Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS: The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Treatment Progress in Diminished Ovarian Reserve: Western and Chinese Medicine.

Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.

Efficacy and Mechanism of Buxue Yimu Pills on Gynecological Anemia: A Combination of Clinical and Network Pharmacology Study.

OBJECTIVE: To compare the clinical efficacy and safety of oral administration of Buxue Yimu Pills (BYP, ), ferrous sulfate (FS), and the combination of BYP and FS on gynecological anemia, and investigate the mechanisms using network pharmacology. METHODS: A randomized, controlled, multi-center clinical trial was conducted. Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized (using the block randomization method) into Buxue Yimu Pills group (24 g/d), oral iron group (FS Tablets, 0.9 g/d), and combined treatment group (BYP, 24 g/d plus FS Tablets, 0.9 g/d), 50 patients in each group. At the enrollment and 4-week treatment, complete blood count, serum iron indexes were evaluated. Adverse events, liver and renal functions, as well as blood coagulation were observed. Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP. RESULTS: Ten (20%) and 7 (14%) participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups. All 3 groups showed elevated hemoglobin. The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity. No change in iron indexes was observed in BYP group. The patients in the combination treatment group neither showed significant changes in serum ferritin nor total iron-binding capacity. No significant adverse reactions were observed in the BYP group. The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia. Biological processes and pathways including regulation of inflammation, hormone, angiogenesis and hemostasis, response to decreased oxygen levels, effects on myeloma cell, and response to metal ions were identified. CONCLUSION: BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution. (Trial registration: No. NCT03232554).

Is There An Advantage of Using Dingkun Pill () alone or in Combination with Diane-35 for Management of Polycystic Ovary Syndrome? A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS). METHODS: This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment. RESULTS: Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P<0.05); TC, LDL-C and FFA decreased significantly in the Dingkun Pill group (P<0.01), LDL-C also decreased obviously in the Diane-35 group (P<0.01), while TC increased significantly in the combined group (P<0.01), TG increased significantly in all groups (P<0.01); total testosterone (TT) and menstruation regularity was improved significantly in the Diane-35 and combined groups (P<0.01); acne scores were improved in all groups (P<0.01). After treatment, TC and FFA in the Dingkun Pill group were significantly lower than the Diane-35 group (P<0.05 or P<0.01); TT was lower and regular menstruation rate was higher in the Diane-35 and combined groups than the Dingkun Pill group (P<0.01), and no differences were observed between Diane-35 group and combined group (P>0.05). CONCLUSIONS: Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).

Insulin Resistance in Polycystic Ovary Syndrome Improved by Chinese Medicine Dingkun Pill (): A Randomized Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L2, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05). CONCLUSION: DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).

Comparison Of Cimicifuga foetida extract and different hormone therapies regarding in causing breast pain in early postmenopausal women.

This study aimed to compare the influence between Cimicifuga foetida extract and different hormone therapies on breast pain in early postmenopausal women. A prospective, randomized, controlled clinical trial was conducted among 96 early postmenopausal women. Participants were randomly assigned to three groups: group A received 1 mg/day estradiol valerate plus 4 mg/day medroxyprogesterone acetate on days 19-30; group B received 1 mg/day estradiol valerate plus 100 mg/day micronized progesterone on days 19-30; group C received C. foetida extract, 1talet (contains 33.3 mg extract), t.i.d. Breast pain diary and numerical rating scale was used to access the breast pain. For 6 months' treatment, the total incidence of breast pain in group A and B was significantly higher than that in group C (p < .05). The duration (day) of breast pain in each month decreased over time in group A and B while it was continuously low and without significant change in group C (p > .05). The intensity of breast pain was mild in most participants and did not differ among three groups (p > .05). During treatment of early postmenopausal women with C. foetida extract for 6 months, the incidence and duration of breast pain were lower than upon treatment with E2 plus cyclic MPA or m-P and did not change over time.

A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women.

OBJECTIVE: To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs). METHODS: 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). CONCLUSIONS: 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.

