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

Low et al., bioRxiv, doi:10.1101/2024.02.21.581396
Feb 2024  
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In vitro study showing that andrographolide exhibits broad anti-inflammatory and cytokine inhibiting activity against lipopolysaccharide (LPS) and interferon-γ induced inflammation in murine RAW264.7 and human THP-1 macrophage cell lines. Andrographolide significantly inhibited the release of key proinflammatory mediators involved in cytokine storm including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and interferon-γ (IFN-γ). The cytokine-inhibiting activity of andrographolide was more potent than common nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and diclofenac. Authors suggest the anti-inflammatory mechanism of andrographolide is linked to inhibition of NFκB activation. Results indicate andrographolide may have therapeutic potential for regulating inflammation and cytokine release associated with COVID-19 infection.
9 preclinical studies support the efficacy of andrographolide for COVID-19:
Low et al., 22 Feb 2024, preprint, 8 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperAndrographol..All
The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm
Mitchell Low, Harsha Suresh, Xian Zhou, Deep Jyoti Bhuyan, Muhammad A Alsherbiny, Cheang Khoo, Gerald Münch, Chun Guang Li
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 cytokineinhibiting 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 (IC 50 = 8.8 µM, 95% CI= 7.4 to 10.4 µM) was comparable to that of paracetamol (IC 50 = 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.
Conflicts of Interest: The authors declare no conflict of interest.
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