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Lei K, Chen Y, Wu J, Lin Y, Bai Y, Cao H, Che Q, Guo J, Su Z. Mechanism of liver x receptor alpha in intestine, liver and adipose tissues in metabolic associated fatty liver disease. Int J Biol Macromol 2025; 307:142275. [PMID: 40112983 DOI: 10.1016/j.ijbiomac.2025.142275] [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: 01/15/2025] [Revised: 03/16/2025] [Accepted: 03/17/2025] [Indexed: 03/22/2025]
Abstract
Metabolism associated fatty liver disease (MAFLD) has emerged as a growing global health challenge with limited effective treatments. Research on nuclear receptors offers promising new therapeutic avenues for MAFLD. The liver X receptor (LXR) has gained attention for its roles in tumors and metabolic and inflammatory diseases; However, its effects on MAFLD treatment remain a subject of debate. This review explores the therapeutic role of LXRα in MAFLD, focusing on its functions in the intestine, hepatic and adipose tissue, and summarizes recent advancements in LXRα ligands over the past five years. In the intestine, LXRα activation enhances the efflux of non-biliary cholesterol and reduces inflammation in the gut-liver axis by regulating intestinal high-density lipoprotein synthesis and its interaction with lipopolysaccharide. In the liver, LXRα activation facilitates cholesterol transport, influences hepatic lipid synthesis, and exerts anti-inflammatory effects. In adipose tissue, LXRα helps delay MAFLD progression by managing lipid autophagy and insulin resistance. Ligands that modulate LXRα transcriptional activity show considerable promise for MAFLD treatment.
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Affiliation(s)
- Kaiwen Lei
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yan Chen
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jianxing Wu
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yiyu Lin
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yan Bai
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China
| | - Hua Cao
- School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, China
| | - Qishi Che
- Guangzhou Rainhome Pharm & Tech Co., Ltd, Science City, Guangzhou 510663, China
| | - Jiao Guo
- Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.
| | - Zhengquan Su
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.
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Yi F, Tao S, Wu H. Bilirubin metabolism in relation to cancer. Front Oncol 2025; 15:1570288. [PMID: 40291905 PMCID: PMC12021636 DOI: 10.3389/fonc.2025.1570288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
Bilirubin, a metabolite of hemoglobin, was long thought to be a harmful waste product, but recent studies have found it to have antioxidant and anti-tumor effects. With the extensive research on the mechanism of malignant tumor development, the antioxidant effect of bilirubin is increasingly becoming a hotspot in anti-cancer research. At present, there are two main views on the relationship between bilirubin and cancer, namely, its pro-cancer and anti-cancer effects, and in recent years, studies on the relationship between bilirubin and cancer have not been systematically summarized, which is not conducive to the further investigation of the role of bilirubin on cancer. To understand the multifaceted role of bilirubin in tumorigenesis as well as to develop more effective and affordable antitumor therapies, this review provides an overview of the effects of bilirubin on tumors in terms of oxidative, inflammatory, and cellular signaling pathways, as well as the resulting therapeutic ideas and approaches.
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Affiliation(s)
- Fengyun Yi
- Department of Traditional Chinese Medicine, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, Jiangxi, China
- The Second School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Siyu Tao
- The Second School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Hongze Wu
- Department of Traditional Chinese Medicine, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, Jiangxi, China
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Hajfathalian M, Ghelichi S, Jacobsen C. Anti-obesity peptides from food: Production, evaluation, sources, and commercialization. Compr Rev Food Sci Food Saf 2025; 24:e70158. [PMID: 40111015 PMCID: PMC11924896 DOI: 10.1111/1541-4337.70158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/29/2025] [Accepted: 02/23/2025] [Indexed: 03/22/2025]
Abstract
The global obesity epidemic has heightened interest in natural solutions, with anti-obesity peptides emerging as promising candidates. Derived from food sources such as plants, algae, marine organisms, and products like milk and eggs, these peptides combat obesity through various mechanisms but face challenges in production and scalability. The aim of this review is to explore their sources, mechanisms, measurement, and synthesis methods, including innovative approaches such as de novo synthesis, proteomics, and bioinformatics. Its unique contribution lies in critically analyzing the current state of research while highlighting novel synthesis techniques and their practical relevance in addressing commercialization challenges, offering valuable insights for advancing anti-obesity peptide development. Diverse methods for assessing the anti-obesity properties of these peptides are discussed, encompassing both in vitro and in vivo experimental approaches, as well as emerging alternatives. The review also explores the integration of cutting-edge technologies in peptide synthesis with the potential to revolutionize scalability and cost-effectiveness. Key findings assert that despite the great potential of peptides from various food sources to fight against obesity and advances in their identification and analysis, challenges like scalability, regulatory hurdles, bioavailability issues, high production costs, and consumer appeal persist. Future research should explore the use of bioinformatics tools and advanced peptide screening technologies to identify and design peptides with enhanced efficacy and bioavailability, efficient and cost-effective extraction and purification methods, sustainable practices such as utilizing byproducts from the food industry, and the efficacy of products containing isolated anti-obesity peptides versus whole materials in clinical settings.
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Affiliation(s)
- Mona Hajfathalian
- National Food InstituteTechnical University of DenmarkKongens LyngbyDenmark
| | - Sakhi Ghelichi
- National Food InstituteTechnical University of DenmarkKongens LyngbyDenmark
| | - Charlotte Jacobsen
- National Food InstituteTechnical University of DenmarkKongens LyngbyDenmark
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Lee JH, Hong KW, Park BJ, Choi JE, Jung DH. Gene-Diet Interactions in High-Density Lipoprotein Cholesterol-Related Polymorphisms and Cardiovascular Disease Risk: Insights from the Korean Genome and Epidemiology Study. Nutrients 2025; 17:778. [PMID: 40077648 PMCID: PMC11902253 DOI: 10.3390/nu17050778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Understanding gene-diet interactions is crucial for establishing dietary guidelines for cardiovascular diseases (CVD). This study analyzed the interaction between dietary intake and six genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNP) associated with high-density lipoprotein (HDL) cholesterol levels and their impact on CVD risk. Methods: A total of 68,806 participants in the Korean Genome and Epidemiology Study (KoGES) were analyzed. Six target SNPs (LPL: rs17482753; ABCA1: rs1883025; APOA5: rs651821; LIPC: rs1077835; CETP: rs17231506; and LIPG: rs9953437) were extracted from genome-wide SNP genotype data. Dietary intake was assessed using a food frequency questionnaire. SNP genotyping was conducted using the Korea Biobank Array (Korean Chip), a specialized genotyping platform designed for GWAS of blood biochemical traits in the Korean population. SNP-diet interactions on CVD risk were analyzed using generalized linear models (GLM). Results: Among the six SNPs, ABCA1: rs1883025 and APOA5: rs651821 showed significant gene-diet interactions. For rs1883025 (ABCA1), carriers of the T allele exhibited reduced HDL cholesterol levels. However, in the high-protein intake group, individuals with the T/T genotype had a significantly lower risk of ischemic stroke compared to those in the low-protein intake group (interaction p-value = 0.044). For rs651821 (APOA5), carriers of the T allele also had lower HDL cholesterol levels, but individuals with the C/C genotype (wild-type homozygotes) in the low-fat intake group showed a significantly reduced risk of coronary artery disease (interaction p-value = 0.0155). Conclusions: This study suggests potential interactions between polymorphisms associated with low HDL cholesterol and dietary patterns, particularly high-protein and low-fat diets, in relation to CVD risk. These findings highlight the importance of personalized dietary recommendations based on genetic profiles to reduce CVD risk. They provide a basis for future research aimed at developing precision nutrition guidelines and targeted interventions to manage hypo-HDL cholesterolemia and nutrition-related CVD risks.
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Affiliation(s)
- Jong-Hee Lee
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea; (J.-H.L.); (B.-J.P.)
| | - Kyung-Won Hong
- Institute of Advanced Technology, THERAGEN Health Co., Ltd., Seongnam-si 13493, Republic of Korea; (K.-W.H.); (J.-E.C.)
| | - Byoung-Jin Park
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea; (J.-H.L.); (B.-J.P.)
| | - Ja-Eun Choi
- Institute of Advanced Technology, THERAGEN Health Co., Ltd., Seongnam-si 13493, Republic of Korea; (K.-W.H.); (J.-E.C.)
| | - Dong-Hyuk Jung
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea; (J.-H.L.); (B.-J.P.)
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Dabravolski SA, Orekhov NA, Glanz VY, Sukhorukov VN, Pleshko EM, Orekhov AN. Role of ABCA1 in Atherosclerosis: Novel Mutations and Potential Plant-derived Therapies. Curr Med Chem 2025; 32:2069-2092. [PMID: 38529605 DOI: 10.2174/0109298673291917240315113845] [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: 12/21/2023] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 03/27/2024]
Abstract
ATP-binding cassette transporter A1 (ABCA1) is one of the key proteins regulating cholesterol homeostasis and playing a crucial role in atherosclerosis development. ABCA1 regulates the rate-limiting step of reverse cholesterol transport, facilitates the efflux of surplus intracellular cholesterol and phospholipids, and suppresses inflammation through several signalling pathways. At the same time, many mutations and Single Nucleotide Polymorphisms (SNPs) have been identified in the ABCA1 gene, which affects its biological function and is associated with several hereditary diseases (such as familial hypo-alpha-lipoproteinaemia and Tangier disease) and increased risk of cardiovascular diseases (CVDs). This review summarises recently identified mutations and SNPs in their connection to atherosclerosis and associated CVDs. Also, we discuss the recently described application of various plant-derived compounds to modulate ABCA1 expression in different in vitro and in vivo models. Herein, we present a comprehensive overview of the association of ABCA1 mutations and SNPs with CVDs and as a pharmacological target for different natural-derived compounds and highlight the potential application of these phytochemicals for treating atherosclerosis through modulation of ABCA1 expression.
