The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, the HIF-1 and its subunits have been considered to be hopeful anti-cancer targets. Various natural compounds were reported to persuade cell cytotoxicity through targeting and downregulation of the HIF-1. The genus Salvia is a rich source of bioactive terpenoids which show promising anti-cancer activities. Here, the identification of natural anti-proliferative compound targeting the HIF-1α expression was reported. A bioassay-guided isolation was employed for the discovery of natural anti-proliferative compounds from Salvia extracts using MTT assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC₅₀ value of 35 μg/mL) which was confirmed by genotoxicity and apoptosis detection analyses. The quantitative qPCR analysis showed that the expression level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and clerodermic acid have significant potential for reducing HIF-1α expression and could be considered for further studies for cancer therapy.

实体肿瘤对低氧/营养环境的适应性由缺氧诱导因子-1（HIF-1）的关键转录作用介导。因此，HIF-1及其亚基被认为是有希望的抗癌靶标。据报道，各种天然化合物通过靶向和下调HIF-1来说服细胞毒性。丹参属是生物活性萜类化合物的丰富来源，其显示出有希望的抗癌活性。在此，报道了针对HIF-1α表达的天然抗增殖化合物的鉴定。采用生物测定指导的分离技术，用于从丹参中发现天然抗增殖化合物MTT分析法针对A549细胞提取提取物。在此方向上，从鼠尾草中纯化了作为有效的细胞毒性化合物的盐酸二十二烷（CDA），并使用1D和2D NMR分析对其进行了鉴定。结果表明，CDA具有抗增殖活性（IC ₅₀值为35μg/ mL），已通过遗传毒性和凋亡检测分析得到证实。定量qPCR分析显示，与未处理的细胞耐受的缺氧相比，在用CDA处理的缺氧细胞中，HIF-1α的表达水平受到了强烈抑制。研究发现，沙门氏菌和氯皮肤酸具有降低HIF-1α表达的巨大潜力，可以考虑用于癌症治疗的进一步研究。