Capsaicin

Capsaicin (CAS 404-86-4) is a natural vanillamide compound and a TRPV1 activator that activates the transient receptor potential vanilloid subtype 1 (TRPV1) ion channel and competitively and reversibly inhibits lysine-specific demethylase 1A (KDM1A/LSD1). It exhibits analgesic and anti-inflammatory effects, inhibits the proliferation, migration, and invasion of gastric cancer cells and reverses epithelial-mesenchymal transition (EMT), and modulates itch perception in chronic dermatitis.

Key activity data show a biochemical IC50 of 0.6 ± 0.0421 μM for KDM1A inhibition, an IC50 of 4.659 μM for inhibiting the proliferation of human gastric cancer BGC-823 cells, and an IC50 of 29.981 μM after KDM1A knockdown. In animal experiments, capsaicin is commonly used as an interventional agent in models including SADBE-induced chronic dermatitis mouse models, imiquimod-induced psoriasis mouse models, gastric cancer cell xenograft models, and neuropathic pain/osteoarthritis pain models.

Common dosing concentrations: in cell culture, BGC-823 gastric cancer cells typically use 0.25-2 μM and mouse trigeminal ganglion/dorsal root ganglion neurons typically use 500 μM; in animal experiments, chronic dermatitis mice receive a 500 μM (20 μL) buccal subcutaneous injection, pain models receive local/intrathecal administration, and tumor models receive oral administration; clinically, an 8% topical patch is used for chronic neuropathic pain; effective concentrations are 0.25-1 μM at the cellular level (markedly inhibiting the malignant phenotype of gastric cancer cells), 500 μM at the animal level (activating TRPV1 in lesional tissue and modulating itch responses), and an 8% topical patch clinically for relieving chronic pain.

References

[1] Jia G, Cang S, Ma P, Song Z. Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers. Bioorg Chem. 2020 Oct;103:104161. doi: 10.1016/j.bioorg.2020.104161. Epub 2020 Aug 21. PMID: 32889380.

[2] Mogi M, Mendonza AE, Chastain J, Demirs JT, Medley QG, Zhang Q, Papillon JPN, Yang J, Gao Y, Xu Y, Stasi K. Ocular Pharmacology and Toxicology of TRPV1 Antagonist SAF312 (Libvatrep). Transl Vis Sci Technol. 2023 Sep 1;12(9):5. doi: 10.1167/tvst.12.9.5. PMID: 37672251; PMCID: PMC10484039.

[3] Yu G, Liu P, Huang X, Qi M, Li X, Feng W, Shang E, Zhou Y, Wang C, Yang Y, Zhu C, Wang F, Tang Z, Duan J. 20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis. Theranostics. 2024 Feb 4;14(4):1615-1630. doi: 10.7150/thno.85214. PMID: 38389848; PMCID: PMC10879873.

[4] Hefner S, Oprita G, Pantke S, Hage A, Leffler A. Nav1.8, TRPV1 and TRPA1 as possible targets of ambroxol when used for topical treatment of neuropathic pain. J Pain. 2025 Dec;37:105563. doi: 10.1016/j.jpain.2025.105563. Epub 2025 Sep 16. PMID: 40967389.