Artesunate inhibits PDE4 leading to intracellular cAMP accumulation, reduced ERK/MAPK signaling, and blockade of influenza A virus vRNP nuclear export

Yang, Xia; Long, Feixiang; Jia, Weixin; Zhang, Mingxin; Su, Guanming; Liao, Ming; Zeng, Zhenling; Chen, Weisan; Chen, Jianxin

doi:10.1016/j.antiviral.2023.105635

Cited by 8 publications

(3 citation statements)

References 70 publications

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“…In addition, it has been demonstrated that the MAPK (ERK, P38 and JNK ) and NF κ B signaling pathways play important roles in influenza virus replication, and activating these pathways is beneficial for IAV infection (50)(51)(52). Inhibiting p38 MAPK activation can inhibit IAV replication, vRNP output, and cell apoptosis (50).…”

Section: Discussionmentioning

confidence: 99%

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High-throughput drug screening for inhibition of influenza A virus infection based on human SIRT1 promoter and Genipin suppressing influenza A virus by activation of AMPK-SIRT1-PGC-1α signaling pathway

Ye,

Liu,

Wang

et al. 2024

Preprint

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The energy metabolism crisis is considered an important risk factor for severe influenza A virus (IAV) infection. During virus replication, the host cell’s “metabolic reprogramming” is beneficial for increasing the energy demand of the virus. SIRT1 plays a major role in altering metabolic reprogramming, and upregulation of SIRT1 expression can defend against viral infection. This study established a high-throughput drug screening method for human SIRT1 promoter. Nine natural medicines were selected from 134 traditional Chinese medicines. Among them, the activity ofGardenia jasminoidesEllis was relatively high. Further research has found that the plant extract and its active compound Genipin and its derivatives can significantly inhibit IAV replication, improve the survival rate of infected mice, and inhibit pneumonia. In addition, Genipin significantly increased the levels of energy metabolism core regulatory factors SIRT1, PPAR γ, PGC-1 α, and p-AMPK, inhibited IAV induced activation of MAPKs and NF-κB, and alleviated inflammatory response. The pharmacological antagonists of SIRT1 and PGC-1 α, as well as siRNA, significantly counteracted the effects of Genipin on IAV replication and inflammation. In summary, we found that Genipin and its derivatives could significantly inhibit IAV replication and inflammation, possibly by activating the AMPK-SIRT1-PGC-1α signaling pathway and altering metabolic reprogramming.

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Section: Discussionmentioning

confidence: 99%

“…Inhibiting ERK activation can block the nuclear entry and nuclear output of IAV vRNP (51). Inhibiting JNK and NF -κB activation can impair the synthesis of IAV vRNA and reduce the expression level of pro-inflammatory factors (52).…”

Section: Discussionmentioning

confidence: 99%

High-throughput drug screening for inhibition of influenza A virus infection based on human SIRT1 promoter and Genipin suppressing influenza A virus by activation of AMPK-SIRT1-PGC-1α signaling pathway

Ye,

Liu,

Wang

et al. 2024

Preprint

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“…AS is well known as the first-line therapeutic agent for severe malaria, and has garnered extensive attention from researchers due to the discovery of its diverse pharmacological activities in recent years ( Figure 2 ). These activities include regulating blood glucose and lipids [ 24 ], providing neuroprotection and analgesia [ 25 ], inducing pro-apoptosis, inhibiting angiogenesis, and suppressing osteoclastogenesis [ 26 ], as well as displaying anti-inflammatory [ 27 ], antiviral [ 28 ], and antibacterial effects [ 29 ]. Such findings underscore its therapeutic potential across various diseases such as obesity [ 30 ], diabetes mellitus [ 31 , 32 , 33 ], Alzheimer’s disease [ 34 ], chronic pain [ 35 ], asthma [ 36 ], and cancer [ 37 , 38 ].…”

Section: Pharmacological Properties Of Asmentioning

confidence: 99%

Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms

Zhu,

Wang,

Han

et al. 2024

Antioxidants

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The human body comprises numerous organs and tissues operating in synchrony, it facilitates metabolism, circulation, and overall organismal function. Consequently, the well-being of our organs and tissues significantly influences our overall health. In recent years, research on the protective effects of artesunate (AS) on various organ functions, including the heart, liver, brain, lungs, kidneys, gastrointestinal tract, bones, and others has witnessed significant advancements. Findings from in vivo and in vitro studies suggest that AS may emerge as a newfound guardian against organ damage. Its protective mechanisms primarily entail the inhibition of inflammatory factors and affect anti-fibrotic, anti-aging, immune-enhancing, modulation of stem cells, apoptosis, metabolic homeostasis, and autophagy properties. Moreover, AS is attracting a high level of interest because of its obvious antioxidant activities, including the activation of Nrf2 and HO-1 signaling pathways, inhibiting the release of reactive oxygen species, and interfering with the expression of genes and proteins associated with oxidative stress. This review comprehensively outlines the recent strides made by AS in alleviating organismal injuries stemming from various causes and protecting organs, aiming to serve as a reference for further in-depth research and utilization of AS.

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Biotechnological approaches in the production of plant secondary metabolites for treating human viral diseases: Prospects and challenges

Mahmoudieh,

Naghavi,

Sobri

et al. 2024

Biocatalysis and Agricultural Biotechnology

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Artesunate inhibits PDE4 leading to intracellular cAMP accumulation, reduced ERK/MAPK signaling, and blockade of influenza A virus vRNP nuclear export

Cited by 8 publications

References 70 publications

High-throughput drug screening for inhibition of influenza A virus infection based on human SIRT1 promoter and Genipin suppressing influenza A virus by activation of AMPK-SIRT1-PGC-1α signaling pathway

High-throughput drug screening for inhibition of influenza A virus infection based on human SIRT1 promoter and Genipin suppressing influenza A virus by activation of AMPK-SIRT1-PGC-1α signaling pathway

Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms

Biotechnological approaches in the production of plant secondary metabolites for treating human viral diseases: Prospects and challenges

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