The effect of flavonols in Anacardium occidentale L. leaf extracts on skin pathogenic microorganisms.

Cashew (Anacardium occidentale L.) leaf is traditionally used to treat skin infections. Although many flavonols have been identified from its leaf extract, their inhibitory effects on skin pathogens are not yet determined. The aims of this study were to determine the antimicrobial (against skin pathogenic microbes) and antioxidant activities of four flavonol glycosides from the crude extract and three flavonol aglycones from the hydrolyzed extract. The hydrolyzed extract was found to show higher activities than the crude extract. Myricetin showed the highest activity against all the tested bacteria and yeast with the lowest Minimum Inhibition Concentration (MIC) of 7.81 µg/mL on Corynebacterium minutissimum ATCC23348. Myricetin also exhibited good primary antioxidant activities with the effective concentration with 50% of activity (EC50) values ranged between 2.23 µg/mL and 6.40 µg/mL. The highest secondary antioxidant activity was indicated by myricetin-3-O-rhamnoside. Thus, myricetin can be considered as a bioactive compound of the hydrolyzed extract.

The influence of chemical composition of potent inhibitors in the hydrolyzed extracts of anti-hyperuricemic plants to their xanthine oxidase activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Anti-hyperuricemic plant parts that were selected for this study, are traditionally used to treat gout in Malaysia. Caffeic acid (a hydroxycinnamic acid), apigenin (a flavone), myricetin, quercetin and kaempferol (flavonols), were reported to act as potent xanthine oxidase inhibitors. These compounds can be found in some of the selected ethnomedicinal plants. However, there is still lack of published research works on the quantification of these inhibitors from these urate-lowering phytotherapies. AIMS OF THE STUDY: The compounds were quantified from 21 hydrolyzed extracts of the phytotherapies for gout. The activity-content contributions of the compounds to the potent extracts were determined. MATERIALS AND METHODS: The anti-hyperuricemic activities of the extracts and the compounds were determined using a xanthine oxidase inhibitory assay. Ultra-Performance Liquid Chromatography (UPLC) coupled with Photodiode Array Detector (PDA) was used to quantify the compounds in the extracts. RESULTS: The results revealed higher activity of the hydrolyzed extracts. The hydrolyzed extract of the flower bud of Syzygium aromaticum Merr. & L.M.Perry exhibited the highest activity (EC50 = 39.58 ± 0.10 µg/mL) due to the highest content of myricetin (42,297.55 ± 159.47 µg/g). The activity-content contribution of myricetin was 7.69%. Due to the highest activity of apigenin (EC50 = 3.27 ± 0.09 µg/mL), the highest contribution of this flavone (29.96%) to the hydrolyzed extract of Orthosiphon aristatus (Blume) Miq. was observed. CONCLUSION: The results revealed different contents and activities of xanthine oxidase inhibitors in the hydrolyzed extracts of anti-hyperuricemic plants can play a major role to influence the activity.

In Vitro Efficacy of Aqueous and Methanol Extract of Cassia siamea Against the Motility of Caenorhabditis elegans.

Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL-1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 µg mL-1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL-1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.

Tualang Honey Ameliorates Hypoxia-induced Memory Deficits by Reducing Neuronal Damage in the Hippocampus of Adult Male Sprague Dawley Rats.

