Food & Function
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2019
·Vol. 10
·期 8
·4868-4876
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IF 3.241
Xiaoyong Chen,Xiong Li,Xiaobo Zhang,Lijun You,Peter Chi-Keung Cheung,Riming Huang,Jianbo Xiao
In this study, a polysaccharide was extracted from Physalis pubescens L. (named PP). Its antihyperglycemic and antihyperlipidemic activities were evaluated in STZ-induced diabetic mice. Results showed that PP was determined to be composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glc) and galactose (Gal) with molar percentages of 4.65%, 17.34%, 1.43%, 6.24%, 5.52%, 45.5%, and 19.31%, respectively. The average molecular weight (Mw) was found to be 20.0 kDa. It had a strong α-glucosidase inhibitory activity in vitro. PP treatment could enhance the oral glucose tolerance, and increase the levels of SOD, GSH, CAT, vitamin C, vitamin E, HDL-c, C-peptide, GCK and hepatic glycogen in diabetic mice. Besides, PP treatment could also decrease the levels of MDA, TG, TC, LDL-c, BUN and G-6-Pase. The regulating effects were stronger in high dose PP treatment than those in the low and medium dose treatments. In short, PP played an important role in protecting STZ-induced diabetic mice, and the effect was closely related to its activities in antioxidation and regulating glucose and lipid metabolism.
研究领域:
药理学
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代谢生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yu Zhang,Bingjie Yang,Wei Sun,Xun Sun,Jing Zhao,Quanhong Li
A novel natural water-soluble acidic polysaccharide (PWESP-3) was isolated from squash with a molecular mass of 140.519 kDa, which was composed of arabinose (Ara, 35.30 mol%), galactose (Gal, 61.20 mol%), glucose (Glc, 1.80 mol%), and Mannuronic acid (ManA, 1.70 mol%) and contained Araf-(1→, →3)-Araf-(1→, →5)-Araf-(1→, Glcp-(1→, Galp-(1→, →3,5)-Araf-(1→, →2)-Glcp-(1→, →2)-Manp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →3)-Galp-(1→, →6)-Galp-(1→, →3,4)-Galp-(1→, →4,6)-Galp-(1→ residues in the backbone. Moreover, the structure of PWESP-3 was identified by NMR spectra. The branch chain was connected to the main chain by the O-3 and O-4 atom of Gal. In addition, the effect of PWESP-3 on STZ-induced type I diabetes mellitus model in MIN6 cells was investigated. The results showed that PWESP-3 can increase the viability and insulin secretion of MIN6 cells and reduce the oxidative stress caused by ROS and NO. Meanwhile, PWESP-3 can also reduce the content of ATP, Ca 2+ , mitochondrial membrane potential and Caspase-3 activity in MIN6 cells. Furthermore, treatment with PWESP-3 can prevent single or double stranded DNA breaking to form DNA fragments and improve DNA damage in MIN6 cells, thereby avoiding apoptosis. Therefore, the above data highlight that PWESP-3 can improve the function of insulin secretion in STZ-induced MIN6 cells in vitro and can be used as an alternative food supplement to diabetes drugs.
研究领域:
生物化学
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药理学
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细胞生物学
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糖尿病研究
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PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 84
·期 12
·2491-2498
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IF 1.516
Liang Haohui,Pan Yanna,Teng Yilong,Yuan Shilin,Wu Xiao,Yang Hongjie,Zhou Ping
The pancreatic β-cell death or dysfunction induced by oxidative stress plays an important effect on the development and progression of diabetes mellitus. Based on our previous findings, a natural proteoglycan extracted from Ganoderma Lucidum, named FYGL, could treat T2DM in vivo. In this study, we investigated the effects of FYGL on STZ‐induced apoptosis of INS-1 cells and its underlying mechanisms. The results showed that FYGL significantly improved the cell viability and alleviated the apoptosis in STZ‐treated INS‐1 cells. Moreover, FYGL markedly decreased the intracellular ROS accumulation and NO release, and deactivated NF-κB, JNK, and p38 MAPK signaling pathways in STZ-induced INS-1 cells. Furthermore, FYGL improved the insulin secretion through inhibiting the activation of JNK and improving the expression of Pdx-1 in INS-1 cells damaged by STZ. These results indicated that FYGL could protect pancreatic β-cells against apoptosis and dysfunction, and be used as a promising pharmacological medicine for diabetes management.Abbreviations: T2DM: type 2 diabetes mellitus; FYGL: Fudan-Yueyang G. lucidum; ROS: reactive oxygen species; NO: reactive oxygen species; NF-κB: nuclear factor kappa beta; JNK: c-jun N-terminal kinase; MAPK: mitogen-activated protein kinase; Pdx-1: Pancreatic duodenal homeobox 1
研究领域:
药理学
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糖尿病
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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
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2016
·
IF 2.371
Xue Liu,Ershun Liang,Xiuhui Song,Zhanhui Du,Yun Zhang,Yuxia Zhao
Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl–prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone. Pin1 inhibition alleviates cardiac fibrosis and dysfunction. In vitro, high glucose increases Pin1 expression with an accompanying increase in phospho-Akt (Ser 473), p -Smad2, p -Smad3, TGF-β1, and α-SMA in cardiac fibroblasts (CFs). These increases are effectively prevented by the inhibition of Pin1 by juglone. Furthermore, Pin1 inhibition inhibits HG-induced CF proliferation and migration. Our results indicate that Pin1 inhibition attenuates cardiac extracellular matrix deposition by regulating the phosphorylation of Akt, TGF-β1/Smads, MMP activities, and α-SMA expression in diabetic mice.
