Flavonoid glycosides from the leaves of Michelia champaca.

Michelia champaca L. (Magnoliaceae) was cultivated in large scale for flowers as cosmetic raw materials, whereas the value of its leaves remains to be discovered. Our chemical study on the leaves yielded four new flavonol diglycosides, champaflavosides A-D (1-4), together with twenty-three known flavonoid glycosides (5-27). Their structures were determined by spectroscopic and chemical methods. Compounds 5-21 and 23-27 were not previously reported from the genus Michelia, and kaempferol 3-O-rutinoside (22) was obtained from this species for the first time. All the compounds were evaluated for antioxidant activity by four in vitro assays. Compounds 3-12 and 20 showed more potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than l-ascorbic acid (l-AA). Compounds 2-23, 25, and 27 exhibited 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity superior to l-AA. The ferric reducing antioxidant powers (FRAP) of compounds 2-13, 17, and 19 were higher than l-AA. Further, eighteen compounds demonstrated cellular reactive oxygen species (ROS) scavenging activity, of which champaflavoside D (4), rhamnetin 3-O-neohesperidoside (8), quercetin 3-O-(6-O-E-p-coumaroyl)-neohesperidoside (9), and liquiritin (27) were more potent than curcumin. The results revealed that the renewable leaves of M. champaca are a rich source of flavonoids and antioxidants.

Octadecadienoate derivatives from Michelia champaca seed extract as potential larvicide and pupicide against Dengue vector Aedes albopictus.

The present study was designed aiming at finding novel botanicals for controlling the vector population. Objective was to evaluate the larvicidal and pupicidal efficacies of crude and solvent extracts of Michelia champaca seed against the notorious dengue vector Aedes albopictus. 0.5% concentration of the crude extractive and 40 ppm concentration of ethyl acetate extractive were enough to execute 100% of larval mortality of all the instars after 72 h of exposure and the LC50 and LC90values (95% confidence level) of ethyl acetate extractive were 0.9880 ppm and 36.0491 ppm. In case of pupicidal bioassay, 100% mortality was observed at 200 ppm of ethyl acetate extract. Through TLC techniques, the bioactive compounds were isolated, which caused remarkable larval toxicity at 15 ppm concentration. Three-way factorial ANOVA analysis showed different concentrations, time intervals, and instars revealed a significant difference in larval death. FT-IR analysis revealed the presence several important functional groups. Presence of methyl 5,12-octadecadienoate and ethyl 9cis,11trans-octadecadienoate were ascertained by GC-MS analysis. The said bioactive compounds showed very low toxicity in non-target organisms such as damselfly (Ischnura sp.) and water bug (Diplonychus sp.) Thus, proclaiming the potentialities of Michelia champaca seed extracts as larvicidal and pupicidal agents against Ae. albopictus.

A Study of the Chemical Composition and Biological Activity of Michelia macclurei Dandy Heartwood: New Sources of Natural Antioxidants, Enzyme Inhibitors and Bacterial Inhibitors.

The wood of Michelia macclurei Dandy (MD) is an excellent material that is widely used in the furniture, handicraft, and construction industries. However, less research has been conducted on the chemical composition and biological activity of heartwood, which is the main valuable part of the wood. This study aimed to investigate the chemical composition and biological activities of the heartwood of Michelia macclurei Dandy (MDHW) and to confirm the active ingredients. Triple quadrupole gas chromatography-mass spectrometry (GC-MS) was used to characterize the volatile components of MDHW, while ultra-performance liquid chromatography-mass spectrometry was used to analyze the non-volatile components (UPLC-MS). The total reducing power, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assays, acetylcholinesterase and α-glucosidase inhibition assays, and an antimicrobial test of 4 gram bacteria were used to describe the in vitro bioactivities. The GC-MS analysis showed that the volatile components of MDHW were mainly fatty compounds and terpenoids, with sesquiterpenes and their derivatives dominating the terpene composition. ß-elemene was the main terpene component in the steam distillation (11.88%) and ultrasonic extraction (8.2%) methods. A total of 67 compounds, comprising 45 alkaloids, 9 flavonoids, 6 lignans, and others, were found by UPLC-MS analysis. The primary structural kinds of the non-volatile components were 35 isoquinoline alkaloids. Alkaloids were the predominant active constituent in all MDHW extracts, including crude extracts, alkaloid fractions, and non-alkaloid fractions. These extracts all demonstrate some biological effects in terms of antioxidant, enzyme inhibition, and bacterial inhibition. The findings of this study show that MDHW is abundant in chemical structure types, has great bioactivity assessment, and has the potential to be used to create natural antioxidants, products that postpone Alzheimer's disease and lower blood sugar levels and antibacterial agents.

