14-Deoxy-11,12-didehydroandrographolide inhibits apoptosis in influenza A(H5N1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity
ANTIVIRAL RESEARCH
Authors: Cai, Wentao; Wen, Haimei; Zhou, Qinyang; Wu, Lei; Chen, Yong; Zhou, Hongbo; Jin, Meilin
Abstract
Influenza A virus (IAV) infection represents a global health challenge. Excavating antiviral active components from traditional Chinese medicine (TCM) is a promising anti-IAV strategy. Our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (DAP), a major ingredient of a TCM herb called Andrographis paniculata, shows anti-IAV activity that is mainly effective against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), and A/PR/8/34 (H1N1) in vitro and in vivo. However, the underlying anti-IAV molecular mechanism of DAP needs further investigation. In the present work, we found that DAP can significantly inhibit the apoptosis of human lung epithelial (A549) cells infected with A/chicken/Hubei/327/ 2004 (H5N1). After DAP treatment, the protein expression levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all obviously downregulated. However, DAP had no inhibitory effect on caspase-8 activity and cleaved caspase-8 production. Meanwhile, the efficacy of DAP in reducing the apoptotic cells was lost after using the inhibitor of caspase-3 or caspase-9 but remained intact after the caspase-8 inhibitor treatment. Moreover, DAP efficiently attenuated the dissipation of mitochondrial membrane potential, suppressed cytochrome c release from the mitochondria to the cytosol, and decreased the protein expression ratio of Bax/Bcl-2 in the mitochondrial fraction. Furthermore, the silencing of caspase-9 reduced the yield of nucleoprotein (NP) and disabled the inhibitory ability of DAP in NP production in A549 cells. Overall results suggest that DAP exerts its antiviral effects by inhibiting H5N1-induced apoptosis on the caspase-9-dependent intrinsic/mitochondrial pathway, which may be one of the anti-H5N1 mechanisms of DAP.
SARS-CoV-2-host dynamics: Increased risk of adverse outcomes of COVID-19 in obesity
DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS
Authors: Yadav, Rakhee; Aggarwal, Sandeep; Singh, Archna
Abstract
Background and aim: The pandemic of COVID-19 has put forward the public health system across countries to prepare themselves for the unprecedented outbreak of the present time. Recognition of the associated risks of morbidity and mortality becomes not only imperative but also fundamental to determine the prevention strategies as well as targeting the high-risk populations for appropriate therapies. Methods: We reviewed, collated and analysed the online database i.e. Pubmed, Google scholar, Researchgate to highlight the demographic and mechanistic link between obesity and associated risks of severity in COVID-19. Results: We observed a changing dynamic in the reporting from the time of initial pandemic in China to currently reported research. While, initially body mass index (BMI) did not find a mention in the data, it is now clearly emerging that obesity is one of the profound risk factors for complications of COVID-19. Conclusion: Our review will help clinicians and health policy makers in considering the importance of obesity in making the prevention and therapeutic strategies of COVID-19. An extra attention and precaution for patients with obesity in COVID-19 pandemic is recommended. (c) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.