The peroxisome proliferator-activated receptor (PPAR) α/γ-adenosine 5-monophosphate- (AMP-) activated protein kinase- (AMPK-) sirtuin-1 (SIRT1) pathway and fatty acid metabolism are reported to be involved in influenza A virus (IAV) replication and IAV-pneumonia. Through a cell-based peroxisome proliferator responsive element- (PPRE-) driven luciferase bioassay, we have investigated 145 examples of traditional Chinese medicines (TCMs). Several TCMs, such as Polygonum cuspidatum, Rheum officinale Baillon, and Aloe vera var. Chinensis (Haw.) Berg., were found to possess high activity. We have further detected the anti-IAV activities of emodin (EMO) and its analogs, a group of common important compounds of these TCMs. The results showed that emodin and its several analogs possess excellent anti-IAV activities. The pharmacological tests showed that emodin significantly activated PPARα/γ and AMPK, decreased fatty acid biosynthesis, and increased intracellular ATP levels. Pharmaceutical inhibitors, siRNAs for PPARα/γ and AMPKα1, and exogenous palmitate impaired the inhibition of emodin. The in vivo test also showed that emodin significantly protected mice from IAV infection and pneumonia. Pharmacological inhibitors for PPARα/γ and AMPK signal and exogenous palmitate could partially counteract the effects of emodin in vivo. In conclusion, emodin and its analogs are a group of promising anti-IAV drug precursors, and the pharmacological mechanism of emodin is linked to its ability to regulate the PPARα/γ-AMPK pathway and fatty acid metabolism.

中文翻译：

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大黄素及其类似物通过调节 PPARα/γ-AMPK-SIRT1 通路和脂肪酸代谢的抗甲型流感病毒作用和机制

过氧化物酶体增殖物激活受体（PPAR）α / γ-腺苷5-单磷酸-（AMP-）活化蛋白激酶-（AMPK-）sirtuin-1（SIRT1）途径和脂肪酸代谢据报道参与甲型流感病毒(IAV) 复制和 IAV-肺炎。通过基于细胞的过氧化物酶体增殖物反应元件 (PPRE-) 驱动的荧光素酶生物测定，我们研究了 145 个中药 (TCM) 实例。虎杖、大黄、芦荟等多种中药变种 Chinensis (Haw.) Berg. 被发现具有高活性。我们进一步检测了大黄素（EMO）及其类似物的抗IAV活性，这是这些中药中常见的重要化合物。结果表明大黄素及其几种类似物具有优异的抗IAV活性。药理试验表明，大黄素显著活化PPAR α / γ和AMPK，降低的脂肪酸生物合成，以及增加的胞内ATP水平。药物抑制剂、PPAR α / γ和 AMPK α 1 的siRNA以及外源性棕榈酸酯会削弱大黄素的抑制作用。体内试验还表明，大黄素显着保护小鼠免受 IAV 感染和肺炎。PPAR 的药理抑制剂α / γ和 AMPK 信号和外源性棕榈酸酯在体内可以部分抵消大黄素的作用。总之，大黄素及其类似物是一类有希望的抗IAV药物前体，和大黄素的药理作用机制被链接到其以调节PPAR能力α / γ -AMPK途径和脂肪酸代谢。