Biological activities, identification, method development, and validation for analysis of polyphenolic compounds in Nymphaea rubra flowers and leaves by UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS.

INTRODUCTION: Nymphaea rubra belongs to the Nymphaea family and is regarded as a vegetable used in traditional medicine to cure several ailments. These species are rich in phenolic acid, flavonoids, and hydrolysable tannin. OBJECTIVE: This study aimed to assess the biological activities of Nymphaea rubra flowers (NRF) and leaves (NRL) by identifying and quantifying their polyphenolic compounds using ultra-performance liquid chromatography coupled to quadrupole cyclic ion mobility time-of-flight mass spectrometry (UHPLC-Q-cIM-TOF-MS) and triple quadrupole mass spectrometry (UHPLC-TQ-MS). METHODOLOGY: NRF and NRL powder was extracted with methanol and fractionated using hexane, ethylacetate, and water. Antioxidant and α-glucosidase, and tyrosinase enzyme inhibitory activities were evaluated. The polyphenolic components of NRF and NRL were identified and quantified using UHPLC-Q-cIM-TOF-MS and UHPLC-TQ-MS. The method was validated using linearity, precision, accuracy, limit of detection (LOD), and lower limit of quantification (LLOQ). RESULTS: Bioactive substances and antioxidants were highest in the ethylacetate fraction of flowers and leaves. Principal component analysis showed how solvent and plant components affect N. rubra's bioactivity and bioactive compound extraction. A total of 67 compounds were identified, and among them 21 significant polyphenols were quantified. Each calibration curve had R2 > 0.998. The LOD and LLOQ varied from 0.007 to 0.09 µg/mL and from 0.01 to 0.1 µg/mL, respectively. NRF contained a significant amount of gallic acid (10.1 mg/g), while NRL contained abundant pentagalloylglucose (2.8 mg/g). CONCLUSION: The developed method is simple, rapid, and selective for the identification and quantification of bioactive molecules. These findings provide a scientific basis for N. rubra's well-documented biological effects.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review.

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Tyrosinase inhibitory activity of Sargassum fusiforme and characterisation of bioactive compounds.

INTRODUCTION: Sargassum fusiforme (Harvey) Setchell, also known as Tot (in Korean) and Hijiki (in Japanese), is widely consumed in Korea, Japan, and China due to its health promoting properties. However, the bioactive component behind the biological activity is still unknown. OBJECTIVES: We aimed to optimise the extraction conditions for achieving maximum tyrosinase inhibition activity by using two sophisticated statistical tools, that is, response surface methodology (RSM) and artificial neural network (ANN). Moreover, high-resolution mass spectrometry (HRMS) was used to tentatively identify the components, which are then further studied for molecular docking study using 2Y9X protein. METHODOLOGY: RSM central composite design was used to conduct extraction using microwave equipment, which was then compared to ANN. Electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was used to tentatively identify bioactive components, which were then docked to the 2Y9X protein using AutoDock Vina and MolDock software. RESULTS: Maximum tyrosinase inhibition activity of 79.530% was achieved under optimised conditions of time: 3.27 min, temperature: 128.885°C, ethanol concentration: 42.13%, and microwave intensity: 577.84 W. Furthermore, 48 bioactive compounds were tentatively identified in optimised Sargassum fusiforme (OSF) extract, and among them, seven phenolics, five flavonoids, five lignans, six terpenes, and five sulfolipids and phospholipids were putatively reported for the first time in Sargassum fusiforme. Among 48 bioactive components, trifuhalol-A, diphlorethohydroxycarmalol, glycyrrhizin, and arctigenin exhibited higher binding energies for 2Y9X. CONCLUSION: Taken together, these findings suggest that OSF extract can be used as an effective skin-whitening source on a commercial level and could be used in topical formulations by replacing conventional drugs.

Antioxidant, Tyrosinase, α-Glucosidase, and Elastase Enzyme Inhibition Activities of Optimized Unripe Ajwa Date Pulp (Phoenix dactylifera) Extracts by Response Surface Methodology.

