Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level

{ 'indexed': {'date-parts': [[2024, 2, 22]], 'date-time': '2024-02-22T01:05:12Z', 'timestamp': 1708563912154}, 'reference-count': 42, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 2, 21]], 'date-time': '2024-02-21T00:00:00Z', 'timestamp': 1708473600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2024, 2, 21]], 'date-time': '2024-02-21T00:00:00Z', 'timestamp': 1708473600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100001809', 'name': 'the National Natural Science Foundation of China', 'doi-asserted-by': 'crossref', 'award': ['82074397']}, { 'name': 'Chinese Medicine\n' 'Intervention Study on Prevention and Control of Novel Coronavirus Pneumonia ' 'Community Infections', 'award': ['2020-YYCM(UM)']}, {'name': 'Young “Qihuang Scholar” Support Program', 'award': ['2020-7']}, { 'name': '“Hundred Talents Program” of the Hospital of Chengdu University of Traditional ' 'Chinese Medicine', 'award': ['20-L01']}, { 'name': 'the central government guides local science and technology development projects of ' 'Sichuan Provincial Science and Technology Department', 'award': ['2021ZYD0107']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>The SARS-CoV-2 virus, belonging to the ' '<jats:italic>Coronavirus</jats:italic> genus, which poses a threat to human health worldwide. ' 'Current therapies focus on inhibiting viral replication or using ' 'anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ' 'ingredients of traditional Chinese medicine compounds ideal therapies due to their proven ' 'safety and minimal toxicity. Previous research suggests that andrographolide and baicalin ' 'inhibit coronaviruses; however, their synergistic effects remain unclear. Here, we studied ' 'the antiviral mechanisms of their synergistic use in vitro and in vivo. We selected the ' 'SARS-CoV-2 pseudovirus for viral studies and found that synergistic andrographolide and ' 'baicalein significantly reduced angiotensin-converting enzyme 2 protein level and viral entry ' 'of SARS-CoV-2 into cells compared to singal compound individually and inhibited the major ' 'protease activity of SARS-CoV-2. This mechanism is essential to reduce the pathogenesis of ' 'SARS-CoV-2. In addition, their synergistic use in vivo also inhibited the elevation of ' 'pro-inflammatory cytokines, including IL-6 and TNF-α—the primary cytokines in the development ' 'of acute respiratory distress syndrome (the main cause of COVID-19 deaths). In conclusion, ' 'this study shows that synergistic andrographolide and baicalein treatment acts as potent ' 'inhibitors of coronavirus mechanisms in vitro and in vivo—and is more effective together than ' 'in isolation.</jats:p>', 'DOI': '10.1038/s41598-024-54722-5', 'type': 'journal-article', 'created': {'date-parts': [[2024, 2, 21]], 'date-time': '2024-02-21T11:03:07Z', 'timestamp': 1708513387000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by ' 'downregulation of ACE2 protein level', 'prefix': '10.1038', 'volume': '14', 'author': [ {'given': 'Lina', 'family': 'Wan', 'sequence': 'first', 'affiliation': []}, {'given': 'Yuchen', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wenhao', 'family': 'Liao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lizhen', 'family': 'Lei', 'sequence': 'additional', 'affiliation': []}, {'given': 'Maoyuan', 'family': 'Zhao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jinhao', 'family': 'Zeng', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ziyi', 'family': 'Zhao', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jianyuan', 'family': 'Tang', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 2, 21]]}, 'reference': [ { 'key': '54722_CR1', 'doi-asserted-by': 'publisher', 'author': 'A Sharma', 'year': '2021', 'unstructured': 'Sharma, A., Ahmad Farouk, I. & Lal, S. 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