Hepatitis is an inflammatory condition that can develop hepatocellular carcinoma. Traditional medicine has always been the pillar of medical practice. However, it became less compatible with the current understanding of the diseases and the possible treatment. Therefore, in silico tools could be utilized for building the bridge between the legacy of the past and the current medical approaches allowing access to new therapeutic discoveries. In this work, a Chinese traditional medicine database was screened using structure-based virtual screening to identify molecules that could inhibit p38 alpha mitogen-activated protein kinase (MAPK). Out of the identified compounds, four selected compounds: chrysophanol, physcion, curcumin and hesperidin were isolated from their respective sources and their structures were confirmed by spectroscopic methods. These compounds decreased the gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1β) in lipopolysaccharide (LPS) induced inflammation in a hepatocellular carcinoma cell line (HepG2) in a dose-dependent manner. The molecular docking study revealed the specificity of these compounds towards p38 MAPK rather than other MAPKs. In conclusion, the molecular and in silico studies suggest that the isolated compounds could be a potential treatment for hepatitis by resolving inflammation controlled by MAPKs, thus limiting the development of further complications and lower side effects.

To investigate the possible modulating role of “Nigella sativa” (NS), a plant commonly used in Egyptian traditional medicine, on premalignant perturbations in three glycol-regulatory enzymes in an experimental rat model of hepatocellular carcinoma (HCC). Thirty-six (36) male albino rats were divided into four groups (n = 9). Group 1 served as a normal control, group 2 was treated with methanolic extract of Nigella sativa (MENS) (1 g/kg/day, orally) for 14 weeks, group 3 received a single intraperitoneal dose of diethyl nitrosamine (DENA) (200 mg/kg), followed 2 weeks later by a subcutaneous injection of carbon tetrachloride (CCl₄, 3 ml/kg/week/6 weeks) and group IV was treated with MENS for 2 weeks prior to administration of the carcinogenic combination (DENA + CCl₄, as in group 3) until the end of the experiment. The total period of the experiment was 14 weeks. In the DENA + CCl₄-treated group, there was a significant increase in the relative liver weight, serum alpha fetoprotein level and the activities of hexokinase, glyceraldehyde phosphate dehydrogenase and glucose 6 phosphate dehydrogenase in both the serum and liver homogenate; this was accompanied by a subsequent decrease in body weight. Pre-treatment with MENS significantly maintained these parameters close to the normal condition. Based on these results, we conclude that MENS has a chemo-preventive effect against the progression into liver malignancy through its modulation of the energy metabolic pathways (i.e. glycolysis) that may be involved in hepatocarcinogenesis.