Study on therapeutic mechanism of total salvianolic acids against myocardial ischemia-reperfusion injury based on network pharmacology, molecular docking, and experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae, also known as Danshen in Chinese, effectively activates the blood and resolves stasis. Total salvianolic acids (SA) is the main active ingredient of Danshen, and related preparations, such as salvianolate injection are commonly used clinically to treat myocardial ischemia-reperfusion injury (MIRI). However, the potential targets and key active ingredients of SA have not been sufficiently investigated. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of SA in treating MIRI. MATERIALS AND METHODS: Network pharmacology and molecular docking techniques were used to predict SA targets against MIRI. The key acting pathway of SA were validated by performing experiments in a rat MIRI model. RESULTS: Twenty potential ingredients and 54 targets of SA in treating MIRI were identified. Ingredient-target-pathway network analysis revealed that salvianolic acid B and rosmarinic acid had the highest degree value. Pathway enrichment analysis showed that SA may regulate MIRI through the IL-17 signaling pathway, and this result was confirmed in the rat MIRI experiment. CONCLUSION: The results of this study indicate that SA may protect MIRI by regulating the IL-17 pathway.

[Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review].

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)-ß/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.

Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia via Nrf2 Antioxidation Pathway-Dependent Cerebral Microvascular Protection.

Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT's anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT's therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.

Berberine Protects against TNF-α-Induced Injury of Human Umbilical Vein Endothelial Cells via the AMPK/NF-κB/YY1 Signaling Pathway.

Endothelial injury, characterized by an inflammatory response and increased permeability, is an initial stage of atherosclerosis (AS). Adenosine 5'-monophosphate (AMP), activated protein kinase (AMPK), and Nuclear Factor kappa B (NF-κB)/Yin Yang 1(YY1) signaling pathways play important roles in the process of endothelial injury. Berberine (BBR), a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including anti-inflammatory, antimicrobial, antidiabetic, anticancer, and antioxidant activities. Previous studies showed a protective effect of berberine against endothelial injury. However, the underlying mechanism remains unclear. We explored the potential effect of BBR on TNF- (tumor necrosis factor-) α-induced injury of human umbilical endothelial cells (HUVECs) and studied its possible molecular mechanism. In the present study, HUVECs were divided into three groups. HUVEC viability was measured with Cell Counting Kit-8 assay. Extracellular lactic dehydrogenase (LDH) concentration was measured with LDH leakage assay. Endothelial microparticle (EMP) numbers were evaluated by flow cytometry analysis assay. The expression of proinflammatory cytokines was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of NF-κB and YY1 was detected by Real-Time PCR (RT-PCR). The protein expression of NF-κB, YY1, and AMPK was detected by immunofluorescence microscopy assay or western blot analysis. The results showed that LDH concentration, EMPs numbers, and the expression of proinflammatory cytokines (IL-6, IL-8, and IL-1ß) increased in TNF-α-induced injured HUVECs, but ameliorated by BBR pretreatment. BBR pretreatment upregulated the expression of phosphorylated AMPK and downregulated the expressions of NF-κB and YY1 in injured HUVECs induced by TNF-α, which were offset by the AMPK inhibitor Compound C (CC). The results indicated that BBR protected against TNF-α-induced endothelial injury via the AMPK/NF-κB/YY1 signaling pathway.

[Observation on clinical efficacy of activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility].

OBJECTIVE: To discuss the clinical efficacy of the activating renal blood circulation and ovarian stimulation formula in treating ovulation failure infertility. METHOD: 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. RESULT: 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%. CONCLUSION: 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).

[Systematic evaluation of kidney-tonifying and blood-activating traditional Chinese medicines in treatment of ovulatory disorder infertility].

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.