Essential Oils of The Leaves of Syzygium hemilamprum (F. Muell.) Craven & Biffin.: Chemical Analysis, Antimicrobial, Mosquito Larvicidal, ADMET, and Molecular Docking Studies.

Chemical constituents from essential oil and n-hexane extract of S hemilamprum leaves were first identified. The obtained essential oil was dominated by monoterpene hydrocarbons (71.55%), and their oxygenated derivatives (20.2%), in which ß-pinene (31.5%), limonene (19.4%), α-pinene (12.3%), and α-terpineol (7.4%) were the principal agents. The n-hexane extract was characterized by monoterpene hydrocarbons (42.2%) and non-terpenic compounds (34.0%) with ß-pinene (32.8%), and n-hexadecane (10.2%) being the major compounds. Both two samples showed antimicrobial activity against the Gram (+) bacterium Staphylococcus aureus ATCC 6538, the Gram (-) bacterium Pseudomonas aeruginosa ATCC 9027, and the yeast Saccharomyces cerevisiae ATCC 2601 with the same MIC value of 128 µg/mL. Remarkably, they strongly inhibited mosquito larvicidal activity against Aedes aegypti and Culex quinquefasciatus larvae with the LC50 and L90 values of less than 20 µg/mL for 24 and 48 h treatments. A molecular docking study suggested limonene and α-terpineol as potent inhibitors of the mosquito odorant binding protein. In silico study on the physicochemical and ADMET properties of the main components of essential oils was also conducted.

Undescribed Triterpenes from the Leaves of Syzygium myrsinifolium with Their α-Glucosidase and α-Amylase Inhibition Activity.

Two undescribed triterpenes, syzyfolium A (1) and syzyfolium B (2), together with twelve known compounds, terminolic acid (3), actinidic acid (4), piscidinol A (5), threo-dihydroxydehydrodiconiferyl alcohol (6), lariciresinol-4-O-ß-D-glucoside (7), icariol A2 (8), 14ß,15ß-dihydroxyklaineanone (9), garcimangosone D (10), (+)-catechin (11), myricetin-3-O-α-L-rhamnopyranoside (12), quercitrin (13), and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-ß-D-glucopyranoside (14) were isolated from the leaves of Syzygium myrsinifolium. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 3 and 4 inhibited significantly α-glucosidase with IC50 values of 23.99 and 36.84, respectively, and compounds 1 and 2 inhibited significantly α-amylase with IC50 values of 35.48 and 43.65 µM, respectively.

Syzygium cumini ameliorates high fat diet induced glucose intolerance, insulin resistance, weight gain, hepatic injury and nephrotoxicity through modulation of PTP1B and PPARγ signaling.

Metabolic disorders are majorly associated with insulin resistance and an impaired glucose tolerance. Since, many of the currently available drugs exhibit adverse effects and are resistant to therapies, natural products are a promising alternate in the alleviation of complex metabolic disorders. In the current study, Syzygium cumini methanolic extract (SCE) was investigated for its anti-diabetic and anti-adipogenic potential using C57BL/6 mice fed on high fat diet (HFD). The HFD fed obese mice were treated with 200 mg/kg SCE and compared with positive controls Metformin, Pioglitazone and Sodium Orthovanadate. The biometabolites in SCE were characterized using Fourier transform infrared and gas chromatography and mass spectroscopy. A reduction in blood glucose levels with improved insulin sensitivity and glucose tolerance was observed in SCE-treated HFD obese mice. Histopathological and biochemical investigations showed a reduction in hepatic injury and nephrotoxicity in SCE-administered HFD mice. Results showed inhibition of PTP1B and an upregulation of IRS1 and PKB-mediated signaling in skeletal muscle. A significant decrease in lipid markers such as TC, TG, LDL-c and VLDL-c levels were observed with increased HDL-c in SCE-treated HFD mice. A significant decrease in weight and adiposity was observed in SCE-administered HFD mice in comparison to controls. This decrease could be due to the partial agonism of PPARγ and an increased expression of adiponectin, an insulin sensitizer. Hence, the dual-modulatory effect of SCE, partly due to the presence of 26% Pyrogallol, could be useful in the management of diabetes and its associated maladies.

