Genomic analysis reveals genes that encode the synthesis of volatile compounds by a Bacillus velezensis-based biofungicide used in the treatment of grapes to control Aspergillus carbonarius.

Fungal control strategies based on the use of Bacillus have emerged in agriculture as eco-friendly alternatives to replace/reduce the use of synthetic pesticides. Bacillus sp. P1 was reported as a new promising strain for control of Aspergillus carbonarius, a known producer of ochratoxin A, categorized as possible human carcinogen with high nephrotoxic potential. Grape quality can be influenced by vineyard management practices, including the use of fungal control agents. The aim of this study was to evaluate, for the first time, the quality parameters of Chardonnay grapes exposed to an antifungal Bacillus-based strategy for control of A. carbonarius, supporting findings by genomic investigations. Furthermore, genomic tools were used to confirm that the strain P1 belongs to the non-pathogenic species Bacillus velezensis and also to certify its biosafety. The genome of B. velezensis P1 harbors genes that are putatively involved in the production of volatiles and hydrolytic enzymes, which are responsible for releasing the free form of aroma compounds. In addition to promote biocontrol of phytopathogenic fungi and ochratoxins, the treatment with B. velezensis P1 did not change the texture (hardness and firmness), color and pH of the grapes. Heat map and hierarchical clustering analysis (HCA) of volatiles evaluated by GC/MS revealed that Bacillus-treated grapes showed higher levels of compounds with a pleasant odor descriptions such as 3-hydroxy-2-butanone, 2,3-butanediol, 3-methyl-1-butanol, 3,4-dihydro-ß-ionone, ß-ionone, dihydroactinidiolide, linalool oxide, and ß-terpineol. The results of this study indicate that B. velezensis P1 presents desirable properties to be used as a biocontrol agent.

Correlation study on microbial communities and volatile flavor compounds in cigar tobacco leaves of diverse origins.

To elucidate the significant influence of microorganisms on geographically dependent flavor formation by analyzing microbial communities and volatile flavor compounds (VFCs) in cigar tobacco leaves (CTLs) obtained from China, Dominica, and Indonesia. Microbiome analysis revealed that the predominant bacteria in CTLs were Staphylococcus, Aerococcus, Pseudomonas, and Lactobacillus, while the predominant fungi were Aspergillus, Wallemia, and Sampaiozyma. The microbial communities of CTLs from different origins differed to some extent, and the diversity and abundance of bacteria were greater than fungi. Metabolomic analysis revealed that 64 VFCs were identified, mainly ketones, of which 23 VFCs could be utilized to identify the geographical origins of CTLs. Sixteen VFCs with OAV greater than 1, including cedrol, phenylacetaldehyde, damascone, beta-damascone, and beta-ionone, play important roles in shaping the flavor profile of CTLs from different origins. Combined with the correlation analysis, bacterial microorganisms were more closely related to key VFCs and favored a positive correlation. Bacillus, Vibrio, and Sphingomonas were the main flavor-related bacteria. The study demonstrated that the predominant microorganisms were essential for the formation of key flavor qualities in CTLs, which provided a theoretical reference for flavor control of CTLs by microbial technology. KEY POINTS: • It is the high OAV VFCs that determine the flavor profile of CTLs. • The methylerythritol phosphate (MEP) pathway and the carotenoid synthesis pathway are key metabolic pathways for the formation of VFCs in CTLs. • Microbial interactions influence tobacco flavor, with bacterial microorganisms contributing more to the flavor formation of CTLs.

Dietary supplementation with α-ionone alleviates chronic UVB exposure-induced skin photoaging in mice.

