Ultrasonic-Assisted Biphasic Aqueous Extraction of Polyphenols from Vaccinium Dunalianum Leaves: Optimization, Antioxidant, and Tyrosinase Inhibition Activities.

To optimize the ultrasonic-assisted biphasic aqueous extraction conditions for polyphenolic compounds from Vaccinium dunalianum Wight leaves and investigate their antioxidant and tyrosinase inhibition activities, single-factor experiments were conducted to investigate the effects of ethanol volume fraction (%), ammonium sulfate mass fraction (%), solid-liquid ratio (g/mL), ultrasonic temperature (°C), and ultrasonic time (min) on polyphenolic content during extraction. Based on these experiments, three key factors influencing extraction were selected for response surface methodology (RSM) optimization. The results indicated that under conditions of 26% ethanol, 20% ammonium sulfate, a solid-liquid ratio of 1:30, and extraction for 35 minutes at 50°C, the polyphenol content reached 61.62 mg/g. The relative contents of 6'-O-caffeoylarbutin, ß-arbutin, and chlorogenic acid were 34.45%, 4.56%, and 31.06%, respectively. The DPPH· and ABTS+· scavenging rates were above 95% and 96%, respectively, and the ferric reducing ability exhibited a significant dose-effect relationship. The inhibition rates of monophenolase and diphenolase activities of tyrosinase were 43.84% and 35.73%, respectively. The optimized process for ultrasonic-assisted biphasic aqueous extraction of polyphenols from Vaccinium dunalianum Wight leaves demonstrated significant antioxidant and tyrosinase inhibition activities.

Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum.

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase.

Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 ± 0.06 µM). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.

Comparative Analysis of the Wood Metabolites of Three Poplar Clones Using UPLC-Triple-TOF-MS.

Poplar, a woody tree species, is widely used for industrial production and as a protective forest belt. Different clones of poplar exhibit clear variation in terms of morphological and physiological features, however, the impact of the genetic variation on the composition and abundance of wood metabolite have not been fully determined. In this study, ultra-high pressure liquid chromatography-triple time of flight-mass spectrometer (UPLC-Triple-TOF-MS) was used to explore the metabolite changes in poplar wood from three clones, including Populus deltoides CL. '55/65', P. deltoides CL. 'Danhong', and P. nigra CL. 'N179'. A total of 699 metabolites were identified. Clustering analysis and principal component analysis display that the metabolic differences of wood have allowed distinguishing different species of poplar. Meanwhile, eight significantly different metabolites were screened between P. deltoides and P. nigra, which may be considered as valuable markers for chemotaxonomy. In addition, the highly discriminant 352 metabolites were obtained among the three clones, and those may be closely related to the distinction in unique properties (e.g., growth, rigidity and tolerance) of the poplar wood cultivars. This study provides a foundation for further studies on wood metabolomics in poplar, and offers chemotaxonomic markers that will stimulate the early screening of potentially superior trees.

Rational Design of Zincophilic Ag/Permselective PEDOT:PSS Heterogeneous Interfaces for High-Rate Zinc Electrodeposition.

Designing artificial interface is a promising strategy to protect Zn metal anode but achieving long Zn plating/stripping lifespans and efficient nucleation/deposition kinetics, particularly at high current densities, remains a challenge. In this study, a permselective zincophilic heterogeneous interface consisting of metallic Ag layer and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is designed via a simple chemical displacement and drop casting process. The artificial interface plays a multifunctional role in inhibiting dendrite growth/side reactions by reducing the nucleation barrier through a large number of Zn nucleation sites offered by the bottom Ag layer, homogenizing electrical field/Zn2+ flux and shielding SO4 2- migration via the compact, conducting, and Zn2+ -permselective PEDOT:PSS supporting layer. Moreover, the heterogeneous interface demonstrates enhanced structural integrity owing to the binder effect of PEDOT:PSS. As a result, the modified Zn anode demonstrates a cyclic lifespan of 200 h and a reduced voltage hysteresis of ≈150 mV at 20 mA cm-2 /5 mAh cm-2 , far surpassing its counterparts. Moreover, the protected Zn anode allows the LiMn2 O4 -based full cells with remarkable rate and cycling performance. These findings provide new insight into the design of an efficient artificial interface for highly reversible and high-rate Zn electrodeposition.

A novel "turn on" fluorescence probe based on a caffeic acid skeleton for detecting Al3+ and bioimaging application.

The specificity detection of Al3+ is important for monitoring life health and environmental pollution. A fluorescence enhancement probe based on caffeic acid HAM was synthesized for detecting Al3+ with high sensitivity and good selectivity. When Al3+ was added in the aqueous solution of HAM, the formation of HAM-Al3+ complexes inhibited the PET process, which led to great enhancement of fluorescence. The addition of other metal ions cannot induce the change of fluorescence intensity. The sensing mechanism was proved by 1H NMR titration, MS, and Job's plot. Moreover, probe HAM exhibited excellent properties, such as high sensitivity (LOD = 0.168 µM), fast response time (30 s), wide pH range (3-11), and good interference ability. Based on the above results, probe HAM was used to explore its bioimaging application in biological samples.

