.[38]

9. Anti-Neoplastic Properties: Guduchi has been effective against brain tumors, specifically in reducing the proliferation and differentiation rates in C-6 glioma cells.[39]

Conclusion

The findings suggest that Tinospora cordifolia possesses substantial anti-cancer properties through multiple mechanisms, including apoptosis induction, antioxidative effects, and modulation of enzymatic activities. Compared to synthetic chemotherapeutic agents, which often have severe side effects, T. cordifolia represents a safer alternative for cancer treatment, making it a valuable candidate for further research and potential clinical applications in oncology.[40]

Anti Toxin Activity of Guduchi (Tinospora cordifolia Anti-Toxin Activity)

Overview: Guduchi, or Tinospora cordifolia, is noted for its remarkable anti-toxin properties, primarily attributed to its alkaloid content. Research has shown that it can effectively scavenge free radicals and modulate various hormone and mineral levels, offering protective effects against different toxins.

Mechanisms of Action:

1. Aflatoxin Toxicity Reversal:

In studies involving Swiss albino mice, T. cordifolia demonstrated the ability to reverse kidney toxicity induced by aflatoxins. This was linked to a substantial increase in glutathione levels and enhanced enzyme activities, such as catalase and glutathione reductase, alongside a reduction in reactive oxygen species (ROS).[41]

2. Lead Nitrate Toxicity Mitigation:

Lead nitrate exposure resulted in decreased erythrocyte and leucocyte counts in blood serum. However, oral administration of Guduchi leaf and stem extracts counteracted these hematological alterations, demonstrating a protective effect against lead-induced toxicity [42]. This included normalization of liver enzyme levels, with decreased glutamic pyruvic transaminase (GPT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), while enhancing catalase activity.[43]

3. Cyclophosphamide-Induced Toxicity:

T. cordifolia also exhibited protective effects against cyclophosphamide-induced toxicity by significantly increasing reduced glutathione (GSH) levels and cytokine production while decreasing levels of inflammatory cytokines like tumor necrosis factor (TNF) in urinary bladder and hepatic cells.[44]

Conclusion: The anti-toxin activity of Guduchi is multifaceted, involving the modulation of antioxidant levels and enzymatic activities to combat various forms of toxicity. Its potential as a therapeutic agent in toxin-induced damage highlights the significance of this herbal plant in traditional and modern medicine.

Immunomodulatory Activity of Guduchi (Tinospora cordifolia)

Overview: Guduchi (Tinospora cordifolia) is recognized for its immunomodulatory properties, attributed to various bioactive compounds such as cordifolioside A and syringin. These compounds enhance immune responses and play a protective role in various disease contexts.[54]

Mechanisms of Action:

1. Enzyme Regulation and Immune Cell Stimulation:

The stem extract of T. cordifolia alters enzyme levels, including catalase, and stimulates lymphocyte proliferation, thereby strengthening immune defenses.[55]

2. Enhanced Macrophage Function:

Exposure to T. cordifolia extracts increases the production of enzymes like myeloperoxidase in macrophages, enhancing their antimicrobial capabilities and phagocytic activity. This contributes to improved immunity and pathogen defense.[56]

3. Nitric Oxide Production:

The plant stimulates increased nitric oxide production in macrophages and splenocytes, indicating its anti-tumor and immunoprotective activities.[57]

4. Effects on Cytokine Levels:

Clinical studies have shown that T. cordifolia lotion can reduce interleukin levels (IL-1 and IL-6) in animal models of scabies, inhibiting inflammatory responses and hyperkeratosis, thereby showcasing its anti-inflammatory and anti-scabies properties.[58]

5. Cellular Activation and Mitotic Induction:

Aqueous extracts of Guduchi promote cellular mitosis and the production of cytokines and immune effector cells, enhancing overall immune function.[59]

6. Prophylactic Potential:

The extract increases neutrophil activity and immune cell responses, suggesting its use as a preventive measure against immune-susceptible diseases.[60]

7. Immuno-Protective Compounds:

Various compounds, including alkaloids and polysaccharides (e.g., G1-4A), have been shown to enhance the proliferation and differentiation of T-cells and B-cells, linked to anti-apoptotic gene expression[61,62].