The Ajwa date (Phoenix dactylifera L., Arecaceae family) is a popular edible fruit consumed all over the world. The profiling of the polyphenolic compounds of optimized unripe Ajwa date pulp (URADP) extracts is scarce. The aim of this study was to extract polyphenols from URADP as effectively as possible by using response surface methodology (RSM). A central composite design (CCD) was used to optimize the extraction conditions with respect to ethanol concentration, extraction time, and temperature and to achieve the maximum amount of polyphenolic compounds. High-resolution mass spectrometry was used to identify the URADP's polyphenolic compounds. The DPPH-, ABTS-radical scavenging, α-glucosidase, elastase and tyrosinase enzyme inhibition of optimized extracts of URADP was also evaluated. According to RSM, the highest amounts of TPC (24.25 ± 1.02 mgGAE/g) and TFC (23.98 ± 0.65 mgCAE/g) were obtained at 52% ethanol, 81 min time, and 63 °C. Seventy (70) secondary metabolites, including phenolic, flavonoids, fatty acids, and sugar, were discovered using high-resolution mass spectrometry. In addition, twelve (12) new phytoconstituents were identified for the first time in this plant. Optimized URADP extract showed inhibition of DPPH-radical (IC50 = 87.56 mg/mL), ABTS-radical (IC50 = 172.36 mg/mL), α-glucosidase (IC50 = 221.59 mg/mL), elastase (IC50 = 372.25 mg/mL) and tyrosinase (IC50 = 59.53 mg/mL) enzymes. The results revealed a significant amount of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.

Blue mold rot caused by Penicillium expansum on Polygonatum odoratum var. pluriflorum.

Polygonatum odoratum var. pluriflorum, called "Dunggulle", is cultivated in East Asia to obtain rhizomes. In Korea and China, these rhizomes are used in traditional teas, health beverages, and herbal medicines (Zhao and Li, 2015). In 2019, Dunggulle was cultivated in 47 hectares, with an annual output of 120M/T in Korea. In November 2020, Dunggulle rhizomes with symptoms of blue mold rot were observed at a Dunggulle farm storage (36°06'01''N, 127°29'20''E) in Geuman, Korea, where the temperature ranged from 9 to 13°C, with an average humidity of 70%. The disease incidence was 2 to 3% out of 200 rhizomes across all markets surveyed. The disease begins with a greenish blue mold covering the rhizome surface (30 to 60%), followed by rhizome rot with a dark brown color as the disease progresses. Leading edges of the rotten rhizome pieces were sterilized with 1% NaOCl and 70% ethanol and placed on MEA (Malt Extract Agar) with penicillin G and streptomycin (both 50 µg/mL). After 7 days of incubation at 25°C, greenish-blue colonies appeared, from which a monospore was isolated. A representative isolated strain was deposited in the Korean Agricultural Culture Collection (KACC, Wanju, Korea) with Acc. No. KACC 49832. The strain grew slowly on MEA at 25°C (8 to 18 mm diam. after 7 days), producing greenish blue conidia. The conidiophores were hyaline and mostly terverticillate; the branches were appressed against the main axis; the stipes were smooth-walled; and the metulae were cylindrical, 10 to 13 × 2.7 to 3.2 µm, with 6 to 10 flask-shaped phialides, measured 9 to 12 × 2.7 to 3.1 µm. The conidia were globose or subglobose and 2.8 to 4.1 µm diam. These morphological characteristics fit well with the description of Penicillium expansum (Frisvad & Samson, 2004). Genomic DNA was extracted from the mycelia of the KACC 49832 MEA plate. ITS rDNA, beta-tubulin (BenA), and calmodulin (CaM) gene regions were sequenced for identification (Houbraken et al., 2020), and the rsulting sequences were deposited in GenBank (Acc. Nos. MZ189258, MZ226688, and MZ226689, respectively). Comparison with the GenBank sequences revealed that the Korean isolate was highly similar to P. expansum (ITS rDNA 99.8%, BenA 98.6%, and CaM 97.8%). Phylogenetic results based on the maximum-likelihood analysis revealed that KACC 49832 was grouped with P. expansum. To demonstrate pathogenicity, 10 µL of conidial suspension (1.3 × 105 conidia/mL) was dropped on the surface of three Dunggulle rhizomes scratched with a syringe needle. For the control, sterile water was applied on three control rhizomes. All rhizomes were surface-sterilized as referred above before being sprayed and dried. All inoculated and control rhizomes were kept in incubator at 25°C and 90-95% relative humidity. After a week, the inoculated points showed symptoms similar to those of the initial infection, whereas controls remained symptomless. The re-isolated fungus matched KACC 49832 based on morphological and sequence analyses, thereby fulfilling Koch's postulates. The experiment was performed three times. To our knowledge, this is the first report of P. expansum as a Dunggulle rhizome pathogen in Korea. As this pathogen is known to produce patulin, a carcinogenic fungal metabolite, further studies on the mycotoxicity of the infected rhizomes are required. This report might help manage the storage conditions of Dunggulle rhizomes to prevent the blue mold rot.

