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Alfadda AA, Abdel Rahman AM, Benabdelkamel H, AlMalki R, Alsuwayni B, Alhossan A, Aldhwayan MM, Abdeen GN, Miras AD, Masood A. Metabolomic Effects of Liraglutide Therapy on the Plasma Metabolomic Profile of Patients with Obesity. Metabolites 2024; 14:500. [PMID: 39330507 PMCID: PMC11433991 DOI: 10.3390/metabo14090500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/09/2024] [Accepted: 09/14/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. METHODS A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). RESULTS The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. CONCLUSIONS The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug's multifaceted impact on overall metabolism in patients with obesity.
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Affiliation(s)
- Assim A. Alfadda
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia; (H.B.); (A.M.)
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia
- Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia
| | - Anas M. Abdel Rahman
- Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; (A.M.A.R.); (R.A.)
| | - Hicham Benabdelkamel
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia; (H.B.); (A.M.)
| | - Reem AlMalki
- Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; (A.M.A.R.); (R.A.)
| | - Bashayr Alsuwayni
- Corporate of Pharmacy Services, King Saud University Medical City, Riyadh 11461, Saudi Arabia;
| | - Abdulaziz Alhossan
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11461, Saudi Arabia;
| | - Madhawi M. Aldhwayan
- Department of Community Health Science, Clinical Nutrition, College of Applied Medical Sciences, King Saud University, Riyadh 11461, Saudi Arabia; (M.M.A.); (G.N.A.)
| | - Ghalia N. Abdeen
- Department of Community Health Science, Clinical Nutrition, College of Applied Medical Sciences, King Saud University, Riyadh 11461, Saudi Arabia; (M.M.A.); (G.N.A.)
| | - Alexander Dimitri Miras
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolic Medicine, Hammersmith Hospital, Imperial College London, London SW7 2AZ, UK;
- School of Medicine, Ulster University, Derry BT1 6DN, UK
| | - Afshan Masood
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia; (H.B.); (A.M.)
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Misiakiewicz-Has K, Maciejewska-Markiewicz D, Szypulska-Koziarska D, Kolasa A, Wiszniewska B. The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2. Int J Mol Sci 2024; 25:5418. [PMID: 38791455 PMCID: PMC11121859 DOI: 10.3390/ijms25105418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 05/08/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague-Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones.
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Affiliation(s)
- Kamila Misiakiewicz-Has
- Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (D.S.-K.); (A.K.); (B.W.)
| | | | - Dagmara Szypulska-Koziarska
- Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (D.S.-K.); (A.K.); (B.W.)
| | - Agnieszka Kolasa
- Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (D.S.-K.); (A.K.); (B.W.)
| | - Barbara Wiszniewska
- Department of Histology and Embryology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (D.S.-K.); (A.K.); (B.W.)
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Ma ZA, Wang LX, Zhang H, Li HZ, Dong L, Wang QH, Wang YS, Pan BC, Zhang SF, Cui HT, Lv SQ. Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways. World J Diabetes 2024; 15:502-518. [PMID: 38591083 PMCID: PMC10999033 DOI: 10.4239/wjd.v15.i3.502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 12/21/2023] [Accepted: 01/30/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.
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Affiliation(s)
- Zi-Ang Ma
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050000, Hebei Province, China
| | - Li-Xin Wang
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Hui Zhang
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Han-Zhou Li
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Li Dong
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Qing-Hai Wang
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Yuan-Song Wang
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Bao-Chao Pan
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Shu-Fang Zhang
- Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
| | - Huan-Tian Cui
- The First School of Clinical Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 065000, Yunnan Province, China
| | - Shu-Quan Lv
- Department of Endocrinology, Hebei Cangzhou Hospital of Integrative Medicine, Cangzhou 061000, Hebei Province, China
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Li J, Zhu N, Wang Y, Bao Y, Xu F, Liu F, Zhou X. Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment. Diabetes Metab Syndr Obes 2023; 16:4269-4282. [PMID: 38164418 PMCID: PMC10758184 DOI: 10.2147/dmso.s441399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 11/21/2023] [Indexed: 01/03/2024] Open
Abstract
Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.
