Danshen-Chuanxiong (DS-CX) was a classic herb pair commonly used to treat ischemic stroke. Nevertheless, the metabolic conversion and pharmacokinetic behavior of DS-CX in vivo remains unclear. This work aimed to reveal the in vivo metabolic behavior of DS-CX through establishing metabolic profiles and performing multicomponent pharmacokinetics analysis. The mass defect filtering (MDF) strategy integrated with UHPLC-QTOF-MS was firstly developed to characterize the metabolites of DS-CX in rats' plasma and brain. Moreover, a sensitive UHPLCQQQ-MS method was utilized to perform the comparative pharmacokinetic studies of major active ingredients of DS-CX in rats' plasma. A total of 111 exogenous compounds (29 prototype compounds and 82 metabolites) were identified in rat biological samples. The major metabolic pathways were hydroxylation, methylation, deoxidation, dehydration, hydrogenation, demethylation, hydrolysis, decarboxylation and glucuronidation binding reactions. According to the results of metabolites profiling, sixteen active compounds (8 phenolic acids, 5 phthalides and 3 tanshinones) were selected as markers for further comparative pharmacokinetics study. Compared with the oral administration of DS or CX alone, the higher C-max of salvianolic acid B, crytotanshinone and tanshinone IIA; the shorter T-max of lithospermic acid, rosmarinic acid and tanshinone IIA; as well as the higher AUC0(_ infinity )of ferulic acid, rosmarinic acid, salvianolic acid B, senkyunolide I and crytotanshinone, could be found after co-administration of DS-CX (P < 0.05). This study provided the overall knowledge of metabolites profiling of DS-CX in vivo, which would help to understand the effective material basis and promote the clinical application of DC-CX herb pair.

Human skin wounds primarily heal through reparative wound healing without pilosebaceous units or other appendages, rather than regenerative wound healing. Hair follicle (HF) regeneration is a significant challenge for skin wound healing. The effects and underlying mechanisms of Isaria cicadae Miquel rice fermentation extract (IMFRE) remain unclear, although it has anti-inflammatory, antioxidant, and reparative effects on oxidative damage in keratinocytes. We assessed the regenerative wound healing ability of IMFRE and its related molecular mechanisms through experimental validation and network pharmacology analysis. Our findings suggest that IMFRE could be an important potential solution for regenerative wound healing of skin hair follicle by utilizing the Hippo pathway regulatory mechanism. • IMFRE was found to significantly enhance the wound healing rate of mouse skin. • CK15 and CD34 were significantly increased by high-dose IMFRE intervention. • IMFRE could inhibit EGFR, GPCR, and Integrin expression.

ObjectiveTo investigate the role of quercetin-added pancreatic prescription food in regulating metabolic homeostasis in dogs.MethodsThe experimental dogs were divided into a control diet group and a prescription diet group. The control group was fed regular food, while the prescription group was fed pancreatic prescription food (3.9 g of quercetin was added in per 1 kg of food) for 8 weeks. Canine physical examination, complete blood count, and serum biochemical tests were conducted at 0 w, 4 w, and 8 w. Non-targeted metabolomics tests were performed using plasma samples at 0 w and 8 w.ResultsDogs that received a quercetin-added pancreatic diet supplemented with quercetin showed no changes in the body weight, fasting blood glucose, body condition score, the indexes of whole blood program of red blood cells, white blood cells and platelets, and most blood biochemical indexes, but increased lipase levels in plasma at 8 w. Quercetin significant improved in metabolic homeostasis, especially in fatty acid, amino acid, and bile acid metabolism. Untargeted metabolomics analysis revealed that quercetin activates ABC transport and arginine/proline pathways, suggesting potential benefits for pancreatitis in large animals, while maintaining comparable safety parameters.ConclusionsQuercetin-added prescription food enhances fatty acid and amino acid metabolism, demonstrating its potential to promote pancreatic function and sustain metabolic homeostasis.

