Ethnopharmacological relevance Myocardial infarction (MI), a leading cause of morbidity and mortality, may be treated by enhancing glycolysis in myocardial microvascular endothelial cells to promote angiogenesis. Salvia miltiorrhiza provides cardioprotection by modulating energy metabolism and angiogenesis. While our previous research identified an optimal proportion (OP) of its active components for myocardial protection, it remains unclear whether this mechanism involves the regulation of endothelial glycolysis to promote angiogenesis. Aim of the study To clarify the therapeutic mechanism by which OP exerts cardioprotective effects by promoting angiogenesis through the upregulation of myocardial endothelial glycolysis. Materials and methods In this study, oxygen-glucose deprivation (OGD)-treated H9c2 cells were used to detect glycolysis levels, and OGD-treated short hairpin (sh)-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase3 (PFKFB3) human umbilical vein endothelial cells (HUVECs), and MI C57BL/6 mice were used to detect glycolysis and angiogenesis. Results The results demonstrated that OP could increase glycolysis levels through adenosine 5’-monophosphate-activated protein kinase (AMPK)/PFKFB3, and then activate hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) to promote angiogenesis, improve myocardial histopathological morphology, attenuate myocardial fibrosis, reduce levels of myocardial enzymes, enhance cardiac function, and ultimately exert myocardial protective effects in MI mice. Conclusion OP can enhance myocardial glycolysis through AMPK/PFKFB3, and then activate HIF-1α/VEGF/VEGFR2 to promote angiogenesis and serve as a therapy for MI. The preliminary elucidation of the efficacy and therapeutic mechanism of OP in MI provides a methodological basis for the clinical application and drug development of Salvia miltiorrhiza.

Salvia miltiorrhiza (SM)-Dalbergia odorifera (DO) is a commonly used circulating blood and transforming stasis drug pair for the treatment of cardiovascular and cerebrovascular diseases, but systematic studies on the optimal ratio for the treatment of cerebrovascular diseases have not been reported. In this study, we determined the optimal ratio of SM-DO for the treatment of ischemic stroke (IS) through the mixture design.Five different ratios of SM and DO were applied to middle cerebral artery occlusion (MCAO) mice using an enhanced simplex center-of-mass mixture design by Minitab 17 software. The experimental ratios of SM and DO as independent variables and dependent variables including modified neurological severity scores, corner test, sticker removal test, cylinder test, 2,3,5-triphenyltetrazolium chloride staining, lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, and the optimal ratio of the two herbs was obtained by fitting regression equations through mixture design and multi-objective synchronization optimization. The therapeutic effects of the optimal ratio of SM-DO on MCAO mice were verified and evaluated by the indicators of neurological function, brain swelling, cerebral infarction volume, brain histopathological morphology, and the levels of LDH and NSE. The optimal ratio of SM:DO = 0.61:0.39 was obtained by multi-objective synchronization optimization. The results of pharmacodynamic validation showed that the optimal ratio of SM-DO significantly improved the neurological function scores of MCAO mice, the motor functions of the left forelimb, the sensory functions of the left paw, the motor functions of the right steering, the cerebral infarct volume, and the release of LDH and NSE and exerted the therapeutic effect on IS. The optimal ratio of SM (0.61) and DO (0.39) was found to be effective in the treatment of IS mice based on mixture design.

