Antidiabetic and Antihyperlipidemic Activities and Molecular Mechanisms of Phyllanthus emblica L. Extract in Mice on a High-Fat Diet.

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3ß (GSK3ß) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice.

Antidiabetic and Immunoregulatory Activities of Extract of Phyllanthus emblica L. in NOD with Spontaneous and Cyclophosphamide-Accelerated Diabetic Mice.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)/Th2/Th17/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-γ and tumor necrosis α (TNF-α) by Th1 cells, and reduced interleukin (IL)-1ß and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-ß1 (TGF-ß1) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4+ subsets T cell distribution of CD4+IL-17 and CD4+ interferon gamma (IFN-γ), but increased the CD4+ subsets T cell distribution of CD4+IL-4 and CD4+Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4+IL-17 and CD4+IFNγ, and increased CD4+IL-4 and CD4+Foxp3 compared with the Cyp-NOD Con group (p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-γ and TNF-α by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1ß by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing ß cells (brown), and but also enhanced the percentage of Bcl-2 (green)/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas ß cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.

Synthesis and Structure-Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors.

Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC50 values ranging from 4-17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure-activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound 25 displayed excellent anticancer activity, with IC50 values of 0.13-0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.

Caffeic Acid Phenethyl Ester and Caffeamide Derivatives Suppress Oral Squamous Cell Carcinoma Cells.

Caffeic acid phenethyl ester (CAPE) contains antibiotic and anticancer activities. Therefore, we aimed to investigate the anticancer properties and mechanisms of CAPE and caffeamide derivatives in the oral squamous cell carcinoma cell (OSCC) lines SAS and OECM-1. The anti-OSCC effects of CAPE and the caffeamide derivatives (26G, 36C, 36H, 36K, and 36M) were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Cell cycle and total reactive oxygen species (ROS) production were analyzed using flow cytometry. The relative protein expression of malignant phenotypes was determined via Western blot analysis. The results showed that 26G and 36M were more cytotoxic than the other compounds in SAS cells. After 26G or 36M treatment for 48 h, cell cycle S phase or G2/M phase arrest was induced, and cellular ROS increased at 24 h, and then decreased at 48 h in both cell lines. The expression levels of cell cycle regulatory and anti-ROS proteins were downregulated. In addition, 26G or 36M treatment inhibited malignant phenotypes through mTOR-ULK1-P62-LC3 autophagic signaling activated by ROS generation. These results showed that 26G and 36M induce cancer cell death by activating autophagy signaling, which is correlated with altered cellular oxidative stress.

Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner.

Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aß-overexpressing fruit flies, and silencing NRF2 abolishes OST's antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aß-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aß and that NRF2 is necessary for OST's antagonism.

N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice.

The underlying pathological mechanisms of diabetes are complicated and varied in diabetic patients, which may lead to the current medications often failing to maintain glycemic control in the long term. Thus, the discovery of diverse new compounds for developing medicines to treat diabetes and its complications are urgently needed. Polyphenols are metabolites of plants and have been employed in the prevention and treatment of a variety of diseases. Caffeic acid phenethyl ester (CAPE) is a category of compounds structurally similar to polyphenols. In this study, we aimed to investigate the antidiabetic activity and potential molecular mechanisms of a novel synthetic CAPE derivative N-octyl caffeamide (36M) using high-fat (HF) diet induced obese mouse models. Our results demonstrate that 36M prevented the progression of diabetes in the HF diet fed obese mice via increasing phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibiting expression of protein tyrosine phosphatase 1B (PTP1B). We also found that 36M could prevent hepatic lipid storage in the HF diet fed mice via inhibition of fatty acid synthase and lipid droplet proteins, including perilipins and Fsp27. In conclusion, 36M is a potential candidate compound that can be developed as AMPK inhibitor and PTP1B inhibitor for treating diabetes and hepatic steatosis.

