The gut microbiota-brain axis constitutes a dynamic, bidirectional communication network that integrates neural, endocrine, immune, and metabolic pathways to regulate host physiology and behavior. Accumulating evidence indicates that disturbances within this axis have been consistently associated with metabolic, autoimmune, and neuropsychiatric disorders; however, much of the current evidence, particularly from human studies, remains largely correlative, and causal relationships are still under active investigation, highlighting its systemic relevance to health and disease. This review synthesizes current understanding of the structural and functional components of the gut microbiota-brain axis, including microbial community dynamics, neural signaling pathways, and key endocrine and immune mediators. We examine mechanistic insights into how microbial-derived metabolites influence brain function, cognition, mood regulation, stress responses, and disease pathogenesis. In addition, we discuss emerging therapeutic strategies targeting the gut microbiota-brain axis, including psychobiotics and fecal microbiota transplantation, while acknowledging dietary approaches, such as prebiotic supplementation, fiber-rich diets, and fermented food consumption, as complementary strategies that modulate microbiota composition that may indirectly support gut-brain axis function. By integrating mechanistic, clinical, and translational perspectives, this review aims to clarify current knowledge gaps and highlight future directions for leveraging the gut microbiota-brain axis in personalized approaches to neuropsychiatric disease management.

BACKGROUND:Myocardial fibrosis is a major pathological process in the progression of cardiovascular diseases, and its inhibition is crucial for maintaining cardiac function. Shenfu injection (SFI), a traditional Chinese medicine formulation derived from Panax ginseng and aconitum, is used clinically to treat heart failure. However, the key pathological processes and the potential mechanism of its anti-myocardial fibrosis effects are still largely unexplored. PURPOSE:The purpose of this study is to elucidate the treatment effect, key pathological targets, and molecular mechanisms of SFI in myocardial fibrosis. METHODS:In this study, we assessed the anti-myocardial fibrosis efficacy of SFI in vivo and in vitro using a transverse aortic constriction (TAC)-induced mouse model and TGFβ1-stimulated cardiac fibroblasts. Transcriptomic sequencing was performed to identify the key pathological processes and potential molecular mechanisms underlying the effects of SFI, which were then validated by experiments. In addition, the PI3K inhibitor Ly294002 was used to further explore the mechanisms of SFI inhibiting the glycolysis of cardiac fibroblasts. RESULTS:The results showed that SFI treatment significantly improved cardiac function and reduced myocardial inflammation, hypertrophy, and interstitial fibrosis in TAC mice. In vitro, SFI suppressed abnormal proliferation, migration, and activation of TGFβ1-induced cardiac fibroblasts, and downregulated fibrotic markers (collagen I, collagen III, and α-SMA). Transcriptomic analysis revealed that SFI exerts its antifibrotic effects might be related to modulating biological processes of glucose metabolism and the PI3K-AKT and HIF-1 signaling pathways. These findings further confirmed in vitro and in vivo experiments that SFI reduced the expression of key glycolytic enzymes and downregulated the expression of p-PI3K, p-AKT, and HIF-1α proteins. Additionally, the combined treatment with SFI and LY294002 more effectively suppressed the expression of p-AKT, HIF-1α, and downstream glycolytic enzymes than either agent alone, suggesting that the anti-myocardial fibrosis effect of SFI may be associated with its inhibition of glycolysis in cardiac fibroblasts via regulation of the PI3K-AKT/HIF-1 signaling pathway. CONCLUSION:Our results suggest that SFI attenuates myocardial fibrosis in TAC-induced heart failure mice by inhibiting glycolysis through the PI3K-AKT/HIF-1α signaling pathway.

Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.

