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Article: Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications.

Yang, Xi-Ding / Yang, Yong-Yu

2022 Volume 13, Page(s) 853822

Abstract: The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of diabetes mellitus (DM) and its complications is necessary for the development of effective treatments. ... ...

Abstract	The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of diabetes mellitus (DM) and its complications is necessary for the development of effective treatments. Ferroptosis is a newly identified form of programmed cell death caused by the production of reactive oxygen species and an imbalance in iron homeostasis. Increasing evidence suggests that ferroptosis plays a pivotal role in the pathogenesis of diabetes and diabetes-related complications. In this review, we summarize the potential impact and regulatory mechanisms of ferroptosis on diabetes and its complications, as well as inhibitors of ferroptosis in diabetes and diabetic complications. Therefore, understanding the regulatory mechanisms of ferroptosis and developing drugs or agents that target ferroptosis may provide new treatment strategies for patients with diabetes.
MeSH term(s)	Diabetes Complications/etiology ; Diabetes Mellitus/drug therapy ; Ferroptosis ; Homeostasis ; Humans ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2022-03-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.853822
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Article: Potential lipolytic regulators derived from natural products as effective approaches to treat obesity.

Yang, Xi-Ding / Ge, Xing-Cheng / Jiang, Si-Yi / Yang, Yong-Yu

Frontiers in endocrinology

2022 Volume 13, Page(s) 1000739

Abstract: Epidemic obesity is contributing to increases in the prevalence of obesity-related metabolic diseases and has, therefore, become an important public health problem. Adipose tissue is a vital energy storage organ that regulates whole-body energy ... ...

Abstract	Epidemic obesity is contributing to increases in the prevalence of obesity-related metabolic diseases and has, therefore, become an important public health problem. Adipose tissue is a vital energy storage organ that regulates whole-body energy metabolism. Triglyceride degradation in adipocytes is called lipolysis. It is closely tied to obesity and the metabolic disorders associated with it. Various natural products such as flavonoids, alkaloids, and terpenoids regulate lipolysis and can promote weight loss or improve obesity-related metabolic conditions. It is important to identify the specific secondary metabolites that are most effective at reducing weight and the health risks associated with obesity and lipolysis regulation. The aims of this review were to identify, categorize, and clarify the modes of action of a wide diversity of plant secondary metabolites that have demonstrated prophylactic and therapeutic efficacy against obesity by regulating lipolysis. The present review explores the regulatory mechanisms of lipolysis and summarizes the effects and modes of action of various natural products on this process. We propose that the discovery and development of natural product-based lipolysis regulators could diminish the risks associated with obesity and certain metabolic conditions.
MeSH term(s)	Biological Products/pharmacology ; Biological Products/therapeutic use ; Flavonoids ; Humans ; Lipolysis ; Metabolic Diseases/drug therapy ; Obesity/drug therapy ; Obesity/metabolism ; Terpenes/therapeutic use ; Triglycerides/metabolism
Chemical Substances	Biological Products ; Flavonoids ; Terpenes ; Triglycerides
Language	English
Publishing date	2022-09-13
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.1000739
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Article: Pharmacokinetics and bioequivalence of two metoprolol succinate extended release tablets in healthy Chinese subjects under fasting and fed conditions.

Yang, Xiding / Zhu, Ronghua / Chen, Xiaojun / Li, Jingjing / Luo, Guirong / Yang, Lingfeng / Fan, Xiao / Yan, Qiangyong / Peng, Wenxing / Fang, Pingfei

International journal of clinical pharmacology and therapeutics

2024 Volume 62, Issue 2, Page(s) 101–108

Abstract: Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release (ER) tablets in healthy Chinese subjects under fasting and fed conditions.: ...