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Affiliation(s)
- Siarhei A Dabravolski
- Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel, 2161002, Israel
| | - Nikolay A Orekhov
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow, 125315, Russia
| | - Victor Y Glanz
- Petrovsky Russian National Center of Surgery, 2 Abrikosovsky Lane, 119991, Moscow, Russia
| | - Vasily N Sukhorukov
- Petrovsky Russian National Center of Surgery, 2 Abrikosovsky Lane, 119991, Moscow, Russia
| | - Elizaveta M Pleshko
- Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow, 125315, Russia
| | - Alexander N Orekhov
- Petrovsky Russian National Center of Surgery, 2 Abrikosovsky Lane, 119991, Moscow, Russia
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Geng X, Tian W, Zhuang M, Shang H, Gong Z, Li J. Green Radish Polysaccharides Ameliorate Hyperlipidemia in High-Fat-Diet-Induced Mice via Short-Chain Fatty Acids Production and Gut Microbiota Regulation. Foods 2024; 13:4113. [PMID: 39767053 PMCID: PMC11675633 DOI: 10.3390/foods13244113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/14/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
The objective of this study was to examine the hypolipidemic effect and potential mechanism of action of green radish polysaccharide (GRP) in hyperlipidemic mice. We found that in mice fed a high-fat diet, supplementing with GRP reduced body weight and liver index, significantly improved serum lipid levels and markers of liver damage, and mitigated oxidative stress and inflammation. Mechanistically, in these hyperlipidemic mice, the size of fat cells was reduced by GRP, and the abnormal accumulation of lipid droplets was reduced. We also found that GRP regulates the composition of the intestinal microbiota, including the ratio of Firmicutes to Mycobacteria F/B and the levels of Blautia spp., which have been shown to alleviate liver damage and treat hyperlipidemia. Metabolite pathway analysis using the Kyoto Encyclopedia of Genes and Genomes identified the glycolysis/glycolytic metabolism and propionate metabolism pathways as potential targets for GRP in the amelioration of hyperlipidemia.
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Affiliation(s)
| | | | | | | | | | - Jianrong Li
- Department of Food Science and Engineering, College of Food Science and Engineering, Bohai University, Jinzhou 121013, China; (X.G.); (W.T.); (M.Z.); (H.S.); (Z.G.)
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7
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Zhang W, Wang L, Wang Y, Fang Y, Cao R, Fang Z, Han D, Huang X, Gu Z, Zhang Y, Zhu Y, Ma Y, Cao F. Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model. SCIENCE CHINA. LIFE SCIENCES 2024; 67:2678-2691. [PMID: 39225895 DOI: 10.1007/s11427-024-2602-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 04/19/2024] [Indexed: 09/04/2024]
Abstract
Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.
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Affiliation(s)
- Weiwei Zhang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Linghuan Wang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, 300071, China
| | - Yujia Wang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Yan Fang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Ruihua Cao
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Zhiyi Fang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, 300071, China
| | - Dong Han
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Xu Huang
- Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Zhenghui Gu
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Yingjie Zhang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Yan Zhu
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, 300071, China
| | - Yan Ma
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Feng Cao
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China.
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Abbasluo M, Bakhshi Ardakani M, Jafari N, Pazoki M. Evaluation of PPAR-α, PPAR-γ, TLR2, TLR4 Gene Expression In Patients with Coronary Artery Disease (CAD): An Experimental Study. Med J Islam Repub Iran 2024; 38:128. [PMID: 39968463 PMCID: PMC11835405 DOI: 10.47176/mjiri.38.128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Indexed: 02/20/2025] Open
Abstract
Background Coronary artery disease (CAD) is one of the heart diseases that causes the death of many patients in the world. Many genes and molecular pathways are involved in the regulation of inflammation. However, some genes have a regulatory role and control immune responses. In recent studies, few studies have been done regarding the role of TLRs and PPARs in CAD. Hence, the present study aimed to determine and compare the mRNA expression of PPAR-α and PPAR-γ genes and genes of the innate immune system messenger pathway, including TLR2and TLR4, in CAD patients in comparison to normal individuals. Methods This study (case-control) was conducted on 12 patients with coronary arteries and 10 healthy individuals as healthy controls. RNA extraction was performed, cDNA was produced, and then the mRNA expression levels of TLR2, TLR4, PPAR-α, and PPAR-γ genes were examined using Syber green Real-Time PCR. The t-test sample and the related non-parametric tests were used to investigate the relationship between the quantitative variables. The significance level in all tests was considered as less than 0.05. Results The results of data analysis showed that the expression level of TLR2 and TLR4 genes was significantly increased in the patient group compared to the controls (P=0.001). However, although PPAR-α and PPAR-γ genes were up-regulated in patients' samples, the comparison of gene expression levels did not significantly differ between the case and control groups. Conclusion we found meaningful results to the significant role of 2 and TLR4 in the pathogenesis of CAD and emphasize the hypothesis that TLR2 and TLR4 can be considered therapeutic options.
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Affiliation(s)
- Mahbobe Abbasluo
- Department of Biology, Islamic Azad University, Ashkezar Branch, Ashkezar, Iran
| | | | - Negar Jafari
- Department of Cardiology, School of Medicine, Seyedoshohda Hospital, Urmia University of Medical Sciences, Urmia, Iran
| | - Mahboubeh Pazoki
- Department of Cardiology, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran
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Xu R, Cao JW, Geng Y, Xu TC, Guo MY. Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRβ pathway in vivo and in vitro in mice. Arch Toxicol 2024; 98:3713-3725. [PMID: 39096369 DOI: 10.1007/s00204-024-03831-1] [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: 05/25/2024] [Accepted: 07/25/2024] [Indexed: 08/05/2024]
Abstract
Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRβ pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 μg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRβ as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRβ, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRβ pathway thereby influencing skeletal muscle development.
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Affiliation(s)
- Ran Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Jing-Wen Cao
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Yuan Geng
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Tian-Chao Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Meng-Yao Guo
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
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Zhao L, Wang S, Xu X, Guo W, Yang J, Liu Y, Xie S, Piao G, Xu T, Wang Y, Xu Y. Integrated metabolomics and network pharmacology to reveal the lipid-lowering mechanisms of Qizha Shuangye granules in hyperlipidemic rats. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:3265-3274. [PMID: 38087399 DOI: 10.1002/jsfa.13213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/02/2023] [Accepted: 12/09/2023] [Indexed: 12/24/2023]
Abstract
BACKGROUND Qizha Shuangye granules (QSG) comprise six traditional Chinese herbal medicines (TCHMs), which have a long history of treating hyperlipidemia (HLP) in China. This study aimed to evaluate the potential lipid-lowering effects of QSG in an HLP rat model and investigate possible mechanisms. The HLP rat model was induced by a high-fat diet. Lipid-related indicators in serum were detected. Serum and liver metabolites were investigated using a liquid chromatography-mass spectrometry-based metabolomics approach. A herb-compound-target-metabolite (H-C-T-M) network was further constructed to reveal the possible molecular mechanism of QSG to alleviate HLP. RESULTS The administration of QSG inhibited the HLP-induced changes in total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) levels. Additionally, QSG significantly attenuated the liver histopathological changes induced by HLP. Metabolomic analysis showed the serum and liver metabolic disorders presented in HLP rats. QSG can reverse the abnormal metabolism caused by HLP. Through network pharmacology analysis, key proteins such as androgen receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and peroxisome proliferator-activated receptor-α were screened out, and they were speculated to be possible therapeutic targets for QSG to treat HLP. CONCLUSION The present study integrated metabolomics and network pharmacology analysis to reveal the efficacy and possible mechanism of QSG in treating HLP, which provides a new reference for the research and development of QSG as a functional food. © 2023 Society of Chemical Industry.
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Affiliation(s)
- Liang Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- College of Pharmacy, Yanbian University, Yanji, China
- Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Shuyue Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaohang Xu
- Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Wenjun Guo
- Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Jingxuan Yang
- Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Yue Liu
- Key Laboratory for Analysis Methods of Active Ingredients in Traditional Chinese Medicine, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Shengxu Xie
- Key Laboratory for Analysis Methods of Active Ingredients in Traditional Chinese Medicine, Jilin Academy of Chinese Medicine Sciences, Changchun, China
| | - Guangchun Piao
- College of Pharmacy, Yanbian University, Yanji, China
- Key Laboratory for Natural Resource of Changbai Mountain, Yanbian University, Yanji, China
| | - Tunhai Xu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yang Wang
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China
| | - Yajuan Xu
- Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, China
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11
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Chen A, Jiang Z, Cai L, Tang D. On the road to colorectal cancer development: crosstalk between the gut microbiota, metabolic reprogramming, and epigenetic modifications. Carcinogenesis 2023; 44:631-641. [PMID: 37586059 DOI: 10.1093/carcin/bgad058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 07/21/2023] [Accepted: 08/08/2023] [Indexed: 08/18/2023] Open
Abstract
An increasing number of studies have reported the role of gut microbes in colorectal cancer (CRC) development, as they can be influenced by dietary metabolism and mediate alterations in host epigenetics, ultimately affecting CRC. Intake of specific dietary components can affect gut microbial composition and function, and their metabolism regulates important epigenetic functions that may influence CRC risk. Gut microbes can regulate epigenetic modifications through nutrient metabolism, including histone modification, DNA methylation, and noncoding RNAs. Epigenetics, in turn, determines the gut microbial composition and thus influences the risk of developing CRC. This review discusses the complex crosstalk between metabolic reprogramming, gut microbiota, and epigenetics in CRC and highlights the potential applications of the gut microbiota as a biomarker for the prevention, diagnosis, and therapy of CRC.
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Affiliation(s)
- Anqi Chen
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China
| | - Zhengting Jiang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China
| | - Lingli Cai
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China
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12
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Rakateli L, Huchzermeier R, van der Vorst EPC. AhR, PXR and CAR: From Xenobiotic Receptors to Metabolic Sensors. Cells 2023; 12:2752. [PMID: 38067179 PMCID: PMC10705969 DOI: 10.3390/cells12232752] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 11/23/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
Traditionally, xenobiotic receptors are known for their role in chemical sensing and detoxification, as receptor activation regulates the expression of various key enzymes and receptors. However, recent studies have highlighted that xenobiotic receptors also play a key role in the regulation of lipid metabolism and therefore function also as metabolic sensors. Since dyslipidemia is a major risk factor for various cardiometabolic diseases, like atherosclerosis and non-alcoholic fatty liver disease, it is of major importance to understand the molecular mechanisms that are regulated by xenobiotic receptors. In this review, three major xenobiotic receptors will be discussed, being the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Specifically, this review will focus on recent insights into the metabolic functions of these receptors, especially in the field of lipid metabolism and the associated dyslipidemia.
