Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 30
·6017-6028
·
IF 6.331
Di Shen,Haojie Yu,Li Wang,Xiang Chen,Jingyi Feng,Qian Zhang,Wei Xiong,Jin Pan,Yin Han,Xiaowei Liu
Microneedles with insulin-loaded glucose-responsive particles are promising to control the blood glucose levels of diabetic patients. In particular, the long-term usage of these microneedles calls for biodegradable and cost-effective particles, which are still large challenges. In this paper, glucose-responsive 4-carboxy-3-fluorophenylboronic acid-grafted ε-polylysine (CFPBA-g-PL) was synthesized to meet these requirements. CFPBA-g-PL had low cytotoxicity, good hemocompatibility and no tissue reaction. The pharmacokinetics of CFPBA-g-PL were also studied. The self-assembled particles of CFPBA-g-PL were prepared via simple ultrasonic treatment. The insulin-loaded particles of CFPBA-g-PL (named INS/GRP-12.8) presented a glucose-responsive insulin delivery performance based on the disassembly-related mechanism in vitro. The INS/GRP-12.8-encapsulated microneedle patch with a uniform morphology and moderate skin penetration performance was prepared via a molding strategy. INS/GRP-12.8 lasted for more than 8 hours of normoglycemia on STZ-induced diabetic SD rats via subcutaneous injection and the INS/GRP-12.8-encapsulated microneedle patch also showed a blood-glucose-level-lowering performance in vivo via transdermal administration.
研究领域:
药学
·
材料科学
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生物医学工程
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2020
·Vol. 11
·期 12
·1-14
·
IF 6.304
Huang Xiaozhong,Shi Yujuan,Chen Hongjin,Le Rongrong,Gong Xiaohua,Xu Ke,Zhu Qihan,Shen Feixia,Chen Zimiao,Gu Xuemei,Chen Xiaojun,Chen Xiong
Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.
研究领域:
药理学
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糖尿病
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Wen Tao,Diguo Liu,Ziqi Guo,Pengfei Han,Yan Ma,Muci Wu,Rui Zhang,Jingren He
A novel selenylated low molecular weight apple pectin (Se-LMWAP) was prepared through enzymatic modification combined with selenylation. The physicochemical properties, the structural characterization of Se-LMWAP were evaluated by FT-IR, NMR and SEM. Moreover, the antidiabetic activity and potential mechanism of Se-LMWAP were investigated using high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice. The results revealed that the physicochemical properties of Se-LMWAP were distinctly improved after modifications, and the primary structure was not altered significantly compared to apple pectin and low molecular weight apple pectin. Se-LMWAP had a relative molecular weight of 8.91 × 10 3 Da (accounted for 61.3 %) and total selenium content of 148.3 ± 2.0 μg selenium /g sample . It consisted of Rha, Ara, Gal, Glc, Xyl and GalA at a molar ratio of 0.093:0.014:0.132:0.020:0.118:0.622, with the selenium substitution occurred at the C-6 position. Se-LMWAP was able to significantly reduce weight loss, hyperglycemia, oxidative stress and liver, kidney and pancreas damage. Additionally, improved glucose tolerance, relieved lipid metabolism disorders, elevated hepatic glycogen content and ameliorated insulin resistance were observed in the Se-LMWAP group. Overall, Se-LMWAP can be used as a promising dietary selenium supplement to exert -antidiabetic effect through modulating hepatic glucose metabolism and liver insulin-signaling transduction and oxidative stress.
