作者机构：
[Ma, Xinwei; Meng, Mingfang; Xie, Xi] Heilongjiang Univ Tradit Chinese Med, Clin Med Coll 1, Harbin, Peoples R China.;[Gao, X; Lou, Hongjun; Gao, Xi] Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 1, Harbin 150040, Heilongjiang, Peoples R China.;[Shi, Ye; Gan, Guang] Hunan Univ Tradit Chinese Med, Coll Integrated Chinese & Western Med, Changsha, Peoples R China.;[Deng, Hanqing] Hunan Univ Tradit Chinese Med, Clin Med Coll 1, Changsha, Peoples R China.
通讯机构：
[Gao, X ] H;Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 1, Harbin 150040, Heilongjiang, Peoples R China.
关键词：
chronic kidney disease;Liuwei Dihuanng pill;mechanism of action;molecular docking;network pharmacology
摘要：
BACKGROUND: Chronic kidney disease (CKD) is a progressive disease that poses a huge economic burden to society. Liuwei Dihuanng pill is an effective treatment for chronic kidney disease, but its treatment mechanism is unclear. The rapid development of network pharmacology has provided new strategies for studying Chinese medicine. METHOD: The traditional Chinese medicine systems pharmacology database and analysis platform was used to obtain the bioactive components and targets of Liuwei Dihuanng pill. The sources for the CKD-related targets were then obtained from the Genecards, OMIM, TTD, and DisGeNET databases. R was used to identify the intersecting genes for Liuwei Dihuang pill and CKD-related targets. Analysis of protein-protein interactions (PPI) was performed using STRING, and PPI networks and drug-component-target networks were constructed using Cytoscape software. Kyoto encyclopedia of genes and genomes pathway and gene ontology enrichment analyses were performed using R. Finally, molecular docking was performed to determine the binding activity between bioactive components and the targets. RESULT: After screening and data de-duplication of 74 active components, 209 drug targets, and 14,794 disease targets, a total of 204 drug-disease targets were acquired. Subsequently, a drug-component-target network and PPI network were established. The primary components of Liuwei Dihuang pill included quercetin, stigmasterol, kaempferol, beta-sitosterol, tetrahydroalstonine, kadsurenone, hederagenin, hancinone C, diosgenin, and sitosterol. In addition, JUN, AKT1, TP53, RELA, MAPK1, FOS, TNF, IL6, ESR1, and RXRA were identified as the main targets. Gene ontology function enrichment analysis revealed that these targets were involved in reactive oxygen species metabolic processes, responses to metal ions and to chemical stimuli, G protein-coupled amine receptor activity, and nuclear factor receptor activity. Kyoto encyclopedia of genes and genomes enrichment analysis showed that these targets were involved in the AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. Molecular docking results indicated good binding activity between the core targets and core components. CONCLUSION: The potential mechanism of Liuwei Dihuanng pill in the treatment of CKD was preliminarily discussed in this study, providing a theoretical basis and evidence for further experimental research.
摘要：
<正>《灵枢·岁露论》曰：“人与天地相参，与日月相应也。”古人在这种“天人合一”的哲学思维影响下，将疾病的发生、治疗以及预防同自然规律紧紧联系起来，强调遵循自然运行规律。《黄帝内经》中还有很多关于节律变化的记载，尤以日节律、四时节律及生长节律对人体影响最大。中医认为，遵循“时序”可以规避外界“贼邪”，失于“时序”则是疾病发生的重要原因[1]。男性迟发性性腺功能减退症(Late-Onset Hypogonadism in male,LOH)的发生与血清生物活性睾酮随着年龄增加减少相关[2]，而睾酮的分泌受到生物节律的调控，具有明显的节律变化。我们认为天癸与睾酮在分泌节律及生理作用方面存在诸多一致性，提出“天癸睾酮”相关论[3]，构建起LOH中西医认识的桥梁。结合LOH“肾虚”“肝郁”的中医病机[4-5]，探讨节律因素在LOH发病过程中的作用，以及节律变化对LOH治疗的指导价值，不仅可以丰富LOH中医发病学，还将为LOH的治疗提供新思路。
摘要：
BACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work. OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH. METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25mg/kg, 50mg/kg, and 100mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri‑hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits. RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage. CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.
摘要：
Background: Evidence indicates that chronic stress promotes progression of colorectal liver me-tastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-alpha) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-beta 1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.
作者机构：
[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Song, ZY; Luo, Rongsiqing; He, Chunxiang; He, Jiawei; Xia, Xiaofang; Lin, Fan; Hou, Mirong; Cheng, SW; Pan, Ying] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Song, ZY; Luo, Rongsiqing; He, Chunxiang; He, Jiawei; Cheng, SW] Hunan Univ Chinese Med, Coll integrated Chinese & western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan; Song, ZY] Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.;[He, Pan] Res Inst Zhong Nan Grain & Oil Foods, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Song, ZY ; Cheng, SW] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll integrated Chinese & western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.
摘要：
The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.
