The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

[Effect of Electroacupuncture on the Expression of Hippocampal eNSCs in MCAO Model Rats].

Objective To observe the effects of electroacupuncture (EA) on hippocampal en- dogenous neural stem cells (eNSCs) expression of middle cerebral artery occlusion (MCAO) model rats after cerebral ischemia-reperfusion (I/R) at different time points, and to observe possible mechanisms of EA for keeping away from damage in acute cerebral infarction (ACI). Methods MCAO model was pre- pared in male SPF grade SD rats by suture method. Totally 90 rats were divided into the sham-operated group, the model group, and the EA group according to random number table, 30 in each group. Rats in the sham-operated group only received surgical trauma. Rats in the model group only received MCAO I/R injury. Rats in the EA group received EA at Baihui (DU20) and Dazhui (DU14) , once per day, 30 min each time. Nerve defects of rats were tested by neural function defect scale at day 1 , 7, 14 of treatment, respectively. Meanwhile, 6 rats were executed randomly from each group. Their hippocampus tissues were isolated. Then the proliferation and differentiation expression of eNSCs in the hippocampus area were detected by immunofluorescence method. Results (1) The scores of nerve function defect scale: The scores of the model group increased at day 1, 7, 14 of treatment, being higher as compared with those of the sham-operated group (P <0. 05). The scores of the EA group were lower than those of the model group at day 1, 7, 14 of treatment (P <0. 05). (2) The expression of BrdU positive cells: Com- pared with the sham-operated group, the expression of BrdU positive cells in the model group were in- creased at day 1, 7, 14 of treatment (P <0. 05). Compared with the model group at each time points, the expression of BrdU positive cells in the EA group were increased more at day 1, 7, 14 of treatment (P < 0. 05). (3) The expression of Nestin positive cells: The expression of Nestin positive cells were in- creased more in the model group than in the sham-operated group at day 1 , 7, 14 of treatment (P < 0. 05). Compared with the model group, the expression of Nestin positive cells increased more in the EA group, but only with statistical difference at day 7 of treatment (P <0. 05). (4) the expression of DCX positive cells: the expression of DCX positive cells were increased more in the model group than in the sham-operated group at day 1 and 7 of treatment (P <0. 05). Compared with the model group, the ex- pression of DCX positive cells were increased more in the EA group at day 7 and 14 of treatment (P < 0. 05). (5) the expression of NeuN positive cells: The expression NeuN of positive cells were increased more in the model group than in the sham-operated group at day 1, 7, and 14 of treatment, but only with statistical difference at day 14 of treatment (P <0. 05). Compared with the model group, the expression of NeuN positive cells were increased more obviously, but only with statistical difference at day 1 and 14 of treatment (P <0.05). (6) the expression of GFAP positive cells: The expression of GFAP positive cells increased more obviously in the model group than in the sham-operated group at day 1 , 7, and 14 of treatment (P <0. 05). Compared with the model group, the expression of GFAP positive cells were not obviously increased in the EA group, but only with statistical difference at day 14 of treatment (P <0. 05). Conclusions The proliferation and differentiation of eNSCs exist in the hippocampus area after cerebral I/R in MCAO model rats. EA could improve the recovery of damaged nerve function. Its possible mecha- nism might lie in that EA could promote the proliferation and differentiation of eNSCs in hippocampus area, inhibit excessive differentiation of eNSCs into astrocytes , promote differentiation of eNSCs into neu- rons, and improve regeneration of nerve cells.

Detection of herb-symptom associations from traditional chinese medicine clinical data.

Background. Traditional Chinese medicine (TCM) is an individualized medicine by observing the symptoms and signs (symptoms in brief) of patients. We aim to extract the meaningful herb-symptom relationships from large scale TCM clinical data. Methods. To investigate the correlations between symptoms and herbs held for patients, we use four clinical data sets collected from TCM outpatient clinical settings and calculate the similarities between patient pairs in terms of the herb constituents of their prescriptions and their manifesting symptoms by cosine measure. To address the large-scale multiple testing problems for the detection of herb-symptom associations and the dependence between herbs involving similar efficacies, we propose a network-based correlation analysis (NetCorrA) method to detect the herb-symptom associations. Results. The results show that there are strong positive correlations between symptom similarity and herb similarity, which indicates that herb-symptom correspondence is a clinical principle adhered to by most TCM physicians. Furthermore, the NetCorrA method obtains meaningful herb-symptom associations and performs better than the chi-square correlation method by filtering the false positive associations. Conclusions. Symptoms play significant roles for the prescriptions of herb treatment. The herb-symptom correspondence principle indicates that clinical phenotypic targets (i.e., symptoms) of herbs exist and would be valuable for further investigations.