8. Stimulation of Hematopoietic Activity:

Oral administration of Guduchi extracts has been shown to increase white blood cell (WBC) counts and stimulate bone marrow activity, indicating robust immunomodulatory effects.[63]

9. Ayurvedic Preparations:

The classical Ayurvedic preparation "Ghana" has demonstrated significant immunostimulatory action in edema rat models, reducing edematogenic agents and highlighting its therapeutic potential[64].

Conclusion: The immunomodulatory activity of Guduchi is supported by its ability to enhance immune cell function, regulate cytokine levels, and stimulate hematopoiesis. Its various bioactive compounds provide a strong foundation for its use in traditional medicine as an immuno-protective agent, with potential applications in modern therapeutic contexts.

Anti-Microbial Activity of Guduchi (Tinospora cordifolia)

Overview: Guduchi (Tinospora cordifolia) exhibits significant anti-microbial properties against a range of bacteria and fungi, making it a valuable plant in both traditional and modern medicinal applications.

Key Findings:

1. Silver Nanoparticles:

Silver nanoparticles synthesized from T. cordifolia stems have shown notable antibacterial activity, particularly against Pseudomonas aeruginosa, a common pathogen in burn injuries.[65]

2. Broad-Spectrum Antibacterial Activity:

Extracts from T. cordifolia have demonstrated effectiveness against various bacterial strains, including Salmonella typhi, Klebsiella pneumoniae, Escherichia coli, and Aeruginosa. These extracts inhibit bacterial growth and mitigate the presence of these pathogens.[66,67,68]

3. Specific Compounds:

Active compounds isolated from the stem of T. cordifolia have shown efficacy against Enterococcus faecalis and Bacillus subtilis, as well as fungal pathogens such as Trichophyton simii and Trichophyton rubrum.[69]

4. Mastitis Prevention:

In a bovine model of mastitis induced by Staphylococcus aureus, hydroalcoholic extracts of T. cordifolia effectively reduced inflammation by enhancing granulocyte activity, showcasing its antimicrobial and anti-inflammatory properties.[70,71]

5. Urinary Pathogen Inhibition:

The stem and leaves of T. cordifolia exhibited maximum inhibitory effects against clinical urinary pathogens, particularly Klebsiella pneumoniae, indicating its potential use in treating urinary tract infections.[72]

Conclusion: Guduchi demonstrates robust anti-microbial activity through various mechanisms, including the production of silver nanoparticles and the presence of bioactive compounds. Its effectiveness against a wide array of bacterial and fungal pathogens underscores its potential as a natural antimicrobial agent in both therapeutic and preventive healthcare settings.[73,74]

Anti-Oxidant Activity of Guduchi (Tinospora cordifolia)

Overview: Guduchi (Tinospora cordifolia) is recognized for its potent antioxidant properties, which are crucial in scavenging free radicals and mitigating oxidative stress. These effects are particularly significant in various health conditions, including diabetes and exposure to radiation.

Key Findings:

1. Free Radical Scavenging:

Extracts of T. cordifolia demonstrate strong potential in scavenging free radicals and reducing reactive species, contributing to its antioxidant capacity.[75]

2. Lipid Peroxidation Reduction:

In a diabetic rat model (alloxan-induced), T. cordifolia significantly decreases lipid peroxidation levels and reduces the presence of reactive free radicals. It enhances the activity of antioxidant enzymes such as catalase and glutathione, indicating robust antioxidant effects[76,77,78].

3. GSH and Gene Regulation:

Clinical studies show that T. cordifolia extracts increase levels of glutathione (GSH) while reducing the expression of the inducible nitric oxide synthase (iNOS) gene, suggesting a protective role against oxidative stress.