Abstract	Aims: The aims of this study were to evaluate and compare the pharmacokinetic profiles and establish bioequivalence of test and reference metoprolol succinate extended-release (ER) tablets in healthy Chinese subjects under fasting and fed conditions. Materials and methods: Subjects were randomly assigned to either the fasting or the fed group and also to one of the two treatment sequences (test-reference or reference-test), according to which they received a single 47.5-mg dose of the test or reference metoprolol ER tablet in the study periods. During each period, blood samples were collected at pre-dose and at intervals up to 48 hours after dosing. Plasma concentrations of metoprolol were determined by liquid chromatography. The safety of both ER tablets was monitored throughout the study. Results: 60 subjects were enrolled and all completed the study, with 30 participants each in the fasting and fed groups. In both groups, the 90% confidence intervals for AUC Conclusion: The test metoprolol ER tablet was bioequivalent to the reference metoprolol ER tablet (Betaloc ZOK) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.
MeSH term(s)	Humans ; Therapeutic Equivalency ; Metoprolol/adverse effects ; Cross-Over Studies ; Fasting ; Area Under Curve ; Healthy Volunteers ; Tablets ; China
Chemical Substances	Metoprolol (GEB06NHM23) ; Tablets
Language	English
Publishing date	2024-01-04
Publishing country	Germany
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	124384-6
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
DOI	10.5414/CP204474
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Article ; Online: Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis.

Yang, Xiding / Yan, Qiangyong / Yang, Lingfeng / Li, Jingjing / Fan, Xiao / Chen, Jindong / Wu, Haishan / Yang, Yongyu / Zhu, Ronghua / Fang, Pingfei

European journal of clinical pharmacology

2024

Abstract: Purpose: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we ... ...

Abstract	Purpose: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we performed a meta-analysis to evaluate the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients. Methods: We included 16 retrospective studies on the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients, with data from both generic and brand name treatment phases in eight clozapine bioequivalence studies conducted in a single center in China from 2018 to 2022. Review Manager 5.4 was used for meta-analysis of the included studies. Results: The SMDs with 95% CIs of AUC Conclusion: The combination with propranolol could significantly increase systemic exposure and extended T
Language	English
Publishing date	2024-04-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-024-03690-w
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Article ; Online: First-in-human phase I studies of YJ001 spray applied to local skin in healthy subjects and patients with diabetic neuropathic pain.

Yang, Xiding / Zhu, Ronghua / Zhang, Jing / Hou, Zaihua / Yang, Lingfeng / Fan, Xiao / Yan, Qiangyong / Li, Jingjing / Zhou, Zhiguang / Fang, Pingfei

Expert opinion on investigational drugs

2023 Volume 32, Issue 6, Page(s) 553–562

Abstract: Background: The study aimed to investigate the safety, pharmacokinetics (PK), and efficacy of YJ001 spray, a candidate drug for diabetic neuropathic pain (DNP) therapy.: Research design & methods: Forty-two healthy subjects received one of four ... ...

Abstract	Background: The study aimed to investigate the safety, pharmacokinetics (PK), and efficacy of YJ001 spray, a candidate drug for diabetic neuropathic pain (DNP) therapy. Research design & methods: Forty-two healthy subjects received one of four single doses (240, 480, 720, 960 mg) of YJ001 spray or placebo, and 20 patients with DNP received repeated doses (240 and 480 mg) of YJ001 spray or placebo via topical route of administration to the local skin of both feet. Safety, and efficacy assessments were performed, and blood samples were collected for PK analyses. Results: The pharmacokinetic results revealed that the concentrations of YJ001 and its metabolites were low, and most of them were lower than the lower limit of quantitation. In patients with DNP, treatment with a 480 mg YJ001 spray dose significantly reduced pain and improved sleep quality compared with placebo. No serious adverse events (SAEs) or clinically significant findings of the safety parameters were observed. Conclusion: Systemic exposure to YJ001 and its metabolites is low after YJ001 spray is applied locally to the skin, which will reduce systemic toxicity and adverse reactions. YJ001 appears to be well tolerated and potentially effective in the management of DNP and is a promising new remedy for DNP.
MeSH term(s)	Humans ; Administration, Topical ; Diabetes Mellitus/drug therapy ; Diabetic Neuropathies/drug therapy ; Double-Blind Method ; Healthy Volunteers ; Neuralgia/drug therapy
Language	English
Publishing date	2023-05-30
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2023.2219388
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Article ; Online: Esculin protects against methionine choline-deficient diet-induced non-alcoholic steatohepatitis by regulating the Sirt1/NF-B p65 pathway

