6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways
Methamphetamine (METH) is a synthetic psychostimulant drug that has detrimental effects on the health of its users. Although it has been investigated as a cause of neurodegenerative disease due to its neurotoxicity, whether small molecules derived from natural products attenuate these side effects r...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/9/2442 |
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| author | Hyun-Su Lee Gil-Saeng Jeong |
| author_facet | Hyun-Su Lee Gil-Saeng Jeong |
| author_sort | Hyun-Su Lee |
| collection | DOAJ |
| description | Methamphetamine (METH) is a synthetic psychostimulant drug that has detrimental effects on the health of its users. Although it has been investigated as a cause of neurodegenerative disease due to its neurotoxicity, whether small molecules derived from natural products attenuate these side effects remains elusive. 6,7,4′-trihydroxyflavanone (THF) is a flavanone family that possesses various pharmacological activities, including anti-rheumatic, anti-ischemic, anti-inflammatory, anti-osteoclastogenic, and protective effects against METH-induced deactivation of T cells. However, little is known about whether THF protects neuronal cells from METH-induced neurotoxicity. Here, we investigated the protective effects of THF on neurotoxicity induced by METH exposure by enhancing the Nrf2/HO-1 and PI3K/Akt/mTOR signaling pathways in SH-SY5y cells. Treatment with THF did not lead to cytotoxicity, but attenuated METH-induced neurotoxicity by modulating the expression of apoptosis-related proteins, METH-induced oxidative stress, and PI3K/Akt/mTOR phosphorylation in METH-exposed SH-SY5y cells. Moreover, we found THF induced Nrf2 nuclear translocation and HO-1 expression. An inhibitor assay confirmed that the induction of HO-1 by THF attenuates METH-induced neurotoxicity. Therefore, we suggest that THF preserves neuronal cells from METH-induced neurotoxicity by upregulating HO-1 expression through the Nrf2 and PI3K/Akt/mTOR signaling pathways. Thus, THF has therapeutic potential for use in the treatment of METH-addicts suffering from neurodegenerative diseases. |
| first_indexed | 2024-03-10T12:04:48Z |
| format | Article |
| id | doaj.art-7da02f6154214b388b2063606b94d76b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:04:48Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7da02f6154214b388b2063606b94d76b2023-11-21T16:40:25ZengMDPI AGMolecules1420-30492021-04-01269244210.3390/molecules260924426,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling PathwaysHyun-Su Lee0Gil-Saeng Jeong1College of Pharmacy, Keimyung University, Daegu 42601, KoreaCollege of Pharmacy, Keimyung University, Daegu 42601, KoreaMethamphetamine (METH) is a synthetic psychostimulant drug that has detrimental effects on the health of its users. Although it has been investigated as a cause of neurodegenerative disease due to its neurotoxicity, whether small molecules derived from natural products attenuate these side effects remains elusive. 6,7,4′-trihydroxyflavanone (THF) is a flavanone family that possesses various pharmacological activities, including anti-rheumatic, anti-ischemic, anti-inflammatory, anti-osteoclastogenic, and protective effects against METH-induced deactivation of T cells. However, little is known about whether THF protects neuronal cells from METH-induced neurotoxicity. Here, we investigated the protective effects of THF on neurotoxicity induced by METH exposure by enhancing the Nrf2/HO-1 and PI3K/Akt/mTOR signaling pathways in SH-SY5y cells. Treatment with THF did not lead to cytotoxicity, but attenuated METH-induced neurotoxicity by modulating the expression of apoptosis-related proteins, METH-induced oxidative stress, and PI3K/Akt/mTOR phosphorylation in METH-exposed SH-SY5y cells. Moreover, we found THF induced Nrf2 nuclear translocation and HO-1 expression. An inhibitor assay confirmed that the induction of HO-1 by THF attenuates METH-induced neurotoxicity. Therefore, we suggest that THF preserves neuronal cells from METH-induced neurotoxicity by upregulating HO-1 expression through the Nrf2 and PI3K/Akt/mTOR signaling pathways. Thus, THF has therapeutic potential for use in the treatment of METH-addicts suffering from neurodegenerative diseases.https://www.mdpi.com/1420-3049/26/9/2442methamphetamine6,7,4′-trihydroxyflavanoneNrf2HO-1PI3Kneurotoxicity |
| spellingShingle | Hyun-Su Lee Gil-Saeng Jeong 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways Molecules methamphetamine 6,7,4′-trihydroxyflavanone Nrf2 HO-1 PI3K neurotoxicity |
| title | 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways |
| title_full | 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways |
| title_fullStr | 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways |
| title_full_unstemmed | 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways |
| title_short | 6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways |
| title_sort | 6 7 4 trihydroxyflavanone mitigates methamphetamine induced neurotoxicity in sh sy5y cells via nrf2 heme oxyganase 1 and pi3k akt mtor signaling pathways |
| topic | methamphetamine 6,7,4′-trihydroxyflavanone Nrf2 HO-1 PI3K neurotoxicity |
| url | https://www.mdpi.com/1420-3049/26/9/2442 |
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