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Affiliation(s)
- Jing Li
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, People’s Republic of China
| | - Na Zhu
- Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China
| | - Yaqiong Wang
- Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China
| | - Yanlei Bao
- Department of Pharmacy, Liaoyuan People’s Hospital, Liaoyuan, People’s Republic of China
| | - Feng Xu
- Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China
| | - Fengjuan Liu
- Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China
| | - Xuefeng Zhou
- Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China
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Zhu R, Yuan Y, Qi R, Liang J, Shi Y, Weng H. Quantitative profiling of carboxylic compounds by gas chromatography-mass spectrometry for revealing biomarkers of diabetic kidney disease. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1231:123930. [PMID: 38029665 DOI: 10.1016/j.jchromb.2023.123930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/05/2023] [Accepted: 11/13/2023] [Indexed: 12/01/2023]
Abstract
Diabetic kidney disease (DKD), a common microvascular complication of diabetes, currently lacks specific diagnostic indicators and therapeutic targets, resulting in miss of early intervention. To profile metabolic conditions in complex and precious biological samples and screen potential biomarkers for DKD diagnosis and prognosis, a rapid, convenient and reliable quantification method for carboxyl compounds by gas chromatography-mass spectrometry (GC-MS) was established with isobutyl chloroformate derivatization. The derivatives were extracted with hexane, injected into GC-MS and quantified with selected ion monitoring mode. This method showed excellent linearity(R2 > 0.99), good recoveries (81.1%-115.5%), good repeatability (RSD < 20%) and sensitivity (LODs: 0.20-499.90 pg, LOQs: 2.00-1007.00 pg). Among the 37 carboxyl compounds analyzed, 12 metabolites in short-chain fatty acids (SCFAs) metabolism pathway and amino acid metabolism pathway were linked with DKD development and among them, 6 metabolites were associated with both development and prognosis of DKD in mice. In conclusion, a reliable, convenient and sensitive method based on isobutyl chloroformate derivatization and GC-MS analysis is established and successfully applied to quantify 37 carboxyl compounds in biological samples of mice and 12 potential biomarkers for DKD development and prognosis are screened.
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Affiliation(s)
- Rongrong Zhu
- School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Yan Yuan
- School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Rourou Qi
- School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Jianying Liang
- School of Pharmacy, Fudan University, Shanghai 201203, China.
| | - Yan Shi
- Institute for Clinical Trials of drug, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
| | - Hongbo Weng
- School of Pharmacy, Fudan University, Shanghai 201203, China.
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Zhang Y, Liu Y, Sun J, Zhang W, Guo Z, Ma Q. Arachidonic acid metabolism in health and disease. MedComm (Beijing) 2023; 4:e363. [PMID: 37746665 PMCID: PMC10511835 DOI: 10.1002/mco2.363] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 08/13/2023] [Accepted: 08/17/2023] [Indexed: 09/26/2023] Open
Abstract
Arachidonic acid (AA), an n-6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory-related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.
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Affiliation(s)
- Yiran Zhang
- Department of Orthopedic SurgeryOrthopedic Oncology InstituteThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
| | - Yingxiang Liu
- Department of Orthopedic SurgeryOrthopedic Oncology InstituteThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
| | - Jin Sun
- Department of Orthopedic SurgeryOrthopedic Oncology InstituteThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
| | - Wei Zhang
- Department of PathologyThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
| | - Zheng Guo
- Department of Orthopedic SurgeryOrthopedic Oncology InstituteThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
| | - Qiong Ma
- Department of Orthopedic SurgeryOrthopedic Oncology InstituteThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
- Department of PathologyThe Second Affiliated Hospital of Air Force Medical UniversityXi'anChina
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Hou Y, Bai L, Wang X, Zhang S, Liu S, Hu J, Gao J, Guo S, Ho CT, Bai N. Gut Microbiota Combined with Serum Metabolomics to Investigate the Hypoglycemic Effect of Actinidia arguta Leaves. Nutrients 2023; 15:4115. [PMID: 37836402 PMCID: PMC10574697 DOI: 10.3390/nu15194115] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
Actinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-β-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.
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Affiliation(s)
- Yufei Hou
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
| | - Lu Bai
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
- Instrument Analysis Center, Xi’an Jiaotong University, 28 Xianning West Road, Xi’an 710048, China
| | - Xin Wang
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
| | - Shanshan Zhang
- Department of Pharmaceutical Engineering, College of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi’an 710069, China
| | - Shaojing Liu
- Department of Pharmaceutical Engineering, College of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi’an 710069, China
- College of Pharmacy, Xi’an Medical University, 1 Xinwang Road, Xi’an 710021, China
| | - Jiabing Hu
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
| | - Jing Gao
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
| | - Sen Guo
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA
| | - Naisheng Bai
- College of Food Science and Technology, Northwest University, 229 Taibai North Road, Xi’an 710069, China; (Y.H.); (S.G.)
