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Background: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown., Purpose: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms., Methods: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/β-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC., Results: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/β-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/β-catenin pathway., Conclusions: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years., Aim of the Study: To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments., Materials and Methods: Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components., Results: Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role., Conclusion: The results indicate that six targets, especially VKORC1, are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

Objective: To investigate the effect of Yiqifumai injection (YQFM), a compound Chinese medicine, and its main active ingredients on lipopolysaccharide (LPS)-induced microvascular disturbance in mesentery and ileum., Methods: Rats were infused with LPS (5 mg/kg/h) for 90 min. Thirty minutes after initiation of LPS administration, YQFM (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), or Rb1+Sch (5 mg/kg/h + 2.5 mg/kg/h) was infused until 90 min. Human umbilical vein endothelial cells (HUVECs) were incubated with LPS (100 ng/ml) for 90 min. YQFM (1 mg/ml), Rb1 (100 µM), Sch (100 µM), or Rb1+Sch (200 µM) was added 30 min after initiation of LPS stimulation., Results: Yiqifumai injection and Rb1+Sch inhibited mesenteric venule hyperpermeability, suppressed microvillar erosion and submucosal edema, and protected claudin-5 from downregulation and interleukin-1β from upregulation in ileal tissues after LPS. Study in HUVECs confirmed the effect of YQFM and Rb1+Sch on JAM-1 after LPS and revealed a similar effect on other junction proteins. Moreover, YQFM and Rb1+Sch attenuated the dysfunctional energy metabolism and the activation of TLR-4/Src/NF-κB signaling with Rb1 and Sch being partially effective., Conclusion: These results demonstrated the beneficial effect of post-treatment with YQFM, which is attributable to its main ingredient Rb1 and Sch, and likely mediated by targeting TLR-4/Src/NF-κB signaling pathway., (© 2021 John Wiley & Sons Ltd.)

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Objective: To investigate the effects of Bushen Tiaoxue Granules and Kunling Wan, the two Chinese medicines, on vascular dysfunction and the impairment of endometrial receptivity caused by controlled ovarian hyperstimulation and its underlying mechanism., Methods: Female Sprague Dawley rats with regular estrous cycle were enrolled and given Bushen Tiaoxue Granules or Kunling Wan by gavage for 12 days, and then, controlled ovarian hyperstimulation model was induced. We assessed endometrial microvessels, endometrial blood flow, levels of estradiol and progesterone in serum, vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium, and pregnancy outcome., Results: Pre-treatment of Bushen Tiaoxue Granules or Kunling Wan increases endometrial blood flow of controlled ovarian hyperstimulation rats, up-regulates vascular endothelial growth factor A and microvessels, improves the endometrial morphology of controlled ovarian hyperstimulation rats during implantation, decreases the super physiological concentration of estradiol and progesterone in serum, and increases the expression of vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium. In addition, Bushen Tiaoxue Granules or Kunling Wan elevates the lysophosphatidic acid receptor 3 that participates in vascularization and increases the expression of leukemia inhibitory factor through up-regulating the expression of p53 in the endometrium, ultimately affecting pregnancy outcome., Conclusion: This study demonstrated Bushen Tiaoxue Granules or Kunling Wan as a potential strategy for prevention of impairment in angiogenesis and endometrial receptivity induced by controlled ovarian hyperstimulation., (© 2019 John Wiley & Sons Ltd.)

Objective: Yiqifumai injection is a compound Chinese medicine used to treat microcirculatory disturbance-related diseases clinically. Our previous study proved that Yiqifumai injection pretreatment inhibited lipopolysaccharide-induced venular albumin leakage in rat mesentery. This study aimed to investigate whether Yiqifumai injection attenuated cerebral microvascular hyperpermeability and corresponding contribution of its main ingredients., Methods: Rats were challenged by lipopolysaccharide infusion (5 mg/kg/h) for 90 minutes. Yiqifumai injection (160 mg/kg/h), Rb1 (5 mg/kg/h), Sch (2.5 mg/kg/h), and Rb1 (5 mg/kg/h) + Sch (2.5 mg/kg/h) were infused 30 minutes before (pretreatment) or after (post-treatment) lipopolysaccharide administration., Results: Both pretreatment and post-treatment with Yiqifumai injection attenuated cerebral venular albumin leakage during lipopolysaccharide infusion and cerebrovascular hyperpermeability at 72 hours after lipopolysaccharide infusion. Yiqifumai injection restrained the decreased junction protein expression, adenosine triphosphate content, and mitochondria complex I, II, IV, and V activities. Moreover, Yiqifumai injection inhibited toll-like receptor-4 expression, Src phosphorylation, and caveolin-1 expression. Its main ingredients Rb1 and Sch alone worked differently, with Rb1 being more effective for enhancing energy metabolism, while Sch attenuating toll-like receptor-4 expression and Src activation., Conclusion: Yiqifumai injection exerts a protective and ameliorated effect on cerebral microvascular hyperpermeability, which is more effective than any of its ingredients, possibly due to the interaction of its main ingredients through a multi-pathway mode., (© 2019 John Wiley & Sons Ltd.)

Coronary heart disease remains a major threaten for public health worldwide, and pharmacological or mechanical coronary reperfusion are currently used for treatment of acute coronary syndrome. However, restoration of blood flow to ischemic myocardium leads to ischemia/reperfusion (I/R) injury. Microcirculatory disturbance and cardiac injury after I/R occur via a complex pathologic process including metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase. Obviously, any treatment targeting a single link is insufficient to cope with I/R injury. Investigation in the past decade in our laboratory as well as in other's demonstrated the cardioprotection potential of QiShenYiQi Pills (QSYQ) and ingredients in experimental animal models of I/R injury. These results have offered insight into the mechanism thereby QSYQ prevents against cardiac I/R injury in clinic. This review will outline the results with respect to the effect of QSYQ and major bioactive ingredients on I/R-induced microcirculatory disturbance, cardiac injury and fibrosis, with emphasis on the underlying mechanisms., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial fibrosis after I/R-induced myocardium injury, and the role of different compounds of QSYQ, focusing especially on the involvement of chemokine ribosomal protein S19 (RP S19) dimer and monocyte migration. Male Sprague-Dawley rats were subjected to left anterior descending coronary artery occlusion for 30 min followed by reperfusion with or without administration of QSYQ (0.6, 1.2, or 1.8 g/kg) once daily by gavage for 6 days. Post-treatment with QSYQ diminished I/R-induced infarct size, alleviated myocardium injury, attenuated myocardial fibrosis after 6 days of reperfusion, and restored heart function and myocardial blood flow after I/R. In addition, the drug significantly inhibited monocyte infiltration and macrophage polarization towards M2, which was attributable to chemokine RP S19 dimer. Moreover, Western blots revealed that QSYQ blocked I/R-induced increase in TGFβ1 and TGFβRⅡ and reversed its relevant gene expression, such as Smad3,4,6,7, and inhibited the increase of MMP 2,9 expression. As the major components of QSYQ, astragaloside IV (AsIV), 3,4-dihydroxy-phenyl lactic acid (DLA), and notoginsenoside R1 (R1) were assessed as to the contribution of each of them to the expression of the proteins concerned. The results showed that the effect of AsIV was similar to QSYQ, while DLA and R1 only partly simulated the effect of QSYQ. The results provide evidence for the potential role of QSYQ in treating myocardial fibrosis following I/R injury. This effect may be associated with QSYQ's inhibition effect on monocyte chemotaxis and TGFβ1/Smads signaling pathway with different component targeting distinct link (s) of the signaling., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling. NEW & NOTEWORTHY Prolonged exercise may impact some people leading to pathological cardiac hypertrophy. This study using an animal model of fatigue-induced cardiac hypertrophy provides evidence showing the potential of QiShenYiQi Pills, a novel traditional Chinese medicine, to prevent the cardiac adaptive hypertrophy from development to pathological hypertrophy and demonstrates that this effect is correlated with its capacity for regulating energy metabolism through interacting with insulin-like growth factor-1 receptor.

