JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Xina Yu,Shanshan Song,Zhanhua Li,Tiantian Wang,Hui Huang,Qing Shen,Zongyuan Wu,Pei Luo
Panaxynol is a bioactive polyacetylene in food plants; however, its specific benefits in diabetes and metabolic disorders remain unclear. Previous studies have mainly focused on biochemical indicators and clinical evaluations. Limited research has systematically elucidated the beneficial effects of panaxynol from the oxylipins perspective. In this study, we employed an oxylipin analysis platform we previously established using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) based on the multiple reaction monitoring (MRM) method for the profiling of oxylipins. After a 7-week administration of panaxynol to db/db mice, significant alterations in serum oxylipins and potential benefits to hyperglycemia, insulin resistance, and hepatic steatosis were observed. Our analysis also revealed correlations among epoxygenase products derived from arachidonic acid (AA), linoleic acid (LA), and α-linolenic acid (ALA) via cytochrome P450 (CYP) pathways. Furthermore, six potential oxylipins were identified, as offering insights into the mechanisms by which panaxynol may modulate diabetes. These results provide the first in vivo evidence of the impact of panaxynol on oxylipin metabolism and lay the foundation for developing panaxynol as a nutraceutical for diabetes management.
研究领域:
代谢组学
·
营养学
·
药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaohan Li,Yue Zhang,Chunxiao Yu,Xu Guo,Xiangxiang Fu,Shiqi Chen,Yanguo Gao,Yu Zhang,Qin Xiang,Wei Lu,Yonghong Zhang,Qibin Wang,Li Chen,Tao Zheng
Background Scrophularia ningpoensis Hemsl. (SN) is a traditional herbal medicine used for treating diabetes mellitus (DM). Previous studies indicated that the aqueous extract of SN (AESN) improves type 2 DM (T2DM) by activating AMPK, but the active components were unclear. Purpose This study aimed to identify the compound in AESN responsible for AMPK activation and to verify its therapeutic effects on T2DM. Methods Rats were administered AESN intragastrically. The absorbed compounds in serum samples were analyzed using LC-MS/MS and subjected to molecular docking with AMPK. The compound with the highest docking score was further verified using SPR, CETSA, and TR-FRET to confirm its effects on AMPK activation. Primary mouse hepatocytes were used to examine the effects of ANC on AMPK activity, Akt/GSK3β signaling, NLRP3 inflammasome activation, and lipid accumulation. An AMPK inhibitor was used to determine whether the effects were AMPK-dependent. In type 2 diabetic db/db mice, various dosages of ANC were administered intragastrically to observe its therapeutic effects. Results Among the 17 absorbed prototype compounds, ANC exhibited the strongest binding ability to AMPK. SPR, CETSA, and TR-FRET assays confirmed that ANC binds to and activates AMPK. In hepatocytes, ANC activated the Akt/GSK3β signaling, suppressed NLRP3 inflammasome activation, and inhibited lipid accumulation in an AMPK-dependent manner. In db/db mice, ANC intervention improved glucose and lipid metabolic disorders, insulin resistance, and histopathological abnormalities in a dose-dependent manner, while activating AMPK and alleviating lipid metabolic disorders and metabolic inflammatory responses. Conclusion ANC can treat T2DM by directly binding to and activating AMPK.
研究领域:
药理学
·
代谢病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
·
2018
·
IF 3.247
Na Zhang,Yahui zhou,Qingxin Yuan,Yao Gao,Yan Wang,Xingyun Wang,Xianwei Cui,Pengfei Xu,Chenbo Ji,Xirong Guo,Lianghui You,Nan Gu,Yu Zeng
T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q<0.05), differentially expressed in db/db mice skeletal muscle. Gene Ontology analysis, Pathway analysis and Gene Set Enrichment Analysis of network gene expression revealed the potential functions of dysregulated lncRNAs may involve skeletal muscle function, fatty acid metabolism and the PPAR signaling pathway. In addition, differentially expressed lncRNAs were verified in skeletal muscle from the widely known IR mouse models ( db/db and ob/ob mice). Further validation of lncRNAs in C2C12 myotubes exposed with various concentrations of palmitate uncovered that lncRNAs were responsive to palmitate exposure at the high concentrations (0.5mM and 0.75mM). Coexpression analysis revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Moreover, we characterized two candidate lncRNAs Gm15441 and 3110045C21Rik by a comprehensive examination of their genomic context and validated their expression with neighboring genes (Txnip and Ddr2) by the Spearman correlation analysis. Collectively, these findings improve our understanding of lncRNAs that mediate skeletal muscle insulin resistance in diabetes and represent potential molecular therapeutic targets to improve insulin sensitivity and associated metabolic diseases.
