JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Xiuwen Zheng,Qianrong Xue,Yinghuan Wang,Lu Lu,Yipeng Pan,Jian Xu,Junqing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance is a perennial natural medicine herbivorous plant, has been used in the management of treat stomach pain and diabetes, it is abundantly cultivated in Qiongzhong, Baisha and other places. P. cablin (Blanco) Benth, one of the most important traditional Chinese plants, which plays functions in antioxidant and gastrointestinal regulation, has been extensively planted in Hainan, Guangdong and other regions. Aim of the study In this study, we investigated the role and underlying molecular mechanism of AP on diabetic gastroparesis (DGP) in vitro and in vivo . Materials and methods In this study, using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum Hance– P. cablin (Blanco) Benth drug pair (AP). Molecular docking were utilized to explore the potential mechanism of AP treatment of DGP. In in vitro assays, gastric smooth muscle cells (GSMCs) were treated with 35 mM glucose to promote apoptosis and construct the DGP model, which was treated with different concentrations of AP. Furthermore, transfection technology was used to overexpress RAGE in GSMCs and elucidate the underlying mechanisms of alleviation of DGP by AP. Results Using UPLC-MS/MS analysis, nine components of AP were identified. We found that AP effectively blocked the increase in apoptosis, oxidative stress, and intracellular Ca 2+ concentrations. For in vivo experiments, mice were fed with a high-fat irregular diet to construct DGP model, and AP was co-administered via oral gavage daily to prevent the development of DGP. Compared with DGP mice, AP significantly decreased fasting blood glucose levels and increased gastric emptying levels. Consistent with in vitro experiments, AP also considerably decreased the increase in oxidative stress in DGP mice. Mechanistically, AP alleviates apoptosis and DGP by decreasing oxidative stress and intracellular Ca 2+ concentrations via the inhibition of the AGE/RAGE axis. Conclusions Collectively, this study has established that AP can improve DGP, and the mechanism may be related to the inhibition the AGE/RAGE axis to mitigate apoptosis and DGP. To summarize, this study provides a novel supplementary strategy for DGP treatment.
研究领域:
民族药理学
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药理学
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分子生物学
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糖尿病
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Sun Hui,Wang ZiTong,Tu BingHua,Shao ZiChen,Li YiDan,Han Di,Jiang YinJie,Zhang Peng,Zhang WeiChang,Wu YunYan,Wu XiaoMing,Liu Chi-Ming
Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.
研究领域:
药理学
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内分泌学
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糖尿病
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前列腺健康
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信号转导
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2022
·Vol. 5
·期 1
·1-15
·
IF 6.548
Yang Yan,Liu Guoyu,Li Feng,Carey Lucas B.,Sun Changjin,Ling Kaiping,Tachikawa Hiroyuki,Fujita Morihisa,Gao Xiao-Dong,Nakanishi Hideki
In mammals, both professional phagocytes and nonprofessional phagocytes (NPPs) can perform phagocytosis. However, limited targets are phagocytosed by NPPs, and thus, the mechanism remains unclear. We find that spores of the yeast Saccharomyces cerevisiae are internalized efficiently by NPPs. Analyses of this phenomenon reveals that RNA fragments derived from cytosolic RNA species are attached to the spore wall, and these fragments serve as ligands to induce spore internalization. Furthermore, we show that a multiligand receptor, RAGE (receptor for advanced glycation end-products), mediates phagocytosis in NPPs. RAGE-mediated phagocytosis is not uniquely induced by spores but is an intrinsic mechanism by which NPPs internalize macromolecules containing RAGE ligands. In fact, artificial particles labeled with polynucleotides, HMGB1, or histone (but not bovine serum albumin) are internalized in NPPs. Our findings provide insight into the molecular basis of phagocytosis by NPPs, a process by which a variety of macromolecules are targeted for internalization.
