Anserine is an orally active dipeptide with the carboxylic group (pKa=2.64), the amino group of the β-alanine residue (pKa=9.49), and the imidazole ring in histidine (pKa=7.04)[1]. Anserine alleviates hyperuricaemia and renal inflammation phenotypes, inhibited uric acid biosynthesis, promotes uric acid excretion, and inhibits NLRP3 inflammasome and TLR4/MyD88/NF-κB signalling pathway activation[2]. Anserine has been widely used as a proton (H+) buffer, antioxidant, radical scavenger, and Ca2+ handling regulator in preclinical models[3].
In vitro, Anserine treatment (2mM) for 7 days restored antioxidant capacity and normalized ZO-1 expression in immortalized renal tubular epithelial cells derived from the patient with methylmalonyl-CoA mutase deficiency (mut0)[4]. Treatment with 2.5mM Anserine for 48 hours induced H2S production and promoted HSP70 expression in HK-2 cells[5]. Incubation with 50mM Anserine for 20 minutes inhibited IgE-induced degranulation of RBL-2H3 cells and increased JNK phosphorylation[6]. Treatment with 500μg/ml Anserine for 24 hours alleviated TNF-α-induced cell injury in human umbilical vein endothelial cells (HUVECs), promoted cellular NO release, and decreased the levels of P-selectin and E-selectin[7].
In vivo, Anserine treatment via daily oral administration at a dose of 200mg/kg for 8 consecutive weeks inhibited cardiac hypertrophy and prevented systolic dysfunction in mice with transverse aortic constriction (TAC)[8]. Daily oral administration of Anserine at a dose of 120mg/kg for 16 consecutive weeks alleviated high-fat diet-induced atherosclerosis in ApoE−/− mice, decreased Surf4 expression levels in the liver, and suppressed low-density lipoprotein cholesterol synthesis[9].
References:[1] Wu G. Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health[J]. Amino acids, 2020, 52(3): 329-360.
[2] Han J, Wang Z, Lu C, et al. The gut microbiota mediates the protective effects of anserine supplementation on hyperuricaemia and associated renal inflammation[J]. Food & function, 2021, 12(19): 9030-9042.
[3] de Souza Gonçalves L, Pereira W R, da Silva R P, et al. Anserine is expressed in human cardiac and skeletal muscles[J]. Physiological Reports, 2023, 11(19): e15833.
[4] Köpfer F, Bartosova Medvid M, Fleming T, et al. Effects of anserine on oxidative stress and on cell barrier integrity in methylmalonic aciduria[J]. Scientific Reports, 2025, 15(1): 32933.
[5] Wetzel C, Pfeffer T, Bulkescher R, et al. Anserine and carnosine induce HSP70-dependent H2S formation in endothelial cells and murine kidney[J]. Antioxidants, 2022, 12(1): 66.
[6] Yamaki K, Kamiki N, Nakatsuka N, et al. Naturally occurring imidazole peptides, carnosine and anserine inhibit the degranulation of mast cells and basophils by modulating intracellular signaling[J]. International Journal of Peptide Research and Therapeutics, 2024, 30(3): 26.
[7] Li Y, Ge J, Yin Y, et al. Exploration on the effect of anserine on the alleviation of DVT and its molecular mechanism[J]. Frontiers in pharmacology, 2024, 15: 1402758.
[8] Sunagawa Y, Tsukabe R, Irokawa Y, et al. Anserine, a histidine-containing dipeptide, suppresses pressure overload-induced systolic dysfunction by inhibiting histone acetyltransferase activity of p300 in mice[J]. International Journal of Molecular Sciences, 2024, 25(4): 2344.
[9] Luo J, Chen M, Ji H, et al. Anserine alleviates atherosclerosis in ApoE−/− mice by regulating lipid metabolism[J]. Journal of the Science of Food and Agriculture, 2025, 105(15): 8574-8585.