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.

Insecticidal and Attractant Activities of Magnolia citrata Leaf Essential Oil against Two Major Pests from Diptera: Aedes aegypti (Culicidae) and Ceratitis capitata (Tephritidae).

In this study, Magnolia citrata Noot and Chalermglin (Magnoliaceae) essential oil (MCEO) was evaluated for insecticidal activity against the yellow fever mosquito Aedes aegypti and attractant activity for the Mediterranean fruit fly Ceratitis capitata. The leaves of Magnolia citrata (Gioi chanh) were collected from northwestern Vietnam, and the water-distilled MCEO was analyzed by gas-chromatography and mass spectrometry (GC-MS). The major constituents of MCEO were identified as linalool 19%, geranial 16%, citronellal 14%, neral 14%, and sabinene 12%. MCEO showed 100% mortality at 1 µg/µL against 1st instar larvae of Ae. aegypti (Orlando strain, ORL), and the oil exhibited 54% (ORL) and 68% (Puerto Rico strain) mortality at 5 µg/mosquito against Ae. aegypti adult females. Initial screens showed that MCEO had weak insecticidal activity compared to the positive control permethrin. In bioassays with sterile male C. capitata, MCEO exhibited moderately strong attraction, comparable to that observed with a positive control, Tetradenia riparia essential oil (TREO). Herein, the insecticidal and attractant activities of MCEO are reported for the first time.

Dilignans with a Chromanol Motif Discovered by Molecular Networking from the Stem Barks of Magnolia obovata and Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activity.

Natural products have been fundamental materials in drug discovery. Traditional strategies for observing natural products with novel structure and/or biological activity are challenging due to large cost and time consumption. Implementation of the MS/MS-based molecular networking strategy with the in silico annotation tool is expected to expedite the dereplication of secondary metabolites. In this study, using this tool, two new dilignans with a 2-phenyl-3-chromanol motif, obovatolins A (1) and B (2), were discovered from the stem barks of Magnolia obovata Thunb. along with six known compounds (3-8), expanding chemical diversity of lignan skeletons in this natural source. Their structures and configurations were elucidated using spectroscopic data. All isolates were evaluated for their PCSK9 mRNA expression inhibitory activity. Obovatolins A (1) and B (2), and magnolol (3) showed potent lipid controlling activities. To identify transcriptionally controlled genes by 1 along with downregulation of PCSK9, using small set of genes (42 genes) related to lipid metabolism selected from the database, focused bioinformatic analysis was carried out. As a result, it showed the correlations between gene expression under presence of 1, which led to detailed insight of the lipid metabolism caused by 1.

Chitosan packaging functionalized with Cinnamodendron dinisii essential oil loaded zein: A proposal for meat conservation.

The nanoencapsulation of essential oils for biodegradable films functionalization is a viable alternative for the production of active food packaging. In this study, the Cinnamodendron dinisii Schwanke essential oil was nanoencapsulated using zein as wall material, and applied in chitosan matrix to produce an active nanocomposite film packaging for food conservation. The chemical composition of the Cinnamodendron dinisii Schwanke essential oil showed a variety of unexplored bioactive compounds, and 1,8-cineole was the major compound. The oil nanoencapsulation produced stable and homogeneous nanoparticles with zeta potential close to 30 mV and polydispersity index lower than 0.2. The nanoparticles size showed a size variation between 70 and 110 nm. The chitosan films obtained functionalized with nanoparticles demonstrated antioxidant activity and antimicrobial activity. The active packaging containing zein nanoparticles was efficient in the conservation of ground beef, stabilizing the deterioration reactions and preserving the color.

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.

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.

An Aqueous Extract of Tuberaria lignosa Inhibits Cell Growth, Alters the Cell Cycle Profile, and Induces Apoptosis of NCI-H460 Tumor Cells.

Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared by infusion and decoction) was investigated in three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and HCT-15 (human colorectal adenocarcinoma). Both extracts inhibited the growth of these cell lines; the most potent one being the T. lignosa extract obtained by infusion in the NCI-H460 cells (GI50 of approximately 50 µg/mL). Further assays were carried out with this extract in NCI-H460 cells. At 100 µg/mL or 150 µg/mL it caused an increase in the percentage of cells in the G0/G1 phase and a decrease of cells in S phase of the cell cycle. Additionally, these concentrations caused an increase in the percentage of apoptotic cells. In agreement, a decrease in total poly (ADP-ribose) polymerase (PARP) and pro-caspase 3 levels was found. In conclusion, the T. lignosa extract obtained by infusion was more potent in NCI-H460 cells, altering the cell cycle progression and inducing apoptosis. This work highlights the importance of T. lignosa as a source of bioactive compounds with tumor cell growth inhibitory potential.

