Computational and Comparative In Vitro Evaluation of GC-MS Profiled Cannabis sativa Inflorescence Extracts' Metabolites on Selected Diabetes Therapeutic Targets.

Chinheya R.; Ngoungoure V.; Ali I.; Olofinsan K.; Jim T.; Tankeu F.; Matsabisa M. · Chemistry & biodiversity · 2026

**Background & Methods** This in vitro and computational study evaluated the antidiabetic potential of Cannabis sativa inflorescence extracts by sequential extraction using hexane, dichloromethane, and methanol solvents. The 36 identified metabolites were analyzed using GC-MS and tested against multiple diabetes-related therapeutic targets including α-amylase, α-glucosidase, glucose uptake pathways, and antioxidant mechanisms, with molecular docking simulations performed against key diabetes-related proteins. **Key Findings** • The hexane extract demonstrated the strongest bioactivity profile, achieving α-amylase inhibition with an IC50 of 727 µg/mL, DPPH free radical scavenging activity (IC50: 478.62 µg/mL), and nitric oxide inhibition (IC50: 356.51 µg/mL), suggesting multimodal antidiabetic mechanisms. • Computational docking analyses identified three cannabinoid compounds—8-hydroxy-delta-9-THC, cannabivarin, and 9-tetrahydrocannabinol—as exhibiting strong binding affinities to DPP-4, PTP1B, and other diabetes-related target proteins, indicating potential for therapeutic intervention at molecular levels relevant to glucose homeostasis. • The sequential extraction approach revealed solvent-dependent bioactivity variations, with nonpolar extracts (hexane) outperforming more polar solvents, suggesting the antidiabetic active principles are predominantly lipophilic compounds. **Dosage & Administration** Not reported. This study did not evaluate therapeutic dosing or administration routes, being limited to in vitro screening concentrations expressed as IC50 values in µg/mL. **Safety & Adverse Effects** Not reported. The study did not assess safety profiles, toxicity, or adverse effects in any biological system. **Evidence Quality** This review represents preliminary in vitro and computational evidence with significant limitations. The study lacks in vivo validation, animal models, and clinical trial data necessary to establish therapeutic efficacy or safety in humans. IC50 values in the range of 350-727 µg/mL suggest moderate potency requiring substantial extract concentrations. Computational docking provides only theoretical binding predictions without functional confirmation. The absence of pharmacokinetic, bioavailability, or metabolism studies limits translational potential. Cannabis regulatory status and variability in plant cannabinoid profiles across cultivars present additional practical barriers. While the findings are encouraging as a proof-of-concept, substantial further research including pharmacological validation and clinical trials is essential before therapeutic recommendations can be made.

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