Photoaging is widely regarded as the most significant contributor to skin aging damage. It is triggered by prolonged exposure to ultraviolet (UV) light and typically manifests as dryness and the formation of wrinkles. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. In previous studies, we demonstrated that α-ionone had ameliorating effects on photoaging in both epidermal keratinocytes and dermal fibroblasts. Here, we investigated the potential anti-photoaging effects of dietary α-ionone using a UVB-irradiated male C57BL/6N mouse model. Our findings provided compelling evidence that dietary α-ionone alleviates wrinkle formation, skin dryness, and epidermal thickening in chronic UVB-exposed mice. α-Ionone accumulated in mouse skin after 14 weeks of dietary intake of α-ionone. α-Ionone increased collagen density and boosted the expression of collagen genes, while attenuating the UVB-induced increase of matrix metalloproteinase genes in the skin tissues. Furthermore, α-ionone suppressed the expression of senescence-associated secretory phenotypes and reduced the expression of the senescence marker p21 and DNA damage marker p53 in the skin of UVB-irradiated mice. Transcriptome sequencing results showed that α-ionone modifies gene expression profiles of skin. Multiple pathway enrichment analyses on both the differential genes and the entire genes revealed that α-ionone significantly affects multiple physiological processes and signaling pathways associated with skin health and diseases, of which the p53 signaling pathway may be the key signaling pathway. Taken together, our findings reveal that dietary α-ionone intervention holds promise in reducing the risks of skin photoaging, offering a potential strategy to address skin aging concerns.

Study of Glycosidically Bound Volatile Precursors as Variety Markers to Reveal Not-Allowed Practices in White Wines Winemaking.

Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) can provide identification of grape metabolites which are variety markers. White grapes are poorer in polyphenolics, and the main secondary metabolites which contribute the sensorial characteristics of wines are the glycosidically bound volatile precursors and their aglycones. The profiles of three white grape juices (Pinot grigio, Garganega, and Trebbiano) were characterized by LC/HRMS, and 70 signals of putative glycosidic terpenols, norisoprenoids, and benzenoids were identified. Four signals found only in Pinot grigio corresponded to a norisoprenoid hexose-hexose, 3-oxo-α-ionol (or 3-hydroxy-ß-damascone) rhamnosyl-hexoside, monoterpene-diol hexosyl-pentosyl-hexoside, and hexose-norisoprenoid; three signals were found only in Garganega (putative isopropyl alcohol pentosyl-hexoside, phenylethanol rhamnosyl-hexoside, and norisoprenoid hexose-hexose isomers), and a monoterpenol pentosyl-hexoside isomer only in Trebbiano. These variety markers were then investigated in juice blends of the three varieties. This approach can be used to develop control methods to reveal not-allowed grape varieties and practices in white wines winemaking.

Organ-specific volatiles from Sonoran desert Krameria flowers as potential signals for oil-collecting bees.

The evolution of flowers that offer oils as rewards and are pollinated by specialized bees represents a distinctive theme in plant-pollinator co-diversification. Some plants that offer acetylated glycerols as floral oils emit diacetin, a volatile by-product of oil metabolism, which is utilized by oil-collecting bees as an index signal for the presence of floral oil. However, floral oils in the genus Krameria (Krameriaceae) contain ß-acetoxy-substituted fatty acids instead of acetylated glycerols, making them unlikely to emit diacetin as an oil-bee attractant. We analyzed floral headspace composition from K. bicolor and K. erecta, native to the Sonoran Desert of southwestern North America, in search of alternative candidates for volatile index signals. Using solid-phase microextraction, combined with gas chromatography-mass spectrometry, we identified 26 and 45 floral volatiles, respectively, from whole flowers and dissected flower parts of these two Krameria species. As expected, diacetin was not detected. Instead, ß-ionone emerged as a strong candidate for an index signal, as it was uniquely present in dissected oil-producing floral tissues (elaiophores) of K. bicolor, as well as the larval cells and provisions from its oil-bee pollinator, Centris cockerelli. This finding suggests that the floral oil of K. bicolor is perfused with ß-ionone in its tissue of origin and retains the distinctive raspberry-like scent of this volatile after being harvested by C. cockerelli bees. In contrast, the elaiophores of K. erecta, which are not thought to be pollinated by C. cockerelli, produced a blend of anise-related oxygenated aromatics not found in the elaiophores of K. bicolor. Our findings suggest that ß-ionone has the potential to impact oil-foraging by C. cockerelli bees through several potential mechanisms, including larval imprinting on scented provisions or innate or learned preferences by foraging adults.

The apocarotenoid ß-ionone regulates the transcriptome of Arabidopsis thaliana and increases its resistance against Botrytis cinerea.

