Dropping Pill Research Articles

Protective effects of Shexiang-Tongxin dropping pill against acute myocardial infarction in rats through inhibition of apoptosis and ERK/MAPK signaling pathways

Protective effects of Shexiang-Tongxin dropping pill against acute myocardial infarction in rats through inhibition of apoptosis and ERK/MAPK signaling pathways

Efficacy and safety of Qishen Yiqi drop pill for coronary heart disease: An overview of systematic review and meta-analysis

Efficacy and safety of Qishen Yiqi drop pill for coronary heart disease: An overview of systematic review and meta-analysis

Exploring therapeutic targets and molecular mechanisms for treating diabetes mellitus-associated heart failure with Qishen Yiqi dropping pills: A network pharmacology and bioinformatics approach.

Diabetes mellitus (DM) and heart failure frequently coexist, presenting significant public health challenges. QiShenYiQi Dropping Pills (QSDP) are widely employed in the treatment of diabetes mellitus concomitant with heart failure (DM-HF). Nevertheless, the precise mechanisms underlying their efficacy have yet to be elucidated. Active ingredients and likely targets of QSDP were retrieved from the TCMSP and UniProt databases. Genes associated with DM-HF were pinpointed through searches in the GeneCards, OMIM, DisGeNET, and TTD databases. Differential genes connected to DM-HF were sourced from the GEO database. Enrichment analyses via gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways, as well as immune infiltration assessments, were conducted using R software. Further analysis involved employing molecular docking strategies to explore the interactions between the identified targets and active substances in QSDP that are pertinent to DM-HF treatment. This investigation effectively discerned 108 active compounds and 257 targets relevant to QSDP. A protein-protein interaction network was constructed, highlighting 6 central targets for DM-HF treatment via QSDP. Gene ontology enrichment analysis predominantly linked these targets with responses to hypoxia, metabolism of reactive oxygen species, and cytokine receptor interactions. Analysis of Kyoto Encyclopedia of Genes and Genomes pathways demonstrated that these targets mainly participate in pathways linked to diabetic complications, such as AGE-RAGE signaling, dyslipidemia, arteriosclerosis, the HIF-1 signaling pathway, and the tumor necrosis factor signaling pathway. Further, immune infiltration analysis implied that QSDP's mechanism in treating DM-HF might involve immune-mediated inflammation and crucial signaling pathways. Additionally, molecular docking studies showed that the active substances in QSDP have strong binding affinities with these identified targets. This research presents a new model for addressing DM-HF through the use of QSDP, providing novel insights into incorporating traditional Chinese medicine (TCM) principles in the clinical treatment of DM-HF. The implications of these findings are substantial for both clinical application and further scientific inquiry.

Network Meta-analysis of Chinese patent medicines in treatment of chronic pulmonary heart disease

Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.

Shexiang tongxin dropping pill alleviates myocardial injury induced by coronary microembolization by down-regulating APOC1 to inhibit STAT3 signaling pathway.

This study determines to validate the mechanism of Shexiang Tongxin dropping pill (STDP) in attenuating coronary microembolization (CME) induced myocardial injury. CME rat models were established and underwent corresponding treating. Gene chip analysis was performed in rat myocardial tissues for GO and KEGG enrichment analysis. The differentially expressed genes were detected by qRT-PCR. H&E staining and ELISA were used for pathological analysis and detection of troponin (cTnI) and Creatine Kinase Isoenzyme (CK-MB). Lipopolysaccharide (LPS) treated primary cardiomyocytes were used to mimic inflammatory in vitro models. Cell viability and apoptosis of cardiomyocytes were determined by MTT and flow cytometry. The expressions of inflammatory cytokines, apoptotic proteins and proteins related to the STAT3 signal pathway were detected by western blot. APOC1 mRNA expression was detected by qRT-PCR. Immunofluorescence (IF) was used for subcellular localization of p-STAT3 and the binding of APOC1 with STAT3 was verified using Co-IP. STDP can attenuate myocardial injury in CME rat models, and lead to decreased expression of APOC1 and suppressed STAT3 signal pathway. In vitro models found STDP can suppress the cell viability and cell apoptosis of primary cardiomyocytes, in addition to suppressing the secretions of IL-6, IL-1β and TNF-α, while the protective effect of STDP can be reversed by overexpression of APOC1. Co-IP found that APOC1 can bind STAT3 directly. APOC1 can increase p-STAT3 expression in the nucleus to activate the STAT3 signal pathway. STDP can suppress APOC1 and STAT3 signal pathway to inhibit inflammation and cell apoptosis of cardiomyocytes. APOC1 may be one of the key regulatory factors in CME-induced myocardial injury.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Revealing the pharmacological mechanisms of nao-an dropping pill in preventing and treating ischemic stroke via the PI3K/Akt/eNOS and Nrf2/HO-1 pathways.

Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen-glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Mechanism of Shexiang Tongxin Dropping Pills in treating diabetic cardiomyopathy based on network pharmacology and animal experiments

This study aimed to explore the mechanism of Shexiang Tongxin Dropping Pills(STDP) in treating diabetic cardiomyopathy(DCM) based on network pharmacology, molecular docking, and animal experiments. BATMAN, TCMSP, and GeneCards were searched for the active ingredients and targets of STDP against DCM. STRING and Cytoscape were used to build the protein-protein interaction(PPI) network and &quot;drug-active ingredient-target&quot; network. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the targets were carried out based on DAVID. The molecular docking of key receptor proteins with corresponding active ingredients was performed using AutoDock Vina. The rat model of DCM was established by a high-fat diet combined with intraperitoneal injection of streptozotocin. Rats were assigned into control, model, low-(20 mg·kg~(-1)) and high-dose(40 mg·kg~(-1)) STDP, and metformin(200 mg·kg~(-1)) groups. After 8 weeks of continuous administration, the cardiac function, myocardial pathological changes, and myocardial collagen fiber deposition of rats in each group were detected by echocardiography, hematoxylin-eosin(HE) staining, and Sirius red staining, respectively. The myocardial hypertrophy was detected by WGA staining. The expression levels of p38 mitogen-activated protein kinase(p38), phosphorylation-p38(p-p38), c-Jun N-terminal kinase(JNK), phosphorylation-JNK(p-JNK), caspase-3, and C-caspase-3 in the myocardial tissue of rats in each group were measured by Western blot. The network pharmacology predicted 199 active ingredients and 1 655 targets of STDP and 463 targets of DCM. One hundred and thirty-four potential targets of STDP for treating DCM were obtained, and the AGE-RAGE signaling pathway in diabetic complications was screened out. Molecular docking results showed that miltirone, dehydromiltirone, and tryptanthrin had strong binding affinity with RAGE. The results of animal experiments confirmed that STDP effectively protected the cardiac function of DCM rats. Compared with the DCM model group, the STDP groups showed significantly down-regulated protein levels of p-p38, p-JNK, and C-caspase-3. To sum up, STDP may protect the cardiac function of DCM rats by regulating the AGE-RAGE signaling pathway.

Integration of transcriptomics and metabolomics reveals toxicological mechanisms of ZhuRiHeng drop pill in the 180-day repeated oral toxicity study.

Background: ZhuRiHeng Drop Pill (ZRH) is a traditional Mongolian medicinal preparation. Despite its long history of use for the treatment of coronary heart disease, there have been few toxicological studies of the safety profile of ZRH. Purpose: In order to comprehensively elucidate the underlying mechanisms behind the observed toxicity of ZRH on rat livers in the 180-day repeated oral toxicity study, we conducted a comprehensive analysis by integrating transcriptomic and metabolomic data. Methods: High-resolution mass spectrometry was conducted to evaluate the constituents of ZRH. For the acute oral toxicity study, mice were administered a dose of 32g/(kg·d) of ZRH, while rats were instead orally administered 0.934, 1.868, or 3.736g/(kg·d) of ZRH over a 180-day period in a 180-day repeated oral toxicity study. Conventional index and organ weights/histology were then monitored to detect any potential ZRH treatment-related toxicity. To identify key genes and metabolites involved in ZRH toxicological processes, we performed transcriptomic and metabolomic analyses of liver tissue upon ZRH treatment using RNA-seq techniques, qPCR and liquid chromatography-mass spectrometry analyses. Results: A total of 60 compounds in ZRH were identified and speculated in positive and negative ion modes. Mice in the acute toxicity study exhibited no signs of ZRH-related toxicity. In a protracted oral toxicity investigation spanning 180 days, discernible elevations in liver ratios were noted in both male and female rats across all three dose cohorts, relative to the control group (p < 0.05 or p < 0.01). Upon subjecting to ZRH treatment, our transcriptomic and qPCR analyses unveiled notable upregulation of crucial genes, exemplified by Abcb1b and Cyp2b2, known for theirs involvement in liver drug transport and metabolism function. Furthermore, our untargeted metabolomic analysis provided supplementary insights, revealing significant regulation in pyrimidine metabolism, as well as alanine, aspartate, and glutamate metabolism pathways. Conclusion: Our study unveils a panoramic understanding of the temporal, dosage-specific, and gene dimensions surrounding the metabolic and transcriptional shifts induced by ZRH exposure. As we peer into the future, recommendations emerge for further exploration, encompassing aspects such as time dynamics, dosage considerations, and gene-centric avenues to enhance therapeutic efficacy.