Myocarditis-induced Sudden Death after BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing on Histopathological Findings.

We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later. Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance. Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates. Extensive contraction band necrosis was observed in the atria and ventricles. There was no evidence of microthrombosis or infection in the heart and other organs. The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine.

Template Engineering of CuBi2 O4 Single-Crystal Thin Film Photocathodes.

To develop strategies for efficient photo-electrochemical water-splitting, it is important to understand the fundamental properties of oxide photoelectrodes by synthesizing and investigating their single-crystal thin films. However, it is challenging to synthesize high-quality single-crystal thin films from copper-based oxide photoelectrodes due to the occurrence of significant defects such as copper or oxygen vacancies and grains. Here, the CuBi2 O4 (CBO) single-crystal thin film photocathode is achieved using a NiO template layer grown on single-crystal SrTiO3 (STO) (001) substrate via pulsed laser deposition. The NiO template layer plays a role as a buffer layer of large lattice mismatch between CBO and STO (001) substrate through domain-matching epitaxy, and forms a type-II band alignment with CBO, which prohibits the transfer of photogenerated electrons toward bottom electrode. The photocurrent densities of the CBO single-crystal thin film photocathode demonstrate -0.4 and -0.7 mA cm-2 at even 0 VRHE with no severe dark current under illumination in a 0.1 m potassium phosphate buffer solution without and with H2 O2 as an electron scavenger, respectively. The successful synthesis of high-quality CBO single-crystal thin film would be a cornerstone for the in-depth understanding of the fundamental properties of CBO toward efficient photo-electrochemical water-splitting.

Arctigenin induces necroptosis through mitochondrial dysfunction with CCN1 upregulation in prostate cancer cells under lactic acidosis.

Arctigenin, a mitochondrial complex I inhibitor, has been identified as a potential anti-tumor agent, but the involved mechanism still remains elusive. Herein, we studied the underlying mechanism(s) of action of arctigenin on acidity-tolerant prostate cancer PC-3AcT cells in the lactic acid-containing medium. At concentration showing no toxicity on normal prostate epithelial RWPE-1 and HPrEC cells, arctigenin alone or in combination with docetaxel induced significant cytotoxicity in PC-3AcT cells compared to parental PC-3 cells. With arctigenin treatment, reactive oxygen species (ROS) levels, annexin V-PE positive fractions, sub-G0/G1 peak in cell cycle analysis, mitochondrial membrane depolarization, and cell communication network factor 1 (CCN1) levels were increased, while cellular ATP content and phospho (p)-Akt level were decreased. Pretreatment with ROS scavenger N-acetylcysteine effectively reversed the series of phenomena caused by arctigenin, suggesting that ROS served as upstream molecules of arctigenin-driven cytotoxicity. Meanwhile, arctigenin increased the levels of p-receptor-interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like pseudokinase (p-MLKL) as necroptosis mediators, and pretreatment with necroptosis inhibitor necrostatin-1 restored their levels and cell viability. Treatment of spheroids with arctigenin resulted in necroptotic cell death, which was prevented by N-acetylcysteine. The siRNA-based knockdown of CCN1 suppressed the levels of MLKL, B-cell lymphoma 2 (Bcl-2), and induced myeloid leukemia cell differentiation (Mcl-1) with increased cleavage of Bcl-2-associated X (Bax) and caspase-3. Collectively, these results provide new insights into the molecular mechanisms underlying arctigenin-induced cytotoxicity, and support arctigenin as a potential therapeutic agent for targeting non-Warburg phenotype through induction of necroptosis via ROS-mediated mitochondrial damage and CCN1 upregulation.

