Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress
Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underly...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Journal of Ginseng Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1226845321001342 |
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| author | Tae Jin Kim Do Hyeon Pyun Myeong Jun Kim Ji Hoon Jeong A.M. Abd El-Aty Tae Woo Jung |
| author_facet | Tae Jin Kim Do Hyeon Pyun Myeong Jun Kim Ji Hoon Jeong A.M. Abd El-Aty Tae Woo Jung |
| author_sort | Tae Jin Kim |
| collection | DOAJ |
| description | Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. Methods: C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4–5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. Results: CK treatment attenuated ER stress markers, such as eIF2α phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. Conclusion: These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity. |
| first_indexed | 2024-04-13T08:43:18Z |
| format | Article |
| id | doaj.art-5c74e253c1d94e579d8591eed696c927 |
| institution | Directory Open Access Journal |
| issn | 1226-8453 |
| language | English |
| last_indexed | 2024-04-13T08:43:18Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ginseng Research |
| spelling | doaj.art-5c74e253c1d94e579d8591eed696c9272022-12-22T02:53:50ZengElsevierJournal of Ginseng Research1226-84532022-05-01463444453Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stressTae Jin Kim0Do Hyeon Pyun1Myeong Jun Kim2Ji Hoon Jeong3A.M. Abd El-Aty4Tae Woo Jung5Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of KoreaState Key Laboratory of Biobased Material and Green Papermaking, College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Science, Jinan, China; Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, TurkeyDepartment of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Corresponding author. Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 06974, Republic of Korea.Background: Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. Methods: C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4–5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. Results: CK treatment attenuated ER stress markers, such as eIF2α phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. Conclusion: These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity.http://www.sciencedirect.com/science/article/pii/S1226845321001342Compound KAMPKAutophagyER stressMyogenesisSarcopenia |
| spellingShingle | Tae Jin Kim Do Hyeon Pyun Myeong Jun Kim Ji Hoon Jeong A.M. Abd El-Aty Tae Woo Jung Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress Journal of Ginseng Research Compound K AMPK Autophagy ER stress Myogenesis Sarcopenia |
| title | Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress |
| title_full | Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress |
| title_fullStr | Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress |
| title_full_unstemmed | Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress |
| title_short | Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress |
| title_sort | ginsenoside compound k ameliorates palmitate induced atrophy in c2c12 myotubes via promyogenic effects and ampk autophagy mediated suppression of endoplasmic reticulum stress |
| topic | Compound K AMPK Autophagy ER stress Myogenesis Sarcopenia |
| url | http://www.sciencedirect.com/science/article/pii/S1226845321001342 |
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