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Affiliation(s)
- Leonida Rakateli
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (L.R.); (R.H.)
- Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), RWTH Aachen University, 52074 Aachen, Germany
| | - Rosanna Huchzermeier
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (L.R.); (R.H.)
- Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), RWTH Aachen University, 52074 Aachen, Germany
| | - Emiel P. C. van der Vorst
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany; (L.R.); (R.H.)
- Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), RWTH Aachen University, 52074 Aachen, Germany
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, 80336 Munich, Germany
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany
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13
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Xie J, Peng L, Wang T, Yang C, Chen N, Feng X, Wu T, Xu T, Chen Y. QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/β-ABCA1 pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 315:116684. [PMID: 37230281 DOI: 10.1016/j.jep.2023.116684] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/13/2023] [Accepted: 05/22/2023] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE QiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. AIM OF STUDY The aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. MATERIALS AND METHODS Eight-week-old male apoE-/- mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. RESULTS After eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/β-ABCA1 in atherosclerotic plaque. CONCLUSION The anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque.
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Affiliation(s)
- Jing Xie
- Graduate School, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
| | - Li Peng
- Department of Cardiovascular Internal Medicine, Second Hospital, Guizhou University of Traditional Chinese Medicine, 550001, Guiyang, Guizhou, China.
| | - Taotao Wang
- Graduate School, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
| | - Chengyong Yang
- Graduate School, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
| | - Nanting Chen
- Graduate School, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
| | - Xue Feng
- Graduate School, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
| | - Tingchun Wu
- Department of Cardiovascular Internal Medicine, Second Hospital, Guizhou University of Traditional Chinese Medicine, 550001, Guiyang, Guizhou, China.
| | - Tao Xu
- Department of Cardiovascular Internal Medicine, Second Hospital, Guizhou University of Traditional Chinese Medicine, 550001, Guiyang, Guizhou, China.
| | - Yunzhi Chen
- Basic Medical College, Guizhou University of Traditional Chinese Medicine, 550025, Guiyang, Guizhou, China.
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14
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Gu YY, Cui XB, Jiang J, Zhang YX, Liu MH, Cheng SB, Li YY, Liu LL, Liao RX, Zhao P, Jin W, Jia YH, Wang J, Zhou FH. Dingxin recipe Ⅲ ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 312:116483. [PMID: 37059245 DOI: 10.1016/j.jep.2023.116483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 04/03/2023] [Accepted: 04/09/2023] [Indexed: 05/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. AIM OF THE STUDY Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia. MATERIALS AND METHODS The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. RESULTS DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1. CONCLUSION DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.
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Affiliation(s)
- Yu-Yan Gu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Xiao-Bing Cui
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Department of Cardiology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China
| | - Jing Jiang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Ya-Xin Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Meng-Hua Liu
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Sai-Bo Cheng
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Yu-Ye Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Lin-Ling Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Rong-Xin Liao
- Center of TCM Preventive Treatment, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China
| | - Peng Zhao
- Center of TCM Preventive Treatment, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China
| | - Wen Jin
- Department of Cardiac Intensive Care Unit, Cardiovascular Hospital, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China
| | - Yu-Hua Jia
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
| | - Jing Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
| | - Feng-Hua Zhou
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China; Center of TCM Preventive Treatment, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China.
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15
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Cheng X, Han X, Zhou L, Sun Y, Zhou Q, Lin X, Gao Z, Wang J, Zhao W. Cabernet sauvignon dry red wine ameliorates atherosclerosis in mice by regulating inflammation and endothelial function, activating AMPK phosphorylation, and modulating gut microbiota. Food Res Int 2023; 169:112942. [PMID: 37254366 DOI: 10.1016/j.foodres.2023.112942] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/28/2023] [Accepted: 05/02/2023] [Indexed: 06/01/2023]
Abstract
Limited evidence suggests that the abundance of antioxidant polyphenols in dry red wine (DRW) may prevent cardiovascular diseases, a benefit likely attributed to abundant antioxidant polyphenols present in DRW. Here, we examined the anti-atherosclerotic effect of Cabernet Sauvignon DRW (CSDRW) in a mouse model of atherosclerosis (AS) using metabolomic profiling and molecular techniques. Oral administration of CSDRW reduced atherosclerotic lesion size in ApoE-/- mice, alleviated hyperlipidemia, ameliorated hepatic lipid accumulation mediated by AMPK activation, and promoted lipid metabolism via PPARγ-LXR-α-ABCA1 pathway regulation. CSDRW increased the relative abundance of beneficial gut microbiota, including Bacteroidetes, Verrucomicrobiota, and Akkermansiaceae. Metabolic analysis using liquid chromatography-tandem mass spectrometry revealed that CSDRW contained various polyphenols, including flavanol, phenolic acid, flavonol, and resveratrol, which possibly mediate the beneficial effects in AS by reducing inflammation, restoring normal endothelial function, regulating hepatic lipid metabolism, and modulating gut microbiota composition.
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Affiliation(s)
- Xinlong Cheng
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Xue Han
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China; School of Public Health, Hebei University, Baoding 071000, PR China
| | - Liangfu Zhou
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Yasai Sun
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Qian Zhou
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Xuan Lin
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Zhe Gao
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Jie Wang
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China
| | - Wen Zhao
- Department of Nutrition and Food Safety, College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, PR China.
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16
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Xu P. Nuclear Receptors in Health and Diseases. Int J Mol Sci 2023; 24:9153. [PMID: 37298107 PMCID: PMC10252477 DOI: 10.3390/ijms24119153] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/11/2023] [Accepted: 05/18/2023] [Indexed: 06/12/2023] Open
Abstract
Nuclear receptors (NRs) are a vital superfamily of transcription factors that play crucial roles in physiology and pharmacology [...].
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Affiliation(s)
- Pengfei Xu
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China;
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
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17
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Miao M, Wang X, Liu T, Li YJ, Yu WQ, Yang TM, Guo SD. Targeting PPARs for therapy of atherosclerosis: A review. Int J Biol Macromol 2023:125008. [PMID: 37217063 DOI: 10.1016/j.ijbiomac.2023.125008] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 05/16/2023] [Accepted: 05/19/2023] [Indexed: 05/24/2023]
Abstract
Atherosclerosis, a chief pathogenic factor of cardiovascular disease, is associated with many factors including inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are widely expressed with tissue- and cell-specificity. They control multiple genes that are involved in lipid metabolism, inflammatory response, and redox homeostasis. Given the diverse biological functions of PPARs, they have been extensively studied since their discovery in 1990s. Although controversies exist, accumulating evidence have demonstrated that PPAR activation attenuates atherosclerosis. Recent advances are valuable for understanding the mechanisms of action of PPAR activation. This article reviews the recent findings, mainly from the year of 2018 to present, including endogenous molecules in regulation of PPARs, roles of PPARs in atherosclerosis by focusing on lipid metabolism, inflammation, and oxidative stress, and synthesized PPAR modulators. This article provides information valuable for researchers in the field of basic cardiovascular research, for pharmacologists that are interested in developing novel PPAR agonists and antagonists with lower side effects as well as for clinicians.
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Affiliation(s)
- Miao Miao
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Xue Wang
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Tian Liu
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Yan-Jie Li
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Wen-Qian Yu
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Tong-Mei Yang
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China
| | - Shou-Dong Guo
- Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang 261053, China.
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18
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Roy PK, Islam J, Lalhlenmawia H. Prospects of potential adipokines as therapeutic agents in obesity-linked atherogenic dyslipidemia and insulin resistance. Egypt Heart J 2023; 75:24. [PMID: 37014444 PMCID: PMC10073393 DOI: 10.1186/s43044-023-00352-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 03/28/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND In normal circumstances, AT secretes anti-inflammatory adipokines (AAKs) which regulates lipid metabolism, insulin sensitivity, vascular hemostasis, and angiogenesis. However, during obesity AT dysfunction occurs and leads to microvascular imbalance and secretes several pro-inflammatory adipokines (PAKs), thereby favoring atherogenic dyslipidemia and insulin resistance. Literature suggests decreased levels of circulating AAKs and increased levels of PAKs in obesity-linked disorders. Importantly, AAKs have been reported to play a vital role in obesity-linked metabolic disorders mainly insulin resistance, type-2 diabetes mellitus and coronary heart diseases. Interestingly, AAKs counteract the microvascular imbalance in AT and exert cardioprotection via several signaling pathways such as PI3-AKT/PKB pathway. Although literature reviews have presented a number of investigations detailing specific pathways involved in obesity-linked disorders, literature concerning AT dysfunction and AAKs remains sketchy. In view of the above, in the present contribution an effort has been made to provide an insight on the AT dysfunction and role of AAKs in modulating the obesity and obesity-linked atherogenesis and insulin resistance. MAIN BODY "Obesity-linked insulin resistance", "obesity-linked cardiometabolic disease", "anti-inflammatory adipokines", "pro-inflammatory adipokines", "adipose tissue dysfunction" and "obesity-linked microvascular dysfunction" are the keywords used for searching article. Google scholar, Google, Pubmed and Scopus were used as search engines for the articles. CONCLUSIONS This review offers an overview on the pathophysiology of obesity, management of obesity-linked disorders, and areas in need of attention such as novel therapeutic adipokines and their possible future perspectives as therapeutic agents.
