Five Constituents Contributed to the Psoraleae Fructus-Induced Hepatotoxicity via Mitochondrial Dysfunction and Apoptosis

Abstract

Backgrounds: Psoraleae Fructus (PF)-induced hepatotoxicity has been reported in clinical and animal experiments. However, the hepatotoxic constituents and mechanisms underlying PF-induced toxicity have remained unclear. Therefore, this study explored the potentially toxic PF components and revealed their relative mechanisms.Methods: The hepatotoxicity of PF water (PFW) and ethanol (PFE) extracts was compared using Kunming mice. The different compositions between PFW and PFE, which were considered toxic compositions, were identified using the UHPLC-Q-Exactive MS method. Then, L02 and HepG2 cell lines were used to evaluate the toxicity of these compositions. Cell viability and apoptosis were determined through the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. An automatic biochemical analyzer detected the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Lastly, we used high-content screening (HCS) to determine the levels of reactive oxygen species (ROS), lipid, and mitochondrial membrane potential (MMP).Results: The ethanol extraction process aggravated the hepatotoxicity of PF, causing more severe injuries. The content of psoralen, isopsoralen, bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol was higher in the PFE than PFW. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol induced cell apoptosis and the AST, ALT, and ALP leakages. Furthermore, these five constituents increased intracellular lipid accumulation and ROS levels but decreased the MMP level.Conclusion: The ethanol extraction process could induce severe PF hepatotoxicity. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol are the main hepatotoxic ingredients. This mechanism could be associated with oxidative stress and mitochondrial damage-mediated apoptosis. Taken together, this study provides a basis for the clinical application of PF that formulates and improves its herbal standards.

Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane

“…in PF were medium toxic. The IC 50 values were various to different cell lines and most of them ranged between 20 and 200 μg/ml ( Song et al, 2018 ; Guo et al, 2021 ; Chen et al, 2022 ). In this study, the total content of IBCL and 4MBCL in PFPE was 18.18%, other compounds (49.26%) mentioned above may have low cytotoxicity to Caco-2 cells.…”

Detoxification technology and mechanism of processing with Angelicae sinensis radix in reducing the hepatotoxicity induced by rhizoma Dioscoreae bulbiferae in vivo

“…Results displayed that DB content in RDB and processed products of ASR-processed RDB all decreased to a certain extent, and the DB content in the processed products of A 3 B 2 C 1 decreased the most, which was 0.958 mg/g, with the reversal rate of 21.9%, suggested that processing with ASR reduced the toxicity induced by RDB, and the A 3 B 2 C 1 group had the best attenuating effect. Under physiological conditions, there were only trace amounts of ALT and AST in the blood (Yuan et al, 2018;Guo et al, 2021). When hepatocytes were damaged, large amounts of ALT and AST will enter the blood, resulting in an obvious augment in serum ALT and AST levels (Salahshoor et al, 2018;Kaya et al, 2021;Li H. et al, 2021).…”

“…Under physiological conditions, there were only trace amounts of ALT and AST in the blood ( Yuan et al, 2018 ; Guo et al, 2021 ). When hepatocytes were damaged, large amounts of ALT and AST will enter the blood, resulting in an obvious augment in serum ALT and AST levels ( Salahshoor et al, 2018 ; Zhang et al, 2018 ; Wang L. et al, 2019 ; Kaya et al, 2021 ; Li H. et al, 2021 ).…”

Synthesis and evaluation of new pirfenidone derivatives as anti-fibrosis agents

“…The KM mice, originally from Switzerland, introduced into Kunming Central Epidemic Prevention Office of China from Haine Institute of India in 1946, and widely used in the evaluation of drug safety and effectiveness at present, were used for the evaluation. [24][25][26] The mice (5 male and 5 female in each group) were randomly divided into experimental group and control group, and were caudal vein injected with 9d at a dose of 100/150/300 mg kg À1 , and the control group was caudal vein injected with physiological saline. The results showed no death and obvious toxicological reactions in mice within 24 hours aer administration.…”