Dihydroberberine is a potent haematopoietic prostaglandin D2 synthase (H-PGDS), with an IC50 value of 3.7µM [1]. Dihydroberberine inhibits respiration in L6 myotubes and muscle mitochondria, through a specific effect on respiratory complex I, and activates AMP-activated protein kinase [2]. Dihydroberberine has been widely used in various animal models to lower blood sugar and improve glucose tolerance[3].
In vitro, Dihydroberberine treatment for 48h significantly inhibited the growth of A549, NCI-H460, and NCI-H1299 cells with IC50 values of 11.17, 46.33 and 37.91μM, respectively[4]. The perfusion of 10μM Dihydroberberine into HEK293 cells for 10 minutes significantly inhibited the expression of the human ether-a-go-go-related gene (hERG) potassium channel and reduced the transport of hERG protein[5].
In vivo, Dihydroberberine treatment via oral administration at a dose of 50mg/kg/day for one week significantly alleviated renal damage in mice with hyperuricemia, as evidenced by a significant decrease in serum creatinine and blood urea nitrogen levels and a reduction in inflammatory cytokine levels (TNF-α, IL-1β, IL-6, and IL-18)[6]. Administering Dihydroberberine (40mg/kg/day) by intragastric administration daily for 7 consecutive days could significantly reduce the swelling degree of paw edema, tissue damage extent, and inflammatory cell infiltration in mice treated with carrageenan[7]. Daily intragastric administration of Dihydroberberine (50mg/kg/day) for 8 days alleviated the symptoms of ulcerative colitis induced by dextran sulfate sodium (DSS) in mice and significantly improved the intestinal barrier function[8].
References:
[1] Li C H, Tung M C, Tsai C K, et al. Discovery and characterization of novel hematopoietic prostaglandin D synthase inhibitors from traditional Chinese medicine: the bioactive potential of dihydroberberine in treatments of Duchenne muscular dystrophy and inflammation-related diseases[J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2025, 40(1): 2555624.
[2] Turner N, Li J Y, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action[J]. Diabetes, 2008, 57(5): 1414-1418.
[3] Purwaningsih I, Maksum I P, Sumiarsa D, et al. A review of Fibraurea tinctoria and its component, berberine, as an antidiabetic and antioxidant[J]. Molecules, 2023, 28(3): 1294.
[4] Dai B, Ma Y, Wang W, et al. Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI‐H460 cells by repressing MAP kinase pathways and inflammatory mediators[J]. Journal of Cellular and Molecular Medicine, 2017, 21(10): 2573-2585.
[5] Yu D, Lv L, Fang L, et al. Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells[J]. PLoS One, 2017, 12(8): e0181823.
[6] Xu L, Lin G, Yu Q, et al. Anti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate-and hypoxanthine-induced hyperuricemic mice[J]. Frontiers in Pharmacology, 2021, 12: 645879.
[7] Tan L, Wang Y, Ai G, et al. Dihydroberberine, a hydrogenated derivative of berberine firstly identified in Phellodendri Chinese Cortex, exerts anti-inflammatory effect via dual modulation of NF-κB and MAPK signaling pathways[J]. International Immunopharmacology, 2019, 75: 105802.
[8] Li C, Dong N, Wu B, et al. Dihydroberberine, an isoquinoline alkaloid, exhibits protective effect against dextran sulfate sodium-induced ulcerative colitis in mice[J]. Phytomedicine, 2021, 90: 153631.