Brevilin A, a Sesquiterpene Lactone, Inhibits the Replication of Influenza A Virus In Vitro and In Vivo

Zhang, Xiaoli; Xia, Yiping; Yang, Li; He, Junyu; Li, Yao-Lan; Xia, Chuan

doi:10.3390/v11090835

Cited by 32 publications

(15 citation statements)

References 32 publications

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“…Brevilin A (BA), namely [(1S,3aR,5R,5aR,8aR,9S, 9aR)-1,5,8a-trimethyl-2,8-dioxo-3a,4,5,5a,9,9a-hexahydro -1H-azuleno [6,5-b] furan-9-yl] (Z)-2-methylbut-2-enoate (Figure 1), is a sesquiterpene lactone extracted from Centipeda minima (L.) A. Br. et Aschers., and has been reported to exhibit anti-viral and anti-cancer effects, 5,6 in cancers such as colon carcinoma, glioblastoma and nasopharyngeal carcinoma. [7][8][9] However, the effects of BA on TNBC have not yet been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Zhao

Lin

Mok

et al. 2020

OTT

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Purpose: Triple-negative breast cancer (TNBC) is a a breast cancer subtype characterized by a lack of estrogen receptor, progesterone receptor and human epidermal growth receptor 2 and is associated with poorer prognoses when compared to other breast cancers. Thus, novel anti-cancer agents with high efficacy are urgently needed. Brevilin A (BA), a natural sesquiterpene lactone, has been reported to exhibit anti-cancer effects. However, the effects of BA on TNBC have not yet been demonstrated. In this study, we investigated the anti-TNBC effects and the underlying mechanism of BA, in vitro and in vivo. Methods: Two TNBC cell lines and a xenograft mouse model were employed to assess the effects of BA. Cell viability was detected by MTT assay. Cell cycle status and apoptosis were evaluated by flow cytometry. Cell migration was measured by wound-healing assay. Protein expression was measured by Western blotting analysis. The in vivo anti-cancer activity of BA was assessed in orthotopic tumor xenograft mice. Results: BA significantly inhibited the growth of TNBC cells in a dose-and time-dependent manner via induction of cell cycle arrest at G2/M phase arrest and apoptosis. BA also inhibited tumor cell migration. BA significantly downregulated the expression of Akt, mTOR, Stat3 and their phosphorylation, and thus inhibiting the activation of the Akt/mTOR and STAT3 signaling pathways. Furthermore, oral administration of BA at 25 or 50 mg/kg leads to significant inhibition of tumor growth and proliferation in tumor xenograft model mice. Conclusion: BA significantly inhibited the growth and migration of TNBC cells, and induced cell cycle arrest and apoptosis. These inhibitory effects were associated with the suppression of the Akt/mTOR and Stat3 signal pathways. Based on our findings, BA possesses a promising candidate for development as an anti-cancer therapeutic drug against TNBC.

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Section: Introductionmentioning

confidence: 99%

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Zhao

Lin

Mok

et al. 2020

OTT

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“…Previously, we showed the antiviral activities of betulinic acid from Zizyphus jujuba , and hederasaponin F isolated from Hedera helix L. against influenza virus ( 5 31 ). Previous studies also suggested that pterodontic acid from Laggera pterodonta ( 32 ), silymarin ( 33 ), and brevilin A ( 34 ) inhibited the replication of influenza virus. More interestingly, quercetin, which has a chemical structure similar to morin hydrate, inhibited the influenza virus from entering the host cells ( 35 ).…”

Section: Discussionmentioning

confidence: 97%

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

et al. 2020

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Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2′,4′-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/ PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

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“…Quercetin 3-glucoside (Q3G), an analogous flavonoid obtained from the methanol extract of D. superbus , was the most active fraction in blocking IFV replication via a time-dependent assay ( Nile et al, 2020 ). Specially, brevilin A and C-methylated flavonoid that were determined to be (E)-4,2′,4′-trihydroxy-6′-methoxy-3′,5′-dimethylchalcone have the similar bioactive mechanism as Q3G ( Dao et al, 2010 ; Zhang et al, 2019 ).…”

Section: Natural Products With Reported Activities Against Viral Pneumonia: Focus On Medicinal Plantsmentioning

confidence: 99%

Overview of Viral Pneumonia Associated With Influenza Virus, Respiratory Syncytial Virus, and Coronavirus, and Therapeutics Based on Natural Products of Medicinal Plants

Lin

Chen

et al. 2021

Front. Pharmacol.

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Viral pneumonia has been a serious threat to global health, especially now we have dramatic challenges such as the COVID-19 pandemic. Approximately six million cases of community-acquired pneumonia occur every year, and over 20% of which need hospital admission. Influenza virus, respiratory virus, and coronavirus are the noteworthy causative agents to be investigated based on recent clinical research. Currently, anaphylactic reaction and inflammation induced by antiviral immunity can be incriminated as causative factors for clinicopathological symptoms of viral pneumonia. In this article, we illustrate the structure and related infection mechanisms of these viruses and the current status of antiviral therapies. Owing to a set of antiviral regiments with unsatisfactory clinical effects resulting from side effects, genetic mutation, and growing incidence of resistance, much attention has been paid on medicinal plants as a natural source of antiviral agents. Previous research mainly referred to herbal medicines and plant extracts with curative effects on viral infection models of influenza virus, respiratory virus, and coronavirus. This review summarizes the results of antiviral activities of various medicinal plants and their isolated substances, exclusively focusing on natural products for the treatment of the three types of pathogens that elicit pneumonia. Furthermore, we have introduced several useful screening tools to develop antiviral lead compounds.

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Brevilin A, a Sesquiterpene Lactone, Inhibits the Replication of Influenza A Virus In Vitro and In Vivo

Cited by 32 publications

References 32 publications

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

Overview of Viral Pneumonia Associated With Influenza Virus, Respiratory Syncytial Virus, and Coronavirus, and Therapeutics Based on Natural Products of Medicinal Plants

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