The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Diterpenes*/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal*/pharmacology ; Cytokines*/metabolism; Animals ; Mice ; Humans ; RAW 264.7 Cells ; Nitric Oxide/metabolism ; Anti-Inflammatory Agents/pharmacology ; Cytokine Release Syndrome/drug therapy ; NF-kappa B/metabolism ; Dinoprostone/metabolism ; Lipopolysaccharides/pharmacology ; THP-1 Cells ; Macrophages/drug effects ; Macrophages/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Ibuprofen/pharmacology ; Ibuprofen/therapeutic use ; Interferon-gamma/metabolism ; E-Selectin/metabolism

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 μM, 95% CI = 7.4 to 10.4 μM) was comparable to that of paracetamol (IC50 = 7.73 μM, 95% CI = 6.14 to 9.73 μM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.
Competing Interests: NO authors have competing interests.
(Copyright: © 2024 Low et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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410105JHGR (andrographolide)
0 (Diterpenes)
0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (Cytokines)
31C4KY9ESH (Nitric Oxide)
0 (Anti-Inflammatory Agents)
0 (NF-kappa B)
K7Q1JQR04M (Dinoprostone)
0 (Lipopolysaccharides)
0 (Tumor Necrosis Factor-alpha)
WK2XYI10QM (Ibuprofen)
82115-62-6 (Interferon-gamma)
0 (E-Selectin)

Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240719

20240719

PMC11253928

10.1371/journal.pone.0299965

39018291