Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo
Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (<i>Piper betle<...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/374 |
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| author | Md Badrul Alam Na Hyun Park Bo-Rim Song Sang-Han Lee |
| author_facet | Md Badrul Alam Na Hyun Park Bo-Rim Song Sang-Han Lee |
| author_sort | Md Badrul Alam |
| collection | DOAJ |
| description | Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (<i>Piper betle</i> L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC<sub>50</sub> value of 41.52 ± 1.02 μg/mL, 45.60 ± 0.56 μg/mL, and 51.42 ± 1.25 μg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC<sub>50</sub> = 7.72 ± 0.98 μg/mL, 20.59 ± 0.83 μg/mL and 24.78 ± 0.56 μg/mL, respectively). According to gas chromatography–mass spectrometry, PBL is abundant in caryophyllene, eugenol, <i>O</i>-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent. |
| first_indexed | 2024-03-11T09:14:20Z |
| format | Article |
| id | doaj.art-be5ff54fc6cc4725bac23ca563f41763 |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:20Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-be5ff54fc6cc4725bac23ca563f417632023-11-16T18:47:17ZengMDPI AGAntioxidants2076-39212023-02-0112237410.3390/antiox12020374Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In VivoMd Badrul Alam0Na Hyun Park1Bo-Rim Song2Sang-Han Lee3Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Republic of KoreaEach individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (<i>Piper betle</i> L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC<sub>50</sub> value of 41.52 ± 1.02 μg/mL, 45.60 ± 0.56 μg/mL, and 51.42 ± 1.25 μg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC<sub>50</sub> = 7.72 ± 0.98 μg/mL, 20.59 ± 0.83 μg/mL and 24.78 ± 0.56 μg/mL, respectively). According to gas chromatography–mass spectrometry, PBL is abundant in caryophyllene, eugenol, <i>O</i>-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent.https://www.mdpi.com/2076-3921/12/2/374antioxidantautophagycAMPmelanogenesis<i>Piper betle</i> |
| spellingShingle | Md Badrul Alam Na Hyun Park Bo-Rim Song Sang-Han Lee Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo Antioxidants antioxidant autophagy cAMP melanogenesis <i>Piper betle</i> |
| title | Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo |
| title_full | Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo |
| title_fullStr | Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo |
| title_full_unstemmed | Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo |
| title_short | Antioxidant Potential-Rich Betel Leaves (<i>Piper betle</i> L.) Exert Depigmenting Action by Triggering Autophagy and Downregulating MITF/Tyrosinase In Vitro and In Vivo |
| title_sort | antioxidant potential rich betel leaves i piper betle i l exert depigmenting action by triggering autophagy and downregulating mitf tyrosinase in vitro and in vivo |
| topic | antioxidant autophagy cAMP melanogenesis <i>Piper betle</i> |
| url | https://www.mdpi.com/2076-3921/12/2/374 |
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