Ethnopharmacological relevance: Qingfu Juanbi Tang (QFJBT), a novel and improved Chinese herbal formulation, has surged in recent years for its potential in the therapy of rheumatoid arthritis (RA). Anti-arthritic effects and underlying molecular mechanisms of QFJBT have increasingly become a focal point in research. Aim of the study: This study utilized network pharmacology, molecular docking, and experimental validation to elucidate effective ingredients and anti-arthritic mechanisms of QFJBT. Materials and methods: Targets associated with QFJBT and RA were identified from relevant databases and standardized using the Uniprot for gene nomenclature. A "QFJBT-ingredient-target network" and a "Venn diagram of QFJBT and RA targets" were created from the data. The overlap in the Venn diagram highlighted potential targets of QFJBT in the treatment of RA. These targets were subjected to PPI network, GO, and KEGG pathway analysis. The findings were subsequently confirmed through molecular docking and pharmacological experiments to propose the mechanism of action of QFJBT. Results: The study identified 236 active ingredients in QFJBT, with 120 predicted to be effective against RA. Molecular docking showed high binding affinity of key targets (JUN, PTGS2, and TNF-alpha) with bioactive compounds (rhein, sinomenine, calycosin, and paeoniflorin) of QFJBT. Pharmacodynamic evaluation demonstrated the effects of QFJBT at the dose of 4.56 g/kg in ameliorating symptoms of AIA rats and in reducing levels of JUN, PTGS2, and TNF-alpha in synovial tissues. In vitro studies further exhibited that rhein, paeoniflorin, sinomenine, calycosin, and QFJBT-containing serum significantly inhibited abnormal proliferation of RA fibroblast-like synoviocytes. Interestingly, rhein and paeoniflorin specifically decreased p-JUN/JUN expression and TNF-alpha release, respectively, while sinomenine and calycosin selectively increased PTGS2 expression. Consistently, QFJBT-containing serum demonstrated similar effects as those active ingredients identified in QFJBT did. Conclusions: QFJBT, QFJBT-containing serum, and its active ingredients (rhein, paeoniflorin, sinomenine, and calycosin) suppress inflammatory responses in RA. Anti-arthritic effects of QFJBT and its active ingredients are likely linked to their modulatory impact on identified hub targets.

The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.

Phellodendron chinense C.K.Schneid., Rutaceae, is a traditional Chinese medicine that is considered to have heat-clearing and detoxifying actions and is widely used for bacteriostatic and anti-inflammatory effects in clinical treatment and healthcare products. The aim of this study was to discover the pharmacological activity of P. chinense against inflammation. A rat model with carrageenan-induced inflammation model was used to systematically evaluate the anti-inflammatory effect of P. chinense extract on the degree of foot swelling and expression of NF-kB and myeloperoxidase. HPLC-QTOF/MS/MS was used to identify the components in the P. chinense extract. A bivariate correlation analysis was performed on the relative contents of components of serum from P. chinense–treated rats and the rates of inhibition of paw edema and COX-2 levels at different time points, and their correlation coefficients were calculated. The results showed that P. chinense significantly reduced the carrageenan-induced paw edema at 0.5 to 8 h and the levels of NF-κB and myeloperoxidase at 0.5 h, and the anti-inflammatory effects were similar to those of indomethacin. A total of 19 peaks were identified in total ion current chromatograms of the P. chinense extract, including 6 alkaloids, 11 phenolic acids, and 2 flavonoids. A total of 13 peaks were identified in the total ion current chromatograms of the serum of the rats with carrageenan-induced inflammation, including 3 alkaloids and 10 phenolic acids. Correlation coefficients above 0.5 with COX-2 or inhibitory actions on paw edema were found for phellodendrine, palmatine, berberine, quinic acid, caffeic acid, dihydrocaffeic acid sulphate, 3-O-feruloylquinic acid, 4-O-feruloylquinic acid, and 5-O-feruloylquinic acid. This result suggests that the main active components from P. chinense for anti-inflammation are alkaloids and phenolic acids such as quinic acid, caffeic acid, and their metabolites.

•Both compound discoverer platform and mass frontier software, a strategy for automatic finding and identification of chemical constituents, were used in this study.•A systematically chemical profile of JHT via UPLC-Q-TOF/MS was characterized, and the best compounds were selected for network pharmacological analysis.•A disease drug compound target network was constructed, and CG treatment candidate targets were identified.•The hub targets screened in the PPI network showed the active factors involved in the main biological functions on treatment CG of JHT.•The chronic gastritis model was established to observe the effect of JHT, and then the key targets obtained by network pharmacology were verified by ELISA.

