Vitamin K3 Regulates Reactive Oxygen Species and Extracellular-Regulated Protein Kinase in Differentiated PC-12 Cells within a Safe Dose Range

Objective:Acupuncture can relieve pain by acting on the mitogen-activated protein kinase(MAPK)signal pathway,which plays a critical role in the balance between hyperalgesia and inflammation.Our previous studies have suggested that acupoint injection of Vitamin K3(Vit K3)had an intensive analgesic effect on primary dyspareunia.However,the mechanism by which Vit K3 worked on nerve cells has not been elucidated.Methods:Cell apoptosis,mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)changes of PC-12 cells with Vit K3 treatment,for which the concentration gradient was 0,5,10,20,40,and 60μmol/L,were quantified by flow cytometry.The expression and phosphorylation of c-Jun N-terminal kinase,p38,and extracellular-regulated protein kinase(ERK),the three critical molecules of the MAPK pathway,were further assessed using Western blotting.Results:The level of ROS first decreased and then increased with Vit K3 at 20μmol/L,but no change in neither apoptosis nor MMP was evident.In addition,only ERK level decreased at 20μmol/L and the relative phosphorylation level increased.Changes in ROS were negatively correlated with the expression of ERK.Conclusions:The rapid analgesic effect of Vit K3 acupoint injection may be through the reduction of ROS in nerve cells with a small dose of Vit K3 or by influencing the expression of ERK but without damaging the nerve cells themselves.

Efficacy and Safety of SanJieZhenTong Capsules,a Traditional Chinese Patent Medicine,on Long-term Management of Endometriosis:A Randomized Controlled Trial

Objective:To compare the efficacy of the traditional Chinese medicine SanJieZhenTong(SJZT)capsules versus gonadotropin-releasing hormone analogs(GnRHa)or oral contraceptives(OCs)in the postoperative treatment of moderate-to-severe endometriosis.Methods:In this prospective clinical trial,women with stage III-IV endometriosis according to the revised American Fertility Society scoring system received three doses of GnRHa immediately after laparoscopic conservative surgery,followed by random assignment to receive treatment with SJZT,GnRHa,or OCs for another 6 months.The primary endpoint was 2-year recurrence,and the secondary endpoints were adverse events,changes in physical function,and quality of life(QoL).Recurrence was assessed using Kaplan-Meier curves and log-rank tests.Generalized estimating equations were used to determine the parameters of the secondary endpoints.Results:A total of 66 women were randomly assigned to the SJZT(n=21),GnRHa(n=21),and OCs(n=24)groups.At a median follow-up of 22 months,no difference in recurrence was found(P=0.72),with one(4.8%),two(9.5%),and one(4.2%)incidence in the SJZT,GnRHa,and OCs groups,respectively.Expectedly,the incidence of side effects such as hot flush,insomnia,and arthralgia in the SJZT and OCs groups was significantly lower than that in the GnRHa group(P=0.00).In addition,the female sexual function index was significantly improved in the SJZT group,with a higher value than that in the GnRHa(odds ratio[OR]=5.25,95%confidence interval[CI]:2.09-13.14,P=0.00)and OCs(OR=3.94,95%CI:1.58-9.83,P=0.00)groups.Conclusions:SJZT showed more effective pain relief and QoL improvement in patients with moderate-to-severe endometriosis than GnRHa or OCs did.Fewer adverse events than those observed with other agents indicate that this alternative medicine,SJZT,could be a novel option for the long-term management of endometriosis.