Fermented Taiwanofungus camphoratus Extract Ameliorates Psoriasis-Associated Response in HaCaT Cells via Modulating NF-𝜠B and mTOR Pathways.

Psoriasis is a chronic autoimmune disease, and until now, it remains an incurable disease. Therefore, the development of new drugs or agents that ameliorate the disease will have marketing potential. Taiwanofungus camphoratus (TC) is a specific fungus in Taiwan. It is demonstrated to have anticancer, anti-inflammation, and hepatoprotective effects. However, the effects of TC fermented extract on psoriasis are under investigation. In this research, we studied the ability of TC on antioxidative activity and the efficacy of TC on interleukin-17 (IL-17A)-induced intracellular oxidative stress, inflammation-relative, and proliferation-relative protein expression in human keratinocytes. The results of a DPPH radical scavenging assay, reducing power assay, and hydroxyl peroxide inhibition assay indicated that TC has a potent antioxidant ability. Furthermore, TC could reduce IL-17A-induced intracellular ROS generation and restore the NADPH level. In the investigation of pathogenesis, we discovered TC could regulate inflammatory and cell proliferation pathways via p-IKKα/p-p65 and p-mTOR/p-p70S6k signaling pathways in human keratinocytes. In conclusion, TC showed characteristics such as antioxidant, anti-inflammatory, and anti-psoriatic-associated responses. It is expected to be developed as a candidate for oxidative-stress-induced skin disorders or psoriasis treatment.

In Vitro Antimicrobial Potential of CAPE and Caffeamide Derivatives against Oral Microbes.

Caffeic acid phenethyl ester (CAPE) is a natural component isolated from propolis and used in traditional medicine. We aimed to investigate the antimicrobial properties and action mechanism of CAPE and caffeamide derivatives (26G and 36M) against oral disease microbes. We resolved the minimum inhibitory and bactericidal concentrations of 26G and 36M and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation and antibiotic resistance gene expression in methicillin-resistant Staphylococcus aureus (MRSA). Our results revealed that 26G and 36M showed the best anticancer and antimicrobial activities, respectively, compared with the other four caffeamide derivatives. Both 26G and 36M showed heat-dependent decreases in antimicrobial activity. The 36M derivative was stable irrespective of pH, whereas 26G was not stable under high pH conditions. Biofilm formation and antibiotic resistance-related gene expression were consistent with their respective phenotypes. This study provides evidence for the potential application of CAPE and caffeamide derivatives in dental medicine to cure or prevent oral diseases.

Secondary Metabolites with Antimicrobial Activities from Chamaecyparis obtusa var. formosana.

Seven new compounds, including one dimer novel skeleton, chamaecyformosanin A (1); three diterpenes, chamaecyformosanins B-D (2-4); one sesquiterpene, chamaecyformosanin E (5); and two monoterpenes, chamaecyformosanins F and G (6 and 7) were isolated from the methanol extract of the bark of Chamaecyparis obtusa var. formosana. Their structures were established by the mean of spectroscopic analysis and the comparison of NMR data with those of known analogues. Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry. Furthermore, the isolated compounds were subjected to an evaluation of their antimicrobial activity. Metabolites 1, 3, and 4 present antibacterial activities. It is worth mentioning that the chemical composition of the bark of C. obtusa var. formosana has never been studied in the past. This is the first time the barks from C. obtusa var. formosana were studied and two new skeleton compounds, 1 and 7, were obtained.

Correction: Chen et al. Secondary Metabolites with Anti-Inflammatory from the Roots of Cimicifuga taiwanensis. Molecules 2022, 27, 1657.

The authors wish to make the following changes to their paper [...].

Correction: Wu et al. Secondary Metabolites with Antimicrobial Activities from Chamaecyparisobtusa var. formosana. Molecules 2022, 27, 429.

The authors wish to make the following changes to their paper [...].

Secondary Metabolites with Anti-Inflammatory from the Roots of Cimicifuga taiwanensis.