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Taximaimaiti X, Abdulla R, Xin X, Zhao Y, Liu Y, Aisa HA, Deng D, Wu T. Rapid identification of chemical components in Xuelian granule by UHPLC-Q-orbitrap-HRMS based on enzyme activity in vitro. BMC Complement Med Ther 2023; 23:222. [PMID: 37407958 PMCID: PMC10321019 DOI: 10.1186/s12906-023-04025-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 06/04/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND Xuelian granule (XL), a traditional Chinese medicine (TCM) formula, has been used for the treatment of diabetic nephropathy for a long time as a hospital preparation. Because the active ingredients in the XL that can help to treat diabetic nephropathy are still unclear, which limits the interpretation for its pharmacological mechanism, further development and subsequent study on the material basis of its efficacy. METHODS In this study, a screening method based on inhibition activity against aldose reductase (AR) was employed for activity-directed chemical analysis of XL using ultra-high performance liquid chromatography combined with quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS) technique. RESULTS A total of 178 compounds, including 46 terpenes, 47 organic acids, 25 flavonoids, 29 phenylethanoid glycosides, and 31 other types, were tentatively identified from XL which might responsible for its AR inhibition activity. CONCLUSION This is the first study for a systematic, rapid, and accurate qualitative analysis of XL. This research provides a scientific and experimental basis for further researches on pharmacodynamics material basis and quality control of XL.
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Affiliation(s)
- Xiatiguli Taximaimaiti
- The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Rahima Abdulla
- The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
| | - Xuelei Xin
- The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
| | - Yuan Zhao
- Urumqi Hospital of Traditional Chinese Medicine, Urumqi, 830000, China
| | - Yi Liu
- Urumqi Hospital of Traditional Chinese Medicine, Urumqi, 830000, China
| | - Haji Akber Aisa
- The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China
| | - Deqiang Deng
- Urumqi Hospital of Traditional Chinese Medicine, Urumqi, 830000, China.
| | - Tao Wu
- The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China.
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Jia S, Li J, Yu B, Li M, Cui B. Improvement of myocardial injury and gut microbiota disturbance in type 2 diabetic mice by inulin with various degrees of polymerization. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.102318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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10
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Cui Y, Tian Z, Yu M, Deng D, Lu H, Song M, Ma X, Wang L. Guanidine acetic acid supplementation altered plasma and tissue free amino acid profiles in finishing pigs. Porcine Health Manag 2022; 8:24. [PMID: 35672811 PMCID: PMC9172011 DOI: 10.1186/s40813-022-00269-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 05/30/2022] [Indexed: 11/21/2022] Open
Abstract
Background As a nutritive feed additive, guanidine acetic acid (GAA) participates in the metabolism of energy and proteins. This study aimed to investigate the effects of GAA on growth performance, organ index, plasma and tissue free amino acid profiles, and related metabolites in finishing pigs. A total of 72 crossbred pigs (body weight 86.59 ± 1.16 kg) were randomly assigned to 1 of 4 dietary treatments (GAA0, GAA500, GAA1000, and GAA1500). They were fed the basal diets supplemented with 0, 500, 1000, or 1500 mg/kg GAA for 42 days, respectively. The growth performance and organ weight were evaluated, and the contents of crude protein, free amino acids, and metabolites in plasma and tissues were determined. Spearman correlation between plasma and tissue free amino acids and related metabolites was also analyzed. Results Growth performance in pigs was not altered by GAA (P > 0.05). The absolute and relative weight of kidneys increased (quadratic, P < 0.05). As dietary GAA concentration was increased, the contents of plasma glycine, serine, leucine, ornithine, and ratio of ornithine/arginine decreased (linear or quadratic, P < 0.05), but the contents of plasma isoleucine and taurine and the ratios of alanine/branched-chain amino acids and proline/ornithine increased quadratically (P < 0.05). The hepatic γ-amino-n-butyric acid content increased linearly and quadratically (P < 0.001), while the carnosine content decreased (quadratic, P = 0.004). The contents of renal arginine, proline, cystine, glutamate, and total amino acids (TAA) decreased quadratically (P < 0.05), but the contents of glycine (quadratic, P = 0.015) and γ-amino-n-butyric acid (linear, P = 0.008) increased. The pancreatic tryptophan content (quadratic, P = 0.024) increased, while the contents of pancreatic proline (linear, P = 0.005) and hydroxyproline (quadratic, P = 0.032) decreased in response to GAA supplementation. The contents of cardiac essential amino acids (EAA), nonessential amino acids (NEAA), and TAA in GAA1000 were higher than those in GAA1500 (P < 0.05). Supplementing with GAA linearly increased the contents of methionine, threonine, valine, isoleucine, leucine, phenylalanine, tryptophan, lysine, histidine, arginine, serine, alanine, glutamine, asparagine, tyrosine, proline, taurine, cystathionine, α-aminoadipic acid, β-aminoisobutyric acid, EAA, NEAA, and TAA in the spleen (P < 0.05). A strong Spearman correlation existed between plasma and tissue free amino acids and related metabolites. Conclusion GAA supplementation did not altered pig growth performance, but it altered plasma and tissue free amino acid profiles and the contents of related metabolites in pigs in a tissue-dependent manner.