Background: Gualou Xiebai decoction (GLXB), a multi-component herbal formula, has been widely used to treat coronary heart disease (CHD) in China for centuries. Several studies have revealed part of its pharmacological activities, whereas its active compounds and mechanisms of action are still unknown because of its complex composition., Purpose: Discover the major active compounds and the pharmacological mechanisms of GLXB by network pharmacology methods., Methods: The main candidate target network was constructed by predicting targets of absorbable chemical compounds of GLXB, collecting therapeutic targets of cardiovascular drugs, constructing target network and layers of screening. Community detection and edge-betweenness calculation were applied to analyze the main candidate target network. Cell viability test, Western blot and flow cytometry were performed to validate the predicted results in cardiomyocytes hypoxia/reoxygenation model., Results: Five clusters and eight cross-talk targets were found in the main candidate target network. Their functions combined together might explain the multifunctional role of GLXB against CHD. Among the cross-talk targets, ESR1 (Estrogen receptor alpha, ERα) and MAPK14 (Mitogen-activated protein kinase 14, p38) were both drug targets and therapeutic targets whose interaction exhibited the greatest edge-betweenness value, suggesting their crucial role in the protective effect of GLXB. The compounds targeting on ESR1 and MAPK14 were identified as apigenin and 25S-macrostemonoside P respectively which were regard as the major bioactive compounds. The predicted results including the major bioactive compounds, their targets and the synergic effects between them were validated., Conclusion: This study screened out major bioactive compounds from GLXB and offered a new understanding of the protection mechanism of GLXB against CHD by network pharmacology method and provides a combination strategy to explore mechanisms of action of multi-component drugs from a holistic perspective., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Backgroud: Finding effective compounds of TCMs has always been the basis for achieving marker-based quality control which is currently most widely used quality control strategy. Gualou Xiebai Decoction (GLXB), a classical TCM formula, is recorded and proven as a therapy for curing coronary heart disease but the effective constituents are unidentified and the substantial basis of the therapeutic effects is not clear., Purpose: The present research is an investigation on the chemistry of this formula aiming at finding and precisely identifying effective compounds., Study Design and Methods: This research started with screening for effective fractions of GLXB by rat myocardial infarction model and H9c2 cell hypoxia/reoxygenation model, then compounds in effective fractions were isolated and identified by phytochemical and spectroscopic methods. The cardio-protective activities of the compounds were tested in vitro and one of the effective compounds was taken as example to investigate the mechanisms., Results: The water-insoluble parts of GLXB were identified as effective parts in both in vitro and in vivo experiments. Systematic isolation of compounds in the effective fractions resulted in the isolation of 34 compounds including 7 new compounds, whereas 8 compounds were effective in protecting H9c2 cells against hypoxia/reoxygenation injury. One of the effective compounds, macrostemonoside P (MP) possibly exerted its effect by activating RISK pathway and attenuating apoptosis., Conclusion: An array of effective constituents of GLXB were discovered, and discovery of these compounds contributed to elucidating the substantial basis for the therapeutic effects of this formula, and provides fundaments for establishing Q-markers for further reliable quality control of GLXB., (Copyright © 2018. Published by Elsevier GmbH.)

Animal medicine injection is an important part of traditional Chinese medicine (TCM) injections. All or part of animals with a significant curative effect and little side reactions as raw materials as well as modern technology are used to produce traditional Chinese medicine injections with a reliable and rapid drug efficacy and high bioavailability. Due to the complex composition of traditional Chinese medicine injections, imperfect quality standards, and unreasonable clinical use, the incidence of adverse reactions of traditional Chinese medicine injections has been significantly higher than that of traditional Chinese medicine for oral use. Animal medicine injections contain rich protein and fat, and heteroproteins are the main sensitization source in animal medicine injections. At present, the adverse reactions of animal medicine injections are mainly manifested in the anaphylaxis-like reactions at skin, mucous membranes and organ systems. The adverse reactions that occur during the first medication are more common. Specific causes for allergic-like adverse reactions in animal injections and related substances in traditional Chinese medicine injections made of animals that induce allergies or anaphylactoid reactions are currently not specifically reported. This article reviews the current adverse reactions of animal TCM injections, allergies and pseudoallergic reactions of animal TCM injections, the pharmacokinetics of animal TCM injections, and the combined use of drugs, in order to improve the quality standards of Chinese medicine injections for animals and provide reference for further safety related research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background and Purpose- tPA (tissue-type plasminogen activator) is the only recommended intravenous thrombolytic agent for ischemic stroke. However, its application is limited because of increased risk of hemorrhagic transformation beyond the time window. T541 is a Chinese compound medicine with potential to attenuate ischemia and reperfusion injury. This study was to explore whether T541-benefited subjects underwent tPA thrombolysis extending the time window. Methods- Male C57BL/6 N mice were subjected to carotid artery thrombosis by stimulation with 10% FeCl 3 followed by 10 mg/kg tPA with/without 20 mg/kg T541 intervention at 4.5 hours. Thrombolysis and cerebral blood flow were observed dynamically until 24 hours after drug treatment. Neurological deficit scores, brain edema and hemorrhage, cerebral microvascular junctions and basement membrane proteins, and energy metabolism in cortex were assessed then. An in vitro hypoxia/reoxygenation model using human cerebral microvascular endothelial cells was used to evaluate effect of T541 on tight junctions and F-actin in the presence of tPA. Results- tPA administered at 4.5 hours after carotid thrombosis resulted in a decrease in thrombus area and survival rate, whereas no benefit on cerebral blood flow. Study at 24 hours after tPA administration revealed a significant angioedema and hemorrhage in the ischemia hemisphere, a decreased expression of junction proteins claudin-5, zonula occludens-1, occludin, junctional adhesion molecule-1 and vascular endothelial cadherin, and collagen IV and laminin. Meanwhile, ADP/ATP, AMP/ATP, and ATP5D (ATP synthase subunit) expression and activities of mitochondria complex I, II, and IV declined, whereas malondialdehyde and 8-Oxo-2'-deoxyguanosine increased and F-actin arrangement disordered. All the insults after tPA treatment were attenuated by addition of T541 dose dependently. Conclusions- The results suggest T541 as a potential remedy to attenuate delayed tPA-related angioedema and hemorrhage and extend time window for tPA treatment. The potential of T541 to upregulate energy metabolism and protect blood-brain barrier is likely attributable to its effects observed.

