Chemical characterizations dataset of flavonoid glycoside isomers and other constituents from Ficus deltoidea Jack.

Phytochemical data for Ficus deltoidea Jack, a plant widely studied for its anti-hyperglycemic effect, are scarce. In the pursuit of characterizing the chemical constituents of this species, extraction and purifications were conducted using multiple chromatographic procedures on selected varieties (var. deltoidea, var. kunstleri and var. trengganuensis). Twenty-two constituents were unambiguously identified through NMR, MS and UV data. These included gallocatechin (S1), afzelechin-4-8″-gallocatechin (S2), catechin (S3), afzelechin-4-8″-catechin (S4), afzelechin (S5), epicatechin (S6), hovetrichoside C (S7), 6,8-di-C-glucopyranosylapigenin (vicenin-2) (S8), afzelechin-4-8″-epiafzelechin (S9), epiafzelechin (S10), 6-C-xylopyranosyl-8-C-glucopyranosylapigenin (vicenin-1) (S11), orientin (S13), schaftoside (S14), 6-C-glucopyranosyl-8-C-xylopyranosylapigenin (vicenin-3) (S16), vitexin (S17), vitexin 2″-O-rhamnoside (S19), isovitexin 2″-O-rhamnoside (S20), 6,8-di-C-arabinopyranosylapigenin (S21), 6,8-di-C-xylopyranosylapigenin (S22), 6-C-arabinopyranosyl-8-C-xylopyranosylapigenin (S23), rhoifolin (S24) and cerberic acid A (S26). The presented phytochemical data can assist ethnobotanists, chemists, and natural product researchers in investigating the medicinal properties of F. deltoidea by facilitating the dereplication of its constituents.

Molecular networking-based mass spectral identification of Brucea javanica (L.) Merr. metabolites and their selective binding affinities for dengue virus enzymes.

Brucea javanica, a valued traditional medicinal plant in Malaysia, known for its fever-treating properties yet remains underexplored for its potential antiviral properties against dengue. This study aims to simultaneously identify chemical classes and metabolites within B. javanica using molecular networking (MN), by Global Natural Product Social (GNPS), and SIRIUS in silico annotation. Liquid chromatography-mass spectrometry (LC-MS2)-based MN explores chemical diversity across four plant parts (leaves, roots, fruits, and stem bark), revealing diverse metabolites such as tryptophan-derived alkaloids, terpenoids, and octadecadenoids. Simultaneous LC-MS2 and MN analyses reveal a discriminative capacity for individual plant components, with roots accumulating tryptophan alkaloids, fruits concentrating quassinoids, leaves containing fusidanes, and stem bark primarily characterised by simple indoles. Subsequently, extracts were evaluated for dengue antiviral activity using adenosine triphosphate (ATP) and plaque assays, indicates potent efficacy in the dichloromethane (DCM) extract from roots (EC50 = 0.3 µg/mL, SI = 10). Molecular docking analysis of two major compounds; canthin-6-one (264) and 1-hydroxy-11-methoxycanthin-6-one (275) showed potential binding interactions with active sites of NS5 RNA-dependent RNA polymerase (RdRp) of dengue virus (DENV) protein. Subsequent in vitro evaluation revealed compounds 264 and 275 had a promising dengue antiviral activity with SI value of 63 and 1.85. These identified metabolites emerge as potential candidates for further evaluation in dengue antiviral activities.

Mirror, mirror on the wall, which phytochemicals in Clinacanthus nutans inhibits advanced glycation end products of them all?