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11
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Zhang F, Li DX, Lu DY, Lu YF, Zhang R, Zhao LL, Ji S, Guo MZ, Du Y, Tang DQ. Analysis of plasma free amino acids in diabetic rat and the intervention of Ginkgo biloba leaves extract using hydrophilic interaction liquid chromatography coupled with tandem mass-spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2022; 1196:123230. [PMID: 35349934 DOI: 10.1016/j.jchromb.2022.123230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/10/2022] [Accepted: 03/15/2022] [Indexed: 11/18/2022]
Abstract
Amino acids (AAs) are important metabolites that are related with diabetes. However, their roles in the initiation and development of diabetes mellitus (DM), especially in the treatment of Ginkgo biloba leaves extract (GBE) have not been fully explored. Thus, we investigated the roles that AAs played in the progression and GBE supplementation of DM rat induced by streptozotocin. The rats were randomly divided into a normal control group treated with drug-free solution, a normal control group treated with GBE, a DM group treated with drug-free solution, and DM group treated with GBE; and maintained on this protocol for 9 weeks. Rat plasma was collected from the sixth week to the ninth week and then analyzed with the optimized hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method. A total of 17 AAs with differential levels were monitored to indicate dysfunction of AAs metabolism to confirm the occurrence and development of DM. Treatment with GBE partially reversed the changes seen in seven AAs including leucine, isoleucine, tyrosine, glutamic acid, asparagines, lysine and alanine in DM rats, indicating that GBE could prevent the occurrence and development of DM by acting on AAs metabolism. The improvement of those AAs metabolism disorders may play a considerable role in the treatment of GBE on the occurrence and development of DM. Those findings potentially promote the understanding of the pathogenic progression of DM and reveal the therapeutic mechanism of GBE against DM.
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Affiliation(s)
- Fan Zhang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Ding-Xiang Li
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Dong-Yu Lu
- Department of Pharmacy, Suining People's Hospital, Suining, China
| | - Yi-Fan Lu
- The Second Clinical College, Xuzhou Medical University, Xuzhou, China
| | - Ran Zhang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Lin-Lin Zhao
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Shuai Ji
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, China
| | - Meng-Zhe Guo
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, China
| | - Yan Du
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Dao-Quan Tang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Suining People's Hospital, Suining, China; Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou, China.
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12
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Tao Y, Zhu F, Pan M, Liu Q, Wang P. Pharmacokinetic, Metabolism, and Metabolomic Strategies Provide Deep Insight Into the Underlying Mechanism of Ginkgo biloba Flavonoids in the Treatment of Cardiovascular Disease. Front Nutr 2022; 9:857370. [PMID: 35399672 PMCID: PMC8984020 DOI: 10.3389/fnut.2022.857370] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/21/2022] [Indexed: 12/18/2022] Open
Abstract
Ginkgo biloba, known as the "living fossil," has a long history of being used as botanical drug for treating cardiovascular diseases and the content of flavonoids as high as 24%. More than 110 different kinds of flavonoids and their derivatives have been separated from G. biloba, including flavones, flavonols, biflavonoids, catechins, and their glycosides, etc., all of which display the ability to dilate blood vessels, regulate blood lipids, and antagonize platelet activating factor, and protect against ischemic damage. At present, many types of preparations based on G. biloba extract or the bioactive flavonoids of it have been developed, which are mostly used for the treatment of cardiovascular diseases. We herein review recent progress in understanding the metabolic regulatory processes and gene regulation of cellular metabolism in cardiovascular diseases of G. biloba flavonoids. First, we present the cardioprotective flavonoids of G. biloba and their possible pharmacological mechanism. Then, it is the pharmacokinetic and liver and gut microbial metabolism pathways that enable the flavonoids to reach the target organ to exert effect that is analyzed. In the end, we review the possible endogenous pathways toward restoring lipid metabolism and energy metabolism as well as detail novel metabolomic methods for probing the cardioprotective effect of flavonoids of G. biloba.
