Chemical Constituents from the Roots and Rhizomes of Asarum heterotropoides var. mandshuricum and the In Vitro Anti-Inflammatory Activity

Abstract

Anti-inflammatory compounds were investigated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum, a traditional Chinese medicine called Xixin and used for pain and inflammatory. Nine new compounds were isolated, including six new lignans, neoasarinin A–C (1–3), neoasarininoside A and B (4 and 5), and asarinin B (7), and one new monoterpene, asarincin A (8), two new amides, asaramid II and III (10 and 11), and one new natural monoterpene, asaricin B (9), along with 37 known compounds (6, 12–47). Their structures and absolute configurations were elucidated on the basis of spectroscopic methods and chemical analyses. This is the first report of the absolute configuration of asarinin A (6). The 8-O-4′ neolignans (1–5) were reported in the genus Asarum for the first time. The 15 compounds 17, 19, 22–25, 28, 31, 36, 40, 42, 43, 45–47 were isolated from the genus Asarum, and compounds 16, 32, 33, 37 and 39 were isolated from A. heterotropoides var. mandshuricum for the first time. Thirty-seven of the isolates were evaluated for anti-inflammatory activity against the release of β-glucuronidase in polymorphonuclear leukocytes (PMNs) induced by the platelet-activating factor (PAF), and compounds 1, 4, 7, 8, 14, 17–19, 22, 24, 25, 29, 30, 32, 33, 40–43, 45, and 46 showed potent anti-inflammatory activities in vitro, with 27.9%–72.6% inhibitions at 10−5 mol/L. The results of anti-inflammatory assay suggested that lignans obtained from the CHCl3 extract might be the main active components of Xixin.

TlR2 and TlR4 are involved in the treatment of rheumatoid arthritis synovial fibroblasts with a medicated serum of asarinin through inhibition of Th1/Th17 cytokines

“…Mice deficient in IL-17 exhibit reduced severity of arthritis, and mice with increased IL-17 levels exhibit exacerbated levels of the disease (41,42). Inflammatory cytokines are selectively recruited to the synovial cavity in RA and various relevant cytokines in the synovial tissue were detected in the present study (13,43). IL-1 and TNF-α stimulate the proliferation of FLS to secrete cytokines and prostaglandins, inducing FLS proliferation (44).…”

“…Xixin is a commonly used herbal medicine in China and other Asian countries. Asarinin is one of the main active chemical components isolated from Xixin (13). Despite a previous study revealing that asarinin significantly inhibited the macroscopic score and cartilage destruction of collagen-induced arthritis (17), little is known about the effect of asarinin on RA synovial fibroblasts.…”

“…isolated from Xixin (13)(14)(15)(16). Many pharmacological effects have been identified in asarinin, including anti-inflammatory effects, antipyretic properties and immune inhibition (13)(14)(15)(16).…”

“…(Aristolochiaceae), and is a commonly used herbal medicine in China (13). Xixin is used to treat colds, fever, chills, headaches, acute toothaches, sinusitis, coughs and RA in traditional Chinese medicine (13). Asarinin (molecular weight, 354.35) is one of the main active chemical components…”

Amelioration of CIA by Asarinin Is Associated to a Downregulation of TLR9/NF-κB and Regulation of Th1/Th2/Treg Expression

“…Similar to its progenitor plant, asarinin has a variety of pharmacological properties, including antipyretic effects, antiinflammatory effects and immunosuppressive properties. [9][10][11][12] The pharmacological characteristics of asarinin prompted us to study the potential effect of asarinin on RA. 13) T cells and DCs are involved in the inflammatory response of RA, so we focus our research on the immunoregulatory effects of asarinin on CIA, and the possible roles of T cells and DCs in the pathological process of arthritis.…”