研究领域:
心脏病学
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糖尿病
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分子生物学
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药理学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2025
·
IF 7.7
Yue-Yang Zhang,Le-Yu Huang,Huiling Wang,Sixuan Meng,Fei Yang,Shi-Yu Liu
Carboxylesterase 2 (CES2), an extensively expressed serine esterase which widely distributed in various organs and tissues, exerts important roles in maintaining normal physiological function while abnormal expression of CES2 was correlated with many metabolic diseases and cancers. Thus, to develop efficient tool for detection of CES2 activity is of great importance in related clinical diagnosis and research of physiological function of CES2. To date, several enzyme-activated fluorescent probes were developed for CES2 sensing. Among which regulation of CES2 in diseases such as diabetics, colitis, cancers and liver injury could be visualized. However, even though CES2 displayed relatively high expression level in kidney, its regulation in pathological process of kidney injury was rarely studied, and thus related preliminary investigation is in urgent demand. Herein, by rational design and construction of an enzyme-activated fluorescent probe (named as DDXB ) with high catalytic efficacy, sensitivity and specificity toward CES2, down-regulation of CES2 activity in acetaminophen (APAP)-induced liver injury and dextran sulfate sodium (DSS)-induced colitis model was successfully visualized. Most importantly, aberrant up-regulation of CES2 in streptozotocin (STZ), renal ischemia reperfusion (IR) injury (RIRI) and cisplatin (CDDP)-induced kidney injury model was first revealed via DDXB- based fluorescence imaging and further confirmed by immunohistochemistry (IHC) staining. Thus, preliminary evidence for identifying CES2 as potential biomarker of kidney injury were first provided, and the newly developed probe could serve as an efficient tool for related diagnosis or further investigation of CES2 physiological function in more diseases.
研究领域:
生物化学
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医学诊断
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病理学
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DOI
高影响因子
Chinese Journal of Natural Medicines
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2013
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IF 0
Xue-Jian LI,Zheng-Cai DU,Yan HUANG,Bu-Ming LIU,Wen-Ji HU,Wen-Jie LU,Jia-Gang DENG
Aim To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. Methods Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. Results 7, 2′, 3′, 4′, 6′-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2′, 3′, 4′, 6′-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2′, 3′, 4′-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS, 1 H, 13 C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg −1 ), HPM group (0.5, 0.25 mmol·kg −1 ), and HBM group (0.5, 0.25, 0.125 mmol·kg −1 ) mice showed strong hypoglycemic activity ( P < 0.01); mangiferin group (1, 0.5 mmol·kg −1 ), PAM group (0.125 mmol·kg −1 ) and HPM group (0.125 mmol·kg −1 ) showed marginal hypoglycemic activity ( P < 0.05); mangiferin group (0.25 mmol·kg −1 ) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. Conclusion Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.