In this study, different batches of Xingnaojing injection products were first selected for pseudoallergic mice test, and the results showed that after injection of 6.6-fold clinical dose Xingnaojing injection, the mice showed a slight pseudoallergic reaction, while other mice injected with other batches of injections showed no obvious pseudoallergic reaction. Therefore, it is preliminarily believed that this mice model can effectively indicate the risk of pseudoallergic reactions in the clinical application of Xingnaojing injections. In addition, by changing some of the processes, a high concentration of Xingnaojing injection was prepared for mice pseudoallergic test and guinea pig systemic allergy test. The results showed no significant type Ⅰ allergic reaction in guinea pigs. Mild pseudoallergic reactions occurred in mice after a 6.6-fold clinical dose injection. Therefore, it is considered that for sensitive or idiosyncratic people, the concentration of certain chemical components in Xingnaojing injection will increase after entering the body, which may increase the risk of pseudoallergic reaction. However, due to the limitations of test models, the risk of Xingnaojing injection to induce allergic reactions cannot be ruled out. Finally, by increasing the content of borneol and Tween and (or) sodium chloride in Xingnnaojing Injection and testing its pseudoallergic reactions, the results showed that the combination of these three ingredients may produce new trace sensitization substance and induce pseudoallergic reactions., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study aimed to explore the characteristics and the influencing factors of Qingkailing injection (QKLI) pseudoallergic reaction, and screen out the possible pseudoallergenic substances. The results showed that ICR and Kunming mice had stronger pseudoallergic reactions than BALB/c and C57 mice after being injected with the same dose of QKLI. The pseudoallergic reaction induced by QKLI that was prepared with 0.9% saline was stronger than that prepared with 5% glucose. When the dose was twice of the clinical dose, some batches of QKLI could cause significant or suspected pseudoallergic reactions; when the dose dropped to clinically equal times, all of the batches did not induce pseudoallergic reactions in mice. Different batches of QKLI induced different pseudoallergic reactions in mice. Therefore, QKLI's pseudoallergic reactions might have a certain relationship with different body constitutions. Different solvents might affect the safety of QKLI. QKIL-induced pseudoallergic reactions had the different characteristics between batches, and the dosage should be strictly controlled in clinical use. After the comparison of pseudoallergic reactions induced by different components and different intermediates of QKLI in mice, it was preliminary believed that pseudoallergenic substances might exist in intermediate Isatidis Radix extracts and Gardenia extracts, but specific pseudoallergens shall be furthered studied in subsequent experiences., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for >2000years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on. CCM contains diverse bioactive components with potential for energy metabolism regulation; antioxidant effect; inhibiting inflammatory cytokines release; adhesion molecule expression in leukocyte, platelet, and vascular endothelial cells; and the protection of thrombosis, albumin leakage, and mast cell degranulation. This review covers the major works with respect to the effects and underlying mechanisms of CCM and its ingredients on microcirculatory dysfunction and organ injury after I/R, providing novel ideas for dealing with this threat., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this study, by the means of the active systemic allergy test in guinea pigs, passive skin allergy test in rats and pseudoallergic test in mice, it was determined that the "allergic reaction" of Shuxuening injection(SXNI) may not be a true IgE-mediated allergic reactions, but mainly of pseudoallergic reaction. Further pseudoallergic test proved that the pseudoallergic reactions of SXNI had difference between batches and showed dose dependence, so it was recommended to establish SXNI pseudoallergic reaction detection method for timely detecting and controlling the product risk of each batch products. In addition, as the pseudoallergic reactions of SXNI were dose-dependent, the dose and concentration of SXNI should be strictly controlled in clinical use. Then the main pseudoallergenic reaction test was conducted for the main monomer components in SXNI and the different fractions of Ginkgo biloba extract in mice, and the results showed that the sensitizing substances may mainly exist in YXY-3 fractions containing flavonol glycosides. By further chemically separating YXY-3, we got four chemical components. Among these four components, YXY-3-1 and YXY-3-2 were testified as the main allergenic components in SXNI through pseudoallergic test in mice. To make sure the specific chemical constituent that is responsible for the pseudoallergic reaction, in-depth study in follow-up experiments should be needed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Frequent and drastic ambient temperature variation may cause respiratory diseases such as common cold and pneumonia, the mechanism for which is not fully understood, however, due to lack of appropriate animal models. Ma-Huang-Tang (MHT) is widely used in China for treatment of respiratory diseases. The present study aimed to investigate the effect of MHT on temperature alternation induced rat lung injury and explore underlying mechanisms. Male Sprague-Dawley rats were exposed to a cold environment for 1 h and then shifted to a warm environment for 30 min. This cold and warm alteration cycled 4 times. Rats were administrated with MHT (1.87 g/kg) by gavage 6 h after cold-warm-cycles. Cold-warm-cycles induced pulmonary microcirculatory disorders, lung edema and injury, decrease in the expression of tight junction proteins, increase in VE-cadherin activation, increase in the expression and activation of Caveolin-1, Src and NF-κB, and NADPH oxidase subunits p47 phox , p40 phox and p67 phox membrane translocation and inflammatory cytokines production. All alterations were significantly ameliorated by post-treatment with MHT. This study showed that rats subjected to cold-warm-cycles may be used as an animal model to investigate ambient temperature variation-induced lung injury, and suggested MHT as a potential strategy to combat lung injury induced by temperature variation.

Objective: This study was designed to examine the effect of KDZ, on the BBB disruption in rat underwent MCAO and reperfusion., Methods: Male Sprague-Dawley rats (260-280 g) were subjected to 60 minutes MCAO followed by reperfusion. KDZ (4 mL/kg) was administrated before ischemia. The Evans blue extravasation, albumin leakage, brain water content, TJ proteins, caveolin-1, p-caveolin-1, Src, and p-Src were evaluated. Neurological scores, cerebral infarction, and CBF were assessed. The binding affinity of KDZ to Src was examined., Results: I/R evoked a range of insults including Evans blue extravasation, albumin leakage, brain water content increase, CBF decrease, cerebral infarction, and neurological deficits, all of which were attenuated by KDZ. Meanwhile, KDZ inhibited TJ proteins down-expression, expression of caveolin-1, phosphorylation of caveolin-1 and Src after I/R. In addition, SPR revealed binding of KDZ to Src with high affinity., Conclusions: KDZ protects BBB from disruption and improves cerebral outcomes following I/R via preventing the degradation of TJ proteins, caveolin-1 expression, and inhibiting p-caveolin-1 and p-Src, which were most likely attributable to the ability of its main ingredients to bind to Src and inhibit its phosphorylation., (© 2016 John Wiley & Sons Ltd.)