New insights on the phytochemical intervention for the treatment of neuropsychiatric disorders using the leaves of Michelia champaca: an in vivo and in silico approach.

CONTEXT: Michelia champaca L. (Magnoliaceae) has been known since ancient times for its rich medicinal properties. OBJECTIVE: The ethanol extract of Michelia champaca leaves (EEMC) was evaluated on depression and anxiety using in vivo and in silico studies. MATERIALS AND METHODS: Swiss albino mice were divided into control, standard, 100 and 200 mg/kg b.w. EEMC groups and for drug administration using oral gavage. The antidepressant activity was evaluated using forced swim test (FST) and tail suspension test (TST) whereas the anxiolytic activity through elevated plus maze and light and dark tests. The in silico studies included molecular docking against human potassium channel KCSA-FAB and human serotonin transporter, and ADME/T analysis. RESULTS: Open arm duration and entries were comparable between 200 mg/kg b.w. group (184.45 ± 1.00 s and 6.25 ± 1.11, respectively) and that of diazepam treated group (180.02 s ± 0.40 and 6.10 ± 0.05, respectively). Time spent in the light cubicle was higher (46.86 ± 0.03%), similar to that of diazepam (44.33 ± 0.64%), suggesting its potent anxiolytic activity. A delayed onset of immobility and lowered immobility time was seen at both the treatment doses (FST: 93.7 ± 1.70 and 89.1 ± 0.40 s; TST: 35.05 ± 2.75 and 38.50 ± 4.10 s) and the standard drug imipramine (FST: 72.7 ± 3.72 and TST: 30.01 ± 2.99 s), indicative of its antidepressant ability. In silico studies predicted doripenem to induce anxiolytic and antidepressant activity by inhibiting human potassium channel KCSA-FAB and human serotonin transporter proteins, respectively. CONCLUSIONS: EEMC is a rich source of bioactive compounds with strong antidepressant and anxiolytic properties.

Phytochemistry, Bioactivities and Traditional Uses of Michelia × alba.

Michelia × alba (M. alba) is a flowering tree best known for its essential oil, which has long been used as a fragrance ingredient for perfume and cosmetics. In addition, the plant has been used in traditional medicine in Asia and dates back hundreds of years. To date, there is a limited number of publications on the bioactivities of M. alba, which focused on its tyrosinase inhibition, antimicrobial, antidiabetic, anti-inflammatory, and antioxidant activities. Nevertheless, M. alba may have additional unexplored bioactivities associated with its bioactive compounds such as linalool (72.8% in flower oil and 80.1% in leaf oil), α-terpineol (6.04% flower oil), phenylethyl alcohol (2.58% flower oil), ß-pinene (2.39% flower oil), and geraniol (1.23% flower oil). Notably, these compounds have previously been reported to exhibit therapeutic activities such as anti-cancer, anti-inflammation, anti-depression, anti-ulcer, anti-hypertriglyceridemia, and anti-hypertensive activities. In this review paper, we examine and discuss the scientific evidence on the phytochemistry, bioactivities, and traditional uses of M. alba. Here, we report a total of 168 M. alba biological compounds and highlight the therapeutic potential of its key bioactive compounds. This review may provide insights into the therapeutic potential of M. alba and its biologically active components for the prevention and treatment of diseases and management of human health and wellness.

