Effect of Huanglian Jiedu Decoction on cardiac endoplasmic reticulum stress in spontaneously hypertensive rats

Huanglian Jiedu Decoction(HLJDD)is a quintessential prescription renowned for its heat-clearing and detoxifying properties.It is primarily prescribed to counteract the syndrome characterized by the excessive heat of the Sanjiao fire.Notably,the hyperactivity of liver fire is frequently linked with hypertension,where wind fire and wind toxicity emerge as pivotal pathogenic factors.This study aimed to investigate the impact of HLJDD on the endoplasmic reticulum in spontaneously hypertensive rats(SHR),further delving into the interplay between endoplasmic reticulum stress(ERS)and myocardial remodeling and damage.Fifty SHR rats were stratified randomly into five cohorts:model,low-dose HLJDD,medium-dose HLJDD,high-dose HLJDD,and captopril groups.For comparison,a set of Wistar-Kyoto(WKY)rats served as the baseline control group,with each group comprising 10 rats.While the model and control groups received equivalent volumes of normal saline via gavage,the other groups were administered the respective drug dosages through the same route daily for a span of 6 weeks.Upon the experiment’s conclusion,metrics such as the heart mass index(HWI)and left ventricular mass index(LVWI)were assessed.Cardiac tissue anomalies were identified using H&E staining,while ERS-related protein and mRNA expression levels were ascertained via Western blotting analysis and qPCR.Moreover,TUNEL staining was employed to detect cardiomyocyte apoptosis.The findings indicated that increasing HLJDD concentrations corresponded with escalated HWI and LVWI in rat hearts(P<0.05).There was a marked enhancement in myocardial structural integrity,accompanied by a notable reduction in collagen fibers.The mRNA and protein expressions of myocardial inositol-dependent enzyme 1α(IRE1α),X-box binding protein 1(XBP1),glycoregulatory protein 78(GRP78),and CCAAT enhancer binding protein homologous protein(CHOP)in the medium and high-dose groups saw significant declines(P<0.05).These effects mirrored those observed in the captopril group.The study underscored HLJDD’s efficacy in mitigating myocardial tissue damage in SHR.This therapeutic effect was potentially attributed to the downregulation of IRE1α,XBP1,GRP78,and CHOP,curbing excessive ERS,diminishing cardiomyocyte apoptosis,and thereby conferring cardioprotection.

Effect of Huanglian Jiedu Decoction on vascular endothelium factor and expression of RhoA protein factor in young spontaneously hypertensive rats

To investigate the mechanism of effect of Huanglian Jiedu Decoction(HLJD) on vascular endothelium, we assessed the protective effect of HLJD on vascular endothelium in spontaneously hypertensive rats(SHR) and the expression of RhoA in thoracic aorta. A total of 40 SHR rats were randomly and evenly divided into model group(SHR group), positive group(captopril group), HLJD high-dose group, and HLJD low-dose group. Simultaneously, 10 Wistar Kyoto rats were used in the blank group. All groups were treated by gavage for 6 weeks. The changes of nitric oxide synthase(NOS), von Willebrand factor(vWF), endothelin(ET-1) and calmodulin(CAM) in rat serum were tested by enzyme linked immunosorbent assay(ELISA) method. The expression of RhoA at the protein and mRNA levels in thoracic aorta was determined by Western blotting(WB) and quantitative real-time PCR, respectively. Compare with the blank group after 6 weeks, the levels of ET-l and VWF in serum of the model group were significantly increased(P<0.01), and the levels of NOS and CAM were significantly decreased(P<0.01). Conversely, the levels of ET-1 and vWF in the positive and HLJD groups were significantly decreased(P<0.01 or P<0.05), and the levels of NOS and CAM were significantly increased(P<0.01 or P<0.05) compared with the model group. The expression of Rho A at the mRNA and protein levels was decreased obviously(P<0.05) in HLJD high-dose group. The results shown that HLJD increased diastolic factor(CAM and NOS) in the vascular endothelial of rats, leading to reduced contraction factor(ET-1 and vWF). HLJD revealed the preventive function in the vascular endothelial dysfunction of the early stage hypertension through adjusting secretion of blood vessel endothelium(BVE) relaxing factor and improving vascular endothelial function. The mechanism might be associated with the inhibition of the activity of RhoA protein factor.