Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Research progress on the biological effects of HIF-1α on follicle development and ovulation / 生理学报

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Effect of Yinxing Mihuan Oral Solutionon P2RX7/NLRP3 Signaling Pathway in Depression Model Rats Induced by Isolation Combined with Chronic Unpredictable Mild Stress / 中国实验方剂学杂志

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， interleukin-6 （IL-6） and tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （<italic>P</italic><0.05， <italic>P</italic><0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1<italic>β</italic>， IL-6 and TNF-<italic>α</italic> in the hippocampus of the model group increased significantly as compared with the blank control group （<italic>P</italic><0.05， <italic>P</italic><0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1<italic>β</italic> remarkably increased in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1<italic>β </italic>was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

Advances of studies on role of microRNAs in regulating blood-brain barrier integrity in ischemic stroke / 中国药理学通报

The destruction of the blood-brain barrier, one of the main pathological processes of ischemic stroke, has become a new target for the treatment of ischemic stroke. miRNAs are versatile regulatory molecules that influence almost every aspect of BBB structure and function. This review summarizes the recent progress in studies on the role of miRNAs in BBB dysfunction in hypoxic/ischemic brain injury, and highlights the specific and key role of miRNAs in the regulation of BBB structure and function in ischemic stroke.

Effect of Euphorbiae Ebarcteolatae Radix Bacteriostasis Ointment on Chronic Eczema in Mice / 中国实验方剂学杂志

Objective:To observe the anti-inflammatory effect and its mechanism of Euphorbiae Ebarcteolatae Radix bacteriostasis ointment in eczema mice induced by 2,4-dinitrochlorobenzene (DNCB). Method:A total of 40 ICR adult mice were randomly divided into control group，model group，hydrocortisone Butyrate cream group (0.09g·kg-1) and Euphorbiae Ebarcteolatae Radix bacteriostasis ointment group (0.09 g·kg-1), with 10 mice in each group. Except for the normal group, other groups were given DNCB to induce the chronic eczema model. Twenty-four hours after DNCB stimulation, they were given the corresponding drugs through auricle and back, twice a day for 10 days. After drug intervention, efforts were made to measure the change of thickness and weight of the middle ear, assess the allergic effect, and calculate the spleen index of the mice. Optical microscope was used to observe the pathological changes in ear tissues of mice. And the levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4) in mice were determined by multiplex immunoassay. Result:Compared with control group, the thickness and weight of right ears, score of allergic effect, spleen index and the levels of IL-2 and IL-4 in serum showed significant increases in model group (P<0.05，P<0.01). The histopathology injuries of ear were aggravated. Compared with model control group, Euphorbiae Ebarcteolatae Radix bacteriostasis ointment could reduce ear thickness and score of allergic effect, regulate the spleen index, decrease the inflammation factor in serum such as IL-2 and IL-4 (P<0.05，P<0.01), and improve ear histopathology injuries. Conclusion:Euphorbiae Ebarcteolatae Radix bacteriostasis ointment may have a good effect on eczema.

Effect of Dingkundan on Sex Hormone and Follicle Count in Mice of Tripterygium Wilfordii Polyglycosides Induced Diminished Ovarian Reserve / 中国实验方剂学杂志