Background Salvia miltiorrhiza-Dalbergia odorifera (SM-DO) is a commonly used herb pair for treating cardiovascular diseases. It can treat myocardial infarction (MI) by regulating glycolysis and angiogenesis, but the optimal proportion of its active components remains unclear. Materials Based on the enhanced simplex-centroid mixture design using Minitab 19 software, 19 proportions of salvianolic acid B (Sal-B), butein (But), tanshinone IIA (Tan IIA), and formononetin (For) were applied to an oxygen-glucose deprivation (OGD)-treated human cardiac microvascular endothelial cells (HCMVECs)-AC16 cells co-culture system. The proportions were independent variables, and viability, lactic acid, vascular endothelial growth factor (VEGF) of HCMVECs, and cardiac troponin I (cTnI) of AC16 cells were dependent variables. Regression equations were fitted and multi-objective optimization was performed to determine the OP, and experimental verification was conducted. Results Stepwise regression analysis yielded regression equations for the four response indicators. The R 2 and adjusted R 2 of each model were at reasonable levels, and the predicted R 2 showed no significant decay. Multi-objective simultaneous optimization revealed OP of 60% Sal-B, 5% But, 5% Tan IIA, and 30% For. Experimental validation results showed that OP could promote lactic acid and VEGF production in OGD HCMVECs, enhance HCMVEC viability, and inhibit cTnI release in OGD AC16 cells. In vivo , OP increased levels of lactic acid, total protein lactylation (Pan-Kla), and VEGF in the myocardium of MI mice, and decreased levels of cTnI, creatine kinase-myocardial band (CK-MB), and myoglobin (Myo) in serum, alleviated pathological injury and fibrosis in myocardial tissues, and enhanced cardiac function in mice. Conclusion This study preliminarily clarifies the OP composed of Sal-B, But, Tan IIA, and For that improves glycolysis and angiogenesis-related indicators and exerts cardioprotective effects, providing a new strategy for studies on active component formulations of traditional Chinese medicines. It is expected to lay a methodological foundation for the clinical application of SM-DO and the development of new drugs.

[This corrects the article DOI: 10.34133/research.0706.].

Cardiovascular diseases (CVDs) are life-threatening disorders arising from interactions between genetic and environmental factors, imposing a heavy global health burden with high morbidity and mortality. Emerging evidence suggests that dysregulated epigenetic modifications, particularly lysine succinylation, play a critical role in the pathogenesis of CVD. Characterized by the covalent addition of a succinyl group to lysine residues, succinylation dynamically alters the functions of proteins, including those involved in transcriptional regulation, and directly affects energy metabolism, oxidative stress, inflammation, apoptosis, and fibrosis. This modification has been linked to the development of various CVDs, such as atrial fibrillation, myocardial ischemia-reperfusion injury, myocardial infarction, heart failure, aortic aneurysm and dissection, diabetic cardiomyopathy, hypertrophic cardiomyopathy, and atherosclerosis. Its effects on key biological processes contribute to these conditions through multiple mechanisms. This review systematically summarizes current research on the role of succinylation in cardiovascular pathophysiology, with a particular focus on its function as a “metabolic switch” in CVDs. It further highlights the critical role of succinylation in regulating redox homeostasis and maintaining the balance of SIRT5-mediated desuccinylation. By integrating mechanistic insights from preclinical and clinical studies, we aim to provide a comprehensive framework for understanding the multifaceted roles of succinylation in CVDs and to identify potential therapeutic targets for future translational research.

Chikusetsu saponin IVa (CHS) is an essential active triterpenoid saponin found in various medicinal herbs, such as Aralia taibaiensis, Panax japonicus, and Aralia elata. While multiple health benefits have been documented, the effect of CHS on aging remains unclear. By employing the D-galactose-induced aging mice and the replicative senescence of primary mouse embryonic fibroblasts (MEFs) as the aging models, we found that CHS significantly attenuated aging both in vitro and in vivo. RNA sequencing analysis revealed that CHS greatly improved autophagy and mitophagy. Corresponding to the improved mitophagy, CHS remarkably reduced mitochondrial ROS and enhanced mitochondrial respiratory function. Mitophagy inhibition and Atg 7 genetic knockout (KO) almost abolished the anti-aging effect of CHS. AMPK pathway was activated during the attenuation of aging by CHS treatment, and a specific AMPK inhibitor reversed the induction of mitophagy and autophagy, as well as the attenuation of aging by CHS. Molecular docking data indicated AMPK as the direct binding target of CHS. In conclusion, our study initially demonstrates that CHS exhibits a potent anti-aging effect both in vitro and in vivo. CHS may directly bind to AMPK and activate the AMPK-dependent pathway to enhance autophagy and mitophagy, thereby reducing mitochondrial ROS and improving mitochondrial respiratory function, contributing to the anti-aging effect. These findings offer a new clue for the promising application of CHS in the improvement of aging and aging-related diseases in the future.