Lablab Purpureus Protects HaCaT Cells from Oxidative Stress-Induced Cell Death through Nrf2-Mediated Heme Oxygenase-1 Expression via the Activation of p38 and ERK1/2.

Ultraviolet B (UV-B) radiation induces the extreme production of either reactive oxygen species (ROS) or inflammatory mediators. The aim of this study was to evaluate the antioxidant activities of 70% ethanolic extract of Lablab purpureus (LPE) and the underlying mechanisms using HaCaT cells exposed to UV-B. High-performance liquid chromatography (HPLC) confirmed the presence of gallic acid, catechin, and epicatechin in LPE. LPE was shown to have a very potent capacity to scavenge free radicals. The results showed that LPE prevented DNA damage and inhibited the generation of ROS in HaCaT cells without causing any toxicity. LPE increased the expression of endogenous antioxidant enzymes such as superoxide dismutase-1 and catalase. Furthermore, LPE treatment facilitates the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), boosting the phase II detoxifying enzyme heme oxygenase-1 (HO-1) leading to the combatting of oxidative stress. However, pretreatment of LPE also caused the phosphorylation of mitogen-activated protein kinases (MAPK kinase) (p38 kinase) and extracellular signal-regulated kinase (ERK), whereas treatment with p38 and ERK inhibitors substantially suppressed LPE-induced Nrf2 and heme oxygenase (HO)-1 expression. These findings suggest that LPE exhibits antioxidant activity via Nrf-2-mediated HO-1 signaling through the activation of p38 and ERK, indicating that LPE can potentially be used as a remedy to combat oxidative stress-induced disorder.

Metabolite Profiling of Manilkara zapota L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase, and Elastase Inhibition Assays.

High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of Manilkara zapota L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against α-glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of α-glucosidase enzyme at a lower concentration (IC50 2.51 ± 0.15 µg/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 ± 0.15% following the treatment with ZLE at 30 µg/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC50 27.51 ± 1.70 µg/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI-MS) detected more m/z peaks than electrospray ionization mass spectrometry (ESI-MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting α-glucosidase activity and enhancing glucose uptake.

Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells.

Apigenin, a naturally occurring flavonoid, is known to exhibit significant anticancer activity. This study was designed to determine the effects of apigenin on two malignant mesothelioma cell lines, MSTO-211H and H2452, and to explore the underlying mechanism(s). Apigenin significantly inhibited cell viability with a concomitant increase in intracellular reactive oxygen species (ROS) and caused the loss of mitochondrial membrane potential (Δ𝚿m), and ATP depletion, resulting in apoptosis and necroptosis in monolayer cell culture. Apigenin upregulated DNA damage response proteins, including the DNA double strand break marker phospho (p)- histone H2A.X. and caused a transition delay at the G2/M phase of cell cycle. Western blot analysis showed that apigenin treatment upregulated protein levels of cleaved caspase-3, cleaved PARP, p-MLKL, and p-RIP3 along with an increased Bax/Bcl-2 ratio. ATP supplementation restored cell viability and levels of DNA damage-, apoptosisand necroptosis-related proteins that apigenin caused. In addition, N-acetylcysteine reduced ROS production and improved Δ𝚿m loss and cell death that were caused by apigenin. In a 3D spheroid culture model, ROS-dependent necroptosis was found to be a mechanism involved in the anti-cancer activity of apigenin against malignant mesothelioma cells. Taken together, our findings suggest that apigenin can induce ROS-dependent necroptotic cell death due to ATP depletion through mitochondrial dysfunction. This study provides us a possible mechanism underlying why apigenin could be used as a therapeutic candidate for treating malignant mesothelioma.

