Innovative Combined Therapy Using Chinese Herb Astragalus and Methotrexate Targets Drug Resistance in Autoimmune Diseases

Researchers from the University of Hong Kong's School of Chinese Medicine have developed a novel combined therapy that merges the traditional Chinese medicinal herb Astragalus membranaceus with the Western pharmaceutical methotrexate (MTX) to combat drug resistance in autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome.

This groundbreaking study addresses the persistent challenge of long-term medication side effects and drug resistance commonly faced by patients managing chronic autoimmune conditions. Although MTX is a frontline treatment known for reducing inflammation, its prolonged use can lead to decreased effectiveness and severe adverse effects like liver toxicity.

The research team thoroughly analyzed 1,640 Chinese medicine formulations used over four decades to treat various autoimmune disorders. Their findings highlight Astragalus membranaceus as the most frequently prescribed herb. Using both innovative mouse models and clinical patient data, the team demonstrated that Astragalus can effectively inhibit "T follicular helper cells" (Tfh cells), which are immune cells responsible for attacking healthy tissues—particularly relevant in autoimmune pathology.

Interestingly, while MTX does not significantly suppress Tfh cells and may even promote their increase, Astragalus exhibits a remarkable capacity to regulate these cells, offering a promising therapeutic avenue. The researchers also isolated calycosin, a bioactive compound from Astragalus, which significantly inhibits Tfh cell responses by targeting BATF, a key protein in Tfh cell differentiation. Since BATF shares 99% structural identity between humans and mice, calycosin’s potential for cross-species and clinical application is highly promising.

Calycosin’s ability to precisely inhibit BATF results in reduced Tfh cell activation and lowered autoantibody production, effectively addressing the limitations associated with MTX therapy. When combined, calycosin and MTX work synergistically—amplifying treatment effectiveness while minimizing drug toxicity. This combination has demonstrated protective effects on affected organs even during chronic inflammation phases in mouse models of Sjögren’s disease.

According to Professor Lin Xiang of HKU’s School of Chinese Medicine, this combined approach allows for reduced doses of MTX without sacrificing therapeutic potency, thereby improving safety. The team has also filed an international patent for calycosin’s use in autoimmune treatments, marking an important step in the modernization and integration of traditional Chinese medicine into contemporary medical practices.

Furthermore, a humanized mouse model of Sjögren’s disease was developed to better mimic patient immune responses. Validation in this model supports the potential of this combined therapy to proceed to clinical trials. The findings, presented at the 2025 EULAR Congress and published in prominent journals, suggest a promising future for personalized and safer autoimmune disease treatments.

For more details, refer to the publication in Acta Pharmacologica Sinica: [DOI: 10.1038/s41401-025-01536-4], and the Journal of Leukocyte Biology: [DOI: 10.1093/jleuko/qiae155]. This research is a significant step forward in the modernization and efficacy of treatments for autoimmune diseases, combining traditional Chinese medicine insights with advanced scientific validation.