ETHNOPHARMACOLOGICAL RELEVANCEHeart failure with preserved ejection fraction (HFpEF) has emerged as a condition with high incidence and mortality rates in recent years. Dengzhan Shengmai capsule (DZSMC) is a Chinese patent medicine based on the classic recipe "Shengmai powder". The relevant Chinese medicine ratio of Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A.Mey., Schisandra chinensis (Turcz.) Baill., and Ophiopogon japonicus (Thunb.) Ker Gawl. Is 30 : 6: 6 : 11. Traditional Chinese medicine (TCM) is being increasingly explored as a safe and effective treatment modality for HFpEF. Clinical studies have shown that DZSMCs can effectively treat heart failure, however, the mechanism of action of DZSMCs in the treatment of HFpEF are still not clear.AIM OF THE STUDYTo investigate the efficacy and underlying mechanisms of Dengzhan Shengmai capsule (DZSMC), in the treatment of HFpEF by focusing on its ability to treat microvascular inflammation.MATERIALS AND METHODSFirst, the efficacy of DZSMCs against HFpEF was predicted by network pharmacology. After 3 days of adaptive feeding in SPF-grade polypropylene cages, the mice in the Model group, DZSMC group, and Captopli group underwent single kidney resection, and micropumps were implanted in their backs for continuous infusion of aldosterone at a rate of 0.3 μg/h for 4 weeks. Moreover, the mice were given DZSMCs or Captopli via oral gavage for four weeks. Overall, cardiac function was evaluated in mice, and cardiac ultrasound and blood biochemical indices were evaluated in HFpEF mice.RESULTSDZSMCs can ameliorate myocardial hypertrophy and cardiomyocyte damage caused by excessive myocardial stress, ultimately mitigating long-term cardiac impairment; it aids in the restoration of myocardial fibre proliferation and enhances mitochondrial morphology and function. In a murine model of ventricular hypertrophy and left ventricular dysfunction, which are indicative of cardiac insufficiency, the administration of DZSMCs resulted in notable improvements. Echocardiographic and overall assessments of cardiac function revealed a reduction in cardiac dysfunction and ventricular hypertrophy post-DZSMC intervention. Moreover, intervention with DZSMCs led to a reduction in the serum levels of several markers associated with chronic systemic inflammation, such as sST2, IL1RL1, CRP, and IL-6. Simultaneously, the levels of indicators of microvascular inflammation, including VCAM and E-SELECTIN, also decreased following DZSMC intervention. These findings suggest the potential multifaceted impact of DZSMCs in alleviating cardiac abnormalities, mitigating systemic inflammation, and reducing microvascular inflammatory markers, highlighting their promising therapeutic role in managing myocardial health.CONCLUSIONSThese results provide novel evidence that DZSMCs improve HFpEF by regulating microvascular inflammation.

2024-03-01·Journal of Pharmaceutical Analysis

Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Article

作者: Liu, Wei ; Wang, Fushun ; Zhang, Xiaxia ; Li, Tong ; Yang, Caishui ; Zhao, Binbin ; Wang, Linshuang ; Chen, Qingjie ; Wang, Ping ; Li, Zefei ; Long, Qinghua ; Ma, Tao ; Zhang, Zhanjun ; Wei, Dongfeng ; Chen, Linlin

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ₄₂-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ₄₂-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

2023-07-01·Phytomedicine

Dengzhan Shengmai capsule attenuates cardiac fibrosis in post-myocardial infarction rats by regulating LTBP2 and TGF-β1/Smad3 pathway

Article

作者: Xi, Yujie ; Wang, Menglan ; Wang, Maolin ; Xu, He ; Yang, Hongjun ; Zhao, Jie

BACKGROUNDCardiac fibrosis contributes to myocardial remodeling after myocardial infarction (MI), which may facilitate the progression to end-stage heart failure. Dengzhan Shengmai capsule (DZSMC), a traditional Chinese formula derived from Shen-mai powder, has shown remarkable therapeutic effects against cardiovascular diseases. However, the effect of DZSMC on cardiac fibrosis and its potential mechanism are ill-defined.PURPOSETo evaluate the effects of DZSMC on cardiac fibrosis after myocardial infarction (MI) and investigate its underlying mechanism.METHODIn vivo, MI rat models were established by permanently ligation of left anterior descending coronary arteries (LAD) and then were intragastrically treated with DZSMC or captopril for 5 weeks. Ex vivo, an everted intestinal sac model was used to study the intestinal absorption components of DZSMC, which were further identified through an ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method. In vitro, a myocardium fibrotic model was constructed by stimulating primary cardiac fibroblasts (CFs) with 1 μM Ang II. Subsequently, the absorbent solution of DZSMC from the intestinal sac was performed on the cell models to further elucidate its anti-fibrotic effects and underling mechanism.RESULTSIn vivo results showed that DZSMC significantly improved cardiac function and inhibited pathological myocardial fibrosis in post-MI rats in a dose dependent manner. Histological analysis and western blot results demonstrated that DZSMC treatment significantly reduced the expression of extracellular matrix (ECM)-related proteins, including LTBP2, TGF-βR1, Smad3 and pSmad3, in myocardial tissue of MI rats. Ex vivo results showed that 18 absorbed components were identified, mainly consisting of phenolic acids, flavonoids and lignans, which may be responsible for the anti-fibrotic effects. Further in vitro results validated that DZSMC attenuated myocardial fibrosis by suppressing the expression of LTBP2, TGF-β1 and pSmad3.CONCLUSIONDZSMC ameliorates cardiac function and alleviates cardiac fibrosis, which may be mediated by inhibition of CFs activation and reduction of excessive ECM deposition via LTBP2 and TGF-β1/Smad3 pathways.

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适应症	最高研发状态	国家/地区	公司	日期
动脉粥样硬化	临床3期	中国	大道隆达（北京）医药科技发展有限公司	2013-06-03
大脑梗塞	临床3期	中国	大道隆达（北京）医药科技发展有限公司	2013-06-03