研究领域:
药理学
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有机化学
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糖尿病研究
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DOI
Food & Function
·
2026
·
IF 6.3
Fenglin Song,Huafang Ding,Yun Chen,Xiangzhen Ge,Ruixue Guo,Fangfang Wu,Yu Guo,Renyou Gan,Zhen-Yu Chen
The interaction between polyphenols and platelets is an emerging area in understanding how diet affects heart disease. Platelet hyperactivity is one of critical drivers of cardiovascular complications in Type 2 diabetes mellitus (T2DM). As one of the abundant polyphenols in nature, dihydromyricetin (DHM) has been shown to inhibit platelet activation and aggregation in vitro. This study aimed to investigate the in vivo effects and potential mechanisms of dietary DHM supplementation on platelet hyperactivity in diabetic mice. T2DM mouse model was established by feeding a high-fat diet (HFD) combined with streptozotocin (STZ) injection, followed by dietary supplementation with DHM (500 or 1000 mg/kg in diets) for eight weeks. Flow cytometric analysis revealed that DHM significantly reduced platelet surface expression of CD62P, CD63, and CD40 ligands, decreased integrin αIIbβ3 activation, and suppressed intraplatelet reactive oxygen species (ROS) production. The exaggerated platelet aggregation and ATP secretion induced by thrombin and collagen were also markedly attenuated. Additionally, DHM reduced plasma levels of in vivo platelet activation markers, soluble P-selectin, platelet factor 4, thromboxane B2, and the oxidative stress marker 8-iso-prostaglandin F2α. DHM administration also delayed collagen/epinephrine-induced pulmonary embolism formation without prolonging tail bleeding time in T2DM mice. Molecular docking suggested binding interactions between DHM with NADPH oxidase-2, aldose reductase, and platelet receptor PAR 1, GPVI, as well as COX 1. Collectively, dietary DHM attenuated platelet hyperactivity and thrombus formation in T2DM mice, primarily through suppression of intraplatelet ROS formation. These findings highlight DHM as a promising natural candidate for preventing diabetic cardiovascular complications.
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2025
·
IF 4.3
Wanying Cheng,Cenzhu Wang,Meican Ma,Yu Zhou
Background: Diabetic kidney disease (DKD) is the leading risk factor for end-stage renal disease (ESRD). Hydroxyurea (HU), a sickle cell disease (SCD) drug approved by FDA, shows protective effect in nephropathy. This study aims to understand whether the application of HU could be effective to treat DKD.Methods: The streptozotocin (STZ)-induced diabetic mice, and high glucose (HG)-treated human renal mesangial cells (HRMCs) were used to investigate the effect of HU on DKD. Serum creatinine and blood urea nitrogen levels reflecting renal function were evaluated. Histology was used to evaluate pathological changes. Indicators of inflammation and apoptosis were detected. Lastly, the mTOR-S6K pathway was explored by detecting the protein expression of S6K and phosphorylated S6K.Results: In STZ-induced diabetic mice, administration of HU (20 mg/kg) in drinking water for 16 weeks resulted in significant reductions in creatinine and urea nitrogen levels, alongside mitigating histopathological damage. Additionally, HU effectively suppressed the inflammatory response and apoptosis within the kidneys. HRMC cells were cultivated in HG conditions, and HU effectively attenuated the HG-induced inflammation and apoptosis. Moreover, HU treatment significantly inhibited the mTOR signaling pathway in both in both in vivo and in vitro experiments.Conclusion: This study unveils a new role of HU in alleviating diabetic kidney disease by modulating inflammation and apoptosis through the mTOR-S6K pathway. However, since HU did not significantly affect blood glucose levels, its therapeutic potential may be best realized when used in combination with standard antidiabetic therapies. Such a combination approach could simultaneously address hyperglycemia and renal dysfunction, offering a more comprehensive management strategy for DKD.
研究领域:
医学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·Vol. 53
·期 03
·909-930
·
IF 5.5
Ke Li,Ya-Jun Wang,Kun Wei,Wen-Lin Li,Yong-Bo Liu,Jun-Nan Hu,Wen-Guang Chang,Wen-Xuan Zhang,Long Chen,Wei Li
Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng ( Panax ginseng . C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1 β ) . In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro , suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.
研究领域:
药理学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
·
2017
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IF 2.204
Sha Li YU,Ling Fei XU,Jun Xia WU,Chen Juan YAO,Qiao Yun HU,Chun Xue ZHANG,Xin Yuan ZHAO,Hai Yan WEI,Xiao Ke WANG,Gang CHEN
Objective This study aimed to investigate the susceptibility of mice with streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent inorganic arsenic (iAs V ) and the possible molecular mechanism. Methods TIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na 2 HAsO 4 ·12H 2 O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues. Results The concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na 2 HAsO 4 ·12H 2 O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAs V , were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment. Conclusion The increased uptake of iAs V in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.
