Inhibition of the p38/JNK MAPK pathway mediated by circadian rhythm genes: Study of the mechanism of Linggan Wuwei Jiangxin decoction in the treatment of COPD.

Researchers investigated how a traditional Chinese herbal formula called Linggan Wuwei Jiangxin Decoction (LGWWJXD) might help treat chronic obstructive pulmonary disease (COPD), a serious lung condition causing persistent coughing and breathing difficulties. The study used rats exposed to cigarette smoke, cold temperatures, and bacterial substances to mimic COPD, then treated them with this herbal formula traditionally used for warming the lungs and relieving cough and asthma.

The research team used advanced laboratory techniques to identify active compounds in the herbal formula and track how they work in the body. They discovered that three key ingredients—Asarinin, 6-Shogaol, and Isoliquiritigenin—appear to reduce lung inflammation by affecting genes that control the body's internal clock (circadian rhythm genes). These compounds blocked specific inflammatory pathways in the body, leading to decreased lung damage and improved lung function in the treated rats.

Laboratory tests on human lung cells confirmed these anti-inflammatory effects, particularly for Asarinin, which significantly reduced inflammatory markers. The herbal formula worked through multiple mechanisms: regulating biological rhythms, blocking inflammatory signals, and influencing metabolism pathways related to arginine and purine processing.

For patients with COPD seeking complementary approaches, this research provides scientific evidence supporting the traditional use of LGWWJXD. While this formula represents herbal medicine rather than acupuncture, many practitioners of Traditional Chinese Medicine offer both modalities as integrated treatment approaches for respiratory conditions. If considering acupuncture or herbal medicine for COPD, consult with a licensed acupuncturist or qualified Traditional Chinese Medicine practitioner experienced in treating respiratory conditions.

This study investigated Linggan Wuwei Jiangxin Decoction's (LGWWJXD) mechanism in treating COPD using rat models exposed to cigarette smoke, hypothermia, and lipopolysaccharide. Researchers employed UPLC-MS/MS, metabolomics, transcriptomics, WGCNA, machine learning algorithms, single-cell RNA sequencing, molecular docking, and in vitro validation with BEAS-2B cells. Key findings identified three active compounds—Asarinin, 6-Shogaol, and Isoliquiritigenin—that modulate circadian rhythm genes (Bmal1, Per2, Nr1d1) to inhibit the p38/JNK MAPK signaling pathway. LGWWJXD intervention normalized differential metabolites, particularly through arginine biosynthesis and purine metabolism pathways, while reducing inflammatory cytokines (TNF-α, IL-1β, IL-6) in bronchoalveolar lavage fluid and serum. Histological analysis confirmed reduced pathological lung damage and improved function. In vitro studies demonstrated Asarinin upregulated Bmal1 protein expression, suppressing inflammatory factor release. Clinical relevance: This multi-modal analysis provides mechanistic evidence for LGWWJXD's anti-inflammatory effects in COPD through circadian rhythm regulation, supporting its traditional application for lung warming and phlegm transformation.