Grape seed proanthocyanidins (GSPs) inhibit the growth of cervical cancer by inducing apoptosis mediated by the mitochondrial pathway.

Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been reported to possess a wide array of pharmacological and biochemical properties. Recently, the inhibitory effects of GSPs on various cancers have been reported, but their effects on cervical cancer remain unclear. Here, we explored the effect of GSPs on cervical cancer using in vitro and in vivo models. In vitro, the treatment of HeLa and SiHa cells with GSPs resulted in a significant inhibition of cell viability. Further investigation indicated that GSPs led to the dose-dependent induction of apoptosis in cancer cells. The underlying mechanism was associated with increased expression of the pro-apoptotic protein Bak-1, decreased expression of the anti-apoptotic protein Bcl-2, the loss of mitochondrial membrane potential, and the activation of caspase-3, suggesting that GSPs induced cervical cancer cell apoptosis through the mitochondrial pathway. In addition, the administration of GSPs (0.1%, 0.2%, and 0.4%, w/v) as a supplement in drinking water significantly inhibited the tumor growth of HeLa and SiHa cells in athymic nude mice, and the number of apoptotic cells in those tumors was also increased significantly. Taken together, our studies demonstrated that GSPs could inhibit the growth of cervical cancer by inducing apoptosis through the mitochondrial pathway, which provides evidence indicating that GSPs may be a potential chemopreventive and/or chemotherapeutic agent for cervical cancer.

Puerarin inhibits growth and induces apoptosis in SMMC-7721 hepatocellular carcinoma cells.

Puerarin, a predominant isoflavonoid compound extracted from the Chinese medicinal herb Radix Puerariae, is considered to exhibit an antitumor effect. In the present study, the effects of puerarin on SMMC-7721 human hepatocellular carcinoma cells were investigated. Cell viability was assessed by MTT assay. Apoptosis was detected by flow cytometry with Annexin V-fluorescein isothiocyante staining and morphological observation of nuclear changes by Hoechst staining. The mitochondrial membrane potential (MMP) was monitored using rhodamine 123. The generation of reactive oxygen species (ROS) was quantified using dichloro­dihydro­fluorescein diacetate. Polymerase chain reaction and western blot analysis were used to detect the expression levels of apoptosis­associated genes. The results revealed that high concentrations of puerarin (500, 1,000 and 1,500 µg/ml) significantly inhibited the proliferation of SMMC-7721 cells in a time- and dose-dependent manner. Simultaneously, apoptotic rates were increased and cell morphology was changed following puerarin treatment. Furthermore, puerarin­induced apoptosis of SMMC-7721 cells was associated with loss of MMP and generation of ROS. Puerarin treatment increased caspase­3,8,9 and apoptosis­inducing factor (AIF) mRNA expression levels in SMMC­7721 cells, while the phosphorylation levels of P38, extracellular signal­regulated kinase (ERK1) and c-Jun N­terminal kinase were also increased. Furthermore, caspase-9 and AIF protein expression was upregulated. In conclusion, puerarin inhibited proliferation and induced apoptosis in SMMC­7721 cells via the mitochondria­dependent pathway; however, the specific mechanisms require further investigation.

Chinese Medicine Formula "Jian-Pi-Zhi-Dong Decoction" Attenuates Tourette Syndrome via Downregulating the Expression of Dopamine Transporter in Mice.

Jian-Pi-Zhi-Dong Decoction (JPZDD) is dedicated to the treatment for Tourette syndrome (TS) with the guidance of the theories of Traditional Chinese Medicine (TCM). This study aims to investigate the expression of dopamine transporter (DAT) in the striatum and stereotyped behavior of TS mice model by intervention of JPZDD. Mice were induced by 3,3'-iminodipropionitrile (IDPN, 350 mg kg(-1) day(-1), i.p.) for 7 days and divided into 4 groups (n = 20, each): control and IDPN groups were gavaged with saline and the remaining 2 groups with Tiapride (Tia, 50 mg kg(-1) day(-1)) and JPZDD (20 g kg(-1) day(-1)), respectively. The results showed that the scores of stereotyped behavior in IDPN+JPZDD group were significantly reduced. A noticeably increased (11)C-ß-CFT binding at bilateral striatum was observed after administration of JPZDD versus that of IDPN or Tia. Immunohistochemistry and in situ hybridization studies manifested higher levels of DAT protein and mRNA in IDPN+JPZDD group. These findings not only demonstrated that JPZDD could effectively inhibit the abnormal behaviors of TS mice model, but also increase the level of DAT in striatum. Therefore, JPZDD could be one of potential treatments of patients with TS.