脓毒症是由宿主对感染的反应失调而引起的严重器官功能障碍综合征,该病具有高发病率和高死亡率的特点.脓毒症会严重损害上皮组织,对肠上皮的影响最为严重.反之,肠屏障受损会导致肠菌及内毒素易位进而加剧脓毒症.鉴于目前没有系统深入的关于脓毒症肠屏障功能障碍机制的文献报道,因此,本文从肠上皮细胞、炎症、免疫状态、微循环、凝血功能、肠道酶反应、肠道菌群及短链脂肪酸(SCFAs)等角度系统深入地总结了近10年脓毒症肠屏障功能障碍的分子机制及肠屏障功能障碍在脓毒症中的作用,以期为临床及药物开发从保护肠屏障入手治疗脓毒症提供理论依据及新的治疗靶点.

Stroke is a common central nervous system disease in clinical practice. Stroke patients often have infectious complications, such as pneumonia and infections of the urinary tract and gastrointestinal tract. Although it has been shown that translocation of the host gut microbiota to the lungs and immune dysfunction plays a vital role in the development of infection after ischemic stroke, the occurrence and mechanism of pulmonary infection at different time points after hemorrhagic cerebral remain unclear. In this study, the changes in the immune system and intestinal barrier function in mice during disease development were investigated at 1 day (M 1 d), 3 days (M 3 d) and 7 days (M 7 d) following hemorrhagic stroke to clarify the mechanism of secondary pulmonary infection. The experimental results revealed that after hemorrhagic stroke, model mice showed increased brain damage from day 1 to 3, followed by a trend of brain recovery from day 3 to 7 . After hemorrhagic stroke, the immune system was disturbed in model mice. Significant immunosuppression of the peripheral immune system was observed in the M 3 d group but improved in the M 7 d group. Staining of lung tissues with hematoxylin and eosin (H&E) and for inflammatory factors revealed considerable disease and immune disorders in the M 7 d group. Stroke seriously impaired intestinal barrier function in mice and significantly changed the small intestine structure. From 1 to 7 d after stroke, intestinal permeability was increased, whereas the levels of markers for intestinal tight junctions, mucus and immunoglobulin A were decreased. Analysis based on 16S rRNA suggested that the microflora in the lung and ileum was significantly altered after stroke. The composition of microflora in lung and ileum tissue was similar in the M 7d group, suggesting that intestinal bacteria had migrated to lung tissue and caused lung infection at this time point after hemorrhagic stroke. In stroke mice, the aggravation of intestinal barrier dysfunction and immune disorders after intracerebral hemorrhage, promoted the migration of enteric bacteria, and increased the risk of pneumonia poststroke. Our findings reveal the dynamic process of infection after hemorrhagic stroke and provide clues for the optimal timing of intervention for secondary pulmonary infection in stroke patients.

Central nervous system injuries may lead to the disorders of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and enteric nervous system. These effects then cause the changes in the intestinal microenvironment, such as a disordered intestinal immune system as well as alterations of intestinal bacteria. Ultimately, this leads to an increase in intestinal permeability. Inflammatory factors produced by the interactions between intestinal neurons and immune cells as well as the secretions and metabolites of intestinal flora can then migrate through the intestinal barrier, which will aggravate any peripheral inflammation and the central nervous system injury. The brain-gut-microbiota axis is a complex system that plays a crucial role in the occurrence and development of central nervous system diseases. It may also increase the consequences of preventative treatment. In this context, here we have summarized the factors that can lead to the increased intestinal permeability and some of the possible outcomes.

中药质量控制是其现代化和全球化发展的前提,目前基于化学基准和效应基准的双重质量控制已经得到了国内外学者的共识.人们通过大量的研究已经从药材基源、药材性状及显微特征、物质基础以及药效作用等方面入手,建立了一系列行之有效的质量控制方法.并且在基于化学基准的质量控制研究方面,已经在指纹图谱、DNA条形码、等效成分群、质量标志物等研究方面取得了丰硕的成果.然而由于中药在生长年限、产地、生长环境以及制剂工艺等各种影响因素的差异,导致基于化学基准的中药质量控制仍难以全面反映中药质量.目前仍存在单纯基于化学基准的中药质量标准如何准确体现中药质量的争议,如中药质量标准中所选择的指标性成分难以全面反映中药或其复方中全部成分,并且指标成分与中药效应(有效性和安全性)的关联性尚不明确.鉴于机体多信号通路级联反应及串扰所形成的复杂信号网络,以及中药多成分多靶点的协同调控作用,可能存在不同成分调控同一信号或网络的现象和在一定范围内某些化学成分量的变化并不足以引起相关信号网络效应变化的情况.因此,基于效应基准的中药质量控制可能成为中药质量标准的有益补充,本文提出了基于效应基准的中药质量生物标志物(Q-biomarker)研究策略,以期为中药质量控制研究提供一定方法学参考.

