Shikonin（紫草素，AbMole，M4240）是一種從紫草根中分離的萘醌類化合物，在多種研究中顯示出廣泛的生物活性。在細(xì)胞實驗中，Shikonin對HTR-8/SVneo細(xì)胞的活力表現(xiàn)出濃度和時間依賴性抑制，其作用機(jī)制涉及誘導(dǎo)細(xì)胞的焦亡[1]。Shikonin（CAS No.：517-89-5）在胃癌NCI-N87細(xì)胞中，顯著抑制細(xì)胞增殖，并影響凋亡相關(guān)蛋白Bax和Bcl-2的表達(dá)[2]。此外，Shikonin（紫草素）在SCLC細(xì)胞中通過抑制ERK信號通路和誘導(dǎo)鐵死亡，顯著抑制細(xì)胞增殖、遷移和侵襲[3]。在乳腺癌4T1細(xì)胞中，Shikonin通過誘導(dǎo)線粒體功能障礙和ROS產(chǎn)生抑制細(xì)胞增殖，并在小鼠原位模型中表現(xiàn)出腫瘤生長抑制和免疫調(diào)節(jié)作用[4]。

Shikonin在腎癌Caki-1和ACHN細(xì)胞中，通過濃度依賴性方式觸發(fā)細(xì)胞壞死和凋亡，其作用可被N-乙酰半胱氨酸（Acetylcysteine，NAC，一種ROS清除劑）部分逆轉(zhuǎn)。Shikonin（紫草素）在胰腺癌細(xì)胞中，通過抑制PAK1激酶活性（IC50為7.252 ± 0.054 μM）發(fā)揮抗腫瘤作用[5]。在動物實驗中，Shikonin（50.0 mg/kg）通過調(diào)節(jié)miRNA-140-5p/TLR4信號通路在小鼠急性肺損傷模型中表現(xiàn)出顯著的保護(hù)作用[6]。此外，Shikonin在胚絨毛尿囊膜（CAM）模型中通過抑制細(xì)胞增殖和誘導(dǎo)凋亡顯著減少甲狀腺髓樣癌細(xì)胞的生長[7]。在神經(jīng)炎癥研究中，Shikonin通過抑制海馬區(qū)炎癥反應(yīng)表現(xiàn)出抗抑郁和抗焦慮樣作用[8]。這些研究揭示了Shikonin（紫草素，AbMole，M4240）在多種細(xì)胞模型（如HTR-8/SVneo、NCI-N87、HT29、4T1、Caki-1、ACHN等）和動物模型（如小鼠、雞胚）中的廣泛作用，其機(jī)制涉及焦亡、凋亡、鐵死亡、ROS調(diào)節(jié)、信號通路抑制等多種途徑。

參考文獻(xiàn)及鳴謝
[1] Zeng, F.; Lai, Y.; Huang, Y.; et al. Shikonin from lithospermum erythrorhizon induces pyroptosis in trophoblast cells by activating the CTSB-NLRP3 inflammasome. Annals of medicine 2024, 56 (1), 2394584.
[2] Jia, L.; Zhu, Z.; Li, H.; et al. Shikonin inhibits proliferation, migration, invasion and promotes apoptosis in NCI-N87 cells via inhibition of PI3K/AKT signal pathway. Artificial cells, nanomedicine, and biotechnology 2019, 47 (1), 2662-2669.
[3] Qian, X.; Zhu, L.; Xu, M.; et al. Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation. Chemico-biological interactions 2023, 382, 110588.
[4] Yu, C.; Xing, H.; Fu, X.; et al. Effect and mechanisms of shikonin on breast cancer cells in vitro and in vivo. BMC complementary medicine and therapies 2024, 24 (1), 389.
[5] Ji, W.; Sun, X.; Gao, Y.; et al. Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells. Molecules (Basel, Switzerland) 2022, 27 (9).
[6] Zhang, Y. Y.; Liu, X.; Zhang, X.; et al. Shikonin improve sepsis-induced lung injury via regulation of miRNA-140-5p/TLR4-a vitro and vivo study. Journal of cellular biochemistry 2020, 121 (3), 2103-2117.
[7] Hasenoehrl, C.; Schwach, G.; Ghaffari-Tabrizi-Wizsy, N.; et al. Anti-tumor effects of shikonin derivatives on human medullary thyroid carcinoma cells. Endocrine connections 2017, 6 (2), 53-62.
[8] Shi, C.; Qi, Z.; Yang, C.; et al. Shikonin ameliorates depressive- and anxiogenic-like behaviors in rats via the suppression of inflammation in the hippocampus. Neuroscience letters 2024, 837, 137893.