Yang, Xi-Ding / Chen, Zhuo / Ye, Ling / Chen, Jing / Yang, Yong-Yu

Pharmaceutical Biology. 2021 Jan. 1, v. 59, no. 1 p.920-930

2021

Abstract: Esculin, an active coumarin compound, has been demonstrated to exert anti-inflammatory effects. However, its potential role in non-alcoholic steatohepatitis (NASH) remains unclear. This study explored the hepatoprotective effect and the molecular ... ...

Abstract	Esculin, an active coumarin compound, has been demonstrated to exert anti-inflammatory effects. However, its potential role in non-alcoholic steatohepatitis (NASH) remains unclear. This study explored the hepatoprotective effect and the molecular mechanism of esculin in methionine choline-deficient (MCD) diet-induced NASH. Fifty C57BL/6J mice were divided into five groups: control, model, low dosage esculin (oral, 20 mg/kg), high dosage esculin (oral, 40 mg/kg), and silybin (oral, 105 mg/kg). All animals were fed a MCD diet, except those in the control group (control diet), for 6 weeks. Esculin (20 and 40 mg/kg) inhibited MCD diet-induced hepatic lipid content (triglyceride: 16.95 ± 0.67 and 14.85 ± 0.78 vs. 21.21 ± 1.13 mg/g; total cholesterol: 5.10 ± 0.34 and 4.08 ± 0.47 vs. 7.31 ± 0.58 mg/g), fibrosis, and inflammation (ALT: 379.61 ± 40.30 and 312.72 ± 21.45 vs. 559.51 ± 37.01 U/L; AST: 428.22 ± 34.29 and 328.23 ± 23.21 vs. 579.36 ± 31.93 U/L). In vitro, esculin reduced tumour necrosis factor-α, interleukin-6, fibronectin, and collagen 4A1 levels, but had no effect on lipid levels in HepG2 cells induced by free fatty acid. Esculin increased Sirt1 expression levels and decreased NF-κB acetylation levels in vivo and in vitro. Interfering with Sirt1 expression attenuated the beneficial effect of esculin on inflammatory and fibrotic factor production in HepG2 cells. These findings demonstrate that esculin ameliorates MCD diet-induced NASH by regulating the Sirt1/ac-NF-κB signalling pathway. Esculin could thus be employed as a therapy for NASH.
Keywords	acetylation ; cholesterol ; collagen ; coumarin ; diet ; esculin ; fatty liver ; fibronectins ; fibrosis ; free fatty acids ; hepatoprotective effect ; inflammation ; interleukin-6 ; lipid content ; methionine ; models ; necrosis ; neoplasms ; therapeutics ; triacylglycerols ; Inflammatory cytokine ; acetylation of NF-κB p65
Language	English
Dates of publication	2021-0101
Size	p. 920-930.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2021.1945112
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Esculin protects against methionine choline-deficient diet-induced non-alcoholic steatohepatitis by regulating the Sirt1/NF-

Yang, Xi-Ding / Chen, Zhuo / Ye, Ling / Chen, Jing / Yang, Yong-Yu

Pharmaceutical biology

2021 Volume 59, Issue 1, Page(s) 922–932

Abstract: Context: Esculin, an active coumarin compound, has been demonstrated to exert anti-inflammatory effects. However, its potential role in non-alcoholic steatohepatitis (NASH) remains unclear.: Objective: This study explored the hepatoprotective effect ... ...