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Affiliation(s)
- Probin Kr Roy
- Department of Pharmacy, Regional Institute of Paramedical and Nursing Sciences (RIPANS), Aizawl, Mizoram, 796017, India.
| | - Johirul Islam
- Coromandel International Limited, Hyderabad, Telangana, 500101, India
| | - Hauzel Lalhlenmawia
- Department of Pharmacy, Regional Institute of Paramedical and Nursing Sciences (RIPANS), Aizawl, Mizoram, 796017, India
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19
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Pu L, Meng Q, Li S, Wang Y, Liu B. TXNRD1 knockdown inhibits the proliferation of endothelial cells subjected to oscillatory shear stress via activation of the endothelial nitric oxide synthase/apoptosis pathway. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119436. [PMID: 36754152 DOI: 10.1016/j.bbamcr.2023.119436] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/26/2023] [Accepted: 01/29/2023] [Indexed: 02/10/2023]
Abstract
Atherosclerosis is the main cause of cardiovascular disease, and fluid shear stress is a key factor regulating its occurrence and development. Oscillatory shear stress (Oss) is an important pro-atherosclerosis factor. Oss mainly occurs in areas that are susceptible to atherosclerosis, but the exact mechanism of atherosclerosis induction remains unclear. Therefore, starting from the atheroprone phenotype that Oss stimulates abnormal vascular endothelial cell proliferation, this study aimed to reveal the underlying mechanism of Oss-induced atherosclerosis formation and to identify new targets for the prevention and treatment of atherosclerosis. In this study, the gene encoding thioredoxin reductase 1 (TXNRD1), which is closely related to atherosclerosis development and cell proliferation, was screened by analyzing the transcriptome sequencing data of static and Oss-treated human aortic endothelial cells (HAECs). Moreover, this study successfully verified that TXNRD1 mRNA and protein were significantly upregulated in Oss-treated HAECs. Oss significantly promoted the proliferation, migration, and tube formation of HAECs, whereas TXNRD1 knockdown impaired the proliferation, migration, and tube formation of Oss-treated HAECs, and this process was mainly achieved via activation of the apoptosis pathway. To further clarify whether Oss-sensitive TXNRD1 affects the apoptosis rate and proliferative ability of HAECs by regulating the endothelial nitric oxide synthase (eNOS) pathway, we used NG-nitro-L-arginine methyl ester (L-NAME) to inhibit eNOS activity and nitric oxide (NO) production. L-NAME significantly reversed the promoting effect of TXNRD1 knockdown on Oss-treated HAEC apoptosis, and it also abolished the inhibitory effect of TXNRD1 knockdown on the proliferation and S + G2 phase cell mass of Oss-treated HAECs. In conclusion, this study showed that TXNRD1 knockdown inhibited the proliferation of HAECs exposed to Oss by activating the eNOS/apoptosis pathway, revealing that TXNRD1 is involved in the dysregulation of Oss-induced endothelial cell proliferation. These findings provide new directions and insights into the prevention and treatment of atherosclerosis.
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Affiliation(s)
- Luya Pu
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China
| | - Qingyu Meng
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China
| | - Shuai Li
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China
| | - Yaru Wang
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China
| | - Bin Liu
- Cardiovascular Disease Center, The First Hospital of Jilin University, Changchun, China.
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20
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Carrillo-Tripp M, Reyes Y, Delgado-Coello B, Mas-Oliva J, Gutiérrez-Vidal R. Peptide Helix-Y 12 as Potential Effector for Peroxisome Proliferator-Activated Receptors. PPAR Res 2023; 2023:8047378. [PMID: 37096195 PMCID: PMC10122583 DOI: 10.1155/2023/8047378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 03/29/2023] [Accepted: 04/03/2023] [Indexed: 04/26/2023] Open
Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of lipids and glucose metabolism, and immune response. Therefore, they have been considered pharmacological targets for treating metabolic diseases, such as dyslipidemia, atherosclerosis, and non-alcoholic fatty liver disease. However, the available synthetic ligands of PPARs have mild to significant side effects, generating the necessity to identify new molecules that are selective PPAR ligands with specific biological responses. This study aimed to evaluate some components of the atheroprotective and hepatoprotective HB-ATV-8 nanoparticles [the amphipathic peptide Helix-Y12, thermozeaxanthin, thermozeaxanthin-13, thermozeaxanthin-15, and a set of glycolipids], as possible ligands of PPARs through blind molecular docking. According to the change in free energy upon protein-ligand binding, ∆G b, thermozeaxanthins show a more favorable interaction with PPARs, followed by Helix-Y12. Moreover, Helix-Y12 interacts with most parts of the Y-shaped ligand-binding domain (LBD), surrounding helix 3 of PPARs, and reaching helix 12 of PPARα and PPARγ. As previously reported for other ligands, Tyr314 and Tyr464 of PPARα interact with Helix-Y12 through hydrogen bonds. Several PPARα's amino acids are involved in the ligand binding by hydrophobic interactions. Furthermore, we identified additional PPARs' amino acids interacting with Helix-Y12 through hydrogen bonds still not reported for known ligands. Our results show that, from the studied ligand set, the Helix-Y12 peptide and Tzeaxs have the most significant probability of binding to the PPARs' LBD, suggesting novel ligands for PPARs.
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Affiliation(s)
- Mauricio Carrillo-Tripp
- Biomolecular Diversity Laboratory, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Vía del Conocimiento 201, PIIT, C.P. 66600, Apodaca, Nuevo León, Mexico
| | - Yair Reyes
- Metabolic Diseases Laboratory, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Vía del Conocimiento 201, PIIT, C.P. 66600, Apodaca, Nuevo León, Mexico
- Universidad Politécnica de Puebla, Tercer Carril del Ejido, Serrano s/n, Cuanalá, C.P. 7264, Puebla, Mexico
| | - Blanca Delgado-Coello
- Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, C.P. 04510, CDMX, Mexico
| | - Jaime Mas-Oliva
- Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, C.P. 04510, CDMX, Mexico
| | - Roxana Gutiérrez-Vidal
- Metabolic Diseases Laboratory, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Vía del Conocimiento 201, PIIT, C.P. 66600, Apodaca, Nuevo León, Mexico
- Programa de Investigadoras e Investigadores por México, Conacyt, CDMX, Mexico
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May L, Bartolo B, Harrison D, Guzik T, Drummond G, Figtree G, Ritchie R, Rye KA, de Haan J. Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery. Clin Sci (Lond) 2022; 136:1731-1758. [PMID: 36459456 PMCID: PMC9727216 DOI: 10.1042/cs20210862] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/21/2022] [Accepted: 11/04/2022] [Indexed: 08/10/2023]
Abstract
Cardiovascular disease (CVD) remains the leading cause of death worldwide. An ongoing challenge remains the development of novel pharmacotherapies to treat CVD, particularly atherosclerosis. Effective mechanism-informed development and translation of new drugs requires a deep understanding of the known and currently unknown biological mechanisms underpinning atherosclerosis, accompanied by optimization of traditional drug discovery approaches. Current animal models do not precisely recapitulate the pathobiology underpinning human CVD. Accordingly, a fundamental limitation in early-stage drug discovery has been the lack of consensus regarding an appropriate experimental in vivo model that can mimic human atherosclerosis. However, when coupled with a clear understanding of the specific advantages and limitations of the model employed, preclinical animal models remain a crucial component for evaluating pharmacological interventions. Within this perspective, we will provide an overview of the mechanisms and modalities of atherosclerotic drugs, including those in the preclinical and early clinical development stage. Additionally, we highlight recent preclinical models that have improved our understanding of atherosclerosis and associated clinical consequences and propose model adaptations to facilitate the development of new and effective treatments.
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Affiliation(s)
- Lauren T. May
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
| | | | - David G. Harrison
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville TN, U.S.A
| | - Tomasz Guzik
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, U.K
- Department of Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Grant R. Drummond
- Centre for Cardiovascular Biology and Disease Research, Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, Victoria, Australia
| | - Gemma A. Figtree
- Kolling Research Institute, University of Sydney, Sydney, Australia
- Imaging and Phenotyping Laboratory, Charles Perkins Centre and Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Rebecca H. Ritchie
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia
| | - Kerry-Anne Rye
- Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia
| | - Judy B. de Haan
- Cardiovascular Inflammation and Redox Biology Lab, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Department of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia
- Department Cardiometabolic Health, University of Melbourne, Parkville, Victoria 3010, Australia
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria 3086, Australia
- Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia
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22
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Wang M, Xiang Q, Sun W, Zhang H, Shi R, Guo J, Tong H, Fan M, Ding Y, Shi H, Yu P, Shen L, Wang Q, Chen X. Qihuang Zhuyu Formula Attenuates Atherosclerosis via Targeting PPAR γ to Regulate Cholesterol Efflux and Endothelial Cell Inflammation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2226168. [PMID: 36518993 PMCID: PMC9744610 DOI: 10.1155/2022/2226168] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 10/20/2022] [Accepted: 11/07/2022] [Indexed: 01/19/2024]
Abstract
At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE-/- mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE-/- mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.
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Affiliation(s)
- Mengxi Wang
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Qian Xiang
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Weixin Sun
- Department of Cardiology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng 224000, China
| | - Haowen Zhang
- College of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Ruijie Shi
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jun Guo
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Huaqin Tong
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Manlu Fan
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yuhan Ding
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Haibo Shi
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Peng Yu
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Le Shen
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
| | - Qiong Wang
- Laboratory of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Laboratory of Pharmacology, Jiangsu Province Hospital of Chinese Medicine, 210029 Nanjing, China
| | - Xiaohu Chen
- Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- Department of Cardiology, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China
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23
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Che W, Zhao M, Li X, Li C, Cho WC, Yu S. Current insights in molecular characterization of non-alcoholic fatty liver disease and treatment. Front Endocrinol (Lausanne) 2022; 13:1002916. [PMID: 36523601 PMCID: PMC9744925 DOI: 10.3389/fendo.2022.1002916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 10/14/2022] [Indexed: 11/30/2022] Open
Abstract
There is a continuously rising incidence of non-alcoholic fatty liver disease (NAFLD) around the world, which parallels the increasing incidence of metabolic diseases. NAFLD is a range of liver conditions that contains simple non-alcoholic fatty liver and advanced non-alcoholic steatohepatitis. In serious cases, NAFLD may develop into cirrhosis or even liver cancer. NAFLD has an intense relationship with metabolic syndrome, type 2 diabetes mellitus. It is known that gut microbiota, and functional molecules such as adenosine monophosphate-activated protein kinase JNK, and peroxisome proliferator-activated receptors (PPARs) in progressing and treating NAFLD. Traditionally, the conventional and effective therapeutic strategy is lifestyle intervention. Nowadays, new medicines targeting specific molecules, such as farnesoid X receptor, PPARs, and GLP-1 receptor, have been discovered and shown beneficial effects on patients with NAFLD. In this article, we focus on the molecular mechanisms and therapeutic approaches to NAFLD.