OBJECTIVES: A growing body of evidence indicates that hypoxia exposure causes learning and memory deficits. An effective natural therapeutic approach has, however, not been explored widely. Our previous studies found that Tualang honey administration protected learning and memory functions in ovariectomized rats. Therefore, the present study investigated its efficacy in ameliorating hypoxia-induced memory deficits in adult male Sprague Dawley rats. MATERIALS AND METHODS: The rats were divided into four groups: i) Normoxia treated with sucrose (n=12), ii) Normoxia treated with Tualang honey (n=12), iii) Hypoxia treated with sucrose (n=12), and iv) Hypoxia treated with Tualang honey (n=12). Tualang honey (0.2 g/kg/BW) and sucrose (1 mL of 7.9%) supplementations were administered orally to the rats daily for 14 days. Then the hypoxia groups were exposed to hypoxia (~11%) for 7 days, while the normoxia groups were kept in normal conditions. Following exposure to hypoxia, the rats' memories were analyzed using a novel object recognition task and T-maze test. RESULTS: The data revealed that rats exposed to hypoxia showed significant impairment in short-term memory (STM), spatial memory (p<0.01), and long-term memory (LTM) when compared to the normoxia group. Hypoxia rats treated with Tualang honey showed significant improvement in STM, LTM, and spatial memory (p<0.05) compared with those treated with sucrose (p<0.05). Tualang honey also reduced neuronal damage in the hippocampus of adult male Sprague Dawley rats exposed to hypoxia. CONCLUSION: It is suggested that Tualang honey pretreatment has protective effects against hypoxia-induced memory deficits, possibly through its antioxidant contents.

Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity.

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.

The inhibitory effects of mitragynine on P-glycoprotein in vitro.

Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 µM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.

The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.

Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 µM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 µM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.

Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities.

A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C8H5O(C=O)CH2O(C=O)C6H4X, X = H, Cl, CH3, OCH3 or NO2, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.

A new chalcone structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one: Synthesis, structural characterizations, quantum chemical investigations and biological evaluations.

The structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one (C19H13BrO) crystallized in the triclinic system of P-1 space group. The unit cell dimensions are: a=5.8944 (9)Å, b=7.8190 (12)Å, c=16.320 (2)Å, α=102.4364 (19)°, ß=95.943 (2)°, γ=96.274 (2)° and Z=2. The physical properties of this compound was determined by the spectroscopic methods (FTIR and (1)H and (13)C NMR). Quantum chemical investigations have been employed to investigate the structural and spectral properties. The molecular structure, vibrational assignments, (1)H and (13)C NMR chemical shift values, non-linear optical (NLO) effect, HOMO-LUMO analysis and natural bonding orbital (NBO) analysis were calculated using HF and DFT/B3LYP methods with 6-311++G(d,p) basis set in the ground state. The results show that the theoretical calculation of the geometrical parameters, vibrational frequencies and chemical shifts are comparable with the experimental data. The crystal structure is influenced and stabilized by weak C-H⋯π interactions connecting the molecules into infinite supramolecular one dimensional ladder-like arrangement. Additionally, this compound is evaluated for their antibacterial activities against gram positive and gram negative strains using a micro dilution procedure and shows activities against a panel of microorganisms.

Growth inhibition of human liver carcinoma HepG2 cells and α-glucosidase inhibitory activity of Murdannia bracteata (C.B. Clarke) Kuntze ex J.K. Morton extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: The juice of the entire fresh herb and infusion of dried sample of Murdannia bracteata are consumed to treat liver cancer and diabetes in Malaysia. However, no scientific evidence of these bioactivities has been reported. MATERIALS AND METHODS: To verify the therapeutic potentials of sequential extracts and infusion of this plant by determining its cytotoxicity against human liver carcinoma HepG2 cells and α-glucosidase inhibitory activity. The cytotoxic activities of the extracts against HepG2 were determined using a methylene blue assay, and an α-glucosidase inhibitory assay was used to assess anti-diabetic activity. The molecular basis of the anti-hepatocellular carcinoma activity of the most active extract was determined using RT-PCR. Chemical profiling of the most active extract was performed using GC-MS and UPLC analyses. RESULTS: The results obtained from the cytotoxic screening revealed the dose-dependent growth inhibition of the HepG2 cells by only the hexane extract, with an EC50 value of 37.17±1.00 µg/ml. The HepG2 cell death was found to be apoptotic in nature and based on the significant biphasic induction of caspase-3, suggesting that the extract inhibited cell growth through a caspase-3-dependent pathway. The hexane extract also displayed α-glucosidase inhibitory activity, with an EC50 of 117.04±2.34 µg/ml. GC-MS analysis revealed that α-tocopherol was the major volatile compound in the hexane extract, and two phenolics (apigenin and caffeic acid derivatives) were detected using UPLC. CONCLUSIONS: Based on various published reports, it could be suggested that α-tocopherol and apigenin derivatives might be involved in the apoptosis-based cytotoxicity of the active extract of this plant against HepG2 carcinoma cells. The effects of this plant in the treatment of diabetes can be related to the presence of α-glucosidase inhibitors, such as the caffeic acid derivative identified in the active extract.