Carotenoids are isoprenoid pigments indispensable for photosynthesis. Moreover, they are the precursor of apocarotenoids, which include the phytohormones abscisic acid (ABA) and strigolactones (SLs) as well as retrograde signaling molecules and growth regulators, such as ß-cyclocitral and zaxinone. Here, we show that the application of the volatile apocarotenoid ß-ionone (ß-I) to Arabidopsis plants at micromolar concentrations caused a global reprogramming of gene expression, affecting thousands of transcripts involved in stress tolerance, growth, hormone metabolism, pathogen defense, and photosynthesis. This transcriptional reprogramming changes, along with induced changes in the level of the phytohormones ABA, jasmonic acid, and salicylic acid, led to enhanced Arabidopsis resistance to the widespread necrotrophic fungus Botrytis cinerea (B.c.) that causes the gray mold disease in many crop species and spoilage of harvested fruits. Pre-treatment of tobacco and tomato plants with ß-I followed by inoculation with B.c. confirmed the effect of ß-I in increasing the resistance to this pathogen in crop plants. Moreover, we observed reduced susceptibility to B.c. in fruits of transgenic tomato plants overexpressing LYCOPENE ß-CYCLASE, which contains elevated levels of endogenous ß-I, providing a further evidence for its effect on B.c. infestation. Our work unraveled ß-I as a further carotenoid-derived regulatory metabolite and indicates the possibility of establishing this natural volatile as an environmentally friendly bio-fungicide to control B.c.

A green, efficient and stable platform based on hyperbranched quaternized hydrothermal magnetic chitosan nanospheres integrated cytomembranes for screening drug candidates from natural products.

Compared with traditional tedious organic solvent-assisted separation process in natural medicinal chemistry, cytomembrane (CM) fishing technique became a more appealing and greener choice for screening bioactive components from natural products. However, its large-scale practical value was greatly weakened by the easy fall-off of CMs from magnetic supports, rooted in the instability of common Fe3O4 particles and their insufficient interaction with CMs. In this research, a new green biostable platform was developed for drug screening through the integration of hyperbranched quaternized hydrothermal magnetic carbon spheres (HQ-HMCSs) and CMs. The positive-charged HQ-HMCSs were constructed by chitosan-based hydrothermal carbonization onto Fe3O4 nanospheres and subsequent aqueous hyperbranching quaternization with 1,4-butanediol diglycidyl ether and methylamine. The strong interaction between HQ-HMCSs and CMs was formed via electrostatic attraction of HQ-HMCSs to negative-charged CMs and covalent linkage derived from the epoxy-amine addition reactions. The chemically stable HMCSs and its integration with CMs contributed to dramatically higher stability and recyclability of bionic nanocomposites. With the fishing of osteoblast CMs integrated HQ-HMCSs, two novel potential anti-osteoporosis compounds, narcissoside and beta-ionone, were discovered from Hippophae rhamnoides L. Enhanced osteoblast proliferation, alkaline phosphatase, and mineralization levels proved their positive osteogenesis effects. Preliminary pharmacological investigation demonstrated their potential action on membrane proteins of estrogen receptor alpha and insulin-like growth factor 1. Furthermore, beta-ionone showed apparent therapeutic effects on osteogenic lesions in zebrafish. These results provide a green, stable, cost-efficient, and reliable access to rapid discovery of drug leads, which verifiably benefits the design of nanocarbon-based biocomposites with increasingly advanced functionality.