The genus Cimicifuga is one of the smallest genera in the family Ranunculaceae. Cimicifugae Rhizoma originated from rhizomes of Cimicifuga simplex, and C. dahurica, C. racemosa, C. foetida, and C. heracleifolia have been used as anti-inflammatory, analgesic and antipyretic remedies in Chinese traditional medicine. Inflammation is related to many diseases. Cimicifuga taiwanensis was often used in folk therapy in Taiwan for inflammation. Phytochemical investigation and chromatographic separation of extracts from the roots of Cimicifuga taiwanensis has led to the isolation of six new compounds: cimicitaiwanins A-F (1-6, respectively). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with the literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3-6 exhibited potent anti-NO production activity, with IC50 values ranging from 6.54 to 24.58 µM, respectively, compared with that of quercetin, an iNOS inhibitor with an IC50 value of 34.58 µM. This is the first report on metabolite from the endemic Taiwanese plant-C. taiwanensis.

Novel Antifungal Dimers from the Roots of Taiwania cryptomerioides.

Five new dimer compounds, namely Taiwaniacryptodimers A-E (1-5), were isolated from the methanol extract of the roots of Taiwania cryptomerioides. Their structures were established by mean of spectroscopic analysis and comparison of NMR data with those of known analogues. Their antifungal activities were also evaluated. Our results indicated that metabolites 1, 2, 4, and 5 displayed moderate antifungal activities against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae.

Anti-Inflammatory Constituents of Antrodia camphorata on RAW 264.7 Cells Induced by Polyinosinic-Polycytidylic Acid.

Antrodia camphorata is an endemic mushroom in Taiwan. This study was designed to screen anti-inflammatory compounds from the methanolic extract of the mycelium of A. camphorata on nitric oxide (NO) production in RAW 264.7 cells induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA) known to be present in viral infection. A combination of bioactivity-guided isolation with an NMR-based identification led to the isolation of 4-acetylantroquinonol B (1), along with seven compounds. The structure of new compounds (4 and 5) was elucidated by spectroscopic experiments, including MS, IR, and NMR analysis. The anti-inflammatory activity of all isolated compounds was assessed at non-cytotoxic concentrations. 4-Acetylantroquinonol B (1) was the most potent compound against poly I:C-induced NO production in RAW 264.7 cells with an IC50 value of 0.57 ± 0.06 µM.

Correction: Cheng et al. Novel Antifungal Dimers from the Roots of Taiwania cryptomerioides. Molecules 2022, 27, 437.

The authors wish to make the following changes to their paper [...].

Cytotoxicity Effect of Constituents of Pinus taiwanensis Hayata Twigs on B16-F10 Melanoma Cells.

Pinus taiwanensis Hayata (Pinaceae) is an endemic plant in Taiwan. According to the Chinese Materia Medica Grand Dictionary, the Pinus species is mainly used to relieve pain, and eliminate pus and toxicity. In this study, nineteen compounds were isolated from the ethyl acetate layer of the ethanolic extract of P. taiwanensis Hayata twigs using bioassay-guided fractionation, and their anti-melanoma effects were investigated through a B16-F10 mouse melanoma cell model. The structures of the purified compounds were identified by 2D-NMR, MS, and IR, including 1 triterpenoid, 9 diterpenoids, 2 lignans, 4 phenolics, 1 phenylpropanoid, 1 flavonoid, and 1 steroid. Among them, compound 3 was found to be a new diterpene. Some of the compounds (2, 5, 6, 17, 18) showed moderate cytotoxicity effects. On the other hand, the anti-melanoma effect was no better than that from the original ethyl acetate layer. We presumed it resulted from the synergistic effect, although further experimentation needs to be performed.

Chemical Constituents and Anti-Angiogenic Principles from a Marine Algicolous Penicillium sumatraense SC29.

