A pilot study to evaluate the safety and efficacy of Murraya koenigii (Herbal Extract Formulation) in the management of Obesity

Brief Summary of Obesity NIPER ProtocolVersion 002 PROPOSAL FOR COLLABORATIVE CLINICAL RESEARCH PROJECT A pilot study to evaluate the safety and efficacy of Murraya koenigii Herbal Extract Formulation in the management of Obesity Submitted by Shri Dhanwantry Ayurvedic College and Hospital, Sector 46 B, Chandigarh National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali Title of the Study A pilot study to evaluate the safety and efficacy of Murraya koenigii Herbal Extract Formulation in the management of Obesity Aims and objectives Primary objective To evaluate and compare the efficacy of herbal extract formulations Murraya koenigii and Garcinia cambogia in the management of Obesity. Secondary Objective To evaluate the safety of herbal extract formulations Murraya koenigii and Garcinia cambogia in the management of Obesity To evaluate the efficacy of herbal extract formulations Murraya koenigii and Garcinia cambogia in the management of Obesity Study Design Sample size justification Calculated for piolet study minimal number. Study Intervention Trial DrugIntervention references The preclinical data of the trial drugintervention are as follows Summary of obtained results from in vitro cell viability and antiobesity activity in 3T3L1 cells and in vivo anti obesity activity on C57BL6J mice and repeated dose toxicity study and pharmacokinetic study on Sprague Dawley rats A study described earlier from our lab revealed that dichloromethane, ethyl acetate, and methanol extracts of M. koenigii leaves exhibited more than 80 pancreatic lipase inhibitory activity. The carbazole alkaloids, mahanimbine and koenigicine at concentrations of 15 M, while girinimbine and koenimbine at concentrations of 4 M, did not show any toxicity to 3T3L1 adipocytes. According to in vitro antiobesogenic assay, koenigicine showed lowest lipid accumulation 41.495.53 at 15 M concentration compared to control cells 100 lipid accumulation and positive control, quercetin 50.976.39 at 25 M concentration. Koenimbine and girinimbine at 15 M concentration revealed 45.292.58 and 47.950.13 while mahanimbine showed 50.764.09 lipid accumulation in 3T3L1 adipocytes. Thus, the preclinical studies using 3T3L1 cell lines have provided substantial evidence supporting the efficacy of M. koenigii. Biomarkers identified with good antiadipogenic potential should be further studied in vivo mice models of obesity to gain insights into the futuristic utilization of curry leaves as a nutraceutical intervention for prevention of obesity. Figure 1 Annexure I shows the cell viability assay performed on 3T3L1 adipocytes, and the in vitro antiadipogenic assay of carbazole alkaloids of Murraya koenigii is shown in Figure 2 Annexure I. Both Murraya koenigii methanolic extract MKME and alkaloidenriched fraction AEF displayed antiobesogenic activity at 25 gmL concentration in vitro and showed 54.06 3.86 and 37.46 3.17 lipid accumulation, respectively compared to control. Further, supplementation of AEF and MKME in high fat diet HFDfed C57BL6J mice helped in controlling weight gain, improved dyslipidemia and glucose intolerance significantly. AEF showed better antiobesity activity than MKME both in vitro and in vivo study. AEF not only lowered LDL levels, but simultaneously elevated HDL levels, which is the pivotal insight of the study. Repeated administration of AEF up to 1 gkg dose for 28 days showed no pathological tissue damage. Both MKME and AEF