Chemical composition and cardiotropic activity of Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is a subshrub that is widely distributed in China, Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan. The species is used in traditional medicine for the relief of symptoms connected to cardiovascular diseases like coronary heart disease or hypertension. AIM OF THE STUDY: was to validate traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary hearth diseases using in vivo models and to find active compounds responsible for the activity. MATERIALS AND METHODS: Multiple extracts were obtained from the aerial parts of Z. clinopodioides subsp. bungeana using maceration, liquid-liquid extraction, CO2 extraction and ultrasound-assisted extraction. Preliminary screening studies for the evaluation of the efficacy of Z. clinopodioides subsp. bungeana extracts on the model of hemic hypoxia were performed. The most effective samples were selected and included in the main study. Stage 2 of the study evaluated the cardiotropic activity of the selected extracts on a model of chronic heart failure. Preparations were administered to animals intragastrically once a day for 28 days. For the isolation of individual compounds plant material was extracted with 96% ethanol. The obtained crude extract was sequentially extracted with n-hexane and dichloromethane and separated by chromatography on a Diaion HP-20 column. The obtained fractions were further subjected to Sephadex LH-20 column chromatography and eluted isocratically with 96% ethanol (EtOH) to yield subfractions, which were further separated by preparative HPLC to obtain 13 individual compounds. RESULTS: Extracts obtained from Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. herb were subjected to pharmacological screening for the evaluation of their efficacy on hemic hypoxia. Based on the obtained results, out of the sixteen tested extracts two (AR and US 60%) were selected for further evaluation of their cardiotropic activity. Modeling of chronic heart failure was carried out in accordance with the following stages: 1) anesthesia with chloral hydrate at a dose of 450 mg/kg, intraperitoneally, 2) artificial ventilation of the lungs, 3) thoracotomy, 4) modeling of permanent ischemic or ischemic-reperfusion damage. Both extracts effected the indicators of contraction and output, comparable to the reference drug - Monopril. Based on the extraction methods used to obtain RAF and US60 and data from the literature, it can be assumed that they contain compounds with medium polarity, including polyphenols and terpenoids. At the next stage three previously undescribed monoterpenoid derivatives - Ziziphoric acid (1), Ziziphoroside D (2) and 6'-malonylziziphoroside A (3), along with two previously described megastigmane glucosides - blumenol C glucoside (4), blumenol C 9-O-(6'-O-malonyl-beta-D-glucopyranoside (5) and two previously described monoterpenoids 7a-hydroxymintlactone (6), 7-hydroxypiperitone (7) together with six polyphenols - pinocembrine-7-O-rutinoside (8), chrysine-7-O-rutinoside (9), acacetin-7-O-rutinoside (10), luteolin-7-O-rutinoside (11), rutin (12) and rosmarinic acid (13) were isolated from Z. clinopodioides subsp. bungeana extracts. CONCLUSION: Our results support the traditional use of Z. clinopodioides subsp. bungeana for the treatment of coronary diseases. As a result of Z. clinopodioides subsp. bungeana extracts screening in vivo, two extracts were selected as potential cardiotropic agents. Phytochemical analysis of the plant material led to the isolation of five terpenoid derivatives, two megastigmane glycosides, five flavonoids and one cinnamic acid derivative, which could be responsible for the reported biological activity. Future experiments are required to understand the mechanisms of action for the isolated compounds.

New Ionone Glycosides from the Aerial Parts of Allium sativum and Their Anti-Platelet Aggregation Activity.

The bulbs of Allium sativum known as garlic are widely used as food or seasoning. In China they have been used as a traditional Chinese medicine (TCM) since ancient times for the treatment of scabies, tuberculosis, pertussis, diarrhea and dysentery. A. sativum has reportedly shown platelet aggregation inhibition and has been used in the treatment of cardiovascular diseases. However, there are only few studies focussing on the aerial parts, which are normally discarded during harvest. In this study, two new ionone glycosides, dasuanxinosides D and E (1, 2: ), are isolated from the aerial parts together with 13 known compounds including alkanes derivatives and alkyl glycosides (3 - 15: ), which are reported for the first time from this plant. Their structures are identified by extensive NMR and HRMS analyses. The isolated compounds are evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro.

Chemical components of Aconitum barbatum var. puberulum and their cytotoxic and antibacterial activities.

Nineteen compounds, including seventeen alkaloids O-methylarmepavine (1), (S)-6-methoxy-1-(4-methoxybenzyl)-2-methyl -1,2,3,4-tetrahydroisoquinolin-7-ol (2), (+)-(IR,laR)-lahydroxymagnocurarin (3), (6R,6aS,P)-(+)-corydine (4), (+)-N-methyllaurotetanine (5), magnoflorine (6), 3-hydroxy-1,2-dimethoxy-5-methyl-5H-dibenzoindol-4-one (7), imperialine (8), crispine B (9), (S)-1-(3-methoxyphenyl)-N-methylpropan-2-amine (10), methyl 2- (acetamino)benzoate (11), 2-carboxyoxanilic acid methylester (12), 4-[2-(methoxycarbonyl) anilino]-4-oxobutanoic acid methyl ester (13), N-methylcorydaldine (14), N-methyl-6,7- dimethoxyisoquinolone (15), (5S,6R,7S,8R)-5-amino-(2Z,4Z)-1,2,3-trihybuta-2,4-dienyloxypentane- 6,7,8,9-tetraol (16), nicotinic acid (17), and two megastigmane type compounds, S(+)- dehydrovomifoliol (18) and megastigmane (19), were isolated from the Aconitum barbatum var. puberulum Ledeb. Compounds 1-3 and 5-19 were isolated from this plant for the first time, of which compound 11 was isolated from natural source for the first time. Cytotoxicity evaluation revealed that compound 5 displayed mild cytotoxicity against the Hela cell lines (IC50 13.69 ± 0.036 µM). Antibacterial activity evaluation revealed that compounds 1 and 6 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.