4. Cataract Treatment:

The extract has potential in treating cataracts by inhibiting aldose reductase, an enzyme linked to the complications of diabetes.[79,80]

5. Comparative Extract Efficacy:

Ethanol extracts of T. cordifolia bark exhibit higher free radical scavenging activity and greater phenolic content compared to methanol extracts, highlighting the importance of solvent choice in maximizing bioactive compound extraction.[81]

6. Polysaccharide Activity:

The polysaccharide arabinogalactan, derived from T. cordifolia, has shown protective effects against free radicals in rat models, underscoring the plant's diverse range of antioxidant compounds.[82]

7. Radiation Protection:

T. cordifolia offers protection against gamma radiation-induced oxidative damage by inhibiting lipid peroxidation processes, specifically those induced by ferrous sulfate.[83]

8. Ayurvedic Formulations:

In Ayurvedic medicine, the herbomineral formulation Pepticare, which includes T. cordifolia, has been reported to have significant antioxidant effects in rat models.[84]

Conclusion: Guduchi exhibits substantial antioxidant activity through multiple mechanisms, including free radical scavenging and the enhancement of antioxidant enzyme levels. Its protective effects against oxidative stress render it a valuable component in both traditional and modern therapeutic applications, especially for conditions like diabetes and radiation exposure.

Anti-HIV Activity of Guduchi (Tinospora cordifolia)

Overview: Guduchi (Tinospora cordifolia) has garnered attention for its potential in supporting the treatment of HIV positive patients. Its immunomodulatory effects may enhance the efficacy of antiretroviral therapies and improve overall immune function.

Key Findings:

1. Support in Antiretroviral Therapy:

T. cordifolia is noted for reducing resistance to retroviral regimens in HIV positive patients, suggesting its role in enhancing the effectiveness of conventional treatments[85].

2. CD4 T-Cell Count Increase:

The extract has been shown to increase CD4 T-cell counts, which are crucial for maintaining immune function in individuals infected with HIV.

3. Eosinophil Count Reduction:

T. cordifolia helps decrease the count of eosinophils (a type of white blood cell), which can be beneficial in managing immune responses in HIV patients.

4. Enhanced Phagocytic Activity:

The extract significantly enhances the phagocytic and intracellular bactericidal activity of immune cells, indicating improved ability to fight infections.

5. Macrophage Stimulation:

T. cordifolia stimulates peritoneal macrophages, enhancing their function in the immune response against pathogens.

6. Stimulation of Immune Cells:

The extract significantly stimulates the activity of B-lymphocytes, polymorphonuclear leukocytes, and macrophages, contributing to a more robust immune response.[86,87,88]

Conclusion: Guduchi demonstrates promising anti-HIV activity through its ability to enhance immune cell function, increase CD4 T-cell counts, and improve the efficacy of antiretroviral treatments. Its immunomodulatory properties position it as a potentially valuable adjunct therapy for managing HIV, emphasizing the need for further research to fully understand its mechanisms and benefits.

Anti-Osteoporotic Activity of Guduchi (Tinospora cordifolia)

Overview: Guduchi (Tinospora cordifolia) has been studied for its potential anti-osteoporotic effects, particularly through its influence on osteoblast proliferation and differentiation, as well as its role in bone mineralization.

Key Findings:

1. Enhancement of Osteoblast Activity:

In vitro studies indicate that alcoholic extracts of Guduchi enhance the proliferation and differentiation of osteoblast cells derived from both human and rat models. This suggests its potential role in promoting bone health.

2. Mineralization and Calcification:

The extract participates in the calcification process, aiding in the production of minerals by osteoblasts, which is crucial for effective bone mineralization and overall bone density.[89]

3. Beta-Ecdysone:

A steroid compound named Beta-Ecdysone (or 20-hydroxyecdysone), isolated from T. cordifolia, has been shown to promote muscle tissue formation in mesenchymal stem cell models. This action may help in preventing osteoporosis by supporting bone density and strength.

4. Therapeutic Potential:

Beyond its anti-osteoporotic properties, T. cordifolia is associated with various other therapeutic activities, which further underline its significance in traditional and modern medicine[90 91].

Conclusion: Guduchi exhibits promising anti-osteoporotic activity through the stimulation of osteoblast proliferation and differentiation, along with its involvement in bone mineralization. The presence of bioactive compounds like Beta-Ecdysone enhances its potential as a therapeutic agent in preventing and managing osteoporosis, warranting further research to explore its mechanisms and applications.

