Hederagenin Exerts Potential Antilipemic Effect via p38MAPK Pathway in Oleic Acid-induced HepG2 cells and in Hyperlipidemic Rats

Abstract

Hederagenin, a natural compound distributed in many medicinal plants, has a variety of pharmacological properties including anti-bacteria, anti-infl ammation, antioxidation, and anti-apoptosis.. The aim of this study was to evaluate the effects of hederagenin on decreasing blood lipid and anti-oxidative stress in oleic acid-induced HepG2 cells and hyperlipidemic rats, and explore underlying mechanisms. In vitro, TG was used as the index to verify the lipid-lowering effect of hederagenin in oleic acid-induced HepG2 cells. In vivo, TC, TG, LDL-C, and HDL-C were used as direct indicators to study the antilipemic effect of hederagenin in hyperlipidemic rats. MDA, SOD, and GSH-PX were measured to analyze the anti-oxidative effect of hederagenin. The signaling pathways of anti-oxidation were evaluated using Western blot. Our results showed that hederagenin (250μmol/L) increased signifi cantly TG clearance rate. In addition, treatment with hederagenin, XZK and simvastatin reduced effectively TC, TG, LDL-C and MDA content, and increased HDL-C, SOD and GSH-PX in HFD rats. Moreover, the phosphorylation level of p38 MAPK was inhibited after administration of hederagenin, XZK and simvastatin.Our results revealed that hederagenin possessed benefi cial potentials for hypolipidemic effects, especially in TG clearance. The mechanism might be associated with inhibition of lipid absorption, reduction of lipid oxidation, and down-regulation of p38MAPK phosphorylation.

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments

“…It was found that (6aR,11aR)‐9,10‐dimethoxy‐6a,11a‐dihydro‐6H‐benzofurano[3,2‐c]chromen‐3‐ol can act on tyrosine tRNA synthetase and tryptophanyl tRNA synthetase TrpRS to modulate the biosynthesis of aminoacyl‐tRNA, regulate DNA damage and apoptosis (Chen et al., 2018). Hederagenin has a variety of pharmacological effects such as reversing hyperlipidemia, anti‐depression, anti‐lipid peroxidation, liver protection, and anti‐inflammation (Choi et al., 2001; Gülçin et al., 2006; Lin et al., 2021; Shen et al., 2023; Yamahara et al., 1979; Yang et al., 2022). Notably, hederagenin can play a protective role in blood vessel wall by modulating lipid metabolism disorder and lipid deposition (Lu et al., 2015).…”

Study on the Mechanism of Liuwei Dihuang Pill in Treating Hypothyroidism Based on Network Pharmacology

“…According to the drug-active ingredient-target network analysis, quercetin, kaempferol, beta-sitosterol, diosgenin, kadsurenone, hederagenin, sitosterol and stigmasterol may play a main role in the treatment of hypothyroidism.Modern pharmacological studies have shown that [17] quercetin has anti-inflammatory, antioxidant, immunomodulatory and anti-tumor effects.Studies have shown [18] that quercetin can activate TPO of rats, make them produce well-differentiated metabolite 3,5-L-diiodotyrosine, and promote the expression of TPO and the production of L-thyroxine.Quercetin also has certain regulatory effect on inflammatory release and apoptosis of epithelial cells [19] ;Stigmasterol has the effects of anti-inflammation, lowering cholesterol and improving memory [20][21][22] ;β-sitosterol can inhibit apoptosis of granulosa cells, which is related to regulation of endocrine hormone, neuroprotection and anti-inflammation [21][22][23][24] ;Kaempferol has antioxidant, anti-inflammatory, heart protection, nerve protection, anti-diabetes, anti-osteoporosis, anti-anxiety effects [25].Diosgenin can improve cardiac function and reduce inflammatory reaction, which is related to cell apoptosis and endocrine hormone regulation process [26][27].Kadsurenone inhibits inflammatory mediators [28].Hederagenin is neuroprotective, anti-inflammatory, anti-apoptotic, and lipid-lowering [29][30].Conclusion: These components may be the core components of Liuwei Dihuang pill in the treatment of hypothyroidism, and have certain clinical research value.…”