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Jiang M, Li P, Han X, Jiang L, Han L, He Q, Yang C, Sun Z, Wang Y, Cao Y, Liu X, Wu W. Marine-Derived Bioactive Compounds: A Promising Strategy for Ameliorating Skeletal Muscle Dysfunction in COPD. Mar Drugs 2025; 23:158. [PMID: 40278279 PMCID: PMC12028452 DOI: 10.3390/md23040158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/26/2025] [Accepted: 03/31/2025] [Indexed: 04/26/2025] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in COPD patients. Owing to the unique physicochemical conditions of the marine environment, marine-derived bioactive compounds exhibit potent anti-inflammatory and antioxidant properties, demonstrating therapeutic potential for ameliorating COPD skeletal muscle dysfunction. This review summarizes marine-derived bioactive compounds with promising efficacy against skeletal muscle dysfunction in COPD, including polysaccharides, lipids, polyphenols, peptides, and carotenoids. The discussed compounds have shown bioactivities in promoting skeletal muscle health and suppressing muscle atrophy, thereby providing potential strategies for the prevention and treatment of COPD skeletal muscle dysfunction. These findings may expand the therapeutic strategies for managing COPD skeletal muscle dysfunction.
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Affiliation(s)
- Meiling Jiang
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Peijun Li
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (P.L.); (L.J.); (Y.W.)
| | - Xiaoyu Han
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Linhong Jiang
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (P.L.); (L.J.); (Y.W.)
| | - Lihua Han
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Qinglan He
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Chen Yang
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Zhichao Sun
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Yingqi Wang
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (P.L.); (L.J.); (Y.W.)
| | - Yuanyuan Cao
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
| | - Xiaodan Liu
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (P.L.); (L.J.); (Y.W.)
| | - Weibing Wu
- Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; (M.J.); (X.H.); (L.H.); (Q.H.); (C.Y.); (Z.S.); (Y.C.)
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Giacomello E, Nicoletti C, Canato M, Toniolo L. Exercise Mimetics in Aging: Suggestions from a Systematic Review. Nutrients 2025; 17:969. [PMID: 40289996 PMCID: PMC11944853 DOI: 10.3390/nu17060969] [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: 02/17/2025] [Revised: 03/03/2025] [Accepted: 03/08/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Growth in the aging world population is accompanied by an increase in comorbidities, profoundly impacting the quality of life of older people. This development has motivated a large effort to investigate the mechanisms underlying aging and the search for countermeasures. The most investigated strategies envisage the control of diet and physical exercise, which exploit both common and distinct mechanisms to promote health. Since the application of nutritional and exercise protocols to aged persons introduces several issues due to their disabled state, some strategies have been developed. The nutritional approach exploits a wide range of compounds, including calorie restriction mimetics, supplements, antioxidants, and others. In the context of exercise, in recent years, molecules able to provide similar effects to exercise, the so-called exercise mimetics, have been developed. Methods: To have a better perspective on exercise mimetics and their connection with nutrition, we performed a systematic search of the PubMed and Scopus databases using the term "exercise mimetics". Results: In total, 97 research articles were selected and discussed. The present review provides evidence of the presence of multiple exercise-mimetic compounds and physical strategies that can target metabolic pathways, oxidative stress defense mechanisms, or myokine modulation. Conclusions: Interestingly, this review highlights that an important number of exercise mimetics are represented by products of natural origin and supplements assimilable with diet. This evidence provides a further link between exercise and nutrition and confers a central role on nutrition in the context of exercise mimetics.
