Background: Water extract (WAE) and ultrafine powder (UFP) are two types of commonly used supplements in preparing various pharmaceutical products and functional foods. However, the correlations of the chemical compositions with the traditional functions between WAE and the herb itself, as well as the potential problems of safety for UFP have been more and more concerned by many doctors and customers. Methods: In this study, a new whole ingredients extract of Astragalus (WIE) was prepared using the gradient solvent extraction method. The chemical compositions of WIE and WAE were comparatively analysed using spectrophotometric and chromatographic approaches. In addition, the in vivo immunomodulatory effect of WIE, WAE and UFP of Astragalus were comprehensively compared in cyclophosphamide (Cy)-induced immunosuppressive mice. Results: The compositions and contents of main active ingredients (polysaccharides, saponins and flavonoids) in WIE were determined to be more abundant than those in WAE. In Cy-induced immunosuppressive mice, oral administered with low dosage of WIE (equalled to 1.0 g herb/kg/day) for 18 consecutive days significantly improved the immune-related responses (body weight, number of peripheral white blood cells, thymus and spleen indexes, splenocyte proliferations, natural killer cell activity, splenic lymphocyte subset, and serum levels of immunoglobulins G and M). The potency of three Astragalus preparations on immunomodulation was observed to be WIE ≥ UFP > WAE. Conclusions: WIE maximally retained the chemical integrity of astragalus, and presented better therapeutic effectiveness than UFP and WAE. It can be further developed as new strategy for reasonable use of medicinal/edible herb-derived supplement (extract) for pharmaceutical and healthcare applications.

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1β-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs.