Demethyleneberberine

Demethyleneberberine (DMB), as a natural active component of medicinal plant Cortex phellodendri chinensis, has favorable bioactivity^[1]. Demethyleneberberine also, as a natural mitochondria-targeted antioxidant, can inhibit oxidative stress, mitochondrial dysfunction, and steatosis in an alcoholic hepatic disease model^[2].

In vitro experiment it shown that with 0, 10, 20, 40, 80, and 160 µmol/L DMB (Demethyleneberberine) obviously inhibit proliferation of HSCs in a concentration dependent manner. The IC50 of DMB(Demethyleneberberine) for HSC-T6 cells at 48 h was 36.7 µmol/L^[3]. In vitro, Demethyleneberberine has the inhibition of monoamine oxidase B (MAO-B) with IC50 of 9.06 µM^[4].

In vivo efficacy test it demonstrated that mice were administrated 50 mg/kg/d orally Demethyleneberberine for 98 days markedly improved colon atrophy, colonic tissue mass score, neutrophil infiltration and histological damage, which was mainly attributed to the anti-inflammatory effect of Demethyleneberberine^[5]. In vivo, methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice were injected with 20 or 40 mg/kg intraperitoneally can reduce hepatic lipid accumulation. In addition, DMB treatmentthe can obviously attenuate oxidative damage and inflammation induced by NAFLD(Non-alcoholic fatty liver disease)^[6]. In vivo, inflammatory colitis mice were administrated with 150 and 300 mg/kg orally Demethyleneberberine caused the reduction of weight loss and myeloperoxidase (MPO) activity, while significantly decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibited the activation of NF-κB signaling pathway^[7].

References:

[1] Liu J, et al. Demethyleneberberine induces cell cycle arrest and cellular senescence of NSCLC cells via c-Myc/HIF-1α pathway. Phytomedicine. 2021 Oct;91:153678.

[2] Zhang P., et al. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model. J. Pharmacol. Exp. Ther. 2015;352:139–147.

[3] Wang Y, et al. Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling. Int J Mol Sci. 2016 Jun 30;17(7):1036.

[4] Tao C, et al. Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine. Neurochem Int. 2020 Oct;139:104807.

[5] Zhao Y, et al. Demethyleneberberine blocked the maturation of IL-1β in inflammation by inhibiting TLR4-mitochondria signaling. Int Immunopharmacol. 2022 Dec;113(Pt A):109319.

[6] Qiang X, et al. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress. Biochem Biophys Res Commun. 2016 Apr 15;472(4):603-9.

[7] Chen YY, et al. Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis. Inflamm Res. 2017 Feb;66(2):187-196.