In our quest to discover advanced glycation end products (AGEs) inhibitors from Clinacanthus nutans (Burm.f.) Lindau leaves, we conducted a bioactivity-based molecular networking. This approach integrates LC-MS2 profiling and in vitro antiglycation data to predict bioactive compounds. We began by screening three extracts: 100% ethanol, 70% ethanol and 100% water alongside the in vitro antioxidant activity, total phenolics content (TPC) and schaftoside content. Among these extracts, 100% ethanol extract exhibited the highest total AGEs inhibition effects (IC50 = 80.18 ± 11.6 µg/mL), DPPH scavenging activity (IC50 = 747.40 ± 10.30 µg/mL) and TPC (26.54 ± 2.09 µg GAE /mg extract). Intriguingly, 100% ethanol extract contained the lowest amount of schaftoside, suggesting the involvement of other phytochemicals in the antiglycation effects. The molecular networking and in silico structural annotations of 401 LC-MS features detected in the fractions from 100% ethanol extract predicted 21 bioactive compounds (p < 0.05, r > 0.90), including several C40 carotenoids, alkaloids containing tetrapyrrole structures and fatty acids. On the contrary, all phenolics showed weak correlations with antiglycation effects. These predictions were further validated in vitro, where carotenoid lutein showed half maximal inhibitory concentration, IC50 = 96 ± 8 µM and selected flavonoid-C-glycosides exhibited weaker inhibitions (IC50 between 568 and 1922 µM). Notably, lutein content was higher in freeze-dried leaves (12.42 ± 0.82 mg/100 g) than oven-dried, although the former was associated with elevated mercury levels. In summary, C. nutans exhibited potential antiglycation and antioxidant activity, and lutein was identified as the main bioactive principle.

Biomarker triterpenoids of Centella asiatica as potential antidepressant agents: Combining in vivo and in silico studies.

Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5 mg/kg, i.p), on the behavioural and cortisol level of unpredictable chronic stress (UCS) zebrafish model. Based on the findings from the behavioural study, the cortisol levels in the zebrafish body after treatment with the two most effective compounds were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, a molecular docking study was conducted to predict the inhibitory impact of the triterpenoid compounds on serotonin reuptake. The in vivo results indicate that madecassoside (1.25, 2.5, and 5 mg/kg), asiaticoside and asiatic acid (5 mg/kg) activated locomotor behaviour. Madecassoside at all tested doses and asiaticoside at 2.5 and 5 mg/kg significantly decreased cortisol levels compared to the stressed group, indicating the potential regulation effect of madecassoside and asiaticoside on the hypothalamic-pituitary-adrenal axis overactivity. This study highlights the potential benefits of madecassoside and asiaticoside in alleviating depressive symptoms through their positive effects on behaviour and the hypothalamic-pituitary-adrenal (HPA)- axis in a chronic unpredictable stress zebrafish model. Furthermore, the in silico study provided additional evidence to support these findings. These promising results suggest that C. asiatica may be a valuable and cost-effective therapeutic option for depression, and further research should be conducted to explore its potential benefits.

Data on LC-MS profile of Brucea javanica (L.) Merr. and the NMR data of its major indole alkaloids.

This article presents two types of phytochemical data obtained from Brucea javanica (L.) Merr. roots, a medicinal plant belonging to the Simaroubaceae family. The high-resolution LC-MS dataset comprised the chemical profile of dichloromethane extract, which was utilised to annotate 35 chemical constituents. For annotations, the measured spectral data were compared with the in-silico spectral data generated from 920 molecular structures previously reported in Simaroubaceae. Indole alkaloids, quassinoids, aliphatics and lignan were the chemical groups identified in the root extract. The second dataset provides NMR spectra (1H, 13C, COSY, HMQC and HMBC) for the six indole alkaloids previously detected in LC-MS analysis and isolated through centrifugal partition chromatography. The chemical structures of all compounds were confirmed based on NMR data as bruceolline J (compound 7), canthin-6-one-N-oxide (compound 10), bruceolline E (compound 15), 5-methoxycanthin-6-one (compound 16), canthin-6-one (compound 20), and 1­hydroxy-11-methoxycanthin-6-one (compound 22). This phytochemical data was generated to support an ongoing anti-cancer and anti-dengue study.

Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model.

Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p < 0.0001) compared to the CUS group. A significant increase in total distance travelled, and contact duration was observed only in the fluoxetine-treated group (t-test, p = 0.0007) and (t-test, p = 0.0207), respectively. A significant increase in highly mobile duration was observed in both treatment groups. Andrographolide (50 mg/kg, i.p.) acute treatment showed a significant reduction in freezing duration (p = 0.0042), duration in a dark area (p = 0.0338) and cortisol level (p = 0.0156) and increased total distance travelled (p = 0.0144). Twenty-six compounds were tentatively characterized by LC-MS/MS method, and andrographolide content is 0.042 µg/g. According to cortisol analysis, A. paniculata's LC50 is 627.99 mg/L, while andrographolide's EC50 was determined as 26.915 mg/kg. Further assessment of the cellular and molecular underpinnings of the anti-depressive effect of andrographolide is strongly recommended to evaluate the potential as an antidepressant.

Annona muricata: Comprehensive Review on the Ethnomedicinal, Phytochemistry, and Pharmacological Aspects Focusing on Antidiabetic Properties.

Plants have played an important role over the centuries in providing products that have been used to help combat ailments and diseases. Many products originating from fresh, dried-plant materials, or extracts are utilized as community remedies in traditional practices or even in modern medicine. The Annonaceae family contains different types of bioactive chemical properties, such as alkaloids, acetogenins, flavonoids, terpenes, and essential oil, meaning the plants in this family are potential therapeutic agents. Belonging to the Annonaceae family, Annona muricata Linn. has recently attracted the attention of scientists for its medicinal value. It has been utilized as a medicinal remedy since ancient times to treat and improve various diseases, for example, diabetes mellitus, hypertension, cancer, and bacterial infections. This review, therefore, highlights the important characteristic and therapeutic effect of A. muricata along with future perspectives on its hypoglycemic effect. The most-common name is soursop, referring to its sour and sweet flavors, while in Malaysia, this tree is commonly called 'durian belanda'. Furthermore, A. muricata contains a high content of phenolic compounds in the roots and leaves. In vitro and in vivo studies have shown that A. muricata has the pharmacological effects of anti-cancer, anti-microbial, antioxidant, anti-ulcer, anti-diabetic, anti-hypertensive, and wound healing. With regard to its anti-diabetic effect, mechanisms of inhibiting glucose absorption via α-glucosidase and α-amylase activity inhibition, increasing glucose tolerance and glucose uptake by peripheral tissues, and stimulating insulin release or acting like insulin were deeply discussed. There is still a significant research gap, and future studies are required to conduct detailed investigations and gain a better molecular understanding of A. muricata's anti-diabetic potential, especially by using the metabolomics approach.

Correlation of chemical profiles obtained from 1 H-NMR and LC-MS metabolomics with α-glucosidase inhibition activity for varietal selections of Ficus deltoidea.

INTRODUCTION: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia to treat various ailments, including diabetes. The presence of several varieties raises essential questions regarding which is the potential bioactive variety and what are the bioactive metabolites. OBJECTIVES: Here, we explored the phytochemical diversity of the seven varieties from Peninsular Malaysia using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS) analyses and correlated it with the α-glucosidase inhibitory activity. METHODOLOGY: The Nuclear Overhauser Effect Spectroscopy (NOESY) One-Dimensional (1D)-NMR and LC-MS data were processed, annotated, and correlated with in vitro α-glucosidase inhibitory using multivariate data analysis. RESULTS: The α-glucosidase results demonstrated that different varieties have varying inhibitory effects, with the highest inhibition rate being F. deltoidea var. trengganuensis and var. kunstleri. Furthermore, diverse habitats and plant ages could also influence the inhibitory rate. The heat map from NMR and LC-MS profiles showed unique patterns according to varying levels of α-glucosidase inhibition rate. The Partial Least Squares (PLS) model constructed from both NMR and LC-MS further confirmed the correlation between the α-glucosidase inhibition rate of F. deltoidea varieties and its metabolite profiles. The Variable Influence on Projection (VIP) and correlation coefficient (p(corr)) values values were used to determine the highly relevant metabolites for explaining the anticipated inhibitory action. CONCLUSION: NMR and LC-MS annotations allow the identification of flavan-3-ols and proanthocyanidins as the key bioactive factors. Our current results demonstrated the value of multivariate data analysis to predict the quality of herbal materials from both biological and chemical aspects.

Carica papaya Leaf Juice for Dengue: A Scoping Review.