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Affiliation(s)
- Emiliana Giacomello
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy
| | - Claudio Nicoletti
- Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy;
| | - Marta Canato
- Laboratory of Muscle Biophysics, Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
| | - Luana Toniolo
- Laboratory of Muscle Biophysics, Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
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Tonphu K, Mueangaun S, Lerkdumnernkit N, Sengking J, Tocharus J, Benjakul S, Mittal A, Tocharus C. Chitooligosaccharide-epigallocatechin gallate conjugate ameliorates lipid accumulation and promotes browning of white adipose tissue in high fat diet fed rats. Chem Biol Interact 2025; 406:111316. [PMID: 39577827 DOI: 10.1016/j.cbi.2024.111316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 11/14/2024] [Accepted: 11/20/2024] [Indexed: 11/24/2024]
Abstract
The prevalence of obesity has increased progressively worldwide. Obesity is characterized by excessive accumulation of fat in adipose tissues, leading to metabolic impairment. The anti-obese effects of chitooligosaccharide (COS) and epigallocatechin-3-gallate (EGCG) have been extensively clarified. This study aimed to investigate the effects and potential mechanisms of the COS-EGCG conjugate (CE) on anti-obesity, specifically by alleviating lipid accumulation and promoting the browning of white adipose tissue (WAT) in obese rats. Obesity as a consequence of a high-fat diet (HFD) was induced in male Wistar rats. The HFD was given for 16 weeks and the rats were then randomly subdivided into five groups namely: vehicle (control group), HFD plus CE at 150 mg/kg/day, HFD plus CE at 600 mg/kg/day, HFD plus COS at 600 mg/kg/day, and HFD plus atorvastatin at 10 mg/kg/day for 4 weeks. CE could reduce body weight, improve serum lipid profiles, and promote lipid metabolism via activation of AMP-activated protein kinase (AMPK) in WAT and enhance the processes of WAT browning by activating sirtuin 1 (Sirt 1), peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), and uncoupling the protein 1 (UCP1) signaling pathway. CE reduced obesity and promoted WAT browning in HFD-fed rats. Therefore, CE might be a new therapy for metabolic syndrome and obesity.
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Affiliation(s)
- Kanokrada Tonphu
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Sirikul Mueangaun
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Natcha Lerkdumnernkit
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Jirakhamon Sengking
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Jiraporn Tocharus
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Soottawat Benjakul
- International Center of Excellence in Seafood Science and Innovation, Faculty of Agro-Industry, Prince of Songkla University, Hat Yai, 90110, Thailand
| | - Ajay Mittal
- International Center of Excellence in Seafood Science and Innovation, Faculty of Agro-Industry, Prince of Songkla University, Hat Yai, 90110, Thailand
| | - Chainarong Tocharus
- Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Functional Food Research Center for Well-being, Chiang Mai University, Chiang Mai, 50200, Thailand.
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Yang K, Chen Y, Wang M, Zhang Y, Yuan Y, Hou H, Mao YH. The Improvement and Related Mechanism of Microecologics on the Sports Performance and Post-Exercise Recovery of Athletes: A Narrative Review. Nutrients 2024; 16:1602. [PMID: 38892536 PMCID: PMC11174581 DOI: 10.3390/nu16111602] [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: 04/24/2024] [Revised: 05/20/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
The diversity and functionality of gut microbiota may play a crucial role in the function of human motor-related systems. In addition to traditional nutritional supplements, there is growing interest in microecologics due to their potential to enhance sports performance and facilitate post-exercise recovery by modulating the gut microecological environment. However, there is a lack of relevant reviews on this topic. This review provides a comprehensive overview of studies investigating the effects of various types of microecologics, such as probiotics, prebiotics, synbiotics, and postbiotics, on enhancing sports performance and facilitating post-exercise recovery by regulating energy metabolism, mitigating oxidative-stress-induced damage, modulating immune responses, and attenuating bone loss. Although further investigations are warranted to elucidate the underlying mechanisms through which microecologics exert their effects. In summary, this study aims to provide scientific evidence for the future development of microecologics in athletics.
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Affiliation(s)
- Keer Yang
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Yonglin Chen
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Minghan Wang
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Yishuo Zhang
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Yu Yuan
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Haoyang Hou
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
| | - Yu-Heng Mao
- School of Exercise and Health, Guangzhou Sport University, Guangzhou 510500, China; (K.Y.); (Y.C.); (M.W.); (Y.Z.); (Y.Y.); (H.H.)