Abstract	Context: Esculin, an active coumarin compound, has been demonstrated to exert anti-inflammatory effects. However, its potential role in non-alcoholic steatohepatitis (NASH) remains unclear. Objective: This study explored the hepatoprotective effect and the molecular mechanism of esculin in methionine choline-deficient (MCD) diet-induced NASH. Materials and methods: Fifty C57BL/6J mice were divided into five groups: control, model, low dosage esculin (oral, 20 mg/kg), high dosage esculin (oral, 40 mg/kg), and silybin (oral, 105 mg/kg). All animals were fed a MCD diet, except those in the control group (control diet), for 6 weeks. Results: Esculin (20 and 40 mg/kg) inhibited MCD diet-induced hepatic lipid content (triglyceride: 16.95 ± 0.67 and 14.85 ± 0.78 vs. 21.21 ± 1.13 mg/g; total cholesterol: 5.10 ± 0.34 and 4.08 ± 0.47 vs. 7.31 ± 0.58 mg/g), fibrosis, and inflammation (ALT: 379.61 ± 40.30 and 312.72 ± 21.45 vs. 559.51 ± 37.01 U/L; AST: 428.22 ± 34.29 and 328.23 ± 23.21 vs. 579.36 ± 31.93 U/L). Conclusions: These findings demonstrate that esculin ameliorates MCD diet-induced NASH by regulating the Sirt1/ac-NF-κB signalling pathway. Esculin could thus be employed as a therapy for NASH.
MeSH term(s)	Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Cell Survival/drug effects ; Choline Deficiency ; Cytokines/drug effects ; Esculin/pharmacology ; Fatty Acids, Nonesterified ; Fibrosis/drug therapy ; Hep G2 Cells ; Hepatocytes/drug effects ; Humans ; Inflammation/drug therapy ; Lipids/blood ; Liver/drug effects ; Liver/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Models, Animal ; NF-kappa B/metabolism ; Non-alcoholic Fatty Liver Disease/chemically induced ; Non-alcoholic Fatty Liver Disease/drug therapy ; Non-alcoholic Fatty Liver Disease/metabolism ; RNA, Small Interfering ; Signal Transduction ; Silybin/pharmacology ; Sirtuin 1/genetics ; Sirtuin 1/metabolism
Chemical Substances	Cytokines ; Fatty Acids, Nonesterified ; Lipids ; NF-kappa B ; RNA, Small Interfering ; Esculin (1Y1L18LQAF) ; Silybin (4RKY41TBTF) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Sirtuin 1 (EC 3.5.1.-)
Language	English
Publishing date	2021-07-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1440131-9
ISSN	1744-5116 ; 1388-0209
ISSN (online)	1744-5116
ISSN	1388-0209
DOI	10.1080/13880209.2021.1945112
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Article: Topical treatments for diabetic neuropathic pain.

Yang, Xi-Ding / Fang, Ping-Fei / Xiang, Da-Xiong / Yang, Yong-Yu

Experimental and therapeutic medicine

2019 Volume 17, Issue 3, Page(s) 1963–1976

Abstract: Diabetic neuropathic pain (DNP) has a huge impact on quality of life and can be difficult to treat. Oral treatment is the most frequently used method for DNP, but its use is often limited by systemic side effects. Topical use of drugs as an alternative ... ...

Abstract	Diabetic neuropathic pain (DNP) has a huge impact on quality of life and can be difficult to treat. Oral treatment is the most frequently used method for DNP, but its use is often limited by systemic side effects. Topical use of drugs as an alternative option for DNP treatment is currently gaining interest. In the present review, a summary is provided of the available agents for topical use in patients with DNP, including lidocaine plasters or patches, capsaicin cream, gel or patches, amitriptyline cream, clonidine gel, ketamine cream, extracts from medicinal plants including nutmeg extracts and
Language	English
Publishing date	2019-01-15
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2019.7173
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Article ; Online: Piperazine ferulate prevents high-glucose-induced filtration barrier injury of glomerular endothelial cells.

Yang, Yong-Yu / Chen, Zhuo / Yang, Xi-Ding / Deng, Rong-Rong / Shi, Ling-Xing / Yao, Liang-Yuan / Xiang, Da-Xiong

Experimental and therapeutic medicine

2021 Volume 22, Issue 4, Page(s) 1175

Abstract: Filtration barrier injury induced by high glucose (HG) levels leads to the development of diabetic nephropathy. The endothelial glycocalyx plays a critical role in glomerular barrier function. In the present study, the effects of piperazine ferulate (PF) ...