Mediating oxidative stress enhances α-ionone biosynthesis and strain robustness during process scaling up.

BACKGROUND: α-Ionone is highly valued in cosmetics and perfumery with a global usage of 100-1000 tons per year. Metabolic engineering by microbial fermentation offers a promising way to produce natural (R)-α-ionone in a cost-effective manner. Apart from optimizing the metabolic pathways, the approach is also highly dependent on generating a robust strain which retains productivity during the scale-up process. To our knowledge, no study has investigated strain robustness while increasing α-ionone yield. RESULTS: Built on our previous work, here, we further increased α-ionone yield to 11.4 mg/L/OD in 1 mL tubes by overexpressing the bottleneck dioxygenase CCD1 and re-engineering the pathway, which is > 65% enhancement as compared to our previously best strain. However, the yield decreased greatly to 2.4 mg/L/OD when tested in 10 mL flasks. Further investigation uncovered an unexpected inhibition that excessive overexpression of CCD1 was accompanied with increased hydrogen peroxide (H2O2) production. Excessive H2O2 broke down lycopene, the precursor to α-ionone, leading to the decrease in α-ionone production in flasks. This proved that expressing too much CCD1 can lead to reduced production of α-ionone, despite CCD1 being the rate-limiting enzyme. Overexpressing the alkyl hydroperoxide reductase (ahpC/F) partially solved this issue and improved α-ionone yield to 5.0 mg/L/OD in flasks by reducing oxidative stress from H2O2. The strain exhibited improved robustness and produced ~ 700 mg/L in 5L bioreactors, the highest titer reported in the literature. CONCLUSION: Our study provides an insight on the importance of mediating the oxidative stress to improve strain robustness and microbial production of α-ionone during scaling up. This new strategy may be inspiring to the biosynthesis of other high-value apocarotenoids such as retinol and crocin, in which oxygenases are also involved.

Characteristics of a new carotenoid cleavage dioxygenase NtCCD10 derived from Nicotiana tabacum.

MAIN CONCLUSION: A new carotenoid cleavage dioxygenase NtCCD10 from tobacco was characterized. There is some difference between NtCCD10 and CCD1 in structure. NtCCD10 can cleave the C5-C6 (C5'-C6') and C9-C10 (C9'-C10') double bonds of carotenoids and has high catalytic activity. Carotenoid cleavage dioxygenases (CCDs) cleave carotenoids to produce a variety of apocarotenoids, which have important biological functions for organisms in nature. There are eleven CCDs subfamilies in the plant kingdom, many of which have been extensively characterized in their functions. However, as a newly classified subfamily, the function of CCD10 has rarely been studied. In this work, the function of an NtCCD10 gene from dicotyledonous Nicotiana tabacum was cloned and characterized, and its phylogeny, molecular structural modeling and protein structure were also systematically analyzed. Like other CCDs, NtCCD10 also possesses a seven bladed ß-propeller with Fe2+ cofactor in its center constituting the active site of the enzyme. The Fe2+ is also coordinated bonding with four conserved histidine residues. Meanwhile, NtCCD10 also has many unique features, such as its α1 and α3 helixes are not anti-parallel, a special ß-sheet and a longer access tunnel for substrates. When expressed in engineered Escherichia coli (producing phytoene, lycopene, ß-carotene, and zeaxanthin) and Saccharomyces cerevisiae (producing ß-carotene), NtCCD10 could symmetrically cleave phytoene and ß-carotene at the C9-C10 and C9'-C10' positions to produce geranylacetone and ß-ionone, respectively. In addition, NtCCD10 could also cleave the C5-C6 and C5'-C6' double bonds of lycopene to generate 6-methyl-5-heptene-2-one (MHO). NtCCD10 has higher catalytic activity than PhCCD1 in yeast, which provides a good candidate CCD for biosynthesis of ß-ionone and has potential applications in biotechnological industry. This study identified the taxonomic position and catalytic activity of the first NtCCD10 in dicotyledonous plants. This will provide a reference for the discovery and functional identification of CCD10 enzymes in dicotyledons.