Antimicrobial Activity of Syzygium aromaticum Essential Oil in Human Health Treatment.

The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case of multidrug-resistant (MDR) microorganisms-mediated infections. The drug resistance phenomenon is today a global problem, so it is important to have available substances able to counteract MDR infections. Syzygium aromaticum (L.) Merr. & L.M. Perry (commonly called clove) is a spice characterized by several biological properties. Clove essential oil (EO) consists of numerous active molecules, being eugenol as the principal component; however, other compounds that synergize with each other are responsible for the biological properties of the EO. S. aromaticum is traditionally used for bowel and stomach disorders, cold and flu, oral hygiene, tooth decay, and for its analgesic action. Its EO has shown antioxidant, antimicrobial, anti-inflammatory, neuro-protective, anti-stress, anticancer, and anti-nociceptive activities. This review aims to investigate the role of E. S. aromaticum EO in the counteraction of MDR microorganisms responsible for human disorders, diseases, or infections, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Candida albicans, Giardia lamblia, Streptococcus mutans, Porphyromonas gingivalis, and Klebsiella pneumoniae. This study might orient clinical researchers on future therapeutic uses of S. aromaticum EO in the prevention and treatment of infectious diseases.

Identification of Novel -Glucosidase Inhibitors from Syzygium jambos (L.) Using Spectroscopy and Molecular Docking.

Fruits of Syzygium jambos (L.) are recognized as a "food", exhibiting significant antidiabetic activities. However, the α-glucosidase inhibition of the components from Syzygium jambos (L.) have not yet been investigated. In this study, a total of 14 compounds were isolated from Syzygium jambos (L.) Alston, eight of which showed significant inhibitory effects on α-glucosidase, with IC50 values in the range of 0.011-0.665 mM. Notably, compounds 1-3 (IC50: 0.013, 0.011 and 0.030 mM, respectively) exhibited much stronger activity than acarbose (IC50: 2.329 ± 0.109 mM). The enzyme kinetics study indicated that compound 1 was an uncompetitive inhibitor, and compounds 2-8 were mixed-type inhibitors. Moreover, the interactions between compounds and α-glucosidase were investigated by molecular docking, which further revealed that the number of olefin double bonds and 2-COOH of heptadeca-phenols had a notable effect on the α-glucosidase inhibitory activity. This study demonstrated that Syzygium jambos (L.) fruit might serve as a functional food for the prevention of diabetes mellitus.

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Underground trees inhabit varied environmental extremes across the Afrotropics.

BACKGROUND AND AIMS: Geoxyles, a distinctive feature of Afrotropical savannas and grasslands, survive recurrent disturbances by resprouting subshrub branches from large belowground woody structures. Underground trees are a type of geoxyle that independently evolved within woody genera of at least 40 plant families in Africa. The environmental limits and determinants of underground tree biogeography are poorly understood with the relative influence of frost and fire debated in particular. We aim to quantify variability in the niche of underground tree species relative to their taller, woody tree/shrub congeners. METHODS: Using occurrence records of four Afrotropical genera, Parinari (Chrysobalanaceae), Ozoroa (Anacardiaceae), Syzygium (Myrtaceae) and Lannea (Anacardiaceae), and environmental data of nine climate and disturbance variables, the biogeography and niche of underground trees are compared with their open and closed ecosystem congeners. KEY RESULTS: Along multiple environmental gradients and in a multidimensional environmental space, underground trees inhabit significantly distinct and extreme environments relative to open and closed ecosystem congeners. Niche overlap is low among underground trees and their congeners, and also among underground trees of the four genera. Of the study taxa, Parinari underground trees inhabit hotter, drier and more seasonal environments where herbivory pressure is greatest. Ozoroa underground trees occupy relatively more fire prone environments, while Syzygium underground trees sustain the highest frost frequency and occur in relatively wetter conditions with seasonal waterlogging. Lannea underground trees are associated with the lowest temperatures, highest precipitation, and varying exposure to disturbance. CONCLUSIONS: While underground trees exhibit repeated convergent evolution, distinct environments shape the ecology and biogeography of this iconic plant functional group. The multiplicity of extreme environments related to fire, frost, herbivory and waterlogging that different underground tree taxa occupy, and the distinctiveness of these environments, should be recognised in the management of African grassy ecosystems.