Complex diseases always involve some strait episode, such as myocardial hypertrophy and fibrosis caused by hypertension, microcirculation dysfunction and injury in heart, brain, lever, and intestine following ischemia and reperfusion, endotoxin induced multiorgan injury, and recovery after intestinal mucosa damage, for which intervention by a single medicine remains unsatisfied in clinic.Chinese medicine has been applied in clinic for more than two thousand years, which presents as a healthcare system using compound formula preparation, treatment based on syndrome differentiation and individualization thus has advantage in dealing with strait episode of complex diseases. However, the mechanism underlying Chinese medicine is not fully understood up till now.This report will explain the mechanisms underlying the beneficial role of Chinese medicine in therapy of strait episode of complex diseases based on the resent outcomes in study of aforementioned complex diseases. The speaker, using the theory of blood stasis and activating blood to remove stasis in Chinese medicine, classified microcirculation dysfunction induced by different causes, such as ischemia and reperfusion, stress, LPS, common cold, investigated the pathogenesis and progressing of each of which. Furthermore, the report explored the material basis and mechanism for compound formula of Chinese medicine with potential of tonifying Qi and activating blood, removing heat to cool blood, identified the ingredient in the compound formula responsible for respective effect.(Presented at the 1920th Meeting, June 3, 2016).

Objective: To study the effect of Wenyang Decoction (WD) on the differentiation of CD34+ progenitor cells of occupational asthma (OA) model rats., Methods: Fifty healthy male SD rats were randomly divided into five groups, i.e., the model group, the blank control group,the WD group,the Western medicine group,the combined group, 10 in each group. Prednisone suspension (10 mg/kg) was administered to rats in the Western medicine group by gastrogavage. WD (20 g/kg) was administered to rats in the WD group by gastrogavage. Prednisone suspension plus WD was administered to rats in the combined group by gastrogavage. Normal saline was administered to rats in the model group and the blank control group by gastrogavage. The general condition of rats was observed. Expression levels of peripheral blood IL-5 and eotaxin, eosinophils (EOS), CD34+, CC chemokine receptor 3 (CCR3+) in bone marrow suspension were detected by ELISA, Wirght-Giemsa, and flow cytometry, respectively., Results: Compared with the blank control group,expression levels of IL-5 and eotaxin in peripheral blood were significantly higher (P < 0.01), and the count of EOS and CD34+ cells, as well as CD34+ /CCR3+ significantly increased (P < 0.01) in the model group. Compared with the model group, expression levels of IL-5 and eotaxin, the count of EOS, CD34+ cells, CD34+ / CCR3+ were lowered in three treated groups (P < 0.01). Compared with the Western medicine group, the count of EOS and CD34+ / CCR3+ decreased in the combined group (P < 0.01). The count of EOS was significantly lower in the combined group than in the WD group (P < 0.01)., Conclusion: WD could reduce levels of in vivo inflammatory factors, and restrain the differentiation and recruitment of EOS,thereby alleviating the differentiation of CD34 progenitor cells to EOS.

The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode.

Pseudoallergic reactions occured after the first administration of patients, and the pathogenic mechanisms of them were different from the allergic reactions which needed excitation after antigen sensitization. To provide a basis for evaluation, clinical use and drug development of pseudoallergic reactions, the models were established by two kinds of Chinese herbal injections (CHI) both on different strain or gender mice. With the use of ICR, Kunming, BALB/C, C57 mice, pseudoallergic tests of two CHI were conducted to compare the sensitivity of four strains mice, and compared the differences in male and female animals. Test substances contain 0.8% Evans blue (EB) were intravenously injected into different strain and gender mice. Scores of ear blue staining and quantitation of ear EB exudation were the parameters for pseudoallergic reaction. Results of strain difference indicated that both CHI A and B could cause severe pseudoallergic reactions indicated by obvious vascular hyperpermeability on ICR mice. The pseudoallergic reactions in ICR mice are more obvious under the the same dose of injection, which stated the sensibility of ICR mice. And the reactions of KM mice and BALB/C mice were slightly reduced which compared to ICR mice, even alomost nothing on C57 mice. Comparison results of gender difference showed that one CHI was not have significant difference in male and female animals, but male animals were more susceptible than females on another CHI. Therefore, ICR mice were preferable experimental strain on the model of pseudoallergic reactions induced by CHI A and B. Because of female animals were easily influenced by estrous cycle, the pseudoallergic reactions induced by CHI A and B select and use male mice befittingly.

Choosing the right solvent and timely use is the basis of rational drug use and the most direct and efficient way to improve the safety of traditional Chinese medicine injections. This study aimed to evaluate the influence of solvent and drug preparation time on Shuanghuanglian injection inducing pseudo-allergic reactions with mouse mode. The two tests were carried out: (1) Comparative experiment between different solvent: Shuanghuanglian injection preparation to the appropriate concentration with 0.9% sodium chloride injection and 5% dextrose injection, mixed with Evans blue, at one time intravenous injected into mice, 30 minutes later, the mouse ears vascular permeability were observed and compared. (2) Comparative experiment among different preparation time: placed 10 min, 2.5 h, 6 h and 24 h after Shuanghuanglian injection were prepared and then to detect the pseudo-allergic reactions in mice using the same methods as in (1). The results showed that there was no significant difference in the pseudo-allergic reactions in mice which induced by the same dose of Shuanghuanglian injection, respectively with 0.9% sodium chloride injection and 5% dextrose injection preparation, and with the extension of preparation time, the degree of pseudo-allergic reactions of Shuanghuanglian injection was gradually severe.

In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.

Objective: To study whether co-stimulatory molecule CD40 of alveolar macrophage (AM) participated in the occurrence and development of silicosis, and to explore the intervention of Yiqi Huoxue Decoction (YHD) in the fibrosis of silicosis patients., Methods: Totally 46 silicosis inpatients and outpatients were recruited and randomly assigned to the Western treatment group (A) and the Chinese medicine (CM) treatment group (B), 23 in each group. Patients in Group A received routine symptomatic treatment such as anti-inflammation, phlegm resolving, anti-spasm, and asthma relief, and so on. Patients in Group B additionally took YHD, one dose daily for 14 successive days. Besides, another 18 patients with chronic cough and sense of laryngeal foreign bodies were recruited as the normal control group, who had no obvious lesion confirmed by bronchofi6roscope and clinical diagnosis of the lung. They were treated by symptomatic supporting treatment. The alveolar lavage fluid was collected from all patients and isolated, and AM cells were cultured. The level of CD40 mRNA was detected by RT-PCR. The expression of CD40 protein was detected by Western blot., Results: Compared with the normal control group, expression levels of CD40 mRNA and CD40 protein significantly increased in Group A (P < 0.01). Compared with Group A, expression levels of CD40 mRNA and CD40 protein significantly decreased in Group B (P < 0.01)., Conclusions: Highly expressed co-stimulatory molecule CD40 of AM might participate in pulmonary fibrosis. YHD could hinder its roles, inhibit the progression of fibrosis, thereby playing an interventional role of treatment.