Objective:To establish a mouse model of diminished ovarian reserve （DOR） induced by tripterygium wilfordii polyglycosides （TWP）， and to explore the therapeutic effect of Dingkundan （DKD） on DOR， so as to provide scientific basis for its clinical application. Method:The 60 female Blab/c mice with regular estrous cycle were randomly divided into blank group， model group， low，medium and high-dose DKD group， DKD group and estradiol valerate group， with 10 mice in each group. Except the blank group， the other groups were given 40 mg·kg-1 TWP suspension. Meantime，low，medium and high-dose DKD group were given 1.64，3.28，6.56 g·kg-1 DKD suspension respectively， and estradiol valerate group was given 0.15 mg·kg-1 estradiol valerate suspension by gastric lavage once a day for 30 days. The general condition， body weight， estrous cycle and gonad index of mice were observed， serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and estradiol （E2） were determined by radioimmunoassay， ovarian morphology and follicle count were observed by hematoxylin-eosin staining （HE） staining. Result:Compared with the blank group， most of the mice in model group had disordered estrous cycle， uterine and ovarian indexes decreased （P<0.05）， serum FSH increased （P<0.05）， LH was on an upward trajectory， E2 was on a downward trend， and the number of growth follicles and corpus luteum decreased and the number of atresia follicles increased（P<0.05）. Compared with the model group， half of the mice in DKD group resumed regular estrous cycle， however， the estrous cycles of mice in estradiol valerate group were stagnated during estrous period. In medium-dose， high-dose DKD group and estradiol valerate group， the uterine and ovarian indexes of the mice were increased， the serum FSH value decreased （P<0.05） and serum LH was on a downward trend， high-dose DKD group and estradiol valerate group increased the levels of serum E2 （P<0.05）. In DKD group， the number of growth follicles and corpus luteum were increased and the number of atresia follicles were reduced （P<0.05）， with the best effect at medium dosage. And in estradiol valerate group， the number of primitive follicles， sinusoidal follicles and corpus luteum were increased （P<0.05）， but the number of atresia follicles had no difference to the model group. Conclusion:DKD can improve serum sex hormones， promote follicular development and reduce follicular atresia， which can play a therapeutic role in the treatment of DOR.

Systematic evaluation of kidney-tonifying and blood-activating traditional Chinese medicines in treatment of ovulatory disorder infertility / 中国中药杂志

To evaluate clinical studies on effect of traditional Chinese medicines in treating ovulatory disorder infertility by using evidence-based medical method. According to the standard of Cochrane Handbook, the selection standard of the randomized controlled clinical trail on kidney-tonifying and blood-activating traditional Chinese medicines in the treatment of ovulatory disorder infertility was formulated. Literatures in line with the standard were searched through computers among Chinese and English databases. The literatures included were evaluated by evidence-based medicine method, and analyzed with Revman 5. 1. There were 19 articles in line with the standard. Data for pregnancy rate, ovulation rate and miscarriage rate was extracted from them, and heterogeneity test was conducted with Meta, which showed no statistical heterogeneity. Results showed pregnancy rate (n = 17) , RRp 1. 66, 95% C1 [1. 45, 1.92], Z7.06 (P<0.000 01); ovulation rate (n =11) , RRo 1.05, 95% CI[0.97,1. 12], Z 1.25 (P=0.21); miscarriage rate (n =5) , RRM, 0. 24, 95% CI[0. 11,0. 56] , Z 3.33 (P =0. 000 9). After analysis and comparison, it is found that the Chinese medical treatment group was superior to the Western medicine control group in terms of pregnancy rate, which showed statistic significance. Both groups showed no obvious difference in the ovulation rate, and no statistic significance; the miscarriage rate of the Chinese medicine group is obviously lower than that of the Western medicine control group, which indicated statistic significances. This study preliminarily proves the good efficacy and unique advantages of kidney-tonifying and blood-activating traditional Chinese medicines in treating ovulatory disorder infertility.

Observation on clinical efficacy of activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the clinical efficacy of the activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility.</p><p><b>METHOD</b>Eighty-six cases were randomly divided into two groups: the treatment group and the control group. The treatment group is administered with the activating renal blood circulation and ovarian stimulation formula (composed of 15 g Cuscutae Semen, 15 g Dipsaci Asperoidis Radix, 15 g Lycii Fructus, 15 g Spatholobi Caulis, 10 g Ligustri Lucidi Fructus, 15 g Lycopi Herba, 10 g Typhae Polleu, 10 g Angelicae Sinensis Radix, 15 g Cyathulae Radix etc.), whereas the control group was given clomiphene.</p><p><b>RESULT</b>The treatment group showed a pregnancy rate of 58.14%, with an ovulation rate of 68.6%. While the control group showed a pregnancy rate of 36.67%, with an ovulation rate of 70%.</p><p><b>CONCLUSION</b>The comparison between the two groups showed that the activating renal blood circulation and ovarian stimulation formula was significantly different from clomiphene in statistical analysis (P < 0.05), without notable difference in the ovulation rate. Before and after the treatment, there is no significant difference in diameter of dominant follicles between the two groups, with remarkable difference in endometrium (P < 0.05).</p>