Potential Roles and Key Mechanisms of Hawthorn Extract against Various Liver Diseases

Abstract

The genus Crataegus (hawthorn), a flowering shrub or tree, is a member of the Rosaceae family and consists of approximately 280 species that have been primarily cultivated in East Asia, North America, and Europe. Consumption of hawthorn preparations has been chiefly associated with pharmacological benefits for cardiovascular diseases, including congestive heart failure and angina pectoris. Treatment with hawthorn extracts can be related to improvements in the complex pathogenesis of various hepatic and cardiovascular disorders. In this regard, the present review described that the presence of hawthorn extracts ameliorated hepatic injury, lipid accumulation, inflammation, fibrosis, and cancer in an abundance of experimental models. Hawthorn extracts might have these promising activities, largely by enhancing the hepatic antioxidant system. In addition, several mechanisms, including AMP-activated protein kinase (AMPK) signaling and apoptosis, are responsible for the role of hawthorn extracts in repairing the dysfunction of injured hepatocytes. Specifically, hawthorn possesses a wide range of biological actions relevant to the treatment of toxic hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Accordingly, hawthorn extracts can be developed as a major source of therapeutic agents for liver diseases.

Keywords: Crataegus; antioxidant; hawthorn; liver.

Figure 1

Hepatoprotective roles of hawthorn extract against liver damage induced by diet, alcohol, toxicant, heavy metals, and partial hepatectomy. ARE, antioxidant response element; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; DPPH, 2,2-diphenyl-1-picrylhydrazyl; GSH-Px, glutathione peroxidase; GST, glutathione S-transferase; HO-1, heme oxygenase-1; LDL, low-density lipoprotein; MPO, myeloperoxidase; Nrf-2, nuclear factor erythroid-2-related factor 2; PARP, poly-ADP ribose polymerase; P. Carbonyl, protein carbonyl; rGCS, r-glutamylcysteine synthethase; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactive substances; and TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labelling.

Figure 2

Inducer, rodent, hawthorn species, experimental results, and underlying mechanism of preclinical studies on hawthorn extract exhibiting antisteatotic activities related to liver pathogenesis. ApoE, apolipoprotein E; AMPK, AMP-activated protein kinase; LDL, low-density lipoprotein; MCD, methionine choline deficient; TC, total cholesterol; and TG, triglyceride.

Figure 3

Anti-inflammatory effects and antifibrotic effects of hawthorn extract through apoptosis suppression, AMPK and NIK activation, HSC inactivation, and antioxidant defense system. AMPK, AMP-activated protein kinase; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; CAT, catalase; CCl₄, carbon tetrachloride; GSH-Px, glutathione peroxidase; HSC, hepatic stellate cell; IKK, IκB kinase; LPS, lipopolysaccharides; MDA, malondialdehyde; MPO, myeloperoxidase; NFκB, nuclear factor kappa B; NIK, NFκB inducing kinase; P. carbonyl, protein carbonyl; PPAR, peroxisome proliferator-activated receptor; SIRT, silent information regulator T; SOD, superoxide dismutase; SMA, smooth muscle actin; and TGF, transforming growth factor.

Figure 4

Anticancer effects of hawthorn extract by inhibiting cell viability and cell proliferation in human hepatoma cell lines.