A new anti-fibrinolytic hemostatic compound 8-O-acetyl shanzhiside methylester extracted from Lamiophlomis rotata.

BACKGROUND: Fibrinolysis prevents blood clots from growing and becoming problematic. Antifibrinolytics are used as inhibitors of fibrinolysis. Aprotinin was doubted after identification of major side effects, especially on kidney. Lysine analogues has their own defects and whether they are adequate substitutes for aprotinin is still under doubt. Lamiophlomis rotata (Benth.) Kudo. was previous found to have hemostatic activity. But the active compound in L. rotata and its hemostatic mechanism were unknown. OBJECTIVES: To find the major hemostatic compound in L. rotata and identify its haemostasis mechanism. METHODS: Traumatic hemorrhage model and coagulant activity assays were monitored in mice and platelets in drug treatment group and control group. Hyperfibrinolysis model was established by intravenous administration of urokinase in mice. Capillary blood clotting time (CBCT), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and euglobulin clot lysis time (ECLT) were measured. RESULTS: The anti-fibrinolytic activity come from 8-O-Acetyl shanzhiside methylester (ASM) one of the highest iridoid glycosides contents in TIG extracted from L. rotata. ASM significantly (P<0.05) shorten CBCT and reduced blood loss volume in vivo, but did not influence mice APTT, PT or TT. In particular, it significantly prolonged ECLT in hyperfibrinolysis mice. It indicated that ASM could inhibit fibrinolysis. ASM was also effective in CBCT, traumatic bleeding volume and ECLT in hyperfibrinolysis mice model. CONCLUSIONS: ASM was the major hemostatic compound in L. rotata. The haemostasis mechanism of ASM was achieved by anti-fibrinolytic activity. ASM was a new fibrinolysis inhibitor as iridoid glycoside compound.

Ultrasonographic observation of the breast in early postmenopausal women during therapy with Cimicifuga foetida extract and sequential therapy with estrogen and progestin.

BACKGROUND: It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. METHODS: This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. RESULTS: In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check. CONCLUSIONS: In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart.

Apigenin (Api), a mainly bioactive component of Apium graveolens L. var. dulce DC. (a traditional Chinese medicinal herb), possesses a wide range of biological activities, including antioxidant effects. It also has been shown to associate with lower prevalence of cardiovascular diseases, but its mechanisms of action remain unclear. The aim of the present study is to investigate the role of Api in isolated rat heart model of ischemia/reperfusion (I/R). Langendorff-perfused isolated rat hearts were used in our study. Api was added to the perfusate before ischemia and during reperfusion in the isolated pulsed rat heart exposed to 30-min ischemia followed by 50-min reperfusion. The treatment with Api conferred a cardioprotective effect, and the treated hearts demonstrated an improved ischemic cardiac functional recovery, a decreased myocardial infarct size, a reduced activities of creatine kinase isoenzyme and lactate dehydrogenase in the coronary flow, a reduced number of apoptotic cardiomyocytes, a reduced activity of caspase-3, up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax. In addition, Api inhibited the phosphorylation of p38 MAPKS during I/R. In conclusion, these observations provide preliminary evidence that Api can protect cardiomyocytes from I-/R-induced injury, at least partially, through the inhibition of p38 MAPKS signaling pathway.

Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women.