Reproductive toxicity research takes an important place in traditional Chinese medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment includes drug-related miscarriage, fetal death, teratism, and adverse effects on fertility, genital system, embryonic development and fetus, which is different from contraindicated in pregnancy in traditional Chinese medicine theory. Now the three-phases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. Besides that, alternative methods of whole embryos culture and embryonic stem cell test are also used in traditional Chinese medicine embryo toxicity evaluation. This article reviews research progress and pre-clinical evaluation on reproductive toxicity of traditional Chinese medicine.

Objective: The aim of present study was to investigate the efficacy of MXSGT, a traditional Chinese medicine formula used for treatment of respiratory system diseases, in the LPS-induced rat ALI particularly with a focus on its effect on lung microvascular hyperpermeability and inflammatory reaction., Methods: Male Sprague-Dawley rats were injected with LPS (7.5 mg/kg, 1.5 mg/mL) intraperitoneally. MXSGT (0.52 g or 2.61 g/kg) was given by gavage six hours after LPS injection., Results: LPS stimulation resulted in a reduced survival rate, deteriorated vital signs, an increase in the number of leukocytes adhering to lung venules, the albumin leakage, the activity of MPO in lung tissues, the production of pro-inflammatory cytokines and lung perivascular edema. After LPS stimulation, western blot analysis revealed an increase in the expression of ICAM-1 and toll-like receptor 4, a decrease in tight junction proteins and an activation of cav-1, Src, and NF-κB. All the LPS-induced alterations were significantly attenuated by posttreatment with MXSGT., Conclusions: This study demonstrated MXSGT as a potential strategy for lung microvascular hyperpermeability and inflammatory reaction in ALI, and suggested that the beneficial role of MXSGT was correlated with toll-like receptor 4, Src, and NF-κB., (© 2014 John Wiley & Sons Ltd.)

Objective: TSI is a new drug derived from Chinese medicine for treatment of ischemic stroke in China. The aim of this study was to verify the therapeutic effect of TSI in a rat model of MCAO, and further explore the mechanism for its effect., Methods: Male Sprague-Dawley rats were subjected to right MCAO for 60 minutes followed by reperfusion. TSI (1.67 mg/kg) was administrated before reperfusion via femoral vein injection. Twenty-four hours after reperfusion, the fluorescence intensity of DHR 123 in, leukocyte adhesion to and albumin leakage from the cerebral venules were observed. Neurological scores, TTC staining, brain water content, Nissl staining, TUNEL staining, and MDA content were assessed. Bcl-2/Bax, cleaved caspase-3, NADPH oxidase subunits p47(phox)/p67(phox)/gp91(phox), and AMPK/Akt/PKC were analyzed by Western blot., Results: TSI attenuated I/R-induced microcirculatory disturbance and neuron damage, activated AMPK, inhibited NADPH oxidase subunits membrane translocation, suppressed Akt phosphorylation, and PKC translocation., Conclusions: TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC., (© 2014 John Wiley & Sons Ltd.)

Objective: To observe the effect of Huanglian Jiedu Decoction (HLJDD) in in vivo regulating differentiation of monocytes in an apolipoprotein E knockout (ApoE(-/-)) mouse model, and to observe the effect of HLJDD-containing serum in in vitro regulating differentiation of macrophages and foam cells., Methods: Fifteen apoE(-/-) mice were randomly divided into the common diet group, the hyperlipidemia group, and the hyperlipidemia +HLJDD treatment group, 5 in each group. Mice in the common diet group were fed with a chow diet. Mice in the hyperlipidemia group were fed with high cholesterol wild diet (WD). Those in the hyperlipidemia +HLJDD treatment group were fed with high cholesterol WD supplemented with HLJDD. All mice were fed for 4 weeks. Five C57BL/6 wild types were recruited as the wild common diet control group. HLJDD was administered to mice in the hyperlipidemia + HLJDD treatment group by gastrogavage at the daily dose of 5 g/kg. Equal volume of purified water was given by gastrogavage to mice in the rest 3 groups. Four weeks later, subtypes of monocytes in the peripheral blood were detected by FACS. HLJDD administered to another 30 SD rats by gastrogavage at the daily dose of 5 g/kg, once for every 12 h for 5 times in total, thereby preparing 5% HLJDD containing serum to intervene the differentiation of in vitro primary bone marrow-derived macrophage (BMDM) and foam cells. The M2 subtype surface receptor CD206 of macrophages and foam cells were detected by FACS. The expression of Nos2 and Arg1 genes were assayed by Real-time PCR., Results: The ratio of inflammatory subset of monocytes (Ly6C(high)) increased in the peripheral blood after ApoE(-/-) mice were fed with high fat diet for 4 weeks. HLJDD significantly decreased the ratio of inflammatory subset of monocytes (P < 0.05). Compared with the vehicle serum, 5% HLJDD containing serum significantly increased differentiation of CD206 + M2 BMDM (P = 0.034). Results of real-time quantitative PCR showed that the expression level of Arg1 mRNA could be up-regulated by HLJDD containing serum (P < 0.05), and that of Nos2 mRNA down-regulated (P = 0.017). ox-LDL induced the differentiation of M2 subtype foam cells from BMDM, and HLJDD containing serum could further elevate the ratio of CD206 + M2 foam cells and increase the Arg1 mRNA expression level (both P < 0.01). HLJDD containing serum could inhibit the inversion of M2 subtype of foam cells to M1 subtype induced by Th1 factors, significantly elevate the Arg1 mRNA expression level, and decrease the Nos2 mRNA expression level (all P < 0.01)., Conclusions: HLJDD could lower hyperlipidemia induced inflammatory monocyte subtype ratios in the peripheral blood of ApoE(-/-) mice. HLJDD containing serum promoted in vitro differentiation of M2 macrophages and foam cells. HLJDD attenuated and inhibited the occurrence and development of atherosclerosis induced by hyperlipidemia possibly through regulating the functional differentiation of monocytes, macrophages, and foam cells.