Analyzing trait-climate relationships within and among taxa using machine learning and herbarium specimens.

PREMISE: Continental-scale leaf trait studies can help explain how plants survive in different environments, but large data sets are costly to assemble at this scale. Automating the measurement of digitized herbarium collections could rapidly expand the data available to such studies. We used machine learning to identify and measure leaves from existing, digitized herbarium specimens. The process was developed, validated, and applied to analyses of relationships between leaf size and climate within and among species for two genera: Syzygium (Myrtaceae) and Ficus (Moraceae). METHODS: Convolutional neural network (CNN) models were used to detect and measure complete leaves in images. Predictions of a model trained with a set of 35 randomly selected images and a second model trained with 35 user-selected images were compared using a set of 50 labeled validation images. The validated models were then applied to 1227 Syzygium and 2595 Ficus specimens digitized by the National Herbarium of New South Wales, Australia. Leaf area measurements were made for each genus and used to examine links between leaf size and climate. RESULTS: The user-selected training method for Syzygium found more leaves (9347 vs. 8423) using fewer training masks (218 vs. 225), and found leaves with a greater range of sizes than the random image training method. Within each genus, leaf size was positively associated with temperature and rainfall, consistent with previous observations. However, within species, the associations between leaf size and environmental variables were weaker. CONCLUSIONS: CNNs detected and measured leaves with levels of accuracy useful for trait extraction and analysis and illustrate the potential for machine learning of herbarium specimens to massively increase global leaf trait data sets. Within-species relationships were weak, suggesting that population history and gene flow have a strong effect at this level. Herbarium specimens and machine learning could expand sampling of trait data within many species, offering new insights into trait evolution.

Enantiomeric pairs of macrocyclic acylphloroglucinols from Syzygium szemaoense.

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.

New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production.

A new isopropyl chromone (1) and a new flavanone glucoside (2) together with eleven known compounds (3-13) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one (1), 5,7-dihydroxyflavanone 7-O-ß-D-(6''-O-galloylglucopyranoside) (2), strobopinin (3), demethoxymatteucinol (4), pinocembrin-7-O-ß-D-glucopyranoside (5), (2S)-hydroxynaringenin-7-O-ß-D-glucopyranoside (6), afzelin (7), quercetin (8), kaplanin (9), endoperoxide G3 (10), grasshopper (11), vomifoliol (12), litseagermacrane (13) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1, 2, 5, 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC50 values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 µM, respectively, while the IC50 values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 µM, compared to that of the positive control, NG -monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 32.50±1.00 µM.

Clove Buds Volatile Compounds: Inhibitory Activity on Mycobacterium Growth and Molecular Docking on Mmr Efflux Pump Drug Resistance.

Syzygium aromaticum is used in traditional and modern medicine for its various and outstanding pharmacological properties. Here, we studied the chemical composition of hexane extract and non-polar fractions (NPF) obtained from the maceration and fractionation of clove buds, in order to evaluate their in vitro antimycobacterial activity, as well as their contribution against efflux pump (EP) resistance through molecular docking experiments. The gas chromatography-mass spectrometry (GC-MS) analysis of the volatile profiles revealed the presence of eugenol, followed by eugenyl acetate, and ß-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H37 Rv strain was sensitive to all volatile samples at concentration range between 10 and 100 µg/mL. The NPF of ethanol extract was the best inhibitor with a MIC=10 µg/mL. The in silico study revealed a strong binding affinity between eugenol and Mmr EP protein (-8.1 Kcal/mol), involving two binding modes of hydrogen bond and π-alkyl interactions. The non-polarity character of clove volatile constituents, and their potential additive or synergistic effects could be responsible for the antimycobacterial activity. In addition, these findings suggest the benefic effect of eugenol in the management of mycobacterium drug resistance, whether as potential inhibitor of Mmr drug EP, or modulator during combination therapy.

