Cryptotanshinone is a natural compound extracted from the roots of Salvia miltiorrhiza Bunge, exhibiting antitumor activity by inhibiting Signal Transducer and Activator of Transcription 3 (STAT3) with an IC50 value of 4.6μM[1, 2]. Cryptotanshinone possesses multiple biological activities, including antitumor, anti-inflammatory, anti-fibrotic, and anti-angiogenic effects[3, 4].
In vitro, Cryptotanshinone (20μM) treatment of A549 cells for 24h reduced the percentage of cells in the G0/G1 phase, increased the percentage of cells in the G2/M phase, induced G2/M phase arrest, and promoted apoptosis along with the expression of apoptotic genes[5]. In another study, pretreatment of H9C2 cells with Cryptotanshinone (3μM) for 1h significantly prevented chronic hypoxia-induced cell injury, restored cellular ATP levels, reduced mitochondrial superoxide levels, and decreased intracellular NO and calcium levels[6].
In vivo, Cryptotanshinone (50mg/kg/day) administered via gastric gavage for 4 weeks in a mouse model of cardiac remodeling induced by aortic banding (AB) surgery improved pressure overload-induced cardiac dysfunction, attenuated cardiac hypertrophy, and reduced cardiac fibrosis[7]. Additionally, Cryptotanshinone (40mg/kg/day) administered orally in a CCl4-induced liver fibrosis mouse model ameliorated liver fibrosis, inhibited the activation of hepatic stellate cells, and suppressed collagen production[8].
References:
[1] Zheng J, Zhou Y, Zhang P, et al. Salvia miltiorrhiza Bunge: Bioactive Compounds and Bioactivities[J]. Int. J. Trad. Nat. Med, 2015, 5(1): 52-81.
[2] Hua Y, Yuan X, Shen Y, et al. Novel STAT3 inhibitors targeting STAT3 dimerization by binding to the STAT3 SH2 domain[J]. Frontiers in Pharmacology, 2022, 13: 836724.
[3] Li H, Gao C, Liu C, et al. A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen[J]. Biomedicine & Pharmacotherapy, 2021, 137: 111332.
[4] Hur J M, Shim J S, Jung H J, et al. Cryptotanshinone but not tanshinone IIA inhibits angiogenesis in vitro[J]. Experimental & molecular medicine, 2005, 37(2): 133-137.
[5] Chen L, Wang H J, Xie W, et al. Cryptotanshinone inhibits lung tumorigenesis and induces apoptosis in cancer cells in vitro and in vivo[J]. Molecular medicine reports, 2014, 9(6): 2447-2452.
[6] Jin H J, Li C G. Tanshinone IIA and cryptotanshinone prevent mitochondrial dysfunction in hypoxia‐induced H9c2 cells: association to mitochondrial ROS, intracellular nitric oxide, and calcium levels[J]. Evidence‐Based Complementary and Alternative Medicine, 2013, 2013(1): 610694.
[7] Li W, Yan H, Zhou Z, et al. Cryptotanshinone attenuated pathological cardiac remodeling in vivo and in vitro experiments[J]. Oxidative Medicine and Cellular Longevity, 2023, 2023(1): 4015199.
[8] Li Z, Zheng Y, Zhang L, et al. Cryptotanshinone alleviates liver fibrosis via inhibiting STAT3/CPT1A-dependent fatty acid oxidation in hepatic stellate cells[J]. Chemico-Biological Interactions, 2024, 399: 111119.
Cryptotanshinone是从丹参（Salvia miltiorrhiza Bunge）的根中提取的天然化合物，具有抗肿瘤活性，能够抑制信号转导及转录激活蛋白3（STAT3），IC50值为4.6μM[1, 2]。Cryptotanshinone具有抗肿瘤、抗炎、抗纤维化、抗血管生成等活性[3, 4]。
在体外，Cryptotanshinone（20μM）处理A549细胞24h，降低了G0/G1期细胞的百分比，增加了G2/M期的百分比，导致了细胞G2/M期停滞，诱导了细胞凋亡和凋亡基因的表达[5]。Cryptotanshinone（3μM）预处理H9C2细胞1h，显著预防了慢性缺氧诱导的细胞损伤，恢复了细胞ATP含量，降低了线粒体内超氧化物水平，降低了细胞内NO和钙水平[6]。
在体内，Cryptotanshinone（50mg/kg/day）通过胃灌注治疗主动脉束缚（AB）手术构建的心脏重塑模型小鼠4周，改善了小鼠压力超负荷引起的心脏功能障碍，减弱了心脏肥大并减少心脏纤维化[7]。Cryptotanshinone（40mg/kg/day）通过口服治疗CCl4诱导的肝纤维化小鼠，改善了小鼠的肝纤维化，抑制了小鼠肝星状细胞的激活，抑制了胶原蛋白的产生[8]。