Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, PR China.
J Ethnopharmacol. 2020 Sep 15;259:112948. doi: 10.1016/j.jep.2020.112948. Epub 2020 May 15.
Chronic inflammation has an important role in the development of cancers. Hypericum sampsonii, known as "Yuanbao Cao", is mainly distributed in the southwest of China. As a folk medicinal plant, "Yuanbao Cao" is traditionally used for treatment of various inflammation-related diseases including swelling, burns, arthritis, and dermatitis, etc. The plant is a promising anticancer herb. However, there is no research on the antitumor potential of this plant from the view of cancer-related inflammation strategy.
To explore the H. sampsonii in relation to cancer-related chemical constituents with anti-inflammatory and cytotoxic activity in cancer-related inflammation.
The chemical constituents of H. sampsonii were isolated by repeated chromatography techniques, and their structures were identified mainly by spectroscopic methods and compared to published data. The chemical profile of the herb was analyzed using HPLC. The cytotoxicities of compounds against five cancer cell lines: human melanoma cell (A375), human breast cancer cell (MDA-MB-231), human gastric cancer cell (SGC-7901), human colon cancer cell (SiHa), and human bone marrow neuroblastoma cell (SHSY-5Y), were tested using MTT assay; their anti-inflammatory activities were evaluated by inhibition on NO production in LPS-stimulated RAW 264.7, THP-1 and BV-2 microglial cells.
Twenty-five compounds, including four phenols (1-4), two anthraquinonoids (5 and 6), six xanthones (7-12), one benzophenone (13), one phloroglucinol (14), nine flavonoids (15-23), one sterol (24) and one alkaloid (25), were isolated from the EtOH extract of H. sampsonii. Of them, compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were reported in H. sampsonii for the first time. HPLC analysis showed that flavonoids were the main constituents in the herb. MTT assay revealed that compounds 1, 2, 5-14, 15, 17, 18, 20, 21, 22 and 25 had selective cytotoxic activities (IC: 7.52-158.90 μM) against tested cancer cells, in which compound 5, 6, 13 and 14 displayed high activities against A375, MDA-MB-231, SiHa and SHSY-5Y. In the screening experiment of anti-inflammatory activity, most compounds (1-2, 5-23) showed considerable high anti-inflammatory activities (IC: 10.59-42.75 μM), in which compounds 5, 6, 13, 14, and 15 exhibited high anti-inflammatory activities in LPS-stimulated RAW264.7, THP-1 and BV-2 microglial cells.
Compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were isolated for the first time from H. sampsonii. Compound 5, 6, 13 and 14 displayed high cytotoxic activities against the tested cancer cell lines. Compounds (1-2, 5-23) showed anti-inflammatory activities, of them, compounds 5, 6, 13, 14 and 15 exhibited the high activity. From the view of cancer-related inflammation point, not only the compounds with high cytotoxicity, but those compounds with anti-inflammatory activities, especially the flavonoids, contribute to the antitumor potential of H. sampsonii. The results and viewpoint of present study provide a different insight to better understand the antitumor potential of H. sampsonii, and may also promote the reasonable usage of this folk medical herb.
慢性炎症在癌症的发展中起着重要作用。贯叶金丝桃，俗称“元宝草”，主要分布在中国西南部。作为一种民间药用植物，“元宝草”传统上用于治疗各种与炎症相关的疾病，如肿胀、烧伤、关节炎和皮炎等。这种植物是一种很有前途的抗癌草药。然而，从癌症相关炎症策略的角度来看，尚未有研究关注该植物的抗肿瘤潜力。
探讨元宝草中与具有抗炎和细胞毒性活性的癌症相关炎症的化学组成部分相关的化合物。
采用反复色谱技术从贯叶金丝桃中分离出化学成分，主要通过光谱方法确定其结构，并与已发表的数据进行比较。采用高效液相色谱法分析该草药的化学特征。采用 MTT 法测定化合物对五种癌细胞系（人黑色素瘤细胞（A375）、人乳腺癌细胞（MDA-MB-231）、人胃癌细胞（SGC-7901）、人结肠癌细胞（SiHa）和人骨髓神经母细胞瘤细胞（SHSY-5Y））的细胞毒性；通过抑制 LPS 刺激的 RAW 264.7、THP-1 和 BV-2 小胶质细胞中 NO 的产生来评估其抗炎活性。
从贯叶金丝桃的乙醇提取物中分离出 25 种化合物，包括 4 种酚类化合物（1-4）、2 种蒽醌类化合物（5 和 6）、6 种酮类化合物（7-12）、1 种苯甲酮类化合物（13）、1 种间苯三酚类化合物（14）、9 种类黄酮类化合物（15-23）、1 种甾体类化合物（24）和 1 种生物碱类化合物（25）。其中，化合物 3、4、6、7、10-14、17、19、22 和 23 首次在贯叶金丝桃中报道。HPLC 分析表明，黄酮类化合物是该草药的主要成分。MTT 分析显示，化合物 1、2、5-14、15、17、18、20、21、22 和 25 对测试的癌细胞具有选择性细胞毒性活性（IC：7.52-158.90 μM），其中化合物 5、6、13 和 14 对 A375、MDA-MB-231、SiHa 和 SHSY-5Y 表现出高活性。在抗炎活性筛选实验中，大多数化合物（1-2、5-23）表现出相当高的抗炎活性（IC：10.59-42.75 μM），其中化合物 5、6、13、14 和 15 在 LPS 刺激的 RAW264.7、THP-1 和 BV-2 小胶质细胞中表现出高抗炎活性。
化合物 3、4、6、7、10-14、17、19、22 和 23 首次从贯叶金丝桃中分离出来。化合物 5、6、13 和 14 对测试的癌细胞系表现出高细胞毒性活性。化合物（1-2、5-23）表现出抗炎活性，其中化合物 5、6、13、14 和 15 表现出高活性。从癌症相关炎症的角度来看，不仅具有高细胞毒性的化合物，而且具有抗炎活性的化合物，特别是黄酮类化合物，有助于贯叶金丝桃的抗肿瘤潜力。本研究的结果和观点为更好地理解贯叶金丝桃的抗肿瘤潜力提供了不同的视角，并可能促进对这种民间药用植物的合理使用。