Abstract	Filtration barrier injury induced by high glucose (HG) levels leads to the development of diabetic nephropathy. The endothelial glycocalyx plays a critical role in glomerular barrier function. In the present study, the effects of piperazine ferulate (PF) on HG-induced filtration barrier injury of glomerular endothelial cells (GEnCs) were investigated and the underlying mechanism was assessed. Immunofluorescence was used to observe the distribution of the glycocalyx as well as the expression levels of syndecan-1 and Zonula occludens-1 (ZO-1). Endothelial permeability assays were performed to assess the effects of PF on the integrity of the filtration barrier. Protein and mRNA expression levels were measured by western blotting and reverse transcription-quantitative PCR analyses, respectively.
Language	English
Publishing date	2021-08-13
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2021.10607
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Article ; Online: Piperazine ferulate attenuates high glucose‑induced mesangial cell injury via the regulation of p66

Yang, Yong-Yu / Deng, Rong-Rong / Chen, Zhuo / Yao, Liang-Yuan / Yang, Xi-Ding / Xiang, Da-Xiong

Molecular medicine reports

2021 Volume 23, Issue 5

Abstract: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Hyperglycemia‑induced glomerular mesangial cells injury is associated with microvascular damage, which is an important step in the development of DN. Piperazine ferulate (PF) ... ...

Abstract	Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Hyperglycemia‑induced glomerular mesangial cells injury is associated with microvascular damage, which is an important step in the development of DN. Piperazine ferulate (PF) has been reported to exert protective effects against the progression of DN. However, whether PF prevents high glucose (HG)‑induced mesangial cell injury remains unknown. The aim of the present study was to investigate the effects of PF on HG‑induced mesangial cell injury and to elucidate the underlying mechanisms. Protein and mRNA expression levels were determined via western blot analysis and reverse transcription‑quantitative PCR, respectively. IL‑6 and TNF‑α levels were measured using ELISA. Reactive oxygen species levels and NF‑κB p65 nuclear translation were determined via immunofluorescence analysis. Apoptosis was assessed by measuring lactate dehydrogenase (LDH) release, as well as using MTT and flow cytometric assays. The mitochondrial membrane potential of mesangial cells was determined using the JC‑1 kit. The results revealed that LDH release were increased; however, cell viability and mitochondrial membrane potential were decreased in the HG group compared with the control group. These changes were inhibited after the mesangial cells were treated with PF. Moreover, PF significantly inhibited the HG‑induced production of inflammatory cytokines and the activation of NF‑κB in mesangial cells. PF also attenuated the HG‑induced upregulation of the expression levels of fibronectin and collagen 4A1. Furthermore, the overexpression of p66
MeSH term(s)	Acute Kidney Injury/chemically induced ; Acute Kidney Injury/drug therapy ; Acute Kidney Injury/genetics ; Acute Kidney Injury/pathology ; Animals ; Collagen Type IV/genetics ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/pathology ; Disease Models, Animal ; Fibronectins/genetics ; Gene Expression Regulation/drug effects ; Glucose/toxicity ; Humans ; Hyperglycemia/complications ; Hyperglycemia/drug therapy ; Hyperglycemia/genetics ; Hyperglycemia/pathology ; Interleukin-6/genetics ; Mesangial Cells/metabolism ; Mesangial Cells/pathology ; Mice ; Piperazine/pharmacology ; RNA, Messenger/genetics ; Repressor Proteins/genetics ; Transcription Factor RelA/genetics ; Tumor Necrosis Factor-alpha/genetics
Chemical Substances	Col4a1 protein, mouse ; Collagen Type IV ; Fibronectins ; GATAD2A protein, human ; Interleukin-6 ; RNA, Messenger ; Rela protein, mouse ; Repressor Proteins ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha ; interleukin-6, mouse ; Piperazine (1RTM4PAL0V) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-03-24
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2469505-1
ISSN	1791-3004 ; 1791-2997
ISSN (online)	1791-3004
ISSN	1791-2997
DOI	10.3892/mmr.2021.12013
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