CONCLUSION

Tinospora cordifolia, commonly known as Guduchi, is a highly resourceful plant that is rich in biologically active compounds with significant therapeutic potential. Numerous pharmacological and clinical studies validate its curative and remedial roles in addressing a variety of ailments. The diverse bioactive compounds found in T. cordifolia—including alkaloids, steroids, glycosides, and sesquiterpenoids—demonstrate substantial applications, particularly as immunomodulators and antioxidants. Research indicates that T. cordifolia is effective across multiple therapeutic domains, including anti- toxin, anti-diabetic, anticancer, immunomodulatory, antioxidant, and antimicrobial activities. Importantly, it has shown no adverse or toxic effects, reinforcing its safety profile as a medicinal agent. Overall, this review underscores the extensive potential of T. cordifolia in both traditional and modern medicine, laying a solid foundation for further research aimed at developing novel drug therapies. Its multifaceted benefits position it as a valuable candidate for future studies and applications in healthcare.

ACKNOWLEDGEMENT

The authors express their gratitude for the financial support provided by the Indian Council of Medical Research (ICMR), New Delhi, India (Grant No. 45/5/2013/BMS/TRM). This fellowship has been instrumental in facilitating our research and contributions to the study of Tinospora cordiofolia

REFERENCES

1. Preeti S. Tinospora cordifolia (Amrita)-a miracle herb and lifeline too many diseases. Int J Med Aromat Plants. 2011;1(2):57-61.
2. Pandey G. DraVyaguna Vijnana (Materia Medica-Vegetable Drugs) Part I
3. Singh SS, Pandey SC, Srivastava S, Gupta VS, Patro B, et al. (2003) Chemistry and Medicinal properties of Tinospora cordifolia (Guduchi). Indian J Pharmacol 35: 83-91.
4. Pandey M, Chikara SK, Vyas MK, Sharma R, Thakur GS, et al. (2012) Tinospora cordifolia: A climbing shrub in health care management. Anc Sci Life 3: 612-628.
5. Mittal J, Sharma MM, Batra A (2014) Tinospora cordifolia: a multipurpose medicinal plant a review. J Med Plants Res 2: 32-47.
6. Sharma R, Amin H, Galib R, Prajapati PK (2014) Therapeutic vistas of guduchi (Tinospora cordifolia): A medico- historical memoir. J Res Educ 1-16.
7. Khan M, Haque MS, Chowdhury SS (2016) Medicinal use of unique plant Tinospora cordifolia: evidence from the traditional medicine and recent research. Asian Journal of Medical and Biological Research 2: 508-512.
8. Singh SS, Pandey SC, Srivastava S, Gupta VS, Patro B, et al. (2003) Chemistry and Medicinal properties of Tinospora cordifolia (Guduchi). Indian J Pharmacol 35: 83-91.
9. Sinha K, Mishra NP, Singh J, Khanuja SPS (2004) Tinospora cordifolia (Guduchi) a reservoir plant for therapeutic applications: A review. Indian J Traditional Knowledge 3: 257- 270.
10. Bansal D, Bhasin P, Punia A, Sehrawat AR (2012) Evaluation of antimicrobial activity and phytochemical screening of extracts of Tinospora cordifolia against some pathogenic microbes. J Pharm Res 5: 127-129.
11. Joshi BC, Uniyal S (2017) Pharmacognostical review of tinospora cordifolia. Inventi Rapid Planta Activa 1: 1-10.
12. Tripathi BM, Singh DC, Chaubey S, Kour G, Arya R (2017) A critical review of tinospora cordifolia (Guduchi). Int J Curr Res 9: 55006-55009.
13. Joshi BC, Uniyal S (2017) Pharmacognostical review of tinospora cordifolia. Inventi Rapid Planta Activa 1: 1-10.
14.  Joshi BC, Uniyal S (2017) Pharmacognostical review of tinospora cordifolia. Inventi Rapid Planta Activa 1: 1-10.