Resin from Virola oleifera Protects Against Radiocontrast-Induced Nephropathy in Mice.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event for which there is not yet a successful therapy. Increasing evidence in rodents has suggested that this disease is associated with renal tubular and vascular injury that is triggered directly by oxidative stress. In the present study, we evaluated whether the antioxidant resin from Virola oleifera (RV) could attenuate renal damage in an experimental mouse model of CIN. Adult male Swiss mice were divided into six groups and pre-treated orally with RV (10, 100 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the induction of CIN and Control group. Renal function was assessed by measuring plasma creatinine and urea levels. Additionally, renal oxidative stress and apoptosis/cell viability were determined with flow cytometry. Finally, kidney tissues were sectioned for histopathological examination. In this CIN model, pre-treatment with RV improved renal function, lowered the mortality rate, and reduced oxidative stress and apoptosis in both the medulla and cortex renal cells in a dose-dependent manner. Moreover, the RV treatment had beneficial effects on kidney histopathology that were superior to the standard treatment with N-acetylcysteine. These data suggest that because of its antioxidative and antiapoptotic effects and its ability to preserve renal function, resin from Virola oleifera may have potential as a new therapeutic approach for preventing CIN.

Biofunctional Constituents from Michelia compressa var. lanyuensis with Anti-Melanogenic Properties.

Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (-)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (-)-bornesitol and ß-sitostenone. These compounds were screened for anti-proliferation and anti-tyrosinase activities in B16F10 cells. Liriodenine, pressalanine A, (-)-bornesitol and ß-sitostenone displayed cytotoxicity at high concentration (100 µM), but liriodenine (5 µM), (-)-N-acetylanonaine (10 µM), and ß-sitostenone (5 µM) inhibit tyrosinase activity and reduce the melanin content in B16F10 cells without cytotoxicity, suggesting that liriodenine and ß-sitostenone could be safe and potentially used in cosmetic skin whitening.

Antifungal compounds produced by Colletotrichum gloeosporioides, an endophytic fungus from Michelia champaca.

In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated phytopathogenic fungi. Chemical investigation of EtOAc extracts of the endophytic fungus Colletotrichum gloeosporioides resulted in the isolation of one new compound, 2-phenylethyl 1H-indol-3-yl-acetate (1), and seven known compounds: uracil (2), cyclo-(S*-Pro-S*-Tyr) (3), cyclo-(S*-Pro-S*-Val) (4), 2(2-aminophenyl)acetic acid (5), 2(4-hydroxyphenyl)acetic acid (6), 4-hydroxy- benzamide (7) and 2(2-hydroxyphenyl)acetic acid (8). All of the compound structures were elucidated using 1D and 2D NMR and MS analyses. The antifungal and AChE inhibitory activities of compounds 1-8 were evaluated in vitro. Compound 1 exhibited promising activity against Cladosporium cladosporioides and C. sphaerospermum that was comparable to that of the positive control nystatin.

Antimicrobial Constituents of the Mature Carpels of Manglietiastrum sinicum.

Seven new compounds, including a eupodienone-type lignan (1), a dibenzocyclooctadiene-type lignan (2), three tetrahydrofuran-type lignans (3-5), and two 1-phenylbutyl benzoates (6, 7), together with six known compounds, were isolated from the mature carpels of Manglietiastrum sinicum. The structures of new compounds 1-7 were defined by spectroscopic techniques, and the absolute configuration of manglisin A (1) was determined by X-ray crystallography. Compounds 1-4 exhibited moderate antimicrobial activities (MIC values: 0.016-0.14 µM) against Staphylococcus aureus, MRSA 82(#), MRSA 92(#), MRSA 98(#), and MRSA 331(#). Compounds 2 and 3 showed weak cytotoxic activity against five human tumor cell lines.

The constituents of Michelia compressa var. formosana and their bioactivities.

Phytochemical investigation of the heartwood of Michelia compressa afforded forty-four compounds, which were identified by comparison of experimental and literature analytical and spectroscopic data. Some compounds were evaluated for their anti-inflammatory and anticancer bioactivities. The result showed that soemerine (1) and cyathisterol (2) exhibited significant nitric oxide (NO) inhibition, with IC50 values of 8.5±0.3 and 9.6±0.5 µg/mL, respectively. In addition, liriodenine (3) and oliveroline (4) exhibited cytotoxicity to human nasopharyngeal carcinoma (NPC-TW01), non-small cell lung carcinoma (NCI-H226), T cell leukemia (Jurkat), renal carcinoma (A498), lung carcinoma (A549) and fibrosarcoma (HT1080) cell lines with IC50 values in the range of 15.7-3.68 µM.

Bioactive 30-noroleanane triterpenes from the pericarps of Akebia trifoliata.

