Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.@*METHODS@#Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.@*RESULTS@#Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).@*CONCLUSION@#KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Mechanism and experimental verification of antioxidant action of Heyan Kuntai Capsule based on systematic pharmacology / 中草药

Objective: To explore and verify the potential antioxidation mechanism of traditional Chinese medicine Heyan Kuntai Capsule (HKC). Methods: Gene targets of 21 ingredients of HKC were searched for through Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. Further, the anti-oxidative function of HKC was validated in an in vitro H2O2-induced oxidative stress model in MII oocytes. Results: A total of 151 genes were obtained as targets to 21 components of HKC, whose GO were further significantly enriched in mitochondrion, superoxide dismutase activity and energy pathways, while KEGG showed the enrichment in PI3K/AKT, mTOR and ErbB1 signaling pathways. Afterwards, it was confirmed that HKC increased ATP production in H2O2-treated MII oocytes by improving mitochondrial function and reduced the dissipation of mitochondrial membrane potential (ΔΨm) to exert the antioxidation effect. Conclusion:s HKC exerts anti-oxidative effect by improving mitochondrial function.

Effects of Kuntai capsule on GnRH-a-induced perimenopause symptoms:a prospective randomized controlled study / 中国实用妇科与产科杂志

OBJECTIVE: To evaluate the effect of Kuntai capsule on the gonadotrophin releasing hormone agonist(GnRH-a)-induced perimenopaus symptoms and the sex hormone levels.METHODS: A total of 99 patients with uterine fibroids,adenomyosis or moderate to severe endometriosis who needed the treatment of GnRH-a at Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2015 to March 2016 were collected and randomly divided into research group(Kuntai capsule)and control group(Tibolone). GnRH-a was injected once every 28 days and first injection of GnRH-a was administered on the 2 nd to 4 th day of menstrual period or retraction bleeding after surgery.Kuntai capsule or Tibolone was orally taken beginning from the first GnRH-a injection,and the co-administration of Caltrate D-600 and alfacalcidol was given in both groups.The Kupperman scores,sex hormone levels including folliclestimulating hormone(FSH)and estrogen(E_2),and adverse events were recorded.RESULTS: Kuntai capsule kept the perimenopause symptoms at mild level with the slow increase of Kupperman scores,whose effect was significantly superior to Tibolone(P<0.05)after 8 weeks of treatment,especially in paresthesia,nervousness,and formication.The FSH and E_2 levels in both Kuntai and Tibolone groups were obviously decreased when compared with the pre-treatment(P<0.05),and these hormone levels in Kuntai group were comparable to those in Tibolone group.No adverse events occurred in either group. CONCLUSION: In the short-term treatment of GnRH-a,Kuntai capsule exhibits significant alleviating effects on perimenopause symptoms caused by GnRH-a with high safety and few adverse reactions.

Effect of calcitriol combined with Kuntai capsule on serum monocyte chemotactic factor -1 and leptin and pregnancy rate of prognosis in patients with polycystic ovary syndrome / 中国综合临床

Objective To investigate the application effect of calcitriol combined with Kuntai capsule in patients with polycystic ovary syndrome. Methods Ninety-seven cases with polycystic ovary syndrome were enrolled in the study and were randomly divided into two groups, 48 cases in the control group were given clomifene citrate capsules, and 49 cases in the observation group were treated with calcitriol combined with Kuntai capsule on the basis of the control group. The treatment effect,endometrial thickness,number of mature follicles,cervical mucus score and sex hormones (luteinizing hormone (LH),androgen,testosterone (T),follicle stimulating hormone (FSH),estradiol (E2)) before and after the treatment,the serum monocyte chemotactic factor -1 (MCP-1) and Leptin level of the two groups were observed and compared. And the rate of pregnancy and the incidence of adverse reactions were recorded. Results The total efficiency of the observation group was 95.92%(47/49),higher than that of the control group (79.17%(38/48))(χ2 ＝6.277,P＝0.012).The endometrial thickness,the number of mature follicles and the cervical mucus score of the observation group were significantly higher than those of the control group(t＝4. 978,7. 175,7. 387,P＜0. 05). After 3 months,the serum levels of T,FSH,LH,MCP-1 and Leptin in the observation group were lower than those in the control group,and the serum E2 level was higher than in the control group(P＜0. 05). The pregnancy rate of the observation group the was 69. 39%( 34/49 ), higher than that of the control group ( 47. 92%( 23/48 )), the difference was statistically significant (χ2＝4. 613,P＝0. 032). The incidence of adverse reactions was 12. 24%(6/49) in the observation group and 8. 33%(4/48) in the control group. There was no significant difference between the two groups(P＞0. 05). Conclusion Calcitriol combined with Kuntai capsule can improve the serum MCP-1,Leptin levels and sex hormone levels in patients with polycystic ovary syndrome,and improve the prognosis of pregnancy rate. Besides,the effect is remarkable with high medication safety.