Bioprospecting medicinal plants for antioxidant components.

OBJECTIVE: To evaluate antioxidant activities of seven medicinal plant species and their fractions, and to identify their phenolic compounds. METHODS: Two extractions were processed and further fractionated by column chromatography to evaluate the concentration that inhibit 50% of 2,2'-azinobis (3-ethylbenzothiazoline-6-suslfonic acid, 1,1-diphenyl-2-picryl-hydrazyl radicals, and their ferric reducing antioxidant power. The identification of the fractions of phenolic compounds was done by ultra performance liquid chromatography. RESULTS: The aqueous-acetone extracts of Feretia apodanthera and Ozoroa insignis exhibited the highest antioxidant potentials comparable to those of the standard quercetin. Their subsequently silica gel column fractionation showed three most active fractions from which the major constituents quercetin, myricetin, kampferol, rutin and isoquercetin were identified. CONCLUSIONS: These plant species have potent antioxidant profiles and polyphenol compounds that may help to manage with radical related disease and aging.

Antioxidant and α-glucosidase inhibitory activities of 40 tropical juices from Malaysia and identification of phenolics from the bioactive fruit juices of Barringtonia racemosa and Phyllanthus acidus.

The present study compared pH, total soluble solids, vitamin C, and total phenolic contents, antioxidant activities, and α-glucosidase inhibitory activities of 40 fresh juices. The juice of Baccaurea polyneura showed the highest yield (74.17 ± 1.44%) and total soluble solids (32.83 ± 0.27 °Brix). The highest and lowest pH values were respectively measured from the juices of Dimocarpus longan (6.87 ± 0.01) and Averrhoa bilimbi (1.67 ± 0.67). The juice of Psidium guajava gave the highest total phenolic (857.24 ± 12.65 µg GAE/g sample) and vitamin C contents (590.31 ± 7.44 µg AAE/g sample). The juice of Phyllanthus acidus with moderate contents of total phenolics and vitamin C was found to exhibit the greatest scavenging (613.71 ± 2.59 µg VCEAC/g sample), reducing (2784.89 ± 3.93 µg TEAC/g sample), and α-glucosidase inhibitory activities (95.37 ± 0.15%). The juice of Barringtonia racemosa was ranked second in the activities and total phenolic content. Gallic and ellagic acids, which were quantified as the major phenolics of the respective juices, are suggested to be the main contributors to the antioxidant activities. The α-glucosidase inhibitory activity of the juices could be derived from myricetin and quercetin (that were previously reported as potent α-glucosidase inhibitors) in the hydrolyzed juice extracts. The juice of Syzygium samarangense, which was found to be highest in metal chelating activity (82.28 ± 0.10%), also was found to have these phenolics.

Cytotoxic and Apoptotic Effects of Ethyl Acetate Extract of Elephantopus mollis Kunth. in Human Liver Carcinoma HepG2 Cells Through Caspase-3 Activation.

Previous cytotoxic (anticancer) evaluations ofElephantopus molliswere mainly focused on its elephantopin derivatives neglecting the combined effect of the phytochemicals in its traditionally used extracts. In this study, the cytotoxic mechanism of its extracts was investigated using methylene blue assay. The cytotoxic screening results revealed the ethyl acetate extract as the most potent extract by displaying prominent dose-dependent and time-dependent growth inhibitions in human liver carcinoma HepG2 cells with the lowest EC50value of 9.38 ± 0.43 µg/mL after 72 hours of treatment. Acute exposure of the HepG2 cells to the ethyl acetate extract produced a significant regulation of caspase-3 with the peak expression at 8 hours of treatment (P< .05). DNA fragmentation indicated by DeadEnd Apoptosis Detection System-labeled nuclei cells confirmed that the extract induced apoptotic cell death through caspase-3-dependent pathway in HepG2 cells.

Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells.

Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.

Physalin F from Physalis minima L. triggers apoptosis-based cytotoxic mechanism in T-47D cells through the activation caspase-3- and c-myc-dependent pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalin F (a secosteroid derivative), is well recognized as a potent anticancer compound from Physalis minima L., a plant that is traditionally used to treat cancer. However, the exact molecular anticancer mechanism remains to be elucidated. AIM OF THE STUDY: We have recently reported the apoptosis-based cytotoxic effect of the chloroform extract of this plant. Here, we investigated the cytotoxicity and possible cell death mechanism elicited by the active constituent, physalin F on human breast T-47D carcinoma. MATERIALS AND METHODS: Cytotoxic-guided fractionation of the chloroform extract of Physalis minima has led to the isolation of physalin F. The cytotoxicity activity was assayed using MTS assay. The effect of the compound to induce apoptosis was determined by biochemical and morphological observations through DeadEnd Colorimetric and annexin V assays, respectively, and RT-PCR analysis of mRNA expression of the apoptotic-associated genes. RESULTS: Cytotoxicity screening of physalin F displayed a remarkable dose-dependent inhibitory effect on T-47D cells with lower EC50 value (3.60 µg/ml) than the crude extract. mRNA expression analysis revealed the co-regulation of c-myc- and caspase-3-apoptotic genes in the treated cells with the peak expression at 9 and 12h of treatment, respectively. This apoptotic mechanism is reconfirmed by DNA fragmentation and phosphatidylserine externalization. CONCLUSION: These findings indicate that physalin F may potentially act as a chemopreventive and/or chemotherapeutic agent by triggering apoptosis mechanism via the activation of caspase-3 and c-myc pathways in T-47D cells.

Antioxidant and α-glucosidase inhibitory activities of cucurbit fruit vegetables and identification of active and major constituents from phenolic-rich extracts of Lagenaria siceraria and Sechium edule.

Antioxidant and α-glucosidase activities and total phenolic contents (TPC) in sequential extracts of dried pulps from seven cucurbit fruit vegetables were determined for the first time. The highest TPC and metal chelating activity were obtained from the chloroform extracts of Luffa acutangula (28.04 ± 0.37 mg GAE/g extract) and Benincasa hispida (EC50 = 0.44 ± 0.03 mg/mL), respectively. The ethyl acetate extract of Sechium edule showed the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (951.73 ± 29.14 mM TE/g extract). The highest reducing and anti-α-glucosidase activities were shown by the methanol and ethyl acetate extracts of Momordica charantia (692.56 ± 43.38 mM AscAE/g extract; 66.64 ± 2.94%, respectively). The highest correlation (r = 0.99) was observed between the TPC and DPPH values of S. edule. Although caffeic acid was quantified as the major constituent in the methanol extract of Lagenaria siceraria , isoquercetin was found to be the main contributor to the activities. Gallic acid was identified as both the main and most active antioxidant constituent in the ethyl acetate extract of S. edule.

Identification of small molecule inhibitors of p27(Kip1) ubiquitination by high-throughput screening.