研究领域:
免疫学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Natural Product Communications
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2024
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IF 1.5
Liu Tang,Tianshuai Wang,Ruzhen Peng,Jingyi Guo,Liping Li,Benhong Zhou,Guangwen Luo,Shasha Fang,Xiao Jiang
Background: Atopic dermatitis, often referred to as AD, is a common chronic and relapsing skin disease with few treatment options. Epigallocatechin 3-gallate (EGCG), the most abundant catechin derived from green tea, has gained widespread attention due to its excellent anti-inflammatory and anti-oxidative properties. This research aims to investigate the effect and mechanism of EGCG in alleviating AD by integrative approach of an in vivo AD mouse model, network pharmacology and molecular docking. Materials and Methods: EGCG was administered by intragastric administration at the dose of 100 mg/kg, once daily for 14 consecutive days to AD mice, a model established by repeated application of 2, 4-dinitrofluorobenzene (DNFB) to the mouse dorsal skin. Results: Macroscopical and histopathological examination showed that oral administration with EGCG could markedly relieve AD-like skin phenotypes, as evidenced by a substantial reduction in severity score, serum immunoglobulin E (IgE) level, epidermal thickness, and the infiltration of inflammatory cells and mast cells into the dermal layers. Mechanistically, the network pharmacology analysis indicated that the protective effects of EGCG against AD were mainly related to the regulation of AGE-RAGE signaling pathway in diabetic complications, Th17 cell differentiation, IL-17 signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, etc. In silico molecular docking demonstrated the high binding affinity of EGCG to the core targets such as ABCB1, MMP2, MMP9, MAPK14 and STAT1. Furthermore, western blotting (WB) results showed that EGCG obviously downregulated the expression of RAGE and STAT1, thereby regulating the AGE-RAGE signaling pathway to improve AD. Conclusions: These findings indicated that EGCG can be a promising therapeutic candidate for AD.
研究领域:
药理学
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皮肤病学
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分子生物学
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DOI
高影响因子
Autophagy
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2024
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IF 14.6
Qingyuan Zhang,Chunhui Chen,Ye Ma,Xinyi Yan,Nianhong Lai,Hao Wang,Baogui Gao,Anna Meilin Gu,Qinrui Han,Qingling Zhang,Lei La,Xuegang Sun
Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH2-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.
研究领域:
肿瘤学
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细胞生物学
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肌肉生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Chang Liu,Xiaojun Zhang,Huiying Yang,Meijun Zhao,Yanhong Liu,Risheng Zhao,Ziqing Li,Meng Sun
Ischemic heart disease (IHD) is a cardiac disorder in which myocardial damage occurs as a result of myocardial ischemia and hypoxia. Evidence suggests that oxidative stress and inflammatory responses are critical in the development of myocardial ischemia. Therefore, the combination of antioxidant and anti-inflammatory applications is an effective strategy to combat ischemic heart disease. In this paper, polyethylene glycol (PEG)-modified cationic liposomes were used as carriers to deliver apigenin (Apn) with small interfering RNA (siRNA) targeting the receptor for glycosylation end products (RAGE) (siRAGE) into cardiomyocytes to prevent myocardial ischemic injury through antioxidant and anti-inflammatory effects. Our results showed that we successfully prepared cationic PEG liposomes loaded with Apn and siRAGE (P-CLP-A/R) with normal appearance and morphology, particle size and Zeta potential, and good encapsulation rate, drug loading and in vitro release degree. In vitro , P-CLP-A/R was able to prevent oxidative stress injury in H9C2 cells, downregulate the expression of RAGE, reduce the secretion of cellular inflammatory factors and inhibit apoptosis through the RAGE/NF-κB pathway; In vivo , P-CLP-A/R was able to prevent arrhythmia and myocardial pathological injury, and reduce apoptosis and the area of necrotic myocardium in rats. In conclusion, P-CLP-A/R has a protective effect on myocardial ischemic injury and is expected to be a potential drug for the prevention of ischemic heart disease in the future.
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-11
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IF 3.9
Kong Linghong,Wang Hui,Jiang Weiwei,Chen Yun,Du Zhuoling,Zhang Qiong,Dong Jianyue,Zeng Changchun,Liu Hanping
Advanced Glycation End Products (AGEs) are the molecular mediators that contribute to the progression of diabetic complications. However, there is a paucity of research on effective AGEs inhibitors and strategies for blocking the AGEs-RAGE pathway. To solve the problem, we synthesized polymetformin (PL), which for the first time proved the ability to inhibit AGEs formation and block the AGEs-RAGE pathway to protect the vascular from being damaged. Based on gene ontology (GO) analysis and Kegg enrichment, we found that PL could antagonize AGEs. Molecular docking and dynamics analyses showed that PL formed stable structures with AGEs through electrostatic interactions and hydrogen bonding. PL treatment altered AGEs structures have been proven in FT-IR results. The study discovered that PL interacted with AGEs via both non-covalent and covalent modifications, altering AGEs’ binding sites and antagonizing the AGEs-RAGE pathway. Immunofluorescence assays indicated lower levels of RAGE, IL-1β, and TNFα, while ROS assays demonstrated lower ROS levels, highlighting PL’s inhibitory effects and biocompatibility. Our work underscores PL’s potential to treat diabetic complications by elucidating its mechanism of action against the AGEs-RAGE pathway and inflammatory factors for the first time. This research provides insights for managing chronic illnesses linked to the AGEs-RAGE pathway beyond diabetes complications.