Establishment of CME Mouse Model Based on Autologous Thrombotic Particles and the Effect of Shexiang Tongxin Dropping Pill on the Coronary Microvascular Blood Flow in This Model

Coronary microvascular disease poses significant clinical harm and is closely associated with major cardiovascular adverse events. Existing research has highlighted coronary microvascular embolism (CME) as an important factor. Previous studies have utilized microspheres to construct a mouse model of CME, which can partially simulate coronary microvascular disease. However, there are notable discrepancies from the clinical reality. Shexiang Tongxin Dropping Pill (SXDP), a traditional Chinese patent medicine, is widely used in Chinese hospitals for treating coronary heart disease. Our preliminary research has indicated that SXDP effectively alleviates chest pain symptoms and improves coronary thrombolysis in myocardial infarction (TIMI) blood flow in patients with angina pectoris. Nonetheless, the specific mechanism remains unclear. To address this, the current study aimed to explore the size and concentration of autologous thrombotic particles to construct a CME mouse model, taking reference from previous studies on microsphere parameters (size: 9 µm; concentration: 500 000/50 µl). Additionally, we aimed to observe the effect of SXDP on coronary microvascular blood flow in this model. The experiments revealed that the average size of 400-mesh thrombus particles closely approximated 9 µm, and the concentration suspension at a ratio of 1 : 0.15, with a volume of 50 µl, contained approximately 500 000 particles. Concurrently, we observed that 400-mesh blood clot particles induced T-wave elevation in the electrocardiogram, decreased region of interest value in laser speckle examination, downregulated CD31 and Lectin in vascular endothelium, caused thrombosis in coronary microvessels, and led to myocardial infarction. Moreover, a decrease in serum nitric oxide levels and an increase in endothelin-1 (ET-1) were observed. Furthermore, we investigated the effects of SXDP on this animal model and identified potential mechanisms underlying its ability to reverse the aforementioned pathological changes. The research findings suggest that 400-mesh blood clot particles can successfully establish a CME mouse model, and SXDP can improve coronary microvascular blood perfusion, potentially through the improvement of endothelial function.

Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

The Effect of Ginkgo Biloba Leaf Dropping Pill Combined with Butylphthalide Capsule on Cognitive Dysfunction in Patients after Acute Ischemic Stroke and Its Impact on Serum Cytokines

The Effect of Ginkgo Biloba Leaf Dropping Pill Combined with Butylphthalide Capsule on Cognitive Dysfunction in Patients after Acute Ischemic Stroke and Its Impact on Serum Cytokines

Clinical efficacy and safety of adjunctive treatment of chronic ischemic heart failure with Qishen Yiqi dropping pills: a systematic review and meta-analysis.

Our study was to evaluate the effect of Qishen Yiqi Dropping Pills(QSYQ) on the prognosis of chronic ischemic heart failure(CIHF) and its safety. Databases including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, The Cochrane Library and EMbase were searched from their inception to April 2023 to screen relevant randomized controlled trials (RCTs). Primary indicators included readmission rates, rates of major adverse cardiovascular events (MACE), and all-cause mortality rates. The quality of the literature was assessed according to the Cochrane Reviewers' Handbook 5.0 and the Modified Jadad Scale (with a score of 4-7 rated as high quality). Meta-analysis was performed using the meta-package created by R software version 4.2.3, continuous data were compared using SMDs, and dichotomous and ordered data were compared using ORs; and the I2 test was used to assess the heterogeneity. Fifty-nine studies out of 1,745 publications were finally included, totalling 6,248 patients. Most studies were poorly designed and had some publication bias, with only 26 high-quality papers (Jadad score ≥4). Meta-analysis showed that the combined application of QSYQ was able to reduce the readmission rate [OR = 0.42, 95% CI (0.33, 0.53), P < 0.001], all-cause mortality rate [OR = 0.43, 95% CI (0.27, 0.68), P < 0.001], and the incidence of MACE [OR = 0.42, 95% CI (0.31, 0.56), P < 0.001]. Also, the treatment method can improve clinical effectiveness [OR = 2.25, 95% CI (1.97, 2.58), P < 0.001], increase 6-min walking distance (6MWD) [SMD = 1.87, 95% CI (1.33, 2.41), P < 0.0001] and left ventricular ejection fraction (LVEF) [SMD = 1.08, 95% CI (0.83, 1.33), P < 0.0001], and decrease the Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores [SMD = -2.03, 95% CI (-3.0, -1.07), P < 0.0001], BNP levels [SMD = -2.07, 95% CI (-2.81, -1.33), P < 0.0001] and NT-ProBNP levels [SMD = -2.77, 95% CI (-4.90, -0.63), P < 0.05]. A total of 21 studies (n = 2,742) evaluated their adverse effects, of which 13 studies reported no adverse effects and 8 studies reported minor adverse effects. Our results suggest that the combined application of QSYQ can further improve patients' cardiac function and exercise tolerance, improve their quality of life, and ultimately improve patients' prognosis with a favorable safety profile. Nonetheless, limited by the quality and high heterogeneity of the literature, we must be conservative and cautious about the present results. PROSPERO (CRD42023449251).