研究领域:
分子生物学
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代谢疾病
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遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 20
·4413
·
IF 6.706
Hanlei Wang,Kun Zhang,Xuelin Chen,Mei Han,Jing Lu,Yumei Zhang
In folk medicine,Ficus tikoua(F. tikoua) has been used to treat diabetes for a long time, but there is a rare modern pharmacological investigation for its antidiabetic effect and mechanisms. Our study aimed to evaluate its hypoglycemic effect using in vitro and in vivo experimental models and then explore the possible mechanisms. In the ethanol extracts and fractions ofF. tikoua, n-butanol fraction (NBF) exhibited the most potent effect on inhibitingα-glucosidase activity (IC50= 0.89 ± 0.04 μg/mL) and promoting glucose uptake in 3T3-L1 adipocytes. Further animal experiments showed that NBF could play an antidiabetic role by ameliorating random blood glucose, fasting blood glucose, oral glucose tolerance, HbA1c level, and islets damage in diabetic mice. Then, the activities of the five subfractions of NBF (NBF1-NBF5) were further evaluated; NBF2 showed strongerα-glucosidase inhibition activities (IC50= 0.32 ± 0.05 μg/mL) than NBF. Moreover, NBF2 also possessed the ability to promote glucose uptake, which was mediated via P13K/AKT and AMPK pathways. This study demonstrated thatF. tikouapossesses antidiabetic efficacy in vitro and in vivo and provided a scientific basis for its folk medicinal use. NBF2 might be potential natural candidate drugs to treat diabetes mellitus. It is the first time the antidiabetic activity and the potential mechanisms of NBF2 were reported.Keywords:Ficus tikouaBur.;diabetes mellitus;α-glucosidase;3T3-L1 adipocytes;db/dbmice
研究领域:
药理学
·
糖尿病研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Diabetes Metabolic Syndrome and Obesity-Targets and Therapy
·
2021
·
IF 3.168
Hongfang Zeng,Xiaoli Li,Duanfang Zhou,Ning Wang,Xiaoping Yu,Liangyuan Long,Hao Cheng,Shuyu Zhou,Zhengze Shen,Weiying Zhou
Purpose To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice. Materials and Methods Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses. Results Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice. Conclusion The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.
研究领域:
药理学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 15
·3031
·
IF 6.706
Jie Hao,Zhiming Qian,Zijian Liu,Guirong Zhang,Di Wang,Weiwei Han
The aim of this study was to provide a practical experimental basis for the development of Neocryptotanshinone (NCTS) as an effective hypoglycemic drug and a theoretical method for the rapid screening of natural compounds with hypoglycemic effects. Molecular docking was used to screen the most suitable ligand. Hematoxylin and eosin, immunohistochemical staining, enzyme-linked immunosorbent assay and Western Blotting approved the hypoglycemic effect of NCTS. According to the free energy of binding, among 180 active compounds from the Traditional Chinese Medicine Integrated Database, NCTS was finally chose for investigation its hypoglycemic effects. In db/db mice, NCTS significantly reduced body weight and plasma glucose, improved glucose tolerance and levels of fasting plasma glucose and glycated hemoglobin A1c, and decreased insulin resistance after six-week administration. NCTS restored the pathological state in the liver of db/db mice and significantly decreased protein tyrosine phosphatase 1B (PTP1B) expression in the liver and muscle of db/db mice, which is related to the regulatory effect of NCTS on insulin receptor substrate 1. In conclusion, we successfully explored the hypoglycemic effect of NCTS in db/db mice via regulating the expression of PTP1B.Keywords:virtual screening;molecular docking;NCTS;Diabetes mellitus;PTP1B
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
✓ 已验证
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1395-1405
·
IF 2.693
Dan Wang,Zikun Zhang,Zekun Si,Yanlin Yang,Shuangshuang Li,Yaoming Xue
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
研究领域:
药理学
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免疫学
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糖尿病学
·
肾病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xiaowei Zhang,Liang Zhao,Shixie Xiang,Yiran Sun,Pan Wang,Jenny Jie Chen,Brian Sheng-Xian Teo,Zhishen Xie,Zhenqiang Zhang,Jiangyan Xu
Ethnopharmacological relevance Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation. Aim of the study To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1. Materials and methods The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J ( db/db ) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells. Results YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen , alpha smooth muscle actin , type IV collagen , and fibronectin in vitro and in vivo , resulting in ameliorating of renal fibrosis . YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment. Conclusions YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.
研究领域:
药理学
·
内分泌学
·
分子生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2022
·
IF 5.223
Jie Gao,Xue Gu,Manqian Zhang,Xingwang Zu,Fukui Shen,Xiaotao Hou,Erwei Hao,Gang Bai
Lipid metabolic disorders impair quality of life in humans. Ferulic acid (FA), a ubiquitous phenolic nutrient existing in daily human food, exerts beneficial effects in improving glucose and lipid metabolisms. However, the underlying mechanisms are still unclear. In this study, FA treatment significantly attenuated metabolic disorders in db/db mice. Nontargeted metabolomics results suggested the participation of lipid metabolism regulation. Target fishing identified long-chain acyl-CoA synthase 1 (ACSL1) as the target of FA. FA provided a free fatty acid residue as the substrate of ACSL1 and triggered the mitochondrial membrane distribution of ACSL1. This distribution led to the upregulation of adenosine monophosphate (AMP)/adenosine triphosphate (ATP), which was sensed by AMP-activated protein kinase (AMPK) and in turn caused AMPK phosphorylation, further inhibiting the synthesis of triglyceride and cholesterol. In conclusion, FA might be explored as a potential complementary and alternative nutrient agent targeting ACSL1 to ameliorate lipid metabolism in diabetes.