研究领域:
食品科学
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营养学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Hong Yang,Yongxin Chen,Guoping Wu,Pengyan Ren,Tingting Chen,Jia Liu,Bao Zhang,Xiao Ma,Feng Jiang,Yue Li,Ling Tao,Xiangchun Shen
Fructus Alpiniae Zerumbet (FAZ), a folk medicinal herb used by the Miao people in Guizhou, China, is rich in 1,8-Cineole — a bioactive monoterpene oxide with antioxidant and neuroprotective properties. However, its therapeutic potential against pancreatic β cells dysfunction, a hallmark of type 2 diabetes mellitus (T2DM), remains unexplored. This study investigated the molecular mechanism by which 1,8-Cineole mitigates hyperglycemia induced β cells ferroptosis. Using high-fat and high-sugar diet / streptozotocin (HFSD/STZ) diabetes mellitus type 2-induced model (DM) and high glucose (HG)-treated β cells model. We demonstrated that 1,8-Cineole ameliorated pancreatic islet structural disorganization and pathological glycogen deposition in diabetic mice. Mechanistically, 1,8-Cineole suppressed lipid peroxidation and iron overload while restoring the expression of ferroptosis markers (GPX4 and COX2). It concurrently resolved autophagy deficiency, evidenced by upregulated LC3II/I ratio, enhanced Beclin-1 expression, and stabilized p62. Bioinformatic analysis of diabetic pancreatic transcriptomes (GEO dataset GSE25724) linked ferroptosis and PI3K/AKT/mTOR signaling to β cells dysfunction. Cellular thermal shift assay (CETSA) and molecular docking confirmed direct binding of 1,8-Cineole to PI3K with favorable binding energy at the catalytic site. Pharmacological validation using 740-YP (YP, a PI3K agonist) and LY294002 (LY, a PI3K inhibitor) revealed that 1,8-Cineole exerted its anti-ferroptotic effects via PI3K/AKT/mTOR pathway activation. Co-treatment with 740-YP synergistically enhanced β cells protection, whereas LY294002 abrogated 1,8-Cineole’s efficacy. Collectively, these findings unveil 1,8-Cineole as a novel PI3K/AKT/mTOR activator that rescues β cells function via coordinated regulation of autophagy and ferroptosis, thereby providing a mechanistic foundation for its therapeutic application in DM.
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PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Daozheng Fang,Qixiang Shang,Zhihao Liu,Xinyue Li,Quanrun He,Yining Liu,Yong Zhu,Haimeng Li,Tong Wu,Yan-Fang Xian,Jianping Chen,Jihang Chen
Schisandra berry , an edible fruit of the Schisandra genus, produces two main lignans known as Schisandrin A (SchA) and Schisandrin B (SchB). These compounds have garnered significant attention for their beneficial effects in alleviating diabetes and its complications, such as diabetic nephropathy and diabetic neuropathy. However, their protective effects and mechanisms of action against diabetic cardiomyopathy remained largely unknown. In this study, the diabetic cardiomyopathy in vivo model was established by intraperitoneal injection of streptozotocin (STZ) in mice, followed by 2 months of continuous oral administration of SchA and SchB. A positive control group receiving dapagliflozin (DAP) treatment was also included. We conducted a comprehensive evaluation of the protective effects of SchA and SchB against diabetic cardiomyopathy in Type 1 diabetes mellitus (T1DM) mice through a series of experiments, including echocardiography, immunofluorescence staining, immunohistochemistry, western blotting, transcriptomics, and molecular docking simulations, etc. Both SchA and SchB treatment significantly reduced fasting blood glucose level and inhibited dysfunction of pancreatic β-cells. Echocardiography revealed that both SchA and SchB substantially improved cardiac function, including changes in left ventricular muscle thickening, ejection fraction, and fractional shortening. This was accompanied by a reduction in ventricular hypertrophy and myocardial fibrosis following SchA or SchB treatment. Additionally, SchA and SchB treatment exhibited anti-inflammatory and antioxidant effects in mouse heart tissues. Transcriptomics analysis suggested that SchA and SchB may exert their protective effects against diabetic cardiomyopathy by inhibiting the complement cascade, as evidenced by decreased expression levels of genes such as C3, C3a, and C5a. Docking simulations further supported complement factor B as a potential target of SchA and SchB. Our study demonstrated that SchA and SchB exerted protective effects within the framework of T1DM on pancreatic tissues by suppressing apoptosis and preserving the ability of insulin secretion of β-cells. In addition, both SchA and SchB could protect against diabetic cardiomyopathy by inhibiting the complement pathway. These findings highlight the potential therapeutic applications of SchA and SchB in managing diabetic cardiomyopathy in the future.