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Affiliation(s)
- Wensheng Che
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ming Zhao
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xiaoqing Li
- Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chunlong Li
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China
| | - Shan Yu
- Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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24
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Liu Y, Wang K, Li G, Chen Z. Differential expression pattern, bioinformatics analysis, and validation of circRNA and mRNA in patients with arteriosclerosis. Front Cardiovasc Med 2022; 9:942797. [PMID: 36176992 PMCID: PMC9513155 DOI: 10.3389/fcvm.2022.942797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/04/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundLower limb arteriosclerosis obliterans (ASO) is the formation of atherosclerotic plaques in lower limb arteries, leading to vascular stenosis and occlusion, and is a major factor leading to lower limb amputation. The ASO seriously endangers the physical and mental health of patients. As living standards improve, the disease tends to occur in younger patients, and the incidence keeps increasing year by year. The circular RNAs (circRNAs) have been found to be tissue-specific, and they play an important role in a variety of diseases, but there are few studies on the pathogenic role and expression of circRNAs in ASOs.MethodThree diseased arteries from patients with ASO and three healthy arteries from healthy donors were collected for second-generation sequencing, and the pathogenic pathways and possible pathogenic circRNAs related to ASO were screened through bioinformatics analysis. PCR and agarose gel electrophoresis were used to validate the sequencing results. The expression of circRNA-0008706 in human arterial smooth muscle cells (HASMCs) was knocked down using siRNA technology to explore its function.ResultWe identified 480 differentially expressed (DE) circRNAs and 2,997 DEmRNAs. Functional analysis revealed that epithelial-to-mesenchymal transition (EMT), lipid transport, regulation of extracellular matrix disassembly, regulation of cardiac muscle cell proliferation, branched-chain amino acid biosynthetic process, and positive regulation of cell growth and migration were enriched. Based on our previous microRNA array results, we constructed an ASO disease-specific competing endogenous (ceRNA) network. After validation, circRNA-0008706 was selected for functional analysis. Knockdown of circRNA-0008706 significantly suppressed the proliferation and migration phenotype of HASMCs and decreased the BCAT1 expression, which may be due to the specific binding of circRNA-0008706 to microRNA-125b-5p.ConclusionThis study is the first to compare the circRNA and mRNA expression profiles of ASOs and healthy arterial specimens and to construct a disease-specific ceRNA network for ASOs. This study may provide a new therapeutic target for ASO.
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Affiliation(s)
- Yunyun Liu
- Department of Gynecologic Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kangjie Wang
- Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Guanhua Li
- Division of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Guanhua Li
| | - Zhibo Chen
- Division of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Zhibo Chen
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25
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Morris G, Gevezova M, Sarafian V, Maes M. Redox regulation of the immune response. Cell Mol Immunol 2022; 19:1079-1101. [PMID: 36056148 PMCID: PMC9508259 DOI: 10.1038/s41423-022-00902-0] [Citation(s) in RCA: 206] [Impact Index Per Article: 68.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/29/2022] [Indexed: 12/20/2022] Open
Abstract
AbstractThe immune-inflammatory response is associated with increased nitro-oxidative stress. The aim of this mechanistic review is to examine: (a) the role of redox-sensitive transcription factors and enzymes, ROS/RNS production, and the activity of cellular antioxidants in the activation and performance of macrophages, dendritic cells, neutrophils, T-cells, B-cells, and natural killer cells; (b) the involvement of high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), and oxidized phospholipids in regulating the immune response; and (c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB, HIF1α, the mechanistic target of rapamycin, the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated protein kinase, and peroxisome proliferator-activated receptor. The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS. They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2, and the HDL/ApoA1/PON1 complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.
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26
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Rumora AE, Kim B, Feldman EL. A Role for Fatty Acids in Peripheral Neuropathy Associated with Type 2 Diabetes and Prediabetes. Antioxid Redox Signal 2022; 37:560-577. [PMID: 35152728 PMCID: PMC9499450 DOI: 10.1089/ars.2021.0155] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 01/19/2022] [Accepted: 01/25/2022] [Indexed: 11/12/2022]
Abstract
Significance: As the global prevalence of diabetes rises, diabetic complications are also increasing at an alarming rate. Peripheral neuropathy (PN) is the most prevalent complication of diabetes and prediabetes, and is characterized by progressive sensory loss resulting from nerve damage. While hyperglycemia is the major risk factor for PN in type 1 diabetes (T1D), the metabolic syndrome (MetS) underlies the onset and progression of PN in type 2 diabetes (T2D) and prediabetes. Recent Advances: Recent reports show that dyslipidemia, a MetS component, is strongly associated with PN in T2D and prediabetes. Dyslipidemia is characterized by an abnormal plasma lipid profile with uncontrolled lipid levels, and both clinical and preclinical studies implicate a role for dietary fatty acids (FAs) in PN pathogenesis. Molecular studies further show that saturated and unsaturated FAs differentially regulate the nerve lipid profile and nerve function. Critical Issues: We first review the properties of FAs and the neuroanatomy of the peripheral nervous system (PNS). Second, we discuss clinical and preclinical studies that implicate the involvement of FAs in PN. Third, we summarize the potential effects of FAs on nerve function and lipid metabolism within the peripheral nerves, sensory neurons, and Schwann cells. Future Directions: Future directions will focus on identifying molecular pathways in T2D and prediabetes that are modulated by FAs in PN. Determining pathophysiological mechanisms that underlie the injurious effects of saturated FAs and beneficial properties of unsaturated FAs will provide mechanistic targets for developing new targeted therapies to treat PN associated with T2D and prediabetes. Antioxid. Redox Signal. 37, 560-577.
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Affiliation(s)
- Amy E. Rumora
- Department of Neurology, Columbia University, New York, New York, USA
- Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
| | - Bhumsoo Kim
- Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
| | - Eva L. Feldman
- Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
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27
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The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells. Int J Mol Sci 2022; 23:ijms23179708. [PMID: 36077103 PMCID: PMC9456565 DOI: 10.3390/ijms23179708] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 11/22/2022] Open
Abstract
The peroxisome proliferator-activated receptor PPAR-γ is one of three PPAR nuclear receptors that act as ligand-activated transcription factors. In immune cells, the skin, and other organs, PPAR-γ regulates lipid, glucose, and amino acid metabolism. The receptor translates nutritional, pharmacological, and metabolic stimuli into the changes in gene expression. The activation of PPAR-γ promotes cell differentiation, reduces the proliferation rate, and modulates the immune response. In the skin, PPARs also contribute to the functioning of the skin barrier. Since we know that the route from identification to the registration of drugs is long and expensive, PPAR-γ agonists already approved for other diseases may also represent a high interest for psoriasis. In this review, we discuss the role of PPAR-γ in the activation, differentiation, and proliferation of skin and immune cells affected by psoriasis and in contributing to the pathogenesis of the disease. We also evaluate whether the agonists of PPAR-γ may become one of the therapeutic options to suppress the inflammatory response in lesional psoriatic skin and decrease the influence of comorbidities associated with psoriasis.
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28
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Egea MB, Pierce G, Park SH, Lee SI, Heger F, Shay N. Consumption of Antioxidant-Rich “Cerrado” Cashew Pseudofruit Affects Hepatic Gene Expression in Obese C57BL/6J High Fat-Fed Mice. Foods 2022; 11:foods11172543. [PMID: 36076729 PMCID: PMC9455023 DOI: 10.3390/foods11172543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
The pseudofruit of A. othonianum Rizzini, “Cerrado” cashew pulp, has been described as rich in flavonoids, phenolic compounds, and vitamin C. The objective of this work was to evaluate the beneficial health effects seen with the addition of “Cerrado” cashew pulp (CP) to an obesogenic high fat diet provided to C57BL/6J male mice. In week 9, the HF-fed group had a significantly higher baseline glucose concentration than the LF- or HF+CP-fed groups. In RNAseq analysis, 4669 of 5520 genes were found to be differentially expressed. Among the genes most upregulated with the ingestion of the CP compared to HF were Ph1da1, SLc6a9, Clec4f, and Ica1 which are related to glucose homeostasis; Mt2 that may be involved steroid biosynthetic process; and Ciart which has a role in the regulation of circadian rhythm. Although “Cerrado” CP intake did not cause changes in the food intake or body weight of fed mice with HF diet, carbohydrate metabolism appeared to be improved based on the observed changes in gene expression.
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Affiliation(s)
- Mariana Buranelo Egea
- Goiano Federal Institute, Campus Rio Verde, Rio Verde 75901-970, Brazil
- Departament of Food Science and Technology, Oregon State University, Corvallis, OR 97330, USA
| | - Gavin Pierce
- Departament of Food Science and Technology, Oregon State University, Corvallis, OR 97330, USA
| | - Si-Hong Park
- Departament of Food Science and Technology, Oregon State University, Corvallis, OR 97330, USA
| | - Sang-In Lee
- Departament of Food Science and Technology, Oregon State University, Corvallis, OR 97330, USA
| | - Fabienne Heger
- Department of Flavor Chemistry, Institute of Food Science and Biotechnology, University of Hohenheim, Schloss Hohenheim 1, 70599 Stuttgart, Germany
| | - Neil Shay
- Departament of Food Science and Technology, Oregon State University, Corvallis, OR 97330, USA
- Correspondence:
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29
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Current Options and Future Perspectives in the Treatment of Dyslipidemia. J Clin Med 2022; 11:jcm11164716. [PMID: 36012957 PMCID: PMC9410330 DOI: 10.3390/jcm11164716] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/02/2022] [Accepted: 08/10/2022] [Indexed: 12/22/2022] Open
Abstract
Low-density lipoprotein cholesterol (LDL-C) plays a crucial role in the development of atherosclerosis. Statin therapy is the standard treatment for lowering LDL-C in primary and secondary prevention. However, some patients do not reach optimal LDL-C target levels or do not tolerate statins, especially when taking high doses long-term. Combining statins with different therapeutic approaches and testing other new drugs is the future key to reducing the burden of cardiovascular disease (CVD). Recently, several new cholesterol-lowering drugs have been developed and approved; others are promising results, enriching the pharmacological armamentarium beyond statins. Triglycerides also play an important role in the development of CVD; new therapeutic approaches are also very promising for their treatment. Familial hypercholesterolemia (FH) can lead to CVD early in life. These patients respond poorly to conventional therapies. Recently, however, new and promising pharmacological strategies have become available. This narrative review provides an overview of the new drugs for the treatment of dyslipidemia, their current status, ongoing clinical or preclinical trials, and their prospects. We also discuss the new alternative therapies for the treatment of dyslipidemia and their relevance to practice.
