Sophoridine

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 May;31(5):585-9.

Sophoridine suppresses inflammatory cytokine secretion by lipopolysaccharide-induced RAW264.7 cells and its mechanism.[Pubmed: 25940281]

To observe the effects of Sophoridine on lipopolysaccharide (LPS)-induced secretion of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) as well as the expressions of Toll-like receptor 4 (TLR4) and c-Jun in RAW264.7 cells and explore the molecular mechanism of anti-LPS of Sophoridine.
METHODS AND RESULTS:
RAW264.7 cells were cultured and divided into four groups: macrophage control group (using serum-free DMEM to incubate cells), Sophoridine control group (using 31.25 mg/L Sophoridine-added DMEM to incubate cells), LPS group and Sophoridine intervention group (using 100 μg/L LPS DMEM to incubate cells for 60 minutes, then throwing away LPS and adding serum-free DMEM or 31.25 mg/L Sophoridine DMEM to incubate cells). Cells and culture medium were collected respectively at 5, 30, 60 and 120 minutes after the above treatment. The expression levels of TLR4 and c-Jun mRNA were determined by reverse transcription PCR (RT-PCR), and the expression of c-Jun protein in RAW264.7 cells was measured by immunocytochemistry and Western blotting; The levels of TNF-α and IL-1β in cell culture medium were analyzed by ELISA. Compared with macrophage control group, Sophoridine control group had no statistical difference in each index. Compared with macrophage control group, the expressions of TLR4 mRNA, c-Jun mRNA and protein as well as the secretion of TNF-α and IL-1β significantly increased at each time point in LPS group, and maintained the level to 120 minutes. Sophoridine suppressed the expressions of TLR4 mRNA, c-Jun mRNA and protein, and reduced the secretion of TNF-α and IL-1β in LPS-stimulated RAW264.7 cells in Sophoridine intervention group.
CONCLUSIONS:
Sophoridine down-regulated the secretion of TNF-α and IL-1β in LPS-induced RAW264.7 cells via inhibiting the expressions of TLR4 and c-Jun.

Zhongguo Yao Li Xue Bao. 1999 Jun;20(6):517-20.

Anti-arrhythmic effects of sophoridine and oxysophoridine.[Pubmed: 10678144]

To compare the effects of oxySophoridine (Oxy) and Sophoridine (Sop) on experimental arrhythmias and myocardial physiologic properties.
METHODS AND RESULTS:
Arrhythmias were induced by drugs and myocardial ischemia. Physiologic properties were determined on isolated heart atria. Oxy 500 mg.kg-1 (1/6 LD50) decreased the incidence of ventricular arrhythmias induced by aconitine (P < 0.01), increased the threshold dose of ouabain-induced ventricular premature (VP, P < 0.05), ventricular tachycardia (VT, P < 0.05), ventricular fibrillation (VF, P < 0.01), and cardiac arrest, (P < 0.01). After i.v. Oxy 500 mg.kg-1 into the rats with ligation of left anterior descending coronary artery, the total numbers of ectopic beats were decreased (P < 0.05), the incidence of VF was lowered, and the duration of VT was shortened (P < 0.01). Oxy 250 mg.kg-1 (1/13 LD50) i.v. shortened the duration of arrhythmias induced by BaCl2 (P < 0.01) and delayed the onset of arrhythmias induced by chloroform-epinephrine (P < 0.05). Oxy produced dose-dependent positive inotropic effects in the isolated left atrial of guinea pigs, increased the concentration of epinephrine to elicit automaticity in left atria, decreased slightly the excitability, and prolonged the functional refractory period. Sop produced the similar effects on arrhythmias as Oxy.
CONCLUSIONS:
Oxy produced the similar anti-arrhythmic effects as Sop did at the equivalent effective dose.

Int J Clin Exp Med. 2015 Jan 15;8(1):464-71.

Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line.[Pubmed: 25785018]

Sophoridine, a natural product obtained from medicinal plants, which has a variety of pharmacological effects, including anti-cancer effects, and selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of Sophoridine on the induction of apoptosis in human Glioma U87MG cells.
METHODS AND RESULTS:
Here, we found that Sophoridine can significantly inhibited cell proliferation, G2/M phase arrest, induced cell apoptosis and caused reactive oxygen species (ROS) generation and GSH content reduction. Sophoridine also triggered significant down-regulated the expression of p27, CDK2, Survivin, Livin, Bcl-2, E2F1 and the transcriptional activity of FoxM1, NF-κb and AP-1, meanwhile, up-regulated the expression of caspase-3/8, p53, Smac, c-JNK and p38-MAPK. Moreover, we found that Sophoridine significantly inhibited ubiquitin-proteasome in tumor cells.
CONCLUSIONS:
In conclusion, Sophoridine shows obvious anti-cancer activity on glioma cells by inducing cell apoptosis, inducing ROS accumulation, and activating mitochondrial signal pathways. Eventually, we believe Sophoridine could be used as a new drug for the treatment of glioma.

Brain Res Bull. 2012 Jul 1;88(4):379-84.

Neuroprotective effect of early and short-time applying sophoridine in pMCAO rat brain: down-regulated TRAF6 and up-regulated p-ERK1/2 expression, ameliorated brain infaction and edema.[Pubmed: 22521762]

Matrine has been proven to protect ischemic injury in brain and Sophoridine (SOP) is an isomeride of matrine. It is unknown whether SOP has this protective effect on ischemic injury in brain. We therefore investigated the potential neuroprotective role of SOP and the underlying mechanism.
METHODS AND RESULTS:
Male, Sprague-Dawley rats were randomly assigned into five groups: Vehicle (pMCAO+saline), High dose (pMCAO+SOP 10 mg/kg), Middle dose (pMCAO+SOP 5 mg/kg), Low dose (pMCAO+SOP 2.5 mg/kg) and Sham operated group. Permanent middle cerebral artery occlusion (pMCAO) model was used and SOP was administered intraperitoneally immediately after cerebral ischemia and once daily in the following days. Neurological deficit was evaluated using a modified six point scale; brain water content and infarct volume were measured. The expression of TRAF6 and ERK1/2 were measured by immunohistochemistry, Western blotting. Compared with Vehicle group, the cerebral edema was alleviated in High dose group (P<0.05), and the infarct volume was decreased in Low dose group (P<0.05). Consistent with these results, immunohistochemistry and Western blot analysis indicated that TRAF6 expression was significantly decreased in SOP administrated groups at 24 h, and the expression of phosphorylated ERK1/2 increased in Low dose at 72 h.
CONCLUSIONS:
SOP protected the brain from damage caused by pMCAO, and this effect may be through down-regulation of TRAF6 expression and up-regulation of ERK1/2 phosphorylation expression.