Gouqi-derived nanovesicles (GqDNVs) inhibited dexamethasone-induced muscle atrophy associating with AMPK/SIRT1/PGC1α signaling pathway.

Xiaolei Zhou, Shiyin Xu, Zixuan Zhang, Mingmeng Tang, Zitong Meng, Zhao Peng, Yuxiao Liao, Xuefeng Yang, Andreas K Nüssler, Liegang Liu, Wei Yang
Author Information
  1. Xiaolei Zhou: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  2. Shiyin Xu: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  3. Zixuan Zhang: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  4. Mingmeng Tang: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  5. Zitong Meng: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  6. Zhao Peng: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  7. Yuxiao Liao: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  8. Xuefeng Yang: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  9. Andreas K Nüssler: Department of Traumatology, BG Trauma Center, University of Tübingen, Schnarrenbergstr. 95, 72076, Tübingen, Germany.
  10. Liegang Liu: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China.
  11. Wei Yang: Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, China. yw8278@hotmail.com.

Abstract

With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as "Gou qi zi" in China, is a traditional Chinese herb that can enhance the structure and function of muscles and bones. Otherwise, previous excellent publications illustrated that plant-derived exosome-like nanoparticles can exert good bioactive functions in different aging or disease models. Thus, we issued the hypothesis that Gouqi-derived nanovesicles (GqDNVs) may also have the ability to improve skeletal muscle health, though the effect and its mechanism need to be explored. Hence, we have extracted GqDNVs from fresh berries of Lycium barbarum L. (goji) and found that the contents of GqDNVs are rich in saccharides and lipids. Based on the pathway annotations and predictions in non-targeted metabolome analysis, GqDNVs are tightly associated with the pathways in metabolism. In muscle atrophy model mice, intramuscular injection of GqDNVs improves the cross-sectional area of the quadriceps muscle, grip strength and the AMPK/SIRT1/PGC1α pathway expression. After separately inhibiting AMPK or PGC1α in C2C12 cells with dexamethasone administration, we have found that the activated AMPK plays the chief role in improving cell proliferation induced by GqDNVs. Furthermore, the energy-targeted metabolome analysis in the quadriceps muscle demonstrates that the GqDNVs up-regulate the metabolism of amino sugar and nucleotide sugar, autophagy and oxidative phosphorylation process, which indicates the activation of muscle regeneration. Besides, the Spearman rank analysis shows close associations between the quality and function of skeletal muscle, metabolites and expression levels of AMPK and SIRT1. In this study, we provide a new founding that GqDNVs can improve the quality and function of skeletal muscle accompanying the activated AMPK/SIRT1/PGC1α signaling pathway. Therefore, GqDNVs have the effect of anti-aging skeletal muscle as a potential adjuvant or complementary method or idea in future therapy and research.

