Protective Effect of Hedyotis diffusa Willd. Ethanol Extract on Isoniazid-Induced Liver Injury in the Zebrafish Model

Abstract

This study aims to investigate the hepatoprotective effect and molecular mechanism of Hedyotis diffusa Willd. ethanol extract (HDWE) against isoniazid (INH)-induced liver injury in the zebrafish model. Methods: INH-induced liver injury model was established by adding an immersion bath of INH in 3 days post-fertilisation (dpf) healthy transgenic zebrafish with liver-specific fluorescence (L-FABP: EGFP). HDWE and INH were given to the zebrafish to observe liver morphology and pathology, fluorescence intensity, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and superoxide dismutase (SOD), as well as the content of glutathione (GSH). The chemical composition of HDWE was analysed using high-performance liquid chromatography coupled with a quadrupole-time-of flight hybrid mass spectrometer (HPLC-Q-TOF-MS). The bioactive compounds, molecular targets and signalling pathways of HDWE were predicted using network pharmacology. Subsequently, molecular docking was adopted to analyze the affinities between the bioactive components and targets by Autodock. Finally, in vitro experiments were conducted to further verify the findings. Results: Our findings showed that HDWE had a remarkable protective effect on INH-induced liver injury in zebrafish. Twenty compounds in HDWE were identified. Nineteen hub targets were identified as possible targets of HDWE, and a compound-targetpathway network was constructed. Nine bioactive compounds, ten molecular targets, and seven key signalling pathways were found to play a pivotal role in the hepatoprotective effect of HDWE against INH-induced liver injury. In vitro studies revealed that the important bioactive compound quercetin-3-O-sambubioside (QSA) could significantly reverse INH-induced cell viability decreases and had a significant effect on the associated targets predicted by network pharmacology and molecular docking. Conclusion:In this study, through the research of hepatoprotective effect of HDWE and bioinformatics analysis, the bioactive compounds, important pathways and key molecular targets were discovered. These findings could provide scientific evidence for the use of HDW in liver injury and prove to help explore its efficacy and the mechanism of action.

Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis

“…Quercetin-3-O-sanburoside is a glycoside derivative of quercetin that was mentioned in a study by Wang et al, which focused on the hepatoprotective effects of Hedyotis diffusa Willd [63]. The researchers observed significant protective effects against liver injury and identified quercetin-3-O-sambubioside as the key active compound.…”

Network pharmacology, bioinformatics, and experimental validation to identify the role of Hedyotis diffusa willd against gastric cancer through the activation of the endoplasmic reticulum stress

“…In traditional Chinese medicine, Hedyotis diffusa Willd (Family Rubiaceae) is commonly known as Bai Hua She Cao (BHSSC) in pinyin. According to contemporary pharmacological research, BHSSC possesses a wide range of pharmacological properties, including anti-inflammatory [ 4 ], hepatoprotective effect [ 5 , 6 ], antiviral efficacy [ 7 ], antioxidant [ 8 ] and neuroprotective [ 9 ], anti-tumor [ 10 ], and other biological activities.…”

Neohesperidin Dihydrochalcone Improves Hyperglycemia and Insulin Resistance in Diabetic Zebrafish

“…It is an ideal animal model in many biological fields, including toxicological research, pharmacological analysis, and genetic analysis . The zebrafish genome is highly similar to the human genome, and the functional and histological features of zebrafish pancreas are similar to those of mammalian pancreas. , In addition, other tissues and organs that participate in glycometabolism, such as skeletal muscle, liver, and other adipocyte tissues, are highly conserved . This implies that the results of drug experiments on zebrafish are, in most cases, also applicable to humans.…”