Dementia is a series of diseases with severe cognitive decline caused by brain diseases, that closely related to kidney deficiency in traditional Chinese medicine, including Alzheimer's disease (AD), dementia caused by cerebral stroke, vascular dementia (VAD) and so on. Dipsaci Radix is the dried root of Dipsacus asper Wall. ex Henry and its curative effects mainly focus on nourishing the liver and kidney, strengthening muscles and bones, as well as dredging blood vessels. The main chemical components of Dipsaci Radix are triterpenoid saponins and iridoid glycosides. In recent years, studies have found that Dipsaci Radix and its active compounds could ameliorate dementia symptoms via multiple targets and molecular mechanisms. In this review, we summarize the recent research progress of Dipsaci Radix in dementia prevention, which will provide reference for further exploration of its mechanism and application in the prevention and treatment of dementia.

Compared with the traditional two-dimensional (2D) monolayer culture, three-dimensional (3D) organoid can better simulate the physiological and pathological microenvironment of organs and tissues. In this study, 3D cardiac organoids were constructed using cardiac fibroblasts (CFs), cardiac myocytes (CMs) and endothelial cells (ECs) isolated from hearts of 1-3-day Sprague-Dawley (SD) neonatal rats. The experimental scheme was approved by the Experimental Animal Welfare and Ethics Committee of Tianjin University of Traditional Chinese Medicine and met the standards of experimental animal welfare and ethics. Optimal seeding cell density and culture time were determined by observing the sphere diameter and pulsation. The hierarchical structure and cardiac-like function were evaluated by fluorescence staining. The results showed that the cardiac-like microspheres constructed with cell number of 1×10⁴ still beated spontaneously even after 34 days in culture, and maintained characteristic cellular hierarchical structure. Then, based on these cardiac microspheres, a phenylephrine (PE)-induced cardiac hypertrophy model was established and evaluated by mitochondrial mass, intracellular Ca²⁺ concentration and mitochondrial membrane potential. Guanxinning Injection (GXNI) was tested to verify that the established model can be used for myocardial hypertrophy drug screen. The results showed that GXNI significantly reversed the enlargement of cardiac microsphere area and diameter, the increase of mitochondrial mass, intracellular Ca²⁺ concentration and the decrease of mitochondrial membrane potential caused by PE, and reduced upregulation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC). In conclusion, this study successfully established a 3D in vitro model of cardiac remodeling induced by cardiac hypertrophy. In this new system, cardiac microspheres not only have cardiac-like morphology and extracellular matrix components, but also exhibit spontaneous and rhythmic systolic and diastolic function. Therefore, the cardiac microsphere is an effective model to investigate the pathological mechanism of cardiac hypertrophy and screen related drugs.

Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of certain types of tumors. However, DOX have some serious side effects in the body after long-term use, especially acute and chronic cardiotoxicity. This study explored the protective effect of tanshinone I (Tan I) on acute cardiotoxicity induced by DOX and its underlying molecular mechanisms. In vivo and in vitro acute cardiotoxicity models were established by injecting DOX (6 mg·kg^-1, twice per week) into the tail vein of C57 mice and stimulating H9C2 cardiomyocytes with DOX. In in vivo experiments, Tan I (10 mg·kg^-1) was administered daily by oral 5 days before the tail vein injection, till the end of the experiment. The effects of Tan I on mice heart function, myocardial tissue morphology and serological indicators were detected. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Beijing University of Traditional Chinese Medicine. In in vitro experiments, the specific mechanism of Tan I against oxidative stress was further studied. Immunofluorescence was used to detect the expression of Nrf2 and its transcription into the nucleus. In addition, the levels of oxidative stress related proteins, protein kinase B (Akt), nuclear erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), were detected by Western blot. Finally, AutoDock software was used for molecular docking verification. The results showed that Tan I significantly improved cardiac function in mice. Meanwhile, the expression levels of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) in serum were decreased. Immunofluorescence results indicated that Tan I could increase Nrf2 expression level in H9C2 cells and promote Nrf2 entry into the nucleus. Western blot results also indicated that the levels of oxidative stress related proteins, P-Akt, Nrf2, HO-1 and NQO1 in DOX plus Tan I group were significantly increased compared with DOX group. These results suggest that Tan I can alleviate DOX-induced acute cardiotoxicity by inhibiting oxidative stress through up-regulating the Akt-Nrf2 pathway, thereby alleviating DOX-induced acute myocardial injury.

