This work represents a comparative metabolomic study of extracts of wild grapes obtained from six different places in the Primorsky and Khabarovsk territories (Far East Russia) and extracts of grapes obtained from the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources (St. Petersburg). The metabolome analysis was performed by liquid chromatography in combination with ion trap mass spectrometry. The results showed the presence of 118 compounds in ethanolic extracts of V. amurensis grapes. In addition, several metabolites were newly annotated in V. amurensis. The highest diversity of phenolic compounds was identified in the samples of the V. amurensis grape collected in the vicinity of Vyazemsky (Khabarovsk Territory) and the floodplain of the Arsenyevka River (Primorsky Territory), compared to the other wild samples and cultural grapes obtained in the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources.

LC-MS/MS Screening of Phenolic Compounds in Wild and Cultivated Grapes Vitis amurensis Rupr.

Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

https://www.mdpi.com/2072-6643/13/8/2528/pdf

Experimental Evidence for Therapeutic Potentials of Propolis

Proteolysis-targeting chimeras (PROTACs) is a fast-growing technology providing many strengths over inhibition of protein activity directly and is attracting increasing interest in new drug discovery and development. However, efficiently identifying potent and drug-like degraders is still challenging in the development of PROTACs. Complementary to traditional PROTACs, several emerging types of PROTACs, such as homobivalent PROTACs based on two E3 ligases (e.g., CRBN, VHL, MDM2, TRIM24), chemical- or biological-based trivalent/multitargeted PROTACs, and covalent PROTACs, are rising for targeted protein degradation. These new types of PROTACs have several advantages over the traditional PROTACs including high selectivity, low toxicity, better therapeutic effects, and so on. In this perspective, we will summarize the latest development of representative PROTACs focusing on research mainly in past 10 years and discuss their advantages and disadvantages. Moreover, the outlook and perspectives on the associated challenges and future directions will be provided.

Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation.

Three types of Zostera marina L. collection were extracted using the supercritical CO2-extraction method. For the purposes of supercritical CO2-extraction, old seagrass ejection on the surf edge, fresh seagrass ejection on the surf edge and seagrass collected in water were used. Several experimental conditions were investigated in the pressure range 50–350 bar, with the used volume of co-solvent ethanol in the amount of 1% in the liquid phase at a temperature in the range of 31–70 °C. The most effective extraction conditions are: pressure 250 Bar and temperature 60 °C for Z. marina collected in sea water. Z. marina contain various phenolic compounds and sulfated polyphenols with valuable biological activity. Tandem mass-spectrometry (HPLC-ESI–ion trap) was applied to detect target analytes. 77 different biologically active components have been identified in Z. marina supercritical CO2-extracts. 38 polyphenols were identified for the first time in Z. marina.

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Zostera marina L.: Supercritical CO2-Extraction and Mass Spectrometric Characterization of Chemical Constituents Recovered from Seagrass

Aim Acute liver injury (ALI) can occur for various reasons by induced inflammation and apoptosis of liver cells including hepatocytes, Kupffer cells, and hepatic stellate cells. Thioacetamide (TAA), which is a classic hepatotoxin, causes oxidative stress, membrane damage, and accumulation of lipid droplets and subsequently provokes consecutive liver injury. In the current study, we tested whether Paeoniae Radix Alba (PR) could alleviate TAA-induced ALI. Methods Thirty-five male rats were equally separated into five groups. The first group was the normal group, which received distilled water only. The remaining four groups received intraperitoneal TAA (200 mg/kg) for 3 days to induce ALI. The four groups were divided into the control group (no treatment), silymarin-treated, 100 mg/kg PR-treated, and 200 mg/kg PR-treated. The efficacy of PR against hepatotoxicity was evaluated in terms of the serum biochemical index and protein expression associated with inflammation and apoptosis. Moreover, the dissected livers were analyzed by hematoxylin and eosin stain. Results PR alleviated liver dysfunction as evidenced by decreased levels of aspartate aminotransferase, alanine aminotransferase, and ammonia. Phosphorylated AMP-activated protein kinase (AMPK) and Sirtuin 1 (Sirt1) levels were obviously decreased in the TAA control group, whereas PR reversed these changes. PR also prevented deteriorative effects through inhibition of inflammation and apoptosis via nuclear transcription factor-kappa Bp65 (NF-κBp65) inactivation. Moreover, we found that the hepatoprotective effect of PR pretreatment was mediated by restoration of histopathological changes. Conclusion PR efficiently blocked both the inflammatory response and apoptosis through activating the AMPK/Sirt1/NF-κBp65 pathway. Therefore, PR is considered a potential therapeutic agent against ALI.