It has been demonstrated that glutamine is a key player in boosting endothelial cell (EC) proliferation. However, despite its importance, the role of endothelial glutaminolysis in diabetes remains largely unexplored. Our research aimed to investigate the function of glutaminolysis in ECs within the context of diabetes and to evaluate the potential therapeutic effects of salvianolic acid B (SalB) and α-ketoglutarate (α-KG) on diabetic vascular complications. Histological analysis of skin wounds in diabetic patients revealed delayed restoration of vascularization and collagen synthesis during wound healing, accompanied by decreased glutaminase 1 (GLS1) expression and reduced colocalization with the EC marker platelet-endothelial cell adhesion molecule-1 (CD31). Additionally, a significant decline in GLS1 activity and expression was observed in ECs isolated from diabetic hearts. In vitro studies using cultured ECs demonstrated that exposure to high glucose and high fat (HGHF) reduced GLS1 expression and suppressed glutaminolysis, impairing EC proliferation and tube formation. These adverse effects were mitigated by treatment with SalB or supplementation with α-KG plus nonessential amino acids (NEAAs). Among diabetic mice subjected to myocardial ischemia/reperfusion (MI/R), SalB administration or α-KG supplementation promoted myocardial revascularization and improved cardiac dysfunction. Notably, endothelial-specific GLS1 deletion in mice blocked the beneficial effects afforded by SalB but not those afforded by α-KG. Furthermore, SalB administration accelerated angiogenesis and cutaneous wound healing in diabetic mice, and these influences were removed by pharmacological inhibition of GLS1 using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) or genetic deletion of endothelial GLS1. These findings indicate that defective endothelial glutaminolysis contributes to impaired angiogenesis and poor ischemic tissue repair in diabetes. Improving endothelial glutaminolysis by treatment with SalB or metabolic supplementation with α-KG promotes angiogenesis and ischemic tissue repair in diabetic mice, emphasizing the possibility of GLS1 as a treatment target.

It has been demonstrated that glutamine is a key player in boosting endothelial cell (EC) proliferation. However, despite its importance, the role of endothelial glutaminolysis in diabetes remains largely unexplored. Our research aimed to investigate the function of glutaminolysis in ECs within the context of diabetes and to evaluate the potential therapeutic effects of salvianolic acid B (SalB) and α-ketoglutarate (α-KG) on diabetic vascular complications. Histological analysis of skin wounds in diabetic patients revealed delayed restoration of vascularization and collagen synthesis during wound healing, accompanied by decreased glutaminase 1 (GLS1) expression and reduced colocalization with the EC marker platelet-endothelial cell adhesion molecule-1 (CD31). Additionally, a significant decline in GLS1 activity and expression was observed in ECs isolated from diabetic hearts. In vitro studies using cultured ECs demonstrated that exposure to high glucose and high fat (HGHF) reduced GLS1 expression and suppressed glutaminolysis, impairing EC proliferation and tube formation. These adverse effects were mitigated by treatment with SalB or supplementation with α-KG plus nonessential amino acids (NEAAs). Among diabetic mice subjected to myocardial ischemia/reperfusion (MI/R), SalB administration or α-KG supplementation promoted myocardial revascularization and improved cardiac dysfunction. Notably, endothelial-specific GLS1 deletion in mice blocked the beneficial effects afforded by SalB but not those afforded by α-KG. Furthermore, SalB administration accelerated angiogenesis and cutaneous wound healing in diabetic mice, and these influences were removed by pharmacological inhibition of GLS1 using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) or genetic deletion of endothelial GLS1. These findings indicate that defective endothelial glutaminolysis contributes to impaired angiogenesis and poor ischemic tissue repair in diabetes. Improving endothelial glutaminolysis by treatment with SalB or metabolic supplementation with α-KG promotes angiogenesis and ischemic tissue repair in diabetic mice, emphasizing the possibility of GLS1 as a treatment target.

AIM:Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective.METHODS:The model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB).RESULTS:EB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2.CONCLUSION:The therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.

