School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 260 Baichuan St, Hangzhou, 311402, People's Republic of China.
School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China.
J Nat Med. 2024 Sep;78(4):1003-1012. doi: 10.1007/s11418-024-01820-3. Epub 2024 May 22.
The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC of 14.3 μM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1β and IL-8 at 10 μM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.
在中国，中草药治疗 COVID-19 的实践对控制死亡率和缩短康复时间发挥了重要作用。环烯醚萜类化合物是许多清热解毒中药的主要成分之一，在中国被大量种植并广泛应用于临床实践。从几种常用中药中获得了 23 种具有代表性的高含量环烯醚萜类化合物，并通过 SARS-CoV-2 假病毒进入抑制试验、活 HCoV-OC43 病毒感染试验和 SARS-CoV-2 3CL 蛋白酶抑制 FRET 试验对其进行了测试，随后进行了分子对接模拟。进一步在 TNF-α诱导的 A549 细胞炎症模型上评估了它们的抗肺炎症活性，并得出了初步的 SARs。结果表明，獐牙菜苦苷（7）、山茱萸苷（12）、新獐牙菜苦苷（15）和獐牙菜苦苷 III（21）表现出有前景的抗病毒活性，而新獐牙菜苦苷（15）可以抑制 3CL 蛋白酶，IC 为 14.3 μM。对接计算表明，化合物 15 可以通过多种氢键和疏水相互作用与 3CL 蛋白酶结合。在抗肺炎症试验中，山茱萸苷（12）、梓醇（16）、莫诺苷（17）和山栀苷甲酯（18）在 10 μM 时可以强烈降低 IL-1β 和 IL-8 的含量。化合物 17 还可以显著上调抗炎细胞因子 IL-10 的表达。这些环烯醚萜类化合物具有抗冠状病毒和抗肺炎症活性，这对于它们在中草药中的存在意义重大，也为它们在医药和食品工业中的潜在应用提供了理论依据。
