Anti‐influenza activity of berberine improves prognosis by reducing viral replication in mice

Yan, Yuqi; Fu, Yingjie; Wu, Sha; Qin, Hong-Qiong; Zhang, Xiao; Song, Bi-Mei; Weng, Yiyun; Wang, Pengcheng; Chen, Xiaoyin; Jiang, Zhuhua

doi:10.1002/ptr.6196

Cited by 61 publications

(51 citation statements)

References 30 publications

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“…BBR alleviated pulmonary inflammation and pulmonary edema induced by influenza virus in mice 31,57 . Our results also confirmed this beneficial effects of BBR in mice with influenza viral pneumonia.…”

Section: Discussionsupporting

confidence: 83%

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS

Liu

You

et al. 2020

Journal of Leukocyte Biology

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Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR‐mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species‐Nod‐like receptor protein 3 (ROS‐NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion‐targeted superoxide dismutase mimetic (Mito‐TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule‐associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3‐methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus‐infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl‐2/adenovirus E18‐19‐kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR‐induced mitophagy may be, at least in part, mediated in a BNIP3‐dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR‐mediated alleviation of influenza virus‐induced inflammatory lesions.

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Section: Discussionsupporting

confidence: 83%

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS

Liu

You

et al. 2020

Journal of Leukocyte Biology

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“…[248][249][250] Berberine suppressed viral infection-induced upregulation in the TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the Mrna and protein levels, as well as significantly inhibited the viral-induced increases in Th1/Th2 and Th17/Treg ratios and inflammatory cytokine production. 251 In addition, berberine inhibited EV71…”

Section: Antiviral Activitymentioning

confidence: 97%

Biologically active isoquinoline alkaloids covering 2014–2018

Shang

Yang

Morris‐Natschke

et al. 2020

Medicinal Research Reviews

117

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Isoquinoline alkaloids, an important class of N-based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014-2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti-inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.

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“…The results obtained with a second commonly used model based on A549 cells are also slightly confusing. While the activity of BBR has been reported in these cells [21], other reports show a strong cytotoxic activity of BBR towards cancerous cells, including A549 cells [10,30]. Indeed, while the effective concentration was rather low, the cytotoxic concentration was also low, and it was impossible to determine whether the observed effect is not an artifact.…”

Section: Discussionmentioning

confidence: 91%

“…We conclude that BBR hampers replication of the influenza A virus in MDCK cells, but to a much lesser extent than in other in vitro models [19,28]. Next, the human pulmonary tumor cell line A549 was assayed, as inhibition of the influenza virus by BBR in this cell line has been consistently reported [19,21]. Many reports show a high toxicity of BBR to cancer cells, including the A549 cell line [29,30], therefore BBR has been proposed as an antineoplastic drug candidate.…”

Section: The Antiviral Effect Of Bbr Is Cell-type Dependentmentioning

confidence: 82%

Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

Botwina

Owczarek

Rajfur

et al. 2020

Viruses

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Background: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. Methods: A panel of cell lines (Madin-Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied. Results and conclusions: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication.

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Anti‐influenza activity of berberine improves prognosis by reducing viral replication in mice

Cited by 61 publications

References 30 publications

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS

Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS

Biologically active isoquinoline alkaloids covering 2014–2018

Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

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