Alam Md Badrul, Park Na Hyun, Song Bo-Rim, Lee Sang-Han
Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Republic of Korea.
Food and Bio-Industry Research Institute, Inner Beauty/Antiaging Center, Kyungpook National University, Daegu 41566, Republic of Korea.
Antioxidants (Basel). 2023 Feb 3;12(2):374. doi: 10.3390/antiox12020374.
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 ( 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 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 = 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, -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.
每个人的肤色都基于黑色素的类型和数量而独一无二，氧化应激是黑色素生成调节中的关键因素。本研究旨在了解槟榔叶提取物（PBL）的体外和体内抗氧化及美白特性及其潜在机制。PBL的乙酸乙酯馏分（PBLA）表现出优异的酚类含量（342±4.02mgGAE/g）以及较强的1,1-二苯基-2-三硝基苯肼（DPPH）、2,2'-联氮-二（3-乙基苯并噻唑啉-6-磺酸）二铵盐（ABTS）自由基清除活性和一氧化氮（NO）清除活性，其半数抑制浓度（IC）值分别为41.52±1.02μg/mL、45.60±0.56μg/mL和51.42±1.25μg/mL。相反，PBL的乙醇提取物（PBLE）表现出较强的对蘑菇、小鼠和人酪氨酸酶的抑制活性（IC分别为=7.72±0.98μg/mL、20.59±0.83μg/mL和24.78±0.56μg/mL）。根据气相色谱-质谱分析，PBL富含石竹烯、丁香酚、β-丁香酚、3-烯丙基-6-甲氧基苯基乙酸酯和胡椒酚。体外和体内研究表明，与未处理的对照相比，PBLE抑制酪氨酸酶（Tyr）、酪氨酸酶相关蛋白-1和-2（Trp-1和Trp-2）以及小眼相关转录因子（MITF），减少黑色素的形成。PBLE通过阻止环磷酸腺苷（cAMP）的合成来降低环磷酸腺苷对元件结合蛋白（CREB）磷酸化的反应。此外，它激活c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（p38），破坏Tyr和MITF并避免黑色素生成。较高水平的微管相关蛋白轻链3（LC3-II）、自噬相关蛋白5（Atg5）、Beclin 1以及较低水平的p62表明，PBLE在体外和体内均通过自噬诱导机制表现出显著的抗黑色素生成作用。此外，PBLE在体内显著降低脂质过氧化量，同时提高几种抗氧化酶的活性，如过氧化氢酶、谷胱甘肽、超氧化物歧化酶和硫氧还蛋白。因此，PBLE可作为一种有效的皮肤美白剂用于局部制剂。
