Bioactivity Assessment and In Silico Target Engagement of Clerodendrum infortunatum Extracts: Correlating Experimental Outcomes With DFT and Docking Pre

ABSTRACT

Clerodendrum infortunatum (Lamiaceae) is commonly employed in traditional healing practices to manage inflammation, fever, pain, and gastrointestinal ailments. Despite its widespread use, there is limited scientific evidence supporting these therapeutic claims and insufficient characterization of its active phytochemicals. This study aimed to investigate the anti‐inflammatory, analgesic, antipyretic, and antidiarrheal properties of the methanolic extract (MECI) and n‐hexane fraction (NHF) derived from C. infortunatum leaves through integrated in vivo and in silico methodologies. Anti‐inflammatory activity was evaluated using protein denaturation and carrageenan‐induced paw edema models; analgesic effects were assessed via acetic acid‐induced writhing and tail immersion tests; antipyretic and antidiarrheal activities were examined using yeast‐induced pyrexia and castor oil‐induced diarrhea models, respectively. Additionally, molecular docking, ADME/T (absorption, distribution, metabolism, excretion/toxicity), DFT, and PASS (Prediction of Activity Spectra for Substances) analyzes were performed to explore the pharmacokinetic profiles and potential molecular targets of the identified compounds. MECI demonstrated strong inhibition of protein denaturation (89.29%) with an IC₅₀ of 44.10 μg/mL, comparable to diclofenac sodium. Both MECI and NHF significantly attenuated carrageenan‐induced paw edema and writhing responses in a dose‐dependent manner ( p  < 0.001), increased latency in the tail immersion test, and effectively reduced both yeast‐induced fever and castor oil‐induced diarrhea. In silico docking revealed that hydrocinnamic acid, o‐[(1,2,3,4‐tetrahydro‐2‐naphthyl)methyl]‐, exhibited high binding affinities for COX‐2 (−9.1) and the M ₃ muscarinic receptor (−10.2 kcal/mol), while ethyl isoallocholate showed notable affinity for mPGES‐1 (−5.6 kcal/mol). ADME/T, DFT, and PASS predictions indicated favorable oral bioavailability and low toxicity for the major constituents. The findings substantiate the traditional medicinal uses of C. infortunatum , demonstrating its multi‐target pharmacological actions mediated through COX‐2, mPGES‐1, and M3 muscarinic receptor pathways. Hydrocinnamic acid derivatives and ethyl isoallocholate emerge as promising candidates for the development of new anti‐inflammatory, analgesic, and antipyretic therapeutics.