The salvianolate lyophilized injection (SLI) has been widely used for the treatment of acute cerebral infarction; however, the molecular mechanism of how it strengthens blood brain barrier (BBB) function is not well understood. Here, we investigated the effects of SLI on BBB function in bEnd.3 cells as well as in rats. In oxygen glucose deprivation/reoxygenation (OGD/R)-damaged bEnd.3 cells, SLI increased transepithelial electrical resistance and decreased sodium fluorescein flux. SLI-treated cells showed increased expression of tight junction proteins, including Zonula occludens-1 (ZO-1), Claudin-5 and Occludin. Furthermore, SLI led to the decrease of phosphorylation of ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of SLI on barrier function were abolished in cells in which ERK1/2 and Ak signaling were inhibited. Moreover, in MCAO model rats, SLI effectively alleviated brain leakage of Evans blue, increased brain tissue ZO-1 expression and inhibited phosphorylation of ERK1/2 and Akt. Overall, these data suggest that SLI strengthens BBB function was interrelated ERK1/2 and Akt signaling pathways in cerebral vascular diseases.

•The incidence and treatment of infection after CNS injury.•Mechanism of intestinal bacterial translocation mediated infection after CNS injury.•Interaction of SNS, PNS and HPA axis in CNS injury induced immunodeficiency and infection.•Pharmacological intervention and immunomodulatory therapies the CNS injury induced infection.

目的 探究玄归滴丸对不同机能状态小鼠胃肠运动和家兔离体肠管运动的影响,为其治疗平滑肌痉挛引起的腹痛提供实验基础.方法 选择小鼠肠推进实验方法,利用新斯的明、阿托品等药物复制小鼠胃肠运动功能障碍模型,测定各组小鼠的胃残留率和小肠推进率;采用家兔离体肠管平滑肌实验,考察并记录给予不同受试药物后家兔离体肠管的肌张力变化.结果 玄归滴丸临床等效4倍剂量、8倍剂量使正常小鼠胃残留率升高(P＜ 0.05,P＜ 0.01),小肠推进率降低(P＜0.05);与正常对照组比较,新斯的明致小鼠胃肠运动亢进,给予玄归滴丸4倍剂量、8倍剂量组后能够明显地抑制胃肠运动,增加胃残留率(P＜ 0.05,P＜ 0.01),降低小肠推进率(P＜0.01);与正常对照组比较,阿托品可致胃肠运动抑制,给予玄归滴丸4倍剂量、8倍剂量组后可以进一步抑制胃肠运动,进一步增加胃残留率(P＜ 0.05,P＜ 0.01),降低小肠推进率(P＜0.05,P＜ 0.01);家兔离体肠管平滑肌实验结果也进一步表明,玄归滴丸使家兔离体肠管的肌张力降低.结论 玄归滴丸对胃肠运动具有一定的抑制作用,对痉挛性胃肠道疾病具有潜在的治疗效果.

