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Anti-Inflammatory Activity of Bixin via Modulation of TLR4/NF-κB, PI3K/Akt and TXNIP/NLRP3 Inflammasome Pathways
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  • Mindy Hausler started the conversation

    This study investigated the anti-inflammatory potential of bixin, a major apocarotenoid from Bixa orellana seeds, across various inflammatory disease models. In vivo studies showed bixin (15-200 mg/kg, oral/intraperitoneal) reduced carrageenan-induced paw edema in rats by inhibiting myeloperoxidase activity, ameliorated UV-induced skin damage in mice by downregulating IL-6 and TNF-α, and protected against high-fat diet-induced cardiac injury and liver steatosis by suppressing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). In asthmatic mice (acute, chronic, steroid-resistant), bixin (50-100 mg/kg) attenuated airway hyperresponsiveness and reversed remodeling. In vitro, bixin (40-80 μM) inhibited LPS-induced inflammation in H9C2 cardiac cells by reducing TLR4/MyD88/NF-κB signaling. It also suppressed neuroinflammation in EAE mice (multiple sclerosis model) via TXNIP/NLRP3 inflammasome inhibition and Nrf2 activation. These studies demonstrate that bixin exerts broad-spectrum anti-inflammatory effects by targeting key signaling pathways, supporting its potential for treating inflammation-related diseases.The in vivo and in vitro evaluation of bixin's anti-inflammatory activity was conducted through controlled experiments. Animal models included carrageenan-induced paw edema (rats), UV-induced skin damage (SKH-1 mice), high-fat diet-induced cardiac/liver injury (C57BL/6 mice), ovalbumin-induced asthma (Balb/c mice), and EAE (C57BL/6 mice). Bixin was administered via oral gavage, intraperitoneal injection, or as loaded nanoparticles. In vitro assays used H9C2 cardiac cells and MLE12 airway epithelial cells treated with LPS or TGF-β1. Inflammatory markers (cytokines, TLR4, NF-κB p65, PI3K/Akt phosphorylation, TXNIP/NLRP3) were measured via Western blot, qPCR, and ELISA. Histopathological analysis assessed tissue inflammation and remodeling. Toxicity studies confirmed bixin's safety at therapeutic doses (up to 540 mg/kg in rats) with no severe adverse effects.