Natural Product Communications, vol.21, no.4, 2026 (SCI-Expanded, Scopus)
Objective: Delta-9-tetrahydrocannabinol (Δ9-THC), the primary active component of cannabis, was isolated from the cannabis plant in 1964, and ever since then, scientists focused more on compounds that activate this receptor and created synthetic cannabinoid derivatives to study the pharmacological and toxicological effects of cannabinoids. Following this, analogues of Δ9-THC began to be synthesized especially for medical use of cannabis. Synthetic cannabinoids may be employed in autoimmune illnesses, and further research on cannabis derivatives is necessary to understand how they affect immune system cells. Methods: We have used MDMB-4en-PINACA, which is an indazole-based synthetic cannabinoid. Methods: In our study, the immunomodulatory effects of MDMB-4en-PINACA and its derivative were evaluated on mammalian macrophages. ELISA was used to quantify pro-inflammatory cytokine levels and assess their impact on macrophages. Following that, the intracellular mechanism of action of synthetic cannabis derivative was tested by measuring the amounts of phosphorylated PI3K using flow cytometry. Results: Our findings imply MDMB-4en-PINACA and its derivative stimulated the anti-inflammatory cytokines in the lipopolysaccharide (LPS)-stimulated macrophages. Conclusion: Consequently, these compounds may be used as therapeutic possibilities for autoimmune and inflammatory diseases.