Dysregulation of p27(Kip1) due to proteolysis that involves the ubiquitin ligase (SCF) complex with S-phase kinase-associated protein 2 (Skp2) as the substrate-recognition component (SCF(Skp2)) frequently results in tumorigenesis. In this report, we developed a high-throughput screening system to identify small-molecule inhibitors of p27(Kip1) degradation. This system was established by tagging Skp2 with fluorescent monomeric Azami Green (mAG) and CDK subunit 1 (Cks1) (mAGSkp2-Cks1) to bind to p27(Kip1) phosphopeptides. We identified two compounds that inhibited the interaction between mAGSkp2-Cks1 and p27(Kip1): linichlorin A and gentian violet. Further studies have shown that the compounds inhibit the ubiquitination of p27(Kip1) in vitro as well as p27(Kip1) degradation in HeLa cells. Notably, both compounds exhibited preferential antiproliferative activity against HeLa and tsFT210 cells compared with NIH3T3 cells and delayed the G1 phase progression in tsFT210 cells. Our approach indicates a potential strategy for restoring p27(Kip1) levels in human cancers.

Evaluation of in vitro cytochrome P450 induction and inhibition activity of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L.

Drug metabolism involving cytochrome P450 (CYP) enzymes is a key determinant of significant drug interactions. Deoxyelephantopin was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4, and protein expression and resultant enzymatic activity. The mRNA and protein expression of cytochrome isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis, respectively. Human CYP3A4 protein expression was determined using an optimized hCYP3A4-HepG2 cell-based assay and the enzymatic activity was evaluated using P450-Glo™ CYP3A4 assay. The molecular interaction and possible inhibition of deoxyelephantopin of the CYP3A4 enzyme was determined in silico and further validated using substrate-specific CYP3A4 inhibition assays. Deoxyelephantopin produced no significant effect on the CYP1A2 and CYP2D6 mRNA and protein expression. However, it has a weak induction effect on CYP3A4 at the transcriptional level. In silico docking simulation showed that deoxyelephantopin has a weak interaction with CYP3A4 enzyme and it minimally affects the metabolism of CYP3A4 substrates. Deoxyelephantopin is not an in vitro CYP1A2 and CYP2D6 inducer. It is both a weak in vitro CYP3A4 inducer and inhibitor and is unlikely to elicit a clinically significant effect in human.

Polyphenolic and vitamin C contents and antioxidant activities of aqueous extracts from mature-green and ripe fruit fleshes of Mangifera sp.

Mature-green and ripe fleshes from 12 samples of Mangifera were selected for this study. The mature-green fleshes were found to have higher vitamin C contents than the ripe fleshes. However, not all higher total or individual phenolic contents were measured from the mature-green fleshes. The highest contents of vitamin C and total phenolics were respectively measured from the aqueous extracts of mature-green (255.86 ± 12.98 µg AAE/g sample) and ripe (142.57 ± 0.38 µg GAE/g sample) fleshes of M. petandra cv. Pauh. Gallic acid and mangiferin were detected in all aqueous extracts. The extracts of the mature-green flesh of M. indica cv. Chokanan and the ripe flesh of M. indica cv. Siku Raja, respectively, exhibited the greatest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH)-scavenging activity (408.21 ± 5.37 µg TE/g sample) and metal chelating activity (93.68 ± 0.74%). The combined or potentiation effects of the moderate vitamin C, gallic acid, and mangiferin contents in both extracts may be responsible for the activities. The highest mangiferin content (31.72 ± 2.57 µg/g sample) in the mature-green M. caesia (Binjai) could be the major contributor to its highest FRAP activity (868.29 ± 2.71 µg TE/g sample). This paper reports apparently the first comparative study highlighting the antioxidant activities of these fruit fleshes.

Spectaflavoside A, a new potent iron chelating dimeric flavonol glycoside from the rhizomes of Zingiber spectabile Griff.

The rhizomes of Zingiber spectabile yielded a new dimeric flavonol glycoside for which the name kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside-(I-6,II-8)-kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside; spectaflavoside A (1) was proposed, along with kaempferol and its four acetylrhamnosides (2-6), demethoxycurcumin (7) and curcumin (8). The structure of spectaflavoside A was elucidated by spectroscopic methods including, 1D and 2D NMR techniques. This is the first report on the occurrence of a dimeric flavonol glycoside in the Zingiberaceae and the second in nature. Spectaflavoside A was found to be a potent iron chelating agent.