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产品关联
DOI
PubMed
高影响因子
mSystems
·
2021
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IF 6.496
Xiaoyan Jing,Yanhai Gong,Teng Xu,Yu Meng,Xiao Han,Xiaolu Su,Jianmei Wang,Yuetong Ji,Yuandong Li,Zhongjun Jia,Bo Ma,Jian Xu
Soil harbors arguably the most metabolically and genetically heterogeneous microbiomes on Earth, yet establishing the link between metabolic functions and genome at the precisely one-cell level has been difficult. Here, for mock microbial communities and then for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) platform, which identifies, sorts, and sequences precisely one bacterial cell via its anabolic (incorporating D from heavy water) and physiological (carotenoid-containing) functions. We showed that (i) metabolically active cells from numerically rare soil taxa, such as Corynebacterium spp., Clostridium spp., Moraxella spp., Pantoea spp., and Pseudomonas spp., can be readily identified and sorted based on D2O uptake, and their one-cell genome coverage can reach ∼93% to allow high-quality genome-wide metabolic reconstruction; (ii) similarly, carotenoid-containing cells such as Pantoea spp., Legionella spp., Massilia spp., Pseudomonas spp., and Pedobacter spp. were identified and one-cell genomes were generated for tracing the carotenoid-synthetic pathways; and (iii) carotenoid-producing cells can be either metabolically active or inert, suggesting culture-based approaches can miss many such cells. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at exactly one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint “who is doing what” in complex ecosystems.IMPORTANCE Soil is home to an enormous and complex microbiome that features arguably the highest genomic diversity and metabolic heterogeneity of cells on Earth. Their in situ metabolic activities drive many natural processes of pivotal ecological significance or underlie industrial production of numerous valuable bioactivities. However, pinpointing “who is doing what” in a soil microbiome, which consists of mainly yet-to-be-cultured species, has remained a major challenge. Here, for soil microbiota, we established a Raman-activated gravity-driven single-cell encapsulation and sequencing (RAGE-Seq) method, which identifies, sorts, and sequences at the resolution of precisely one microbial cell via its catabolic and anabolic functions. As a Raman-activated cell sorter (RACS) family member that can establish a metabolism-genome link at one-cell resolution from soil, RAGE-Seq can help to precisely pinpoint “who is doing what” in complex ecosystems.
研究领域:
微生物学
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分子生物学
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环境科学
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基因组学
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DOI
PubMed
高影响因子
Cells
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2022
·Vol. 11
·期 10
·1594
·
IF 7.666
Xu-Dong Yu,Dan Zhang,Chu-Li Xiao,Yu Zhou,Xing Li,Le Wang,Zhiming He,James Reilly,Zhi-Yong Xiao,Xinhua Shu
Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1β and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression.Keywords:depression;p-coumaric acid;inflammation;AGE-RAGE signaling pathway;network pharmacology
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Meimei Zhao,Ziteng Yu,Xinyi Zhao,Ruijiao Zhu,Mengcong Li,Lu Yu,Ziwei Song,Jiangwei Lv
Lipotoxicity is increasingly recognized as a potential cause of metabolic syndrome, yet effective treatments are still lacking. Boletus edulis ( B. edulis ) Bull: Fr., is a classical mushroom used in traditional Chinese medicine. Polysaccharides, its primary pharmacological components, are widely known to offer various health benefits, but their anti-lipotoxicity properties remain poorly understood. This study aimed to investigate a natural B. edulis Bull: Fr. polysaccharide (BP) for its effectiveness and underlying molecular mechanisms in mitigating hepatic lipotoxicity. In vitro , BP enhanced glucose uptake and reduced lipid accumulation and oxidative stress in Oleic acid (OA)-treated LO2 cells. It downregulated receptor for advanced glycation end-products (RAGE) expression, inhibited mitogen-activated protein kinase (MAPK) activation, and normalized key proteins involved in glucose and lipid metabolism, thereby alleviating OA-induced lipotoxicity. In vivo , high-fat diet-fed mice injected with BP exhibited similar metabolic improvements, with the reversal of RAGE/reactive oxygen species (ROS)/MAPK signaling in liver tissue, further supporting the molecular mechanisms observed in vitro in modulating lipotoxicity. Collectively, these findings underscore BP as a potent bioactive preparation with significant pharmacological potential in alleviating hepatic lipotoxicity.
