Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Chemical Constituents with Anti-Lipid Droplet Accumulation and Anti-Inflammatory Activity from Elaeagnus glabra.

Non-alcoholic fatty liver disease (NAFLD) is a type of steatosis caused by excess lipids accumulating in the liver. The prevalence of NAFLD has increased annually due to modern lifestyles and a lack of adequate medical treatment. Thus, we were motivated to investigate the bioactive components of Formosan plants that could attenuate lipid droplet (LD) accumulation. In a series of screenings of 3000 methanolic extracts from the Formosan plant extract bank for anti-LD accumulation activity, the methanolic extract of aerial parts of Elaeagnus glabra Thunb. showed excellent anti-LD accumulation activity. E. glabra is an evergreen shrub on which only a few phytochemical and biological studies have been conducted. Here, one new flavonoid (1), two new triterpenoids (2 and 3), and 35 known compounds (4-38) were isolated from the ethyl acetate layer of aerial parts of E. glabra via a bioassay-guided fractionation process. Their structures were characterized by 1D and 2D NMR, UV, IR, and MS data. Among the isolated compounds, methyl pheophorbide a (37) efficiently reduced the normalized LD content to 0.3% with a concentration of 20 µM in AML12 cell lines without significant cytotoxic effects. 3-O-(E)-Caffeoyloleanolic acid (13) and methyl pheophorbide a (37) showed inhibitory effects on superoxide anion generation or elastase release in fMLP/CB-treated human neutrophils (IC50 < 3.0 µM); they displayed effects similar to those of the positive control, namely, LY294002. These findings indicate that E. glabra can be used for developing a new botanical drug for managing LD accumulation and against inflammation-related diseases.

Formulation Approaches to Crystalline Status Modification for Carotenoids: Impacts on Dissolution, Stability, Bioavailability, and Bioactivities.

Carotenoids, including carotenes and xanthophylls, have been identified as bioactive ingredients in foods and are considered to possess health-promoting effects. From a biopharmaceutical perspective, several physicochemical characteristics, such as scanty water solubility, restricted dissolution, and susceptibility to oxidation may influence their oral bioavailability and eventually, their effectiveness. In this review, we have summarized various formulation approaches that deal with the modification of crystalline status for carotenoids, which may improve their physicochemical properties, oral absorption, and biological effects. The mechanisms involving crystalline alteration and the typical methods for examining crystalline states in the pharmaceutical field have been included, and representative formulation approaches are introduced to unriddle the mechanisms and effects more clearly.

Chemical investigations and cytotoxic effects of metabolites from Antrodia camphorata against human hepatocellular carcinoma cells.

Antrodia camphorata is used as a medicinal fungus in Taiwan to treat fatigue, food intoxication, and enhance liver function. Here we identified fermented metabolic components from the mycelium of A. camphorata KH37 and explored their anti-hepatoma potentials with study models of human hepatoblastoma cell lines. Bioassay-guided fractionation of the solid fermentation powder of A. camphorata KH37 led to the isolation of one new quinonol, antroquinonol Z (1), and nine known compounds (2-10). Treatment with 10 µM antrocamols LT1 (2) or LT3 (3) reduced cell viability of HepG2 and Huh-7 cells to about 60% in 48 hours. Antroquinonol Z (1) exhibited mild cytotoxicity against Huh-7 cells in 48 and 72 hours. Interestingly, two fractions showed cytotoxicity in HepG2 and Huh-7 cells, even better than compounds isolated from these fractions. The significant cytotoxicity of partially purified samples from A. camphorata KH37 exhibited a potential for developing alternative or complementary therapeutics against hepatoma.

Preparatory Conditions Optimization and Characterization of Hierarchical Porous Carbon from Seaweed as Carbon-Precursor Using a Box-Behnken Design for Application of Supercapacitor.

This study has developed an environmentally friendly, simple, and economical process by utilizing seaweed as a carbon precursor to prepare a hierarchical porous carbon for the application of a supercapacitor. In the carbonization process, the design of experiment (DOE) technology is used to obtain the optimal preparatory conditions with the best electrochemical properties for the electrode materials of supercapacitors. Without using strong acid and alkali solution of the green process, NaCl is used as the pore structure proppant of seaweed (SW) for carbonization to obtain hierarchical porous carbon material to improve the pore size distribution and surface area of the material. In the experiment of SW activation, the interaction between factors has been explored by the response surface methodology (RSM) and Box-Behnken design, and the optimal conditions are found. The activated carbon with the specific surface area of 603.7 m2 g-1 and its capacitance reaching 110.8 F g-1 is successfully prepared. At a current density of 1 A g-1, the material still retains 95.4% of the initial capacitance after 10,000 cycles of stability testing. The hierarchical porous carbon material prepared by the design of experiment planning this green process has better energy storage properties than supercapacitors made of traditional carbon materials.