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30
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Liu Z, Wang M, Fan Y, Wang J, Jiang S, Abudureman H. Bidirectional regulation of BDE-47 on 3T3-L1 cell differentiation based on a restricted cubic spline model. Toxicol Ind Health 2022; 38:481-492. [PMID: 35921494 DOI: 10.1177/07482337221100488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BDE-47 (2,2,4,4-tetrabromodiphenyl ether) is a polybrominated diphenyl ether (PBDE) congener, which has the characteristics of high biological detection rate, the highest content and strong biological toxicity, and is widely distributed in organisms. Many studies have found that BDE-47 may also be an environmental risk factor for metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and hypertension. However, the way that PBDEs influence adipocyte differentiation remains unclear. The methylisobutylxanthine, dexamethasone, and insulin method was used to study the effect of BDE-47 on the differentiation of 3T3-L1 cells. The 3T3-L1 cells were exposed by different concentrations of BDE-47, and the effect of cell viability was detected at different stages. In addition, the lipid droplet aggregation of adipocytes was observed and the triglyceride (TG) levels in the cytoplasm were detected after differentiation. The relative mRNA expression levels of leptin, adiponectin, and PPARγ in cells were determined by RT-PCR, and differentially expressed genes were preliminarily screened by digital gene expression profile. Our study found that BDE-47 promoted the differentiation of 3T3-L1 cells. Restriction cubic spline analysis showed that BDE-47 bidirectionally. regulated the mRNA synthesis of TG, PPARγ, and leptin genes and the aggregation of lipid droplets. BDE-47 may induce adipocyte differentiation by activating PPARγ, resulting in the differential expression of genes related to the AMPK signaling pathway, insulin resistance, and other metabolic pathways. The highest and lowest-dose BDE-47 exposure groups had the greatest impact on adipocyte differentiation.
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Affiliation(s)
- Zaoling Liu
- School of Public Health, Xinjiang Medical University, Urumq, China
| | - Menglin Wang
- School of Public Health, Xinjiang Medical University, Urumq, China
| | - Yong Fan
- The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jiasui Wang
- School of Public Health, Xinjiang Medical University, Urumq, China
| | - Shurui Jiang
- School of Public Health, Xinjiang Medical University, Urumq, China
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31
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Chen Y, Liang L, Wu C, Cao Z, Xia L, Meng J, Wang Z. Epigenetic Control of Vascular Smooth Muscle Cell Function in Atherosclerosis: A Role for DNA Methylation. DNA Cell Biol 2022; 41:824-837. [PMID: 35900288 DOI: 10.1089/dna.2022.0278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Atherosclerosis is a complex vascular inflammatory disease in which multiple cell types are involved, including vascular smooth muscle cells (VSMCs). In response to vascular injury and inflammatory stimuli, VSMCs undergo a "phenotypic switching" characterized by extracellular matrix secretion, loss of contractility, and abnormal proliferation and migration, which play a key role in the progression of atherosclerosis. DNA methylation modification is an important epigenetic mechanism that plays an important role in atherosclerosis. Studies investigating abnormal DNA methylation in patients with atherosclerosis have determined a specific DNA methylation profile, and proposed multiple pathways and genes involved in the etiopathogenesis of atherosclerosis. Recent studies have also revealed that DNA methylation modification controls VSMC function by regulating gene expression involved in atherosclerosis. In this review, we summarize the recent advances regarding the epigenetic control of VSMC function by DNA methylation in atherosclerosis and provide insights into the development of VSMC-centered therapeutic strategies.
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Affiliation(s)
- Yanjun Chen
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
| | - Lingli Liang
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
| | - Chunyan Wu
- The Third Affiliated Hospital of University of South China, Hengyang, China
| | - Zitong Cao
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
| | - Linzhen Xia
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
| | - Jun Meng
- Functional Department, The First Affiliated Hospital of University of South China, Hengyang, China
| | - Zuo Wang
- Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
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Asuquo EA, Nwodo OFC, Assumpta AC, Orizu UN, Oziamara ON, Solomon OA. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation. Open Life Sci 2022; 17:641-658. [PMID: 35800074 PMCID: PMC9202533 DOI: 10.1515/biol-2022-0067] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 02/07/2022] [Accepted: 03/05/2022] [Indexed: 11/15/2022] Open
Abstract
The Fat Mass and Obesity-associated (FTO) gene has been shown to play an important role in developing obesity, manifesting in traits such as increased body mass index, increased waist-to-hip ratio, and the distribution of adipose tissues, which increases the susceptibility to various metabolic syndromes. In this study, we evaluated the impact of fruit-based diets of Solanum melongena (SMF) and Solanum aethiopicum fruits (SAF) on the FTO gene expression levels in a high-fat diet (HFD)-induced obese animals. Our results showed that the mRNA level of the FTO gene was downregulated in the hypothalamus, and white and brown adipose tissue following three and six weeks of treatment with SMF- and SAF-based diets in the HFD-induced obese animals. Additionally, the Solanum fruit supplementation exhibited a curative effect on obesity-associated abrasions on the white adipose tissue (WAT), hypothalamus, and liver. Our findings collectively suggest the anti-obesity potential of SMF and SAF via the downregulation of the FTO gene.
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Affiliation(s)
- Edeke Affiong Asuquo
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
| | | | - Anosike Chioma Assumpta
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
| | - Uchendu Nene Orizu
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
| | - Okoro Nkwachukwu Oziamara
- Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
| | - Odiba Arome Solomon
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
- Department of Molecular Genetics and Biotechnology, Faculty of Biological Sciences, University of Nigeria, 410001, Nsukka, Enugu State, Nigeria
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Griffett K. Targeting Nuclear Receptors for Chronic Inflammatory Pain: A Potential Alternative. ACS Pharmacol Transl Sci 2022; 5:440-444. [PMID: 35711817 DOI: 10.1021/acsptsci.2c00063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Indexed: 11/28/2022]
Abstract
Pain is the unpleasant consequence of detrimental neuronal activity that can be triggered by chronic inflammation, noxious stimuli, and nerve damage. In the case of chronic inflammatory pain, the establishment and maintenance of pain states often depend on the chronic activation and immune response occurring at the site of the peripheral nerve injury. Many current analgesic drugs lack efficacy in long-term pain management. Targeting the nuclear receptor family of transcription factors may provide a novel avenue for the treatment of chronic inflammatory pain. Peroxisome proliferator-activated receptor (PPAR) ligands have demonstrated efficacy in several diabetic-related neuropathic pain models, while the REV-ERB receptors play a key role in the regulation of both P2X7 receptor expression and NLRP3 inflammasome expression and activation. As such, activating the REV-ERB receptor may provide an anti-inflammatory and analgesic option for chronic inflammatory pain sufferers.
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Affiliation(s)
- Kristine Griffett
- College of Veterinary Medicine, Department of Anatomy, Physiology & Pharmacology, Auburn University, Auburn, Alabama 36849, United States
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Tetramethylpyrazine: A review on its mechanisms and functions. Biomed Pharmacother 2022; 150:113005. [PMID: 35483189 DOI: 10.1016/j.biopha.2022.113005] [Citation(s) in RCA: 100] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 04/15/2022] [Accepted: 04/19/2022] [Indexed: 11/21/2022] Open
Abstract
Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.
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Consumption of oils and anthocyanins may positively modulate PPAR-γ expression in chronic non-communicable diseases: a systematic review. Nutr Res 2022; 105:66-76. [DOI: 10.1016/j.nutres.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 06/07/2022] [Accepted: 06/09/2022] [Indexed: 11/22/2022]
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Gao J, Ma L, Yin J, Liu G, Ma J, Xia S, Gong S, Han Q, Li T, Chen Y, Yin Y. Camellia ( Camellia oleifera bel.) seed oil reprograms gut microbiota and alleviates lipid accumulation in high fat-fed mice through the mTOR pathway. Food Funct 2022; 13:4977-4992. [PMID: 35452062 DOI: 10.1039/d1fo04075h] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Camellia (Camellia oleifera bel.) seed oil (CO) is extensively used as an edible oil in China and Asian countries owing to its high nutritional and medicinal values. It has been shown that a high-fat diet enhances lipid accumulation and induces intestinal microbiota imbalance in mice. However, it is still to be learned whether CO prevents dyslipidemia through gut microbiota. Here, using 16S rRNA gene sequencing analysis of the gut microbiota, we found that oral CO relieved lipid accumulation and reversed gut microbiota dysbiosis. Compared to mice (C57BL/6J male mice) fed a high-fat diet, treatment with CO regulated the composition and functional profiling communities related to the lipid metabolism of gut microbiota. The abundances of Dubosiella, Lactobacillus, and Alistipes were markedly increased in CO supplementation mice. In addition, the colon levels of isobutyric acid, pentanoic acid, and isovaleric acid were similar between the control and CO supplementation mice. Besides, the results indicated that CO supplementation in mice alleviated lipid droplet accumulation in the hepatocytes and subcutaneous adipose tissue, although the liver index did not show a difference. Notably, CO supplementation for 6 weeks significantly reduced the levels of LDL, TC, and TG, while enhancing the level of HDL in serum and liver. Meanwhile, we also identified that CO supplementation suppressed the mammalian target of rapamycin (mTOR) signaling pathway in high fat-fed (HF-fed) mice. Taken together, our results suggest that CO improved dyslipidemia and alleviated lipid accumulation in HF-fed mice, the molecular mechanisms possibly associated with the reorganization of gut microbiota, in particular, Alistipes and Dubosiella, mediated the inhibition of the mTOR pathway.