Anti-inflammatory effects of ß-ionone-curcumin hybrid derivatives against ulcerative colitis.

A series of ß-ionone-curcumin hybrid derivatives were designed and chosen to merge the biological characteristics of two parent molecules and to obtain a leading compound with higher biological activity. Through the initial screening, the structure activity relationship of their hybrid derivatives as inhibitors of nitric oxide (NO) production showed that meta-substituted derivatives exhibited the best inhibitory activity, among which 1h was the best one. In lipopolysaccharide-induced Raw264.7 macrophage cells, 1h showed anti-inflammatory activity by inhibiting the productions of NO and reactive oxygen species, the expressions of Interleukin-1ß and tumor necrosis factor-α, and the translocation of nuclear factor (NF)-κB from the cytosol to the nucleus. Furthermore, molecular docking simulation displayed that 1h could interact with cluster of differentiation 14 to inhibit the toll-like receptor 4/NF-κB signaling. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) of mice, 100 mg/kg of 1h could significantly reduce the colon length shortening and protect against colon injury, liver injury and oxidative stress in DSS-induced UC of mice. Besides, 1h was safety in vivo. In conclusion, 1h was the potential anti-inflammatory agent, and further investigations were underway in our laboratory.

Four ionones and ionone glycosides from the whole plant of Rehmannia piasezkii.

Four new ionones and ionone glycosides (1-4) were isolated from the whole plant of Rehmannia piasezkii Maxim. Their planar structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. Compounds 1-4 were tested for their cytotoxicity against five human tumor cell lines and ability to inhibit LPS-activated NO production in the BV2 cell line.

First investigation on polyphenols and glycosidic aroma precursors in a spontaneous colour mutant of 'Glera', the principal grape variety of Prosecco sparkling wine.

BACKGROUND: Somatic mutations in Vitis spp. are relatively frequent and can generate new agronomically interesting phenotypes. We report the discovery, genetic and chemical characterization of 'Glera rosa', a mutant for the berry skin colour of 'Glera', the main white cultivar used to produce Prosecco wine. RESULTS: We ascertained the relationship between the skin colour of 'Glera rosa' and the polymorphisms in the Myb-gene transcription factors involved in polyphenol biosynthesis. We established that VvMybA1 was homozygous (VvMybA1a/VvMybA1a) in 'Glera' but heterozygous (VvmybA1a/VvmybA1b) in the 'Glera rosa' mutant. We verified that the VvMybA1a non-functional allele contained Grapevine Retrotransposon 1 (Gret1), while in the VvmybA1b allele Gret1 was missing, and the gene function was partially restored. The effects of mutation on 'Glera rosa' grape metabolites were studied by high-resolution mass spectrometry and gas chromatography/mass spectrometry analysis. Fifteen anthocyanins and five unique flavonols were found in the 'Glera rosa' mutant. The mutation also increased the contents of trans-resveratrol and its derivatives (i.e., piceatannol, E-ε-viniferin, cis- and trans-piceid) and of some flavonols in grape. Finally, the mutation did not significantly affect the typical aroma precursors of Glera grape such as glycosidic monoterpenes, norisoprenoids and benzenoids. CONCLUSION: 'Glera rosa' could be an interesting genetic source for the wine industry to produce Prosecco DOC rosé typology (made by adding up to 15% of 'Pinot Noir'), which was introduced to the market in 2020 with a worldwide massive success. © 2022 Society of Chemical Industry.

In vivo, in vitro and Molecular Modelling Analysis of Isoquercetin, Roseoside, Coreximine, Anonaine, and Arianacin Molecules.

