Pre- Clinical and Clinical Evaluation of Folk Medicinal Plants of Cholistan Desert for Antidiabetic Activity

Abstract

Diabetes mellitus (DM) is a chronic disease and one of the most important public health challenges facing mankind. The use of the folkloric remedies for the wellbeing of the mankind has been in practice since ancient times. Citrullus colocynthis (Cucurbitaceae), Capparis decidua (Capparaceae) and Fagonia cretica L. (Zygophyllaceae) are the medicinal plants used widely in Punjab, Pakistan. A recent survey has demonstrated that traditional healers and herbalists frequently use these plants to treat diabetes. Initially all the three plants were characterized in vitro and in vivo animal studies to identify the most potent plant amongst these. In the current study, the traditional medicine (TM) of the most effective plant (Fagonia cretica L.) was prepared as a tea and the profile of the main metabolites present in TM, was analyzed via LC/MS/MS. The TM inhibits α-glucosidase in vitro with an IC50 of 4.62±0.27 μg/ml. The hypoglycemic effect of the TM was evaluated in normoglycemic and Streptozotocin-Nicotinamide treated diabetic rats, using glibenclamide as internal control. The hypoglycemic effects were observed upto 3 hrs. The preparation (250 or 500mg/kg body weight) was administered one a day for 21 consecutive days. The dose of 500mg/kg was effective in the management of the disease causing a 45% decrease in plasma glucose level at the end of experimental period on Day 21. Histological analysis of pancreatic sections confirmed that STZ/NIC treatment caused destruction of pancreatic islet cells while pancreatic sections from treatment groups showed that both the extract and Glibenclamide partially prevented this deterioration. The mechanism of this protective effect is unclear. The radical scavenging potential of the ethyl acetate fraction (93%) and the cytotoxic efficiency (4.7±0.21) of the dichloromethane fraction is an edge of Fagonia cretica L. over the other plants under investigation. However, such a finding coupled with the safety profile observed by the biochemical parameters as marker of toxicity, suggests that ingestion of the tea could confer addition benefits and should be investigated further. The formulated tablets of Fagonia cretica L. lyophilized powder showed the physical variables of the formulation (Weight variation, Hardness, Friability and Disintegration) within the pharmacopoeial (BP) limits. The clinical trials of the formulation conducted at Bahawal Victoria Hospital, Bahawalpur have further proven the efficacy of this folkloric medicinal plant in the management of the disease. Fasting and postprandial blood glucose levels coupled with glycosylated haemoglobin levels (HbA1c -an excellent tool to assess the glycemic control over the entire period of time) confirms the claims made by the local healers of the area. Glycaemic control and the safety profile at preliminary levels suggest the incorporation of this folkloric remedy of the area into the treatment options for the management of the disease. However long term clinical trials on lager number of subjects and safety profile for a longer period of time are necessary elements for the integration of this important plant into the main stream treatment options. We have the faith on the basis of the undertaken studies that use of the remedy made from lyophilized powder of the plant extract could be a supportive tool for the claim made by the local healers for the management of disease in Pakistan.