Trichosanthes pericarpium water fraction prevents myocardial cells from apoptosis induced by ox-LDL via increasing its sensitivity to FGF21

BACKGROUND: The traditional Chinese medicine (TCM) Trichosanthes pericarpium (TP) exerts uniquely therapeutic effect on a TCM syndrome of coronary heart disease, the phlegm turbid obstruction syndrome, the primary characteristic of which is severe lipid metabolism disorder. However, the mechanism underlying the remains elusive. OBJECTIVE: We speculated that protecting heart from damaged by hyperlipidemia via evoking fibroblast growth factor 21 (FGF21) signaling may partly account for above mechanism. METHODS: Rat primary myocardial cells (MCs) was isolated from the heart of neonatal rats, and were exposure to oxidized low density lipoprotein (ox-LDL), together with or without the water fraction (TP-W), the effective constituents of TP. RESULTS: Severe apoptosis was could be observed in MCs exposure to ox-LDL, meanwhile, the level of FGF21 in cells and medium increased significantly; however, the upregulation of βKlotho expression was suppressed dramatically, fibroblast receptor substrate 2α (p-FRS2α) could not be adequately phosphorylated too. In cells incubated with both ox-LDL and TP-W, the expression of FGF21 was accelerated notably; moreover, the level of βKlotho and p-FRS2α was promoted memorably while the apoptosis was reduced signally. CONCLUSIONS: TP-W could rescue the apoptosis stimulated by ox-LDL via activating FGF21 signaling, restoring its sensitivity to FGF21 in MCs.