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Tinospora cordifolia

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General Features                  Clinical Study                  Chemical Intervention                 Pharmacological Aspects                 
Radiobiological Aspects                  Biological Models                  Biological Target                  Toxicity                 


BIOLOGICAL TARGET

Action of Extract: Radioprotected macrophage, splenocytes[18]
stimulation of hemaatopoietic recovery in irradiated mice[18]
Kupffer cell function was improved by treatement of T. cordifolia in liver damage of rat[1]
ethanolic extract of T. cordifolia exerted antineoplastic effect on Ehrlich ascites tunour cells in mice[2]
Administration of Tinospora cordifolia stem methanolic extract to BALB/c mice (200 mg/kg, i.p, daily for 5 days) increased the total white blood cell count significantly. It also increased bone marrow cellularity and α-esterase positive cells in bone marrow indicating increased maturation of stem cells. Administration of the extract was also found to increase plaque-forming cells in the spleen[3]
Intraperitoneal administration of alcoholic extract of Tinospora cordifolia in Dalton's lymphoma-bearing mice augmented the basic function of macrophages[4]
T.cordifolia provided protection against radiation-induced mortality in mice in vivo by protecting against GI and bone marrow syndromes[19]
Action on cell cycle:
ethanolic extract of T. cordifolia treatment was observed to arrest the C6 glioma cells in G0/G1 and G2/M phase[5]
T. cordifolia treatment increased cell population in S-phase, increasing DNA synthesis[20]
Target: Nucleic Acid
cytotoxic effect of stem extract of T. cordifolia in HeLa S3 cells in vitro was speculated to be due to DNA damage[6]
T. cordifolia extract significantly diminished the expression of iNOS gene and elevated expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes in rat hippocampal slices in vitro subjected to oxygen glucose deprivation[7]
Treatment with hexane extract fraction of T. cordifolia of Ehrlich ascites tumor cells bearing mice increased expression of Bax gene and decreased expression of Bcl-2 gene in tumor cells[8]
methylene chloride stem extract caused the concentration dependent increase in molecular DNA damage and is due to its ability to cause DNA strand breaks in HeLa cells in vitro. [21].
proteins:
T. cordifolia extract elevated GSH levels in rat hippocampal slices in vitro subjected to oxygen glucose deprivation[7], also root extract restored GSH content and catalase activity to normal levels in irradiated mice testis[31]
ethanolic extract of T. cordifolia treatment is found to be suppressing the expression of G1/S phase specific protein cyclin D1 and anti-apoptotic protein Bcl-xL in C6 glioma cells[5]
hydroalcoholic (80% ethanol: 20% distilled water) extract of aerial roots of Tinospora cordifolia (50 and 100 mg/kg body wt./day for 2 weeks) increased levels of acid-soluble sulfhydryl (–SH) and cytochrome P450 contents, and enzyme activities of cytochrome P450 reductase, cytochrome b5 reductase, GST, DTD, SOD, catalase, GSH peroxidase and GSH reductase in liver and extrahepatic organs of Swiss albino mice[9]
cytotoxic effect of stem extract of T. cordifolia in HeLa S3 cells in vitro was speculated to be due to inhibition of topoisomerase II, increased LDH accompanied by a decrease in GST activity[6]
Administration of aqua-alcoholic stem extract before irradiation increased endogenous production of IL-1β and GM-CSF in the serum of lethally irradiated mice[18]
aqua-alcoholic stem extract treatment retarded the radiation-induced adverse effects on cytoskeleton components actin, tubulin in mice[18]
aqua-alcoholic stem extract treatment in mice is speculated to inhibit the C3 convertase resulting in decreased phagocytic activity[18]
Tinospora cordifolia (Willd.)Miers hydroalcoholic extract root extract increased GSH level in irradiated mice ovaries[22]
Pre-treatment with TCE provided noticeable recovery in radiation induced elevation in SOD and catalase activity in plasma which provide reasonable radioprotection to the organism and increase the tolerance of animals through the detoxification of ROS. Pretreatment of TCE did not significantly influence the endogenous GSH levels in blood, but its mere presence protects the radiation induced endogenous GSH depletion[23]
T. cordifolia is speculated to inhibit the action of topoisomerase II activity[21]
T. cordifolia increases the activity of hexokinase in the liver, also active principles of T. cordifolia enhance the IgG antibodies[24]