Tyrosinase Inhibitors Derived from Chemical Constituents of Dianella ensifolia.

Dianella ensifolia is a perennial herb with thickened rhizome and is widely distributed in tropical and subtropical regions of Asia, Australia, and the Pacific islands. This plant has the potential to be used as a source of herbal medicine. This study investigated further phytochemistry and tyrosinase inhibitory effect of some constituents isolated from D. ensifolia. Four new flavans, (2S)-4'-hydroxy-6,7-dimethoxyflavan (1), (2S)-3',4'-dihydroxy-7-methoxy-8-methylflavan (2), (2S)-2'-hydroxy-7-methoxyflavan (3), and (2S,1'S)-4-hydroxy-4-(7-methoxy-8-methylchroman-2-yl)-cyclohex-2-enone (4), together with 67 known compounds, including 10 flavans (5−14), 5 flavanones (15−19), 3 flavone (20−22), 5 chalcones (23−27), 3 chromones (28−30), 15 aromatics (31−45), 7 phenylpropanoids (46−52), one lignan (53), 7 steroids (54−60), one monoterpene (61), one diterpene (62), 4 triterpenes (63−66), a carotenoid (67), 2 alkaloids (68 and 69), and 2 fatty acids (70 and 71) were isolated from D. ensifolia. Their structures were elucidated on the basis of physical and spectroscopic data analyses. Moreover, compounds 1−4, 8, 10−15, 20, 21, and 41 were evaluated for their mushroom tyrosinase inhibitory effect. Compounds 11 and 14 strongly inhibited mushroom tyrosinase activity with IC50 values of 8.6 and 14.5 µM, respectively.

Undescribed alkyne-geranylcyclohexenetriols from the endophyte Diaporthe caulivora 09F0132 and their anti-melanogenic activity.

To explore valuable endophytic fungus from Formosan Lauraceous plants as natural medicinal products, the fungus, Diaporthe caulivora isolated from leaves of Neolitsea daibuensis, was investigated. Through a thorough investigation of the ethanolic extract of the solid fermentation of D. caulivora 09F0132, six undescribed alkyne-geranylcyclohexenetriols, caulivotrioloxins A-F, one undescribed trichopyrone, diapopyrone, two undescribed sesquiterpenes, caulibysins A-B, one compound firstly isolated from the natural source, 3-O-desmethyl phomentrioloxin, and eight known compounds have been successfully identified. The absolute configuration of caulibysin A was confirmed by single-crystal X-ray diffraction, and those of (3R,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide and (3S,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide were determined by circular dichroism (CD) spectra. Among the isolated compounds, caulivotrioloxin A concentration-dependently decreased the cellular melanin contents and tyrosinase activities in mouse melanoma B16-F10 cells, suggesting the anti-melanogenic potentials. The anti-melanogenic effects of caulivotrioloxin A involved the decrease in the protein expressions of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Taken together, these results suggested that the isolates from D. caulivora could be served as natural melanogenesis inhibitors for cosmeceutical applications.

Anti-Inflammatory Effects of Cycloheterophyllin on Dinitrochlorobenzene-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice.

Atopic dermatitis (eczema) is a condition that makes skin red and itchy. Though common in children, the condition can occur at any age. Atopic dermatitis is persistent (chronic) and tends to recur periodically. It may be accompanied by asthma or hay fever. No cure has been found for eczema. Therefore, it is very important to develop ingredients that aid the prevention and treatment of atopic dermatitis. Cycloheterophyllin is derived from Artocarpus heterophyllus and has antioxidant and anti-inflammatory activities. However, it still is not understood whether cycloheterophyllin is an anti-atopic dermatitis agent. Keratinocytes (HaCaT cells) and BALB/c mice for inducing AD-like cutaneous lesions were used to evaluate the potential of cycloheterophyllin as an anti-atopic dermatitis agent. The release of pro-inflammatory cytokines induced by treatment of TNF-α/IFN-γ was reduced after pretreatment with cycloheterophyllin. The inhibitory effects could be a contribution from the effect of the MAP kinases pathway. Moreover, the symptoms of atopic dermatitis (such as red skin and itching) were attenuated by pretreatment with cycloheterophyllin. Epidermal hyperplasia and mast cell infiltration were decreased in the histological section. Finally, damage to the skin barrier was also found to recover through assessment of transepidermal water loss. Taken together, prenylflavone-cycloheterophyllin from Artocarpus heterophyllus is a potential anti-atopic dermatitis ingredient that can be used in preventing or treating the condition.

Eupafolin Suppresses P/Q-Type Ca2+ Channels to Inhibit Ca2+/ Calmodulin-Dependent Protein Kinase II and Glutamate Release at Rat Cerebrocortical Nerve Terminals.

