| Description: |
Sinomenine shows neuroprotective, anti- rheumatoid arthritis, anti-inflammatory and immunosuppressive effects, it can attenuate 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and the therapeutic mechanism may be related to the reduction of up-regulated colonic TNF-alpha and IFN-gamma production caused by TNBS. Sinomenine also provides a novel therapy to treat ICH induced brain injury. Sinomenine can prevent galactosamine (GalN)/lipopolysaccharide (LPS) -treated hepatic failure by suppressing TNF production and/or reactive oxygen generation. |
| In vitro: |
| Mol Immunol. 2014 Aug;60(2):109-14. | | Sinomenine inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage.[Pubmed: 24815539] | Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Microglial activation mediated cytokine and protease secretion contributes to brain injury in ICH. Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact role in ICH.
METHODS AND RESULTS:
In the present study, to investigate the effect of sinomenine on microglial cells inflammation, we treated ICH-challenged BV2 microglial cells with sinomenine in vitro, and explored its neuroprotection role in intracerebral hemorrhage in vivo. Changes in inflammatory cytokines, such as TNF-α, IL-1β and IL-6, reactive oxygen species (ROS) and NF-κB activation NF-κB were observed. In addition, the neurological deficit and cerebral water content of ICH mice were studied. The results demonstrated that sinomenine could inhibit the release of these cytokines and attenuate ROS production in a dose-dependent manner, and reduce NF-κB activation. Furthermore, sinomenine markedly inhibited cerebral water content and neurological deficit.
CONCLUSIONS:
In conclusion, our findings suggest that sinomenine played the protective effects through inhibition of microglial inflammation, and the findings also provided a novel therapy to treat ICH induced brain injury. | | J. Neuroinflamm., 2007, 4(1):23. | | Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase[Pubmed: 17880684] |
METHODS AND RESULTS:
Sinomenine showed equivalent efficacy in protecting against dopaminergic (DA) neuron death in rat midbrain neuron-glial cultures at both micro- and sub-picomolar concentrations, but no protection was seen at nanomolar concentrations. The neuroprotective effect of Sinomenine was attributed to inhibition of microglial activation, since SN significantly decreased tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2) and reactive oxygen species (ROS) production by microglia. In addition, from the therapeutic point of view, we focused on sub-picomolar concentration of SN for further mechanistic studies. We found that 10-14 M of Sinomenine failed to protect DA neurons against MPP+-induced toxicity in the absence of microglia. More importantly, Sinomenine failed to show a protective effect in neuron-glia cultures from mice lacking functional NADPH oxidase (PHOX), a key enzyme for extracellular superoxide production in immune cells. Furthermore, we demonstrated that Sinomenine reduced LPS-induced extracellular ROS production through the inhibition of the PHOX cytosolic subunit p47phoxtranslocation to the cell membrane.
CONCLUSIONS:
Our findings strongly suggest that the protective effects of Sinomenine are most likely mediated through the inhibition of microglial PHOX activity. These findings suggest a novel therapy to treat inflammation-mediated neurodegenerative diseases. |
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| In vivo: |
| Mol Immunol. 2015 May;65(1):94-103. | | Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues.[Pubmed: 25656802] | Sinomenine (SIN) has long been used as a therapeutic agent of rheumatoid arthritis (RA) in China. However, the discrepancy between low oral bioavailability and higher minimal effective concentration made its action mode mysterious.
METHODS AND RESULTS:
The present study aimed to gain insight into the mechanisms by which SIN suppressed collagen-induced arthritis (CIA) in rats in view of Th17 and regulatory T (Treg) cell balance. SIN was orally administered, and the clinical symptoms of CIA rats were monitored; inflammatory cytokines levels in serum were measured by ELISA; pharmacokinetic studies were performed in normal and CIA rats; Th17 and Treg cell frequencies were analyzed by flow cytometry. The data showed that SIN treatment resulted in a dramatic decrease of arthritis scores and paw volume of CIA rats, which was accompanied by down-regulation of IL-17A and up-regulation of IL-10 in rat serum. The frequency of Treg cells was increased and the frequency of Th17 cells was decreased in the gut lymphoid tissues of SIN-treated rats. Immunohistochemistry assay demonstrated that more α4β7-positive cells were detained in joint tissues after SIN treatment. Moreover, the anti-arthritis efficacy of SIN disappeared when it was given by intraperitoneal injection, further confirming the action of SIN was gut-dependent.
CONCLUSIONS:
In conclusion, SIN exerts anti-RA action probably through modulating the frequencies of Treg cells and Th17 cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from gut to joint. | | Biochem Pharmacol. 1994 Aug 30;48(5):1050-2. | | Protection by sinomenine against endotoxin-induced fulminant hepatitis in galactosamine-sensitized mice.[Pubmed: 8093093] | Sinomenine, an epimorphinan alkaloid, was tested for protecting hepatitis induced by lipopolysaccharide (LPS) in galactosamine (GalN)-sensitized mice.
METHODS AND RESULTS:
Sinomenine protected against the hepatic injuries in the dose range of 10-100 mg/kg in a dose-dependent manner and suppressed the production of tumor necrosis factor (TNF), which appeared in serum earlier than aminotransferases in GalN/LPS-treated mice. Sinomenine significantly suppressed the in vitro production of superoxide anion and hydrogen peroxide in the macrophage cultures stimulated with phorbol 12-myristate acetate.
CONCLUSIONS:
It is discussed that sinomenine prevents GalN/LPS-treated hepatic failure by suppressing TNF production and/or reactive oxygen generation. |
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