Insulin resistance (IR) is a vital hallmark of type 2 diabetes mellitus, which is characterized by an impaired ability of insulin to promote glucose uptake and utilization. Lipid deposition is closely associated with impaired insulin sensitivity. PPARγ plays an important role in glucose homeostasis, adipocyte differentiation, and insulin sensitivity. Likewise, DGAT2 also exerts a crucial role in integrating carbohydrate and lipid metabolism in the liver. The present study is aimed at evaluating a Chinese medicinal formula, Tangduqing granules (TDQ), with multifaceted actions against lipid and glucose metabolism disorder and IR of type 2 diabetes. An animal model of type 2 diabetes was developed by high-fat diet feeding plus low-dose streptozotocin injection. After oral administration of TDQ for 5 weeks, the effects on glucose and lipid metabolism and the underlying mechanism were evaluated by biochemical, histological, RT-PCR, and western blotting methods. The results showed that TDQ decreased fasting blood glucose, ameliorated glucose tolerance, and improved IR. Besides, TDQ regulated hyperlipidemia symptoms, decreased serum lipid levels and liver TG, and reduced hepatic steatosis in a type 2 diabetic rat model. Furthermore, TDQ reversed diabetes-induced decrease in the mRNA and protein expression of PPARγ and elevation in the mRNA and protein levels of DGAT2 in the liver. In addition, we showed that interference of TDQ ameliorated palmitate-induced glucose and lipid metabolic abnormalities in HepG2 cells. TDQ are, therefore, a potential Chinese medicinal formula that relieves IR and lipid metabolism disorder might be through promotion of PPARγ and decrease of DGAT2 expression.

Cor pulmonale is characterized by severe right ventricular dysfunction caused by lung disease, particularly chronic obstructive pulmonary disease, which can lead to pulmonary hypertension. Our previous study has demonstrated that Fuzi and Beimu compatibility (FBC), a traditional TCM compatibility taboo, improves lung function in early-stage of pulmonary hypertension through the synergistic action of β-ARs signals. However, FBC increases cardiotoxicity with prolonged treatment and disease progression. Considering that the compatibility environment influences the exertion of the medicine, we selected ginseng for coordinating the compatibility environment to improve the security and extend the therapeutic time window of FBC. Monocrotaline-induced cor pulmonale rats were treated with FBC, ginseng, or ginseng combined with FBC (G/FBC). Then, the pulmonary and cardiac functions of the rats were examined to evaluate the toxicity and efficacy of the treatments. The crosstalk between PKA and Epac pathways was also studied. Results showed that G/FBC ameliorated lung function similar to or even better than FBC treatment did. Furthermore, G/FBC treatment attenuated FBC-induced cardiotoxicity, which significantly restored cardiac dysfunction and clearly decreased myocardial enzymes and apoptosis. The βAR-Gs-PKA/CaMKII pathway was inhibited and the Epac1/ERK1/2 axis was activated in G/FBC group. These findings indicate that ginseng compatibility environment could improve pulmonary function and attenuate cardiotoxicity in cor pulmonale via the coordinated crosstalk of PKA and Epac pathways, implying that ginseng could be used to prevent detrimental cardiotoxicity in cor pulmonale treatment.

肠黏膜屏障是指肠黏膜阻止肠腔内有害物质如致病微生物、多种生物大分子和抗原进入血液循环而形成的屏障,以维护人体健康.正常菌群在人体某一特定部位黏附、定植和繁殖,形成一层“菌膜屏障”,能够抵抗外源微生物定植,对机体组织免受外来病原菌的侵袭具有重要作用.肠黏膜在休克、缺血、胰腺炎等情况下,其通透性增高引起细菌和内毒素移位、促炎因子释放,加重原发疾病的发生,激发炎症反应,引发胰岛素抵抗、中枢神经系统损伤,甚至诱发多脏器功能衰竭等.中药在治疗肠黏膜屏障功能紊乱疾病方面具有明确的优势,但中药药效成分大多生物利用度低,中药经口服后可先与肠道菌群接触并发生相互作用,进而调节人体相关机能.从肠黏膜机械屏障、免疫屏障、微生物屏障及化学屏障4个角度,系统总结了中药通过调控肠道菌群改善肠黏膜屏障的作用,以期对中药调控肠道菌群治疗肠黏膜屏障功能紊乱相关疾病的研究提供一定线索.