15. Priyanka Sharma, Bharat P. Dwivedee , Dheeraj Bisht, Ashutosh K. Dash, Deepak Kumar. The chemical constituents and diverse pharmacological importance of Tinospora cordifolia. Heliyon, 2019; 5: 02437.
16. Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi). Validation of the Ayurvedic pharmacology through experimental and clinical studies. International Journal of Ayurveda Research, 2010; 1(2):112-121.
17. Promila, Sushila Singh and Parvesh Devi. Pharmacological potential of Tinospora cordifolia (Willd.) Miers ex hook. & Thoms. (Giloy): A review. Journal of Pharmacognosy and Phytochemistry, 2017; 6(6): 1644-1645
18. Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. F. and Thoms (Guduchi)- validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res. 2010;1(2):112.
19. Patel MB, Mishra S. Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine. 2011;18(12):1045-52. 27.
20. Sriramaneni RN, Omar AZ, Ibrahim SM, Amirin S, Zaini AM. Vasorelaxant effect of diterpenoid lactones from Andrographis paniculata chloroform extract on rat aortic rings. Pharmacognosy Res. 2010;2(4):242-6.
21. Dhanasekaran M, Baskar AA, Ignacimuthu S, Agastian P, Duraipandiyan V. Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethyl nitrosamine-induced hepatocellular carcinoma. Invest New Drugs. 2009;27(4):347-55.
22. Lv J, Xu D, Perkovic V, Ma X, Johnson DW, Woodward M, et al. TESTING Study Group. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012;23(6):1108-16.
23. Sundarraj S, Thangam R, Sreevani V, Kaveri K, Gunasekaran P, Achiraman S, et al. ?-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. J Ethnopharmacol. 2012;141(3):803-9.
24. Ly PT, Singh S, Shaw CA. Novel environmental toxins: Steryl glycosides as a potential etiological factor for age- related neurodegenerative diseases. J Neurosci. 2007;85(2):231-7
25. Kim SK, Kim HJ, Choi SE, Park KH, Choi HK, Lee MW. Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E 2 (COX-2) production of flavonoids from seeds of Prunus tomentosa Thunberg. Arch Pharm Res. 2008;31(4):424.
26. Oliveira AM, Conserva LM, DeSouza FJN, Brito FD, Lemos RP, Barreto E. Antinociceptive and anti- inflammatory effects of octacosanol from the leaves of Sabicea grisea var. grisea in mice. Int J Mol Sci. 2012;13(2):1598-611.
27. Thippeswamy G, Sheela ML, Salimath BP. Octacosanol isolated from Tinospora cordifolia down regulates VEGF gene expression by inhibiting nuclear translocation of NF-< kappa> B and its DNA binding activity. Eur J Pharmacol. 2008;588(2-3):141-50
28. Maurya R, Handa SS. Tinocordifolin, a sesquiterpene from Tinospora cordifolia1. Phytochem. 1998;49(5):1343-6.
29. Ghosh AK, Chapsal BD, Weber IT, Mitsuya H. Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc Chem Res. 2007;41(1):78-86.
30. Mukherjee R, De UK, Ram GC. Evaluation of mammary gland immunity and therapeutic potential of Tinospora cordifolia against bovine subclinical mastitis. Trop Anim Health Prod. 2010;42(4):645-51.
31. Devprakash SK, Subburaju T, Gurav S, Singh S. Tinospora cordifolia: A review on its ethnobotany, phytochemical and pharmacological profile. Asian J Biomed Pharmaceut Sci. 2011;4(1):291-302.
32. Jagetia GC, Nayak V, Vidyasagar MS. Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in cultured HeLa cells. Cancer Lett. 1998;127(1):71-82.
33. Singh RP, Banerjee S, Kumar PV, Raveesha KA, Rao AR. Tinospora cordifolia induces enzymes of carcinogen/drug metabolism and antioxidant system and inhibits lipid peroxidation in mice. Phytochem. 2006;13(1-2):74-84.