Undescribed Phenolic Glycosides from Syzygium attopeuense and Their Inhibition of Nitric Oxide Production.

Four undescribed phenolic glycosides including three stilbene derivatives (1 and 3) and sodium salt of 3 (2), and a chalcone glycoside (4), together with thirteen known compounds (5-17) were isolated from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry. Their chemical structures were elucidated to be (Z)-gaylussacin (1), 6''-O-galloylgaylussacin sodium salt (2), 6''-O-galloylgaylussacin (3), 4'-O-[ß-D-glucopyranosyl-(1→6)-glucopyranosyl]oxy-2'-hydroxy-6'-methoxydihydrochalcone (4), gaylussacin (5), pinosilvin 3-O-ß-D-glucopyranoside (6), myricetin-3-O-(2''-O-galloyl)-α-L-rhamnopyranoside (7), myricetin-3-O-(3''-O-galloyl)-α-L-rhamnopyranoside (8), myricetin-3-O-α-L-rhamnopyranoside (9), quercitrin (10), myricetin-3-O-ß-D-glucopyranoside (11), myricetin-3-O-ß-D-galactopyranoside (12), quercetin 3-O-α-L-arabinopyranoside (13), myricetin-3-O-2''-O-galloyl)-α-L-arabinopyranoside (14), (+)-gallocatechin (15), (-)-epigallocatechin (16), and 3,3',4'-trimethoxyellagic acid 4-O-ß-D-glucopyranoside (17) by the analysis of HR-ESI-MS, 1D and 2D NMR spectra in comparison with the previously reported data. Compounds 1-3, 5, and 6 significant inhibition of NO production in LPS-activated RAW264.7 cells, with IC50 values ranging from 18.37±1.38 to 35.12±2.53 µM, compared to a positive control (dexamethasone) with an IC50 value of 15.37±1.42 µM.

First Report of Colletotrichum siamense Causing Anthracnose on Syzygium grijsii in China.

Syzygium grijsii is an evergreen shrub belonging to the family Myrtaceae, and widely cultivated in southern China as an ornamental medicinal plant. In May 2022, anthracnose symptoms were observed on leaves of S. grijsii planted in a nursery (N22°55'46″, E108°22'11″) in Nanning, Guangxi Province, China. More than 30% of leaves were infected. Initially, irregular brown spots (1 to 2 mm in diameter) formed on the leaves, with a slight depression in the center, then expanded into large, dark-brown lesions. In severe infections, lesions coalesced and covered the entire leaf, causing wilt and fall off the plant. To identify the pathogen, 30 diseased leaves were collected from five plants. Leaf tissues (5 × 5 mm) were cut from the infected margins, surface sterilized (75% ethanol 10 s, 2% NaClO 5 min, rinsed three times with sterile water), then placed on potato dextrose agar (PDA), and incubated at 28℃ in darkness. After 5 days, 16 fungal isolates with similar morphology were obtained from 30 plated tissues. Colonies on PDA were abundant with grayish-white fluffy mycelia, and yellowish-white on the back. Conidia were one-celled, hyaline, smooth-walled, cylindrical with narrowing at the center, blunt at the ends, and ranged from 11.35 to 22.14 × 4.88 to 7.67 µm (n=100). Morphological characteristics of the isolates were similar to the descriptions of Colletotrichum sp. (Prihastuti et al. 2009). Five representative isolates (Cs34, Cs31, Cs32, Cs33 and Cs35), which were preserved in the Guangxi Key Laboratory of Biology for Crop Diseases and Insect Pests, were selected for molecular identification. The ITS (Nos. OQ618199, OR539576 to OR539579), TUB2 (Nos. OQ630972, OR545076 to OR545079), ACT (Nos. OQ685919, OR545060 to OR545063), CHS-1 (Nos. OQ685917, OR545068 to OR545071), GAPDH (Nos. OQ685916, OR545072 to OR545075), and CAL (Nos. OQ685918, OR545064 to OR545067) sequences showed >99% identity to those of Colletotrichum siamense ex-type culture ICPM 18578 (Nos. JX010171, JX009924, JX009714 and JX009518) and strain C1315.2 (Nos. JX009865 and JX010404) in GenBank. Multigene phylogenetic analyses (ITS, TUB, ACT, CHS-1, GAPDH, and CAL) using the Maximum likelihood method indicated that the 5 isolates were clustered with C. siamense. To perform pathogenicity tests, three one-year-old healthy S. grijsii plants were inoculated with conidial suspension (1 × 106 conidia/ml) of isolate Cs34 by brushing gently with a soft paintbrush, each plant was inoculated with 3 leaves. The same number of plants were inoculated with sterile water as control, and pathogenicity tests were performed three times. All plants were kept in an artificial climatic box at 28℃, with a 90% humidity and a 12 h light/dark cycle. Similar symptoms to those of the field were observed on all inoculated leaves after 5 days, whereas controls remained symptomless. Reisolated fungi from the diseased leaves were confirmed to be C. siamense by morphology and molecular characterization, confirming Koch's postulates. C. siamense has been reported causing anthracnose on Crinum asiaticum (Khoo et al. 2022) in Malaysia, and Erythrina crista-galli in China (Li et al. 2021). To our knowledge, this is the first report of C. siamense causing anthracnose on S. grijsii in China. The results of pathogen identification provide crucial information for control strategies of the disease.