研究领域:
药理学
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毒理学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
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2019
·
IF 2.635
Panwen Liu,Lingyu Cui,Bo Liu,Weiwei Liu,Toshihiko Hayashi,Kazunori Mizuno,Shunji Hattori,Yuko Ushiki-Kaku,Satoshi Onodera,Takashi Ikejima
Alzheimer's disease (AD) is a neurodegenerative disease, mainly characterized by cognitive dysfunction and memory impairment. Due to its pathological similarities to type 2 diabetes mellitus (T2DM), such as β-amyloid deposition, oxidative stress, inflammation, disordered glucose metabolism, impaired signaling pathways of insulin and insulin-like growth factor-1 (IGF-1), we speculate that AD is another form of brain diabetes. Clarifying the relationship between T2DM and AD is important for us to better understand the exact pathological mechanisms of AD. Silibinin, a polyphenolic flavonoid extracted from the seeds of Silybum marianum , exerts hepatoprotective, anti- diabetic and neuroprotective effects. Streptozotocin (STZ), which is used to disrupt the insulin signal transduction pathway, could well mimic the sporadic AD models by intracerebroventricular (ICV) injection. Therefore, we selected ICV injection of STZ (ICV-STZ) to investigate the neuroprotective effects of silibinin in rats and to make a foundation for further exploring the relationship between AD and T2DM. ICV-STZ obviously caused memory damage, sharply reduced the number of nissl bodies and destroyed morphological structure of hippocampal neuronal cells, while silibinin attenuated the damages. Moreover, silibinin significantly decreased STZ-induced tau hyperphosphorylation (ser404) in hippocampus and cerebral cortex, markedly inhibited apoptosis of neurons induced by STZ, and up-regulated insulin signal transduction pathway. Silibinin exerts neuroprotective effect in STZ-treated rats, indicating the potential of silibinin for the treatment of AD patients with T2DM in future.
研究领域:
神经科学
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药理学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Tingting Wang,Xiaoting Huang,Kefeng Zhai,Jialin Yu,Jiaxi Li,Hong Duan,Jinhong Liu,Zhuojian Lu,Jia Guo,Fei Li
Ethnopharmacological relevance Panax japonicus C. A. Meye (PJ) has unique effects on diseases by “qi” stagnation and blood stasis in ancient. Modern studies have shown that PJ can treat diabetic kidney disease (DKD) caused by deficiency and blood stasis. Aim of the study This study evaluated the potential effects of PJ on DKD, a microvascular complication, and investigated its possible mechanisms. Materials and methods In this study, the chemical constituents of PJ were analyzed by HPLC. In vivo studies, we constructed a diabetic mice model by HDF combined with STZ , then administered PJ to diabetic mice for 6 weeks. Blood lipid, BUN, 24h urine protein, and renal tissue HE staining were detected to comprehensively evaluate the protective effect of PJ on DKD. Metabolomics investigated the metabolic pathways influenced by PJ in the treatment of DKD. Moreover, the potential targets and signal pathways were investigated using network pharmacology . Finally, molecular docking predicts affinity of active compounds and core targets, and western blotting was used to detect core target expression levels. Results In vivo study, PJ can reduce hyperlipidemia , serum BUN, and 24-h urinary protein in diabetic mice, and protect the pathological changes in renal tissue. Metabolomics results showed that PJ had significant regulatory effect on unsaturated fatty acids , glycerophospholipid metabolism, and purine metabolism. Network pharmacology showed that MAPK1, MAPK8, Bcl-2, and Caspase 3 were the core targets in PJ against DKD. Molecular docking revealed that Bcl-2 and Caspase 3 have a strong affinity for Chikusetsusaponin Iva , Ginsenoside Rb1 , and Ginsenoside Rg1 . Moreover, when compared to the model group, the PJ group had higher levels of anti-apoptosis protein Bcl-2 and lower levels of pro-apoptosis protein Caspase 3. Conclusion PJ can reduce blood lipids, regulate the biosynthesis of unsaturated fatty acids and purine metabolism, thereby alleviating the renal injury of diabetic mice. Moreover, it can regulate the Bcl-2/caspase 3 apoptosis signaling pathway to prevent the apoptosis of renal cells and protect the renal function of diabetic mice.
研究领域:
药理学
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代谢组学
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糖尿病研究
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）