A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs).</p><p><b>METHODS</b>From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P <0.01) and there was no significant difference between groups (P >0.05), except that KMI of HYKT group was higher after 3-month treatment (P <0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P <0.01); and HT had a better performance than HYKT in improving hot flush (P <0.05). MENQOL were significantly improved in both groups after treatment (P <0.01); but there was no significant difference between two groups (P >0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P <0.01).</p><p><b>CONCLUSIONS</b>HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.</p>

Effects of Heyan Kuntai Capsule () on Follicular Development and Oocyte Cohesin Levels in Aged Mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Heyan Kuntai Capsule (, HYKT) on the ovarian function of aged mice and expressions of cohesion complexes in oocytes.</p><p><b>METHODS</b>Twenty-five 9-month-old female C57BL/6J mice were randomly divided into 5 groups by block randomization method (n=5 per group), including the control group (saline), 17β-estradiol group [E, 100 μg/(kg•d)], and low-, medium-, and highdose of HYKT groups [0.3, 0.9, 2.7 g/(kg•d), respectively]. All mice were treated by intragastric administration for 4 weeks. Hematoxylin and eosin staining and anti-VASA staining were used to detect the amounts of follicles. The apoptosis of follicles was measured by anti-gamma HA histone family member X (γHAX) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The density of cohesin subunits, REC8 meiotic recombination protein (REC8), structural maintenance of chromosome (SMC) 1β and SMC3 in oocytes were evaluated by immunofluorescent staining.</p><p><b>RESULTS</b>After administration of E and high-dose of HYKT, the total number of follicles as well as the number of primordial and primary follicles were significantly increased (P<0.05). Anti-γHAX staining and TUNEL assay demonstrated that high-dose of HYKT and E partly suppressed the apoptosis of follicles (P<0.05). Furthermore, it showed an increased trend in the levels of REC8 and SMC1β, after administration with E and HYKT, and no obvious change in the level of SMC3.</p><p><b>CONCLUSION</b>HYKT could enhance the number of follicles, suppress apoptosis of oocytes and have a trend to elevate the meiotic-specific cohesin subunits (REC8 and SMC1β) in oocytes of aged mice, indicating a beneficial effect on the ovarian function in terms of the quantity and quality of follicles.</p>

Effect and mechanism of Kuntai Capsule on premature ovarian failure in rats / 药物评价研究

Objective To explore the effect and mechanism of Kuntai Capsule (KC) on premature ovarian failure in rats.Methods Totally 40 SD female rats were randomly divided into four groups:control group,model group,Kuntai Capsule (KC) group and conjugated estrogens tablets (CET) group.The premature ovarian failure model in rats was made by ig administration of 75 mg/kg tripterygium.After the model was established,rats were continually treated with 0.6 and 0.625 g/kg of KC and CET respectively by ig administration for 36 d.HE staining was used to observe the morphology of ovary and count the number of follicle.The enzyme-linked immunosorbent assay (Elisa) method was used for the detection of follicle stimulating hormone (FSH),luteinizing hormone (LH),serum estradiol (E2),and anti-Mueller tube hormone (AMH) level.The real-time fluorescence quantitative PCR (qRT-PCR) method was used to detect the mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).Results Compared with control group,the number of primordial follicles,preantral follicles and antral follicles were significantly reduced,the number of atretic follicles was increased (P ＜ 0.05),E2 and AMH significantly decreased (P ＜ 0.05),FSH and LH levels increased significantly (P ＜ 0.05),and the levels of VEGF and bFGF mRNA in model group were significantly decreased (P ＜ 0.05).Compared with model group,the number of primordial follicles,preantral follicles,and antral follicles were significantly increased,the number of atretic follicles was significantly reduced (P ＜ 0.05),E2 and AMH significantly increased (P ＜ 0.05),FSH and LH levels significantly decreased (P ＜ 0.05),and the levels of VEGF and bFGF mRNA in KC group were significantly increased (P ＜ 0.05).Conclusion By regulating the level of hormone and up-regulating the expression of VEGF and bFGF,KC can repair the damaged ovarian tissue and promote the growth and development of the follicle,so as to inhibit the premature exhaustion of mRNA.