The potential therapeutic effect of Carica papaya leaf juice has attracted wide interest from the public and scientists in relieving dengue related manifestations. Currently, there is a lack of evaluated evidence on its juice form. Therefore, this scoping review aims to critically appraise the available scientific evidence related to the efficacy of C. papaya leaf juice in dengue. A systematic search was performed using predetermined keywords on two electronic databases (PubMed and Google Scholar). Searched results were identified, screened and appraised to establish the association between C. papaya and alleviating dengue associated conditions. A total of 28 articles (ethnobotanical information: three, in vitro studies: three, ex vivo studies: one, in vivo study: 13, clinical studies: 10) were included for descriptive analysis, which covered study characteristics, juice preparation/formulations, study outcomes, and toxicity findings. Other than larvicidal activity, this review also reveals two medicinal potentials of C. papaya leaf juice on dengue infection, namely anti-thrombocytopenic and immunomodulatory effects. C. papaya leaf juice has the potential to be a new drug candidate against dengue disease safely and effectively.

Integration of Choline Chloride-Based Natural Deep Eutectic Solvents and Macroporous Resin for Green Production of Enriched Oil Palm Flavonoids as Natural Wound Healing Agents.

Huge quantities of oil palm (Elaeis guineensis Jacq.) leaves (OPL) are generated as agricultural biomass from oil palm plantations. OPL are known to contain significant amounts of flavonoids. For maximal exploitation of these valuable antioxidant compounds, an innovative and sustainable extraction method employing natural deep eutectic solvents (NaDES) combined with ultrasonic assisted extraction was developed. Various NaDES composed of choline chloride as the hydrogen bond donor (HBD) and 1,2 propanediol (PD), 1,4 butanediol (BD), glycerol (GLY), glucose (GLU), maltose (MAL), and lactic acid (LA) as the hydrogen bond acceptor (HBA) were synthesized. The influence of these compositions, the methods of their synthesis, molar ratios, and water contents on their capacity to extract flavonoids from OPL was evaluated. Based on the results, it was found that methods which incorporate a heating step produced NaDES with the best capacity to extract OPL flavonoids. These thermal methods combined with molar ratios of 1:3 or 1:4 and water contents of 17 to 50% were found to be the optimal conditions for preparing NaDES, specifically when applied to the PD, BD, and GLY NaDES. Subsequently, UHPLC-UV/PDA-MS/MS analysis revealed NaDES extracts recovered by macroporous adsorption resin XAD7HP were able to optimally extract at least twelve luteolin and apigenin derivatives in OPL NaDES extracts prepared from glycerol and 1,4-butanediol demonstrated better and comparable efficiency as aqueous methanol in extracting flavonoids from OPL. The in vitro studies of antioxidant and wound healing properties supported these findings by exhibiting good free radical scavenging, cell proliferation, and migration activities. Additionally, the NaDES extracts also showed non-cytotoxicity effects at 1000 µg/mL and below on 3T3 fibroblast cells. Results of the study showed that NaDES could be a promising eco-friendly green solvent to extract bioactive OPL flavonoids that have great potential for applications as wound healing agents.

Immunomodulatory Activities of Carica papaya L. Leaf Juice in a Non-Lethal, Symptomatic Dengue Mouse Model.

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.

Metabolomics of Myrcia bella Populations in Brazilian Savanna Reveals Strong Influence of Environmental Factors on Its Specialized Metabolism.

Environmental conditions influence specialized plant metabolism. However, many studies aiming to understand these modulations have been conducted with model plants and/or under controlled conditions, thus not reflecting the complex interaction between plants and environment. To fully grasp these interactions, we investigated the specialized metabolism and genetic diversity of a native plant in its natural environment. We chose Myrcia bella due to its medicinal interest and occurrence in Brazilian savanna regions with diverse climate and soil conditions. An LC-HRMS-based metabolomics approach was applied to analyze 271 samples harvested across seven regions during the dry and rainy season. Genetic diversity was assessed in a subset of 40 samples using amplified fragment length polymorphism. Meteorological factors including rainfall, temperature, radiation, humidity, and soil nutrient and mineral composition were recorded in each region and correlated with chemical variation through multivariate analysis (MVDA). Marker compounds were selected using a statistically informed molecular network and annotated by dereplication against an in silico database of natural products. The integrated results evidenced different chemotypes, with variation in flavonoid and tannin content mainly linked to soil conditions. Different levels of genetic diversity and distance of populations were found to be correlated with the identified chemotypes. These observations and the proposed analytical workflow contribute to the global understanding of the impact of abiotic factors and genotype on the accumulation of given metabolites and, therefore, could be valuable to guide further medicinal exploration of native species.