Anti-Diabetes, Anti-Gout, and Anti-Leukemia Properties of Essential Oils from Natural Spices Clausena indica, Zanthoxylum rhetsa, and Michelia tonkinensis.

Essential oils (EOs) of Clausena indica fruits, Zanthoxylum rhetsa fruits, and Michelia tonkinensis seeds were analyzed for their phytochemical profiles and biological activities, including anti-diabetes, anti-gout, and anti-leukemia properties. Sixty-six volatile compounds were identified by gas chromatography-mass spectrometry (GC-MS), in which, myristicin (68.3%), limonene (44.2%), and linalool (49.3%) were the most prominent components of EOs extracted from C. indica, Z. rhetsa, and M. tonkinensis, respectively. In addition, only EOs from C. indica inhibited the activities of all tested enzymes comprising α-amylase (IC50 = 7.73 mg/mL), α-glucosidase (IC50 = 0.84 mg/mL), and xanthine oxidase (IC50 = 0.88 mg/mL), which are related to type 2 diabetes and gout. Remarkably, all EOs from C. indica, Z. rhetsa (IC50 = 0.73 mg/mL), and M. tonkinensis (IC50 = 1.46 mg/mL) showed a stronger anti-α-glucosidase ability than acarbose (IC50 = 2.69 mg/mL), a known anti-diabetic agent. Moreover, the growth of leukemia cell Meg-01 was significantly suppressed by all EOs, of which, the IC50 values were recorded as 0.32, 0.64, and 0.31 mg/mL for EOs from C. indica, Z. rhetsa, and M. tonkinensis, respectively. As it stands, this is the first report about the inhibitory effects of EOs from C. indica and Z. rhetsa fruits, and M. tonkinensis seeds on the human leukemia cell line Meg-01 and key enzymes linked to diabetes and gout. In conclusion, the present study suggests that EOs from these natural spices may be promising candidates for pharmaceutical industries to develop nature-based drugs to treat diabetes mellitus or gout, as well as malignant hematological diseases such as leukemia.

Leaf and Flower Extracts of Six Michelia L.: Polyphenolic Composition, Antioxidant, Antibacterial Activities and in Vitro Inhibition of α-Amylase and α-Glucosidase.

Methanolic extracts of the leaf and flower of Michelia L., an evergreen aromatic genus widely used in landscaping, industry and medicine of various countries, were analyzed. The UPLC-ESI-MS/MS analysis led to the identification of 28 polyphenols from six Michelia species that widely distributed and cultivated in southern China, among which quinic acid and chlorogenic acid were the main components. The flower extract of Michelia maudiae had the most abundant polyphenols content, as well as high contents of total phenolic (117.31±7.26 mg GAE/g DW) and total flavonoid (251.60±15.56 mg CE/g DW). Meanwhile, it also showed outstanding performance in three antioxidant indexes of DPPH, ABTS and FRAP. The leaf extracts of Michelia chapensis and Michelia floribunda exhibited excellent inhibition against four pathogenic bacteria. Moreover, certain inhibitory activities were displayed by Michelia macclurei extracts against α-amylase and α-glucosidase. This study explored the biological activities of six Michelia species, and provided reference for variety selection with the aim of designing novel phyto-pharmaceuticals.

Preparation and quality evaluation of a volatile oil microemulsion from Flos magnoliae and Centipeda minima.

