Suppression of Th1 and Th2 Immune Responses in Mice by Sinomenine, an Alkaloid Extracted from the Chinese Medicinal Plant Sinomenium acutum

Abstract

The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from Sinomenium acutum, on Th1 and Th2 immune responses in mice. For this investigation, mice were S. C. immunized with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0). Varying doses of SIN were orally administered daily over a period of 21 days, commencing on day 0. On day 21, anti-OVA IgG and proliferative responses of spleen cells to the antigen were measured. Anti-OVA IgG2a and IFN-gamma were measured as indicators of Th1 immune responses and anti-OVA IgG1, IgE, and IL-5 as those of Th2 responses. TGF-beta was measured as an indicator of Th3 immune responses. The results showed that treatment with SIN was followed by decreases in anti-OVA IgG and the antigen-specific splenocyte proliferation. Production of all isotypes of antibodies including anti-OVA IgG2a, IgG1 and IgE as well as secretion of cytokines such as IFN-gamma and IL-5 was suppressed by SIN, although the suppression of anti-OVA IgG2a and IFN-gamma by the alkaloid appeared to be greater than that of anti-OVA IgG1, IgE, and IL-5. In addition, SIN enhanced the secretion of TGF-beta. These results suggest that SIN appears to have suppressive effects on both Th1 and Th2 immune responses. The results also suggest that Th1 responses may be more preferentially suppressed by the Sinomenium acutum-derived alkaloid compared to Th2 responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses.

Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid-sensing ion channel 1a and L-type calcium channels

“…Sinomenine (SN), a bioactive alkaloid extracted from the Chinese medicinal plant, Sinomenium acutum , has been used for the clinic treatment of rheumatoid arthritis in China (Xu et al ., 2008). Previous studies have demonstrated that the pharmacological profiles of SN include immunosuppression, anti‐inflammation and cytoprotection (Bao et al ., 2005; Feng et al ., 2006; Qian et al ., 2007). Based on its molecular structure (Figure 1A), SN belongs to the family of dextrorotatory morphinan analogues (Jin et al ., 2008), indicating that it may be capable of transporting across the blood–brain barrier (Long et al ., 2010).…”

Inhibition of the antigen-induced activation of RBL-2H3 cells by sinomenine

“…For example, the alkaloid reduces the production of prostaglandin E 2 (PGE 2 ), leukotrine C 4 (LTC 4 ) and nitric oxide by macrophages [2,3]. Our previous study showed that SIN had suppressive effect on both Th1 and Th2 immune responses [4]. However, little is known about its effect on mast cells functions induced by antigen.…”

Sinomenine, an Antirheumatic Alkaloid, Ameliorates Clinical Signs of Disease in the Lewis Rat Model of Acute Experimental Autoimmune Encephalolmyelitis

“…A series of pharmacological studies on its anti-inflammatory, anti-arthritic, analgesic and immunosuppressive effects had been investigated. [3][4][5]14,[18][19][20] The plasma concentration of SIN is increased with the increase of dose administration, which may be a positive associate with the clinical neurological score of EAE rat from our data. Furthermore, SIN i.p.…”

“…Furthermore SIN has suppressive effects on both Th1 and Th2 immune responses, and Th1 response is more preferentially suppressed by the SIN compared to Th2 response in mice. 5) Experimental autoimmune encephalomyelitis (EAE) is a CD4 ϩ T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) that is commonly used as a model of multiple sclerosis (MS).…”