• 1) J Ethnopharmacol. 2005 Jan 15; 96(3):445-9. E pub 2004 Nov 23.

The efficacy of Tinospora cordifolia (TC) extract in patients of allergic rhinitis was assessed in a randomized double blind placebo controlled trial. Seventy-five patients were randomly given either TC or placebo for 8 weeks. They were clinically examined and Hb %, TLC, DLC and nasal smear was done. At the end of trial baseline investigations were repeated, drug decoded and results analyzed. With TC treatment 100% relief was reported from sneezing in 83% patients, in 69% from nasal discharge, in 61% from nasal obstruction and in 71% from nasal pruritus. In placebo group, there was no relief in 79% from sneezing, in 84.8% from nasal discharge, in 83% from nasal obstruction, and in 88% from nasal pruritus. The difference between TC and placebo groups was highly significant. TLC increased in 69% patients in drug treated group and in only 11% with placebo. After TC, eosinophil and neutrophil count decreased and goblet cells were absent in nasal smear. After placebo, decrease in eosinophil and neutrophil count was marginal and goblet cells were present. TC significantly decreased all symptoms of allergic rhinitis. Nasal smear cytology and leukocyte count correlated with clinical findings. TC was well tolerated.

• 2) Int Immunopharmacol. 2004 Dec 15;4(13):1645-59.

An alpha-D-glucan (RR1) composed of (1-->4) linked back bone and (1-->6) linked branches with a molecular mass of >550 kDa and exhibiting unique immune stimulating properties is isolated and characterized from the medicinal plant Tinospora cordifolia. This novel polysaccharide is noncytotoxic and nonproliferating to normal lymphocytes as well as tumor cell lines at 0-1000 microg/ml. It activated different subsets of the lymphocytes such as natural killer (NK) cells (331%), T cells (102%), and B cells (39%) at 100 microg/ml concentration. The significant activation of NK cells is associated with the dose-dependent killing of tumor cells by activated normal lymphocytes in a functional assay. Immune activation by RR1 in normal lymphocytes elicited the synthesis of interleukin (IL)-1beta (1080 pg/ml), IL-6 (21,833 pg/ml), IL-12 p70 (50.19 pg/ml), IL-12 p40 (918.23 pg/ml), IL-18 (27.47 pg/ml), IFN- gamma (90.16 pg/ml), tumor necrosis factor (TNF)-alpha (2225 pg/ml) and monocyte chemoattractant protein (MCP)-1 (2307 pg/ml) at 100 microg/ml concentration, while it did not induce the production of IL-2, IL-4, IL-10, interferon (IFN)-alpha and TNF-beta. The cytokine profile clearly demonstrates the Th1 pathway of T helper cell differentiation essential for cell mediated immunity, with a self-regulatory mechanism for the control of its overproduction. RR1 also activated the complements in the alternate pathway, demonstrated by a stepwise increase in C3a des Arg components. Incidentally, RR1 stimulation did not produce any oxidative stress or inducible nitric oxide synthase (iNOS) in the lymphocytes or any significant increase in nitric oxide production. The water solubility, high molecular mass, activation of lymphocytes especially NK cells, complement activation, Th1 pathway-associated cytokine profile, together with a low level of nitric oxide synthesis and absence of oxidative stress confer important immunoprotective potential to this novel alpha-D-glucan.

• 3) Fitoterapia. 2006 Jan;77(1):1-11. Epub 2005 Dec 2.

The present study investigates the effect of in vivo administration of alcoholic extract of Tinospora cordifolia whole plant (ALTC) on the proliferation and myeloid differentiation of bone marrow hematopoietic precursor cells in mice bearing a transplantable T cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL). BMC obtained from ALTC administered DL-bearing mice showed an enhanced BMC proliferation and colony forming ability in vitro in response to L929 conditioned medium as a source of colony stimulating factor (CSF). The number of granulocyte-macrophages colony (CFU-GM) was predominantly higher in the cultures of BMC obtained from ALTC administered mice as compared to mice injected with PBS alone. An increase in the count of bone marrow derived macrophages (BMDM) from ALTC administered mice was also observed along with an increase in the count of tumor associated macrophages. The BMDM obtained from ALTC administered mice showed an enhanced response to signal of LPS for activation to produce IL-1 and TNF. This study indicates that the T. cordifolia can influence the myeloid differentiation of bone marrow progenitor cells and the recruitment of macrophages in response to tumor growth in situ.

• 4) Phytomedicine. 2005 Apr;12(4):264-70.

Pepticare, a herbomineral formulation of the Ayurveda medicine consisting of the herbal drugs: Glycyrrhiza glabra, Emblica officinalis and Tinospora cordifolia, was tested for its anti-ulcer and anti-oxidant activity in rats. Effects of various doses (125, 250, 500 and 1000mg/kg, p.o.) of Pepticare were studied on gastric secretion and gastric ulcers in pylorus-ligation and on ethanol-induced gastric mucosal injury in rats. The reduction in ulcer index in both the models along with the reduction in volume and total acidity, and an increase in the pH of gastric fluid in pylorus-ligated rats proved the anti-ulcer activity of Pepticare. It was also found that Pepticare was more potent than G. glabra alone in protecting against pylorus-ligation and ethanol-induced ulcers. The increase in the levels of superoxide dismutase, catalase, reduced glutathione and membrane bound enzymes like Ca2+ ATPase, Mg2+ ATPase and Na+ K+ ATPase and decrease in lipid peroxidation in both the models proved the anti-oxidant activity of the formulation. Thus it can be concluded that Pepticare possesses anti-ulcer activity, which can be attributed to its anti-oxidant mechanism of action.

• 5) BMC Complement Altern Med. 2004 Aug 13;4:11.

BACKGROUND: The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis and ultimately cell death. Rubia cordifolia (RC), Fagonia cretica linn (FC) and Tinospora cordifolia (TC) have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. However, their mechanism of action was largely unknown. We therefore selected these herbs for the present study to test their neuroprotective ability and the associated mechanism in rat hippocampal slices subjected to oxygen-glucose deprivation (OGD). METHODS: Hippocampal Slices were subjected to OGD (oxygen glucose deprivation) and divided into 3 groups: control, OGD and OGD + drug treated. Cytosolic Cu-Zn superoxide dismutase (Cu-Zn SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), nitric oxide (NO) was measured as nitrite (NO2) in the supernatant and protein assays were performed in the respective groups at various time intervals. EPR was used to establish the antioxidant effect of RC, FC and TC with respect to superoxide anion (O2.-), hydroxyl radicals (. OH), nitric oxide (NO) radical and peroxynitrite anion (ONOO) generated from pyrogallol, menadione, DETA-NO and Sin-1 respectively. RT-PCR was performed for the three groups for GCLC, iNOS, Cu-Zn SOD and GAPDH gene expression. RESULTS: All the three herbs were effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as studied by electron paramagnetic resonance spectroscopy. In addition all the three herbs significantly diminished the expression of iNOS gene after 48 hours which plays a major role in neuronal injury during hypoxia/ischemia. CONCLUSIONS: RC, FC and TC therefore attenuate oxidative stress mediated cell injury during OGD and exert the above effects at both the cytosolic as well as at gene expression level and may be an effective therapeutic tool against ischemic brain damage.