/pdf/the-potential-hepatoprotective-effect-of-paeoniae-radix-alba-39sqm3tg.pdf

The Potential Hepatoprotective Effect of Paeoniae Radix Alba in Thioacetamide-Induced Acute Liver Injury in Rats

Propolis has a very complex composition, with antibacterial, anti-inflammatory and other properties. To determine the composition of ethanol extracts of Brazilian green propolis (EEP-B) and their protective effect on mouse aortic endothelial cells (MAECs), the chemical composition of EEP-B was analysed by UPLC/Q-TOF-MS/MS, and the protective effect of EEP-B on the proliferation of lipopolysaccharide (LPS)-induced MAECs was determined by Cell Counting Kit-8 (CCK-8) assays. The protein levels of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA), and ICAM-1, VCAM-1 and MCP-1 expressions were analysed by western blotting. The results showed that a total of 24 compounds belonging to cinnamic acids and flavonoids, including 3,5-diisopentenyl-4-hydroxycinnamic acid (artepillin C), kaempferide, 3-isoprenyl p-coumaric acid, pinocembrin and 4′-methoxy pinobanksin, were identified in EEP-B. Among them, a new component, suggested to be 5-isoprenyl caffeic acid p-coumaric acid ester, was reported for the first time. The LPS-induced levels of TNF-α, IL-6, ICAM-1, VCAM-1 and MCP-1 were downregulated in response to 5, 10 and 20 μg/mL EEP-B. This study revealed that EEP-B could reduce LPS-induced inflammatory reactions, improve cell survival, and protect MAECs by regulating ICAM-1, VCAM-1 and MCP-1 expression. These findings could provide a theoretical basis for MAEC treatment using EEP-B.

https://www.mdpi.com/1420-3049/25/20/4612/pdf

The Chemical Composition of Brazilian Green Propolis and Its Protective Effects on Mouse Aortic Endothelial Cells against Inflammatory Injury

https://doi.org/10.1016/j.apsb.2022.02.022

Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope

Ganoderma lucidum is a traditional Chinese medicine and its major active ingredients are ganoderma triterpenoids (GTs). To screen for transcription factors (TFs) that involved in the biosynthetic pathway of GTs in G. lucidum, the chemical composition in mycelia, primordium and fruiting body were analyzed, and the transcriptomes of mycelia induced by methyl jasmonate (MeJA) were analyzed. In addition, the expression level data of MeJA-responsive TFs in mycelia, primordia and fruiting body were downloaded from the database, and the correlation analysis was carried out between their expression profiles and the content of total triterpenoids. The results showed that a total of 89 components were identified, and the content of total triterpenoids was the highest in primordium, followed by fruiting body and mycelia. There were 103 differentially expressed TFs that response to MeJA-induction including 95 upregulated and 8 downregulated genes. These TFs were classified into 22 families including C2H2 (15), TFII-related (12), HTH (9), fungal (8), bZIP (6), HMG (5), DADS (2), etc. Correlation analysis showed that the expression level of GL23559 (MADS), GL26472 (HTH), and GL31187 (HMG) showed a positive correlation with the GTs content, respectively. While the expression level of GL25628 (fungal) and GL26980 (PHD) showed a negative correlation with the GTs content, respectively. Furthermore, the over expression of the Glmhr1 gene (GL25628) in Pichia pastoris GS115 indicated that it might be a negative regulator of GT biosynthesis through decreasing the production of lanosterol. This study provided useful information for a better understanding of the regulation of TFs involved in GT biosynthesis and fungal growth in G. lucidum.