34. Thippeswamy G, Salimath BP. Induction of caspase-3 activated DNase mediated apoptosis by hexane fraction of Tinospora cordifolia in EAT cells. Environ Toxicol Pharmacol. 2007;23(2):212-20.
35. Chaudhary R, Jahan S, Goyal PK. Chemopreventive potential of an Indian medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice. J Environ Pathol Toxicol Oncol. 2008;27(3):233-43.
36. Rao SK, Rao PS, Rao BN. Preliminary investigation of the radiosensitizing activity of guduchi (Tinospora cordifolia) in tumor-bearing mice. Phytother Res. 2008;22(11):1482-9.
37. Verma R, Chaudhary HS, Agrawal RC. Evaluation of anticarcinogenic and antimutagenic effect of Tinospora cordifolia in experimental animals. J Chem Pharm Res. 2011;3(6):877-81.
38. Ali H, Dixit S. Extraction optimization of Tinospora cordifolia and assessment of the anticancer activity of its alkaloid palmatine. Scientific World Journal. 2013;28: 376216.
39. Mishra R, Kaur G. Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation-based therapy of glioblas tomas. PLoS One. 2013;8(10):e78764.
40. Bala M, Pratap K, Verma PK, Singh B, Padwad Y. Validation of ethno medicinal potential of Tinospora cordifolia for anticancer and immunomodulatory activities and quantification of bioactive molecules by HPTLC. J Ethnopharmacol. 2015;175:131-7.
41. Gupta R, Sharma V. Ameliorative effects of Tinospora cordifolia root extract on histopathological and biochemical changes induced by aflatoxin-B1 in mice kidney. Toxicol Int. 2011;18(2):94.
42. Sharma V, Pandey D. Protective role of Tinospora cordifolia against lead-induced hepatotoxicity. Toxicol Int. 2010;17(1):12.
43. Sharma V, Pandey D. Beneficial effects of Tinospora cordifolia on blood profiles in male mice exposed to lead. Toxicol Int. 2010;17(1):8.
44. Hamsa TP, Kuttan G. Tinospora cordifolia ameliorates urotoxic effect of cyclophosphamide by modulating GSH and cytokine levels. Exp Toxicol Pathol. 2012;64(4):307-14
45. Patel MB, Mishra S. Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine. 2011;18(12):1045-52.
46. Shivananjappa MM. Abrogation of maternal and fetal oxidative stress in the streptozotocin-induced diabetic rat by dietary supplements of Tinospora cordifolia. Nutrition. 2012;28(5):581-7.
47. Stanely P, Prince M, Menon VP. Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. J Ethnopharmacol. 2000;70(1):9-15.
48. Umamaheswari S, Prince Mainzen PS. Antihyperglycemic effect of ‘Ilogen-Excel’, an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus. Acta Pol Pharm. 2007;64;53-61.
49. Stanely Mainzen Prince P, Menon VP. Hypoglycaemic and hypolipidaemic action of alcohol extract of Tinospora cordifolia roots in chemical induced diabetes in rats. Phytother Res. 2003;17(4):410-3.
50. Patel SS, Shah RS, Goyal RK. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats. Indian J Exp Biol. 2009;47(7):564-70.
51. Sangeetha MK, Raghavendran HR, Gayathri V, Vasanthi HR. Tinospora cordifolia attenuates oxidative stress and distorted carbohydrate metabolism in experimentally induced type 2 diabetes in rats. J Nat Med. 2011;65(3- 4):544-50.
52. Chougale AD, Ghadyale VA, Panaskar SN, Arvindekar AU. Alpha glucosidase inhibition by stem extract of Tinospora cordifolia. Journal of Enzyme Inhibition and Med Chem. 2009;24(4):998-1001.
53. Singh CS, Singh AK, Khandelwal S, Vishwkarma R. Anti-Diabetic Activity of Ethanolic Extract of Tinospora cordifolia Leaves. Int J of Drug Discov and Herb Res. 2013;3(1):601-4.
54. Sharma U, Bala M, Kumar N, Singh B, Munshi RK, Bhalerao S. Immunomodulatory active compounds from Tinospora cordifolia. J Ethnopharmacol. 2012;141(3):918-26.