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Affiliation(s)
- Yi Tao
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
| | | | | | | | - Ping Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China
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13
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Mu X, Yang M, Ling P, Wu A, Zhou H, Jiang J. Acylcarnitines: Can They Be Biomarkers of Diabetic Nephropathy? Diabetes Metab Syndr Obes 2022; 15:247-256. [PMID: 35125878 PMCID: PMC8811266 DOI: 10.2147/dmso.s350233] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/13/2022] [Indexed: 12/22/2022] Open
Abstract
Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus (DM), may progress to end-stage renal disease (ESRD). Current biochemical biomarkers, such as urinary albumin excretion rate (UAER), have limitations for early screening and monitoring of DN. Recent studies have identified some metabolites as candidate biomarkers for early detection of DN. In this review, we summarize the role of dysregulated acylcarnitines (AcylCNs) in DN pathophysiology. Lower abundance of short- and medium-chain AcylCNs and higher long-chain AcylCNs often occurred in DM with normal albuminuria and microalbuminuria, compared with advanced stages of DN. The increase of long-chain AcylCNs was supposed to be an adaptive compensation in fat acids (FAs) oxidation in the early stage of DN. Conversely, the decrease of long-chain AcylCNs was due to incomplete oxidation of FAs in advanced stage of DN. Thus, AcylCNs may serve as sensitive biomarkers in predicting the risk of DN.
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Affiliation(s)
- Xiaodie Mu
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Min Yang
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Peiyao Ling
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Aihua Wu
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Hua Zhou
- Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China
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14
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Huang G, Li M, Li Y, Mao Y. OUP accepted manuscript. Lab Med 2022; 53:545-551. [PMID: 35748329 DOI: 10.1093/labmed/lmac041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Guoqing Huang
- Department of Endocrinology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
- School of Medicine, Ningbo University, Ningbo, China
| | - Mingcai Li
- School of Medicine, Ningbo University, Ningbo, China
| | - Yan Li
- Department of Endocrinology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
- School of Medicine, Ningbo University, Ningbo, China
| | - Yushan Mao
- Department of Endocrinology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China
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15
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Roointan A, Gheisari Y, Hudkins KL, Gholaminejad A. Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies. Nutr Metab Cardiovasc Dis 2021; 31:2253-2272. [PMID: 34059383 DOI: 10.1016/j.numecd.2021.04.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 04/12/2021] [Accepted: 04/25/2021] [Indexed: 12/15/2022]
Abstract
AIM Diabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN. DATA SYNTHESIS To identify the significant dysregulated metabolites, meta-analysis was performed by "vote-counting rank" and "robust rank aggregation" strategies. Bioinformatics analyses were performed to identify the most affected genes and pathways. Among 44 selected studies consisting of 98 metabolite profiles, 17 metabolites (9 up-regulated and 8 down-regulated metabolites), were identified as significant ones by both the meta-analysis strategies (p-value<0.05 and OR>2 or <0.5) and selected as DN metabolite meta-signature. Furthermore, enrichment analyses confirmed the involvement of various effective biological pathways in DN pathogenesis, such as urea cycle, TCA cycle, glycolysis, and amino acid metabolisms. Finally, by performing a meta-analysis over existing time-course studies in DN, the results indicated that lactic acid, hippuric acid, allantoin (in urine), and glutamine (in blood), are the topmost non-invasive early diagnostic biomarkers. CONCLUSION The identified metabolites are potentially involved in diabetic nephropathy pathogenesis and could be considered as biomarkers or drug targets in the disease. PROSPERO REGISTRATION NUMBER CRD42020197697.
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Affiliation(s)
- Amir Roointan
- Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Yousof Gheisari
- Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kelly L Hudkins
- Department of Pathology, University of Washington, School of Medicine, Seattle, United States
| | - Alieh Gholaminejad
- Regenerative Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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16
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Li XZ, Jiang H, Xu L, Liu YQ, Tang JW, Shi JS, Yu XJ, Wang X, Du L, Lu Q, Li CL, Liu YW, Yin XX. Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway. Biochem Pharmacol 2021; 192:114675. [PMID: 34252407 DOI: 10.1016/j.bcp.2021.114675] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 12/19/2022]
Abstract
Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3β as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3β signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 μM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3β. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3β signaling pathway and restoring podocyte autophagy.
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Affiliation(s)
- Xi-Zhi Li
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Hong Jiang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Liu Xu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Yi-Qi Liu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Jia-Wei Tang
- School of Medical Information and Engineering, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Jia-Sen Shi
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Xiu-Juan Yu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Xue Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Lei Du
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Qian Lu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Cheng-Lin Li
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
| | - Yao-Wu Liu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.
| | - Xiao-Xing Yin
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.
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17
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Tang ZZ, Zhang YM, Zheng T, Huang TT, Ma TF, Liu YW. Sarsasapogenin alleviates diabetic nephropathy through suppression of chronic inflammation by down-regulating PAR-1: In vivo and in vitro study. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 78:153314. [PMID: 32882582 DOI: 10.1016/j.phymed.2020.153314] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/27/2020] [Accepted: 08/24/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.
