Metabolomics and network pharmacology revealing the transdermal moxibustion compounds and their therapeutic mechanisms for rheumatoid arthritis.

Researchers investigated how moxibustion—a traditional Chinese therapy that burns mugwort (Artemisia argyi) near the skin—might help people with rheumatoid arthritis (RA). While moxibustion has been used clinically for RA with good results, scientists didn't understand which therapeutic compounds actually pass through the skin or how they work in the body.

Using advanced chemical analysis, the research team identified 54 compounds that penetrate the skin during moxibustion treatment. Of these, 16 showed potential anti-arthritis activity. Three compounds stood out as particularly important: Citral, α-Terpineol, and Borneol. These substances appear to work by targeting TNF-α, a key protein involved in RA inflammation.

The researchers tested these compounds both in laboratory cell cultures from RA patients and in rats with induced arthritis. They found that Citral reduced inflammation and slowed the excessive cell growth that damages joints in RA. It accomplished this by blocking the MAPK signaling pathway and reducing inflammatory molecules like TNF-α and COX-2. Meanwhile, α-Terpineol and Borneol helped prevent the invasion of harmful cells into joint tissue by affecting enzymes called matrix metalloproteinases (MMPs).

In the animal studies, applying Citral directly under the skin improved arthritis symptoms, supporting the laboratory findings.

What this means: This study provides scientific evidence for how moxibustion may help rheumatoid arthritis by delivering specific therapeutic compounds through the skin that reduce joint inflammation and damage. If you're considering moxibustion for RA, seek treatment from a qualified, licensed acupuncturist trained in traditional moxibustion techniques.

This study characterized transdermal moxibustion compounds (TMOCs) and their mechanisms in rheumatoid arthritis treatment. Using GC-MS, researchers identified 54 TMOCs in subcutaneous tissue, with 16 demonstrating predicted anti-RA activity. Network pharmacology analysis revealed TNF-α as a central therapeutic target. Three core compounds—Citral, α-Terpineol, and Borneol—showed stable molecular interactions with TNF-α via docking and dynamics simulations.

In vitro studies using primary RA-derived fibroblast-like synoviocytes (RA-FLS) demonstrated that Citral inhibited proliferation, reduced TNF-α and COX-2 secretion, and downregulated ERK1/2, p38, and c-JUN protein expression. α-Terpineol and Borneol inhibited RA-FLS invasion and modulated MMP-1 and MMP-2 mRNA expression. In vivo validation using adjuvant-induced arthritis (AIA) rats confirmed that subcutaneous Citral administration ameliorated arthritic symptoms.

Clinical implications: Moxibustion's therapeutic effects in RA appear mediated through transdermal delivery of bioactive compounds targeting inflammation via MAPK pathway inhibition and MMP-mediated invasion modulation, providing mechanistic support for traditional moxibustion protocols in RA management.