- Guangdong Key Laboratory of Human Sports Performance Science, Guangzhou Sport University, Guangzhou 510500, China
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Ahn Y, Lee HS, Lee SH, Joa KL, Lim CY, Ahn YJ, Suh HJ, Park SS, Hong KB. Effects of gypenoside L-containing Gynostemma pentaphyllum extract on fatigue and physical performance: A double-blind, placebo-controlled, randomized trial. Phytother Res 2023. [PMID: 36877124 DOI: 10.1002/ptr.7801] [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: 03/08/2022] [Revised: 02/01/2023] [Accepted: 02/22/2023] [Indexed: 03/07/2023]
Abstract
This study was conducted to investigate the effect of Gynostemma pentaphyllum extract containing gypenoside L (GPE) on improving the cognitive aspects of fatigue and performance of the motor system. One hundred healthy Korean adults aged 19-60 years were randomized to the treatment (GPE for 12 weeks) and control groups, and efficacy and safety-related parameters were compared between the two groups. Maximal oxygen consumption (VO2 max) and O2 pulse were significantly higher in the treatment group than in the control group (p = 0.007 and p = 0.047, respectively). After 12 weeks, the treatment group showed significant changes such as decreases in the levels of free fatty acids (p = 0.042). In addition, there were significant differences in the rating of perceived exertion (RPE) (p < 0.05) and value of temporal fatigue between the treatment and control groups on the multidimensional fatigue scale (p < 0.05). Moreover, the level of endothelial nitric oxide synthase (eNOS) in the blood was significantly higher in the treatment group than in the control group (p = 0.047). In summary, oral administration of GPE has a positive effect on resistance to exercise-induced physical and mental fatigue.
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Affiliation(s)
- Yejin Ahn
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, South Korea
| | - Hee-Seok Lee
- Department of Food Science and Technology, Chung-Ang University, Anseong, South Korea
| | - Seok-Hee Lee
- Department of Food Science and Biotechnology, Dongguk University, Goyang, South Korea
| | - Kyung-Lim Joa
- Department of Physical & Rehabilitation Medicine, College of Medicine, Inha University School of Medicine, Incheon, South Korea
| | | | - Yu Jin Ahn
- Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea
| | - Hyung Joo Suh
- Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, South Korea.,BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul, South Korea
| | - Sung-Soo Park
- Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea
| | - Ki-Bae Hong
- Department of Food Science and Nutrition, Jeju National University, Jeju, South Korea
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Chang WT, Huang SC, Cheng HL, Chen SC, Hsu CL. Rutin and Gallic Acid Regulates Mitochondrial Functions via the SIRT1 Pathway in C2C12 Myotubes. Antioxidants (Basel) 2021; 10:antiox10020286. [PMID: 33668647 PMCID: PMC7918168 DOI: 10.3390/antiox10020286] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/10/2021] [Accepted: 02/10/2021] [Indexed: 11/16/2022] Open
Abstract
Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.
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Affiliation(s)
- Wei-Tang Chang
- Department of Nutrition and Health Nutrition, Chinese Culture University, Taipei 11114, Taiwan;
| | - Shih-Chien Huang
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
| | - Hsin-Lin Cheng
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
| | - Shiuan-Chih Chen
- Institute of Medicine and School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Chin-Lin Hsu
- Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan; (S.-C.H.); (H.-L.C.)
- Department of Nutrition, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Correspondence: ; Tel.: +886-4-2473-0022; Fax: +886-4-2324-8175
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Kim MB, Kim C, Hwang JK. Standardized Siegesbeckia orientalis L. Extract Increases Exercise Endurance Through Stimulation of Mitochondrial Biogenesis. J Med Food 2019; 22:1159-1167. [DOI: 10.1089/jmf.2019.4485] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Mi-Bo Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
| | - Changhee Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
| | - Jae-Kwan Hwang
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
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Bianchi S, Giovannini L. Inhibition of mTOR/S6K1/4E-BP1 Signaling by Nutraceutical SIRT1 Modulators. Nutr Cancer 2018. [DOI: 10.1080/01635581.2018.1446093] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Sara Bianchi
- Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Pisa, Italy
| | - Luca Giovannini
- Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Pisa, Italy
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Kim MB, Kim T, Kim C, Hwang JK. Standardized Kaempferia parviflora Extract Enhances Exercise Performance Through Activation of Mitochondrial Biogenesis. J Med Food 2017; 21:30-38. [PMID: 29125913 DOI: 10.1089/jmf.2017.3989] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Exercise enhances mitochondrial biogenesis in skeletal muscle. Increased mitochondrial function and content can contribute to the improvement in skeletal muscle function and the benefits of exercise by increasing the response to energy demands. The effect of standardized Kaempferia parviflora extract (KPE) on exercise performance was accessed in L6 myotubes and C57BL/6J mice. KPE significantly activated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and increased mitochondrial density in L6 myotubes. KPE also upregulated the expression of transcription factors for mitochondrial biogenesis (estrogen-related receptor-α [ERRα], nuclear respiratory factor-1 [NRF-1], and mitochondrial transcription factor A [Tfam]) through activation of PGC-1α in L6 myotubes. In vivo models including normal diet mice and high-fat diet obese mice showed that KPE effectively enhanced running endurance and increased the skeletal muscle weight/body weight ratio. Furthermore, these observations were associated with a significant upregulation of mitochondrial biogenesis regulatory genes in skeletal muscle tissue. KPE enhanced the protein expression of the sirtuin 1 (SIRT1)/adenosine monophosphate (AMP)-activated protein kinase (AMPK)/PGC-1α/peroxisome proliferator-activated receptor-δ (PPARδ) signaling pathway components in vitro and in vivo, acting as an exercise metabolism regulator. These results suggest that KPE has the potential to enhance exercise performance through mitochondrial biogenesis and the SIRT1/AMPK/PGC-1α/PPARδ signaling pathways.