HeLa cells treated with extract showed an increase in lactate dehydrogenase and decrease in glutathione- S-transferase activity[25]
root extract administered before irradiation significantly caused decline in glutathione concentration in mice testes[26]
Oral administration of extract caused reduction in radiation-induced elevation in glycogen, total proteins, acid phosphatase and increase radiation-induced decrease in alkaline phosphatase, GSH, catalase and SOD activities[27]
arabinogalactan polysaccharide isolated from Tinospora cordifolia provided significant protection to protein against γ-ray induced damage[28]
Lipids:
arabinogalactan polysaccharide isolated from Tinospora cordifolia provided significant protection against iron-mediated lipid peroxidation of rat brain homogenate.[28]
Oral administration of extract caused reduction in radiation-induced elevation in lipid peroxidation in mice liver[27]
Tinospora cordifolia (Willd.)Miers hydroalcoholic extract root extract decreased lipid peroxidation of membrane in irradiated mice ovaries[22]
The administration of ethanolic extract of T. cordifolia to liver cancer bearing rats reverted the LPO levels, and restored enzymic and nonenzymic antioxidants to near normal[10]
Intraperitoeal administration of alcoholic extract of Tinospora cordifolia to tumor-bearing mice destabilized the membrane integrity of Dalton's lymphoma cells directly or indirectly[4]
hydroalcoholic (80% ethanol: 20% distilled water) extract of aerial roots of Tinospora cordifolia (50 and 100 mg/kg body wt./day for 2 weeks) decreased chemicaaly induced lipid peroxidation in liver of Swiss albino mice[9]
ethanolic leaf extract exhibited lipid peroxidation inhibitory activity in vitro[11],root extract decreased radiation-induced lipi peroxidation in mice testis[31]
stem extract of T. cordifolia caused lipid peroxidation in HeLa S3 cells in vitro[6]
Aqueous extract inhibited ferrous sulphate mediated lipid peroxidation in mice liver homogenate in a dose-dependent manner[29]
Treatment of HeLa cells with various concentrations of extract caused a significant elevation in the lipid peroxidation, which was approximately 3-fold greater than 3 Gy irradiation at 4 hours postirradiation[25]
root extract administered before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation in mice testes[26]
sugars:
Aqueous extraxt inhibited radiation mediated 2-deoxyribose degradation[29]
Mechanism: Direct and indirect antioxidant actions of T. cordifolia, free radical scavenging and metal chelation, immunomodulation, cell proliferation are the properties, suggested to act in corroboration to manifest the overall radioprotective effects.[29]
Increased lipid peroxidation, LDH release, induction of apoptosis and interference with topoisomerase and a decline in GST concentration by dichloromethane extract of guduchi in conjunction with radiation are some of the important events leading to death of tumor cells[25]
The cytotoxic action of guduchi could be attributed to the presence of alkaloids, diterpenoid lactones, glycosides, steroids, sesquiterpenoids, phenolics, aliphatic compounds, or polysaccharides.[25]
The hepato-protective role of root extract is suggested to be due to the synergistic effects of various bioactive constituents that present in its root extract like polyphenols (3- glucosides, gallic acid, tannins), flanonoids (quercetin), alkaloids (berberine), and triterpenoids compounds, inflammatory flavonoid and glycoside derivatives.
Root extract exerts its radio- protective effect due to the ability to limit the initial damage, caused during irradiation by detoxifying radiation induced oxygen species, scavenging of free radicals and increased concentration of endogenous antioxidant system, free radical scavenging, elevation in antioxidant status, and reduction in lipid peroxidation along with stimulation of cellular regeneration in the post- irradiation period (particularly hematopoietic regeneration, liver recovery, gastrointestinal system recovery) and up regulating the activity of early response genes.[27],[19]
arabinogalactan polysaccharide isolated from Tinospora cordifolia is suggested to play a role in protecting cellular glutathione[28]
cordifolioside-A in stem extract of Tinospora cordifolia is reported to be palying role in radioprotective effect in mice in vivo[30]
Interaction with radicals:
arabinogalactan polysaccharide isolated from Tinospora cordifolia offered protective action against DPPH radical, superoxide radicals and the hydroxyl radical. hydroxy radical scavenging property was exhibited by leaf extract[12].
