Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production

Siridechakorn et al., Scientific Reports, doi:10.1038/s41598-023-46249-y

Nov 2023

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In Vitro study analyzing the antiviral and anti-inflammatory properties of extracts and fractions from Andrographis paniculata, against herpes simplex virus-1 (HSV-1) and influenza A virus H3N2 as surrogates for COVID-19. The results showed that certain A. paniculata extracts, particularly the andrographolide-rich fractions, could directly inactivate both viruses and inhibit their replication in infected cells. Interestingly, one andrographolide-free fraction also displayed potent antiviral effects against both viruses. Additionally, specific extracts inhibited nitric oxide production, highlighting their anti-inflammatory potential. The antiviral and anti-inflammatory activities demonstrated in this study suggest that further exploration of A. paniculata extracts as potential treatments for COVID-19 may be warranted.

11 preclinical studies support the efficacy of andrographolide for COVID-19:

4 In Silico studies Dassanayake, Dey, Rajagopal, Thomas

5 In Vitro studies Low, Mohd Abd Razak, Pu, Siridechakorn, Wan

2 In Vivo animal studies Pu, Wan

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1. Dassanayake et al., Molecular Docking and In-Silico Analysis of Natural Biomolecules against Dengue, Ebola, Zika, SARS-CoV-2 Variants of Concern and Monkeypox Virus, International Journal of Molecular Sciences, doi:10.3390/ijms231911131.mdpi.com, doi.org.

2. Dey et al., The role of andrographolide and its derivative in COVID-19 associated proteins and immune system, Research Square, doi:10.21203/rs.3.rs-35800/v1.researchsquare.com, doi.org.

3. Low et al., The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm, bioRxiv, doi:10.1101/2024.02.21.581396.biorxiv.org, doi.org.

4. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

5. Pu et al., The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis, Phytomedicine, doi:10.1016/j.phymed.2023.154753.sciencedirect.com, doi.org.

6. Rajagopal et al., Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Future Journal of Pharmaceutical Sciences, doi:10.1186/s43094-020-00126-x.springeropen.com, doi.org.

7. Siridechakorn et al., Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production, Scientific Reports, doi:10.1038/s41598-023-46249-y.nature.com, doi.org.

8. Thomas et al., Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-024-58532-7.nature.com, doi.org.

9. Wan et al., Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level, Scientific Reports, doi:10.1038/s41598-024-54722-5.nature.com, doi.org.

Siridechakorn et al., 13 Nov 2023, Thailand, peer-reviewed, 9 authors. Contact: bhparvapan@gmail.com, netiw@nu.ac.th.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Andrographol..All

Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production

Ittipon Siridechakorn, Parvapan Bhattarakosol, Thanayod Sasivimolrattana, Sasiprapa Anoma, Eakkaluk Wongwad, Nitra Nuengchamnong, Ekasit Kowitdamrong, Siwaporn Boonyasuppayakorn, Neti Waranuch

Scientific Reports, doi:10.1038/s41598-023-46249-y

Andrographis paniculata (Burm. F.) Nees is a medicinal plant previously reported with broad-spectrum antivirals but the mode of inhibition remains elusive. The objective of this study was to identify the most active fraction from A. paniculata ethanol extract (APE, APE-2A, APE-2B and APE-2C) and dry powder extract (APSP) against influenza A (H3N2), representing RNA viruses, and herpes simplex virus-1 (HSV-1), representing DNA viruses. The results showed that the fractions APSP, APE, APE-2B, and APE-2C directly neutralized the HSV-1 and influenza A (H3N2) when incubated at room temperature for 60 min before infecting the cells. The results also showed that the additional APE-2A fraction also directly neutralized the influenza A (H3N2), but not the HSV-1. The APE, APE-2B and APE-2C inhibited the HSV-1 by more than 0.5 log when the fractions were introduced after infection. Similarly, the APSP and APE inhibited the influenza A (H3N2) more than 0.5 log after infection. Only 50 μg/mL APE-2C inhibited the viruses greater than 0.5 log. In addition, A. paniculata extracts were also evaluated for their interfering capacities against nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. As well, APE-2C potently inhibited NO production at the IC 50 of 6.08 μg/ mL. HPLC and LC-MS analysis indicated that the most actively antiviral fractions did not contain any andrographolide derivatives, whereas the andrographolide-rich fractions showed moderate activity. Andrographis paniculata (Burm. F.) Nees, commonly known in Thailand as "Fah Thalai Jone" belongs to the Acanthaceae family and is found throughout tropical and subtropical Asia and Southeast Asia 1 . A. paniculata extracts exhibit a wide range of pharmacological activities such as immunostimulatory 1,2 , antiviral 3,4 , and antibacterial activities 5 . A. paniculata extracts contain several constituents with a high content of andrographolide. The extract has broad-spectrum antiviral properties including the possibility of in vitro and in vivo anti-HIV 6 , as well as in vitro anti-dengue virus and chikungunya virus activity 7 . A. paniculata extracts are effective against the herpes simplex virus type 1 (HSV-1) that causes herpes 8 as well as reduced the inflammation caused by influenza viruses 9,10 . In addition, these extracts have also been reported to inhibit the division of influenza viruses 11 , hepatitis C virus 12 , and anti-viral mutations that cause resistance to such antiretroviral drugs 13 . The anti-inflammatory 14 and anti-allergic activities 15 of A. paniculata have been attributed to andrographolide, which is the major active compound 16,17 . Because of the COVID-19 pandemic that first arose in December 2019, this virus poses a serious risk to patients. The key mechanism for the manifestation of this disease is the inflammation process, which was the focus of this research which investigated the antiviral efficacy and anti-inflammation of A. paniculata extract. As..

Author contributions Competing interests The authors declare no competing interests.

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