Dehydrocorydaline

Dehydrocorydaline is one of the quaternary ammonium alkaloids from Corydalis Rhizoma^[1]. Dehydrocorydaline inhibits platelet aggregation by a mechanism involving the adenosine diphosphate (ADP)-receptors P2Y₁ and P2Y₁₂, and it can also alter the content of monoamine in brains by limiting uptake-2 monoamine transporters, thus exerting its antidepressant effects^[1-2]. Dehydrocorydaline exhibited potent anti-malarial activity (IC₅₀=38nM) when tested against the P. falciparum 3D7 strain^[3].

In vitro, MCF-7 cells were treated with Dehydrocorydaline (0-200μM) for 24 hours, which significantly inhibited the growth of MCF-7 cells in a dose-dependent manner. When MCF-7 cells were co-incubated with 200μM Dehydrocorydaline and 10μM Z-IETD-FMK, the cell death induced by Dehydrocorydaline could be abrogated^[4]. Treatment of C2C12 myoblasts with Dehydrocorydaline (125-500nM; 2 days) increased the expression levels of muscle‑specific proteins, including MyoD, myogenin, and myosin heavy chain in a dose-dependent manner^[5].

In vivo, after intraperitoneal injection of Dehydrocorydaline (3.6, 6, or 10mg/kg), the onset time of writhing in mice was delayed in a dose-dependent manner in the acetic acid-induced test, and a dose-dependent antinociceptive effect was observed^[6]. Subcutaneous injection of 500µM Dehydrocorydaline (50µL) into mice with subcutaneously implanted MDA-MB-231 cells inhibited the growth of MDA-MB-231 tumor xenografts in SCID mice and decreased cell proliferation in newly formed tumors in vivo^[7].

References:
[1] Jin L, Zhou S, Zhu S, et al. Dehydrocorydaline induced antidepressant-like effect in a chronic unpredictable mild stress mouse model via inhibiting uptake-2 monoamine transporters. Eur J Pharmacol. 2019;864:172725.
[2] Li Y, Zhang L, Zhang P, Hao Z. Dehydrocorydaline Protects Against Sepsis-Induced Myocardial Injury Through Modulating the TRAF6/NF-κB Pathway. Front Pharmacol. 2021;12:709604.
[3] Nonaka M, Murata Y, Takano R, Han Y, Kabir MHB, Kato K. Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts. Malar J. 2018;17(1):244.
[4] Xu Z, Chen X, Fu S, et al. Dehydrocorydaline inhibits breast cancer cells proliferation by inducing apoptosis in MCF-7 cells [published correction appears in Am J Chin Med. 2012;40(6):1323]. Am J Chin Med. 2012;40(1):177-185.
[5] Yoo M, Lee SJ, Kim YK, et al. Dehydrocorydaline promotes myogenic differentiation via p38 MAPK activation. Mol Med Rep. 2016;14(4):3029-3036.
[6] Yin ZY, Li L, Chu SS, Sun Q, Ma ZL, Gu XP. Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines. Sci Rep. 2016;6:27129.
[7] Huang Y, Huang H, Wang S, Chen F, Zheng G. Dehydrocorydaline inhibits the tumorigenesis of breast cancer MDA‑MB‑231 cells. Mol Med Rep. 2020;22(1):43-50.

Dehydrocorydaline是从延胡索中分离得到的一种季铵生物碱^[1]。Dehydrocorydaline通过涉及腺苷二磷酸（ADP）受体P2Y₁和P2Y₁₂的机制抑制血小板聚集，还可以通过限制摄取-2单胺转运体来改变大脑中单胺的含量，从而发挥其抗抑郁作用^[1-2]。在针对恶性疟原虫3D7株的测试中，Dehydrocorydaline展现出强大的抗疟活性（半数抑制浓度IC₅₀ = 38nM）^[3]。

在体外，将MCF-7细胞用Dehydrocorydaline（0-200μM）处理24小时，以剂量依赖性方式显著抑制了MCF-7细胞的生长。当MCF-7细胞与200μM Dehydrocorydaline和10μM Z-IETD-FMK共同孵育时，Dehydrocorydaline诱导的细胞死亡可以被消除^[4]。对C2C12成肌细胞进行Dehydrocorydaline（125-500nM；2天）处理，以剂量依赖性方式增加了肌肉特异性蛋白（包括MyoD、肌生蛋白和肌球蛋白重链）的表达水平^[5]。

在体内，腹腔注射Dehydrocorydaline（3.6, 6, 10mg/kg）后，在醋酸诱导的扭体实验中，小鼠扭体反应的开始时间以剂量依赖性方式延迟，并观察到剂量依赖性的镇痛效果^[6]。将500µM Dehydrocorydaline（50µL）皮下注射到植入了MDA-MB-231细胞的小鼠体内，抑制了SCID小鼠中MDA-MB-231肿瘤异种移植物的生长，并减少了新形成肿瘤中的细胞增殖^[7]。