研究领域:
药理学
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心脏病学
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糖尿病学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Shan Shan Qi,Meng Li Shao,Sun Ze,Hong Xing Zheng
Salidroside from Rhodiola rosea L. has hypoglycemic effects, and has anti-osteoporosis effect in diabetic rats. Whether it has beneficial effects on diabetic nephropathy (DN) has not been fully reported. Here, a DN rat model was established by streptozotocin (STZ). Salidroside (10, and 20 mg kg −1 d −1 ) were orally giving for eight weeks. The purity of salidroside was 99%. The results showed that eight weeks salidroside supplementation dose-dependently decreased blood glucose, serum insulin, serum creatinine, blood urea nitrogen (BUN), as well as urinary albumin of DN rats, repaired the pathological changes of kidney tissue, the renal sclerosis and fibrosis in the kidney of DN rats were improved, and the activities of oxidative defense system associated enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also improved. Serum inflammatory cytokines (including tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, and interleukin-6) were decreased significantly in DN rats after eight weeks salidroside supplementation. Immunohistochemical results showed that fibrosis related proteins such as transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), and phospho-Smad3 (p-Smad3) expression levels were decreased significantly in the kidney of salidroside treated group. Our results indicate that daily salidroside consumption could alleviate DN in rats, the main mechanisms are anti-inflammatory, anti-oxidative stress, and inhibition of the TGF-β1/Smad2/3 pathway. This study suggested that salidroside could be used as a nutrient against DN, as well as diabetes.
研究领域:
药理学
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糖尿病学
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肾病学
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DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Siya Wu,Jihui Zuo,Yang Cheng,Ya Zhang,Zhongshan Zhang,Mingjiang Wu,Yue Yang,Haibin Tong
Type 2 diabetes mellitus (T2DM) is considered a rapidly growing chronic disease that threatens human health worldwide. Extracts of various seaweeds have been shown to have anti-diabetic activity. Sargarsum fusiforme, an edible brown seaweed, has been shown to possess anti-inflammatory, anti-diabetic and anti-obesity activities. In this study, we investigated the beneficial effect of an ethanol extract of S. fusiforme (EE) on type 2 diabetes in mice induced with high-fat diet (HFD) and streptozotocin (STZ). Administering EE to the diabetic mice significantly reduced food intake, water intake and fasting blood glucose (FBG), while improving glucose tolerance, lipid profile and ameliorating hepatic oxidative stress. Furthermore, these animals also exhibited significantly diminished epididymal fat deposition, as well as less pathological changes in the heart and liver tissues, while displaying some highly enriched benign gut bacteria (e.g., Intestinimonas , Oscillibacter , Lachnoclostridium, unidentified_Lachnospiraceae , Roseburia and Anaerotruncus ) and a lower abundance of bacteria associated with diabetes or other metabolic diseases (e.g., Enterorhabdus and Romboutsia ). Metabolomic analysis revealed reduced levels of branched-chain amino acids (BCAA), such as l -valine and l -isoleucine, aromatic amino acids (AAA), such as l -tyrosine and l -phenylalanine, and increased levels of 4-hydroxyphenylacetic acid (4-HPA) in the gut content, suggesting that EE may impact T2DM through modulation of these compounds in the gut of the animals. Taken together, the results implied that S. fusiforme may contain valuable active components other than polysaccharides that have potential benefit in alleviating T2DM.
研究领域:
药理学
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营养学
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糖尿病研究
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 22
·7669
·
IF 4.6
Hongxing Zheng,Yingjun Hu,Mengli Shao,Simin Chen,Shanshan Qi
Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited. In addition, CP reduced the levels of serum inflammatory cytokines, and decreased oxidative stress and apoptosis in the testicular tissue. In conclusion, CP could ameliorate testicular damage in diabetic rats, as well as being a potential testicle-protective nutrient in the future to prevent the testicular damage caused by diabetes.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Jiaying Zhang,Fengjiao Chen,Dingle Yu,Zhenjiang Liang,Fanjia Dai,Hongze Liang,Haiyan Li,Hui Tan,Lingling Zhao
Chitosan-based injectable hydrogels were designed and fabricated through the dynamic crosslinking of dual-reversible covalent bonds (imine and phenylboronate ester) for precise insulin release. The hydrogels contain dual glucose-sensors/responsive elements, featuring high sensitivity and rapid responsiveness to glucose level variation in cumulative and half-hourly pulsed insulin release. The hydrogels demonstrated improved cytocompatibility against HSF cells and histological long-term analysis of tissue after implantation. Evaluation of the glycemic control ability in STZ-induced hyperglycemic mice revealed that the hydrogel system showed excellent glycemic control ability in the glucose tolerance test and maintained blood glucose levels in a normal range for up to 11 days after a single administration. Thus, the hydrogel system showed applicable potential in insulin replacement therapy for diabetes mellitus.