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Affiliation(s)
- Jing Gao
- Research Institute of Oil Tea Camellia, Hunan Academy of Forestry, Shao shan South Road, No. 658, Changsha 410004, China. .,National Engineering Research Center for Oil Tea Camellia, Changsha 410004, China.,Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China.
| | - Li Ma
- Research Institute of Oil Tea Camellia, Hunan Academy of Forestry, Shao shan South Road, No. 658, Changsha 410004, China. .,National Engineering Research Center for Oil Tea Camellia, Changsha 410004, China
| | - Jie Yin
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - Gang Liu
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - Jie Ma
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - SiTing Xia
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - SaiMing Gong
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - Qi Han
- College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
| | - TieJun Li
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China.
| | - YongZhong Chen
- Research Institute of Oil Tea Camellia, Hunan Academy of Forestry, Shao shan South Road, No. 658, Changsha 410004, China. .,National Engineering Research Center for Oil Tea Camellia, Changsha 410004, China
| | - YuLong Yin
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Chinese Academy of Sciences, Changsha, Hunan, China. .,College of Animal Science and Technology, Hunan Co-Innovation Center of Animal Production Safety, Hunan Agricultural University, Changsha, China
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Xu S, Qiao X, Peng P, Zhu Z, Li Y, Yu M, Chen L, Cai Y, Xu J, Shi X, Proud CG, Xie J, Shen K. Da-Chai-Hu-Tang Protects From Acute Intrahepatic Cholestasis by Inhibiting Hepatic Inflammation and Bile Accumulation via Activation of PPARα. Front Pharmacol 2022; 13:847483. [PMID: 35370715 PMCID: PMC8965327 DOI: 10.3389/fphar.2022.847483] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 02/15/2022] [Indexed: 12/12/2022] Open
Abstract
Cholestasis is caused by intrahepatic retention of excessive toxic bile acids and ultimately results in hepatic failure. Da-Chai-Hu-Tang (DCHT) has been used in China to treat liver and gallbladder diseases for over 1800 years. Here, we demonstrated that DCHT treatment prevented acute intrahepatic cholestasis with liver injury in response to α-naphthylisothiocyanate (ANIT) not to bile duct ligation (BDL) induced-extrahepatic cholestasis. ANIT (80 mg/kg) increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBiL), total bilirubin (TBiL), and total bile acids (TBA) which was attenuated by DCHT treatment in a dose-dependent manner. DCHT treatment at high dose of 1.875 g/kg restored bile acid homeostasis, as evidenced by the recovery of the transcription of genes implicated in bile acid biosynthesis, uptake and efflux. DCHT treatment (1.875 g/kg) reversed ANIT-evoked disordered glutathione homeostasis (as determined by GSH/GSSG ratio) and increased in the mRNA levels for Il6, Il1b and Tnfa associated with liver inflammation. Using network pharmacology-based approaches, we identified 22 putative targets involved in DCHT treatment for intrahepatic cholestasis not extrahepatic cholestasis. In addition, as evidenced by dual-luciferase reporter assays, compounds from DCHT with high affinity of PPARα increased luciferase levels from a PPARα-driven reporter. PPARα agonist fenofibrate was able to mimic the cytoprotective effect of DCHT on intrahepatic cholestasis, which was abolished by the PPARα antagonist GW6471. KEGG enrichment and western blot analyses showed that signaling axes of JNK/IL-6/NF-κB/STAT3 related to PPARα might be the principal pathway DCHT affects intrahepatic cholestasis. Taken together, the present study provides compelling evidence that DCHT is a promising formula against acute intrahepatic cholestasis with hepatotoxicity which works via PPARα activation.
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Affiliation(s)
- Shihao Xu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xi Qiao
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peike Peng
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ziyi Zhu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yaoting Li
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,School of Pharmacy, Fudan University, Shanghai, China
| | - Mengyuan Yu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Long Chen
- Experimental Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yin Cai
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Jin Xu
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinwei Shi
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Christopher G Proud
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.,Molecular and Biomedical Sciences, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Jianling Xie
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.,Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA, Australia
| | - Kaikai Shen
- School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Wang W, Zhang J, Li Z, Gu J, Qin J, Li J, Zhang X, Ru S. Bisphenol S exposure accelerates the progression of atherosclerosis in zebrafish embryo-larvae. JOURNAL OF HAZARDOUS MATERIALS 2022; 426:128042. [PMID: 34942454 DOI: 10.1016/j.jhazmat.2021.128042] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/30/2021] [Accepted: 12/06/2021] [Indexed: 06/14/2023]
Abstract
Bisphenol S (BPS), widely utilized in manufacturing of daily necessities, is a toxicant with potential to induce atherosclerotic cardiovascular disease (ASCVD). However, the mode of action by which BPS exposure induces ASCVD remains unknown. Here, macrophages that were exposed to BPS in combination with oxidized low-density lipoprotein (oxLDL) exhibited enhanced formation of foam cells, a hallmark of ASCVD. Furthermore, zebrafish embryo-larvae were exposed to BPS (0, 1, 10 and 100 μg/L) for 15 days (d) and the characteristic symptoms of ASCVD including an inflammatory response, macrophage recruitment around blood vessels, and accumulation of oxLDL on vascular endothelium, were induced in 15-d larvae. After zebrafish were exposed to BPS for 45 d, BPS mobilized fatty acid metabolism and activated peroxisome proliferator-activated receptor signaling in larval liver, the hub of endogenous lipid metabolism, causing an increase in plasma LDL. Driven by high plasma LDL levels, the caudal artery of zebrafish larvae exhibited lipid accumulation and a thickened area with a large number of collagen fibers, accompanied by characteristic lesions, as well as hyperlipidemia, erythrocyte aggregation, thinner blood vessel walls and increased levels of leukocytes and thromboocytes in plasma. Our data demonstrate that BPS accelerates the progression of ASCVD using zebrafish embryo-larvae as a model.
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Affiliation(s)
- Weiwei Wang
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
| | - Jie Zhang
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
| | - Ze Li
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
| | - Jie Gu
- Nanjing Institute of Environmental Sciences, Nanjing 210000, China
| | - Jingyu Qin
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
| | - Jiali Li
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
| | - Xiaona Zhang
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
| | - Shaoguo Ru
- College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
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Lewandowski CT, Laham MS, Thatcher GR. Remembering your A, B, C's: Alzheimer's disease and ABCA1. Acta Pharm Sin B 2022; 12:995-1018. [PMID: 35530134 PMCID: PMC9072248 DOI: 10.1016/j.apsb.2022.01.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/27/2021] [Accepted: 01/07/2022] [Indexed: 12/24/2022] Open
Abstract
The function of ATP binding cassette protein A1 (ABCA1) is central to cholesterol mobilization. Reduced ABCA1 expression or activity is implicated in Alzheimer's disease (AD) and other disorders. Therapeutic approaches to boost ABCA1 activity have yet to be translated successfully to the clinic. The risk factors for AD development and progression, including comorbid disorders such as type 2 diabetes and cardiovascular disease, highlight the intersection of cholesterol transport and inflammation. Upregulation of ABCA1 can positively impact APOE lipidation, insulin sensitivity, peripheral vascular and blood–brain barrier integrity, and anti-inflammatory signaling. Various strategies towards ABCA1-boosting compounds have been described, with a bias toward nuclear hormone receptor (NHR) agonists. These agonists display beneficial preclinical effects; however, important side effects have limited development. In particular, ligands that bind liver X receptor (LXR), the primary NHR that controls ABCA1 expression, have shown positive effects in AD mouse models; however, lipogenesis and unwanted increases in triglyceride production are often observed. The longstanding approach, focusing on LXRβ vs. LXRα selectivity, is over-simplistic and has failed. Novel approaches such as phenotypic screening may lead to small molecule NHR modulators that elevate ABCA1 function without inducing lipogenesis and are clinically translatable.
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PPARγ Regulates Triclosan Induced Placental Dysfunction. Cells 2021; 11:cells11010086. [PMID: 35011648 PMCID: PMC8750171 DOI: 10.3390/cells11010086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/14/2022] Open
Abstract
Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is crucial in placenta development. However, the mechanism of PPARγ in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPARγ worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPARγ and its downstream viability, migration, angiogenesis-related genes HMOX1, ANGPTL4, VEGFA, MMP-2, MMP-9, and upregulated inflammatory genes p65, IL-6, IL-1β, and TNF-α in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPARγ had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPARγ agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPARγ pathway. Our findings reveal that activation of PPARγ might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus.
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KRAS Affects Adipogenic Differentiation by Regulating Autophagy and MAPK Activation in 3T3-L1 and C2C12 Cells. Int J Mol Sci 2021; 22:ijms222413630. [PMID: 34948427 PMCID: PMC8707842 DOI: 10.3390/ijms222413630] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 12/16/2022] Open
Abstract
Kirsten rat sarcoma 2 viral oncogene homolog (Kras) is a proto-oncogene that encodes the small GTPase transductor protein KRAS, which has previously been found to promote cytokine secretion, cell survival, and chemotaxis. However, its effects on preadipocyte differentiation and lipid accumulation are unclear. In this study, the effects of KRAS inhibition on proliferation, autophagy, and adipogenic differentiation as well as its potential mechanisms were analyzed in the 3T3-L1 and C2C12 cell lines. The results showed that KRAS was localized mainly in the nuclei of 3T3-L1 and C2C12 cells. Inhibition of KRAS altered mammalian target of rapamycin (Mtor), proliferating cell nuclear antigen (Pcna), Myc, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein beta (C/ebp-β), diacylglycerol O-acyltransferase 1 (Dgat1), and stearoyl-coenzyme A desaturase 1 (Scd1) expression, thereby reducing cell proliferation capacity while inducing autophagy, enhancing differentiation of 3T3-L1 and C2C12 cells into mature adipocytes, and increasing adipogenesis and the capacity to store lipids. Moreover, during differentiation, KRAS inhibition reduced the levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p38, and phosphatidylinositol 3 kinase (PI3K) activation. These results show that KRAS has unique regulatory effects on cell proliferation, autophagy, adipogenic differentiation, and lipid accumulation.
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Xu J, Guo Y, Huang X, Ma X, Li P, Wang Y, Wang X, Yuan L. Effects of DHA dietary intervention on hepatic lipid metabolism in apolipoprotein E-deficient and C57BL/6J wild-type mice. Biomed Pharmacother 2021; 144:112329. [PMID: 34653759 DOI: 10.1016/j.biopha.2021.112329] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/05/2021] [Accepted: 10/08/2021] [Indexed: 02/08/2023] Open
Abstract
Lipid metabolic disorder occurs when ApoE gene is deficient. However, the role of Docosahexaenoic acid (DHA) in relieving hepatic lipid metabolic disorder in apolipoprotein E-deficient (ApoE -/-) mice remains unknown. We fed 3-month-old C57BL/6J wild-type (C57 wt) and ApoE -/- mice respectively with normal or DHA fortified diet for 5 months. We found ApoE gene deficiency caused hepatic lipid deposition and increased lipid levels in plasma and liver. Hepatic gene expression of SRB1, CD36 and FABP5 in ApoE -/- mice, protein expression of HMGCR, LRP1 in C57 wt mice and protein expression of LRP1 in ApoE -/- mice increased after DHA intervention. In DHA-fed ApoE -/- mice, LXRα/β and PPARα protein expression down-regulated in cytoplasm, but LXRα/β protein expression up-regulated in nucleus. DHA treatment decreased RXRα and RXRβ expression in C57 wt and ApoE -/- female mice. Deletion of ApoE gene caused lipid metabolism disorder in liver of mice. DHA treatment efficiently meliorated lipid metabolism caused by ApoE deficient through the regulation of gene and protein expressions of molecules involved in liver fatty acids transport and lipid metabolism.