作者机构：
[Lu, Baowei; Li, Bonan; Sheng, Wen; Wang, Neng; Liu, Lumei; Ding, Jin; He, Qinghu; Zhong, Zixuan] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ding, Jin] Guangzhou Univ Tradit Chinese Med, Affiliated Baoan Hosp Tradit Chinese Med, Clin Med Coll 7, Dept Androl Clin, Shenzhen, Peoples R China.;[Lu, Baowei; Li, Bonan; Sheng, Wen; Wang, Neng; Liu, Lumei; Ding, Jin; He, Qinghu; Zhong, Zixuan] Hunan Univ Chinese Med, Androl Lab, Changsha, Peoples R China.;[He, Qinghu] Hunan Univ Med, Huaihua, Peoples R China.
通讯机构：
[Wen Sheng; Qinghu He] C;College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Hunan University of Medicine, Huaihua, China
摘要：
Context Guilu-Erxian-Glue (GLEXG) is a traditional Chinese formula used to improve male reproductive dysfunction. Objective To investigate the ferroptosis resistance of GLEXG in the improvement of semen quality in the oligoasthenospermia (OAS) rat model. Materials and methods Male Sprague-Dawley (SD) rats were administered Tripterygium wilfordii polyglycoside, a compound extracted from Tripterygium wilfordii Hook F. (Celastraceae), at a dose of 40 mg/kg/day, to establish an OAS model. Fifty-four SD rats were randomly divided into six groups: sham, model, low-dose GLEXG (GLEXGL, 0.25 g/kg/day), moderate-dose GLEXG (GLEXGM, 0.50 g/kg/day), high-dose GLEXG (GLEXGH, 1.00 g/kg/day) and vitamin E (0.01 g/kg/day) group. The semen quality, structure and function of sperm mitochondria, histopathology, levels of oxidative stress and iron, and mRNA levels and protein expression in the Keap1/Nrf2/GPX4 pathway, were analyzed. Results Compared with the model group, GLEXGH significantly improved sperm concentration (35.73 +/- 15.42 vs. 17.40 +/- 4.12, p < 0.05) and motility (58.59 +/- 11.06 vs. 28.59 +/- 9.42, p < 0.001), and mitigated testicular histopathology. Moreover, GLEXGH markedly reduced the ROS level (5684.28 +/- 1345.47 vs. 15500.44 +/- 2307.39, p < 0.001) and increased the GPX4 level (48.53 +/- 10.78 vs. 23.14 +/- 11.04, p < 0.01), decreased the ferrous iron level (36.31 +/- 3.66 vs. 48.64 +/- 7.74, p < 0.05), and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway. Discussion and conclusions Ferroptosis resistance from GLEXG might be driven by activation of the Keap1/Nrf2/GPX4 pathway. Targeting ferroptosis is a novel approach for OAS therapy.
期刊：
Frontiers in Medicine,2023年9:1042015 ISSN：2296-858X
作者机构：
[Gong, Yuanxun; Tang, Qianli] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Gong, Yuanxun; Tang, Qianli] Youjiang Med Univ Nationalities, Affiliated Hosp, Baise, Peoples R China.;[Jiang, Yan] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inci, Baise, Peoples R China.;[Huang, Jinmei] Guangxi Univ Chinese Med, Grad Sch, Nanning, Peoples R China.;[He, Zuofen] YouJiang Med Univ Nationalities, Grad Sch, Baise, Peoples R China.
摘要：
BackgroundThe incidence of diabetes-related wounds is widespread, and the treatment is challenging. We found that Moist Exposed Burn Ointment (MEBO) promotes the healing of diabetes-related wounds, but the mechanism is not clear. MethodsThis study aimed to explore the mechanism of MEBO on diabetic wound healing, which may be related to the promotion of re-epithelialization. A full-thickness skin resection model was established in streptozotocin (STZ)-induced diabetic mice. MEBO and Kangfuxin (KFX) were applied to the wound area, and the wound healing rate was analyzed by photographing. The granulation tissue and epidermal thickness, the collagen remodeling rate, and the expression of cytokeratin 10 (CK10), cytokeratin 14 (CK14), Ki67, Collagen I, and Collagen III in the regenerated skin were detected by H&E staining, Masson staining, and immunofluorescence staining, respectively. MEBO and KFX were applied to human immortalized keratinocytes (HaCaT), mouse dermal fibrolasts (MDF) cells, and cell viability, cell migration, and differentiation were determined by CCK-8, scratching assay, RT-qPCR, and Western blot (WB), respectively. ResultsWe found that MEBO significantly promoted the formation of wound granulation tissue and collagen remodeling in diabetic mice. The application of MEBO to diabetic wounds not only promoted the formation of hair follicles and sebaceous glands but also promoted the expression of Ki67, CK10, and CK14 in epidermal cells. MEBO had no significant effect on the differentiation process of keratinocytes. ConclusionOur study further proved that MEBO plays a positive role in diabetic wound healing, and its excellent ability to promote re-epithelialization may be an important reason for promoting wound healing.
摘要：
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.