研究领域:
药理学
·
代谢
·
营养学
·
糖尿病
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Xiaoli Li,Duanfang Zhou,Mingpu Liu,Hongfang Zeng,Xiaoping Yu,Yi Song,Qichen He,Xu Liu,Huan Zhang,Zhengze Shen,Zeng Zhu,Mingyan Gu,Xiangnan Hu,Weiying Zhou
Emerging data suggest that cocrystal of two compounds may have a different pharmacological effect from two compounds alone or their physical combination. Glimepiride (Gli) and metformin (Met) are two types of anti-diabetic drugs. Previously we generated the glimepiride/metformin cocrystal (GM). In this study, we evaluated the anti-diabetic effects of GM and explored the underlying mechanisms. Our result showed that GM reduced the blood glucose and HbA1c levels in db/db mice, and low doses of GM can achieve the hypoglycemic effect as Gli or Met alone, and high dose of GM was better than Gli and Met alone in improving the pathological changes of liver. In vivo studies showed that GM activated AMPK and STAT3 signaling, downregulated TXNIP expression and upregulated MaFA expression. Moreover, GM promoted the secretion of insulin in pancreas of db/db mice and in high glucose-treated INS-1 and MIN-6 cells. Together, GM possesses slightly better anti-diabetic effects than Met or Gli alone in db/db mice, and the mechanism of GM protecting β-cell dysfunction induced by glucotoxicity may be associated with activation of the AMPK/TXNIP/MaFA pathway.
研究领域:
药理学
·
糖尿病研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 9
·1036
·
IF 6
Lin Wu,Fei Huang,Zichen Sun,Jinghua Zhang,Siyu Xia,Hongting Zhao,Yutong Liu,Lu Yang,Yibing Ding,Dezhi Bian,Kuanyu Li,Yu Sun
Background: Diabetic peripheral neuropathy (DPN) is considered one of the most common chronic complications of diabetes. Impairment of mitochondrial function is regarded as one of the causes. Iron–sulfur clusters are essential cofactors for numerous iron–sulfur (Fe-S)-containing proteins/enzymes, including mitochondrial electron transport chain complex I, II, and III and aconitase. Methods: To determine the impact of hyperglycemia on peripheral nerves, we used Schwann-like RSC96 cells and classical db/db mice to detect the expression of Fe-S-related proteins, mitochondrially enzymatic activities, and iron metabolism. Subsequently, we treated high-glucose-induced RSC96 cells and db/db mice with pioglitazone (PGZ), respectively, to evaluate the effects on Fe-S cluster biogenesis, mitochondrial function, and animal behavior. Results: We found that the core components of Fe-S biogenesis machinery, such as frataxin (Fxn) and scaffold protein IscU, significantly decreased in high-glucose-induced RSC96 cells and db/db mice, accompanied by compromised mitochondrial Fe-S-containing enzymatic activities, such as complex I and II and aconitase. Consequently, oxidative stress and inflammation increased. PGZ not only has antidiabetic effects but also increases the expression of Fxn and IscU to enhance mitochondrial function in RSC96 cells and db/db mice. Meanwhile, PGZ significantly alleviated sciatic nerve injury and improved peripheral neuronal behavior, accompanied by suppressed oxidative stress and inflammation in the sciatic nerve of the db/db mice. Conclusions: Iron–sulfur cluster deficiency may contribute to hyperglycemia-mediated DPN.
研究领域:
内分泌学
·
神经科学
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药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yaxin Song,Yu Ke,Lianzhu Lin,Mouming Zhao
Lotus leaf is an optimal raw material for the preparation of foods with the function of regulating glycolipid metabolism. However, further investigation is required to elucidate the synergistic regulatory effects of lotus leaf polysaccharide (LLP), flavonoids, and alkaloids, which act as the main active components in lotus leaves. This study optimally prepared LLP and whole functional components (LLE) containing LLP, flavonoids and alkaloids by high-pressure homogenization-assisted dual enzyme extraction with and without pre-/post treatment. LLP and LLE exerted regulatory roles in glycolipid metabolism and alleviated liver, kidney, and pancreas damages of db/db mice. LLP was utilized by gut bacteria, promoting the production of beneficial metabolites i.e. lithodeoxycholic and butyric acids, which reached the liver through blood circulation, activating insulin signaling, and regulating glycolipid metabolism. The combination of polysaccharide, flavonoids and alkaloids promoted the production of butyric acid but different secondary bile acids i.e. deoxycholic and ursodeoxycholic acids, acted in the intestine and liver, and intervened in more metabolic pathways, showing a synergistic effect on glycolipid metabolism. This study provided insights into the rational processing of lotus leaf for hypoglycaemic foods.
研究领域:
食品科学
·
药理学
·
代谢学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）