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Affiliation(s)
- Jingjing Xu
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Yujie Guo
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Xiaochen Huang
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Xiaojun Ma
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Pengfei Li
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Ying Wang
- The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, PR China
| | - Xixiang Wang
- School of Public Health, Capital Medical University, Beijing 100069, PR China
| | - Linhong Yuan
- School of Public Health, Capital Medical University, Beijing 100069, PR China.
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Li Y, Zhang L, Ren P, Yang Y, Li S, Qin X, Zhang M, Zhou M, Liu W. Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 93:153812. [PMID: 34753029 DOI: 10.1016/j.phymed.2021.153812] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 10/01/2021] [Accepted: 10/17/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.
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Affiliation(s)
- Yue Li
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China
| | - Lei Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China
| | - Pan Ren
- Weihai Hospital of Traditional Chinese Medicine, Shandong 264200, China
| | - Yang Yang
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China
| | - Sinai Li
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China
| | - Xiaomei Qin
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China
| | - Meng Zhang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China
| | - Mingxue Zhou
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China..
| | - Weihong Liu
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China.; Beijing Institute of Traditional Chinese Medicine,23 Backstreet of Art Gallery, Dongcheng District, Beijing 100010, China..
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Lee Y, Kim BR, Kang GH, Lee GJ, Park YJ, Kim H, Jang HC, Choi SH. The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE-/-FXR-/- Mice. Endocrinol Metab (Seoul) 2021; 36:1243-1253. [PMID: 34986301 PMCID: PMC8743579 DOI: 10.3803/enm.2021.1100] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 09/07/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency. METHODS En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)-/- and ApoE-/-FXR-/- mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice. RESULTS Compared with ApoE-/- mice, ApoE-/-FXR-/- mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE-/-FXR-/- mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver). CONCLUSION Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.
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Affiliation(s)
- Yenna Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Bo-Rahm Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Geun-Hyung Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Gwan Jae Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hak Chul Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Hee Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Corresponding author: Sung Hee Choi Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7029, Fax: +82-31-787-4052, E-mail:
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Kosmas CE, Pantou D, Sourlas A, Papakonstantinou EJ, Echavarria Uceta R, Guzman E. New and emerging lipid-modifying drugs to lower LDL cholesterol. Drugs Context 2021; 10:dic-2021-8-3. [PMID: 34795777 PMCID: PMC8565402 DOI: 10.7573/dic.2021-8-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/29/2021] [Indexed: 12/14/2022] Open
Abstract
Cardiovascular disease (CVD) represents the leading cause of death worldwide. The role of low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of atherosclerosis and CVD has been well recognized. Statins are the standard of care for the management of hypercholesterolaemia, and their effectiveness in lowering LDL-C and reducing CVD risk in both primary and secondary prevention has been well established. However, several patients fail to attain optimal LDL-C goals or are intolerant to statins, especially at high doses. PCSK9 inhibitors, bempedoic acid, inclisiran, ANGPTL3 inhibitors, PPARβ/δ agonists and LXR agonists are novel or upcoming LDL-C-lowering agents that have shown promising beneficial results. This review aims to present and discuss the current clinical and scientific data pertaining to the new and emerging lipid-modifying LDL-C-lowering drugs.
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Affiliation(s)
- Constantine E Kosmas
- Department of Medicine, Division of Cardiology, Montefiore Medical Center, Bronx, NY, USA.,Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA
| | - Dafni Pantou
- School of Medicine, University of Nicosia, Nicosia, Cyprus
| | | | | | | | - Eliscer Guzman
- Department of Medicine, Division of Cardiology, Montefiore Medical Center, Bronx, NY, USA.,Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA
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Associations between maternal mono-(2-ethylhexyl) phthalate levels, nuclear receptor gene polymorphisms, and fatty acid levels in pregnant Japanese women in the Hokkaido study. Reprod Toxicol 2021; 107:22-32. [PMID: 34801790 DOI: 10.1016/j.reprotox.2021.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 11/04/2021] [Accepted: 11/10/2021] [Indexed: 11/20/2022]
Abstract
We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log10-transformed MEHP levels and maternal genotypes on log10-transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (pint = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A.
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Li X, Ge J, Li Y, Cai Y, Zheng Q, Huang N, Gu Y, Han Q, Li Y, Sun R, Liu R. Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease. Acta Pharm Sin B 2021; 11:3527-3541. [PMID: 34900534 PMCID: PMC8642447 DOI: 10.1016/j.apsb.2021.03.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/03/2021] [Accepted: 02/09/2021] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like Lipe and Lipg. SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1a expression. Bioinformatic analysis further predicted the implication of master transcription factors, including peroxisome proliferator-activated receptor alpha (PPARα), in the protective effects of SSa and SSd. These results were further confirmed in vitro in mouse primary hepatocytes. In summary, our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins (SSs), and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.
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George MY, Menze ET, Esmat A, Tadros MG, El-Demerdash E. Naringin treatment improved main clozapine-induced adverse effects in rats; emphasis on weight gain, metabolic abnormalities, and agranulocytosis. Drug Dev Res 2021; 82:980-989. [PMID: 33537987 DOI: 10.1002/ddr.21800] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/04/2021] [Accepted: 01/20/2021] [Indexed: 11/07/2022]
Abstract
Schizophrenia is one of the major neuropsychiatric disorders affecting people worldwide. Unfortunately, currently available antipsychotic medications possess several side effects. Among them, clozapine is one of the atypical antipsychotics prescribed in schizophrenia wing to its blocking effect on dopamine (D2) and serotonin (5-HT1c ) receptors. However, it has been recently reserved for resistant schizophrenia due to its several side effects. The current research aimed at investigating potential naringin add-on benefit to cease the main side effects of clozapine in ketamine-induced psychosis in rats. In this study, schizophrenia was induced in rats via ketamine administration that could promote neuropathological patterns of schizophrenia. Afterwards, clozapine and naringin were administered to rats in order to improve such effects induced by ketamine. Clozapine administration promoted weight gain, hyperglycemia, dyslipidemia, and agranulocytosis. However, naringin was able to reduce such adverse effects when added to clozapine treatment. Naringin increased total leukocyte count preventing agranulocytosis either when administered alone or in combination with clozapine. In addition, via its metabolic activities, naringin treatment lowered serum total cholesterol and triglycerides levels. Moreover, naringin prevented weight gain when administered. Finally, naringin reduced serum glucose level preventing hyperglycemia associated with clozapine treatment. Collectively, these findings may suggest that naringin possesses a potential add-on benefit to clozapine in treatment of schizophrenia.
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Affiliation(s)
- Mina Y George
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Esther T Menze
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ahmed Esmat
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Mariane G Tadros
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
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Roudsari NM, Lashgari NA, Momtaz S, Roufogalis B, Abdolghaffari AH, Sahebkar A. Ginger: A complementary approach for management of cardiovascular diseases. Biofactors 2021; 47:933-951. [PMID: 34388275 DOI: 10.1002/biof.1777] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 07/26/2021] [Indexed: 12/20/2022]
Abstract
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Inflammation and oxidative stress play critical roles in progression of various types of CVD. Broad pharmacological properties of ginger (the rhizome of Zingiber officinale) and its bioactive components have been reported, suggesting that they can be a therapeutic choice for clinical use. Consistent with its rich phenolic content, the anti-inflammatory and antioxidant properties of ginger have been confirmed in many studies. Ginger modifies many cellular processes and in particular was shown to have potent inhibitory effects against nuclear factor kappa B (NF-κB); signal transducer and activator of transcription; NOD-, LRR-, and pyrin domain-containing proteins; toll-like receptors; mitogen-activated protein kinase; and mammalian target of rapamycin signaling pathways. Ginger also blocks pro-inflammatory cytokines and the activation of the immune system. Ginger suppresses the activity of oxidative molecules such as reactive oxygen species, inducible nitric oxide synthase, superoxide dismutase, glutathione, heme oxygenase, and GSH-Px. In this report, we summarize the biochemical pathologies underpinning a variety of CVDs and the effects of ginger and its bioactive components, including 6-shogaol, 6-gingerol, and 10-dehydrogingerdione. The properties of ginger and its phenolic components, mechanism of action, biological functions, side effects, and methods for enhanced cell delivery are also discussed. Together with preclinical and clinical studies, the positive biological effects of ginger and its bioactive components in CVD support the undertaking of further in vivo and especially clinical studies.
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Affiliation(s)
- Nazanin Momeni Roudsari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Naser-Aldin Lashgari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, Academic Center for Education, Culture and Research, Tehran, Iran
- Toxicology and Disease Group, Pharmaceutical Sciences Research Center, Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran, Iran
| | - Basil Roufogalis
- Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, Australia
- National Institute of Complementary Medicine, Western Sydney University, Westmead, Australia
| | - Amir Hossein Abdolghaffari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Medicinal Plants Research Center, Institute of Medicinal Plants, Academic Center for Education, Culture and Research, Tehran, Iran
- Toxicology and Disease Group, Pharmaceutical Sciences Research Center, Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Gastrointestinal Pharmacology Interest Group, Universal Scientific Education and Research Network, Tehran, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
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Kotlyarov S. Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology. Int J Mol Sci 2021; 22:11545. [PMID: 34768974 PMCID: PMC8584259 DOI: 10.3390/ijms222111545] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/12/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022] Open
Abstract
Atherosclerosis is one of the most important problems in modern medicine. Its high prevalence and social significance determine the need for a better understanding of the mechanisms of the disease's development and progression. Lipid metabolism and its disorders are one of the key links in the pathogenesis of atherosclerosis. Lipids are involved in many processes, including those related to the mechanoreception of endothelial cells. The multifaceted role of lipids in endothelial mechanobiology and mechanisms of atherogenesis are discussed in this review. Endothelium is involved in ensuring adequate vascular hemodynamics, and changes in blood flow characteristics are detected by endothelial cells and affect their structure and function.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia
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