Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs

Abstract

Drug-induced liver injury (DILI) is a common adverse drug reaction (ADR) and a serious threat to health that affects disease treatments. At present, no targeted clinical drugs are available for DILI. Traditional natural medicines have been widely used as health products. Some natural medicines exert specific hepatoprotective effects, with few side effects and significant clinical efficacy. Thus, natural medicines may be a promising direction for DILI treatment. In this review, we summarize the current knowledge, common drugs and mechanisms of DILI, as well as the clinical trials of natural drugs and their bioactive components in anticipation of the future development of potential hepatoprotective drugs.

Keywords: Bioactive components; Drug-induced liver injury; Mechanism; Natural medicines.

Fig. 1

Possible mechanism of Anti-TB drugs (example as INH). Drugs can make hepatic cells continuously release inflammatory cytokines and response-induced stress kills hepatocytes. Direct hepatotoxicity of drugs and their metabolites includes the deformation and necrosis of hepatocytes

Fig. 2

Possible mechanism of NSAIDs (example as APAP). The potential mechanisms involved are CYP450 metabolites interact with cellular macromolecules, destroy protein structure, lipid peroxidation, destroy ion gradient, and disrupt calcium ion transport, inhibit ATP synthesis and bile acid synthesis

Fig. 3

Possible mechanism of Immune idiosyncratic DILI. Drugs or their metabolic products combine with liver specific proteins to become antigens, which can be phagocytosed by phagocytes and expressed on the cell surface. They can be recognized by CD4⁺ cells, stimulate the production of cytokines, activate the CD8⁺T cells of effector cells, and produce cytotoxicity leading to liver damage

Fig. 4

Bioactive components and mechanism of natural drugs for liver protection

Fig. 5

The chemical structures of flavonoids showing anti-DILI activity. (1) α-Mangostin; (2) Dihydromyricetin; (3) L-Epicatehin; (4) (-)-Epicatehin gallate; (5) (-)-epigallocatechin; (6) Martynoside; (7) (+)-Catechin; (8) Licochalcone A; (9) Puerarin; (10) Quercetin; (11) Baicalin; (12) Baicalein; (13) Astlbin; (14) Cuecumin; (15) Hyperoside; (16) (-)-Gallocatechin; (17) (−)-Gallocatechin gallate; (18) Ellagic acid; (19) (+)-Taxifolin; (20) Silymarin; (21) Silicristin

Fig. 6

The chemical structures of Alkaloids showing anti-DILI activity. (1) Ligustrazine; (2) Matrine; (3) Aconine; (4) Berberine; (5) Oxymatrine; (6) Dendrobine; (7) Capsaicin; (8) Piperine

Fig. 7

The chemical structures of Saponin showing anti-DILI activity. (1) Platycodin D; (2) Akebia saponin D; (3) Ginsenoside Rg1; (4) Ginsenoside Rg5; (5) Ginsenoside Rk1; (6) Saikosaponin A; (7) Saikosaponin D; (8) Geniposide; (9) Arjunolic acid; (10) Astragaloside IV; (11) Ginsenoside Rb1; (12) Chiisanoside; (13) Ginsenoside Rg3

Fig. 8

The chemical structures of lignans showing anti-DILI activity. (1) Angeloylgomisin O; (2) Gomisin N; (3) Schizandrol B; (4) Gomisin D; (5) Gomisin G; (6) Gomisin J; (7) Gomisin O; (8) Schisandrin C; (9) Schizandrol A; (10) Gomisin A; (11) Schisanhenol; (12) Schisandrin A; (13) Schizandrin B; (14) Schisantherin A; (15) Schisantherin E; (16) Schisantherin B

Fig. 9

The chemical structures of terpene showing anti-DILI activity. (1) Betulinic acid; (2) Atracylenolide-1; (3) Thymoquinone; (4) Andrographis; (5) Liquiritigenin; (6) Kamebakaueine; (7) Ursolic; (8) Astaxanthin; (9) Thymoquinone; (10) Kamebakaurin; (11) Oleanolic acid