Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner
In this study, we investigated the depigmentation effect of <i>Amorpha fruticosa</i> L. root extract (RE), an herbal medicine. <i>A. fruticosa</i> RE significantly induced depigmentation in α-MSH-treated B16F10 cells at noncytotoxic concentrations. Further, the RE decreased t...
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2022-06-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/7/196 |
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| author | Ki Won Lee Dang Thi Nguyen Minju Kim Si Hyeon Lee Seyeon Lim Jisu Kim Ki Hun Park Jeong Yoon Kim Jiyun Yoo Cheol Hwangbo Kwang Dong Kim |
| author_facet | Ki Won Lee Dang Thi Nguyen Minju Kim Si Hyeon Lee Seyeon Lim Jisu Kim Ki Hun Park Jeong Yoon Kim Jiyun Yoo Cheol Hwangbo Kwang Dong Kim |
| author_sort | Ki Won Lee |
| collection | DOAJ |
| description | In this study, we investigated the depigmentation effect of <i>Amorpha fruticosa</i> L. root extract (RE), an herbal medicine. <i>A. fruticosa</i> RE significantly induced depigmentation in α-MSH-treated B16F10 cells at noncytotoxic concentrations. Further, the RE decreased the protein levels of the melanosomal proteins Tyr and Pmel without decreasing their transcript levels. We found that MG132, a proteasome complex inhibitor, was unable to rescue the protein levels, but PepA/E-64D (a lysosomal enzyme inhibitor), 3-MA (a representative autophagy inhibitor), and <i>ATG5</i> knockdown effectively rescued the protein levels and inhibited the depigmentation effect following RE treatment. Among rotenoids, amorphigenin composed in the RE was identified as a functional chemical that could induce depigmentation; whereas rapamycin, an mTOR inhibitor and a nonselective autophagy inducer, could not induce depigmentation, and amorphigenin effectively induced depigmentation through the degradation of melanosomal proteins. Amorphigenin activated AMPK without affecting mTOR, and knockdown of AMPK offset the whitening effect through degradation of melanosome proteins by amorphigenin. Results from this study suggested that amorphigenin can induce degradation of the melanosome through an AMPK-dependent autophagy process, and has the potential to be used as a depigmentation agent for the treatment of hyperpigmentation. |
| first_indexed | 2024-03-09T12:04:19Z |
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| last_indexed | 2024-03-09T12:04:19Z |
| publishDate | 2022-06-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-0aa26d678acb449492db2f0cdab881072023-11-30T22:59:29ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-06-014472856286710.3390/cimb44070196Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent MannerKi Won Lee0Dang Thi Nguyen1Minju Kim2Si Hyeon Lee3Seyeon Lim4Jisu Kim5Ki Hun Park6Jeong Yoon Kim7Jiyun Yoo8Cheol Hwangbo9Kwang Dong Kim10PMBBRC, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDepartment of Pharmaceutical Engineering, Gyeongsang National University, Jinju 52725, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Applied Life Science, Gyeongsang National University, Jinju 52828, KoreaPMBBRC, Gyeongsang National University, Jinju 52828, KoreaIn this study, we investigated the depigmentation effect of <i>Amorpha fruticosa</i> L. root extract (RE), an herbal medicine. <i>A. fruticosa</i> RE significantly induced depigmentation in α-MSH-treated B16F10 cells at noncytotoxic concentrations. Further, the RE decreased the protein levels of the melanosomal proteins Tyr and Pmel without decreasing their transcript levels. We found that MG132, a proteasome complex inhibitor, was unable to rescue the protein levels, but PepA/E-64D (a lysosomal enzyme inhibitor), 3-MA (a representative autophagy inhibitor), and <i>ATG5</i> knockdown effectively rescued the protein levels and inhibited the depigmentation effect following RE treatment. Among rotenoids, amorphigenin composed in the RE was identified as a functional chemical that could induce depigmentation; whereas rapamycin, an mTOR inhibitor and a nonselective autophagy inducer, could not induce depigmentation, and amorphigenin effectively induced depigmentation through the degradation of melanosomal proteins. Amorphigenin activated AMPK without affecting mTOR, and knockdown of AMPK offset the whitening effect through degradation of melanosome proteins by amorphigenin. Results from this study suggested that amorphigenin can induce degradation of the melanosome through an AMPK-dependent autophagy process, and has the potential to be used as a depigmentation agent for the treatment of hyperpigmentation.https://www.mdpi.com/1467-3045/44/7/196<i>Amorpha fruticosa</i> L.depigmentationautophagyamorphigeninAMPK |
| spellingShingle | Ki Won Lee Dang Thi Nguyen Minju Kim Si Hyeon Lee Seyeon Lim Jisu Kim Ki Hun Park Jeong Yoon Kim Jiyun Yoo Cheol Hwangbo Kwang Dong Kim Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner Current Issues in Molecular Biology <i>Amorpha fruticosa</i> L. depigmentation autophagy amorphigenin AMPK |
| title | Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner |
| title_full | Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner |
| title_fullStr | Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner |
| title_full_unstemmed | Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner |
| title_short | Amorphigenin from <i>Amorpha fruticosa</i> L. Root Extract Induces Autophagy-Mediated Melanosome Degradation in mTOR-Independent- and AMPK-Dependent Manner |
| title_sort | amorphigenin from i amorpha fruticosa i l root extract induces autophagy mediated melanosome degradation in mtor independent and ampk dependent manner |
| topic | <i>Amorpha fruticosa</i> L. depigmentation autophagy amorphigenin AMPK |
| url | https://www.mdpi.com/1467-3045/44/7/196 |
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