Hepatic ischemia-reperfusion injury (HIRI) is the cause of postoperative hepatic dysfunction and failure, and even death. As an important biological effector molecule, hydrogen sulfide (H2S) of mitochondria as a gasotransmitter that is usually used to protect against acute HIRI injury. However, the exact relationship between HIRI and mitochondrial H2S remains tangled due to the lack of an effective analytical method. Herein, we have fabricated a mitochondria-targeted H2S-activatable fluorogenic probe (Mito-GW) to explore the stability of mitochondrial H2S and track the changes in mitochondrial H2S during the HIRI. By virtue of pyridinium electropositivity and its amphiphilicity, Mito-GW could accumulate in mitochondria. It goes through an analyte-prompted immolation when reacts with H2S, resulting in the releasing of the fluorophore (GW). Therefore, the extent of Mito-GW conversion to GW can be used to evaluate the changes of mitochondrial H2S level in living cells and tissues. As proof-of-principle, we have used Mito-GW to demonstrate the mitochondria H2S-levels increase and then decrease during HIRI in vitro and in vivo. Our research highlights the tremendous potential of Mito-GW as a mitochondrial H2S fluorogenic probe in elucidating the pathogenesis of HIRI, providing a powerful tool for promoting future research on hepatology.

OBJECTIVE:To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation. METHODS:Thirty-six male C57BL/6 mice were randomly divided into control group, model group, maggot (1.25%, 2.5%, and 5%) groups, and Benvitimod (1%) group. Psoriasis-like lesions were induced by application of imiquimod cream, and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index (MPASI) score. Auricular swelling of the mice was observed, and histopathological changes of the skin lesions were examined with HE staining. Scratching behavior of the mice was observed and the spleen index was calculated. Toluidine blue staining was used to detect mast cells in the skin lesions, and serum levels of IgG, IgM, the complements CH50, C1s, C3, C3a, C5 and C5a, and the inflammatory factors IL-23, IL-17A and TNF-α were determined with ELISA. RESULTS:In mice with imiquimod-induced psoriasis-like skin lesions, treatment with the maggot at the 3 doses significantly decreased MPASI score, alleviated auricular swelling and pathologies in the skin lesions, reduced scratching behaviors, spleen index, and the number of mast cells in the lesions. Treatment with high-dose maggot significantly lowered serum levels of IgG, C1s, C3a, C5a, IL-23, IL-17A and TNF- α and the levels of C1s, C3, C3a, C5 and C5a in the lesion tissue, and increased serum levels of CH50, C3, and C5. The therapeutic effect of maggot showed a dose-effect dependence. CONCLUSION:Maggot can alleviate psoriasislike skin lesions in mice by inhibiting immune stress and complement activation.

Astragali radix (AR) and anemarrhenae rhizoma (AAR) are used clinically in Chinese medicine for the treatment of chronic heart failure (CHF), but the exact therapeutic mechanism is unclear. In this study, a total of 60 male C57BL/6 mice were divided into 5 groups, namely sham, model, AR, AAR, and AR-AAR. In the sham group, the chest was opened without ligation. In the other groups, the chest was opened and the transverse aorta was ligated to construct the transverse aortic constriction model. After 8 weeks of feeding, mice were given medicines by gavage for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by echocardiography. Heart weight index (HWI) and wheat germ agglutinin staining were used to evaluate cardiac hypertrophy. Hematoxylin-eosin staining was used to observe the pathological morphology of myocardial tissue. Masson staining was used to evaluate myocardial fibrosis. The content of serum brain natriuretic peptide (BNP) was detected by enzyme-linked immunosorbent assay kit. The content of serum immunoglobulin G (IgG) was detected by immunoturbidimetry. The mechanism of AR-AAR in the treatment of CHF was explored by proteomics. Western blot was used to detect the protein expressions of complement component 1s (C1s), complement component 9 (C9), and terminal complement complex 5b-9 (C5b-9). The results show that AR-AAR inhibits the expression of complement proteins C1s, C9, and C5b-9 by inhibiting the production of IgG antibodies from B cell activation, which further inhibits the complement activation, attenuates myocardial fibrosis, reduces HWI and cardiomyocyte cross-sectional area, improves cardiomyocyte injury, reduces serum BNP release, elevates LVEF and LVFS, improves cardiac function, and exerts myocardial protection.