INTRODUCTION: Annona muricata is a member of the Annonaceae family. This plant has a high concentration of acetogenin, which gives it excellent therapeutic property. Researchers have tested this miraculous herb in breast cancer cells treatment and observed that it could be a source of anti-cancer agents. The proposed study focused on screening the anticancer biological activity of Annona muricata plant by using the in vitro, in vivo, and in silico methods. METHODS: In in vitro analysis, the IC50 was determined on two-dimensional and three-dimensional breast cancer cells. 2D cells were cultured on flat dishes typically made of plastic, while 3D cells were cultured using the hanging drop method. In in vivo analysis, Drosophila melanogaster was preferred, and the LC50 was determined. In in silico analysis, molecular docking studies have been carried out on the different classes of Annona muricata acetogenins against the target proteins. Nearly, five acetogenins were selected from the literature, and docking was performed against human Bcl-2, Bad and Akt-1 proteins. RESULTS: In vitro and in vivo results revealed the IC50 value of 2D MDA-MB-231 cells as 330 µg.mℓ-1, of 2D MCF-7 cells as290 µg.mℓ-1, and of 3D MCF-7 and MDA-MB-231 cells about 0.005 g.mℓ-1; the LC50 value of Drosophila melanogaster was determined as 0.1 g.mℓ-1. In silico results revealed that the docked complex formed by Isoquercetin showed better binding affinity towards target proteins. CONCLUSION: As a result of the analysis, the Annona muricata plant has been observed to be effective against cancer and likely to be a potential drug.

Chemical constituents and absolute configuration of megastigmanes' isolated from Sedum sarmentosum Bunge.

Phytochemical investigation of a methanolic extract of Sedum sarmentosum collected from Vietnam resulted in the isolation of a new megastigmane glucoside, named sedumoside K (1), together with 17 previously reported compounds (2-18). Structural elucidation of the new compound was achieved by HRFABMS, NMR spectroscopic analysis, acid hydrolysis and quantum ECD calculations. The absolute configuration of compounds 2-6 has been revised. The major isolates were tested for cytotoxic activity against HeLa human cervical cancer cells, and all showed moderate activities.

Chemical characterization, antiproliferative and antifungal activities of Clinacanthus nutans.

Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1-32), including three new megastigmanes (1-3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 µM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.

Characterization of the major aroma-active compounds in peach (Prunus persica L. Batsch) by gas chromatography-olfactometry, flame photometric detection and molecular sensory science approaches.

Aroma profiles and aroma-active compounds of "Yulu" peach from Fenghua (the peach known for the best flavor and quality in China) were investigated by headspace solid-phase microextraction (HS-SPME), solvent-assisted flavor evaporation (SAFE), gas chromatography-olfactometry (GC-O), gas chromatography-mass spectrometry (GC-MS), and flame photometric detection (FPD). The combination of these methods improved the analysis and identification of aroma substances compared to the combination of a single aroma extraction method and GC-MS. A total of 85 aroma-active compounds, including 10 sulfur compounds were detected. Methional, methyl 3-(methylthio)propionate, methionol, and benzothiazole were first detected in peaches. These aroma compounds cannot only supplement the database of aroma substances of peaches, but also provide data support for traceability of the origins of "Yulu" peaches. In addition, the odor activity value (OAV) was used to identify the contributions of the most important compounds. The results indicated that hexanal, 3-methylbutanal, (E)-2-hexen-1-ol, 3-mercaptohexyl acetate, (E,E)-2,4-decadienal, 2-methylpropanal, γ-decalactone, 2-methylbutanal, theaspirane, and δ-decalactone were the key aroma-active compounds. The key characteristic aroma components were further ascertained by aroma reconstitution and omission experiments, which showed that the fruity, floral, sulfur, and sour notes could be well simulated. Finally, the perceptual interactions between different sulfur compounds and fruity recombination (FR) were explored. 3-mercaptohexanol and 4-methyl-4-mercaptopentan-2-one could significantly decrease the threshold of FR. The possible reason was that these two sulfur compounds had synergistic effects with the aroma compounds in FR, with the U model confirming the results of these synergistic effects. The perceptual interactions provide a basis for the regulation of characteristic fruity aroma of peach products.

Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.