First report of Colletotrichum siamense as a causal agent of anthracnose on wax apple (Syzygium samarangense) in China.

Wax apple (Syzygium samarangense) is an important fruit tree widely cultivated in China. Yield losses are usually serious due to different diseases among which anthracnose (Colletotrichum spp.) is one of the most damaging (He et al, 2019). This disease was found in Yunnan, China and an average incidence of 56.7% diseased leaves was recorded in21 orchards surveyed in July2021. The disease lesions on leaves were circular, angular or oval (7.2-15.6 mm), with whitish center and brown outer area surrounded by a yellow halo; irregular spots or blight areas formed later. It can also infect fruits forming pale-brown, circular and sunken spots before harvest and rot of stored fruits. Diseased leaves were sampled from orchards in Ximeng (N117.78oE39.89o) and Ninger (E101.04oN23.05o) counties of Yunnan for fungal isolation; three and five pure isolates were recovered from Ximeng (LWTJ1-LWTJ3) and Ninger (LB4-LB8) samples, respectively, by plating disinfested tissue (surface-sterilized with 2% NaClO3) on potato dextrose agar (PDA) followed by hyphal tip purification and incubation at 25oC. Two repeated tests following Koch's postulates were conducted to verify pathogenicity of the eight isolates. In each test, three healthy seedlings per isolate were sprayed with conidia suspenson (2.26×105cfu/mL) until runoff from leaves while control plants were sprayed with sterile water. The plants were kept in the dark at RH100 for 24 h in a black box and then in a growth chamber (28oC, RH>90% and lighting 12h/d). Detached fruits were inoculated with mycelial discs on the puncture-wound surface. Anthracnose symptoms developed on all seedlings and fruits inoculated with LWTJ2 or LB4 isolates, which were re-isolated from lesions of inoculated leaf/fruit, completing Koch's postulates. Control plants were healthy and symptomless. LWTJ2 and LB4 isolates were morphologically the same: the colonies on PDA were circular, pale-white, with cottony surface and readily forming orange conidium masses. The hyphae were hyaline, septate, branched mostly in near right angles. The conidia were hyaline, one-celled, smooth-walled, cylindrical with round ends, 9.8-17.5 (av.13.8) µm×4.4-6.5 (5.6) µm. The teleomorph was not observed in culture or on orchard trees. The morphological characters were consistent with those of C. siamense described by Weir et al (2012). The internal transcribed spacer region (ITS) was amplified from the two isolates by PCR and sequenced (1990) and were 545 bp in length (OL963924 & OL413460). BLAST analysis showed that both were 100% identical and they shared 99.08% identity with C. siamense WZ-365 from the ITS region (MN856443).The Tub2 (788 bp, ON637119) and Cal (768 bp, ON622249) genes (Weir et al, 2012) of LB4 were also obtained and they shared closest identity (99.45% & 100%) with those of C. siamense WZ-365 as well. Phylogenetic tree (neighbor-joining) analysis of the concatenated sequence of ITS, Tub2 and Cal genes of LB4 and those of related Colletotrichum spp. showed that LB4 clustered IN the same end-branch with C. siamense ICMP18578 (Bootstrap sup. = 98%). Thus, C. siamense was identified as the pathogen of wax apple anthracnose in Yunnan. It caused anthracnose on other crops as oranges and cacao (Azad et al, 2020). Also, C. fructicola and C. syzygicola were identified as pathogens of wax apple anthracnose in Thailand (Al-Obaidi et al, 2017). To our knowledge, this is the first report of C. siamense causing wax apple anthracnose in China.