Eupafolin, a constituent of the aerial parts of Phyla nodiflora, has neuroprotective property. Because reducing the synaptic release of glutamate is crucial to achieving pharmacotherapeutic effects of neuroprotectants, we investigated the effect of eupafolin on glutamate release in rat cerebrocortical synaptosomes and explored the possible mechanism. We discovered that eupafolin depressed 4-aminopyridine (4-AP)-induced glutamate release, and this phenomenon was prevented in the absence of extracellular calcium. Eupafolin inhibition of glutamate release from synaptic vesicles was confirmed through measurement of the release of the fluorescent dye FM 1-43. Eupafolin decreased 4-AP-induced [Ca2+]i elevation and had no effect on synaptosomal membrane potential. The inhibition of P/Q-type Ca2+ channels reduced the decrease in glutamate release that was caused by eupafolin, and docking data revealed that eupafolin interacted with P/Q-type Ca2+ channels. Additionally, the inhibition of calcium/calmodulindependent protein kinase II (CaMKII) prevented the effect of eupafolin on evoked glutamate release. Eupafolin also reduced the 4-AP-induced activation of CaMK II and the subsequent phosphorylation of synapsin I, which is the main presynaptic target of CaMKII. Therefore, eupafolin suppresses P/Q-type Ca2+ channels and thereby inhibits CaMKII/synapsin I pathways and the release of glutamate from rat cerebrocortical synaptosomes.

Oenothera laciniata Hill Extracts Exhibits Antioxidant Effects and Attenuates Melanogenesis in B16-F10 Cells via Downregulating CREB/MITF/Tyrosinase and Upregulating p-ERK and p-JNK.

Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and superoxide anion (O2-•), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities.

Albanin A, Derived from the Root Bark of Morus alba L., Depresses Glutamate Release in the Rat Cerebrocortical Nerve Terminals via Ca2+/Calmodulin/Adenylate Cyclase 1 Suppression.

Decreasing synaptic release of glutamate may counteract glutamate excitotoxicity in many neurological diseases. In this study, we investigated the effect of albanin A, a constituent in the root bark of Morus alba L., on the release of glutamate in rat cerebral cortex nerve endings (synaptosomes). We found that albanin A at 5-30µM suppressed 4-aminopyridine (4-AP)-induced release of glutamate. This phenomenon was abolished by extracellular calcium removal or by vesicular transporter inhibition, and was associated with a decrease in intrasynaptosomal Ca2+ levels. However, albanin A had no effect on the synaptosomal membrane potential. The inhibition of N- and P/Q-type Ca2+ channels, calmodulin, adenylate cyclase (AC), and protein kinase A, abolished the effect of albanin A on the glutamate release evoked by 4-AP. Moreover, the albanin A-mediated inhibition of glutamate release was prevented by the Ca2+/calmodulin-stimulated AC1 inhibitor. Western blot showed that AC1, but not AC8, was presented in the synaptosomes, and albanin A reduced 4-AP-induced increases in synaptosomal cyclic adenosine monophosphate content. In addition, albanin A pretreatment substantially attenuated neuronal damage in a rat model of kainic acid-induced glutamate excitotoxicity. Our data reveal that albanin A suppresses glutamate release by decreasing Ca2+/calmodulin/AC1 activation in synaptosomes and exerts neuroprotective effect in vivo.

Inhibition of UVA Damage on Human Skin Dermis Fibroblasts by the Isoflavonoid Intermediate Deoxybenzoin-3A.

Ultraviolet rays are the main cause of skin aging. Isoflavone structures are good anti-ultraviolet natural compounds and have an especially strong anti-ultraviolet B (UVB) effect. However, the anti-ultraviolet A (UVA) effect of isoflavones is more controversial. Therefore, this study aims to discover which isoflavone analogue possesses a strong anti-ultraviolet A. We found the isoflavonoid intermediate deoxybenzoin-3A (DOB-3A) to be a similar isoflavone structural compound with strong anti-ultraviolet A effects. Ultraviolet rays with a wavelength of 350 nm are used to irradiate the fibroblasts of the human skin. Western blot, flow cytometry, and transmission electron microscope analyses were used to explore its anti-ultraviolet A mechanism. We established the results that DOB-3A (1) reduced the death of fibroblasts caused by ultraviolet A, (2) avoided the damage to the organelles and structures after UVA irradiation, (3) inhibited the generation of intracellular reactive oxygen species (ROS) and hydrogen peroxide-induced damage, and (4) decreased the phosphorylation of mitogen-activated protein kinases (MAPK) caused by UVA. Based on the above findings, DOB-3A is a very good anti-ultraviolet A isoflavone-related structure. Because it is simple to synthesize and has good effects, DOB-3A is a suitable anti-ultraviolet A product with an isoflavone structure. Moreover, DOB-3A's structure provides a reference for the synthesis of anti-UVA isoflavones.