hydro methanolic Tinospora cordifolia stem extract showed effective free radical scavenging activity in vitro which can be attributed to the presence of alkaloid and phenolics along with other compounds[17]
free radical scavenger against reactive oxygen and nitrogen species[7]
ethanolic(stronger activity) and methanolic bark extract possessed free radical scavenging activity[13]
ethanolic, methanolic leaf extract and essential oil extracted from fresh leaves exhibited DPPH radical scavenging activity in vitro[11],[14],[15]
ethanol leaf extract exhibited mild scavenging activity in vitro[11]
Aqueous extract inhibits superoxide anion[29]
Immunomodulation:
T. cordifolia extracts were reported to exhibit immunomodulatory activity, possible mechanism being activation of macrophages by T. cordifolia extracts to increase in GM-CSF which leads to leucocytosis and improved neutrophil function[16]
Administration of aqua-alcoholic stem extract before irradiation significantly countered radiation induced decrease in antioxidants in blood plasma in mice by 8 hours[18]
aqua-alcoholic stem extract protected splenocytes by stimulating their proliferation and by decreasing apoptosis during cell repair from irradiation-induced damage[18]
increased IL-1β and GMCSF levels after treatment with stem extract in mice is suggested to be responsible for radioprotective ability[18]
The protective role of T. cordifolia extract is suggested to be due to the higher content of secondary metabolites including anthraquinones, terpenoids, and saponins which were present in many extracts in addition to phenolics which have the ability to scavenge free radical and enhance the DNA repair system or DNA synthesis[28]
root extract tratemnt in mice not only prevented radiation- induced damage to testicular injury but also speeded up the recovery process. Its radio- protective potential is speculated to be by boosting up of inherent antioxidant system and free radical scavenging activity of its root constituents[31]
REFERENCES
1. Nagarkatti DS et al, Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage. J Postgrad Med. 1994;40(2):65-7.
http://www.ncbi.nlm.nih.gov/pubmed/0008737554
2. Jagetia GC, Rao SK, Evaluation of the antineoplastic activity of guduchi (Tinospora cordifolia) in Ehrlich ascites carcinoma bearing mice, Biol Pharm Bull. 2006 ;29(3):460-6.
http://doi.org/10.1248/bpb.29.460
3. Mathew S, Kuttan G, Immunomodulatory and antitumour activities of Tinospora cordifolia. Fitoterapia. 1999;70(1):35–43.
http://dx.doi.org/10.1016/S0367-326X(98)00017-3
4. Singh N, Singh SM, Shrivastava P, Immunomodulatory and antitumor actions of medicinal plant Tinospora cordifolia are mediated through activation of tumor-associated macrophages. Immunopharmacol Immunotoxicol. 2004;26(1):145-62.
http://www.ncbi.nlm.nih.gov/pubmed/15106739
5. Mishra R, Kaur G, Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation based therapy of glioblastomas. PLoS One. 2013;8(10):e78764.
http://dx.doi.org/10.1371/journal.pone.0078764
6. Jagetia GC, Rao SK, Evaluation of cytotoxic effects of Dichloromethane extract of Guduchi (Tinospora cordifolia Miers ex Hook F & THOMS) on cultured HeLa cells. Evid Based Complement Alternat Med. 2006 ;3(2):267-72.
http://dx.doi.org/10.1093/ecam/nel011
7. Rawal AK, Muddeshwar MG, Biswas SK, Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation. BMC Complement Altern Med. 2004;4:11.
http://dx.doi.org/10.1186/1472-6882-4-11
8. 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.
http://dx.doi.org/10.1016/j.etap.2006.10.004
9. Singh RP et al, Tinospora cordifolia induces enzymes of carcinogen/drug metabolism and antioxidant system, and inhibits lipid peroxidation in mice. Phytomedicine. 2006;13(1-2):74-84.
http://dx.doi.org/10.1016/j.phymed.2004.02.013
10. Jayaprakash R et al, Antioxidant activity of ethanolic extract of Tinospora cordifolia on Nnitrosodiethylamine (diethylnitrosamine) induced liver cancer in male Wister albino rats. J Pharm Bioallied Sci. 2015 ; 7(Suppl 1): S40–S45.
http://dx.doi.org/10.4103/0975-7406.155791
11. Premanath R, Lakshmidevi N, Studies on anti-oxidant activity of Tinospora cordifolia (Miers.) Leaves using in vitro models. Journal of American Science. 2010;6(10):736-743.
http://www.jofamericanscience.org/journals/am-sci/am0610/86_3706am0610_736_743.pdf
12. Sengupta S et al, Hypoglycemic activity of the antioxidant saponarin, characterized as alpha-glucosidase inhibitor present in Tinospora cordifolia. J Enzyme Inhib Med Chem. 2009;24(3):684-90.
http://dx.doi.org/10.1080/14756360802333075
13. Upadhyay N et al, Free radical scavenging activity of Tinospora cordifolia (Willd.) Miers. Journal of Pharmacognosy and Phytochemistry 2014; 3 (2):63-69.
www.phytojournal.com/archives/2014/vol3issue2/PartB/1.1.pdf
14. Praveen N et al, Antioxidant activity of Tinospora cordifolia leaf extracts through non-enzymatic method. Journal of Medicinal Plants Research 2012; 6(33):4790-4795.
