Protopine, an alkaloid derived from Corydalis ternata, inhibits acetylcholinesterase activity with an IC50 value of 50μM [1]. Protopine inhibits the release and influx of platelet Ca2+, which in turn suppresses platelet aggregation[2]. Protopine has been widely used in cell and animal models as an anti-inflammatory agent to inhibit the expression of inflammatory factors[3].
In vitro, Protopine treatment for 48 hours significantly inhibited the proliferation of PC-3 and DU-145 cells, with IC50 values of 13.0 ± 1.7μM and 15.8 ± 1.6μM, respectively[4]. Treatment with 40μM Protopine for 24 hours significantly inhibited the viability of HepG2 cells and induced apoptosis through an endogenous pathway in a caspase-dependent manner, resulting in the accumulation of reactive oxygen species (ROS) within the cells[5]. 50μM of Protopine pretreatment for 30 minutes can effectively protect PC12 cells from damage caused by H2O2, resulting in a decrease in MDA levels and reversing the decline in SOD, glutathione peroxidase and catalase activities caused by H2O2[6].
In vivo, Protopine pretreatment via oral administration (11mg/kg) twice a day for two consecutive days in rats prior to exposure to CCl4 can prevent the increase in serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) caused by CCl4[7]. Protopine pretreatment (3.92mg/kg/day; i.p.) for three days can reduce the cerebral infarction rate and serum lactate dehydrogenase activity in rats with focal cerebral ischemia, and improve the score of ischemic neurological dysfunction and the histological changes of brain tissue[8].
References:
[1] Kim S R, Hwang S Y, Jang Y P, et al. Protopine from Corydalis ternata has anticholinesterase and antiamnesic activities[J]. Planta medica, 1999, 65(03): 218-221.
[2] Saeed S A, Gilani A H, Majoo R U, et al. Anti-thrombotic and anti-inflammatory activities of protopine[J]. Pharmacological research, 1997, 36(1): 1-7.
[3] Huang W, Kong L, Cao Y, et al. Identification and quantification, metabolism and pharmacokinetics, pharmacological activities, and botanical preparations of protopine: A review[J]. Molecules, 2021, 27(1): 215.
[4] Chen C H, Liao C H, Chang Y L, et al. Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines[J]. Cancer letters, 2012, 315(1): 1-11.
[5] Nie C, Wang B, Wang B, et al. Protopine triggers apoptosis via the intrinsic pathway and regulation of ROS/PI3K/Akt signalling pathway in liver carcinoma[J]. Cancer Cell International, 2021, 21(1): 396.
[6] Xiao X, Liu J, Hu J, et al. Protective effects of protopine on hydrogen peroxide-induced oxidative injury of PC12 cells via Ca2+ antagonism and antioxidant mechanisms[J]. European journal of pharmacology, 2008, 591(1-3): 21-27.
[7] Janbaz K H, Saeed S A, Gilani A H. An assessment of the potential of protopine to inhibit microsomal drug metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents[J]. Pharmacological research, 1998, 38(3): 215-219.
[8] Xiao X, Liu J, Hu J, et al. Protective effect of protopine on the focal cerebral ischaemic injury in rats[J]. Basic & clinical pharmacology & toxicology, 2007, 101(2): 85-89.
Protopine是一种从延胡索中提取的生物碱，可抑制乙酰胆碱酯酶活性（IC50=50μM）[1]。Protopine通过抑制血小板Ca2+释放和内流进而抑制血小板聚集[2]。Protopine作为抗炎剂广泛应用于细胞和动物模型以抑制炎症因子表达[3]。
在体外，Protopine处理48小时可显著抑制PC-3和DU-145细胞增殖，IC50值分别为13.0 ± 1.7μM和15.8 ± 1.6μM[4]。40μM的Protopine处理HepG2细胞24小时能通过caspase依赖性内源通路诱导凋亡，导致细胞内活性氧（ROS）积累[5]。50μM的Protopine预处理PC12细胞30分钟可有效保护细胞免受H2O2损伤，降低MDA水平并逆转H2O2引起的SOD、谷胱甘肽过氧化物酶和过氧化氢酶活性下降[6]。
在体内，大鼠在四氯化碳（CCl4）暴露前连续两天每日两次口服Protopine（11mg/kg）可预防CCl4引起的血清谷草转氨酶（AST）和谷丙转氨酶（ALT）水平升高[7]。连续三天腹腔注射Protopine（3.92mg/kg/day）能降低局灶性脑缺血大鼠的脑梗死率和血清乳酸脱氢酶活性，并改善神经功能障碍评分和脑组织病理学变化[8]。