Objective: To observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice., Methods: Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01)., Conclusions: High fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

Background: QiShenYiQi Pills® (QSYQ) is a compound Chinese medicine used in China for alleviating cardiac function. The present study was designed to explore the effect and mechanism of QSYQ on ischemia-reperfusion (I/R)-induced disorders in myocardial structure and function, with particularly focusing on the regulation of energy metabolism., Methods: Sprague-Dawley rats, with or without QSYQ pretreatment, were subjected to 30 min occlusion of the left anterior descending coronary artery and followed by 90 min or 24h reperfusion. Myocardial blood flow (MBF) and cardiac function were evaluated at baseline, immediately after ischemia and 30, 60, 90 min, and 24h after reperfusion. Myocardial infarction, myocardial histology and ultrastructure were assessed. Double staining of alpha-cardiac actinin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. ATP, ADP and AMP content was determined by Enzyme-Linked Immunosorbent Assay, F-actin in myocardial cells determined by immunofluorescence microscopy and expression of ATP synthase α, ATP5D, and phosphorylated-Myosin Light Chain (P-MLC) determined by western blotting., Results: Pre-treatment with QSYQ protected against I/R-induced MBF decrease, myocardial infarction and apoptosis at 90 min and 24h after reperfusion. Moreover, I/R 90 min caused an impairment on cardiac function, a decrease in the ratio of ADP/ATP and AMP/ATP, accompanying with reduction of ATP 5D expression and increase in the expression of P-MLC, meanwhile, myocardium to exhibit myocardial fiber rupture, interstitial edema, and mitochondria swelling, all of which were significantly ameliorated by pre-treatment with QSYQ., Conclusions: The results of the present study suggest an involvement of regulation of energy metabolism in the action of QSYQ to protect against myocardial I/R injury., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

To investigate the effects of a compound (FF16), compatibility of Rhodiola crenulata, Cordyceps militaris, and Rhum palmatum, on non-alcoholic fatty liver disease in IRF mice induced by high fat diet H&E stain was processed to evaluate the lipid accumulation in liver, and the dynamic microcirculation observation system was applied to determine hepatic microcirculation of IRF mice. Western blot was performed to evaluate IRS-2, HSL and ppar-alpha expression in liver. The results demonstrate that FF16 significantly decreased the liver lipid index and improved liver steatosis in IRF mice. Furthermore, FF16 could ameliorate hepatic microcirculation disturbance in IRF mice through enhancing RBC velocity and shear rates by 62.5% and 49.7%, increasing sinusoids perfusion by 70.0%, inhibiting adhered leukocytes in IRF mice. The abnormal expressions of IRS-2 and HSL were both reversed by the administration of FF16. In conclusion, FF16 could improve non-alcoholic fatty liver disease in IRF mice by improving insulin sensitivity, regulating lipid metabolism and improving microcirculation disturbance.

Objective: The present study was designed to evaluate whether CP was beneficial in alleviating myocardial fibrosis following I/R injury., Methods: Sprague-Dawley rats were subjected to 30 minutes occlusion of the LADCA, followed by reperfusion. CP (0.4 or 0.8 g/kg) was daily administered starting from three hour after reperfusion until day 6. Coronary venular diameter, RBC velocity, albumin leakage, MBF, heart function, myocardial infarction and fibrosis size, myocardium ultrastructure, MPO activity, and MDA level were evaluated. The expression of MCP-1, RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, and the infiltration of leukocytes were examined., Results: CP post-treatment ameliorated I/R-induced myocardial RBC velocity reduction, MBF decrease, cardiac dysfunction, and albumin leakage increase. Moreover, myocardial infarction and fibrosis size, MPO activity, MDA level, the expression of RP S19, TGF-β1, P-Smad3, Smad4, MMP-9 and α-SMA, the number of CD68-positive cells increased significantly after I/R, and myocardium collagen deposition was observed on day 6 after reperfusion. All the alterations after I/R were significantly ameliorated by CP., Conclusions: Post-treatment with CP ameliorates I/R-induced myocardial fibrosis, suggesting that CP may be applied as an option for preventing cardiac remodeling after I/R injury., (© 2012 John Wiley & Sons Ltd.)

Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, for which the current clinical therapy remains unsatisfied. Cerebralcare Granule® (CG) is a compound Chinese medicine widely used in China for treatment of cerebrovascular diseases. CG has been demonstrated efficacy in attenuating the cerebral microcirculatory disturbance and hippocampal neuron injury following global cerebral ischemia. However, the effects of CG on BBB disruption following cerebral ischemia have not been investigated. In this study, we examined the therapeutic effect of CG on the BBB disruption in a focal cerebral ischemia/reperfusion (I/R) rat model. Male Sprague-Dawley rats (250 to 300 g) were subjected to 1h middle cerebral artery occlusion (MCAO). CG (0.4 g/kg or 0.8 g/kg) was administrated orally 3h after reperfusion for the first time and then once daily up to 6 days. The results showed that Evans blue extravasation, brain water content, albumin leakage, infarction volume and neurological deficits increased in MCAO model rats, and were attenuated significantly by CG treatment. T2-weighted MRI and electron microscopy further confirmed the brain edema reduction in CG-treated rats. Treatment with CG improved cerebral blood flow (CBF). Western blot analysis and confocal microscopy showed that the tight junction proteins claudin-5, JAM-1, occludin and zonula occluden-1 between endothelial cells were significantly degradated, but the protein expression of caveolin-1, the principal marker of caveolae in endothelial cells, increased after ischemia, all of which were alleviated by CG treatment. In conclusion, the post-treatment with CG significantly reduced BBB permeability and brain edema, which were correlated with preventing the degradation of the tight junction proteins and inhibiting the expression of caveolin-1 in the endothelial cells. These findings provide a novel approach to the treatment of ischemic stroke., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of the present study was to explore the protective effects of CG on rat cerebral injury after focal cerebral I /R., Methods: Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes followed by reperfusion for 60 minutes or 24 hours. CG (0.4 or 0.8 g/kg) was administrated 90 minutes before ischemia. Brian edema was evaluated by Evan's blue dye extravasations and brain water content, leukocyte adhesion, and albumin leakage were determined with an upright fluorescence microscope, and neuron damage was assessed by 2,3,5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemistry of caspase-3, p53, p53 upregulated modulator of apoptosis., Results: Focal cerebral I/R elicited a prominent brain edema, an increase in leukocyte adhesion, and albumin leakage, as well as neuron damage. All the insults after focal cerebral I/R were significantly attenuated by pretreatment with CG., Conclusions: Pretreatment with CG significantly reduced focal cerebral I/R-induced brain edema, cerebral microcirculatory disturbance, and neuron damage, suggesting the potential of CG as a prophylactic strategy for patients in danger of stroke., (© 2012 John Wiley & Sons Ltd.)