Permutation based testing on covariance separability.

Separability is an attractive feature of covariance matrices or matrix variate data, which can improve and simplify many multivariate procedures. Due to its importance, testing separability has attracted much attention in the past. The procedures in the literature are of two types, likelihood ratio test (LRT) and Rao's score test (RST). Both are based on the normality assumption or the large-sample asymptotic properties of the test statistics. In this paper, we develop a new approach that is very different from existing ones. We propose to reformulate the null hypothesis (the separability of a covariance matrix of interest) into many sub-hypotheses (the separability of the sub-matrices of the covariance matrix), which are testable using a permutation based procedure.We then combine the testing results of sub-hypotheses using the Bonferroni and two-stage additive procedures. Our permutation based procedures are inherently distribution free; thus it is robust to non-normality of the data. In addition, unlike the LRT, they are applicable to situations when the sample size is smaller than the number of unknown parameters in the covariance matrix. Our numerical study and data examples show the advantages of our procedures over the existing LRT and RST.

Oxygen Vacancy Diffusion and Condensation in Lithium-Ion Battery Cathode Materials.

Oxygen vacancies (OV) are native defects in transition metal (TM) oxides and their presence has a critical effect on the physicochemical properties of the oxide. Metal oxides are commonly used in lithium-ion battery (LIB) cathodes and there is still a lack of understanding of the role of OVs in LIB research field. Here, we report on the behavior of OVs in a single-crystal LIB cathode during the non-equilibrium states of charge and discharge. We found that microcrack evolution in a single crystal occurs due to OV condensation in specific crystallographic orientations generated by the continuous migration of OVs and TM ions. Moreover, understanding the effects of the presence and diffusion of OVs in metal oxides enables the elucidation of most of the conventional mechanisms of capacity fading in LIBs and provides new insights for new electrochemical applications.

Arctigenin shows preferential cytotoxicity to acidity-tolerant prostate carcinoma PC-3 cells through ROS-mediated mitochondrial damage and the inhibition of PI3K/Akt/mTOR pathway.

Extracellular acidity in the tumor microenvironment contributes to chemoresistance of malignant tumors. The objective of this study was to determine anticancer effects of arctigenin, a novel anti-inflammatory lignan extracted from seeds of Arctium lappa, on acidity-tolerant prostate cancer PC-3AcT cells. The PC-3AcT cells manifested increased tolerance to low-pH media with enhanced percent cell viability and increased resistance to docetaxel compared to their parental PC-3 cells. Arctigenin alone or in combination with docetaxel induced potent cytotoxicity. Preferential sensitization of PC-3AcT cells to arctigenin was accompanied by increased cell fractions with sub-G0/G1 peak and annexin V-PE(+), increased ROS levels, decreased mitochondrial membrane potential and cellular ATP content, and inhibition of PI3K/Akt/mTOR pathway. A series of changes caused by arctigenin were efficiently reversed through reducing ROS levels by radical scavenger N-acetylcysteine, thus placing ROS upstream of arctigenin-driven cytotoxicity. Collectively, these results demonstrate that arctigenin can increase oxidative stress-mediated mitochondrial damage of acidity-tolerant PC-3AcT cells, suggesting that arctigenin might be a potential therapeutic candidate to overcome acidic-microenvironment-associated chemotherapeutic resistance in prostate cancer.

Inhibition of Migration and Invasion in Melanoma Cells by ß-Escin via the ERK/NF-κB Signaling Pathway.