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Affiliation(s)
- Zhuang-Zhuang Tang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China
| | - Yu-Meng Zhang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China
| | - Ting Zheng
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China
| | - Ting-Ting Huang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China
| | - Teng-Fei Ma
- Institute for Stem Cell and Neural Regeneration; Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yao-Wu Liu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
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18
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Zeki ÖC, Eylem CC, Reçber T, Kır S, Nemutlu E. Integration of GC–MS and LC–MS for untargeted metabolomics profiling. J Pharm Biomed Anal 2020; 190:113509. [DOI: 10.1016/j.jpba.2020.113509] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/24/2020] [Accepted: 07/25/2020] [Indexed: 12/12/2022]
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Wang H, Yuan M, Zou X. Efficacy and safety of Ginkgo biloba for patients with early diabetic nephropathy: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e21959. [PMID: 32871945 PMCID: PMC7458229 DOI: 10.1097/md.0000000000021959] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is not only an important microvascular complication of diabetes but also the main cause of end-stage renal disease. Ginkgo biloba has a variety of biological activities and has been widely used in China to treat kidney diseases such as DN. This article aimed to evaluate the efficacy and safety of G biloba in patients affected with DN in the early stage. METHODS This protocol follows the preferred reporting items for systematic review and meta-analysis protocols and the recommendations of the Cochrane Collaboration Handbook. Seven electronic databases will be searched from inception to July 31, 2020. Two investigators will independently identify relevant randomized controlled trials, fetch data, and assess the risk of bias with tools provided by Cochrane. A comprehensive meta-analysis will be conducted with the Cochrane Collaboration software (Review Manager 5.3) for eligible and appropriate studies. Further, the evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS The results will be published in academic peer-reviewed journals, and the evidence gathered by this project will be dedicated to assessing the efficacy and safety of G biloba for DN patients in the early stage. CONCLUSION This systematic review and meta-analysis will synthesize the available evidence to demonstrate the efficacy of G biloba in delaying the progression of patients with early DN. TRIAL REGISTRATION NUMBER PROSPERO CRD42020166805.
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Affiliation(s)
- Hongyun Wang
- Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine
| | - Meilin Yuan
- Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine
| | - Xinrong Zou
- Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, Hubei Province, China
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20
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Yang T, Heng C, Zhou Y, Hu Y, Chen S, Wang H, Yang H, Jiang Z, Qian S, Wang Y, Wang J, Zhu X, Du L, Yin X, Lu Q. Targeting mammalian serine/threonine-protein kinase 4 through Yes-associated protein/TEA domain transcription factor-mediated epithelial-mesenchymal transition ameliorates diabetic nephropathy orchestrated renal fibrosis. Metabolism 2020; 108:154258. [PMID: 32376130 DOI: 10.1016/j.metabol.2020.154258] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/13/2020] [Accepted: 04/29/2020] [Indexed: 12/19/2022]
Abstract
RATIONALE Tubulointerstitial fibrosis, which is closely related to functional injury of the kidney, can be observed in advanced stages of diabetic nephropathy (DN). Mammalian serine/threonine-protein kinase 4 (MST1), a core component of the Hippo pathway that is involved in cellular proliferation and differentiation, plays a crucial role in the pathogenesis of multiple metabolic diseases, kidney diseases and cancer. METHODS In type 1 and type 2 diabetic animals, as well as in human proximal tubular epithelial cells (HK-2), activation of MST1 was analyzed by immunohistochemistry and western blotting. In db/db mice, MST1 protein was knocked down or overexpressed by shRNA, and renal function, fibrosis, and downstream signaling were then investigated. RNA silencing and overexpression were performed by using an MST1 or YAP knockdown/expression lentivirus to investigate the regulation of MST1-mediated YAP/TEAD signaling pathways in the fibrosis process in HK-2 cells. Luciferase and coimmunoprecipitation (co-IP) assays were used to identify whether YAP directly regulated TEAD activation by forming a YAP-TEAD heterodimer, which ultimately leads to tubulointerstitial fibrosis. RESULTS MST1 activation was significantly decreased in type 1 and type 2 diabetic nephropathy. Notably, the downregulation of MST1 activation was also observed in HK-2 cells in a glucose- and time-dependent manner. In vivo, downregulation of MST1 was sufficient to promote renal dysfunction and fibrosis in db/m mice, whereas overexpression of MST1 ameliorated diabetic nephropathy-induced renal fibrosis. Further mechanistic study demonstrated that activated YAP induced by MST1 inhibition directly upregulated TEAD activation by binding to TEAD and forming a YAP-TEAD heterodimer, resulting in the promotion of epithelial-mesenchymal transition (EMT) and fibrosis in renal tubular epithelial. CONCLUSIONS MST1 activation represents a potential therapeutic strategy to treat or prevent the progression of diabetic nephropathy-induced renal fibrosis.