研究领域:
生物材料
·
生物医学工程
·
糖尿病研究
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2017
·
IF 3.144
Hai Zhang,Shengsheng Zhang,Li Wang,Xiaofei Liu,Yuntang Wu
Previous results from our laboratory showed that chitosan biguanidine hydrochloride (CSGH) and chitooligosaccharide guanidine (COSG) could control glucose uptake by regulating the expression of glucose transporters (GLUTs) in vitro experiments. In this study, we try to delineate changes observed in activation of diacylglycerol (DAG)/protein kinase C- β (PKC- β ) pathway and GLUT2 in kidney. STZ-induced diabetic rats were administered COSG via daily intra-gastric gavage for 8 weeks. Obviously, COSG significantly attenuated fasting blood glucose and blood glucose level by modulating the over-expression of GLUT2 and the level of DAG as well. Immunohistological examination revealed that factors such as PKC- β and transforming growth factor- β (TGF- β ) diminished to various extents after treatment with COSG, which impinged on the synthesis of extracellular matrix (ECM) components like fibronectin (FN). As a result, high glucose-induced activation of DAG/PKC pathway is inhibited, which is associated with the concentration of glucose controlled by the expression of GLUT2 with the treatment of COSG.
研究领域:
药理学
·
糖尿病研究
·
肾病学
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DOI
高影响因子
Food Science & Nutrition
·
2022
·Vol. 10
·期 7
·2455-2469
·
IF 3.553
Xiaoyu Chen,Hongyuan Zhao,Fanqiang Meng,Libang Zhou,Xinyi Pang,Zhaoxin Lu,Yingjian Lu
Surfactin, produced by Bacillus amyloliquefaciens fmb50, was used to treat insulin-resistant (IR) hepatocyte. It was found that surfactin increased glucose consumption in insulin-resistant HepG2 (IR-HepG2) cells and ameliorated IR by increasing glucose transporter 4 (GLUT4) protein expression and AMP-activated protein kinase (AMPK) mRNA expression, promoting GLUT4 translocation and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in IR-HepG2 cells. Meanwhile, surfactin downregulated protein expression of phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase), further inhibiting hepatic gluconeogenesis. In addition, surfactin played important roles in eliminating reactive oxygen species (ROS), improving mitochondrial dysfunction, and inhibiting proinflammatory mediators. We observed that surfactin promoted glucose consumption, meanwhile increased translocation and protein expression of GLUT4 in Caco-2 cells. These results confirmed the conclusion in hepatic cells. Furthermore, surfactin supplement decreased body weight, food intake, and fasting blood glucose of type 2 diabetes mellitus (T2DM) mice induced by streptozotocin (STZ)/high-fat diet (HFD). Our data indicated that surfactin ameliorated insulin resistance and lowered blood glucose in intro and in vivo.
研究领域:
药理学
·
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
Bioengineered
·
2021
·
IF 3.269
Xiaochen Wang,Yaochuan Mi,Wei He,Xiaona Hu,Shuo Yang,Lu Zhao,Yanyang Zhang,Binhong Wen
Diabetic osteoporosis (DOP) is a chronic complication of diabetes in the skeletal system. High level of miR-340-5p may be harmful to the bone formation. In this study, the DOP model of rats was successfully established via streptozotocin (STZ) and ovariectomy (OVX) treatment. It was manifested by reduced body weight, insulin level, alkaline phosphatase (ALP) activity, and osteocalcin (OCN) and collagen-I expressions, as well as increased concentration of fasting blood glucose. Moreover, we found that miR-340-5p expression was increased while runt-related transcription factor-2 (RUNX2) was decreased in femurs. Furthermore, the effects of miR-340-5p on osteogenic differentiation (OD) in high glucose (HG)-treated MC3T3-E1 cells were explored. Exposure to OD and HG contributed to elevated miR-340-5p level. Inhibition of miR-340-5p enhanced ALP level, calcium deposition, and OCN, collagen-I and RUNX2 levels. On the contrary, miR-340-5p overexpression reversed these promotional effects. Luciferase assay indicated that RUNX2 may be a target gene of miR-340-5p. Moreover, RUNX2 deficiency decreased miR-340-5p inhibition-induced ALP activity, calcium accumulation and OCN, collagen-I, RUNX2 levels. In short, the above findings revealed that inhibition of miR-340-5p facilitated osteogenic differentiation through regulating RUNX2 in MC3TC-E1 cells, which provided targeted therapeutic strategies for the treatment of DOP.
研究领域:
分子生物学
·
内分泌学
·
骨生物学
·
糖尿病研究
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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）