Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα
Open accessAbstract
Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.
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Berberine acts as a SIRT1 or AMPK agonist to mimic energy restriction.
“For patients with T2DM, the main function of berberine is as a SIRT1 or AMPK agonist to mimic energy restriction [75–77] and to target on NF-κB [78] to improve insulin resistance and inflammation as well as to alleviate the activation of ox-LDL-induced macrophages [79].”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [77]
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- Authors
- Reddi, K., Li, H., Li, W., & Tetali, S.
- Affiliations
- University of Tennessee Health Science Center (US)
- Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
- University of Hyderabad (IN)
- Corresponding author
- Tetali, Sarada
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2021-08-05
- Volume
- 26
- Issue
- 16
- Pages
- 4733
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8400273
- OpenAlex
- W3190727749
- Cited by
- 35
- References
- 53
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 1
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- berberine, anti-inflammatory activity, lipopolysaccharide, NF-κB signaling, IKKα, arachidonic acid, THP-1 cells, inflammatory cytokines, cyclooxygenase-2, NF-κB nuclear translocation, atherosclerosis, chronic inflammation, molecular docking
- MeSH terms
- THP-1 Cells, Anti-Inflammatory Agents, Berberine, Humans, Inflammation, Lipopolysaccharides, Monocytes, Signal Transduction, NF-kappa B, I-kappa B Kinase
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