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Affiliation(s)
- Tingting Yang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Cai Heng
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Yi Zhou
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Yinlu Hu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Shangxiu Chen
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Haiyan Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Hao Yang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Zhenzhou Jiang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
| | - Sitong Qian
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Yinan Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Jianyun Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Xia Zhu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Lei Du
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
| | - Xiaoxing Yin
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
| | - Qian Lu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
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21
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Sun C, Gao M, Wang F, Yun Y, Sun Q, Guo R, Yan C, Sun X, Li Y. Serum metabolomic profiling in patients with Alzheimer disease and amnestic mild cognitive impairment by GC/MS. Biomed Chromatogr 2020; 34:e4875. [PMID: 32384189 DOI: 10.1002/bmc.4875] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 04/08/2020] [Accepted: 04/14/2020] [Indexed: 01/02/2023]
Affiliation(s)
- Congcong Sun
- Department of NeurologyQilu Hospital of Shandong University Jinan Shandong Province China
| | - Meimei Gao
- Institute of Clinical PharmacologyQilu Hospital of Shandong University Jinan Shandong Province China
| | - Feifei Wang
- Department of NeurologyQilu Hospital of Shandong University Jinan Shandong Province China
| | - Yan Yun
- Brain Research InstituteQilu Hospital of Shandong University Jinan Shandong Province China
| | - Qianwen Sun
- Brain Research InstituteQilu Hospital of Shandong University Jinan Shandong Province China
| | - Ruichen Guo
- Institute of Clinical PharmacologyQilu Hospital of Shandong University Jinan Shandong Province China
| | - Chuanzhu Yan
- Department of NeurologyQilu Hospital of Shandong University Jinan Shandong Province China
| | - Xiulian Sun
- Brain Research InstituteQilu Hospital of Shandong University Jinan Shandong Province China
| | - Yi Li
- Department of NeurologyQilu Hospital of Shandong University Jinan Shandong Province China
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Insulin exacerbated high glucose-induced epithelial-mesenchymal transition in prostatic epithelial cells BPH-1 and prostate cancer cells PC-3 via MEK/ERK signaling pathway. Exp Cell Res 2020; 394:112145. [PMID: 32561286 DOI: 10.1016/j.yexcr.2020.112145] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 05/13/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022]
Abstract
As two most common progressive diseases of aging, type 2 diabetes mellitus (T2DM) and benign prostatic hyperplasia (BPH) were all characterized by endocrine and metabolic disorders. Here, our clinical study showed that there were significant differences in fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR) and prostate volume (PV) between simple BPH patients and BPH complicated with T2DM patients. Further analysis showed that HOMA-IR was positively correlated with PV in BPH complicated with T2DM patients. The in vitro experiment results showed that high glucose (HG) promoted EMT process in a glucose-dependent manner in human prostate hyperplasia cells (BPH-1) and prostate cancer cells (PC-3), and this pathological process was exacerbated by co-culture with insulin. Mechanistically, insulin-induced exacerbation of EMT was depended on the activation of MEK/ERK signaling pathway, and we suggested that insulin and its analogs should be used very carefully for the clinical antihyperglycemic treatment of BPH complicated with T2DM patients.
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23
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Yang T, Huang Y, Zhou Y, Chen S, Wang H, Hu Y, Liu J, Jiang Z, Lu Q, Yin X. Simultaneous quantification of oestrogens and androgens in the serum of patients with benign prostatic hyperplasia by liquid chromatography-Tandem mass spectrometry. Andrologia 2020; 52:e13611. [PMID: 32441855 DOI: 10.1111/and.13611] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 03/29/2020] [Accepted: 04/01/2020] [Indexed: 12/15/2022] Open
Abstract
Benign prostate hyperplasia (BPH) is a common disease in elderly men. It has been found that the occurrence of BPH was closely related to dysregulated steroid hormones. Here, a rapid, sensitive, accurate and specific method for the quantitative profiling of five androgens in man serum was developed and validated by the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using this method, dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), androsterone (A), dihydrotestosterone (DHT), oestrone (E1) and oestradiol (E2) were quantified in serum from man with and without BPH. BPH patients were characterised by the decreases in DHEA, A4 and T as well as increases in DHT, E2 and E1 in serum. Meanwhile, DHEA and DHT in serum were screened as sensitive biomarkers of BPH patients. This study will provide a new perspective of dysregulated steroid hormones for the diagnosis and prevention of BPH.
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Affiliation(s)
- Tingting Yang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Yuhan Huang
- Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Yi Zhou
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Shangxiu Chen
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Haiyan Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Yinlu Hu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Junjie Liu
- Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Zhenzhou Jiang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China
| | - Qian Lu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Xiaoxing Yin
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
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24
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Du L, Wang L, Wang B, Wang J, Hao M, Chen YB, Li XZ, Li Y, Jiang YF, Li CC, Yang H, Gu XK, Yin XX, Lu Q. A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling. Acta Pharmacol Sin 2020; 41:358-372. [PMID: 31645661 PMCID: PMC7470857 DOI: 10.1038/s41401-019-0297-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 08/06/2019] [Indexed: 12/29/2022]
Abstract
Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, β-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mM)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg-1· d-1, ig) or a positive control drug resveratrol (40 mg· kg-1· d-1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5-10 μM) or resveratrol (10 μM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.
