Evaluation of the anti-inflammatory activity of Tinospora cordifolia (Willd.) Miers chloroform extract - a preclinical study.

OBJECTIVES

Tinospora cordifolia (Willd.) Miers is an inevitable ingredient of Ayurvedic rasayanas for the treatment of disorders with unregulated inflammation. However, studies regarding the mechanism of anti-inflammatory potential of this plant at the molecular level are lacking.

METHODS

In vitro evaluations were conducted in RAW264.7 macrophages which were preincubated with chloroform extract of T. cordifolia (CETC) and subsequently stimulated with LPS. The expressions of COX-2, TNF-α and iNOS genes were analysed by SQRT-PCR and Western blot, cytokines (IL-6, IL-1β and PGE2 ) levels by ELISA, NF-κB activation and p38 MAPK phosphorylation by Immunoblot and confocal imaging. Anti-inflammatory potential of CETC was validated further in a rat model of carrageenan-induced hind paw edema. Phytochemical characterisation was carried out using the HPLC technique.

KEY FINDINGS: The LPS-induced upregulation of proinflammatory biomarkers was significantly prevented by CETC, without inhibiting COX-1. CETC- and LPS-incubated cells showed reduced phosphorylated p38 MAPK levels, and higher levels NF-κB were retained in cytoplasm. Rats pretreated with CETC showed a statistically significant decrease in paw oedema (P ≤ 0.05), and HPLC characterisation detected stigmasterol and β-sitosterol. The LD50 of CETC lies above 2000 mg/Kg body weight.

CONCLUSIONS

These findings encourage us strongly to focus on CETC to develop anti-inflammatory drugs with lower degree of inhibition to the constitutively expressing COX-1.