ß-Escin, a natural triterpene saponin was extracted from Aesculus hippocastanum seeds, which have been widely used to treat inflammation in traditional medicine. In an effort to study the possible anti-tumor effects of ß-escin, we performed wound healing, invasion, and adhesion assays to examine the effects of ß-escin on cell migration, invasion, and angiogenesis. Our results revealed that ß-escin inhibits cell migration as well as motility in B16F10 and SK-MEL5 cells in a dose-dependent manner. RT-PCR and Western blot analysis showed that ß-escin increased TIMP-1, -2 while significantly downregulated phosphorylated extracellular signal-regulated kinase (p-ERK) expression, and suppressing nuclear factor-kappa B (NF-κB) and inhibitor of nuclear factor-kappa B (IκB) expression. Overall, the data from the current study suggest that ß-escin has the potential for inhibiting both metastatic and angiogenic activities, and are the earliest evidence for the involvement of the NF-κB/IκB signaling in ß-escin-induced anti-tumor effects.

Cytotoxic properties of the anthraquinone derivatives isolated from the roots of Rubia philippinensis.

BACKGROUND: Cancer is one of the most frequently occurring diseases and is the second leading cause of death worldwide. In this study, anthraquinone derivatives (Compounds 1-5) were evaluated for their anti-cancer potential against various skin and breast cancer cell lines to assess whether these anthraquinone derivatives may serve as a lead for the augmentation of anti-cancer drug. METHODS: Anthraquinone derivatives, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6'-O-acetyl)-α-rhamnosyl(1 → 2)-ß-glucoside (Comp 1), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (Comp 2), and alizarin (Comp 3) were isolated from the dichloromethane fraction of the roots of Rubia philippinensis., whereas ethyl acetate fraction yielded xanthopurpurin (Comp 4) and lucidin-ω-methyl ether (Comp 5). Structures of all the isolated compounds were determined by spectral data analysis. All isolated compounds (Comp 1-5) were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against four different cancer cell lines, i.e. human melanoma (SK-MEL-5), murine melanoma (B16F10), and human breast adenocarcinoma (MCF7 and MDA-MB-231). RESULTS: Significant activity of the compounds 4 and 5 was observed against the breast cancer cell line MDA-MB-231 with IC50 values of 14.65 ± 1.45 and 13.03 ± 0.33 µM, respectively. Encouragingly, IC50 values of 67.89 ± 1.02 and 79.01 ± 0.03 µM against normal kidney epithelial cells (MDCK) were also obtained for compounds 4 and 5, respectively, which indicated very low toxicity and favorable selectivity indices for compounds 4 and 5 in the range of 1.85 to 3.95 and 2.11 to 6.06 against skin cancer cell lines (SK-MEL-5, and B16F10), and breast cancer cell lines (MCF7 and MDA-MB-231), respectively. CONCLUSION: Our results suggested that the compounds 4 (xanthopurpurin) and 5 (lucidin-ω-methyl ether) showed high selective toxicity towards breast cancer cells at lower concentrations without showing toxicity towards normal cells, thus could be of potential as new lead molecules in cancer treatment.

Antimelanogenic Effect of an Oroxylum indicum Seed Extract by Suppression of MITF Expression through Activation of MAPK Signaling Protein.

In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both transcriptional and translational expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein-1 and 2 (TYRP-1 and TYRP-2), were also examined. The results depicted that pretreatment of OISEA significantly inhibits not only tyrosinase activity, but melanin production and intracellular tyrosinase activity. By repressing the expression of tyrosinase, TYRP-1, TYRP-2, and MITF, OISEA interrupted melanin production. Additionally, OISEA interfered with the phosphorylation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), with the reversal of OISEA-induced melanogenesis inhibition after treatment with the specific inhibitors SB239063, U0126, and SP600125. Overall, these results suggest that OISEA can stimulate p38, ERK1/2, JNK phosphorylation, and subsequent suppression of melanin, leading to the inhibition of melanogenic enzymes and melanin production, possibly owing to the presence of polyphenolic compounds.

Dominance of Plasmonic Resonant Energy Transfer over Direct Electron Transfer in Substantially Enhanced Water Oxidation Activity of BiVO4 by Shape-Controlled Au Nanoparticles.

