A Network Pharmacology Study of the Molecular Mechanisms of Hypericum japonicum in the Treatment of Cholestatic Hepatitis with Validation in an Alpha-Naphthylisothiocyanate (ANIT) Hepatotoxicity Rat Model

Abstract

Background This network pharmacology study aimed to identify the active compounds and molecular mechanisms involved in the effects of Hypericum japonicum on cholestatic hepatitis. We validated the findings in an alpha-naphthylisothiocyanate (ANIT) rat model of hepatotoxicity. Material/Methods The chemical constituents and targets of H. japonicum and target genes previously associated with cholestatic hepatitis were retrieved from public databases. A network was constructed using Cytoscape 3.7.2 software and the STRING database and potential protein functions were analyzed based on the public platform of bioinformatics. ANIT was used to induce cholestatic hepatitis in a rat model using 36 Sprague-Dawley rats, and this model was used to investigate intervention with 3 doses of quercetin (low-dose, 50 mg/kg; medium-dose, 100 mg/kg; and high-dose, 200 mg/kg), the main active component of H. japonicum . Levels of serum biochemical indexes were measured by commercial kits, and the messenger RNA (mRNA) levels of markers of liver and mitochondrial function and oxidative stress were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results The main active ingredients of H. japonicum were quercetin, kaempferol, and tetramethoxyluteolin, and their key targets included prostaglandin G/H synthase 2 (PTGS2), B-cell lymphoma-2 (BCL2), cholesterol 7-alpha hydroxylase (CYP7A1), and farnesoid X receptor (FXR). Quercetin intervention promoted recovery from cholestatic hepatitis. Conclusions The findings from this research provide support for future research on the roles of quercetin, kaempferol, and tetramethoxyluteolin in human liver disease and the roles of the PTGS2, BCL2, CYP7A1, and FXR genes in cholestatic hepatitis.

The Mechanisms of Yinchensini Decoction in Treating Hepatitis B were Explored by Network Pharmacology and Existing Literatures

“…For the gene target BCL2, beta-sitosterol can promote the apoptosis of tumor cells by inhibiting BCL2 and PI3K signaling pathways 30 . Quercetin and kaempferol can treat hepatitis and its related diseases by inhibiting BCL2 and its transcription process 31 . Naringenin promotes the apoptosis of tumor cells by inhibiting BCL2 and its downstream mRNA levels, in other words, naringenin inhibits BCL2 transcription 32 .…”

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses

“…Our previous research also proved that Hypericum japonicum has the effect of improving cholestatic hepatitis (Feng et al, 2021). The quercetin 7-rhamnoside (Q7R) is main flavonoid component of Hypericum japonicum, which has strong hepatoprotective, antioxidant, and antiviral activity (Choi et al, 2009;Song et al, 2011).…”

Dietary Polyphenols Alleviate Autoimmune Liver Disease by Mediating the Intestinal Microenvironment: Challenges and Hopes

“…60 In addition, curcumin, quercetin, and sandalwood oil have the potential to alleviate cholestatic AILD and liver injury as plant antitoxins (Table 6). 61,62 Regulating the Liver Epigenetics. Dietary polyphenols have been used as potential regulators of cellular DNA methylation and have the opportunity to be candidates for chemoprevention.…”

“…In addition, curcumin, quercetin, and sandalwood oil have the potential to alleviate cholestatic AILD and liver injury as plant antitoxins (Table ). , …”