摘要：
Osteoarthritis (OA) is a chronic joint disease characterized by progressive cartilage degeneration, which imposes a heavy physical and financial burden on the middle-aged and elderly population. As the pathogenesis of OA has not been fully elucidated, it is of great importance to develop targeted therapeutic or preventive medications. Traditional therapeutic drugs, such as non-steroidal anti-inflammatory drugs, steroids and opioids, have significant side effects, making the exploration for safe and effective alternative therapeutic drugs urgent. In recent years, many studies have reported the role of plant-derived polysaccharides in anti-inflammation, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection, and have demonstrated their great potential in the treatment of OA. Therefore, by focusing on studies related to the intervention of plant-derived polysaccharides in OA, including in vivo and in vitro experiments, this review aimed to classify and summarize the existing research findings according to different mechanisms of action. In addition, reports on plant-derived polysaccharides as nanoparticles were also explored. Then, candidate monomers and theoretical bases were provided for the further development and application of novel drugs in the treatment of OA.
摘要：
Purpose This study aimed to investigate the association between macronutrient intake and biological age.Methods Data were collected from 26,381 adults who participated in the United States National Health and Nutrition Examination Survey (NHANES). Two biological ages were estimated using the Klemera-Doubal method (KDM) and PhenoAge algorithms. Biological age acceleration (AA) was computed as the difference between biological age and chronological age. The associations between macronutrient intakes and AA were investigated.Results After fully adjusting for confounding factors, negative associations were observed between AA and fiber intake (KDM-AA: beta - 0.53, 95% CI - 0.62, - 0.43, P < 0.05; PhenoAge acceleration: beta - 0.30, 95% CI - 0.35, - 0.25, P < 0.05). High-quality carbohydrate intake was associated with decreased AA (KDM-AA: beta - 0.57, 95% CI - 0.67, - 0.47, P < 0.05; PhenoAge acceleration: beta - 0.32, 95% CI - 0.37, - 0.26, P < 0.05), while low-quality carbohydrate was associated with increased AA (KDM-AA: beta 0.30, 95% CI 0.21, 0.38, P < 0.05; PhenoAge acceleration: beta 0.16, 95% CI 0.11, 0.21, P < 0.05). Plant protein was associated with decreased AA (KDM-AA: beta - 0.39, 95% CI - 0.51, - 0.27, P < 0.05; PhenoAge acceleration: beta - 0.21, 95% CI - 0.26, - 0.15, P < 0.05). Long-chain SFA intake increased AA (KDM-AA: beta 0.16, 95% CI 0.08, 0.24, P < 0.05; PhenoAge acceleration: beta 0.11, 95% CI 0.07, 0.15, P < 0.05). omega-3 PUFA was associated with decreased KDM-AA (beta - 0.18, 95% CI - 0.27, - 0.08, P < 0.05) and PhenoAge acceleration (beta - 0.09, 95% CI - 0.13, - 0.04, P < 0.05).Conclusion Our findings suggest that dietary fiber, high-quality carbohydrate, plant protein, and omega-3 PUFA intake may have a protective effect against AA, while low-quality carbohydrate and long-chain SFA intake may increase AA. Therefore, dietary interventions aimed at modifying macronutrient intakes may be useful in preventing or delaying age-related disease and improving overall health.
期刊：
Naunyn-Schmiedeberg's Archives of Pharmacology,2023年396(6):1187-1203 ISSN：0028-1298
通讯作者：
Dan Zhou<&wdkj&>Wei Zhang
作者机构：
[Li, Junxi; Ding, Huang; Zhou, Dan; Zhang, Wei; Liu, Jingze; Yan, Fanchen] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Sun, Zhengji] Hunan Univ Chinese Med, Yueyang Tradit Chinese Med Hosp, Changsha 414021, Hunan, Peoples R China.
通讯机构：
[Dan Zhou; Wei Zhang] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
Buyang Huanwu decoction (BYHWD) is a classical traditional prescription. Glycosides are effective extracts of BYHWD, which have been proven to protect blood vessels and prevent atherosclerosis (AS). However, the mechanism of glycosides in inhibiting abnormal angiogenesis in atherosclerosis is still unclear. The specific amygdalin (AG), paeoniflorin (PF), and astragaloside IV (ASV) contents in the BYHWD-containing serum were detected using mass spectrometry. Network pharmacology and molecular docking are used to screen the targets of glycosides for treating atherosclerosis. The predicted targets were validated in an AS model of rat thoracic aortic endothelial cells (RTAEC) induced by oxidized low-density lipoprotein (ox-LDL). According to the mass spectrometry data, the specific contents of AG, PF, and ASV in the serum were 24.11ng/ml, 20.94ng/ml, and 69.87ng/ml, respectively. Results of bioinformatics analysis show that signal transducer and activator of transcription (STAT)-3, hypoxia-inducible factor (HIF)-1, and vascular endothelial-derived growth factor (VEGF) may be involved in the treatment of AS with glycosides. The results of cell experiments revealed that glycoside combinations could treat atherosclerosis by inhibiting STAT3, HIF-1, and VEGF. AG, PF, and ASV are the effective ingredients of BYHWD. Glycoside combinations significantly ameliorate atherosclerosis by inhibiting STAT3, HIF-1, and VEGF.