Phloroglucinol derivatives with α-glucosidase inhibitory activities from Syzygium fluviatile.

Four new phloroglucinol derivatives (1 - 4) were isolated from the leaves of Syzygium fluviatile. Their structures were elucidated by means of extensive spectroscopic data. Among them, compounds 1 and 3 showed significant inhibitory activity against α-glucosidase with IC50 values of 10.60 and 5.07 µM, respectively. The structure-activity relationship was also discussed briefly.

Multi-Targeting Neuroprotective Effects of Syzygium aromaticum Bud Extracts and Their Key Phytocompounds against Neurodegenerative Diseases.

Alzheimer's disease (AD) is a neurodegenerative disease that causes a gradual loss of normal motor and cognitive function. The complex AD pathophysiology involves various factors such as oxidative stress, neuroinflammation, amyloid-beta (Aß) aggregation, disturbed neurotransmission, and apoptosis. The available drugs suffer from a range of side effects and are not able to cover different aspects of the disease. Therefore, finding a safer therapeutic approach that can affect multiple targets at a time is highly desirable. In the present study, the underlying neuroprotective mechanism of an important culinary spice, Syzygium aromaticum (Clove) extract, and major bioactive compounds were studied in hydrogen peroxide-induced oxidative stress in human neuroblastoma SH-SY5Y cell lines as a model. The extracts were subjected to GC-MS to identify important bioactive components. The extracts and key bio-actives reduced reactive oxygen species (ROS), restored mitochondrial membrane potential (MMP), and provided neuroprotection from H2O2-induced oxidative stress in cell-based assays due to the antioxidant action. They also reduced lipid peroxidation significantly and restored GSH content. Clove extracts have also displayed anti-acetylcholinesterase (AChE) activity, anti-glycation potential, and Aß aggregation/fibrilization inhibition. The multitarget neuroprotective approach displayed by Clove makes it a potential candidate for AD drug development.

Essential Oils of Five Syzygium Species Growing Wild in Vietnam: Chemical Compositions and Antimicrobial and Mosquito Larvicidal Potentials.

The essential oils of five Vietnamese Syzygium species (Syzygium levinei, S. acuminatissimum, S. vestitum, S. cumini, and S. buxifolium) were first hydro-distilled and analyzed using GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry). Monoterpene hydrocarbons, sesquiterpene hydrocarbons, and oxygenated sesquiterpenoids were the main chemical classes in these oils. All these essential oils showed good-excellent antimicrobial activities against Gram-positive bacteria Enterococcus faecalis, Staphylococcus aureus, and Bacillus cereus, and the yeast Candida albicans. S. levinei leaf essential oil, rich in bicyclogermacrene (25.3%), (E)-ß-elemene (12.2%), (E)-caryophyllene (8.2%), and ß-selinene (7.4%), as well as S. acuminatissimum fruit essential oil containing (E)-caryophyllene (14.2%), α-pinene (12.1%), caryophyllene oxide (10.9%), ß-selinene (10.8%), α-selinene (8.0%), and α-humulene (5.7%), established the same MIC value of 8 µg/mL against E. faecalis and B. cereus, which were much better than the positive control streptomycin (MIC 128-256 µg/mL). The studied essential oils showed the potential to defend against mosquitoes since they caused the 24 and 48 h LC50 values of less than 50 µg/mL against the growth of Culex quinquefasciatus and Aedes aegypti larvae. Especially, S. buxifolium leaf essential oil strongly inhibited Ae. aegypti larvae with 24 and 48 h LC50 values of 6.73 and 6.73 µg/mL, respectively, and 24 and 48 h LC90 values of 13.37 and 10.83 µg/mL, respectively. These findings imply that Vietnamese Syzygium essential oils might have potential for use as supplemental antibacterial agents or as "green" alternatives for the control of mosquitoes.