Utility of dry load injection for an efficient natural products isolation at the semi-preparative chromatographic scale.

Semi-preparative HPLC is one of the main techniques used for the purification of natural products (NPs). Generally, the sample has to be solubilized in organic solvent and injected on column through a loop valve. Since the solubility of crude natural extracts is often limited, a high solvent volume is needed for injection. This significantly compromises the resolution and increases the risk of overpressure in the system. To overcome this problem, a dry load injection procedure was developed to ensure optimum resolution even at high sample loading. The approach was first validated with a representative mixture of NPs standards, and successfully applied to two representative crude plant extracts: the dichloromethane extract of Annacardium occidentale and the methanolic extract of Hypericum perforatum. In all cases, the dry loading injection setup enabled an efficient introduction of the samples in the semi-preparative HPLC system. Different overload conditions of the columns were tested and the results demonstrated the robustness of the method and the possibility of applying it with a limited loss of resolution compared to liquid injection and without increasing pressure. The chromatographic resolutions were close to those obtained at the analytical level and separation were of much better quality when compared to liquid injection. This approach is especially relevant when purifying compounds isolated with high resolution from extracts that are poorly soluble in low volume of injection solvent due to the presence of lipophilic compounds and are thus not compatible for loop injection in typical reversed phase conditions. In addition, the dry load setup was also found to be useful when relatively polar components have to be separated in reversed phase conditions. In this case, loop injection with methanol generates strong peak distortion and broadening, while the dry load injection affords symmetrical peaks.

Differentiation of Ficus deltoidea varieties and chemical marker determination by UHPLC-TOFMS metabolomics for establishing quality control criteria of this popular Malaysian medicinal herb.

BACKGROUND: Ficus deltoidea Jack (Moraceae) is a plant used in Malaysia for various diseases including as a supplement in diabetes management. Morphology distinction of the 7 main varieties (var. angustifolia, var. bilobata, var. deltoidea, var. intermedia, var. kunstleri, var. motleyana and var. trengganuensis) is challenging due to the extreme leaf heterophylly and unclear varietal boundaries, making it difficult for quality control of F. deltoidea products. OBJECTIVE: We aimed to compare the phytochemical composition of 7 varieties growing in different conditions at various geographical locations. We also aimed to establish the quality control markers for the authentication of these varieties. METHODS: We applied untargeted UHPLC-TOFMS metabolomics to discriminate 100 leaf samples of F. deltoidea collected from 6 locations in Malaysia. A genetic analysis on 21 leaf samples was also performed to validate the chemotaxonomy differentiation. RESULTS: The PCA and HCA analysis revealed the existence of 3 chemotypes based on the differentiation in the flavonoid content. The PLS-DA analysis identified 15 glycosylated flavone markers together with 1 furanocoumarin. These markers were always consistent for the respective varieties, regardless of the geographical locations and growing conditions. The chemotaxonomy differentiation was in agreement with the DNA sequencing. In particular, var. bilobata accession which showed divergent morphology was also differentiated by the chemical fingerprints and genotype. CONCLUSION: Chemotype differentiation based on the flavonoid fingerprints along with the proposed markers provide a powerful identification tool to complement morphology and genetic analyses for the quality control of raw materials and products from F. deltoidea.

In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3.

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 µg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC-MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 µg/mL, SRB staining of PC3 cells).