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Affiliation(s)
- Mi-Bo Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea
| | - Taeyoon Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea
| | - Changhee Kim
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea
| | - Jae-Kwan Hwang
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea
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Effects of resveratrol, epigallocatechin gallate, and epicatechin on mitochondrial functions in C2C12 myotubes. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Role of nutraceutical SIRT1 modulators in AMPK and mTOR pathway: Evidence of a synergistic effect. Nutrition 2016; 34:82-96. [PMID: 28063518 DOI: 10.1016/j.nut.2016.09.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 08/04/2016] [Accepted: 09/23/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of different natural substances on SIRT1 expression and on AMPK and mTOR phosphorylation. Moreover, we investigated the presence of a synergistic effect between the substances. METHODS Human cervical carcinoma cells were seeded in 12-well plates, then incubated with the nine tested substances (resveratrol, quercetin, berberine, catechin, tyrosol, ferulic acid, niclosamide, curcumin, and malvidin) at different concentrations and left in incubation for 3, 6, and 24 h. The targeting proteins' expression and phosphorylation were evaluated by immunoblotting, and cytotoxicity tests were performed by CellTiter-Blue Cell Viability Assay. RESULTS No statistically significant decrease (P > 0.05) in the number of viable cells was found. The expression of SIRT1 was significantly increased in all experimental groups compared with the control group (P < 0.001). Instead, the simultaneous administration involved a significant and synergistic increase in the expression of SIRT1 for some but not all of the tested compounds. Finally, the individual administration of berberine, quercetin, ferulic acid, and tyrosol resulted in a statistically significant increase in AMPK activation and mTOR inhibition, whereas their associated administration did not reveal a synergistic effect. CONCLUSIONS Our results provide evidence that all compounds have the potential to stimulate SIRT1 and sustain the stimulating action of resveratrol on SIRT1, already widely reported in the literature. In this regard, we confirm the interaction of these substances also with the pathway of AMPK and mTOR, in support of the studies that highlight the importance of SIRT1/AMPK and mTOR pathway in many diseases.
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Kunanusornchai W, Witoonpanich B, Tawonsawatruk T, Pichyangkura R, Chatsudthipong V, Muanprasat C. Chitosan oligosaccharide suppresses synovial inflammation via AMPK activation: An in vitro and in vivo study. Pharmacol Res 2016; 113:458-467. [PMID: 27650754 DOI: 10.1016/j.phrs.2016.09.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/11/2016] [Accepted: 09/14/2016] [Indexed: 12/12/2022]
Abstract
Synovial inflammation plays an important role in the early pathogenesis of osteoarthritis (OA). Chitosan oligosaccharide (COS) has been shown to activate AMPK and suppress inflammatory responses in intestinal epithelial cells. This study aimed to investigate the effect of COS on AMPK activation and synovial inflammation using both primary cultures of synoviocytes and a rabbit model of anterior cruciate ligament (ACL) transection-induced OA. COS induced AMPK activation in both rabbit and human synoviocytes. The mechanism of COS-induced AMPK activation involves an increase in the ADP/ATP ratio but not calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ). Interestingly, COS suppressed the TNFα-induced iNOS and COX-2 expression via an AMPK-dependent mechanism in both rabbit and human synoviocytes. Importantly, oral administration of COS (10mg/kg/day) induced AMPK activation and alleviated signs of inflammation including COX-2 expression in the synovium of a rabbit ACL transection model. Taken together, our results indicate that COS suppresses synovial inflammation in vitro and in vivo via AMPK activation. COS may be useful in the prevention of OA.