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25
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Shao M, Lu H, Yang M, Liu Y, Yin P, Li G, Wang Y, Chen L, Chen Q, Zhao C, Lu Q, Wu T, Ji G. Serum and urine metabolomics reveal potential biomarkers of T2DM patients with nephropathy. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:199. [PMID: 32309346 PMCID: PMC7154445 DOI: 10.21037/atm.2020.01.42] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 01/02/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Diabetes is a metabolic disease and is often accompanied by severe microvascular and macrovascular complications. A comprehensive understanding of its complex mechanisms can help prevent type 2 diabetes mellitus (T2DM) complications, such as diabetic nephropathy (DN). METHODS To reveal the systemic metabolic changes related to renal injury, clinical information of T2DM patients with or without nephropathy was collected, and it was found that serum urea levels of DN patients were significantly higher in T2DM patients without nephropathy. Further along the disease progression, the serum urea levels also gradually increased. We used gas chromatograph coupled with time-of-flight mass spectrometry (GC-TOFMS) metabolomics to analyze the serum and urine metabolites of T2DM patients with or without nephropathy to study the metabolic changes associated with the disease. RESULTS Finally, we identified 61 serum metabolites and 46 urine metabolites as potential biomarkers related to DN (P<0.05, VIP >1). In order to determine which metabolic pathways were major altered in DN, we summarized pathway analysis based on P values from their impact values and enrichment. There were 9 serum metabolic pathways and 12 urine metabolic pathways with significant differences in serum and urine metabolism, respectively. CONCLUSIONS This study emphasizes that GC-TOFMS-based metabolomics provides insight into the potential pathways in the pathogenesis and progression of DN.
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Affiliation(s)
- Mingmei Shao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Hao Lu
- Department of Endocrinology and Metabolism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ming Yang
- Department of Good Clinical Practice Office, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yang Liu
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Peihao Yin
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Guowen Li
- Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Yunman Wang
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Lin Chen
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
| | - Qingguang Chen
- Department of Endocrinology and Metabolism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Cheng Zhao
- Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Qun Lu
- Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Guang Ji
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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26
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Wang L, Du Y, Xu BJ, Deng X, Liu QH, Zhong QQ, Wang CX, Ji S, Guo MZ, Tang DQ. Metabolomics Study of Metabolic Changes in Renal Cells in Response to High-Glucose Exposure Based on Liquid or Gas Chromatography Coupled With Mass Spectrometry. Front Pharmacol 2019; 10:928. [PMID: 31481892 PMCID: PMC6711339 DOI: 10.3389/fphar.2019.00928] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 07/22/2019] [Indexed: 12/14/2022] Open
Abstract
Diabetic nephropathy (DN) is one of the most serious microvascular complications and the leading causes of death in diabetes mellitus (DM). To find biomarkers for prognosing the occurrence and development of DN has significant clinical value for its prevention, diagnosis, and treatment. In this study, a non-targeted cell metabolomics–based ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry and gas chromatography coupled with mass spectrometry was developed and performed the dynamic metabolic profiles of rat renal cells including renal tubular epithelial cells (NRK-52E) and glomerular mesangial cells (HBZY-1) in response to high glucose at time points of 12 h, 24 h, 36 h, and 48 h. Some potential biomarkers were then verified using clinical plasma samples collected from 55 healthy volunteers, 103 DM patients, and 57 DN patients. Statistical methods, such as principal component analysis and partial least squares to latent structure-discriminant analysis were recruited for data analyses. As a result, palmitic acid and linoleic acid (all-cis-9,12) were the potential indicators for the occurrence and development of DN, and valine, leucine, and isoleucine could be used as the prospective biomarkers for DM. In addition, rise and fall of leucine and isoleucine levels in plasma could be used for prognosing DN in DM patients. Through this study, we established a novel non-targeted cell dynamic metabolomics platform and identified potential biomarkers that may be applied for the diagnosis and prognosis of DM and DN.
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Affiliation(s)
- Liang Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, China
| | - Yan Du
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Deparment of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Bing-Ju Xu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Xu Deng
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Qing-Hua Liu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Qiao-Qiao Zhong
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Chen-Xiang Wang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Shuai Ji
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Deparment of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Meng-Zhe Guo
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Deparment of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Dao-Quan Tang
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Deparment of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, China
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