Description

2 ketoglutaric acid is a reversible inhibitor of tyrosinase, with an IC50 value of 15 ± 0.5mM[1]. 2-Ketoglutaric acid is naturally found in organisms and is an intermediate in the production of ATP or GTP in the Krebs cycle[2]. Widely used as an antioxidant, 2-Ketoglutaric acid reduced cyanide-induced GSH depletion and DNA damage in rat in vitro and in vivo models[3].

In vitro, 2-Ketoglutaric acid treatment at 0.1mM for 8 days promoted cell growth in C2C12 cells and decreased intracellular glucose consumption and ammonia production[4]. Pretreatment of rabbit dermal papilla cells with 6mM 2-Ketoglutaric acid for 24h alleviated the H2O2-induced decrease in cell viability, reduced ROS accumulation, and restored mitochondrial membrane potential damaged by oxidative stress[5]. Pretreatment with 5mM 2-Ketoglutaric acid for 30min significantly prevented 5mM potassium cyanide-induced cell toxicity and attenuated mitochondrial dysfunction in rat thymocytes[6].

In vivo, 2-Ketoglutaric acid treatment via oral administration at a dose of 10mg/kg/day for 14 days significantly inhibited dextran sulfate sodium-induced intestinal injury, and prevented disruption of gut microbial homeostasis in a mouse model of colitis[7]. Oral administration of 2-Ketoglutaric acid at a dose of 10mg/kg daily for 10 days helped to repair the intestinal barrier damage induced by high altitude exposure in mice[8].

References:

[1] Gou L, Lee J, Yang J M, et al. The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study[J]. International Journal of Biological Macromolecules, 2017, 105: 1654-1662.

[2] Huergo L F, Dixon R. The emergence of 2-oxoglutarate as a master regulator metabolite[J]. Microbiology and Molecular Biology Reviews, 2015, 79(4): 419-435.

[3] Liu S, He L, Yao K. The antioxidative function of alpha‐ketoglutarate and its applications[J]. BioMed research international, 2018, 2018(1): 3408467.

[4] Yang B, Liu Y, Steinacker J M. α-Ketoglutarate stimulates cell growth through the improvement of glucose and glutamine metabolism in C2C12 cell culture[J]. Frontiers in Nutrition, 2023, 10: 1145236.

[5] Wang X, Li S, Chen J, et al. Exogenous Alpha-Ketoglutaric Acid Alleviates the Rabbit Dermal Papilla Cell Oxidative Damage Caused by Hydrogen Peroxide Through the ERK/Nrf2 Signaling Pathway[J]. Antioxidants, 2025, 14(4): 455.

[6] Bhattacharya R, Rao P V L, Vijayaraghavan R. In vitro and in vivo attenuation of experimental cyanide poisoning by α-ketoglutarate[J]. Toxicology Letters, 2002, 128(1-3): 185-195.

[7] Kim S, Jang S H, Kim M J, et al. Hybrid nutraceutical of 2-ketoglutaric acid in improving inflammatory bowel disease: Role of prebiotics and TAK1 inhibitor[J]. Biomedicine & Pharmacotherapy, 2024, 171: 116126.

[8] Sun X, Li W, Chen G, et al. Faecalibacterium duncaniae Mitigates Intestinal Barrier Damage in Mice Induced by High-Altitude Exposure by Increasing Levels of 2-Ketoglutaric Acid[J]. Nutrients, 2025, 17(8): 1380.

Protocol