Silymarin Exerts Potent Antipruritic Effects Against Chloroquine-Induced Scratching in Mice by Modulating the NO/NF-κB/TRPA1 Pathway

AuthorHosna Bagherien
AuthorAmir Kianien
AuthorMohammad Amin Ali Mohammad Golesorkhien
AuthorAntoni Suredaen
AuthorSamira Shirooieen
OrcidHosna Bagheri [0009-0004-4863-443X]en
OrcidAmir Kiani [0000-0002-7802-2117]en
OrcidSamira Shirooie [0000-0002-5000-3387]en
Issued Date2026-12-31en
AbstractBackground: Pruritus may occur through histamine-dependent or histamine-independent mechanisms. Chronic pruritus, which is often unresponsive to antihistamines, has been associated with nitric oxide (NO) signaling, which can modulate nuclear factor-κB (NF-κB) activity and transient receptor potential ankyrin 1 (TRPA1) function. Objectives: This study investigated the antipruritic potential of silymarin in a mouse model of chloroquine-induced systemic pruritus. Methods: Adult male NMRI mice were allocated to 16 groups. Treatments included silymarin (10, 30, and 60 mg/kg), L-NAME (1 and 10 mg/kg), aminoguanidine, L-arginine (10 and 100 mg/kg), sildenafil (10 and 20 mg/kg), and various combinations of these agents with silymarin. Scratching behavior, including frequency and duration, was recorded for 30 minutes on the second day after chloroquine (CQ) administration. Dorsal root ganglia (DRG) were analyzed by immunofluorescence to assess the expression of NF-κB and TRPA1. Results: Silymarin (60 mg/kg), L-NAME (10 mg/kg), and aminoguanidine significantly reduced chloroquine-induced itching, whereas L-arginine (100 mg/kg) and sildenafil (20 mg/kg) exacerbated it. The combination of subeffective doses of L-NAME (1 mg/kg) and silymarin (10 mg/kg) produced potentiated antipruritic effects, whereas L-arginine and sildenafil counteracted the inhibitory effects of high-dose silymarin. CQ increased NF-κB and TRPA1 expression in the DRG. These changes were ameliorated by silymarin and L-NAME but aggravated by L-arginine and sildenafil. Conclusions: Silymarin alleviated chloroquine-induced itching, suggesting modulation of the NO/NF-κB/TRPA1 signaling pathway and supporting its potential as a therapeutic option for histamine-independent pruritic conditions.en
DOIhttps://doi.org/10.5812/ijpr-169711en
URIhttps://brieflands.com/journals/ijpr/articles/169711en
KeywordSilymarinen
KeywordChloroquineen
KeywordItchingen
KeywordNitric Oxideen
KeywordNF-κB P65en
KeywordPruritusen
PublisherBrieflandsen
TitleSilymarin Exerts Potent Antipruritic Effects Against Chloroquine-Induced Scratching in Mice by Modulating the NO/NF-κB/TRPA1 Pathwayen
TypeResearch Articleen

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