Ethnopharmacological relevance: Shen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics. Aim of study: To compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. Materials and methods: A method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin, plantagoguanidinic acid, rhein, aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C-18 column (3.0 x 50 mm, 1.8 mu m) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. Results: The UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity (r >= 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4 similar to 13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (T-max <= 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC(0-t) and C-max of albiflorin, plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or C-max values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. Conclusions: A sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson’s trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1β, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats.

Cannabidiol (CBD), the most abundant nonpsychoactive constituent of Cannabis sativa plant, is a promising potential pharmacotherapy for the treatment of diabetes and associated comorbidities. Previous studies have shown the potential of CBD to prevent diabetes in mice, the precise mechanisms of action remain unclear. The purpose of this study was to explore the mechanism of CBD alleviating hyperglycemia. The results demonstrated that CBD reduced blood glucose of STZ-induced diabetic mice without causing hypoglycemia. To elucidate the possible mechanisms of CBD effect, RNA-seq analysis was performed on high glucose-induced human mesangial cells (HMCs). By cluster analysis of differential genes, the results showed that advanced glycation end products-receptor of advanced glycation endproducts (AGE-RAGE) pathway-related genes CCL2 and interleukin-1β (IL-1β) play an important role in the biological of CBD. The expression of CCL2 and IL-1β were significantly increased in HMCs. Whereas, treatment with CBD decreased the expression of CCL2 and IL-1β. In addition, CBD significantly reduced AGE-RAGE levels in high glucose-induced HMCs. Similar results were confirmed in diabetic mice. In conclusion, we discovered for the first time that CBD ameliorates hyperglycemia partly through AGE-RAGE mediated CCL2/IL-1β pathway.

The application of traditional Chinese medicines（TCMs） has a history of more than 2000 years, which have the characteristics of multi-component, multi-target, and high safety. Post-infectious cough（PIC）is a respiratory disease with high incidence. It belongs to subacute cough and accounts for as much as40%–50%. Cough is the main clinical manifestation of PIC. PIC seriously affects people’s life quality because of complex etiology, long-term course of disease, treatment difficulties and other characteristics.Western medicines are based on the principle of symptomatic treatment, so they are often difficult to control PIC fundamentally. These factors could due to that PIC is prolonged and unable to heal repeatedly.TCMs have obvious advantages in treating PIC, with accurate curative effects, less side effects and adverse reactions and are effective in improving PIC-related symptoms and indicators, enhancing patients’ life quality and reducing pain. TCMs, guided by holistic concept and syndrome differentiation, advocate determine treatment on the basis of pattern types, and have remarkable clinical treatment effects. As for TCMs etiology, pathogenesis and syndrome types of PIC, TCM scholars have not yet reached a unified standard. However, most of them think that wind pathogen can cause PIC alone, or it can be combined with other evils, which might be the main mechanism of PIC. This paper discusses the advantages and limitations of TCMs in PIC treatment from etiology, pathogenesis, distribution of syndrome types and treatment of TCMs. This article focuses on the treatment methods and pharmacodynamic material basis of wind pathogen, providing ideas in treating PIC of TCMs clinically and innovative drug development.

