Response surface methodology based development of an optimized polyherbal formulation and evaluation of its anti-diabetic and anti-obesity potential in high-fat diet-induced obese mice.

Background and aim: The seeds of Nelumbo nucifera, Chenopodium quinoa and Salvia hispanica are known as super foods due to their various therapeutic properties. The present study aimed to develop an optimized polyherbal formulation from edible seeds aqueous extract and to evaluate its anti-diabetic and lipase inhibitory effect on diet-induced obese diabetic mice. Experimental procedure: Response surface methodology based various formulations were evaluated for their potent anti-diabetic, lipase-inhibitory and antioxidant activities. Acute toxicity of the best optimized formulation was conducted. The mice were fed a high fat diet for 10 weeks resulting in hyperglycemia and obesity. Oral tolerance tests (sucrose, starch and lipid) of the formulation were performed. The mice were supplemented with different doses (125, 250 and 500 mg/kg) of the formulation for 6 weeks. The body weight and blood glucose level were monitored on a weekly basis. Finally, histological alterations and lipid profiles were analysed. Results and conclusion: The formulation containing equal concentration (1.5 mg/ml) of each seed extract showed maximum bioactivities. The formulation was found to be safe during toxicity assay. The tolerance tests supported the anti-diabetic and anti-obesity effect. Higher dose (500 mg/kg) of the formulation significantly (p < 0.01) lowered elevated fasting blood glucose, lipid indices and ameliorated the histological alterations in liver, kidney and pancreas caused by high fat diet. We demonstrated for the first time that the developed aqueous extract optimized formulation possess anti-diabetic and anti-obesity potential and thus could be used as adjuvant therapy for holistic management of type 2 diabetes mellitus.

Amelioration of hyperglycemia and hyperlipidemia in a high-fat diet-fed mice by supplementation of a developed optimized polyherbal formulation.

This study evaluated in vivo anti-diabetic and anti-obesity activity of a polyherbal formulation's methanolic extract containing an optimized ratio of edible seeds (Salvia hispanica, Chenopodium quinoa, Nelumbo nucifera). Diet-induced obese mice model (C57BL/6) was developed by feeding the mice a high-fat diet for 10 weeks resulting in hyperglycemia and obesity. Different doses (125, 250 and 500 mg/kg of body weight) of formulation were administered orally daily for 6 weeks. Fasting blood glucose and body weight were monitored throughout the study. At the end of the study, serum parameters were analyzed and histological examinations were performed. There was a significant reduction in fasting blood glucose levels and body weight in animal groups receiving polyherbal formulation. Lipid profile was improved as revealed by a reduction in serum triglycerides and total cholesterol. Histological study showed an improvement in liver, kidney and pancreatic sections of treated mice. High-performance thin layer chromatography was performed to identify the phytochemicals responsible for the above-mentioned bioactivities. The results revealed the presence of flavonoid (rutin) in seeds of N.nucifera and in the polyherbal formulation. For the first time, this study demonstrated the anti-diabetic and anti-obesity potential of the optimized formulation. The formulation can be used as a potential therapy for management of diabesity.

Human adipose tissue mesenchymal stem cells as a novel treatment modality for correcting obesity induced metabolic dysregulation.

OBJECTIVE: Obesity induced metabolic dysregulation results in cluster of chronic conditions mainly hyperglycemia, hyperinsulinemia, dyslipidemia, diabetes, cardiovascular complications and insulin resistance. To investigate the effect of i.m. injection of human adipose tissue derived mesenchymal stem cells and its secretome in correcting obesity induced metabolic dysregulation in high fat diet fed obese model of mice and understand its mechanism of action. SUBJECTS: We injected human adipose tissue derived mesenchymal stem cells (ADMSCs) suspension (CS), conditioned medium (CM) and the cell lysate (CL) intramuscularly in high fat diet (HFD)-induced C57BL/6 mice. Metformin was used as a positive control. ADMSCs were traced in vivo for its bio distribution after injection at different time points. RESULTS: ADMSCs-treated mice exhibited remarkable decrease in insulin resistance as quantified by HOMA-IR and triglyceride glucose index with concomitant decrease in oxidized LDL and IL6 as compared with the untreated control. CS injection showed improvement in glucose tolerance and reduction in fatty infiltration in the liver, macrophage infiltration in adipose and hypertrophy of the islets resulting from HFD. Upregulation of miRNA-206, MyoD and increase in protein content of the skeletal muscle in CS-treated mice indicates plausible mechanism of action of ADMSCs treatment in ameliorating IR in HFD mice. CONCLUSION: Of all the three treatments, CS was found to be the best. ADMSCs were found to have migrated to different organs in order to bring about the correction in dysregulated metabolism induced by obesity. Our results open up a novel treatment modality for possible therapeutic usage in human subjects by employing autologous or allogeneic ADMSCs for the better management of obesity induced metabolic dysregulation.

Treatment with adipose derived mesenchymal stem cells and their conditioned media reverse carrageenan induced paw oedema in db/db mice.

Mesenchymal stem cells are known for anti inflammatory and immunomodulatory activities. The aim of our study was to evaluate the effect of human adipose derived mesenchymal stem cells (hADMSCs) and its conditioned media (CM) on carrageenan induced acute inflammation in db/db mice. We injected 5×105 ADMSCs or the CM in the inflamed paw. We assessed the paw volume, serum IL6 levels and histopathology of the paw to reveal the anti inflammatory effect. We observed a single injection of hADMSCs or CM could reverse the inflammation within 24h as evidenced by reduction in paw volume, IL6 levels and histological examination. Our result equivocally demonstrates the role of CM in normalising the inflammation better than hADMSCs. This study will pave way for an alternative to anti inflammatory drugs.