In order to improve the water solubility of the volatile oils extracted from Flos magnoliae (FM) and Centipeda minima (CM), they were prepared as a microemulsion (ME), which were then used in the development of an FM and CM volatile oil ME for the treatment of allergic rhinitis (AR). ME was prepared by phase inversion emulsification, and the prescription factors such as emulsifier, co­emulsifier, oil phase, Km, which represents the ratio of the mass of emulsifier to that of the co­emulsifier, and preparation factors such as temperature affecting the formation of the ME were selected according to the formation area of ME in a pseudo­ternary phase diagram. The quality of the ME was evaluated based on its appearance, particle size, Zeta potential and stability. The content of eucalyptol in ME was determined by gas chromatography­mass spectrometry (GC­MS). The cumulative permeability of the ME within 24 h was measured with a transdermal diffusion tester. The results revealed that the best formula for preparation of the ME was as follows: Castor oil polyoxyethylene ether (EL­40) was the emulsifier; the co­emulsifier was anhydrous ethanol; the Km was 2:1; the mixed phase of volatile oil and isopropyl myristate with mass ratio of 1:1 was used as oil phase; and the preparation temperature was 25˚C. The content of eucalyptol in the ME was 2.57 mg/g, and the cumulative permeability of the ME in 24 h was significantly increased compared with that of the reference oil solution. The appearance of the ME was uniform, and the solution was transparent. In conclusion, compared with traditional preparations, FM and CM volatile oil ME is a novel, improved and more effective preparation for the treatment of AR.

The Chimonanthus salicifolius genome provides insight into magnoliid evolution and flavonoid biosynthesis.

Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome-level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein-coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole-genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole-genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius.

Magnoliae Flos Essential Oil as an Immunosuppressant in Dendritic Cell Activation and Contact Hypersensitivity Responses.

Magnoliae Flos is a commonly used traditional medicinal material in Asia. It is used to treat sinusitis, nasal congestion, and hypersensitive skin. Because Magonlia Flos was described as an aromatic material in ancient Chinese texts, we hypothesized that its essential oil may be used to treat immune disorders. Dendritic cells (DCs), regarded as a major target of immunomodulators to control immune responses, play a critical role in the adaptive immune response. In this study, Magnoliae Flos essential oil (MFEO) decreased the production of the cytokines TNF-α, IL-6, and IL-12p70 in lipopolysaccharide (LPS)-stimulated DCs. It also suppressed the surface markers MHC II, CD80, and CD86 in LPS-stimulated DCs. Animal models demonstrated that the 2,4-Dinitro-1-fluorobenzene (DNFB) inducing a contact hypersensitivity response was inhibited following treatment with MFEO. In addition, MFEO inhibited the infiltration of T cells in the ears of DNFB-induced mice. To explore its bioactive compounds, the components of MFEO were analyzed using gas chromatography (GC) and GC-mass spectrometry. The results revealed that the major compounds in MFEO are camphor and 1,8-cineole. Additional DC bioassays confirmed that these compounds substantially suppressed cytokine production in LPS-induced DCs. Therefore, we demonstrated that MFEO exhibits an immunosuppressive effect both in vivo and in vitro, and camphor and 1,8-cineole may be the major components responsible for its immunosuppressive ability. The findings indicate that MFEO has the potential to be developed as a new immunosuppressant for excessive diseases.

An Evaluation of the DNA-Protective Effects of Extracts from Menyanthes trifoliata L. Plants Derived from In Vitro Culture Associated with Redox Balance and Other Biological Activities.

Menyanthes trifoliata L. is a valuable medical plant found in Europe, North America, and Asia, which grows on peat bogs and swamps. It has long been used in folk medicine as a remedy for various ailments. This is the first report to demonstrate the protective antioxidant and anti-inflammatory properties of aqueous methanolic extracts derived from the aerial parts (MtAPV) and roots (MtRV) of in vitro grown plants on human umbilical vein endothelial cells (HUVECs). It describes the influence of the tested extracts on the expression of antioxidant (HO-1, NQO1, NRF2, kEAP1, and GCLC) and inflammation-related genes (IL-1α, IL-1ß, IL-6, TNF-α, and IFN-γ) in cells stimulated with H2O2 or LPS, respectively. In addition, M. trifoliata extracts were found to moderately affect the growth of certain bacterial and fungal pathogens, with the strongest antibacterial effect found against Pseudomonas aeruginosa and Enterococcus faecalis. M. trifoliata extracts demonstrated protective effects against mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage caused by ROS, decreasing the numbers of mtDNA lesions in the ND1 and ND2 genes and nDNA damage in the TP53 and HPRT1 genes and reducing cleavage in PARP1- and γ-H2A.X-positive cells. The root extract of in vitro M. trifoliata (MtRV) appears to have better anti-inflammatory, antioxidant, antimicrobial, and protective properties than the extract from the aerial part (MtAPV). These differences in biological properties may result from the higher content of selected phenolic compounds and betulinic acid in the MtRV than in the MtAPV extract.