Shexiang Tongxin dropping pills protect against ischemic stroke-induced cerebral microvascular dysfunction via suppressing TXNIP/NLRP3 signaling pathway

Ethnopharmacological relevancePatients with ischemic stroke (IS) often continue to exhibit cerebral microcirculatory dysfunction even after receiving thrombolytic therapy. Enhancing the function of cerebral microvascular endothelia represents a pivotal advancement in the therapeutic strategy for ischemic microcirculatory disturbances. A traditional Chinese medicinal formulation named Shexiang Tongxin Dropping Pills (STDP), has been clinically employed to ameliorate microcirculatory abnormalities. Existing literature attests to the beneficial role of STDP on endothelial cells (ECs). Nevertheless, specific impacts and underlying mechanisms of STDP in rectifying IS-induced cerebral microvascular dysfunction warrant further exploration. Aim of the studyThis investigation seeks to delineate the effects of STDP on cerebral microvascular endothelial damage induced by ischemic stroke and to elucidate the underlying mechanism involved. Materials and methodsMiddle cerebral artery occlusion and reperfusion (MCAO/R) technique was employed to established ischemic stroke model in mice. The therapeutic efficacy of STDP on cerebral microvascular function was assessed through laser speckle contrast imaging, behavioral assays, and histological evaluations. Biochemical markers in the brain tissue, including GSH, SOD, MDA, and ROS, were quantified using specific assay kits. In vitro study, oxygen-glucose deprivation and reperfusion (OGD/R) was performed in bEnd.3 cells. The cytoprotective potential of STDP was then evaluated by measuring cell viability, LDH activity, endothelial permeability, and oxidative stress parameters. Important targets in critical pathway were verified by immunoblotting and immunofluorescence both in mice brain slices and bEnd.3 cells. ResultsSTDP decrease brain infarct size, repaired microvascular cerebral blood flow and attenuated neurological deficiency in MCAO/R mice. Moreover, STDP abolished MCAO/R-induced oxidative stress which was reflected by rescuing GSH content, restoration of SOD activity and T-AOC, reduction of MDA and ROS. Ex vivo, STDP increased cerebral microvascular endothelial cells viability, abolished oxidative stress and decreased their permeability after ODG/R. Mechanistically, STDP significantly suppressed endothelial ROS-TXNIP mediated the activation of NLRP3 inflammasome in vivo and in vitro. ConclusionSTDP improves ischemic stroke-induced cerebral microcirculatory deficits by regulating cerebral microvascular endothelial ROS/TXNIP/NLRP3 signaling pathway.

Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the &quot;gemtc&quot; package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

Quantification of nine bufadienolides of Shexiang Tongxin Dropping Pills in rat plasma and tissues using UPLC-MS/MS and its application to healthy and ischemia-reperfusion rats pharmacokinetic studies

Shexiang Tongxin Dropping Pill (STDP) is a well-known compound preparation used in traditional Chinese medicine for treating cardiovascular diseases. Bufadienolides are the major active compounds of toad venom and are the key to the seven medicinal herbs that comprise STDP. In this study, a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative determination of nine bufadienolides (bufalin, gamabufotalin, resibufogenin, marinobufagin, arenobufagin, desacetylcinobufagin, telocinobufagin, hellebrigenin, and hellebrigenol) in rat plasma and tissues (heart and liver). The chromatography column used was a Waters ACQUITY UPLC HSS-T3 column with gradient elution using mobile phase consisting of acetonitrile–water (0.1% formic acid added) at a flow rate of 0.25 mL/min. This method passed the methodological validation of plasma and tissues and was successfully applied to pharmacokinetic and tissue distribution studies after oral administration of STDP in healthy and ischemia-reperfusion (I/R) rats. This indicated that most bufadienolides were well absorbed and quickly distributed in the heart and liver. The area-under-the-curve (AUC)(0−t) of most analytes increased in a dose-dependent manner. Moreover, most of the tested components showed lower plasma and higher tissue concentrations in I/R rats than in healthy rats. The above results on the oral pharmacokinetics and tissue distribution may be helpful for the clinical application of STDP.

