Tetrandrine Alleviates Allergic Rhinitis via REV-ERBα-Dependent Acetylcholine

Area of Science:

• Immunology
• Pharmacology
• Chronobiology

Background:

• Allergic rhinitis is a common chronic inflammatory nasal condition with significant health and economic impacts.
• Current treatments lack comprehensive symptom relief and immune modulation.
• Novel therapeutic strategies targeting underlying mechanisms are needed.

Purpose of the Study:

• To investigate the therapeutic mechanism of tetrandrine in allergic rhinitis.
• To explore tetrandrine's effects on the REV-ERBα pathway and cholinergic system.
• To establish tetrandrine as a potential treatment for allergic rhinitis.

Main Methods:

• Ovalbumin-induced allergic rhinitis mouse model.
• Intranasal administration of tetrandrine.
• Assessment of sneezing, nasal scratching, serum histamine, and substance P levels.
• Measurement of REV-ERBα mRNA and protein expression.
• Choline acetyltransferase expression and acetylcholine levels analysis.
• Gal4 reporter assays and Rev-erbα knockout mice.

Main Results:

• Tetrandrine significantly reduced allergic rhinitis symptoms and inflammatory markers.
• Tetrandrine upregulated REV-ERBα expression and activity in the nasal mucosa.
• REV-ERBα deficiency abolished tetrandrine's therapeutic effects.
• Tetrandrine suppressed choline acetyltransferase and acetylcholine synthesis.
• Inhibition of choline acetyltransferase partially blocked tetrandrine's efficacy.

Conclusions:

• Tetrandrine alleviates allergic rhinitis by activating REV-ERBα and suppressing the cholinergic pathway.
• The therapeutic effect involves REV-ERBα-mediated downregulation of choline acetyltransferase and acetylcholine.
• Tetrandrine represents a novel therapeutic agent targeting circadian clock pathways for allergic rhinitis treatment.