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Affiliation(s)
- Wanlop Kunanusornchai
- Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand
| | - Bhee Witoonpanich
- Department of Orthopedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand
| | - Tulyapruek Tawonsawatruk
- Department of Orthopedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand
| | - Rath Pichyangkura
- Department of Biochemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Phayathai, Bangkok 10330, Thailand
| | - Varanuj Chatsudthipong
- Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand
| | - Chatchai Muanprasat
- Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
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Abstract
Activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) contributes to beneficial effects such as improvement of the hyperglycemic state in diabetes as well as reduction of obesity and inflammatory processes. Furthermore, stimulation of AMPK activity has been associated with increased exercise capacity. A study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) increased the running capacity of mice without any training and thus, prompted the World Anti-Doping Agency (WADA) to include certain AMPK activators in the list of forbidden drugs. This raises the question as to whether all AMPK activators should be considered for registration or whether the increase in exercise performance is only associated with specific AMPK-activating substances. In this review, we intend to shed light on currently published AMPK-activating drugs, their working mechanisms, and their impact on body fitness.
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Han FS, Yang SJ, Lin MB, Chen YQ, Yang P, Xu JM. Chitooligosaccharides promote radiosensitivity in colon cancer line SW480. World J Gastroenterol 2016; 22:5193-5200. [PMID: 27298562 PMCID: PMC4893466 DOI: 10.3748/wjg.v22.i22.5193] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 03/02/2016] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the anti-proliferation and radiosensitization effect of chitooligosaccharides (COS) on human colon cancer cell line SW480.
METHODS: SW480 cells were treated with 0, 1.0, 2.0, 3.0, 4.0 and 5.0 mg/mL of COS for 48 h. CCK-8 assay was employed to obtain the cell survival ratio of SW480 cells, and the anti-proliferation curve was observed with the inhibition ratio of COS on SW480 cells. The RAY + COS group was treated with 1.0 mg/mL of COS for 48 h, while both the RAY and RAY+COS groups were exposed to X-ray at 0, 1, 2, 4, 6 and 8 Gy, respectively. Clonogenic assay was used to analyze cell viability in the two groups at 10 d after treatment, and a cell survival curve was used to analyze the sensitization ratio of COS. The RAY group was exposed to X-ray at 6 Gy, while the RAY+COS group was treated with 1.0 mg/mL of COS for 48 h in advance and exposed to X-ray at 6 Gy. Flow cytometry was employed to detect cell cycle and apoptosis rate in the non-treatment group, as well as in the RAY and RAY + COS groups after 24 h of treatment.
RESULTS: COS inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of COS (P < 0.01). Cell viability decreased as radiation dose increased in the RAY and RAY+COS groups (P < 0.01). Cell viabilities in the RAY+COS group were lower than in the RAY group at all doses of X-ray exposure (P < 0.01), and the sensitization ratio of COS on SW480 cells was 1.39. Compared with the non-treatment group, there was a significant increase in apoptosis rate in both the RAY and RAY + COS groups; while the apoptosis rate in the RAY+COS group was significantly higher than in the RAY group (P < 0.01). In comparing these three groups, the percentage of G2/M phase in both the RAY and RAY + COS groups significantly increased, and the percentage of the S phase and G0/G1 phase was downregulated. Furthermore, the percentage in the G2/M phase was higher, and the percentage in the S phase and G0/G1 phase was lower in the RAY + COS group vs RAY group (P < 0.01).
CONCLUSION: COS can inhibit the proliferation of SW480 cells and enhance the radiosensitization of SW480 cells, inducing apoptosis and G2/M phase arrest.
