Investigation of Potential Activities of Peganum Harmala Seeds: In Silico and in Vitro Analyses

Seeds of Peganum harmala L. have been traditionally used in Algerian medicine. This study investigates whether the antioxidant, antihemolytic, and anti-inflammatory activities of Peganum harmala extracts (PHE) are attributed to polyphenolic compounds, which are abundant in methanol, chloroform, and ethyl acetate extracts. Extraction and fractionation of polyphenols involved solvents with different polarities, resulting in a crude extract (CrE), a chloroform extract (CHE), and an ethyl acetate extract (EAE). The antioxidant potential of CrE and its fractions was assessed using the ferrothiocyanate (FTC) and thiobarbituric acid (TBA) assays. The inhibition of mice erythrocyte hemolysis was evaluated for methanol, chloroform, and ethyl acetate extracts in the presence of the oxidant (AAPH). PMA-induced mouse ear edema was used as an in vivo model for inflammation. The FTC assay demonstrated the strong antioxidant effect of CrE (87.64 ± 0.003%). EAE showed potent antioxidant activity with low MDA absorption levels. Assessment of antihemolytic effects against AAPH-induced oxidative hemolysis revealed significant protective effects of CrE and EAE, with EAE showing the most pronounced effect. In the in vivo model, CrE (100 mg/kg) exhibited substantial anti-inflammatory activity, inhibiting the ear edema. Computational analyses using molecular docking simulations showed that chlorogenic acid, hesperetin, and rutin have promising potential as inhibitors of COX-2 protein, which is a key component in inflammatory pathways. This study highlights the potent antioxidant properties of P. harmala, particularly in CrE, and its anti-inflammatory effects. The bioactive compounds, such as chlorogenic acid, hesperetin, and rutin, exhibit potential as anti-inflammatory agents. P. harmala could be a valuable natural source for potential medical applications, suggesting the need for further exploration in medical treatments.