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ArticleInflammopharmacology2025

Fenchone attenuates CD68-dependent 7-ketocholesterol accumulation, cholesterol dyshomeostasis and inflammatory responses via modulation of macrophage polarization.

Sangeetha Ravi, Livya Catherene Martin, Manikandan Kumaresan, Jaya Suriya Mani, Beulaja Manikandan, Manikandan Ramar

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Article in Inflammopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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5 · Who and what money

Authors and funding

6 authors.

Sangeetha RaviDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Livya Catherene MartinDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Manikandan KumaresanDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Jaya Suriya ManiDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Beulaja ManikandanDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India.
Manikandan RamarDepartment of Zoology, University of Madras, Guindy Campus, Chennai, 600 025, India. manikandanramar@yahoo.co.in.ORCID http://orcid.org/0000-0002-7014-5470

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFoam cell formation, driven by oxidized low-density lipoprotein (Ox-LDL) uptake, particularly 7-ketocholesterol (7KCh), is a pivotal event in lipid-associated inflammatory diseases such as atherosclerosis. Conventional therapies often yield side effects, prompting interest in plant-derived biomolecules. Fenchone, a monoterpene from Foeniculum vulgare, has recently garnered attention for its anti-inflammatory and anti-lipidemic potential. PURPOSE: This study elucidates the pharmacologic efficacy of fenchone in mitigating foam cell formation by modulating cholesterol homeostasis, inflammatory signaling and polarization in macrophages.

methodsMurine IC-21 macrophages were induced with 7KCh and co-treated with fenchone. Cell viability was assessed using alamar blue assay, while lipid and calcium accumulation were analyzed with oil red O and alizarin red S staining. Pinocytosis, phagocytosis and actin cytoskeleton were evaluated with neutral red, goat RBCs uptake and phalloidin, respectively. Molecular changes were determined using ELISA, flow cytometry, PCR, western blot and in silico docking.

resultsFenchone significantly inhibited lipid and calcium accumulation, reduced lipid peroxidation and restored homeostatic endocytosis with anti-inflammatory cytoskeleton. It enhanced anti-inflammatory TGFβ1 and Smad2/3 while suppressing pro-inflammatory NF-κB, IL-1β, IL-6 and TNF-α. In addition, fenchone regulated cholesterol homeostasis via ABCA1, ApoE, LXR, CD36 and promoted M2 polarization by increasing CD163 and CD206 markers, downregulating M1 markers (CD38, CD68 and CD86). Computational analysis indicated the interactive affinity of 7KCh toward the CD68 scavenger receptor, which was prevented by fenchone.

conclusionThese findings highlight the therapeutic potential of fenchone in managing atherosclerosis by targeting CD68-mediated 7KCh uptake and inflammatory cascade, thereby emerging as a potential pharmacotherapeutic agent in inflammatory diseases.

Indexed as

Antigens, CDAntigens, Differentiation, MyelomonocyticCholesterolInflammationKetocholesterolsMacrophagesAnimalsAnti-Inflammatory AgentsCD68 MoleculeCell LineCell SurvivalFoam CellsHomeostasisLipoproteins, LDLMicePhagocytosis7-ketocholesterolAntigens, CDAntigens, Differentiation, MyelomonocyticAnti-Inflammatory AgentsCD68 MoleculeCD68 protein, mouseCholesterolKetocholesterolsLipoproteins, LDLoxidized low density lipoprotein7-ketocholesterolFenchoneInflammationLipidsMacrophage

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.