Background:Myocardial infarction (MI) is a severe clinical condition caused by decreased or complete cessation of blood flow to a portion of the myocardium. Aconite, the lateral roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for treatment of heart failure and related cardiac diseases. The present study is aimed at investigating the cardioprotective effect of aconite on isoproterenol- (ISO)- induced MI.Methods:The qualitative analysis of aqueous extracts from brained aconite (AEBA) was conducted by HPLC. A rat model of MI induced by ISO was established to examine the effects of AEBA. The cardiac function was assessed by echocardiography. The serum levels of SOD, CK-MB, cTnT, and cTnI were detected to estimate myocardial injury. The pathological changes of heart tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Masson's trichrome staining. The expressions of abnormal vascular remodeling and hypoxia-related components and the levels of inflammation-associated genes and proteins were detected by RT-qPCR, western blotting, and immunofluorescence.Results:The contents of benzoylaconine, benzoylmesaconine, benzoylhypacoitine, and hypaconitine in AEBA were 1.35 μg/g, 37.35 μg/g, 57.10 μg/g, and 2.46 μg/g, respectively. AEBA obviously improved heart function through promoting echocardiographic parameters, radial strain, and circumferential strain. The data of TTC staining, HE staining, and Masson's trichrome staining disclosed that AEBA could significantly reduce infarct size, inhibit inflammatory cell infiltration, and decrease the myocardial fibrosis. Moreover, AEBA distinctly suppressed the serum levels of SOD, MDA, CK-MB, cTnT, and cTnI in ISO-induced rats. The results of RT-qPCR indicated that AEBA inhibited the expressions of hypoxia- and inflammation-related genes, including VEGF, PKM2, GLUT-1, LDHA, TNF-α, IL-1β, IL-6, and COX2. In addition, the western blotting and immunofluorescence analyses further confirmed the results of RT-qPCR.Conclusion:In summary, our results indicate that the AEBA could improve ISO-induced myocardial infarction by promoting cardiac function, alleviating myocardial hypoxia, and inhibiting inflammatory response and fibrosis in heart tissue.

Background: Expression of nerve injury-induced protein 1 (Ninj1) is associated with several inflammatory disease. The soluble Ninj1 is an antiatherogenic protein. However, the role of plasma Ninj1 levels in patients with coronary artery disease (CAD) and its correlation with the severity of the disease remains unknown. This study investigated the association between plasma Ninj1 levels and the severity of coronary artery stenosis in patients with CAD. Methods: A total of 207 subjects were recruited in this study. Blood samples were obtained to assess plasma Ninj1 level using enzyme-linked immunosorbent assay. The SYNTAX score calculated from baseline coronary angiography results was used to evaluate the severity of coronary artery stenosis. The least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select the predictive factors. Then, a nomogram based on Ninj1 was constructed to predict the probability of CAD. Results: Patients with CAD had significantly higher plasma Ninj1 than those without CAD (P < 0.001). A positive correlation was established between the Ninj1 levels and SYNTAX score (R = 0.352, P < 0.001). The multivariate logistical regression analysis indicated that plasma Ninj1 (P = 0.024) was an independent predictor of CAD occurrence after adjustment for clinical risk factors. The nomogram based on plasma Ninj1 level demonstrated good calibration and discrimination with the area under the curve 0.814. Conclusions: Plasma Ninj1 levels are increased in patients with CAD. Elevated levels of plasma Ninj1 are associated with CAD and the severity of coronary stenosis. A nomogram based on plasma Ninj1 and sectional clinical characteristics exerted a predictive potential for CAD.

Drug microcrystal (MC) is an important category of long acting injections (LAIs), whose release profile is controlled mainly by particle size, crystal form, drug solubility, and other parameters. In this study, a polymeric H+ depot composed of alginate was combined with drug MC using ginkgolide B (GB) as model drug to reduce the initial burst release of the drugs with elevated solubility in body fluid. The parameters of GB MC preparation by precipitation, including stabilizer type and amount, phase volume ratio, and stirring rate were investigated. And the particle size/distribution, particle morphology, crystallinity, in vitro release of optimized GB MC were characterized. The in vivo dissolution retardation effect of acidified alginate (SAA) was first confirmed by live imaging using fluorescein as probe. And the pharmacokinetic profiles of different GB MC-polymer blends were investigated by UPLC-MS/MS. The prepared GB MC was spherical-like particles with a mean particle size of 5.863 mu m and a span value of 1.634. The crystallinity of GB MC was lowered by the precipitation process compared with that of the crude drug, which resulted in a faster in vitro dissolution with more than 90% of drugs dissolved in 20 min. When administered with SAA, an alginate amount-dependent reduction in C-max (1243.5 & PLUSMN; 281.4 ng/mL of GB-SAA, 1:5, 820.9 & PLUSMN; 84.0 ng/mL of GB-SAA, 1:10, 2850.9 & PLUSMN; 1059.3 ng/mL of GB alone and 2476.9 & PLUSMN; 396.4 ng/mL of GB-HPMC E5, 1:10) and prolongation in T-max (3.2 & PLUSMN; 1.1 h of GB-SAA, 1:5, 6.4 & PLUSMN; 2.2 h of GB-SAA, 1:10, 1.2 & PLUSMN; 0.45 h of GB alone and 1.4 & PLUSMN; 0.55 h of GB-HPMC E5, 1:10) was noticed, indicating the capability of polymeric H+ depot in controlling GB release in vivo. In conclusion, the polymeric H+ depot strategy influenced drug dissolution and outward drug diffusion sequentially to retard the initial burst release of drugs with elevated solubility in body fluid.

