| Description: |
Sophocarpine has anti-cachectic, anti-inflammatory, and neuroprotective effects. It has significant antivirus effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in clinical, can ameliorate the ischemic injury induced by transient focal cerebral ischemia in rats, and may be a potential chemotherapeutic agent for chronic liver diseases. Sophocarpine inhibited the expression of TNF-alpha, IL-6, JNK, iNOS, COX-2, p38 MAPK, NF-κB, TLR4, and activated signaling pathway of AMPK. |
| Targets: |
TGF-β/Smad | TLR | ERK | JNK | p38MAPK | IkB | AMPK | NF-kB | NOS | COX | TNF-α | IL Receptor | IKK |
| In vitro: |
| Toxicol In Vitro. 2013 Apr;27(3):1065-71. | | Sophocarpine alleviates hepatocyte steatosis through activating AMPK signaling pathway.[Pubmed: 23395669] | Sophocarpine, an effective compound derived from foxtail-like sophora herb and seed, has been reported that it can alleviate non-alcoholic steatohepatitis (NASH) in rats and affect adipocytokine synthesis. Meanwhile, adipocytokines could adjust hepatic lipid metabolism through AMPK signaling pathway.
METHODS AND RESULTS:
In the work presented here, primary hepatocytes were isolated from specific pathogen-free male SD rats and incubated with 200 μmol/L oleic acid for 24h to induce steatotic model, then treated with sophocarpine for 72 h. Oil red staining was performed to evaluate steatosis, total RNA and protein of primary hepatocytes were extracted for real-time RT-PCR and western blot analysis. A cluster of aberrances were observed in the model group, including hepatocyte steatosis, increased leptin and decreased adiponectin mRNA expressions. While sophocarpine treatment resulted in: significant improvement of steatosis (>50% decrease), decrease of leptin expression (<0.57-fold) and increase of adiponectin expression (>1.48-fold). Moreover, compared with the model group, sophocarpine could significantly increase P-AMPKα (>5.82-fold), AMPKα (>1.29-fold) and ACC (>3.27-fold) protein expressions, and reduce P-ACC (<0.30-fold) and HNF-4α (<0.20-fold) protein expression. The mRNA expression of Srebp-1c was downregulated significantly simultaneously (<0.68-fold).
CONCLUSIONS:
We concluded that sophocarpine could alleviate hepatocyte steatosis and the potential mechanism might be the activated signaling pathway of AMPK. | | Toxicol In Vitro. 2012 Feb;26(1):1-6. | | Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways.[Pubmed: 21978812] | Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Our previous studies have showed that sophocarpine exerts anti-inflammatory activity in animal models.
METHODS AND RESULTS:
In the present study, anti-inflammatory mechanisms of sophocarpine were investigated in lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells. Furthermore, the cytotoxicity of sophocarpine was tested. The results indicated that sophocarpine could increase the LDH level and inhibit cell viability up to 800μg/ml, and which was far higher than that of the plasma concentration of sophocarpine in clinical effective dosage. The results also demonstrated that sophocarpine (50 and 100μg/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These were associated with the decrease of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, sophocarpine inhibited LPS-mediated nuclear factor-κB (NF-κB) activation via the prevention of inhibitor κB (IκB) phosphorylation. Sophocarpine had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), whereas it attenuated the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun NH(2)-terminal kinase (JNK).
CONCLUSIONS:
Our data suggested that sophocarpine exerted anti-inflammatory activity in vitro, and it might attribute to the inhibition of iNOS and COX-2 expressions via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-κB activation. |
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| In vivo: |
| Brain Res. 2011 Mar 25;1382:245-51. | | Neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1 in rats.[Pubmed: 21232529] | Sophocarpine, one of the major alkaloid compounds isolated from Sophora pachycarpa, is highly valued and important in traditional Chinese medicine. In the present study, we aimed to explore the possible mechanisms underlying sophocarpine-mediated neuroprotection against transient focal cerebral ischemia.
METHODS AND RESULTS:
Sophocarpine (5, 10, or 20mg/kg) was given 30min before focal ischemia was induced in rats by occlusion of the middle cerebral artery. After sophocarpine treatment, the total infarct volume was significantly decreased in comparison to the ischemia-reperfusion values. The results of a neurological evaluation were significantly improved in the sophocarpine treated group when compared to controls. The number of TUNEL-positive cells was significantly reduced compared to the untreated ischemic group. Results of Western blotting and immunohistochemical staining indicated that pretreatment with sophocarpine down-regulated the expression of acid-sensing ion channel 1 (ASIC1) in the ischemic cortex.
CONCLUSIONS:
These results suggest that sophocarpine ameliorated the ischemic injury induced by transient focal cerebral ischemia in rats and that this neuroprotective effect might be related to the anti-ASIC1 channel and anti-apoptotic action of sophocarpine. |
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