[Evaluation of shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation: a randomized, double-blind and controlled multicenter trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicinal shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation. METHODS: From August 2007 to July 2008, Beijing Chaoyang Hospital conducted a multicenter study, select the eleven hospital's outpatient subjects, aged 18 to 75 years old, male or female, paroxysmal atrial fibrillation (at least one electrocardiogram diagnosis) seizure frequency ≥ 2 times/month, according to the ratio 1:1:1, subjects were randomly divided into three groups: a. shensongyangxin group, taking shensongyangxin capsule 4 + propafenone analogues 150 mg, 3 times a day; b. propafenone group, taking propafenone tablets 150 mg + 4 shensongyangxin analogues, 3 times a day; shensongyangxin capsule + propafenone group, taking shensongyangxin capsule 4 + propafenone 150 mg, 3 times a day. The treatment course is 8 weeks, with 3 times of follow-up. RESULTS: Total of 349 cases of paroxysmal atrial fibrillation, which 117 cases in shensongyangxin group, 115 cases in propafenone group; 117 cases in shensongyangxin + propafenone group. The baseline data analysis showed that there were no significantly difference (P > 0.05) among the three groups of atrial fibrillation seizure frequency, vital signs, general condition, medical history, 24-hour ambulatory ECG, 12-lead normal electrocardiogram, cardiac ultrasound and symptoms. The comparison before and after (8 weeks) treatment showed that the frequency (from 6 times/m to 2 times/m in each group, P < 0.01), number of cases [from 46 (43.3%) to 22 (20.8%), 43 (43.4%) to 25 (25.3%), and 40 (40.6%) to 31 (29.2%), respectively P < 0.01] and duration time of attack of atrial fibrillation (from 4 h to 0.5 h, 4 h to 0.5 h, and 4.25 h to 0.5 h, respectively P < 0.01) all decreased in three groups. No significant difference among the three groups comparing the overall effect (62.3%, 58.6%, and 58.5%, respectively, P > 0.05), while the efficacy of TCM symptoms in shensongyangxin group (80.2%) was better than that of propafenone group (67.7%) (P < 0.05). Safety evaluation showed that adverse reaction rate was 1.8% in shensongyangxin group, and 8.2% and 5.4% in propafenone group and shensongyangxin + propafenone group. CONCLUSION: Shensongyangxin capsules and propafenone have comparable efficacies in the treatment of PAF. The efficacy of TCM symptoms is better than propafenone. Shensongyangxin capsules have an excellent profile of safety.

[Effects of Kuntai Capsule and hormone replacement therapy on cognitive function and mental symptoms of early postmenopausal women: a randomized controlled trial].

BACKGROUND: Conjugated equine estrogen (CEE) treatment, a hormone replacement therapy, is restricted for use in perimenopausal and postmenopausal women because of security issues. Consequently, traditional Chinese herbal medicine has become an alternative choice for the patients with contraindications to hormone replacement therapy. OBJECTIVE: To evaluate the efficacy and safety of Kuntai Capsule and CEE in treating cognitive function disorder and mental symptoms of early postmenopausal women. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 57 cases of early postmenopausal women from Outpatient Department of West China Women and Children's Hospital were included. The subjects were randomly divided into two groups: Kuntai group with 28 cases and CEE group with 29 cases. The patients in Kuntai group received 6 g Kuntai capsules three times a day. The patients in CEE group received CEE 0.3 mg and 0.6 mg alternately once a day (average dose of 0.45 mg/d). The patients with intact uterus in CEE group were treated with 2 mg medroxyprogesterone acetate daily. MAIN OUTCOME MEASURES: In one-year treatment course, the recognition function and mental symptoms of each patient were investigated by questionnaires of Mini-Mental State Examination (MMSE), Kupperman, and quality of life (QOL) every three months. Both intention-to-treat (ITT) and per-protocol set (PPS) analyses were done. RESULTS: The MMSE, Kupperman index and QOL scores at each time point were improved as compared with those before treatment (P<0.05), however there were no statistical differences between the two groups (P>0.05). The MMSE scores showed a tendency to escalate while mental symptoms investigated by Kupperman index and QOL scale showed a downtrend. No severe adverse effects occurred in the study phase and no statistical difference in incidence of side effects between the two groups was found except for vaginal bleeding. The incidence rates of vaginal bleeding in CEE and Kuntai groups were 39.3% and 11.1% respectively (P=0.029). CONCLUSION: Both Kuntai Capsule and CEE may contribute to maintain the cognitive function and ameliorate mental symptoms of early postmenopausal women.

[Sexual hormone and traditional Chinese patent medicine for early postmenopausal women: effect on quality of life and cost-utility analysis].

OBJECTIVE: To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women. METHODS: Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA). RESULTS: At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis. CONCLUSION: At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.