Comparative Study of Essential Oils from Different Organs of Syzygium cumini (Pamposia) Based on GC/MS Chemical Profiling and In Vitro Antiaging Activity.

Syzygium cumini L. is an evergreen tree belonging to family Myrtaceae, employed for different traditional uses like diabetes, inflammation, and fever. The current study aimed to compare the chemical compositions of the essential oils (EOs) isolated from different organs of Syzygium cumini (leaves (Scl), fruits (Scf), seeds (Scs), and bark (Scb)) using a GC/MS analysis. Also, a chemometric analysis was applied to explore the main similarities and differences among different organs using a Principal Component Analysis (PCA) and a hierarchal cluster analysis (HCA). Furthermore, in vitro antiaging activities were investigated via anti-collagenase, anti-elastase, and anti-hyaluronidase assays. The GC-MS analysis revealed 82 compounds representing 92.13%, 99.42%, 100%, and 92.97% in Scl, Scf, Scs, and Scb, respectively. The predominant components were α-pinene, ß-pinene, (E)-ß-caryophyllene, α-caryophyllene, caryophyllene oxide, and α-humulene epoxide II with variable percentages. All EOs were positioned on positive PC1, except for Scs, which was positioned on the negative side in a separate quadrant. The HCA dendrogram displayed the closeness of Scl and Scb, which was not clearly recognized in the PCA score plot. Moreover, the Scs oils were totally discriminated from other parts. The Scl and Scs oils showed superior anti-collagenase, anti-elastase, and anti-hyaluronidase activities. Thus, S. cumini oils should be considered for cosmetic preparations to retard skin aging manifestations.

Synergistic combination of Cinnamomum verum and Syzygium aromaticum treatment for cutaneous leishmaniasis and investigation of their molecular mechanism of action.

Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major. However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.

The α-glucosidase inhibitory activity of avicularin and 4-O-methyl gallic acid isolated from Syzygium myrtifolium leaves.

Diabetes Mellitus is the main cause of death on a global scale. In 2019, there were 463 million people with diabetes, and WHO predicts that by 2030, there will be 578 million. As an antidiabetic agent, α-glucosidase inhibitors are one of the methods employed to reduce the prevalence of diabetes. Diabetes is traditionally treated with Syzygium as a primary material, medicine, fruit, ornamental plant, and source of carpentry. This investigation aimed to examine the inhibitory effect of seven species of Syzygium against α-glucosidase enzyme using an in vitro assay and isolate active substances and ascertain their concentrations in each sample. As a solvent, ethanol was used in maceration to extract the substance. Afterward, the extract underwent a series of fractionation techniques, including liquid-liquid extraction, vacuum liquid chromatography, column chromatography, and preparative Thin Layer Chromatography (TLC) for purification and isolation. The compound's structures were elucidated using TLC, UV-Visible spectrophotometry, and nuclear magnetic resonance (NMR) spectroscopy. Based on concentrations of 100 and 200 µg/mL, Syzygium myrtifolium exhibited the most significant inhibitory effect, followed by other species of Syzygium. The proportion of ethyl acetate had the strongest activity (IC50 0.40 ± 0.02 µg/mL) contrasted to positive control acarbose (IC50 55.39 ± 0.67 g/mL) and quercitrin (IC50 6.47 ± 0.40 µg/mL). Avicularin and 4-O-methyl gallic acid were discovered in the ethyl acetate fraction of Syzygium myrtifolium with IC50 values of 17.05 ± 0.75 µg/mL and 25.19 ± 0.21 µg/mL, respectively. As α-glucosidase inhibitory, the results of this study indicate Syzygium myrtifolium can be used as a dietary supplement to manage hyperglycemia.