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Luo Y, Deng L, Deng QJ, Wen L. Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line. ASIAN PAC J TROP MED 2016; 9:601-5. [DOI: 10.1016/j.apjtm.2016.04.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 03/16/2016] [Accepted: 04/08/2016] [Indexed: 02/07/2023] Open
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16
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Kim JH, Pan JH, Lee ES, Kim YJ. l -Carnitine enhances exercise endurance capacity by promoting muscle oxidative metabolism in mice. Biochem Biophys Res Commun 2015; 464:568-73. [DOI: 10.1016/j.bbrc.2015.07.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 07/01/2015] [Indexed: 11/15/2022]
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17
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Wang Y, Zhao Y, Sun C, Hu W, Zhao J, Li G, Zhang L, Liu M, Liu Y, Ding F, Yang Y, Gu X. Chitosan Degradation Products Promote Nerve Regeneration by Stimulating Schwann Cell Proliferation via miR-27a/FOXO1 Axis. Mol Neurobiol 2014; 53:28-39. [PMID: 25399953 DOI: 10.1007/s12035-014-8968-2] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 10/28/2014] [Indexed: 12/20/2022]
Abstract
Natural polysaccharides are biomaterials widely used for constructing scaffolds in tissue engineering. While natural polysaccharides have been shown to robustly promote tissue regeneration, the underlying molecular mechanism remains largely unknown. Here, we show that chitooligosaccharides (COS), the intermediate products of chitosan degradation, stimulate peripheral nerve regeneration in rats. Our experiment also shows that COS stimulate the proliferation of Schwann cells (SCs) during nerve regeneration. By analyzing the transcriptome and gene regulatory network, we identified the miR-27a/FOXO1 axis as the main signaling pathway for mediating the proliferative effects of COS on SCs. COS increase the expression level of miR-27a and cause a reduction of FOXO1, which subsequently accelerates the cell cycle and stimulates SC proliferation to stimulate nerve regeneration. These findings define a basic pathway for oligosaccharides-mediated cell proliferation and reveal a novel aspect of polysaccharide biomaterials in tissue engineering.
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Affiliation(s)
- Yongjun Wang
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Yahong Zhao
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Cheng Sun
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Wen Hu
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Jing Zhao
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Guicai Li
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Luzhong Zhang
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Mei Liu
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Yan Liu
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Fei Ding
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China.,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China
| | - Yumin Yang
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China. .,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
| | - Xiaosong Gu
- Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, 226001, China. .,Co-innovation Center of Neuroregeneration, Nantong, 226001, Jiangsu Province, China.
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18
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Ferraro E, Giammarioli AM, Chiandotto S, Spoletini I, Rosano G. Exercise-induced skeletal muscle remodeling and metabolic adaptation: redox signaling and role of autophagy. Antioxid Redox Signal 2014; 21:154-76. [PMID: 24450966 PMCID: PMC4048572 DOI: 10.1089/ars.2013.5773] [Citation(s) in RCA: 151] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
SIGNIFICANCE Skeletal muscle is a highly plastic tissue. Exercise evokes signaling pathways that strongly modify myofiber metabolism and physiological and contractile properties of skeletal muscle. Regular physical activity is beneficial for health and is highly recommended for the prevention of several chronic conditions. In this review, we have focused our attention on the pathways that are known to mediate physical training-induced plasticity. RECENT ADVANCES An important role for redox signaling has recently been proposed in exercise-mediated muscle remodeling and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) activation. Still more currently, autophagy has also been found to be involved in metabolic adaptation to exercise. CRITICAL ISSUES Both redox signaling and autophagy are processes with ambivalent effects; they can be detrimental and beneficial, depending on their delicate balance. As such, understanding their role in the chain of events induced by exercise and leading to skeletal muscle remodeling is a very complicated matter. Moreover, the study of the signaling induced by exercise is made even more difficult by the fact that exercise can be performed with several different modalities, with this having different repercussions on adaptation. FUTURE DIRECTIONS Unraveling the complexity of the molecular signaling triggered by exercise on skeletal muscle is crucial in order to define the therapeutic potentiality of physical training and to identify new pharmacological compounds that are able to reproduce some beneficial effects of exercise. In evaluating the effect of new "exercise mimetics," it will also be necessary to take into account the involvement of reactive oxygen species, reactive nitrogen species, and autophagy and their controversial effects.
