Phenolic Composition of Crataegus monogyna Jacq. Extract and Its Anti-Inflammatory, Hepatoprotective, and Antileukemia Effects

Abstract

Crataegus monogyna (C. monogyna) is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of C. monogyna leaves and stems. Ultra-high-performance liquid chromatography identified the phenolic profile. The in vitro anticancer activity was evaluated using the MTT assay on HL-60 and K-562 myeloleukemia cells and liver (Huh-7) cell lines. The anti-inflammatory effect was assessed in vivo using carrageenan-induced paw edema in rats. The hepatoprotective effect at 300 and 1000 mg/kg doses against the acetaminophen-induced hepatotoxicity on rats was studied for seven days. Additionally, molecular docking simulations were performed to evaluate the extract's inhibitory potential against key targets: lipoxygenase, cytochrome P450, tyrosine kinase, and TRADD. The extract exhibited significant cytotoxic activity against K-562 and HL-60 cells, but not against lung cancer cells (Huh-7 line). The 1000 mg/kg dose demonstrated the most potent anti-inflammatory effect, inhibiting edema by 99.10% after 6 h. C. monogyna extract displayed promising hepatoprotective properties. Procyanidin (-7.27 kcal/mol), quercetin (-8.102 kcal/mol), and catechin (-9.037 kcal/mol) were identified as the most active molecules against lipoxygenase, cytochrome P450, and tyrosine kinase, respectively. These findings highlight the untapped potential of C. monogyna for further exploration in treating liver damage, inflammation, and leukemia.

Keywords: Crataegus monogyna; hepatotoxicity; human hepatocellular carcinoma; in silico studies; inflammation; leukemia.

Figure 1

LCMS Spectrum of the identified polyphenols.

Figure 2

The cytotoxic effect of the C. monogyna hydroethanolic extract. K562 (a) and HL60 (b) cell lines were treated with different concentrations of the C. monogyna extract (3–100 µg/mL) for 24, 48, and 72 h time points. The IC₅₀ for K562 (c) and HL-60 (d) was estimated using nonlinear regression (GraphPad Prism v. 5 software). The results are expressed as mean ± SD of three independent experiments. Statistical significance compared to the negative control (untreated cells) is denoted as follows: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 3

The effect of C. monogyna hydroethanolic extract on the body weight of mice during the hepatotoxicity test. Results are expressed as mean ± SEM (n = 5). Results are considered statistically significant compared to the negative control group (*** p < 0.001).

Figure 4

Effects of C. monogyna hydroethanolic extract on the liver and kidney biochemical parameters in mice. *** Indicates a significant difference at p < 0.001 from the control group using one-way ANOVA followed by Dunnett test. Values are expressed as mean ± SEM (n = 5).

Figure 5

The 2D viewer of ligand interactions with the active site. (A,D): Procyanidin interactions with the active site of lipoxygenase and TRADD. (B): Quercetin interactions with the active site of human cytochrome P450 2E1. (C): Catechin interactions with the active site of tyrosine kinase.

Figure 5

The 2D viewer of ligand interactions with the active site. (A,D): Procyanidin interactions with the active site of lipoxygenase and TRADD. (B): Quercetin interactions with the active site of human cytochrome P450 2E1. (C): Catechin interactions with the active site of tyrosine kinase.

Figure 6

The 3D viewer of ligand interactions with the active site. (A,D): Procyanidin interactions with the active site of lipoxygenase and TRADD. (B): Quercetin interactions with the active site of human cytochrome P450 2E1. (C): Catechin interactions with the active site of tyrosine kinase.