QiShen YiQi Pills(®) (QSYQ) is a compound Chinese medicine used for treatment of cardiovascular diseases. However, the potential of QSYQ to inhibit cardiac fibrosis in left ventricle hypertrophy is not explored to date. We investigated the effects of post-treatment with QSYQ on rat myocardial fibrosis in left ventricle hypertrophy induced by pressure over-load through ascending aortic stenosis. QSYQ was administrated 4 weeks after the surgery, at a dose of 0.8 g/kg/day over the next 4 weeks, while echocardiography was performed 4 and 8 weeks, respectively, after the surgery. Eight weeks after the surgery, myocardial blood flow was determined by Laser-Doppler Perfusion Imager and the ratio of heart weight to body weight (HW/BW) was estimated, in concurrent evaluation of myocardial histology and ultrastructure, as well as collagen content by sirius red staining, and immunohistochemistry staining for CD68 and transforming growth factor beta 1. Post-treatment with QSYQ significantly alleviated left ventricular posterior wall end diastolic thickness and the HW/BW, increased left ventricle ejection fraction and left ventricle fractional shortening. QSYQ also decreased myocardial fibrosis size. The expression of CD68 and transforming growth factor beta 1 were obviously suppressed after QSYQ treatment. The results suggest that post-treatment with QSYQ attenuates pressure over-load-induced cardiac hypertrophy and myocardial fibrosis through interfering in inflammatory process.

Objective: To assess the intervention of Biantong Huangqi Ointment (BHO) combined with Western medicine (WM) on the recurrence of bronchial asthma (BA)., Methods: Eighty-four BA children patients were randomly assigned to the treatment group (43 cases) and the control group (41 cases). During the period of onset, patients in the two groups were treated by WM alone. During the remission phase, patients in the treatment group took BHO, one dose daily, while those in the control group were treated with atomized inhalation of Budesonide and Salbutamol (0.5 mL each time for those 3 -8 years old; 0.75 mL each time for >or=those 8-12 years old). The therapeutic course for them all was 1 month. The serum levels of IgG and IgE before and after treatment, 6 and 12 months after withdrawal of medication were detected in the two groups, and the recurrence rate of BA observed in the two groups., Results: The recurrence rate of the treatment group was obviously lower than that of the control group after withdrawal of medication (9.5% vs 24.4% for 6 months, 14.0% vs 34.1% for 12 months), showing statistical difference between the two groups (P<0.05). The serum IgG level of children patients in the treatment group increased continuously after medication. The high serum IgE level state obtained long-term and effective relief., Conclusion: BHO showed favorable anti-recurrent effect on children's BA. Its mechanism might be associated with regulating children's immune system.

Objective: To investigate the distribution of monocyte subpopulations and the changes of Toll-like receptor 4 (TLR4), CD163 and CD36 expressions in the peripheral blood of patients with hyperlipidemia of phlegm-stagnancy obstruction syndrome pattern (HLE-PSO), and to evaluate the intervening effects of Qutan Huayu Jiedu (QHJ) herbs on these parameters., Methods: Monocytes in the peripheral blood were sorted using flow cytometry into 3 subpopulations: the CD14high CD16- (Mo1), the CD14high CD16+ (Mo2a) and the CD14low CD16+ (Mo2b) subpopulation. The percentages of various monocyte subpopulations in 83 patients and 42 matched healthy controls were determined and the levels of their surface receptors TLR4, CD163 and CD36 expressions were assayed with flow cytometer. Furthermore, patients allocated in the tested group (10 patients) and the control group (11 patients) were treated with QHJ Herbs and Qutan Huayu (QH, removing Phlegm and dissolving stagnancy but without detoxication) herbs respectively. The changes of monocyte subpopulations percentage and TLR4, CD163 and CD36 expressions were determined 4 weeks after they received treatment., Results: Percentage of Mo2a subpopulation was significantly higher in HLE-PSO patients than the normal range (5.35 +/- 2.57 vs. 3.09 +/- 2.38, P < 0.01), but the deviation of the other two subpopulations in percentage was insignificant. The TLR4 expression on Mo1 monocyte in patients was lower than normal (50.73 +/- 24.45 vs. 69.92 +/- 21.06, P < 0.01), while CD163 and CD36 expressions of all three subpopulations in patients were similar to those in healthy persons respectively. After 4 weeks of treatment, a significant lowered Mo2a proportions were observed in the tested group (3.73 +/- 1.05 vs. 5.50 +/- 2.06, P = 0.043); but not in the control group (4.20 +/- 1.81 vs. 5.65 +/- 1.89, P = 0.097), while the levels of TLR4, CD163 and CD36 were not significantly altered after treatment in both groups., Conclusions: The elevated proportions of Mo2a subpopulation and the lowered TLR4 expression in Mol subpopulation are the characteristic changes in HLE-PSO patients, which might be related with the hyperlipidemia caused immune injury in patients. QHJ herbs could effectively improve the disproportion of Mo2a subpopulation.

Aim of the Study: Cerebralcare Granule (CG) is a Chinese herb compound preparation that has been used for treatment of cerebrovascular related diseases. However, the effect of post-treatment with CG on ischemia and reperfusion (I/R) induced cerebral injury is so far unclear., Materials and Methods: In present study, cerebral global I/R was induced in Mongolian gerbils by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days, and CG (0.4 g/kg or 0.8 g/kg) was administrated 3h after the initiation of reperfusion., Results: Post-treatment with CG for 5 days attenuated the I/R-induced production of hydrogen peroxide in, leukocyte adhesion to, and albumin leakage from cerebral microvessels, and, meanwhile, protected neuron from death, reduced the number of caspase-3- and Bax-positive cells, and increased Bcl-2-positive cells in hippocampal CA1 region., Conclusion: The results suggest that CG given after initiation of reperfusion is able to ameliorate cerebral microvascular dysfunction and hippocampal CA1 neuron damage caused by I/R., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Yiqifumai is a traditional Chinese medicine compound preparation used for the treatment of various vascular diseases in China. However, little is known regarding its role in microcirculation. The present study investigated the effect of pretreatment of yiqifumai on rat mesentery microcirculatory disturbance induced by LPS. Male Wistar rats were continuously infused with LPS (5 mg kg(-1) h(-1)). The parameters evaluated included diameter of and red blood cell velocity in venules, leukocyte adhesion to venular wall, dihydrorhodamine 123 (DHR) fluorescence in the venular walls, fluorescein isothiocyanate-albumin leakage, and mast cell degranulation, which were observed by an inverted intravital microscope. CD11b/CD18 expression on neutrophils was examined using flow cytometry. In some rats, yiqifumai (5, 30, or 80 mg kg(-1)) was given in one shot 10 min before LPS infusion. After infusion of LPS, the number of leukocytes adherent to venular wall, the intensity of DHR fluorescence in the venular walls, albumin leakage from venules, and degranulated mast cells were significantly increased, whereas the red blood cell velocity in venule was decreased. Pretreatment with high-dose yiqifumai (80 mg kg(-1)) significantly reduced the number of adherent leukocytes, the intensity of DHR fluorescence, degranulation of mast cell, albumin leakage, and the expression of CD11b/CD18, whereas the yiqifumai of medium dose (30 mg kg(-1)) only inhibited leukocyte adhesion to the venular wall. The results suggested that pretreatment with yiqifumai attenuated microcirculatory disturbance induced by LPS. This effect may be associated with yiqifumai's inhibition effect on reactive oxygen species production, leukocyte adhesion, and mast cell degranulation.