The performance of plasmonic Au nanostructure/metal oxide heterointerface shows great promise in enhancing photoactivity, due to its ability to confine light to the small volume inside the semiconductor and modify the interfacial electronic band structure. While the shape control of Au nanoparticles (NPs) is crucial for moderate bandgap semiconductors, because plasmonic resonance by interband excitations overlaps above the absorption edge of semiconductors, its critical role in water splitting is still not fully understood. Here, first, the plasmonic effects of shape-controlled Au NPs on bismuth vanadate (BiVO4 ) are studied, and a largely enhanced photoactivity of BiVO4 is reported by introducing the octahedral Au NPs. The octahedral Au NP/BiVO4 achieves 2.4 mA cm-2 at the 1.23 V versus reversible hydrogen electrode, which is the threefold enhancement compared to BiVO4 . It is the highest value among the previously reported plasmonic Au NPs/BiVO4 . Improved photoactivity is attributed to the localized surface plasmon resonance; direct electron transfer (DET), plasmonic resonant energy transfer (PRET). The PRET can be stressed over DET when considering the moderate bandgap semiconductor. Enhanced water oxidation induced by the shape-controlled Au NPs is applicable to moderate semiconductors, and shows a systematic study to explore new efficient plasmonic solar water splitting cells.

DNA Protecting Activities of Nymphaea nouchali (Burm. f) Flower Extract Attenuate t-BHP-Induced Oxidative Stress Cell Death through Nrf2-Mediated Induction of Heme Oxygenase-1 Expression by Activating MAP-Kinases.

This study was performed to investigate the antioxidant activities of Nymphaea nouchali flower (NNF) extract and the underlying mechanism using RAW 264.7 cells. The presence of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin in the NNF was confirmed by high-performance liquid chromatography (HPLC). The extract had a very potent capacity to scavenge numerous free radicals. NNF extract was also able to prevent DNA damage and quench cellular reactive oxygen species (ROS) generation induced by tert-Butyl hydroperoxide (t-BHP) with no signs of toxicity. The NNF extract was able to augment the expression of both primary and phase II detoxifying enzyme, resulting in combat the oxidative stress. This is accomplished by phosphorylation of mitogen-activated protein kinase (MAP kinase) (p38 kinase and extracellular signal-regulated kinase (ERK)) followed by enhancing the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2). This attenuates cellular ROS generation and confers protection from cell death. Altogether, the results of current study revealed that Nymphaea nouchali flower could be a source of natural phytochemicals that could lead to the development of new therapeutic agents for preventing oxidative stress associated diseases and attenuating disease progression.

Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase-Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK-NRF2)-Mediated Antioxidant Pathway.

The leaves of Lannea coromandelica (Houtt.) Merr. are used in the Garo, Pahan, and Teli tribal communities of Bangladesh as a traditional medicinal plant to treat hepatitis, diabetes, ulcers, heart disease, and dysentery. However, there have been limited phytochemical and biological studies on the bark of L. coromandelica. This study aimed to investigate the antioxidant activities of L. coromandelica bark extract (LCBE) and the underlying mechanism using RAW 264.7 cells. The LCBE was analysed by high-pressure liquid chromatography (HPLC) to detect its key polyphenolic compounds. Various in vitro antioxidant assays were performed using RAW 264.7 cells to assess the antioxidant effects of the LCBE and to understand the underlying molecular mechanism. HPLC revealed the presence of gallic acid, (-)-epigallocatechin-3-gallate, catechin, chlorogenic acid, and caffeic acid in the LCBE. The extract showed a very potent capacity to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation and also quenched cellular reactive oxygen species (ROS) generation without showing any toxicity. The LCBE was found to combat the oxidative stress by enhancing the expression, at both transcriptional and translational levels, of primary antioxidant enzymes as well as phase II detoxifying enzymes, especially heme oxygenase 1, through the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated pathway in RAW 264.7 cells via the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK). The LCBE exhibited strong antioxidant activities and mitigated the cellular ROS production. These results provide scientific evidence of its potential as an ideal applicant for a cost-effective, readily available, and natural phytochemical, as well as a strategy for preventing diseases associated with oxidative stress and attenuating disease progress.