55. Aher V, Wahi AK. Biotechnological approach to evaluate the immunomodulatory activity of ethanolic extract of Tinospora cordifolia stem (mango plant climber). Iran J Pharm Res. 2012;11(3):863-72.
56. More P, Pai K. In vitro NADH-oxidase, NADPH-oxidase and myeloperoxidase activity of macrophages after Tinospora cordifolia (guduchi) treatment. Immunopharmacol Immunotoxicol. 2012;34(3):368-72.
57. Upadhyaya R, Pandey RP, Sharma V, Verma Anita K. Assessment of the multifaceted immunomodulatory potential of the aqueous extract of Tinospora cordifolia. Res J Chem Sci. 2011;71-9.
58. Castillo AL, Ramos JD, De Francia JL, Quilala PF, Dujunco MU. Immunomodulatory effects of Tinospora cordifolia lotion on interleukin-1, interleukin-6 and interleukin-8 levels in scabies-infected paediatric patients: a single blind, randomized trial. Int J Pharm Sci. Drug Res. 2014;6(3):204-10.
59. Upadhyaya R, Pandey RP, Sharma V, Verma Anita K. Assessment of the multifaceted immunomodulatory potential of the aqueous extract of Tinospora cordifolia. Res J Chem Sci. 2011;71-9.
60. Sudhakaran DS, Srirekha P, Devasree LD, Premsingh S, Michael RD. Immunostimulatory effect of Tinospora cordifolia Miers leaf extract in Oreochromis mossambicus. Indian J Exp Biol. 2006;44;726-32.
61. Jahfar M. Glycosyl composition of polysaccharide from Tinospora cordifolia. Acta pharmaceutica (Zagreb, Croatia). 2003;53(1):65-9.
62. Raghu R, Sharma D, Ramakrishnan R, Khanam S, Chintalwar GJ, Sainis KB. Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia. Immunol Lett. 2009;123(1): 60-71.
63. Koppada R, Norozian FM, Torbati D, Kalomiris S, Ramachandran C, Totapally BR. Physiological Effects of a Novel Immune Stimulator Drug,(1, 4)-?-d-Glucan, in Rats. Basic Clin Pharmacol Toxicol. 2009;105(4):217-21.
64. Salkar K, Suthar A, Chotalia C. Study of Immunomodulatory activity of Tinospora cordifolia extract. Int J Pharm Bio Sci. 2014;3(4):880-3.
65. Singh K, Panghal M, Kadyan S, Chaudhary U, Yadav JP. Antibacterial activity of synthesized silver nanoparticles from Tinospora cordifolia against multi drug resistant strains of Pseudomonas aeruginosa isolated from burn patients. J Nanomed Nanotechnol. 2014;5(2):1-6.
66. Narayanan A, Raja S, Ponmurugan K, Kandekar S, Natarajaseenivasan K, Maripandi A, et al. Antibacterial activity of selected medicinal plants against multiple antibiotic resistant uropathogens: a study from Kolli Hills, Tamil Nadu, India. Benef Microbes. 2011;2(3):235-43.
67. Jeyachandran R, Xavier TF, Anand SP. Antibacterial activity of stem extracts of Tinospora cordifolia (Willd) Hook. F and Thomson. Ancient Sci Life. 2003;23(1):40-3.
68. Tambekar DH, Khante BS, Chandak BR, Titare AS, Boralkar SS, Aghadte SN. Screening of antibacterial potentials of some medicinal plants from Melghat forest in India. Afr J Tradit Complement Altern Med. 2009;6:228-32.
69. Duraipandiyan V, Ignacimuthu S, Balakrishna K, AL-Harbi NA. Antimicrobial activity of Tinospora cordifolia: an ethno medicinal plant. Asian J Tradit Med. 2012;7(2):59-65
70. Mukherjee R, De UK, Ram GC. Evaluation of mammary gland immunity and therapeutic potential of Tinospora cordifolia against bovine subclinical mastitis. Trop Anim Health Prod. 2010;42(4):645-51
71. Purandare H, Supe A. Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical treatment of diabetic foot ulcers: A prospective randomized controlled study. Indian J Med Sci. 2007;61(6):347-55.
72. Shanthi V, Nelson R. Antibacterial activity of Tinospora cordifolia (Willd) Hook. F. Thoms on urinary tract pathogens. Int J Curr Microbial App Sci. 2013;2(6):190-4.