Phytoconstituents and antioxidant properties among commercial tea (Camellia sinensis L. ) clones of Iran

Background Tea (Camellia sinensis), a well-known beverage is consumed frequently worldwide due to its high antioxidant properties. The present study determines the amount of phytochemicals and antioxidant activities among 12 high yielding tea clones cultivated in Iran. Results Among the 12 clones studied, tea clone Iran 100 had the highest total phenolic content and total flavonoid content with values of 8.44 ± 1.03 mg gallic acid equivalents per gram dry weight and 4.50 ± 0.16 mg rutin equivalents per gram dry weight respectively. High performance Liquid Chromatography (HPLC) analysis of phenolics and flavonoids in 12 clones revealed the presence of (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epigallocatechin-gallate, (-)-epicatechingallate, gallic acid and caffeine. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay showed the existence of variation in the antioxidant activity ranging from 22.67 to 65.36%. The highest antioxidant activity with IC50 value of 218.24 µg/mL was observed in the leaf extract of the clone Iran 100, while the lowest was found in the clone Iran 482 with IC50 value of 234.44 µg/mL. The antioxidant activity had a positive correlation with total phenolic content, total flavonoid content, (-)-epigallocatechin-gallate, (-)-epicatechingallate and caffeine (0.59 = r = 0.97, P < 0.05). Conclusion From the study it can be concluded that the clone Iran 100 has a superior quality compared to any other clones studied due to occurrence of more phenolic compounds and a greater antioxidant activity. Hence, we recommend the use of tea clone Iran 100 for commercial planting.

Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats.

The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD) rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group) at 0 (control), 0.01, 0.14, and 2 g/kg body weight (BW) for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect.

Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum.

BACKGROUND: The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties. METHODS: Each part of the plants were processed, defatted by hexane and sequentially extracted with dichloromethane, methanol and water. The antiplasmodial activities of 54 plant extracts from 14 species were determined by Plasmodium falciparum Histidine Rich Protein II ELISA technique. In order to determine the selectivity index (SI), all plant extracts demonstrating a good antiplasmodial activity were tested for their cytotoxicity activity against normal Madin-Darby Bovine Kidney (MDBK) cell lines by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Twenty three extracts derived from Curcuma zedoaria (rhizome), Curcuma aeruginosa (rhizome), Alpinia galanga (rhizome), Morinda elliptica (leaf), Curcuma mangga (rhizome), Elephantopus scaber (leaf), Vitex negundo (leaf), Brucea javanica (leaf, root and seed), Annona muricata (leaf), Cinnamomun iners (leaf) and Vernonia amygdalina (leaf) showed promising antiplasmodial activities against the blood stage chloroquine resistant P. falciparum (EC50 < 10 µg/ml) with negligible toxicity effect to MDBK cells in vitro (SI ≥10). CONCLUSION: The extracts belonging to eleven plant species were able to perturb the growth of chloroquine resistant P. falciparum effectively. The findings justified the bioassay guided fractionation on these plants for the search of potent antimalarial compounds or formulation of standardized extracts which may enhance the antimalarial effect in vitro and in vivo.

Carica papaya Leaves Juice Significantly Accelerates the Rate of Increase in Platelet Count among Patients with Dengue Fever and Dengue Haemorrhagic Fever.

The study was conducted to investigate the platelet increasing property of Carica papaya leaves juice (CPLJ) in patients with dengue fever (DF). An open labeled randomized controlled trial was carried out on 228 patients with DF and dengue haemorrhagic fever (DHF). Approximately half the patients received the juice, for 3 consecutive days while the others remained as controls and received the standard management. Their full blood count was monitored 8 hours for 48 hours. Gene expression studies were conducted on the ALOX 12 and PTAFR genes. The mean increase in platelet counts were compared in both groups using repeated measure ANCOVA. There was a significant increase in mean platelet count observed in the intervention group (P < 0.001) but not in the control group 40 hours since the first dose of CPLJ. Comparison of mean platelet count between intervention and control group showed that mean platelet count in intervention group was significantly higher than control group after 40 and 48 hours of admission (P < 0.01). The ALOX 12 (FC = 15.00) and PTAFR (FC = 13.42) genes were highly expressed among those on the juice. It was concluded that CPLJ does significantly increase the platelet count in patients with DF and DHF.

Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.