Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, China.
J Ethnopharmacol. 2023 Feb 10;302(Pt A):115761. doi: 10.1016/j.jep.2022.115761. Epub 2022 Oct 26.
Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia.
The purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying.
HCF or HCP were administrated separately or combined in different proportions on influenza virus H1N1 - infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blot, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissues. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestines. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis.
In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by HCF and HCP combination reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediators. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury. The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema.
Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.
蕺菜（HC，三白草科）是一种经典的中药，临床上用于治疗肺炎。总黄酮（HCF）和多糖（HCP）是蕺菜的主要药用成分，参与其对病毒性肺炎的有益作用。
本研究旨在探讨 HCF 和 HCP 联合应用对病毒性肺炎的协同或互补作用及其机制。
流感病毒 H1N1 感染小鼠分别给予 HCF 或 HCP 单独或不同比例联合治疗。记录小鼠的生存和肺重。采用 Chou-Talalay 法计算 HCF 和 HCP 联合的协同作用。进行 H&E 染色以检测肺组织形态。采用 Western blot、免疫组化和酶联免疫吸附试验分析肺和肠组织中代表性蛋白的表达。对肠组织切片进行 AB-PAS 染色，评价肠道组织病理学。提取细菌基因组 DNA 并进行测序，进行肠道微生物组分析。
在 H1N1 致死性感染的小鼠中，与单药治疗相比，HCF 和 HCP 联合给药显著提高了小鼠的存活率并延长了其寿命。HCF 和 HCP 联合治疗显著改善了病毒性肺炎，表现为肺指数降低、肺形态更完整、炎症细胞和介质减少。此外，HCF 和 HCP 的联合治疗调节了肠道微生物群，显著降低了肠道中致病性变形菌的比例和促炎细胞因子的分泌。HCF 和 HCP 联合显示出减轻肺和肠损伤的协同作用。在 HCF 和 HCP 联合治疗中还发现了互补作用，因为 HCF 提供了显著的抗病毒活性，而 HCP 显著改善了肠道物理屏障并增加了涉及水肿清除的蛋白质表达。
我们的研究结果表明，蕺菜 HCF 和 HCP 的联合治疗通过对肺和肠道稳态的多模式调节，协同缓解了 H1N1 诱导的小鼠病毒性肺炎，这可能为治疗病毒性肺炎提供新的治疗策略。
