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Qing Gan Zi Shen Decoction (QGZS) is a traditional Chinese formula. It has been extensively used for decades in the treatment of hypertension combined with metabolic diseases, but its cardioprotective effects and underlying mechanisms are poorly understood. To explore the cardioprotective effects and potential mechanisms of QGZS in an animal model of obese hypertension. In this study, spontaneously hypertensive rats (SHRs) were utilized as an animal model to examine the effects of a high-fat diet and two concentrations of QGZS. Echocardiography, hematoxylin eosin (H&E) staining, and wheat germ agglutinin (WGA) staining were employed to assess the cardiac structure and function of the SHRs throughout a 16-week therapy period. Furthermore, Western blotting (WB) and immunofluorescence (IF) were employed to identify the levels of Nrf2 expression in the mitochondria, cytoplasm, and nucleus of the myocardium. Additionally, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to measure mitochondrial morphology and pro-inflammatory cytokine levels, respectively. Furthermore, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to quantify the levels of marker proteins associated with myocardial fibrosis, cardiac inflammation, oxidative stress, and mitochondrial dysfunction. QGZS inhibited weight gain and depressed systolic and mean arterial pressures in high-fat-fed SHRs. Echocardiographic results demonstrated that QGZS prevented the increase in left ventricular mass, restricted the growth of left ventricular diameter, and improved ejection fraction (EF), fractional shortening (FS), and the ratio of early diastolic peak velocity of transmitral flow (E) to late diastolic peak velocity (A) in high-fat-fed SHRs. This suggested that QGZS prevented ventricular remodeling and protected cardiac systolic and diastolic functions. H&E and WGA staining showed that QGZS improved cardiomyocyte disorders and restricted cardiomyocyte hypertrophy. The underlying mechanisms, QGZS attenuated the oxidative stress state, including reducing the generation of reactive oxygen species (ROS) in the myocardium, revitalizing the antioxidant enzyme system, and protecting mitochondrial function. Moreover, QGZS alleviated the pro-inflammatory state in high-fat-fed SHRs. What's more, QGZS significantly increased the expression level of Nrf2 in nuclei and mitochondria in rat heart tissues, exerting a proximate Nrf2 agonist effect. QGZS exerted cardioprotective effects, in part due to its increasing expression of Nrf2 protein in the heart, which promoted Nrf2 nuclear expression. [Display omitted] • In high-fat-induced obese SHRs, Qing Gan Zi Shen reversed ventricular remodeling and protected cardiac function. • In high-fat-induced obese SHRs, Qing Gan Zi Shen alleviated ventricular remodeling and myocardial fibrosis. • QGZS actived Nrf2 to play a role in reducing cardiac inflammation, inhibiting cardiac oxidative stress, and protecting mitochondrial function. [ABSTRACT FROM AUTHOR]

Scutellaria baicalensis (SB) and Coptis chinensis (CC) are widely used traditional Chinese medicine (TCM) for "heat-clearing and damp-drying" and "purging fire and detoxifying". SB-CC are commonly used as a herbal pair for synergistic treatment of various diseases such as bacteria-related infections, metabolic syndromes, and some inflammatory disorders. This herbal pair is commonly used in many famous TCM formula, like Huang-Lian-Jie-Du, Gegen-Qinlian, Banxia Xiexin decoction. Aryl hydrocarbon receptor (AHR) plays an essential role in the disposition of both xenobiotics and endogenous substances through the induction of cytochrome P450 1A (CYP1A) enzymes. Regulation of the AHR-CYP1A axis is increasingly implicated in drug-drug and drug-herb interactions. Research on SB-CC for regulatory effect on the AHR-CYP1A axis is only limited to few compounds. This study aimed to systematically investigate the regulatory effect of SB-CC and its main constitutes on the AHR-CYP1A axis in vitro and in vivo. The livers of mice treated with SB-CC extract were subjected to RNA-sequencing (RNA-seq). The key target genes related to drug metabolism were screened, and the differential expression genes (DEGs) were validated by qRT-PCR, Western blot, and enzyme activity assay. Luciferase reporter gene, qRT-PCR, and Western blot assays were used to determine whether SB-CC and their main constituents could activate AHR and regulate CYP1A expression in HepG2 cells. The effect of SB-CC on the pharmacokinetics of phenacetin, a CYP1A substrate, were further observed in mice to test the net effect of SB-CC on CYP1A functions. The potential CYP1A inhibitors in SB-CC were screened and their inhibitory mechanisms were also studied using human liver microsomes. AHR and drug metabolism system, especially CYP1A1 and CYP1A2, were strongly affected in the liver of SB-CC-treated mice. These results were further validated by the findings that SB-CC increased CYP1A's mRNA, protein expression and activity in mouse liver. In HepG2 cells, SB, CC, baicalin, baicalein, chrysin, oroxylin A, berberine, coptisine and epiberberine increased CYP1A1 mRNA expression in an AHR-dependent way. Interestingly, SB-CC treatment for 14 days only slightly increased the systemic exposure of paracetamol in mice. In the CYP1A inhibition assay, SB, CC, baicalin, baicalein, wogonoside, wogonin, chrysin, oroxylin A, scutellarein, columbamine, coptisine, palmatine, epiberberine, and berberrubine inhibited CYP1A activity in different degree. These results suggested that SB-CC exerted dual regulatory effect on the AHR-CYP1A axis by increasing CYP1A expression but simultaneously inhibiting CYP1A activity, which may contribute to a tight modulation of AHR signaling for homeostatic control. [Display omitted] [ABSTRACT FROM AUTHOR]

The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in "Zhulinsi fuke mifang" in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation. [Display omitted] [ABSTRACT FROM AUTHOR]