Two new 30-noroleanane triterpenes, 2α,3ß,20α-trihydroxy-30-norolean-12-en-28-oic acid (1), 2α,3ß-dihydroxy-23-oxo-30-norolean-12,20(29)-dien-28-oic acid (2), were isolated from the pericarps of Akebia trifoliata, together with four known ones, 3ß-akebonoic acid (3), 2α,3ß-dihydroxy-30-noroleana-12,20(29)-dien-28-oic acid (4), 3α-akebonoic acid (5) and quinatic acid (6). Their structures were established on the basis of detailed spectroscopic analysis, and they were all isolated from the pericarps of A. trifoliata for the first time. Compounds 3-6 showed in vitro bacteriostatic activity against four assayed Gram-positive bacterial strains. In particular 3 showed antibacterial activity toward MRSA with a MIC value 25 µg/mL, which was more potent than kanamycin (MIC 125 µg/mL). No compounds showed antibacterial activity toward the three Gram-negative bacteria tested. Compounds 4 and 5 showed interesting in vitro growth inhibitory activity against human tumor A549 and HeLa cell lines, with IC50 values ranging from 8.8 and 5.6 µM, respectively. Compounds 1, 2, 5 and 6 were further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 values from 0.035 to 0.367 mM, which were more potent than the reference compound acarbose (IC50 0.409 mM).

The pharmacological activities of (-)-anonaine.

Several species of Magnoliaceae and Annonaceae are used in Traditional Chinese Medicine. (-)-Anonaine, isolated from several species of Magnoliaceae and Annonaceae, presents antiplasmodial, antibacterial, antifungal, antioxidation, anticancer, antidepression, and vasorelaxant activity. This article provides an overview of the pharmacological functions of (-)-anonaine.

Bioactive phenolics and terpenoids from Manglietia insignis.

Four new compounds, maninsigins A-D (1-4), including two new neolignans (1-2) and two new sesquiterpenes (3-4), as well as ten known compounds (5-14), were isolated from the leaves and stems of Manglietia insignis. Their structures were established on the basis of extensive spectroscopic analyses. In addition, some compounds were tested for their cytotoxic and neurite outgrowth-promoting activities, as well as their antagonistic activity toward FXR ligand.

A review of chemical and biological profile of genus Michelia.

The genus Michelia, belonging to family Magnoliaceae, consists of about 80 plant species mainly distributed in South Asian countries. The plants of this genus have been traditionally used in curing various diseases like fever, colic, leprosy, eye disorders, inflammation, antidote for scorpion, etc. Ninety-four compounds isolated from nine species of the genus Michelia like sesquiterpenes, steroids, flavonoids, aporphines, phenols, esters, benzenoid and alkaloids have antibacterial, anticancer and antiplasmodial activities. This review presents first time detailed information on chemical and biological properties of constituents isolated from the genus Michelia.

Michelia alba extract attenuates UVB-induced expression of matrix metalloproteinases via MAP kinase pathway in human dermal fibroblasts.

Solar ultraviolet (UV) radiation can cause skin photoaging by inducing secretion of matrix metalloproteinases (MMPs). It has been reported that MMPs, especially MMP-1, -3 and -9, reduce elasticity of the dermis by degrading collagen. Polyphenols are a group of compounds that exist mainly in glycosides in the plants and they may transform to aglycone after hydrolysis. Polyphenols can inhibit MMP expression and elastase activity. In this study, we investigated the effects of Michelia alba extract (MAE) on expression and activity of MMPs in human skin fibroblast cultures after UVB exposure. The results showed that MAE and its hydrolysates (MAH) inhibited collagenase and elastase activities. In addition, MAE exhibited antioxidant activity, elevated hyaluronic acid content and inhibited UVB-induced MMP-1, MMP-3 and MMP-9 expression. In addition, the zymography assay revealed that MAE also inhibited MMP-9 activity. We also found that MAE inhibited UVB-induced ERK and JNK kinase but not p38 kinase expression, suggesting that MAE may regulate the UVB-induced expression of MMP-1, MMP-3 and MMP-9 via the ERK and JNK kinase pathway. MAE could restore total collagen synthesis reduced by UVB. The results also suggest that MAE treatment may prevent UVB-induced extracellular matrix damage by inhibiting the expression of MMP-1, MMP-3 and MMP-9 through the MAP kinase pathway. Our findings imply that MAE is an effective agent against UVB-induced photodamage.

Bioactive constituents from Michelia champaca.

(-)-Anonaine (1), (-)-asimilobine (2), (-)-nuciferine (3), (-)-anolobine (4), (-)-romerine (5), (-)-N-acetylanonaine (6), liriodenine (7), (+)-syringaresinol (8), N-trans-feruloyltyramine (9), N-cis-feruloyltyramine (10), scopoletin (11), 4-acetonyl-3,5-dimethoxy-p-quinol (12), vanillin (13), vanillic acid (14), syringic acid (15), beta-sitosterol (16) and stigmasterol (17) were isolated from branches of Michelia champaca L. In addition, a cell proliferation assay of five of the isolated compounds on human breast and lung cancer cells showed that liriodenine (7) was the strongest inhibitor.