Abstract:

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.

Key words: Huanglian Jiedu Decoction, Spontaneous hypertension, Endoplasmic reticulum stress, Myocardial remodeling, IRE1α, XBP1, GRP78, CHOP