Comparision of Pharmacological profiles of Curcuma longa Extracts with metformin in rodents

Abstract

Curcuma longa is a plant of the Zingiberaceae family widely cultivated in several tropical parts of Asia. It is also known as “Indian Solid Gold” and “Indian Saffron” due to its yellow colour. Aromatic yellow colored roots or rhizomes of the plant, commonly known as turmeric, are often used in Ayurvedic and other traditionally known systems of medicine as a tonic or as an adjuvant for prevention and cure of chronic inflammatory disorders. The structurally analogous yellow colored diarylheptanoids isolated from turmeric are collectively referred as curcuminoids, which are the quantitatively major bioactive constituents of Curcuma longa. Metformin is currently an antidiabetic drug of first choice for prevention and treatment of diverse spectrums of comorbidities associated with diabetes. Numerous therapeutically interesting bioactivities of metformin are quite analogous to those of curcuminoids, and it has been reported in vitro models that curcuminoids are several hundred folds more effective than metformin. Therefore, it was of interest to experimentally verify the possibility that metformin like stress response modulating efficacies of curcuminoids are also involved in its therapeutically interesting bioactivities observed in animal models. Therefore, present work was designed to evaluate analytically standardized Curcuma longa extract in respect to its qualitative comparison with metformin and to explore its potential in the management of comorbid anxiety and depression like disorders generally associated with diabetes followed by elucidation of its mechanism of action(s). The analytically characterized four different Curcuma longa extracts (CLE-1H: contains total curcuminoids 21.84% w/w by HPLC), (CLE-2B: contains total curcuminoids 18.83% w/w by HPLC), (CLE-3R: contains total curcuminoids 95.49% w/w by HPLC) and (CLE-4M: contains total curcuminoids 16.6% w/w by HPLC) quantified to contain curcumin, demethoxycurcumin and bisdemethoxycurcumin (17.93 %, 3.39 %, 0.52 % w/w), (15.45 %, 2.92%, 0.46 % w/w), (77.94%, 15.03 %, 2.52 % w/w) and (13.88%, 2.46 %, 0.26 % w/w) respectively, were used. On the basis of results obtained from pilot studies, 10 mg/kg dose of CLE-3R was selected to compare its further pharmacological activities with 50 mg/kg dose of metformin. Observations made out from these efforts strongly suggest that broad spectrum of pharmacological activity profile of CLE-3R is possibly due to its ability to protect animals against mental stress induced perturbations. Observation of this study revealed that 10 mg/kg dose of CLE-3R could be suitable dose to prevention and treatment of mental and physical health problems in stressed condition. Results of these experiments also suggest that repeated dose of CLE-3R is necessary for achieving its therapeutic effect. CLE-3R and metformin both have significant adaptogenic activity and both are beneficial in management of altered insulin level, hyperglycemia and dyslipidemia. Results further revealed that, CLE-3R has significant antidepressant and anxiolytic activity than metformin, although hyperglycemia and insulin deficiency during streptozotocin induced diabetes is significantly improved by both, metformin as well as CLE-3R. Brain monoaminergic and oxidative defense mechanisms are also likely to be involved in observed effects of CLE-3R and metformin. Observations concluded that, Curcuma longa is another adaptogenic herb with a uniquely broad psychopharmacological activity profile and could be herbal lead for prevention and treatment of neurological comorbidities commonly associated with diabetes. Curcuminoids are quantitatively the major stress response modulating secondary metabolites of the plant. The bioassay procedure used in this study is well suited for identifying bioactive constituents, therapeutic interesting dose and duration of phytomedicines like Curcuma longa extract. Further efforts to identify the roles of diverse other known bioactive secondary metabolites of the plant are necessary for better understanding of the Ayurvedic pharmacology of Curcuma longa.