Lipid lowering effects of Mikania micrantha kunth extract in hypercholesterolemic rats

Hypercholesterolemia is recognized as a major causative factor for the development of cardiovascular diseases (CVDs) that remains the leading cause of deaths globally. Mikania micrantha Kunth, locally known as “Selaput tunggul” in Malaysia, has been used as a folk medicine to treat hypercholesterolemia and associated cardiovascular diseases. The present study aimed to determine the cholesterol-lowering effects of ethyl acetate M. micrantha stems (EAMMS) extract in hypercholesterolemic-induced Sprague-Dawley rats. Rats were divided into two groups; normal group (NC) and hypercholesterolemia-induced groups (HCD) for initial 4 weeks. After the 4th week of the induction period, the group were divided into five groups: 1% HCD (PC), 1% HCD + Simvastatin (10 mg/kg of body weight (BW)), 1% HCD + EAMMS (50 mg/kg/BW), 1% HCD + EAMMS (100 mg/kg/BW) and 1% HCD + EAMMS (200 mg/kg/BW) during the treatment periods. Blood serum and tissues were collected for haematological, biochemical, histopathological, lipid peroxidation, enzymatic activities and protein expression analyses. LC-MS/MS analysis showed EAMMS extract contained theobromine, ishwarol, pheophorbides and dihydromikanolide. Changes of body weight was observed for all hypercholesterolaemic rats after four weeks of treatment period compared to normal group. Administration of EAMMS extract at 100 mg/kg/BW showed significantly (p<0.05) decreased serum total cholesterol (TC) (1.53±0.11 mmol/L) whereby EAMMS extract at 200 mg/kg/BW significantly (p<0.05) reduced low density lipoprotein (LDL) at 1.02 ± 0.26 mmol/L. Serum liver profiles of alanine aminotransferase (ALT) (134.00 ± 4.95 U/L) and aspartate aminotransferase (AST) (148.5 ± 4.0 U/L) were decreased significantly (p<0.05) by EAMMS extract at 50 mg/kg/BW and 200 mg/kg/BW, respectively. Lipid peroxidation marked a significant (p<0.05) decreased in serum MDA level observed in EAMMS-treated at 100 mg/kg (143.54 ± 2.20 ng/mL) when compared to the PC group. Treatment with EAMMS also exhibited the greatest inhibitory activities of enzymes HMGCR and ACAT2 at the dosages of 100 mg/kg (254.22 ± 8.64 pg/mL) and 50 mg/kg (405.87 ± 0.76 pg/mL), respectively, compared to the PC group. Treatment with EAMMS extract ameliorated and reduced the pathological changes in the liver. From the LC-MS/MS proteomic analysis, twenty-six differentially expressed proteins, comprising of 9 upregulated and 17 downregulated proteins were associated with hypercholesterolemia. In addition, PPI network analysis of all expressed proteins was characterized by 30 nodes and 46 interactions. In conclusion, overall studies demonstrated the potential anti-hypercholesterolemic effects of M. micrantha at the lowest concentration and provide understanding on the molecular targets of EAMMS extract, which could be used for further study on the putative anti-hypercholesterolemic properties.

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