Diabetes mellitus is a metabolic disease often accompanied by a series of complications, such as diabetic nephropathy, retinopathy, and diabetic foot. The survival time of diabetics has been significantly prolonged due to advancements in medicine. However, the prolonged survival time for diabetics can increase the prevalence of diabetic central nervous system disease. Diabetic encephalopathy (DE) has become one of the main complications of the disease, and the main clinical manifestation of DE is cognitive dysfunction. However, the typical morphological and pathological characteristics of the brain in DE are rarely systematically reported. Thus, this phenomenon severely restricts the diagnosis and treatment of DE. This article presents a description of the pathology characteristics of DE, including atrophy of the brain (gray matter, white matter, and hippocampus), changes in cerebrovascular morphology and function, impairment of synaptic plasticity, and dysfunction of neuroglia. In addition, abnormalities in the glymphatic clearance system of the brain are closely related to the progression of DE. A review of typical brain morphological and pathological characteristics would aid in the diagnosis and treatment of DE.

[Objective]To determine the effect of of Radix Aconiti and Rhizoma Bletillae separately and combined on carrageenan-induced mechanical hyperalgesia on rat.[Methods]Thirty-four male SD rats were randomly divided into 5 groups:Normal group(n=4),Model group(n=6),Radix Aconiti group(n=8),Rhizoma Bletillae group(n=8)and Radix Aconiti-Rhizoma Bletillae combined group(n=8)0.1 mL carrageenan solution was injected into the left hind paw of all rats except the normal group. The 5 groups were separately dosed with saline, saline, Radix Aconiti extraction(2.25 mg/kg),Rhizoma Bletillae extraction(2.25 mg/kg)and Radix Aconiti-Rhizoma Bletillae extractions combined(2.25 mg/kg+2.25 mg/kg)1 h post the carrageenan injection.Mechanical hyperalgesia was measured by the paw-pressure test(analgesimeter,Ugo Basile,Italy),Blood flow was measured by Laser Doppler Flowmetry at 1 h and 3 h post the test reagent dosed.[Results]Single dosing of Radix Aconiti extraction(2.25 mg/kg)has significant analgesic effects. Single dosing of Rhizoma Bletillae extraction(2.25 mg/kg)can decreased the blood flow of the inflammation paw.Radix Aconiti-Rhizoma Bletillae extractions combined(2.25 mg/kg+2.25 mg/kg)has analgesic effects and can decreased the blood flow of the inflammation paw. [Conclusion]Radix Aconiti extraction has analgesic effects and Rhizoma Bletillae extraction can decreased the blood flow. When they were dosed combined, don't influenced the other.

Objective: Fuzi Banxia is one of eighteen antagonisms, previous studies have shown that the incompatibility could play special effects in the specific condition of diseases and appropriate compatible environment. The present study aims to evaluate the toxicity-efficacy of ginseng combined with Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale and to explore its mechanism. Methods: Monocrotaline (MCT)-induced cor pulmonale were used in this study. Ultra high-resolution small animal ultrasound real-time imaging system and the right heart catheterization were used to estimate cardiac function. Semi automatic biochemical analyzer was used to test myocardial enzyme LDH, CK, and CK-MB in serum. The heart tissues were stained with HE, and TUNEL assay was used to assess the pathomorphological changes and myocardial apoptosis. The expression of hypertrophy and apoptosis associated genes: ANP, BNP, beta-MHC, Bax, and Bcl-2 in the right ventricle were determined by RT-PCR. Results: Fuzi Banxia combined with ginseng obviously attenuated mortality, decreased RVHI, and increased cardiac index; RVSP and mPAP were significantly reduced, and EF and FS were raised obviously; Myocardial enzymes LDH, CK, and CK-MB were pronounced attenuated; heart diameter reduced, right ventricular dilatation was significantly decreased, inflammatory cell infiltration notably reduced, and cardiac apoptosis rate was decreased obviously. Meanwhile, the expression of hypertrophy-related ANP, BNP, and beta-MHC mRNA were up-regulated, the expression of apoptosis-related Bax mRNA was down-regulated, and the expression of anti-apoptosis-related Bcl-2 mRNA and Bcl-2/Bax ratio were up-regulated. Conclusion: Ginseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes, and thus delay the occurrence and development of heart failure. (C) 2018 Tianjin Press of Chinese Herbal Medicines. Published by Elsevier B.V. All rights reserved.