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Transcriptome profiling of transcription factors in Ganoderma lucidum in response to methyl jasmonate

The high-osmotic-pressure environment of honey is not suitable for the survival of microorganisms, except for osmotic-tolerant fungal and bacterial spores. In this study, shotgun metagenomic sequencing technology was used to identify yeast species present in honey samples. As a result, Zygosaccharomyces spp. yeast, including Zygosaccharomyces rouxii, Z. mellis and Z. siamensis, were isolated. The intracellular trehalose and glycerin concentrations of yeast, as well as the antioxidant-related CAT, SOD and POD enzyme activities, increased under a high-glucose environment (60%, w/v). To learn more about the osmotic resistance of Z. mellis, iTRAQ-based proteomic technology was used to investigate the related molecular mechanism at the protein level, yielding 522 differentially expressed proteins, of which 303 (58.05%) were upregulated and 219 (41.95%) were downregulated. The iTRAQ data showed that the proteins involved in the pathway of the cell membrane and cell-wall synthesis, as well as those related to trehalose and glycerin degradation, were all downregulated, while the proteins in the respiratory chain and TCA cycle were upregulated. In addition, formate dehydrogenase 1 (FDH1), which is involved in NADH generation, displayed a great difference in response to a high-sugar environment. Furthermore, the engineered Saccharomyces cerevisiae strains BY4741△scFDH1 with a knocked-out FDH1 gene were constructed using the CRISPR/Cas9 method. In addition, the FDH1 from Z. mellis was expressed in BY4741△scFDH1 to construct the mutant strain BY4717zmFDH1. The CAT, SOD and POD enzyme activities, as well as the content of trehalose, glycerin, ATP and NADH, were decreased in BY4741△scFDH1. However, those were all increased in BY4717zmFDH1. This study revealed that Z. mellis could increase the contents of trehalose and glycerin and promote energy metabolism to improve hypertonic tolerance. In addition, FDH1 had a significant effect on yeast hypertonic tolerance.

https://www.mdpi.com/2227-9717/10/6/1193/pdf?version=1655301252

Proteomics Analysis of Zygosaccharomyces mellis in Response to Sugar Stress

This study investigated the volatile composition and aromatic features of passion fruit wines using a combination of gas chromatography–quadrupole mass spectrometry (GC-qMS), gas chromatography–Orbitrap–mass spectrometry (GC-Orbitrap-MS), electronic nose (E-nose) and sensory evaluation. The results showed that these passion fruit wines possessed different aromatic features confirmed by E-nose. Seventeen sulfur compounds and seventy-eight volatiles were detected in these passion fruit wines using GC-Orbitrap-MS and GC-qMS, respectively. Forty-four volatiles significantly contributed to the overall wine aroma. These wines possessed passion fruit, mango, green apple, lemon and floral aromas confirmed by sensory evaluation. The partial least squares regression analysis indicated that sulfides, esters and terpenes, and terpenes mainly correlated to the passion fruit, mango and green apple aroma, respectively. Sulfur compounds significantly affected the aroma of passion fruit wine. The findings in this study could provide useful insight toward the quality control of passion fruit wine.

/pdf/aromatic-characteristics-of-passion-fruit-wines-measured-by-1uacgguf.pdf

Yuxuan Zhu

Papers

The Chemical Composition of Brazilian Green Propolis and Its Protective Effects on Mouse Aortic Endothelial Cells against Inflammatory Injury

Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope

Transcriptome profiling of transcription factors in Ganoderma lucidum in response to methyl jasmonate

Proteomics Analysis of Zygosaccharomyces mellis in Response to Sugar Stress

Aromatic Characteristics of Passion Fruit Wines Measured by E-Nose, GC-Quadrupole MS, GC-Orbitrap-MS and Sensory Evaluation