Pharmacology mechanism of Flos magnoliae and Centipeda minima for treating allergic rhinitis based on pharmacology network.

Chinese herbs such as Flos magnoliae (FM) and Centipeda minima (CM) can be effective in treating allergic rhinitis (AR). However, there is little research on the therapeutic mechanism of these two drugs acting on AR at the same time. In order to systematically understand the mechanism of action of two drugs acting on AR at the same time, we searched various databases to obtain 31 components and 289 target proteins of FM, 25 components and 465 target proteins of CM. The interaction networks of FM, CM, and AR proteins were constructed by Cytoscape-v3.2.1 software. The core protein of two network intersections was obtained by using Venny 2.1.0. The R platform was used for the core target protein gene ontology (GO) comment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Thirteen common targets and seven acting pathways were obtained. The results of animal experiments showed that FM and CM volatile oil could effectively improve the symptoms of AR by regulating the common targets. In summary, this study successfully explained the potential therapeutic mechanism of FM and CM in the treatment of AR. At the same time, it indicates that the two drugs can be compatible as a new application.

Hypolipidemic and antioxidant activities of volatile oils from fresh leaves of Michelia martini Levl.

.This study aimed to investigate the hypolipidemic and antioxidant activities of volatile oils from Michelia martini Levl. The antioxidant property of volatile oils from Michelia martini in vitro was investigated by establishment of various systems. High fat diet induced rats were used to assess the hypolipidemic and antioxidant activities of Michelia martini volatile oils in vivo. The level of total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alanine transaminase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase in serum, and the activities of catalase, malondialdehyde, super oxide dismutase and glutathione in liver of rats were assayed by standard procedures. Our results showed that Michelia martini exhibits strong hypolipidemic and antioxidant activities both in vitro and vivo. Our data were also supplemented with histopathological studies on liver tissues and aorta sections of rats.

The Complete Plastid Genome of Magnolia zenii and Genetic Comparison to Magnoliaceae species.

Magnolia zenii is a critically endangered species known from only 18 trees that survive on Baohua Mountain in Jiangsu province, China. Little information is available regarding its molecular biology, with no genomic study performed on M. zenii until now. We determined the complete plastid genome of M. zenii and identified microsatellites. Whole sequence alignment and phylogenetic analysis using BI and ML methods were also conducted. The plastome of M. zenii was 160,048 bp long with 39.2% GC content and included a pair of inverted repeats (IRs) of 26,596 bp that separated a large single-copy (LSC) region of 88,098 bp and a small single-copy (SSC) region of 18,757 bp. One hundred thirty genes were identified, of which 79 were protein-coding genes, 37 were transfer RNAs, and eight were ribosomal RNAs. Thirty seven simple sequence repeats (SSRs) were also identified. Comparative analyses of genome structure and sequence data of closely-related species revealed five mutation hotspots, useful for future phylogenetic research. Magnolia zenii was placed as sister to M. biondii with strong support in all analyses. Overall, this study providing M. zenii genomic resources will be beneficial for the evolutionary study and phylogenetic reconstruction of Magnoliaceae.