Shexiang Tongxin Dropping Pill alleviates M1 macrophage polarization-induced inflammation and endothelial dysfunction to reduce coronary microvascular dysfunction via the Dectin-1/Syk/IRF5 pathway

Ethnopharmacological relevanceShexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine compound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated. Aim of the studyTo explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action. Materials and methodsThe CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury-induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflammation and endothelial dysfunction. ResultsSTDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endothelial dysfunction induced by Dectin-1 overexpression in macrophages. ConclusionSTDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD.

Optimization of dropping process of Xuesaitong dropping pills based on quality by design concept and machine vision

Objective The drooping process of the Xuesaitong dropping pills (XDPs) was optimized based on quality by design concept. Meanwhile, a machine vision (MV) technology was creatively introduced in this study to predict the critical quality attributes (CQAs) rapidly and accurately. Significance This study improves the understanding of dropping process, and has reference value for the guidance of pharmaceutical process research and industrial production. Methods The study mainly consisted of three stages: the first stage involved the prediction model to establish and evaluate the CQAs, and the second stage involved assessing the quantitative relationships between critical process parameters (CPPs) and CQAs by the mathematical models that were established through the Box–Behnken experimental design. Finally, a probability-based design space for the dropping process was calculated and verified according to the qualification criteria of each quality attribute. Results The results show that the prediction accuracy of the random forest (RF) model was high and met the analysis requirements, and the CQAs of dropping pills can meet the standard by running in the design space. Conclusion The MV technology developed in this study can be applied to the optimization process of the XDPs. In addition, the operation in the design space can not only ensure the quality of XDPs to meet the criteria, but also help to improve the consistency of XDPs.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies.

To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF). Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting. The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs. STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

Shexiang Tongxin Dropping Pills improve cardiac function in type 2 diabetic rats by promoting angiogenesis

This study aims to investigate the effect of Shexiang Tongxin Dropping Pills(STDP) on angiogenesis in type 2 diabetic rats. Thirty-two healthy male SD rats were randomized into a control group(n=6) and a type 2 diabetes mellitus(T2 D) group(n=26). The T2 DM rat model was established with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ). The model rats were randomized into a model group, a metformin group(200 mg·kg~(-1)·d~(-1)), a high-dose STDP group(40 mg·kg~(-1)·d~(-1)), and a low-dose STDP group(20 mg·kg~(-1)·d~(-1)). The corresponding agents were administered continuously for 8 weeks. The cardiac function indexes were detected by ultrasound at the experiment endpoint, and the myocardial pathological changes were observed via hematoxylin-eosin(HE) staining. The myocardial collagen fiber deposition was detected by sirius red staining, the myocardial microvascular density by immunohistochemistry, and the myocardial hypertrophy by immunofluorescence assay. Western blot was employed to measure the protein levels of vascular endothelial growth factor(VEGF), phosphorylated vascular endothelial growth factor receptor 2(p-VEGFR2), angiogenin-1(Ang1), and TEK tyrosine kinase endothelial(Tie2) in the myocardial tissue. Compared with the model group, STDP improved the left ventricular ejection fraction(EF) and fractional shortening(FS)(P&lt;0.05), alleivated the arrangement disorder of myocardial cells and local myocardial fiber rupture. Sirius red staining showed that STDP, especially the high-dose group(P&lt;0.01), repaired the deposition of myocardial collagen fibers in the model group. The results of immunohistochemistry showed that the cluster of differentiation 31(CD31) expression in myocardial tissue of the STDP groups was higher than that of the model group(P&lt;0.01). The immunofluorescence results showed that STDP mitigated the hypertrophy of myocardial cells(P&lt;0.01). Furthermore, STDP up-regulated the protein levels of VEGF, p-VEGFR2, Angl, and Tie2 compared with the model group(P&lt;0.01). In conclusion, STDP can effectively promote angiogenesis and improve cardiac function in type 2 diabetic rats by up-regulating the expression of VEGF, p-VEGFR2, Ang1, and Tie2.