73. Bonvicini F, Mandrone M, Antognoni F, Poli F, Angela Gentilomi G. Ethanolic extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial activity towards clinical isolates of methicillin-resistant and carbapenemase-producing bacteria Nat Prod Res. 2014;28(18):1438-45.
74. Narayanan A, Raja S, Ponmurugan K, Kandekar S, Natarajaseenivasan K, Maripandi A, et al. Antibacterial activity of selected medicinal plants against multiple antibiotic resistant uropathogens: a study from Kolli Hills, Tamil Nadu, India. Benef Microbes. 2011;2(3):235-43.
75. Bhawya D, Anilakumar KR. In Vitro Antioxidant Potency of Tinospora cordifolia (gulancha) in Sequential Extracts. Int J Pharm Biolo Arch. 2010;1(5):448-56.
76. Stanely Mainzen Prince P, Menon VP. Hypoglycaemic and hypolipidaemic action of alcohol extract of Tinospora cordifolia roots in chemical induced diabetes in rats. Phytother Res. 2003;17(4):410-3
77. Sivakumar V, Rajan MD. Antioxidant effect of Tinospora cordifolia extract in alloxan-induced diabetic rats. Indian J Pharm Sci. 2010;72(6):795-8.
78. Stanley MPP, Menon VP. Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats. Phytother Res. 2001;15(3):213-8.
79. Gacche RN, Dhole NA. Profile of aldose reductase inhibition, anti-cataract and free radical scavenging activity of selected medicinal plants: an attempt to standardize the botanicals for amelioration of diabetes complications. Food Chem Toxicol. 2011;49(8):1806-13.
80. Rawal A, Muddeshwar M, Biswas S. Effect of Rubia cordifolia, Fagonia cretica linn, and Tinospora cordifolia on free radical generation and lipid peroxidation during oxygen-glucose deprivation in rat hippocampal slices. Biochem Biophys Res Commun. 2004;324(2):588-96.
81. Upadhyay N, Ganie SA, Agnihotri RK, Sharma R. Free radical scavenging activity of Tinospora cordifolia (Willd.) Miers. J Pharmacog Phytochem. 2014;3(2):63-9.
82. Subramanian M, Chintalwar GJ, Chattopadhyay S. Antioxidant properties of a Tinospora cordifolia polysaccharide against iron-mediated lipid damage and ?-ray induced protein damage. Redox Rep. 2002;7(3):137-43.
83. Goel HC, Kumar Prem I, Rana SV. Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection. Indian J Exp Biol. 2002;40;727-34.
84. Bafna PA, Balaraman R. Anti-ulcer and anti-oxidant activity of pepticare, a herbomineral formulation. Phytomedicine. 2005;12(4):264-70.
85. Gupta GD, Sujatha N, Dhanik A, Rai NP. Clinical evaluation of Shilajatu Rasayana in patients with HIV infection. Ayu. 2010;31(1):28-32.
86. Patel A, Bigoniya P, Singh CS, Patel NS. Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A. Indian J Pharmacol. 2013;45(3):237
87. Kalikar MV, Thawani VR, Varadpande UK, Sontakke SD, Singh RP, Khiyani RK. Immunomodulatory effect of Tinospora cordifolia extract in human immunodeficiency virus positive patients. Indian J Pharmacol. 2008;40(3):107-10.
88. Akhtar S. Use of Tinospora cordifolia in HIV infection. Indian J Pharmacol. 2010;42(1):57.
89. Abiramasundari G, Sumalatha KR, Sreepriya M. Effects of Tinospora cordifolia (Menispermaceae) on the proliferation, osteogenic differentiation and mineralization of osteoblast model systems in vitro. J Ethnopharmacol. 2012;141(1):474-80.
90. Gao L, Cai G, Shi X. ?-Ecdysterone induces osteogenic differentiation in mouse mesenchymal stem cells and relieves osteoporosis. Biol Pharm Bull. 2008;31(12):2245-9.
91. Kapur P, Wuttke W, Jarry H, Seidlova-Wuttke D. Beneficial effects of ?-Ecdysone on the joint, epiphyseal cartilage tissue and trabecular bone in ovariectomized rats. Phytomedicine. 2010;17(5):350-5.