Efficacy and safety of Tongfu powder in acute pancreatitis patients with gastrointestinal dysfunction: a clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongfu powder for external application on Shénquè (the umbilicus, hereafter, Tongfu powder) versus mosapride in acute pancreatitis (AP) patients with gastrointestinal dysfunction. METHODS: A total of 102 AP patients were diagnosed using the latest Atlanta Criterion and recruited at the Department of Infectious Disease, Beijing Friendship Hospital (Beijing, People's Republic of China) from August 2014 to December 2016. Patients were randomized into the Tongfu powder group and mosapride group using the random table. Information on scores (eg, the gastrointestinal function score) on days 1 and 7 of hospitalization, biochemical indicators (eg, interleukin [IL]-2 and IL-6), indicators for curative effects (eg, first defecation time, bowel sound recovery time, hospitalization costs, and duration) were collected and compared between the 2 groups. RESULTS: The gastrointestinal function score decreased significantly after treatment, and the changes were significantly different between the Tongfu powder group and the mosapride group (P<0.05). Significantly shorter time to first defecation and bowel sound recovery was observed in the Tongfu powder group versus the mosapride group (P<0.05). The improvements of IL-2, IL-4, intestinal fatty acid binding protein, motilin, and vasoactive intestinal peptide in the Tongfu powder group were higher than those in the mosapride group (P<0.05). There were no significant differences in hospital cost and length of hospital stay between the 2 groups. CONCLUSION: This study suggested that Tongfu powder for external application may improve gastrointestinal function for AP patients compared with mosapride.

Structurally Diverse Sesquiterpenoids from the Endangered Ornamental Plant Michelia shiluensis.

A preliminary phytochemical investigation on the MeOH extract of the leaves and twigs of the endangered ornamental plant Michelia shiluensis led to the isolation of 16 sesquiterpenoids. The isolated compounds comprised germacrane- (1-4, 13, 14), guaiane- (5-9, 15), amorphane- (10), and eudesmane-type (11, 12, 16) sesquiterpenoids. The new structures (1-12) were elucidated by spectroscopic and computational methods, and their absolute configurations (except for 9) were assigned by single-crystal X-ray diffraction crystallographic data and/or electronic circular dichroism spectra. Shiluolides (A-D, 1-4) are unprecedented C16 or C17 homogermacranolides, and their putative biosynthetic pathways are briefly discussed. Shiluone D (8) is a rare 1,10- seco-guaiane sesquiterpenoid featuring a new ether-containing spirocyclic ring, whereas shiluone E (9) represents the first example of a 1,5-4,5-di- seco-guaiane with a rare 5,11 -lactone moiety. Shiluone F (10) is the first amorphane-type sesquiterpenoid possessing an oxetane ring bridging C-1 and C-7. Bioassay evaluations indicated that lipiferolide (13) showed noteworthy cytotoxicities toward human cancer cell lines MCF-7 and A-549, with IC50 values of 1.5 and 7.3 µM, respectively. Shiluone D (8) exerted inhibition against protein tyrosine phosphatase 1B (IC50: 46.3 µM).

Neuroprotective effects of Magnoliae Flos extract in mouse hippocampal neuronal cells.

Magnoliae Flos (MF) is a traditional medicinal herb used for managing rhinitis, sinusitis and headache. The purpose of the present study was to determine the neuroprotective effect of MF against glutamate-induced oxidative stress and to assess the underlying mechanism. Glutamate is a major endogenous excitatory neurotransmitter in the brain and contributes to the development of neurodegenerative diseases by excessive activation. MF extract was subjected to a neuroprotective effect assay in HT22 mouse hippocampal cells. The mechanism underlying the neuroprotective effect of MF extract was evaluated by assaying reactive oxygen species (ROS) levels, intracellular Ca2+ levels, mitochondrial membrane potential, glutathione level and antioxidant enzyme activity in HT22 cells. MF extract significantly decreased glutamate-induced death of HT22 cells (80.83 ± 7.34% relative neuroprotection). MF extract reduced the intracellular ROS and Ca2+ levels and increased the glutathione level and glutathione reductase and glutathione peroxide activities. Moreover, MF extract attenuated the mitochondrial membrane potential in HT22 cells. These results suggested that MF extract exerts a neuroprotective effect against oxidative stress HT22 cells, which was mediated by its antioxidant activity.

Antibacterial and Antioxidant Metabolites of Diaporthe spp. Isolated from Flowers of Melodorum fruticosum.

