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

DOI record: { "DOI": "10.1038/s41598-024-54722-5", "ISSN": [ "2045-2322" ], "URL": "http://dx.doi.org/10.1038/s41598-024-54722-5", "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>", "alternative-id": [ "54722" ], "article-number": "4287", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "9 October 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "15 February 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "21 February 2024" }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 1, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Wan", "given": "Lina", "sequence": "first" }, { "affiliation": [], "family": "Li", "given": "Yuchen", "sequence": "additional" }, { "affiliation": [], "family": "Liao", "given": "Wenhao", "sequence": "additional" }, { "affiliation": [], "family": "Lei", "given": "Lizhen", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Maoyuan", "sequence": "additional" }, { "affiliation": [], "family": "Zeng", "given": "Jinhao", "sequence": "additional" }, { "affiliation": [], "family": "Zhao", "given": "Ziyi", "sequence": "additional" }, { "affiliation": [], "family": "Tang", "given": "Jianyuan", "sequence": "additional" } ], "container-title": "Scientific Reports", "container-title-short": "Sci Rep", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 2, 21 ] ], "date-time": "2024-02-21T11:03:07Z", "timestamp": 1708513387000 }, "deposited": { "date-parts": [ [ 2024, 2, 21 ] ], "date-time": "2024-02-21T11:06:28Z", "timestamp": 1708513588000 }, "funder": [ { "DOI": "10.13039/501100001809", "award": [ "82074397" ], "doi-asserted-by": "crossref", "name": "the National Natural Science Foundation of China" }, { "award": [ "2020-YYCM(UM)" ], "name": "Chinese Medicine\nIntervention Study on Prevention and Control of Novel Coronavirus Pneumonia Community Infections" }, { "award": [ "2020-7" ], "name": "Young “Qihuang Scholar” Support Program" }, { "award": [ "20-L01" ], "name": "“Hundred Talents Program” of the Hospital of Chengdu University of Traditional Chinese Medicine" }, { "award": [ "2021ZYD0107" ], "name": "the central government guides local science and technology development projects of Sichuan Provincial Science and Technology Department" } ], "indexed": { "date-parts": [ [ 2024, 2, 22 ] ], "date-time": "2024-02-22T01:05:12Z", "timestamp": 1708563912154 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 2, 21 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 2, 21 ] ], "date-time": "2024-02-21T00:00:00Z", "timestamp": 1708473600000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 2, 21 ] ], "date-time": "2024-02-21T00:00:00Z", "timestamp": 1708473600000 } } ], "link": [ { "URL": "https://www.nature.com/articles/s41598-024-54722-5.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-024-54722-5", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.nature.com/articles/s41598-024-54722-5.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1038", "published": { "date-parts": [ [ 2024, 2, 21 ] ] }, "published-online": { "date-parts": [ [ 2024, 2, 21 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.3390/v13020202", "author": "A Sharma", "doi-asserted-by": "publisher", "journal-title": "Viruses", "key": "54722_CR1", "unstructured": "Sharma, A., Ahmad Farouk, I. & Lal, S. 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