Study on effect of Kuntai Capsule on mice endometrial receptivity / 重庆医学

Objective To understand the effect of Kuntai Capsule on mice endometrial receptivity by comparing the lyso‐phospholipids acid receptor‐3(LPAR3) expression in endometrium during mouse embryos implantation period .Methods Ninety 6-8 week old Kunming female mice were randomly divided to three groups :the group A [controlled ovarian hyperstimulation (COH)] ,B (COH+Kuntai Capsule) and C(normal saline control) ,30 cases in each group .The vaginal plug was performed on the next day after mating .Five mice in each group were daily killed on 1 -6 d .The serum estradiol(E2) and progesterone(P) levels were detected .The glands number and the immunohistochemical integrated optical density (IOD) were also determined .Results The levels of serum E2 amd P in the group A and B were higher than those in the group C at the same period (P0 .05) .Conclusion Kuntai Capsule may play the role for improving the endometrial receptivity by improving the normal space‐time expression of LPAR3 .

Influence of Kuntai Capsule on ameliorating perimenopausal syndrome to women after hysterectomy / 中草药

Objective: To find out the influence of Kuntai Capsule on ameliorating perimenopausal syndrome to women after hysterectomy. Methods: Collecting 125 cases of hysterectomy due to uterine benign diseases, we divided them into Kuntai and control groups. The patients in the Kuntai group took Kuntai Capsule per os one month after the operation, the capsules were given at the dose of 4 tablets each time, t.i.d, and the patients in the control group took placebos, 4 tablets each time, t.i.d. Patients in both groups should avoid using any drugs that could influence the function of ovary. We tested the levels of follicle-stimulating hormone (FSH) and estradiol (E2) before and three months after the administration. Results: After three months of administration, the incidence of perimenopausal syndrome in Kuntai group was lower than that in control group (P < 0.05), and the E2 level was higher in Kuntai group (P < 0.05). Conclusion: Kuntai Capsule can improve the perimenopausal syndrome effectively.

Application of femoston combined with Kuntai capsule in poor ovarian responders receiving vitro fertilization / 实用医学杂志

Objective To investigate application of femoston combined with Kuntai capsule in poor ovarian responders (PORs) receiving vitro fertilization. Methods 120 women with poor ovarian response after receiving IVF were s randomly elected. Pre-treatment with femoston plus Kuntai capsule was used for three menstrual cycles before the next cycle of assisted reproductive treatment. FSH, LH, E2, AMH, number of antral follicles, PSV, days of Gn, ampoules of Gn, cycle cancellation rate, E2 value of the day of HCG, follicle of less than 16mm, number of oocytes, fertilization rate, and number of good quality embryos were compared before and after treatment used. Results After pre-treatment, levels of FSH and LH were decreased, AMH, PSV were increased, E2 value of the day of HCG, number of antral follicles, follicle of less than 16 mm, oocytes, fertilization rate, and good quality embryos were increased; cycle cancellation rate was decreased, with significant differences (P< 0.05). Conclusions Femoston combined with kuntai capsule can effectively increase the functional reserve of the ovarian in poor ovarian responders, and can improve the outcome of IVF.

Clinical observation of Kuntai Capsule on female menopause insomnia associated with anxiety and depression / 中草药

Objective: To observe the clinical curative effect of Kuntai Capsule on female menopause insomnia associated with anxiety and depression. Methods: Women patients (120 cases) with menopausal insomnia accompanied by anxiety and depression were divided into control and treatment groups, 60 cases in each group. Kuntai Capsule was given to the patients in the treatment group, while oral Estazolam Tablets were given to the patients in the control group, both groups were treated for 10 d as one course of the treatment. After two periods of the treatment, the clinical efficacy for the improvement of sleep quality, anxiety, and depression of patients in the two groups was observed. Results: Compared with the control group, there was no significant difference on the treatment of insomnia and anxiety between the treatment and control groups (P>0.05), while there was the significant difference on the improvement of sleep quality in the treatment group (P<0.05) and the improvement of depression was better than that in the control group (P<0.01). Conclusion: Kuntai Capsule has a good curative effect on the female menopause insomnia associated with anxiety and depression.