Subcritical Water Extraction of Phenolic Compounds from Vaccinium Dunalianum Wight Leaves and Their Antioxidant and Tyrosinase Inhibitory Activities in Vitro.

Subcritical water extraction was used to extract bioactive phenolic compounds from Vaccinium dunalianum Wight leaves. The optimal extraction conditions were determined as an extraction temperature of 150 °C, an extraction time of 40 min, and a liquid-solid ratio of 35 : 1 mL/g. The total phenolic content reached 21.35 mg gallic acid /g, which was 16 % higher than that by hot water extraction. The subcritical water extraction extract exhibited strong scavenging activity of DPPH free radical and ABTS+ free radical, as well as significant tyrosinase inhibitory activity. The study suggests that subcritical water extraction can alter the composition of the extracts, leading to the production of various phenolic compounds, effective antioxidants, and tyrosinase inhibitors from Vaccinium dulciana Wight leaves. These findings confirm the potential of Vaccinium dunalianum Wight as a natural antioxidant molecule source for the medicine and food industries, and for the therapy of skin pigmentation disorders.

C21, C22 pregnane glycosides and cytotoxic C27 spriostanol steroids from Asparagus cochinchinesis.

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C21 (1-4) and one new pregnane (5) glycosides, and four known C27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC50 values of 35.5 and 39.6 µM, respectively.

New potential beneficial effects of actein, a triterpene glycoside isolated from Cimicifuga species, in breast cancer treatment.

Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida (Chinese herb "shengma") which could inhibit the growth of breast cancer cells. Nevertheless, the effect of actein on angiogenesis, which is an essential step for tumor growth and metastasis, has never been reported. Hence, this study aimed to investigate the in vitro and in vivo effects of actein on angiogenesis using human microvascular endothelial cells (HMEC-1), matrigel plug and tumor-bearing mouse models. Our results showed that actein significantly inhibited the proliferation, reduced the migration and motility of endothelial cells, and it could suppress the protein expressions of VEGFR1, pJNK and pERK, suggesting that JNK/ERK pathways were involved. In vivo results showed that oral administration of actein at 10 mg/kg for 7 days inhibited blood vessel formation in the growth factor-containing matrigel plugs. Oral actein treatments (10-15 mg/kg) for 28 days resulted in decreasing mouse 4T1 breast tumor sizes and metastasis to lungs and livers. The apparent reduced angiogenic proteins (CD34 and Factor VIII) expressions and down-regulated metastasis-related VEGFR1 and CXCR4 gene expressions were observed in breast tumors. Our novel findings provide insights into the use of actein for development of anti-angiogenic agents for breast cancer.

Six new physalins from Physalis alkekengi var. franchetii and their cytotoxicity and antibacterial activity.

Six new physalin steroids, 7ß-methoxylisophysalin B (1), 7ß-methoxylphysalin C (2), physalin V (3), physalin VI (4), physalin VII (5), isophysalin I (6), together with 20 known physalins (7-26) were isolated from calyces of Physalis alkekengi var. franchetii. Structures of the new compounds were revealed through 1D and 2D NMR and mass spectroscopic methods. Compounds 1-26 were evaluated for cytotoxicity against human HL-60, SMMC-7721, A-549, MCF-7 and SW-480, and the results indicated that compounds 8, 11, and 14 displayed potent cytotoxicities (IC50<5µM) in vitro. Further antibacterial assay indicated that compounds 8, 14, and 19 showed high antibacterial activities against Bacillus subtilis and Escherichia coli.

Association of disease-predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations.

Melatonin is predominantly involved in signaling circadian and seasonal rhythms, and its synthesis is regulated by the environmental light/dark cycle. The selection pressure by geographically different environmental light/dark cycles, which is predominantly determined by sunshine duration, on the global distribution of genetic polymorphisms in the melatonin pathway is not well understood. Recent genetic association studies identified various disease-predisposition polymorphisms in this pathway. We investigated the correlations between the prevalence of these clinically important single nucleotide polymorphisms (SNPs) and sunshine duration among worldwide human populations from twelve regions in the CEPH-HGDP database rs4753426, a recently reported predisposition SNP for type 2 diabetes in the promoter of the MT(2) melatonin receptor gene (MTNR1B), which was not included in the CEPH-HGDP genotyping array, was additionally genotyped. This SNP showed a marginally significant correlation in 760 CEPH-HGDP DNA samples (r = -0.5346, P = 0.0733), and it showed the most prominent association among the candidate melatonin pathway SNPs examined. To control for population structure, which may lead to a false positive correlation, we genotyped this SNP in a replication set of 1792 subjects from China. The correlation was confirmed among Chinese populations (r = -0.8694, P = 0.0002), and was also statistically significant after correction of other climatic and geographical covariants in multiple regression analysis (beta = -0.907, P = 1.94 x 10(-5)). Taken together, it suggests that the human melatonin signaling pathway, particularly MT(2) melatonin receptor may have undergone a selective pressure in response to global variation in sunshine duration.