Abstract

Purpose Using network pharmacology and in vivo experiments, we investigated the antidrug-induced liver injury components and functional processes of Sedum sarmentosum Bunge (SSBE). Methods The effective components, primary active ingredients, and possible target in the therapy of DILI were predicted using network pharmacology and bioinformatics. APAP was inducing the DILI model. In vivo testing of the pharmacodynamic foundation of SSBE in the treatment of DILI was performed. Results The TCMSP database evaluated five main active components and 299 related targets. In addition, 707 differential genes for DILI were obtained from the DisGeNET database, DigSee database, and OMIM database. 61 related targets were mapped to predict the targets of SSBE acting on DILI. The protein-protein interaction (PPI) core network contained 59 proteins, including IL-β, MARK14, SSP1, and MMP9. These genes are closely related to the Nrf2/ARE signaling pathway, and they may play a key role in the hepatoprotective effect of SSBE. Verification experiment results showed that, in the DILI mouse model, SSBE promoted inflammation diminution and regulation of Nrf2-ARE cascade. SSBE protected normal hepatocyte growth and inhibited apoptosis of normal liver cells induced by APAP. SSBE inhibited the expression of Nrf2 and ARE proteins in the liver tissue of the DILI mouse model in vivo. Conclusion By modulating the Nrf2 signaling pathway, the active components in SSBE may protect against drug-induced liver damage.

Highlights

  • Injury to the liver caused by drugs (drug-induced liver injury (DILI)) refers to abnormalities in liver function tests related to the intake of medicinal compounds, medications, aerobatics, and herbs and is attributed to a significant percentage of patient morbidity and mortality, with an annual incidence rate between 1 and 20 per 100,000 people [1]

  • After data from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was gathered, oral bioavailability (OB) and DL were utilised to screen bioactive components of sarmentosum Bunge (SSBE). e rate and amount of medication absorption to the circulatory system are measured by OB, a key pharmacokinetic parameter of orally given drugs [11]

  • Compounds with OB ≥30% and DL ≥0.18 were chosen for further investigation. e time it takes for the concentration of medicines in blood/the number of drugs in the body to drop to half is referred to as the half-life

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Summary

Introduction

Injury to the liver caused by drugs (drug-induced liver injury (DILI)) refers to abnormalities in liver function tests related to the intake of medicinal compounds, medications, aerobatics, and herbs and is attributed to a significant percentage of patient morbidity and mortality, with an annual incidence rate between 1 and 20 per 100,000 people [1]. Traditional Chinese medicine (TCM) offers unique benefits for treating DILI and has been shown to have hepatoprotective effects. As a traditional medicinal plant, Sedum sarmentosum Bunge (SSBE) has been recorded by Chinese Pharmacopoeia (2010), and various preparations have been developed from it [3]. It is widely used in clinical application to treat many kinds of liver diseases, such as dampness-heat of liver and gallbladder and acute and chronic hepatitis. SSBE mainly contains flavonoids, mainly Sedum sarmentosum total flavonoids (SSTF), and other compounds, which have various biological functions such as liver protection, antitumor, anti-inflammatory, antioxidation, antikidney fibrosis, and strengthening muscle strength [4, 5]

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