Fifty-two strains of endophytic fungi were isolated from flowers of the medicinal plant Melodorum fruticosum. Seven genera were identified including Alternaria, Aspergillus, Colletotrichum, Diaporthe, Fusarium, Greeneria and Nigrospora. All strains were cultured for 30 days and further macerated in ethyl acetate solvent for 3 days. The obtained fungal extracts were examined for antibacterial activity using agar disc diffusion against nine pathogenic bacteria: Staphylococcus aureus, Bacillus subtilis, B. cereus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Shigella flexneri, Vibrio cholerae and V. parahaemolyticus. Forty-three fungal extracts exhibited antibacterial activity against at least one tested pathogen. The antioxidant properties of all extracts were also investigated by DPPH scavenging assay. Sixteen extracts displayed high antioxidant capacity (IC50 ranging from 10 to 50 µg/mL) when compared to the gallic acid and trolox standards (IC50 of 12.46 and 2.55 µg/mL, respectively). The crude extracts of Diaporthe sp. MFLUCC16-0682 and Diaporthe sp. MFLUCC16-0693 exhibited notable antibacterial and antioxidant activities. Analysis of chemical composition using gas chromatography-mass spectrometry suggested that the observed antibacterial activity of the two Diaporthe spp. was possibly due to the presence of abienol, 4-methoxy stilbene, phenethyl cinnamate and 2Z,6Z-farnesal, while their potential antioxidant activity could be attributed to phenolic compounds, such as benzene acetaldehyde, benzyl benzoate, salicylaldehyde, benzoin and benzyl cinnamate. The results suggest that the genus Diaporthe is a potential source of metabolites that can be used in a variety of applications.

Angiostatic actions of capsicodendrin through selective inhibition of VEGFR2-mediated AKT signaling and disregulated autophagy.

Angiogenesis is the formation of new blood vessels from existing vasculature critical for embryonic development and vascular remodeling. Its dysregulation underlies numerous pathologic states ranging from ischemia to tumor growth and as such identifying new targeted- therapies is of significant interest for angiogenesis-based medicine. Here we evaluated the potential angiostatic properties of capsicodendrin (CPCD), a natural compound isolated from Cinnamosma macrocarpa, a plant belonging to the Malagasy Cinnamosma. CPCD potently inhibits endothelial proliferation, migration and capillary tube formation at nanomolar to low micromolar concentrations without inducing cytotoxic effects. We show that CPCD directly inactivates VEGFR2 and downstream AKT signaling, thereby strongly inducing autophagy as determined by increased expression of beclin1, autophagy-related gene (Atg) 3, Atg5 and LC3 cleavage. Ectopic AKT overexpression counteracts the inhibitory effects of CPCD on proliferation and capillary tubule formation. Importantly, CPCD treatment in vivo inhibits sprouting angiogenesis as evidenced by strongly reduced intersegmental vessel (ISV) sprouting and subintestinal vessel (SIV) formation during zebrafish embryonic development, and correlates with increased presence of LC3II along the ISVs despite overall reduced vasculature. These findings demonstrate CPCD as a potent inhibitor of the VEGFR2/AKT pathway at nanomolar concentrations and inducer of autophagy-related angiostatic effects.

Microencapsulation of white champaca (Michelia alba D.C.) extract using octenyl succinic anhydride (OSA) starch for controlled release aroma.

The objective of the study was to optimise the encapsulation of Michelia alba D.C. (MAD) extract using octenyl succinic anhydride (OSA) starch. The MAD extract (5-10 g/100 g of dry starch) and the OSA starch (25-100 g/100 ml of water) was used in microcapsule preparation and analysed for the physicochemical and encapsulation properties. The optimised formula using the MAD extract and the OSA starch were 15.00 g/100 g of dry starch and 96.32 g/100 g water, which provided the highest in yield recovery (40.65% ± 0.99) and encapsulation efficiency (68.91% ± 1.50), with the lowest moisture content (3.19% ± 0.06) and water activity (0.236 ± 0.004). The aroma release from the optimum encapsulated powder in simulated artificial saliva fluid (SSF) suggested that linalool retention in microcapsules was higher than verbenone and 2-methyl butanoic acid. This study shows that the optimised formulation of MAD encapsulated flavour powder was found to be effective for controlling the aroma release.