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.
去亚甲基小檗碱(DMB)作为药用植物黄柏的天然活性成分,具有良好的生物活性[1]。去亚甲基小檗碱作为一种天然的靶向线粒体的抗氧化剂,还可以抑制酒精性肝病模型中的氧化应激、线粒体功能障碍和脂肪变性[2]。
体外实验表明,0、10、20、40、80、160 μmol/L DMB（Demethyleneberberine）浓度依赖性明显抑制HSCs增殖。 DMB(Demethyleneberberine)对HSC-T6细胞48 h的IC50为36.7 μmol/L[3]。在体外,Demethyleneberberine 对单胺氧化酶 B (MAO-B) 具有抑制作用,IC50 为 9.06 μM[4]。
体内药效试验表明,小鼠口服去亚甲基小檗碱50 mg/kg/d,持续98天,显着改善结肠萎缩、结肠组织质量评分、中性粒细胞浸润和组织学损伤,这主要归因于抗炎作用去亚甲基小檗碱[5]。在体内,蛋氨酸和胆碱缺乏症 (MCD) 高脂肪饮食喂养小鼠和 db/db 小鼠腹腔注射 20 或 40 mg/kg 可减少肝脏脂质积累。此外,DMB治疗可明显减轻NAFLD（非酒精性脂肪性肝病）引起的氧化损伤和炎症[6]。在体内,给炎性结肠炎小鼠口服 150 和 300 mg/kg 的去亚甲基小檗碱,导致体重减轻和髓过氧化物酶 (MPO) 活性降低,同时显着降低促炎细胞因子的产生,例如白细胞介素 (IL)-6 和肿瘤坏死因子-α（TNF-α）,抑制NF-κB信号通路的激活[7]。