BACKGROUND: It is now recognized that Cimicifuga foetida extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. This paper compares the clinical effects of different regimens of three-month course on climacteric symptoms in Chinese women, so as to evaluate the efficacy and safety of Cimicifuga foetida extract. METHODS: This was a prospective, randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into 3 groups to take different kinds of medicine for 3 months; participants were given Cimicifuga foetida extract daily in group A (n = 32), given estradiol valerate and progesterone capsule cycle sequentially in group B (n = 32), and given estradiol valerate and medroxyprogesterone acetate cycle sequentially in group C (n = 32). The questionnaires of Kupperman menopause index, Menopause-Specific Quality of Life, and Hospital Anxiety and Depression Scale were finished before and after the treatment. The status of vaginal bleeding and breast tenderness was recorded every day. RESULTS: Eighty-nine participants (89/96, 92.7%) completed the treatment. Kupperman menopause index decreased after taking the medicine for 3 months in each group (with all P < 0.001), but the score after the treatment was higher in group A than in the other 2 groups. Except for the score of sexual domain in group A (P = 0.103), the scores of all domains of the Menopause-Specific Quality of Life decreased significantly after the treatment in all groups (with all P ≤ 0.01). Score of anxiety decreased significantly in group A (P = 0.015) and B (P = 0.003). Incidence of breast tenderness was 12.9% (4/31) in group A, 36.7% (11/30) in group B, and 14.3% (4/28) in group C. Incidence of vaginal bleeding was 6.5% (2/31) in group A, 26.7% (8/30) in group B, and 82.1% (23/28) in group C. CONCLUSIONS: Cimicifuga foetida extract is effective and safe in the treatment of menopausal syndrome. It is worth extending its use in the treatment of climacteric complaints, especially among those having contradiction for hormone replacement therapy.

A new triterpenoid saponin from Abrus precatorius Linn.

A new triterpenoid saponin, 3-O-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl subprogenin D (1), together with six known triterpenoids: subprogenin D (2), abrusgenic acid (3), triptotriterpenic acid B (4), abruslactone A (5), abrusogenin (6) and abrusoside C (7) were isolated from the leaves and stems of Abrus precatorius. Their structures were elucidated on the basis of physical and NMR analysis, respectively. Compounds 5 and 6 showed moderate cytotoxicity against MCF-7, SW1990, Hela, and Du-145 cell lines. Compounds 1, 2 and 4 were isolated from this plant for the first time.

Inhibiting effects of total saponins of panax ginseng on immune maturation of dendritic cells induced by oxidized-low density lipoprotein.

Total saponins of panax ginseng (TSPG) are the major active components in panax ginseng. Dendritic cells (DCs) play an active role in the immunological processes related to atherosclerosis. The purpose of this study was to determine the effect and possible mechanisms of TSPG on the maturation and immune function of DCs. Compared with those untreated, the DCs pre-treated with TSPG and then induced by oxidized-LDL exhibited a significantly lower expression of the maturation-associated markers of CD40, CD86, HLA-DR, and CD1a, together with an increased endocytosic function as well as decreased secretions of cytokine. However, silencing the expression of PPARgamma in DCs, the inhibitory effect of TSPG on the maturation DCs was significantly reduced. In conclusion, TSPG could inhibit the maturation of DCs induced by oxidized-LDL which suggests beneficial effects on atherosclerosis and this effect was partly dependent on the PPARgamma pathway at least.

[Effects of Ginkgo biloba extract 50 on hypoxia induced endothelial dysfunction].

OBJECTIVE: To preliminarily investigate the influence of hypoxia on human umbilical vein endothelial cells (HUVECs), and the effect of Ginkgo biloba extract 50 (GBE50) on it. METHODS: Flow cytometry, TUNEL, RT-PCR, Western blot, etc. were applied, to study the effect of hypoxia and GBE50 on endothelial cells. RESULTS: After being interfered by hypoxia for 24 h, the levels of reactive oxygen species (ROS) in HUVECs and the apoptotic rate either in the early or in the late stage significantly increased, and accompanied with the increased levels of endothelin-1 mRNA (ET-1) and endothelial oxide synthase (eNOS) protein. However, when HUVECs were pretreated with GBE50 (25 [microg/ml) 4 h before hypoxia, the apoptotic rate in the early or late stage and expression of ET-1 mRNA significantly decreased (P < 0.05), and the heightened ROS level and eNOS expression partially decreased (P > 0.05). CONCLUSION: Hypoxia can induce endothelial dysfunction, which could be partially or significantly reversed by GBE50, it shows a certain protective effect on hypoxia induced endothelial dysfunction.