The blood-brain barrier (BBB) plays an important role in maintaining the homeostasis of the central nervous system. BBB is disrupted in many neurological disorders such as ischemic stroke and Alzheimer's disease. Traditional Chinese medicine has great potential to prevent ischemic stroke, but the lack of clinically relevant models has been a challenge. We adapted a BBB organoid model formed by human brain microvascular endothelial cells (HBMEC), human astrocytes (HA), and human brain vascular pericytes (HBVP), and established conditions for oxygen-glucose deprivation/reoxygenation (OGD/R) on the cell vitality, barrier permeability, as well as BBB signature marker expression. The protective effect of Guanxinning injection (GXNI) on OGD/R-induced BBB dysfunction was then investigated in the organoid model. The results showed that OGD/R decreased BBB organoid cell viability, increased permeability (leakage), decreased the level of tight junction proteins zonula occludens-1 (ZO-1), claudin-5, occludin and P-glycoprotein (P-gp). GXNI significantly prevented OGD/R-induced BBB disruption such as the decreased cell viability and increased permeability. This study provides a new human cell-derived 3D ischemic brain disease model for central nervous system-targeted drug research and development and demonstrates that a Chinese injection medicine GXNI effectively protects BBB dysfunction in vitro.

In this study, a research strategy integrating network pharmacology analysis and animal experimental validation was applied to explore the molecular mechanism of Chuanxiong Qingnao Granules (CXQN) in improving migraine headache (MH). All animal experiments were followed the regulation of the Laboratory Animal Ethics Committee of the China Academy of Chinese Medical Sciences. Based on the network pharmacology analysis, the 27 active ingredients and their corresponding 940 targets were obtained, and 99 common targets of CXQN in the treatment of MH were obtained by intersection, and tumor necrosis factor-α (TNF-α), interleukin (IL)-6, vascular endothelial growth factor A (VEGFA), IL-1β, brain-derived neurotrophic factor (BDNF) were screened out as hub targets. Enrichment analysis showed that the targets of CXQN in the treatment of MH were mainly involved in cyclic adenosine monophosphate (cAMP), hypoxia inducible factor-1 (HIF-1), phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathways. In addition, the experimental verification in the MH rat induced by nitroglycerin showed that the CXQN administrated groups could significantly improve the behavioral symptoms and regulate the level of vasoactive substances, and reduce the expression of TNF-α, IL-6, VEGFA, IL-1β, and BDNF at gene and protein levels. This study revealed the multi-component, multi-target, and multi-pathway characteristics of CXQN in the treatment of MH, and elucidated the potential mechanism of CXQN in the treatment of MH, laying a theoretical foundation and scientific basis for its clinical application in the treatment of MH diseases.

In this study, we investigated the pharmacological effect and possible molecular mechanism of higenamine (HG) in isoproterenol (ISO)-induced myocardial infarction (MI). All procedures were approved by the Institutional Animal Care and Use Committee of the Guangzhou University of Chinese Medicine. ISO was used to induce MI model in rats and H9c2 cells. The effects of HG on biomarkers and cardiac function in MI rats were evaluated by enzyme linked immunosorbent assay (ELISA), echocardiography and hematoxylin-eosin staining (HE). The expression of apoptosis and autophagy related proteins were detected by Western blot in myocardial tissue and H9c2 cells, as well as methyltransferase-like 3 (METTL3) and transcription factor EB (TFEB) protein expression. Molecular docking was used to evaluate the interaction between HG and METTL3. The results showed that HG significantly improved cardiac function and pathologic changes in ISO-induced MI, and inhibited the levels of MI-related biomarkers such as creatine kinase Mb (CK-MB), creatine kinase (CK) and lactate dehydrogenase (LDH). Mechanism studies showed that HG inhibited the expression of apoptosis-related proteins (Bax/Bcl2, caspase3, cleaved-caspase3). Interestingly, HG up-regulated the expression of autophagy related protein Beclin1, promoted autophagy flux, and decreased the ratio of light chain 3B-I/light chain 3B-II (LC-3B-I/LC-3B-II). Further studies found that HG increased the autophagy regulator TFEB and inhibited METTL3 expression. Molecular docking results showed that HG had a good interaction with METTL3. Taken together, HG has a potential anti-MI effect via regulating METTL3/TFEB signaling pathway-mediated autophagy.