http://dx.doi.org/10.5897/JMPR12.200
15. Naik D, Dandge C, Rupanar S, Determination of chemical composition and evaluation of antioxidant activity of essential oil from Tinospora cordifolia (Willd.) leaf. Journal of Essential Oil Bearing Plants. 2014;17(2):228-236.
http://dx.doi.org/10.1080/0972060X.2013.831568
16. Thatte UM, Rao SG, Dahanukar SA, Tinospora cordifolia induces colony stimulating activity in serum. J Postgrad Med. 1994;40(4):202-3.
http://www.ncbi.nlm.nih.gov/pubmed/0009136239
17. Dwivedi R et al, Qualitative estimation of phytoconstituents and in vitro antioxidant potential of Tinospora cordifolia stem extract. International Journal of Biological & Pharmaceutical Research. 2014; 5(2): 114-119.
http://www.ijbpr.com/cadmin/article/495_114-119.pdf
18. Singh L et al, Effect of Tinospora cordifolia on Gamma ray-induced perturbations in macrophages and splenocytes. J. Radiat. Res.2007; 48(4): 305–315.
http://dx.doi.org/10.1269/jrr.07001
19. Sharma R, Sharma P, Goyal PK, Appraising radioprotective potential of Tinospora cordifolia (Amrita) extract in Swiss albino mice exposed to different doses of gamma radiation. Pharmacologyonline. 2009; 2: 249-260.
http://pharmacologyonline.silae.it/files/archives/2009/vol2/023.Sharma.pdf
20. Goel HC et al, Radioprotective poential of an herbal extract of Tinospora cordifolia. J. Radiat. Res. 2004;45(1):61-68.
http://dx.doi.org/10.1269/jrr.45.61
21. Jagetia GC, Rao SK, The Indian medicinal plant Giloe (Tinospora cordifolia) induces cytotoxic effects by damaging cellular DNA in HeLa cells: A Comet assay study. Trends in Green Chemistry. 2015;1(1:6):1-9.
http://green-chemistry.imedpub.com/the-indian-medicinal-plant-giloe-tinosporacordifolia-induces-cytotoxic-effects-bydamaging-cellular-dna-in-hela-cells-acomet-assay.pdf
22. Sharma R, In vivo delivery of Tinospora cordifolia root extract preventing radiation-induced dystrophies in mice ovaries. Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 346427, 7 pages.
http://dx.doi.org/10.1155/2015/346427
23. Sharma P, Goyal PK, Modulation of biochemical and antioxidant enzymes in blood by Tinospora cordifolia against gamma radiation mediated damage in mice. Asian J Pharm Clin Res. 2015;8(3):106-112.
http://innovareacademics.in/journals/index.php/ajpcr/article/viewFile/4662/2434
24. Pahadiya S, Sharma J, Alteration of lethal effects of gamma rays in Swiss albino mice by Tinospora cordifolia. Phytother. Res. 2003; 17:552–554.
http://dx.doi.org/10.1002/ptr.1156
25. Rao SK, Rao PS, Alteration in the radiosensitivity of HeLa cells by Dichloromethane extract of Guduchi (Tinospora cordifolia). Integrative Cancer Therapies 2010; 9(4): 378–384.
http://dx.doi.org/10.1177/1534735410387598
26. Sharma P et al, Radiation-induced testicular injury and its amelioration by Tinospora cordifolia (an Indian medicinal plant) extract. Evidence-Based Complementary and Alternative Medicine Volume 2011, Article ID 643847, 9 pages.
http://dx.doi.org/10.1155/2011/643847
27. Sharma P, Goyal PK, Protective action of Tinospora cordifolia extract against radiation induced biochemical alterations in liver. Int J Pharm Pharm Sci. 2014;6(6):305-311.
http://www.ijppsjournal.com/Vol6Issue6/9603.pdf
28. Subramanian M, Chintalwar GJ, Chattopadhyay S, Antioxidant properties of a Tinospora cordifolia polysaccharide against iron-mediated lipid damage and γ-ray induced protein damage. Redox Report. 2002; 7(3):137-143.
http://dx.doi.org/10.1179/135100002125000370
29. Goel HC, Kumar IP, Rana SVS, Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection. Indian J. Exp. Biol. 2002;40:727-734.
http://www.ncbi.nlm.nih.gov/pubmed/12587720
30. Patel A et al, Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A. Indian J Pharmacol. 2013; 45(3): 237–243.
http://dx.doi.org/10.4103/0253-7613.111919
31. Sharma P et al, Radiation induced oxidative stress and its toxicity in testes of mice and their prevention by Tinospora cordifolia extract. Journal of Reproductive Health and Medicine. 2015; 1(2):64–75.
http://dx.doi.org/10.1016/j.jrhm.2015.01.005