Introduction There is limited evidence regarding the effectiveness of drug-coated balloon (DCB) angioplasty in the percutaneous treatment of complex de novo ostial coronary lesions. This study primarily aimed to explore the feasibility and safety of this innovative approach for ostial lesions in the left anterior descending artery (LAD). Methods Patients treated with paclitaxel DCB or second-generation drug-eluting stents (DES) were retrospectively enrolled from two large centers. The primary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, target lesion revascularization (TLR), target vessel revascularization, and recurrent myocardial infarction related to target artery occlusion. Cox regression analysis was used to identify risk factors for MACE, and propensity score matching was performed to minimize selection bias. Results A total of 388 patients were included; among them, 52 were treated with paclitaxel DCB, and 336 with DES for ostial LAD lesions. Using propensity score matching, 49 patients were treated with DCB-only and 49 with the DES strategy. The average follow-up time was 12 months; subsequently, a non-significant decrease in MACE rate was observed in the DCB-only angioplasty treatment group (MACE: 6 vs. 6%, p = 1.0; TLR: 2 vs. 4%, p = 0.56). Cox regression analysis indicated that DCB-only angioplasty was not an independent risk factor for adverse events after adjusting for confounding risk factors (hazard ratio: 1.713, p = 0.43). Conclusion The use of the DCB-only approach is an innovative and optional strategy in the treatment of isolated ostial LAD disease. A further randomized trial is of necessity to confirm the feasibility and safety of drug-coated balloon-only angioplasty for LAD de novo ostial lesions.

Stroke is a major cause of death and disability throughout the world. A combination of Panax Ginseng and Ginkgo biloba extracts (CGGE) is an effective treatment for nervous system diseases, but the neuroprotective mechanism underlying CGGE remains unclear. Both network analysis and experimental research were employed to explore the potential mechanism of CGGE in treating ischemic stroke (IS). Network analysis identified a total number of 133 potential targets for 34 active ingredients and 239 IS-related targets. What’s more, several processes that might involve the regulation of CGGE against IS were identified, including long-term potentiation, cAMP signaling pathway, neurotrophin signaling pathway, and Nod-like receptor signaling pathway. Our studies in animal models suggested that CGGE could reduce inflammatory response by inhibiting the activity of Nod-like receptor, pyrin containing 3 (NLRP3) inflammasome, and maintain the balance of glutamate (Glu)/gamma-aminobutyric acid (GABA) via activating calmodulin-dependent protein kinase type Ⅳ (CAMK4)/cyclic AMP-responsive element-binding protein (CREB) pathway. These findings indicated the neuroprotective effects of CGGE, possibly improving neuroinflammation and excitotoxicity by regulating the NLRP3 inflammasome and CAMK4/CREB pathway.

Diabetes mellitus, a metabolic disease mainly characterized by hyperglycemia, is becoming a serious social health problem worldwide with growing prevalence. Many natural compounds have been found to be effective in the prevention and treatment of diabetes, with negligible toxic effects. Ferulic acid (FA), a phenolic compound commonly found in medicinal herbs and the daily diet, was proved to have several pharmacological effects such as antihyperglycemic, antihyperlipidemic and antioxidant actions, which are beneficial to the management of diabetes and its complications. Data from PubMed, EM-BASE, Web of Science and CNKI were searched with the keywords ferulic acid and diabetes mellitus. Finally, 28 articles were identified after literature screening, and the research progress of FA for the management of DM and its complications was summarized in the review, in order to provide references for further research and medical applications of FA.

Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT's anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT's therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.

Background: Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. Objective: Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear. Methods: In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively. Results: We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1β, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury. Conclusion: Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.