In this study, network pharmacology research and animal experiments were used to predict and validate the potential targets of ShengMaiSan (SMS) in the treatment of diabetic cardiomyopathy. The active components of SMS were obtained through TCMSP and BATMAN databases. The potential targets of the active components and diabetic cardiomyopathy were predicted by Swiss Target Prediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to perform topological analysis to select the core action target. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. To validate the potential targets, a type I diabetic rat model which induced by intraperitoneal injection of streptozotocin (STZ) was prepared. Rats were divided into sham group, model group, SMS group and trimetazidine (TMZ) group. Left ventricular hemodynamics was detected after 4 weeks administrated of SMS or TMZ. Myocardial contraction and calcium transients were detected synchronously in cardiomyocytes, as well as sarcoplasmic reticulum calcium content, calcium leak level and ryanodine receptor 2 (RyR2) expression were detected. Based on network pharmacology, 1 288 targets of SMS, 1 066 targets of diabetic cardiomyopathy, and 180 overlapped targets were obtained. The 39 core targets were screened, and 159 pathways including calcium signaling pathway were screened by KEGG pathway analysis. According to the previous studies and focusing on the contractility of diabetic cardiomyopathy, this study was involved calcium signaling regulation pathway in the SMS protection mechanism. The results showed that, compared with sham group, the systolic function of left ventricular and myocardial cells were decreased, and the calcium transport was in disorder in model group; compared with model group, both SMS group and TMZ group increased the maximum systolic pressure of left ventricle and the maximum systolic rate of left ventricular contraction. In addition, SMS group and TMZ group increased the contraction amplitude of cardiomyocytes, decreased the diastolic calcium concentration, the sarcoplasmic reticulum calcium leak and decreased the phosphorylation level of RyR2. There was no significant difference between SMS and TMZ groups. In summary, SMS could reduce the calcium leak of the sarcoplasmic reticulum and enhance the myofilament sensitivity of calcium to increasing contractile function of diabetic rats. The animal welfare and experiment procedures of this study were in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences.

Autoimmune diseases (AID) are characterized by autoimmune disorder, as autologous tissue is attacked by the autoimmune system. It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly. Peroxisome proliferator-activated receptor γ (PPARγ) which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor. PPARγ combines with retinoid X receptor (RXR) to form heterodimer. When PPARγ is activated, the complex regulates gene expression by binding to a specific peroxisome proliferator response element (PPRE). In addition, PPARγ has diversified biological functions, playing important roles in regulating metabolism, controling inflammation, modulating glucose and lipid metabolism, ameliorating atherosclerosis, anti-tumor, and regulating immune response. However, recently researches indicate that PPARγ participates in the pathogenesis of AID. PPARγ plays key roles in regulating activation and polarization of macrophages, function of dendritic cells, proliferation and differentiation of T cells, and modulation of the function of related stromal cells. This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID, aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.

Leukotriene B₄ (LTB₄) is a proinflammatory lipid mediator that is synthesized by a number of inflammatory cells. Binding of LTB₄ to its receptor leukotriene B₄ receptor 1 (BLT1) can migrate neutrophils and macrophages to inflammatory sites through chemotaxis and up-regulation of adhesion molecules. Many researches have shown that LTB₄-BLT1 axis is related to the occurrence of autoimmune disorders and other inflammatory diseases. Receptor antagonists of LTB₄ are thus expected to be useful therapeutics for these diseases. In this review, we briefly describe the biological function of LTB₄ and summarize the preclinical and clinical developments of LTB₄ receptor antagonists.

Small interfering RNAs (siRNAs) are an emerging class of RNA interference (RNAi) therapeutics with unique pharmacokinetic properties. Five siRNA drugs based on two delivery systems have been approved, and an increasing number of siRNA drugs have already moved to the clinical study phase. Physiologically-based pharmacokinetic (PBPK) modeling is a useful tool and has been demonstrated to have wide ranging utility in drug development and regulatory review. However, PBPK modeling is still in its infancy in guiding the development of siRNA-based drugs in the context of its widespread use in small and large molecule areas. This article reviews the pharmacokinetic profiles of siRNA drugs, outlines the current state of PBPK model building in siRNA drug development, and describes the key parameters required for model building. This article provides insights into the future applications of PBPK models and for optimizing the key parameters when building the model for siRNA drug development.