Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway
Muscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNFα). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits...
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MDPI AG
2022-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/4/390 |
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| author | Ki-Sun Park Hyungjun Kim Hye Jin Kim Kang-In Lee Seo-Young Lee Jieun Kim |
| author_facet | Ki-Sun Park Hyungjun Kim Hye Jin Kim Kang-In Lee Seo-Young Lee Jieun Kim |
| author_sort | Ki-Sun Park |
| collection | DOAJ |
| description | Muscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNFα). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits the progression of TNFα-induced skeletal muscle atrophy after menopause by restoring mitochondrial biosynthesis. Differentiated myoblasts damaged by TNFα were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)—the markers of muscle differentiation. Moreover, diameter of atrophied myotubes was restored by PNF treatment. TNFα-repressed nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) (a major regulator of mitochondrial biosynthesis) were restored by PNF, via regulation by estrogen receptor alpha (ERα), an upregulator of NRF1. This mechanism was confirmed in ovariectomized (OVX) mice with a ~40% reduction in the cross-sectional area of the anterior tibialis muscle. OVX mice administered PNF (100, 300 mg/kg/day) for 12 weeks recovered more than ~20%. Behavioral, rotarod, and inverted screen tests showed that PNF enhances reduced muscle function in OVX mice. ERα restored expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) (mitochondrial fusion markers) and dynamin-related protein (DRP1) and fission 1 (FIS1) (mitochondrial fission markers). Therefore, PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis. |
| first_indexed | 2024-03-09T04:19:35Z |
| format | Article |
| id | doaj.art-07f706f019bc4c268513ed3b03ce011a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T04:19:35Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-07f706f019bc4c268513ed3b03ce011a2023-12-03T13:49:15ZengMDPI AGPharmaceuticals1424-82472022-03-0115439010.3390/ph15040390Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis PathwayKi-Sun Park0Hyungjun Kim1Hye Jin Kim2Kang-In Lee3Seo-Young Lee4Jieun Kim5KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaKM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaMuscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNFα). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits the progression of TNFα-induced skeletal muscle atrophy after menopause by restoring mitochondrial biosynthesis. Differentiated myoblasts damaged by TNFα were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)—the markers of muscle differentiation. Moreover, diameter of atrophied myotubes was restored by PNF treatment. TNFα-repressed nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) (a major regulator of mitochondrial biosynthesis) were restored by PNF, via regulation by estrogen receptor alpha (ERα), an upregulator of NRF1. This mechanism was confirmed in ovariectomized (OVX) mice with a ~40% reduction in the cross-sectional area of the anterior tibialis muscle. OVX mice administered PNF (100, 300 mg/kg/day) for 12 weeks recovered more than ~20%. Behavioral, rotarod, and inverted screen tests showed that PNF enhances reduced muscle function in OVX mice. ERα restored expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) (mitochondrial fusion markers) and dynamin-related protein (DRP1) and fission 1 (FIS1) (mitochondrial fission markers). Therefore, PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis.https://www.mdpi.com/1424-8247/15/4/390muscle atrophypost-menopausal womenestrogen insufficiencypaeoniflorinmitochondrial biogenesisanti-inflammation |
| spellingShingle | Ki-Sun Park Hyungjun Kim Hye Jin Kim Kang-In Lee Seo-Young Lee Jieun Kim Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway Pharmaceuticals muscle atrophy post-menopausal women estrogen insufficiency paeoniflorin mitochondrial biogenesis anti-inflammation |
| title | Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway |
| title_full | Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway |
| title_fullStr | Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway |
| title_full_unstemmed | Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway |
| title_short | Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway |
| title_sort | paeoniflorin alleviates skeletal muscle atrophy in ovariectomized mice through the erα nrf1 mitochondrial biogenesis pathway |
| topic | muscle atrophy post-menopausal women estrogen insufficiency paeoniflorin mitochondrial biogenesis anti-inflammation |
| url | https://www.mdpi.com/1424-8247/15/4/390 |
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