Triacetin

Triacetin (CAS No. 102-76-1) is a short-chain triacylglycerol whose core bioactivities include antitumor effects, metabolic regulation, and anti-adipogenesis. Its targets include histone deacetylases (HDACs, especially HDAC-8), the mTOR complex, Rictor, Caspase-3, and Rpn13. It can also be hydrolyzed to generate acetate and glycerol, activating hepatic AMPK signaling to regulate lipid metabolism genes. The cytotoxic IC50 for retinal ARPE-19 cells is > 46.97 mg/mL at 1 h and 5.34 mg/mL at 24 h. There is no defined inhibitory IC50 for U87MG glioblastoma cells, but it can exert activity at specific concentrations. In in vitro cell experiments, 12.5~25 mM is used to induce apoptosis and G2/M phase arrest in GBM cells, 0.1~1% v/v is used for safety evaluation in ocular formulations, and 5~7.5% (w/w) is used as the oil phase component in ocular nanoemulsions. In animal studies, the intragastric dose in rats is 2 mmol/rat (for metabolic studies), and the reference dose in colorectal cancer xenograft models is 1~100 ng/kg (in combination or alone). Its potential therapeutic applications (anti-GBM, metabolic regulation, anti-obesity) are still at the experimental stage. When used as a food additive or pharmaceutical excipient, the safe concentration in ocular formulations can reach 5~7.5%, and oral administration based on animal experimental doses shows good tolerability.

References:

[1] Vreeke S, Peyton DH, Strongin RM. Triacetin Enhances Levels of Acrolein, Formaldehyde Hemiacetals, and Acetaldehyde in Electronic Cigarette Aerosols. ACS Omega. 2018 Jul 31;3(7):7165-7170. doi: 10.1021/acsomega.8b00842. Epub 2018 Jul 2. PMID: 30087908; PMCID: PMC6068691.

[2] Mahboobian MM, Seyfoddin A, Aboofazeli R, Foroutan SM, Rupenthal ID. Brinzolamide-loaded nanoemulsions: ex vivo transcorneal permeation, cell viability and ocular irritation tests. Pharm Dev Technol. 2019 Jun;24(5):600-606. doi: 10.1080/10837450.2018.1547748. Epub 2019 Jan 15. PMID: 30472913.

[3] Mekala JR, Kurappalli RK, Ramalingam P, Moparthi NR. N-acetyl l-aspartate and Triacetin modulate tumor suppressor MicroRNA and class I and II HDAC gene expression induce apoptosis in Glioblastoma cancer cells in vitro. Life Sci. 2021 Dec 1;286:120024. doi: 10.1016/j.lfs.2021.120024. Epub 2021 Oct 7. PMID: 34626605.

[4] Islas-Gardu?o AL, Romero-Cerecero O, Jiménez-Aparicio AR, Tortoriello J, Montiel-Ruiz RM, González-Cortazar M, Zamilpa A. Pharmacological and Chemical Analysis of Bauhinia divaricata L. Using an In Vitro Antiadipogenic Model. Plants (Basel). 2023 Nov 8;12(22):3799. doi: 10.3390/plants12223799. PMID: 38005696; PMCID: PMC10674420.

[5] Yoshimura Y, Matsui T, Kaneko N, Kobayashi I. Digestion and absorption of triacetin, a short-chain triacylglycerol. Lipids. 2025 Jan 31. doi: 10.1002/lipd.12433. Epub ahead of print. PMID: 39891375.