Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway
Introduction: Insomnia is a chronic disease affecting a third of the global adult population. Hehuan Anshen Decoction (HHASD), an innovative formula derived from Traditional Chinese medicine, has demonstrated therapeutic efficacy in treating insomnia, however, the potential pharmacological mechanism...
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Elsevier
2024-12-01
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| Series: | Pharmacological Research - Modern Chinese Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667142524001465 |
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| author | Qing Deng Yanan Li Wenyun Kui Linting He Yuxia Wang Nana Li Jian Xu Kaiqiang Wang Chunchun Xue Zhongwei Sha |
| author_facet | Qing Deng Yanan Li Wenyun Kui Linting He Yuxia Wang Nana Li Jian Xu Kaiqiang Wang Chunchun Xue Zhongwei Sha |
| author_sort | Qing Deng |
| collection | DOAJ |
| description | Introduction: Insomnia is a chronic disease affecting a third of the global adult population. Hehuan Anshen Decoction (HHASD), an innovative formula derived from Traditional Chinese medicine, has demonstrated therapeutic efficacy in treating insomnia, however, the potential pharmacological mechanism underlying its anti-insomnia effects remains incompletely elucidated. This study aimed to explore the underlying mechanism of HHASD treatment in mice with insomnia induced by p-Chlorophenylalanine (PCPA). Methods: The active constituents of HHASD were analysed by means of UPLCHRMS. PCPA mice were administered HHASD orally for 7 days. The anti-insomnia phenotype of HHASD were assessed by behavioral tests, encompassing the open field test and pentobarbital sodium-induced sleep test, alongside the measurement of hypothalamic 5-HT levels. Then, we conducted an in-depth analysis of specific ferroptosis markers, considering biochemistry, genetics and morphology. Additionally, ferroptosis inhibitor RSL3 was used to observe the underlying mechanism of the effects of HHASD. Results: HHASD could effectively improve the insomnia behaviors induced by PCPA, resulting in increased movement trajectories, decreased sleep latency and prolonged sleep duration. Specifically, HHASD exerted a neuroprotective effect by enhancing the integrity of Nissl bodies in the hypothalamus of the PCPA mice. Mechanistic analysis revealed that HHASD could reverse the hypothalamic ferroptosis phenotype of insomnia mice by restoring the lowered levels of glutathione (GSH), inhibiting iron accumulation and elevated malondialdehyde (MDA), and mitigating mitochondrial cristae damage. Furthermore, HHASD enhanced the expression of SLC7A11 and GPX4 and reduced the ASCL4 in the hypothalamus, while the anti-insomnia effect of HHASD in the PCPA mice was eliminated by the GPX4 inhibitor RLS3. Conclusion: HHASD ameliorates insomnia-related behaviors and protects against neuronal damage by suppressing ferroptosis by regulation GPX4 signaling. This study is not only a valuable attempt to explore the potential mechanism of Traditional Chinese formula but also will provide a novel targeted therapy for the treatment strategy of insomnia. |
| format | Article |
| id | doaj-art-cee191d3a03b4e258f9484ffe35f5168 |
| institution | DOAJ |
| issn | 2667-1425 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research - Modern Chinese Medicine |
| spelling | doaj-art-cee191d3a03b4e258f9484ffe35f51682025-08-20T02:52:24ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252024-12-011310050410.1016/j.prmcm.2024.100504Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathwayQing Deng0Yanan Li1Wenyun Kui2Linting He3Yuxia Wang4Nana Li5Jian Xu6Kaiqiang Wang7Chunchun Xue8Zhongwei Sha9Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), China; School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou (730000), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), ChinaShanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), China; Corresponding authors.Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai (200071), China; Corresponding authors.Introduction: Insomnia is a chronic disease affecting a third of the global adult population. Hehuan Anshen Decoction (HHASD), an innovative formula derived from Traditional Chinese medicine, has demonstrated therapeutic efficacy in treating insomnia, however, the potential pharmacological mechanism underlying its anti-insomnia effects remains incompletely elucidated. This study aimed to explore the underlying mechanism of HHASD treatment in mice with insomnia induced by p-Chlorophenylalanine (PCPA). Methods: The active constituents of HHASD were analysed by means of UPLCHRMS. PCPA mice were administered HHASD orally for 7 days. The anti-insomnia phenotype of HHASD were assessed by behavioral tests, encompassing the open field test and pentobarbital sodium-induced sleep test, alongside the measurement of hypothalamic 5-HT levels. Then, we conducted an in-depth analysis of specific ferroptosis markers, considering biochemistry, genetics and morphology. Additionally, ferroptosis inhibitor RSL3 was used to observe the underlying mechanism of the effects of HHASD. Results: HHASD could effectively improve the insomnia behaviors induced by PCPA, resulting in increased movement trajectories, decreased sleep latency and prolonged sleep duration. Specifically, HHASD exerted a neuroprotective effect by enhancing the integrity of Nissl bodies in the hypothalamus of the PCPA mice. Mechanistic analysis revealed that HHASD could reverse the hypothalamic ferroptosis phenotype of insomnia mice by restoring the lowered levels of glutathione (GSH), inhibiting iron accumulation and elevated malondialdehyde (MDA), and mitigating mitochondrial cristae damage. Furthermore, HHASD enhanced the expression of SLC7A11 and GPX4 and reduced the ASCL4 in the hypothalamus, while the anti-insomnia effect of HHASD in the PCPA mice was eliminated by the GPX4 inhibitor RLS3. Conclusion: HHASD ameliorates insomnia-related behaviors and protects against neuronal damage by suppressing ferroptosis by regulation GPX4 signaling. This study is not only a valuable attempt to explore the potential mechanism of Traditional Chinese formula but also will provide a novel targeted therapy for the treatment strategy of insomnia.http://www.sciencedirect.com/science/article/pii/S2667142524001465FerroptosisInsomniaHehuan Anshen decoctionHypothalamusGlutathione peroxidase 4 |
| spellingShingle | Qing Deng Yanan Li Wenyun Kui Linting He Yuxia Wang Nana Li Jian Xu Kaiqiang Wang Chunchun Xue Zhongwei Sha Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway Pharmacological Research - Modern Chinese Medicine Ferroptosis Insomnia Hehuan Anshen decoction Hypothalamus Glutathione peroxidase 4 |
| title | Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway |
| title_full | Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway |
| title_fullStr | Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway |
| title_full_unstemmed | Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway |
| title_short | Hehuan Anshen decoction inhibits ferroptosis to ameliorate p-Chlorophenylalanine-induced insomnia by activating GPX4 pathway |
| title_sort | hehuan anshen decoction inhibits ferroptosis to ameliorate p chlorophenylalanine induced insomnia by activating gpx4 pathway |
| topic | Ferroptosis Insomnia Hehuan Anshen decoction Hypothalamus Glutathione peroxidase 4 |
| url | http://www.sciencedirect.com/science/article/pii/S2667142524001465 |
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