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Affiliation(s)
- Elisabetta Ferraro
- 1 Pathophysiology and Treatment of Muscle Wasting Disorders Unit, IRCCS San Raffaele Pisana , Rome, Italy
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19
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Seo DB, Jeong HW, Lee SJ, Lee SJ. Coumestrol induces mitochondrial biogenesis by activating Sirt1 in cultured skeletal muscle cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:4298-4305. [PMID: 24712520 DOI: 10.1021/jf404882w] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The mitochondrion is a central organelle in cellular energy homeostasis; thus, reduced mitochondrial activity has been associated with aging and metabolic disorders. This paper provides biological evidence that coumestrol, which is a natural isoflavone, activates mitochondrial biogenesis. In cultured myocytes, coumestrol activated the silent information regulator two ortholog 1 (Sirt1) through the elevation of the intracellular NAD(+)/NADH ratio. Coumestrol also increased the mitochondrial contents and induced the expression of key proteins in the mitochondrial electron transfer chain in cultured myocytes. A Sirt1 inhibitor and Sirt1-targeting siRNAs abolished the effect of coumestrol on mitochondrial biogenesis. Similar to an increase in mitochondrial content, coumestrol improved myocyte function with increased ATP concentration. Taken together, the data suggest that coumestrol is a novel inducer of mitochondrial biogenesis through the activation of Sirt1.
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Affiliation(s)
- Dae-Bang Seo
- College of Life and Environmental Sciences, Division of Food Science, Korea University , Seoul 136-713, Republic of Korea
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20
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Christodoulou MS, Thomas A, Poulain S, Vidakovic M, Lahtela-Kakkonen M, Matulis D, Bertrand P, Bartova E, Blanquart C, Mikros E, Fokialakis N, Passarella D, Benhida R, Martinet N. Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing? MEDCHEMCOMM 2014. [DOI: 10.1039/c4md00268g] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Why is it relevant to propose epigenetic “Nutricures” to prevent diseases linked with ageing?
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21
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Boaventura G, Casimiro-Lopes G, Pazos-Moura CC, Oliveira E, Lisboa PC, Moura EG. Effects of running wheel training on adult obese rats programmed by maternal prolactin inhibition. J Endocrinol 2013; 219:29-37. [PMID: 23863192 DOI: 10.1530/joe-13-0102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The inhibition of maternal prolactin production in late lactation leads to metabolic syndrome and hypothyroidism in adult offspring. Physical training is a therapeutic strategy that could prevent or reverse this condition. We evaluated the effects of a short-duration low-intensity running wheel training program on the metabolic and hormonal alterations in rats. Lactating Wistar rats were treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20, and 21 of lactation, and the training of offspring began at 35 days of age. Offspring were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the onset of weight gain in Bro-Ex offspring, and the food intake did not change during the experimental period. At 180 days, visceral fat mass was higher (+46%) in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running capacity was higher in trained animals. Most parameters observed in the Bro-Sed offspring were consistent with hypothyroidism and metabolic syndrome and were reversed in the Bro-Ex group. Chronic exercise did not influence the muscle glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher plasma lactate dehydrogenase levels, indicating skeletal muscle damage and intolerance of the training program. Low-intensity chronic training is able to normalize many clinical aspects in Bro animals; however, these animals might have had a lower threshold for exercise adaptation than the control rats.
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Affiliation(s)
- G Boaventura
- Departamento de Ciências Fisiológicas, 5° Andar, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro, 87, Rio de Janeiro 20551-030, Brazil
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22
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Preyat N, Leo O. Sirtuin deacylases: a molecular link between metabolism and immunity. J Leukoc Biol 2013; 93:669-80. [PMID: 23325925 DOI: 10.1189/jlb.1112557] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Lysine deacetylation by the NAD(+)-dependent family of sirtuins has been recognized as an important post-translational modification regulating a wide range of cellular processes. These lysine deacetylases have attracted much interest based on their ability to promote survival in response to stress. Sirtuins require NAD(+) for their enzymatic activity, suggesting that these enzymes may represent molecular links between cell metabolism and several human disorders, including diabetes and cancer. Inflammation represents a pathological situation with clear connections to metabolism and aging in humans, raising the possibility that sirtuins may also play an important role during a normal and/or a pathological immune response. A growing body of data has confirmed the immunomodulatory properties of sirtuins, although often with contrasting and opposing conclusions. These observations will be summarized herein and the possible strategies that may lead to the development of novel therapeutic approaches to treat inflammation briefly discussed.
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Affiliation(s)
- Nicolas Preyat
- Laboratory of Immunobiology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies, Belgium
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