Chemical Constituent of ß-Glucuronidase Inhibitors from the Root of Neolitsea acuminatissima.

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4-15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial ß-Glucuronidase (ßG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-ßG inhibitors with no effect on human ßG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-ßG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial ßG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial ßG but not human ßG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action.

Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway.

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.

Cyclocommunol induces apoptosis in human oral squamous cell carcinoma partially through a Mcl-1-dependent mechanism.

BACKGROUND: Crude extract of breadfruit has been reported to have antitumor activity against various cancer cell lines with unknown mechanism. PURPOSE: This study aims to investigate the proapoptotic effect of cyclocommunol (CYC), a prenylflavonoid from breadfruit, in two oral squamous cell carcinoma (OSCC) cell lines, SCC2095 and Ca922. METHODS: The antiproliferative effects of CYC were assessed by MTT assays and PI/annexin V analysis. SCC2095 cells were transiently transfected with Mcl-1 plasmid in overexpression experiment. Other methods used to investigate the mechanism of CYC included Western blotting, acridine orange staining and confocal microscopic visualization. RESULTS: Our results showed that CYC suppressed the viability of SCC2095 and Ca922 with IC50 values at 48 h of 4.2 and 5.0 µM, respectively. This decrease in viability occurred in a caspase-dependent apoptotic manner. In addition, CYC down-regulated the phosphorylation/expression of Akt/mTOR and Mcl-1, accompanied by reactive oxygen species generation, and autophagy induction. Notably, overexpression of Mcl-1 using Mcl-1-tag-myc partially rescued CYC-mediated caspase-3 activation, PARP cleavage, and cytotoxicity. In summary, our study demonstrated the proapoptotic activity of CYC on OSCC, partially through down-regulation of Mcl-1. CONCLUSION: CYC from breadfruit has translational value as a proapoptotic agent for OSCC.

Cudraflavone C Induces Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS Production and MAPK Activation.

Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.

Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress.

Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation.

A new anthraquinone glycoside from Rhamnus nakaharai and anti-tyrosinase effect of 6-methoxysorigenin.

In continual study on the heartwood of Rhamnus nakaharai, a new alaternin-8-O-glucoside, namely 1,2,6,8-tetrahydroxy-3-methylanthraquinone-8-O-ß-glucopyranoside (1), together with some known compounds were further isolated and characterised by 1-D, 2-D NMR and other spectral evidences. The free radical scavenging and antityrosinase activities of the isolates, including alaternin (1a), emodin (2a), emodin-8-O-ß-glucopyranoside (2), 6-methoxysorigenin-8-O-ß-glucopyranoside (3) and 6-methoxysorigenin (3a) were tested. Alaternin (1a) exhibited to be mild DPPH radical scavenger with half as potent as vitamin C, while both alaternin (1a) and emodin-8-O-ß-glucopyranoside (2) exhibited stronger SOD-like activity than that of BHA. 6-Methoxysorigenin (3a), a reported potential antioxidant, and its 8-O-glucoside (3) both performed significant inhibitory effect on mushroom tyrosinase with about twice as potent as kojic acid, the positive control.

Chemical constituents derived from Artocarpus xanthocarpus as inhibitors of melanin biosynthesis.

Twenty-four compounds, including the previously unknown artoxanthocarpuone A, artoxanthocarpuone B, hydroxylakoochin A, methoxylakoochin A, epoxylakoochin A, and artoxanthol, were isolated and characterized spectroscopically. Among them, artoxanthol is stilbene oligomer presumably constructed in a 5,11,12-triphenyl hexahydrochrysene scaffold by a Diels-Alder type of reaction, for which a biosynthetic pathway is proposed. Artoxanthol, alboctalol, steppogenin, norartocarpetin, resveratrol, oxyresveratrol, and chlorophorin potently inhibited mushroom tyrosinase activity with IC50 values from 0.9 to 5.7 µM that were all far stronger than the positive controls. Artoxanthocarpuone A, artoxanthocarpuone B, methoxylakoochin A, lakoochin A, cudraflavone C, artonin A, resveratrol, and chlorophorin reduced tyrosinase activity and inhibited α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells without affecting cell proliferation. Collectively, the results suggest that the constituents of Artocarpus xanthocarpus have potential to be used as depigmentation agents.

New Furanone and Sesquiterpene from the Pericarp of Calocedrus formosana.

One new γ-lactone, namely calolactone (1), together with one new drimane-type sesquiterpene, namely caloterpene (2), were isolated from the pericarp of Calocedrus formosana Florin. Their structures were elucidated by spectroscopic and mass spectrometric analysis.