The effectiveness of herbal medicine in treating diabetes has grown in recent years, but the precise mechanism by which it does so is still unclear to both medical professionals and diabetics. In traditional Chinese medicine, mulberry leaf is used to treat inflammation, colds, and antiviral illnesses. Mulberry leaves are one of the herbs with many medicinal applications, and as mulberry leaf study grows, there is mounting evidence that these leaves also have potent anti-diabetic properties. The direct role of mulberry leaf as a natural remedy in the treatment of diabetes has been proven in several studies and clinical trials. However, because mulberry leaf is a more potent remedy for diabetes, a deeper understanding of how it works is required. The bioactive compounds flavonoids, alkaloids, polysaccharides, polyphenols, volatile oils, sterols, amino acids, and a variety of inorganic trace elements and vitamins, among others, have been found to be abundant in mulberry leaves. Among these compounds, flavonoids, alkaloids, polysaccharides, and polyphenols have a stronger link to diabetes. Of course, trace minerals and vitamins also contribute to blood sugar regulation. Inhibiting alpha glucosidase activity in the intestine, regulating lipid metabolism in the body, protecting pancreatic -cells, lowering insulin resistance, accelerating glucose uptake by target tissues, and improving oxidative stress levels in the body are some of the main therapeutic properties mentioned above. These mechanisms can effectively regulate blood glucose levels. The therapeutic effects of the bioactive compounds found in mulberry leaves on diabetes mellitus and their associated molecular mechanisms are the main topics of this paper’s overview of the state of the art in mulberry leaf research for the treatment of diabetes mellitus.

目的 探讨补骨脂的反成配伍对大鼠肝脏的减毒作用及作用机制.方法 80只SD大鼠采用随机数字表法分为空白组、模型组、补骨脂组、补骨脂+制何首乌1:1组、补骨脂+制何首乌1:2组、补骨脂+制何首乌2:1组、补骨脂+熟地黄1:1组、补骨脂+五味子1:1组,每组10只大鼠.除空白组外,其他组皮下注射氢化可的松(25 mg/kg)制备肾阳虚大鼠模型,每日1次,连续注射14 d.大鼠建立肾阳虚模型后,给予相应药物干预,各组给药剂量均为12.6 g/kg,连续灌胃4周.HE染色观察大鼠肝脏组织病理变化.酶联免疫吸附测定检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、直接胆红素(DBIL)和总胆红素(TBIL)水平,以及肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)表达水平.实时荧光PCR检测核因子E2相关因子2(Nrf2)、Kelch样环氧氯丙烷相关蛋白1(Keap1)、血红素加氧酶-1(HO-1)、醌氧化还原酶1(NQO1)mRNA的表达.蛋白质印迹法检测AMP活化蛋白激酶(AMPK)/糖原合成酶激酶-3β(GSK-3β)/Nrf2信号通路中磷酸化AMP K(p-AMP K)、磷酸化GSK-3β(p-GSK-3β)、Nrf2、HO-1的蛋白表达.结果 与补骨脂组比较,补骨脂与补阴药制何首乌、熟地黄及五味子配伍后大鼠肝小叶结构改善,炎性浸润细胞减少.与补骨脂组比较,补骨脂+制何首乌1:2组、补骨脂+熟地黄1:1组、补骨脂+五味子1:1组大鼠血清中AST、ALT、ALP、DBIL、TBIL水平均降低(P<0.01);补骨脂+制何首乌1:2组大鼠肝组织SOD、GSH-Px、MDA的表达改善(P<0.01);补骨脂+制何首乌1:2组Nrf2、HO-1、NQO1 mRNA水平上调(P<0.01),Keap1 mRNA水平下调(P<0.01);补骨脂+制何首乌1:2组、补骨脂+制何首乌2:1组、补骨脂+熟地黄1:1组、补骨脂+五味子1:1组p-AMPK、p-GSK-3β、Nrf2、HO-1蛋白表达均升高(P<0.05,P<0.01).结论 补骨脂配伍补阴药制何首乌、熟地黄及五味子可改善补骨脂所致的肝损伤,其作用机制可能是通过激活AMP K/GSK-3β/Nrf2信号通路,抑制氧化应激状态来发挥对肝脏的保护作用,补骨脂与何首乌配伍比例1:2减毒效果最佳.

Salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and danshensu (DSS) are the main active monomers of Salvia miltiorrhiza, a plant used in the treatment of myocardial infarction (MI). A mixture design of Sal-A, Sal-B, and DSS was evaluated to determine the optimal proportion of the three monomers for myocardial protection efficacy. Regression models were established based on the experimental data obtained from oxygen-glucose deprivation H9c2 cells. The response variables included cell viability, creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTnI) and myoglobin (Myo). The independent variables were the proportions of the three monomers. An optimal proportion of the three monomers was calculated from the obtained models to simultaneously optimize the four responses: 80 % Sal-A, 10 % Sal-B, and 10 % DSS. The calculated solution proportion was verified experimentally. The results showed that there was no significant difference in the inhibition of cTnI and Myo between the mixture with optimal proportion and the treatment drugs, and the inhibition of CK-MB was even better than that the treatment drugs, including the aqueous extract of S. miltiorrhiza and total salvianolic acid. This study shows that a mixture of 80 % Sal-A, 10 % Sal-B, and 10 % DSS can be the most effective in cardioprotection, providing a basis for the study of the active monomers of S. miltiorrhiza in the treatment of MI.

主要促进因子超家族结构域蛋白2a(MFSD2A)在神经系统疾病和脑血管疾病中的作用近年来日益受到关注,它被认为是突破血脑屏障的关键蛋白.MFSD2A能维持和调节血脑屏障(BBB)的完整性和通透性,对出现BBB损伤症状的多种疾病具有治疗效果,能转运二十二碳六烯酸入脑,预防和治疗阿尔茨海默病、常染色体隐性遗传原发性小头畸形等疾病;也能作为载体蛋白或调节BBB囊泡转运输送药物透过BBB治疗其他脑病.本文综述了目前MFSD2A在阿尔茨海默病、脑卒中、小头畸形等脑病中作用的研究现状,旨在为MFSD2A的基础研究和临床应用提供科学参考.

Ethnopharmacological relevance: Aralia taibaiensis is known for its ability to promote blood circulation and dispel blood stasis, activate meridians and remove arthralgia. The saponins of Aralia taibaiensis (sAT) are the main active components that are often used to treat cardiovascular and cerebrovascular diseases. However, it has not been reported whether sAT can improve ischemic stroke (IS) by promoting angiogenesis. Aim of the study: In this study, we investigated the potential of sAT to promote post-ischemic angiogenesis in mice and determined the underlying mechanism through in vitro experiments. Methods: To establish the middle cerebral artery occlusion (MCAO) mice model in vivo. First of all, we examined the neurological function, brain infarct volume, and degree of brain swelling in MCAO mice. We also observed pathological changes in brain tissue, ultrastructural changes in blood vessels and neurons, and the degree of vascular neovascularization. Additionally, we established the oxygen-glucose deprivation/reoxygenation (OGD/ R)-human umbilical vein endothelial cells (HUVECs) model in vitro to detect the survival, proliferation, migration and tube formation of OGD/R HUVECs. Finally, we verified the regulatory mechanism of Src and PLC & gamma;1 siRNA on sAT promoting angiogenesis by cell transfection technique. Results: In the cerebral ischemia-reperfusion mice, sAT distinctly improved the cerebral infarct volume, brain swelling degree, neurological dysfunction, and brain histopathological morphology due to cerebral ischemia/ reperfusion injury. It also increased the double positive expression of BrdU and CD31 in brain tissue, promoted the release of VEGF and NO and decreased the release of NSE and LDH. In the OGD/R HUVECs, sAT significantly improved cell survival, proliferation, migration and tube formation, promoted the release of VEGF and NO, and increased the expression of VEGF, VEGFR2, PLC & gamma;1, ERK1/2, Src and eNOS. Surprisingly, the effect of sAT on angiogenesis was inhibited by Src siRNA and PLC & gamma;1 siRNA in OGD/R HUVECs. Conclusion: The results proved that sAT promotes angiogenesis in cerebral ischemia-reperfusion mice and its mechanism is to regulate VEGF/VEGFR2 and then regulate Src/eNOS and PLC & gamma;1/ERK1/2.