Keywords

References

  1. Adv Drug Deliv Rev. 2022 Mar;182:114108 [PMID: 34990792]
  2. Front Pharmacol. 2022 Jul 05;13:891762 [PMID: 35865958]
  3. J Nanobiotechnology. 2023 Jan 4;21(1):6 [PMID: 36600299]
  4. Food Chem. 2018 Jul 15;254:377-389 [PMID: 29548467]
  5. Life Sci. 2021 Jul 15;277:119520 [PMID: 33887345]
  6. Cell Cycle. 2011 Aug 15;10(16):2640-6 [PMID: 21799304]
  7. FASEB J. 2020 Sep;34(9):11460-11473 [PMID: 33411401]
  8. Antioxidants (Basel). 2020 Jul 01;9(7): [PMID: 32630279]
  9. Nature. 1993 Aug 5;364(6437):501-6 [PMID: 8393145]
  10. J Agric Food Chem. 2017 Jan 18;65(2):309-316 [PMID: 28027641]
  11. BMC Complement Med Ther. 2021 Aug 17;21(1):212 [PMID: 34404395]
  12. Mol Ther. 2014 Mar;22(3):522-534 [PMID: 23939022]
  13. J Ethnopharmacol. 2018 Mar 1;213:328-339 [PMID: 29051115]
  14. Eur J Nutr. 2022 Apr;61(3):1177-1186 [PMID: 34839399]
  15. Rejuvenation Res. 2012 Feb;15(1):89-97 [PMID: 22352435]
  16. Zhongguo Zhong Yao Za Zhi. 2008 Sep;33(18):2020-7 [PMID: 19160775]
  17. Trends Endocrinol Metab. 2013 May;24(5):247-56 [PMID: 23375520]
  18. Cell Metab. 2023 May 2;35(5):742-757.e10 [PMID: 37040763]
  19. J Cachexia Sarcopenia Muscle. 2019 Apr;10(2):429-444 [PMID: 30793539]
  20. Cancer Cell. 2016 Jan 11;29(1):104-116 [PMID: 26766592]
  21. Nat Commun. 2023 Aug 4;14(1):4675 [PMID: 37542026]
  22. Biomed Pharmacother. 2022 Mar;147:112620 [PMID: 35032768]
  23. FASEB J. 2010 Sep;24(9):3555-61 [PMID: 20460585]
  24. Nano Lett. 2021 Oct 13;21(19):8151-8159 [PMID: 34586821]
  25. J Extracell Vesicles. 2024 Feb;13(2):e12404 [PMID: 38326288]
  26. Meat Sci. 2020 Mar;161:108018 [PMID: 31786441]
  27. Wei Sheng Yan Jiu. 2000 Mar 30;29(2):115-7 [PMID: 12725093]
  28. J Nutr Health Aging. 2011 Jun;15(6):450-5 [PMID: 21623466]
  29. Front Nutr. 2021 Nov 23;8:753643 [PMID: 34888337]
  30. Biomed Pharmacother. 2019 Oct;118:109297 [PMID: 31404771]
  31. Pharmacol Ther. 2022 Jan;229:107921 [PMID: 34174277]
  32. Antioxidants (Basel). 2022 Jan 27;11(2): [PMID: 35204130]
  33. Cell. 1992 Oct 30;71(3):383-90 [PMID: 1330322]
  34. Biomolecules. 2019 Aug 21;9(9): [PMID: 31438522]
  35. Food Chem. 2018 Feb 1;240:759-766 [PMID: 28946340]
  36. Nat Rev Mol Cell Biol. 2022 Feb;23(2):141-161 [PMID: 34621061]
  37. Redox Biol. 2020 Aug;35:101467 [PMID: 32086007]
  38. Science. 2020 Feb 7;367(6478): [PMID: 32029601]
  39. Asian J Pharm Sci. 2022 Jan;17(1):53-69 [PMID: 35261644]
  40. Drug Deliv. 2021 Dec;28(1):1501-1509 [PMID: 34259095]
  41. Biomed Pharmacother. 2023 Sep;165:115147 [PMID: 37473679]
  42. Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2): [PMID: 22300977]
  43. Cell. 2017 Mar 23;169(1):148-160.e15 [PMID: 28340340]
  44. Nat Rev Mol Cell Biol. 2012 Mar 07;13(4):225-238 [PMID: 22395773]
  45. Front Cardiovasc Med. 2022 Apr 18;9:864188 [PMID: 35509278]
  46. Nutr Res. 2009 Jan;29(1):19-25 [PMID: 19185773]
  47. Int J Biol Macromol. 2008 Jun 1;42(5):447-9 [PMID: 18405964]
  48. PLoS One. 2012;7(9):e45845 [PMID: 23029271]
  49. Am J Sports Med. 2020 Jul;48(9):2277-2286 [PMID: 32543878]
  50. Mol Nutr Food Res. 2014 Jul;58(7):1561-73 [PMID: 24842810]
  51. J Biol Chem. 2009 Aug 14;284(33):21872-21880 [PMID: 19553684]
  52. J Nanobiotechnology. 2023 Aug 29;21(1):304 [PMID: 37644475]
  53. Cell Metab. 2012 May 2;15(5):675-90 [PMID: 22560220]
  54. Oncotarget. 2015 Aug 14;6(23):19514-27 [PMID: 26098775]
  55. Nat Commun. 2017 May 25;8:15201 [PMID: 28541289]
  56. Food Funct. 2015 Jun;6(6):2033-40 [PMID: 26021745]
  57. Mol Ther. 2021 Jan 6;29(1):13-31 [PMID: 33278566]

Grants

  1. YCJJ202201012/Fundamental Research Funds for the Central Universities
  2. 2022YFC3600600/National Key Research and Development Program of China
  3. 2021CFB313/Natural Science Foundation of Hubei Province

MeSH Term

Animals
Sirtuin 1
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mice
Signal Transduction
Dexamethasone
AMP-Activated Protein Kinases
Muscular Atrophy
Cell Line
Drugs, Chinese Herbal
Male
Muscle, Skeletal
Mice, Inbred C57BL
Nanoparticles
Exosomes

Chemicals

Sirtuin 1
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Ppargc1a protein, mouse
Dexamethasone
AMP-Activated Protein Kinases
Sirt1 protein, mouse
Drugs, Chinese Herbal

Word Cloud

Created with Highcharts 10.0.0GqDNVsmuscleskeletalpathwayanalysisAMPKcanfunctionAMPK/SIRT1/PGC1αaginghealthGojialsoGouqi-derivednanovesiclesimproveeffectfoundmetabolomemetabolismatrophyquadricepsexpressionactivatedsugarqualitysignalingincreasingtrendglobalsarcopeniabecomesignificantpublicissueberryknown"Gouqizi"ChinatraditionalChineseherbenhancestructuremusclesbonesOtherwisepreviousexcellentpublicationsillustratedplant-derivedexosome-likenanoparticlesexertgoodbioactivefunctionsdifferentdiseasemodelsThusissuedhypothesismayabilitythoughmechanismneedexploredHenceextractedfreshberriesLyciumbarbarumLgojicontentsrichsaccharideslipidsBasedannotationspredictionsnon-targetedtightlyassociatedpathwaysmodelmiceintramuscularinjectionimprovescross-sectionalareagripstrengthseparatelyinhibitingPGC1αC2C12cellsdexamethasoneadministrationplayschiefroleimprovingcellproliferationinducedFurthermoreenergy-targeteddemonstratesup-regulateaminonucleotideautophagyoxidativephosphorylationprocessindicatesactivationregenerationBesidesSpearmanrankshowscloseassociationsmetaboliteslevelsSIRT1studyprovidenewfoundingaccompanyingThereforeanti-agingpotentialadjuvantcomplementarymethodideafuturetherapyresearchinhibiteddexamethasone-inducedassociatingAgingMetabolomeSkeletal

Similar Articles

Cited By