Cerebralcare Granule (CG) is a compound Chinese medicine used for treatment of headache and dizziness associated with cerebrovascular diseases. To clarify the mechanism underlying the clinical outcome of CG, this study investigated the effects of CG on the structure and function of cerebral microvasculature during I/R injury. A total of 138 Mongolian gerbils were included and divided into four groups, each composed of 36 or 30 animals, for evaluating various parameters of concern. A skull window was prepared for microcirculatory observation in animals, which were subjected to I/R with or without pretreatment with CG (0.4 or 0.8 g/kg). The velocity of red blood cells in the venules was observed by a high-speed video camera system, along with intravital confocal microscopic measurements of microvascular diameters, adherent leukocytes, and albumin leakage in the brain cortex. Changes in the fluorescence intensity of dihydrorhodamine 123 in cerebral microvessels and malondialdehyde level in the cortex were measured. The ultrastructure of the microvessels in the cerebral cortex was analyzed using both transmission and scanning electron microscopy. In addition, cerebral blood flow was monitored using the laser Doppler imaging technique. Pretreatment with CG (0.4 or 0.8 g/kg) significantly alleviated I/R injury-induced disorders in cerebral microvasculature, as evidenced by the data observed at 60 min of reperfusion wherein the values in CG (0.4 g/kg) pretreatment group, CG (0.8 g/kg) pretreatment group, and I/R group were 2.43 +/- 0.24, 2.28 +/- 0.18, and 6.00 +/- 0.35 for leukocyte adhesion, 2.51 +/- 0.40, 2.33 +/- 0.29, and 4.77 +/- 0.24 for albumin leakage, 7.06 +/- 0.81, 5.93 +/- 0.42, and 28.38 +/- 2.70 for dihydrorhodamine 123 fluorescence intensity in cerebral microvessels, 16.35 +/- 0.52, 14.34 +/- 0.68, and 21.46 +/- 0.71 for malondialdehyde level in the cortex, and 0.43 +/- 0.07, 0.46 +/- 0.02, and 0.17 +/- 0.08 for cerebral blood flow, respectively. I/R injury-elicited ultrastructural alterations in microvessels in cerebral cortex were also mitigated impressively by CG administration, manifested as attenuation of the reduced number of opening capillaries and the altered fine structures in endothelium, which were characterized by rough inner surface, increased intracellular vesicles, hypertrophy of digitations of intercellular contact, and swollen perivascular astroglial processes. Cerebralcare Granule is able to attenuate I/R injury-induced functional and structural changes in microvessels in the cerebral cortex of gerbils, an ability that is most likely correlated with its antioxidant potential.

3,4-dihydroxy-phenyl lactic acid (DLA) and salvianolic acid B (SAB) are two major water-soluble components of Salvia miltiorrhiza (SM). Previous works have revealed the ability of DLA and SAB to scavenge oxygen free radicals, inhibiting the expression of adhesion molecules CD11b/CD18 in neutrophil. Cardiotonic pills (CP), which is a traditional Chinese medicine compound preparation containing DLA and SAB, was found to inhibit venular thrombosis induced by photochemical reaction (PR) in rat mesentery. The present study addressed the effect of DLA and SAB on PR-induced thrombosis in rat mesentery by utilizing a microcirculation dynamic viewing system. The result demonstrated that both DLA and SAB delayed thrombus-initiation time, while DLA also prolonged thrombus half-size time. The experiments explored the mechanism underlying that the dihydrorhodamine 123 (DHR) fluorescence in the mesenteric venular walls after PR challenge was diminished by pretreatment with either DLA or SAB, the expression of CD18 in neutrophils elicited by PR was depressed by administration of DLA, while mast cell degranulation in rat mesentery induced by PR was damped by SAB. The antioxidant potential of the two substances is likely to be responsible for their most beneficial effects on thrombosis, through either directly scavenging the peroxides produced and/or indirectly depressing the expression of adhesion molecules in neutrophil.

Ischemia and reperfusion (I/R) exerts multiple insults in microcirculation, frequently accompanied by endothelial cell injury, enhanced adhesion of leukocytes, macromolecular efflux, production of oxygen free radicals, and mast cell degranulation. Since the microcirculatory disturbance results in injury of organ involved, protection of organ after I/R is of great importance in clinic. Salvia miltiorrhiza root has long been used in Asian countries for clinical treatment of various microcirculatory disturbance-related diseases. This herbal drug contains many active water-soluble compounds, including protocatechuic aldehyde (PAl), 3,4-dihydroxyphenyl lactic acid (DLA) and salvianolic acid B (SalB). These compounds, as well as water-soluble fraction of S. miltiorrhiza root extract (SMRE), have an ability to scavenge peroxides and are able to inhibit the expression of adhesion molecules in vascular endothelium and leukocytes. Moreover, lipophilic compounds of SMRE also prevent the development of vascular damage; NADPH oxidase and platelet aggregation are inhibited by tanshinone IIA and tanshinone IIB, respectively, and the mast cell degranulation is blunted by cryptotanshinone and 15,16-dihydrotanshinone I. Thus, the water-soluble and lipophilic compounds of SMRE appear to improve the I/R-induced vascular damage multifactorially and synergically. This review will summarize the ameliorating effect of compounds derived from SMRE on microcirculatory disturbance and target organ injury after I/R and will provide a new perspective on remedy with multiple drugs.

Aim: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system., Methods: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITC-albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro., Results: The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo, all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection., Conclusion: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.

Aim: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaertn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/reperfusion (I/R) in rats fed ethanol chronically., Methods: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-alpha and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia., Results: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-alpha and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption., Conclusion: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-alpha production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

It is now well documented that a large proportion of breast tumors express their own aromatase. This intratumoral aromatase produces estrogen in situ and therefore may contribute significantly to the amount of estrogen to which the cell is exposed. Thus it is not only important that aromatase inhibitors potently inhibit the peripheral production of estrogen and eliminate the external supply of estrogen to the tumor cell, but that they in addition potently inhibit intratumoral aromatase and prevent the tumor cell from making its own estrogen within the cell. To study the inhibition of intracellular aromatase, we have examined the aromatase-inhibiting potency of the Scutellaria barbata D. Don. (SB) and Euonymus alatus Sieb. (EA) in myometrial and leiomyomal cells which contain aromatase. We have also used human placental tissues. Although SB and EA are approximately equipotent in a cell-free aromatase system (human placental microsomes), EA is consistently 10-30 times more potent than SB in inhibiting intracellular aromatase in myometrial and leiomyomal cells. To provide insights into the effect of SB and EA on aromatase activity in leiomyomal cells, we examined the cell lines, which is induced to differentiate toward the more transformed cell phenotype by 12-tetradecanoylphorbal-13-acetate (TPA) as a protein kinase C activator and transforming growth factor-beta1 (TGF-beta1). Enzyme activity was inhibited in a time-and dose-dependent fashion by SB and EA and by either 1-50 nM TPA or 0.01-0.5 ng/ml TGF-beta1, with maximal responses after 2-3 h exposure.