In this study, a marine brown alga Sargassum cristaefolium-derived fungal strain, Penicillium sumatraense SC29, was isolated and identified. Column chromatography of the extracts from liquid fermented products of the fungal strain was carried out and led to the isolation of six compounds. Their structures were elucidated by spectroscopic analysis and supported by single-crystal X-ray diffraction as four previously undescribed (R)-3-hydroxybutyric acid and glycolic acid derivatives, namely penisterines A (1) and C-E (3-5) and penisterine A methyl ether (2), isolated for the first time from natural resources, along with (R)-3-hydroxybutyric acid (6). Of these compounds identified, penisterine E (5) was a unique 6/6/6-tricyclic ether with an acetal and two hemiketal functionalities. All the isolates were subjected to in vitro anti-angiogenic assays using a human endothelial progenitor cell (EPCs) platform. Among these, penisterine D (4) inhibited EPC growth, migration, and tube formation without any cytotoxic effect. Further, in in vivo bioassays, the percentages of angiogenesis of compound 3 on Tg (fli1:EGFP) transgenic zebrafish were 54% and 37% as the treated concentration increased from 10.2 to 20.4 µg/mL, respectively, and the percentages of angiogenesis of compound 4 were 52% and 41% as the treated concentration increased from 8.6 to 17.2 µg/mL, respectively. The anti-angiogenic activity of penisterine D (4) makes it an attractive candidate for further preclinical investigation.

Polyketides with Anti-neuroinflammatory Activity from Theissenia cinerea.

Theissenia cinerea 89091602 is a previously reported plant-derived bioactive fungal strain, and the active principles separated from the extracts of its submerged culture were shown to exhibit potent anti-neuroinflammatory activities in both cellular study and animal testing. In a continuation of our previous investigation on the bioactive entities from this fungus, solid state fermentation was performed in an attempt to diversify the bioactive secondary metabolites. In the present study, five previously unreported polyketides, theissenophenol (1), theissenepoxide (2), theissenolactone D (3), theissenone (4), and theissenisochromanone (5), together with the known theissenolactone B (6), theissenolactone C (7), and arthrinone (8), were isolated and characterized through spectroscopic analysis and comparison with the literature data. The configurations of theissenepoxide (2) and theissenisochromanone (5) were further corroborated by single-crystal X-ray diffraction data analysis. Theissenone (4), theissenolactone B (6), theissenolactone C (7), and arthrinone (8) exhibited potent nitric oxide production inhibitory activities in murine brain microglial BV-2 cells with IC50 values of 5.0 ± 1.0, 4.5 ± 0.6, 1.1 ± 0.1, and 3.2 ± 0.3 µM, respectively, without any significant cytotoxic effects.

Chemical Constituents from a Mangrove-Derived Actinobacteria Isoptericola chiayiensis BCRC 16888 and Evaluation of Their Anti-NO Activity.

Cultivation of the actinobacteria strain Isoptericola chiayiensis, a mangrove-derived actinobacteria that was isolated from a mangrove soil collected in Chiayi County, resulted in the isolation of one new 2-furanone derivative, isopterfuranone (1), one new sesquiterpenoid, isopterchiayione (2), one new benzenoid derivative, isopterinoid (3), five new flavonoids, chiayiflavans A-E (4-8), and 4 metabolites isolated for the first time from nature source, methyl 3-(4-methyl-2,5-dioxopyrrolidin-3-yl)propanoate (9), 3-ethyl-4-methylpyrrolidine-2,5-dione (10), chiayiensol (11) and chiayiensic acid (12). Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. Most of the isolates showed potent inhibitory effects on NO production in LPS-stimulated RAW 264.7 murine macrophages cells with IC50 values ranging from 9.36 to 40.02 µM. Of these isolates, 4 and 5 showed NO inhibitory activity with IC50 values of 17.14 and 9.36 µM, stronger than the positive control quercetin (IC50 =36.95 µM). This is the first report on flavan metabolites from the genus Isoptericola.

The Anti-Melanogenesis Effect of 3,4-Dihydroxybenzalacetone through Downregulation of Melanosome Maturation and Transportation in B16F10 and Human Epidermal Melanocytes.

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3ß), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics.