Phytochemical profiling, safety assessment, and pharmacological validation against pain and inflammation of Teucrium chamaedrys L. crude extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Teucrium chamaedrys L. (Lamiaceae) is a medicinal plant broadly exploited in conventional Algerian therapy. These findings provide scientific validation for its folk applications and highlight potential for advanced pharmacological development targeting pain and inflammation. AIM OF THE STUDY: This study aimed to examine the composition and assess the anti-inflammatory, analgesic, toxicological, and in silico capabilities of T. chamaedrys L., collected from northern Algeria. MATERIALS AND METHODS: Phytochemical profiling of T. chamaedrys L. crude extract (CrE) involved determining major classes, including total phenolic and flavonoid contents. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was conducted to tentatively annotate and characterize the phytochemicals present in this plant extract. The in vitro anti-inflammatory activity was investigated by inhibiting BSA denaturation. Acute and sub-acute toxicity were evaluated orally in Albino mice, and anti-inflammatory and analgesic properties were assessed in Wistar rats. Molecular docking was performed to investigate interactions between the tentatively identified compounds and relevant therapeutic targets, while ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions were used to assess their pharmacokinetic properties and potential toxicity. RESULTS: The CrE yielded 19.11 ± 1.07% and was rich in polyphenols (244.65 ± 2.36 μg GAE/mg CrE) and flavonoids (41.45 ± 0.38 μg QE/mg CrE). The results of UHPLC-HRMS analysis showed twenty tentatively identified compounds, including flavonoids and their derivatives (luteolin, naringenin, etc.), phenolic acid (chlorogenic acid), iridoid glycoside (harpagide), phenylethanoid glycosides (teucrioside, verbascoside and poliumoside), triterpenoids (maslinic acid) and a cyclitol and cyclohexanecarboxylic acid (quinic acid). In vitro assays demonstrated a significant anti-inflammatory activity with an IC50 of 437.80 ± 21.11 μg/mL. In vivo studies demonstrated that the CrE did not exhibit any acute or sub-acute toxicity effects in the tested animals. Moreover, significant anti-inflammatory and analgesic effects were recorded at 500 mg/kg b.w., with inhibition values of 76.60 ± 1.96% and 77.77 ± 2.30%, respectively. Molecular docking studies indicated that luteolin and its derivatives, verbascoside, apigenin 7-O-rutinoside, poliumoside and maslinic acid interacted strongly with tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2) and voltage-gated sodium channel 1.7 (NaV1.7), suggesting a possible role in anti-inflammatory and analgesic effects. ADMET and pharmacokinetic assessments indicated that the tentatively identified compounds from CrE have favorable pharmacological properties, including good intestinal absorption, high solubility, and no predicted hepatotoxicity or carcinogenicity, suggesting potential safety in preclinical and therapeutic settings. CONCLUSIONS: T. chamaedrys L. from Algeria appears to be a promising source of bioactive metabolites, with demonstrated safety in acute and sub-acute toxicity studies. It exhibited anti-inflammatory and analgesic activities, supported by both experimental and computational findings. Overall, these findings provide scientific support for the traditional use of T. chamaedrys and offer a basis for future pharmacological investigations.