OBJECTIVESTo explore the effect of extract of Styrax (ES) on myocardial ischemic injury and its molecular mechanism, indirectly providing a theoretical basis for the development of ES.METHODSIn order to assess the impact of ES treatment on ischemic heart disease, both a left anterior descending ligation-induced myocardial infarction (MI) model and an ischemia/hypoxia (I/H)-induced H9c2 cell injury model have been constructed. Specifically, Sprague-Dawley rats were randomly assigned to the following groups (n = 8) and administered intragastrically once a day for seven consecutive days: Sham group, MI group, ES-L (0.2 g/kg) group, ES-M (0.4 g/kg) group, ES-H (0.8 g/kg) group, and trimetazidine (TMZ, 0.02 g/kg) group. The cardiac functions and biochemical assessment of rats were detected. Then, we validated experimentally the targets and mechanism of ES on these pathological processes in I/H-induced H9c2 cell injury model.KEY FINDINGSThese results showed that different doses of ES (0.2 g/kg, 0.4 g/kg, 0.8 g/kg, intragastric) significantly improved myocardial structure and function when compared to the MI group. The results of 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin, and masson staining indicated that ES could significantly reduce infarct size, inhibit myocardium apoptosis, and decrease myocardial fibrosis. Moreover, ES distinctly suppressed the serum levels of lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and creatine kinase-MB (CK-MB), alleviated myocardial mitochondrial morphology, and stimulated adenosine triphosphate (ATP) production, increased the level of succinate dehydrogenase (SDH), complex I and complex V activity. Different doses of ES (5 μg/ml, 10 μg/ml, 20 μg/ml) also improved cardiomyocyte morphology and decreased the apoptosis rate in H9c2 cells that had been exposed to I/H. Furthermore, the results of western blotting and qRT-PCR indicated that ES promoted the expression of proteins and mRNA related to energy metabolism, including phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PCG-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Mechanically, after the administration of Compound C (dorsomorphin), an AMPK inhibitor, these effects of myocardial protection produced by ES were reversed.CONCLUSIONSCollectively, these results demonstrated that ES could improve myocardial mitochondrial function and reduce ischemic injury by activating AMPK/PCG-1α signaling pathway, while indicating its potential advantages as a dietary supplement.

Context: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. Objective: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. Materials and methods: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n 1/4 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOFMS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. Results: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-a, IL-6, and IL-1b, and increase SOD and GSH-Px in ischemic-stroke rats (p< 0.05; MDA, p< 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. Conclusion: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

Abstract Objective A systematic review of the clinical efficacy of irbesartan combined therapy in the treatment of hypertension and erectile function in men. Methods Use computer to search databases such as CNKI, CBM, Weipu, Wanfang, Embase, PubMed and Cochrane, and find all the randomized controlled trials (RCT) about the effect of irbesartan combination on the sexual function of male hypertensive patients. After screening according to the inclusion and exclusion criteria, the Cochrane risk of bias tool was used to evaluate the methodological quality of the included studies,and use Review Manager 5.2 software for system evaluation. Results Finally, 11 eligible RCTs with a total of 1350 participants were screened, and a meta-analysis was completed based on these RCTs. The results of Meta analysis showed that compared with other combination medication groups,Irbesartan combination group was better than other medication groups in the incidence of ED (OR = 0.57, 95％CI=(0.37,0.86), P=0.008), serum T (MD = 1.27, 95％CI=(0.69,1.84), P<0.0001), and SHBG (MD = -0.10, 95％CI=(-0.16,-0.04), P=0.002). There was no statistical difference in the total effective rate of lowering blood pressure, the rate of lowering blood pressure, and erectile function. None of the included RCTs mentioned serious adverse events. Conclusions The combination of irbesartan in the treatment of male hypertensive patients with sexual dysfunction was better than other combination groups, and there were no serious adverse reactions during the treatment. However, due to the generally low quality of the included studies, so a larger sample, multi-center, high-quality clinical trial was needed to prove it.