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产品关联
DOI
PubMed
高影响因子
RENAL FAILURE
·
2026
·
IF 3.8
Chengli Lou,Yijing Zhou,Bo Feng,Xiaoping Fan,Xiuqin Xu,Pingxin Hu,Xiangjing Wang
Idiopathic membranous nephropathy (IMN) is an autoimmune glomerular disease. Current immunosuppressive therapies often cause side effects and high recurrence rates, highlighting the need for new treatments. Baicalin (BAI), a flavonoid isolated from Scutellaria baicalensis, has anti-inflammatory and antioxidant properties. This study examined effects of BAI on IMN using in vitro mouse podocyte clone-5 (MPC-5) cells treated with zymosan-activated serum (ZAS) and in vivo mouse models induced with cationic bovine serum albumin (BSA). Treatments included the BAI and advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) agonist, advanced glycation end products - bovine serum albumin (AGE-BSA). Assessments included cell viability, apoptosis, reactive oxygen species (ROS), inflammatory cytokines, oxidative stress markers, renal function, and histopathology. Potential targets and pathways involved in BAI’s effect on IMN were identified using network pharmacology. Compared to the ZAS-induced MPC-5 cell group, BAI increased cell viability and reduced apoptosis in injured cells. Meantime, BAI significantly reduced the release of pro-inflammatory cytokines tumor necrosis factor α, monocyte chemotactic protein 1, and interleukin 6 and enhanced antioxidant capacity by increasing total superoxide dismutase levels while simultaneously decreasing oxidative stress markers ROS, malondialdehyde, and lactate dehydrogenase in IMN cell models. Similarly, BAI exhibited anti-inflammatory and anti-oxidative effects in an in vitro IMN model and protected renal function in IMN mice with IMN. In addition, BAI downregulated AGE and RAGE in both IMN cell models and mice, and reduced CD68 levels in IMN mice. However, the activation of the AGE/RAGE pathway by AGE-BSA weakened the protective effects of BAI in these IMN models. Collectively, BAI mitigated inflammation and oxidative stress in IMN by repressing the AGE/RAGE pathway, suggesting its potential as a promising therapeutic agent for IMN.
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Xiaoyong Dai,Yibo Hou,Ting Deng,Gaoyang Lin,Yuanxiong Cao,Guiyuan Yu,Wei Wei,Qing Zheng,Laiqiang Huang,Shaohua Ma
Triple-negative breast cancer (TNBC) is an aggressive cancer that poses a significant threat to women's health. Unfortunately, the lack of clinical targets leads the poor clinical outcomes in TNBC. Many cancers demonstrate overexpression of receptor for advanced glycation end products (RAGE), which can contribute to cancer progression. Despite the potential therapeutic value of blocking RAGE for TNBC treatment, effective peptide drugs have yet to be developed. In our study, we observed that RAGE was highly expressed in TNBC and was associated with poor disease progression. We subsequently investigated the antitumor effects and underlying mechanisms of the RAGE antagonist peptide RP7 in both in vitro and in vivo models of TNBC. Our study revealed that RP7 selectively binds to RAGE-overexpressing TNBC cell lines, including MDA-MB-231 and BT549, and significantly inhibits cell viability, migration, and invasion in both cell lines. Furthermore, RP7-treatment suppressed tumor growth in TNBC xenograft mouse models without inducing detectable toxicity in normal tissues. Mechanistically, RP7 was found to inhibit the phosphorylation of ERK1/2, IKKα/β, IKBα, and p65 to block the NF-κB pathway, prevent the entry of p65 into the nucleus, decrease the protein expression of Bcl-2 and HMGB1, and promote the release of cytochrome C from the mitochondria into the cytoplasm. These effects were observed to activate apoptosis and inhibit epithelial-mesenchymal transition (EMT) in TNBC cells. This study highlights RAGE as a candidate therapeutic target for TNBC treatment and suggests that the RAGE antagonist peptide RP7 is a promising anticancer drug for TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
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