Bioactive Research Articles

Detection of antibacterial peptides in artisanal rennet and evaluation of their antibacterial activity

This study assessed the antimicrobial effectiveness of artisanal lamb and goat rennet compared to industrial calf rennet against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Results showed all three rennets were more effective against E. coli than S. aureus. Only lamb rennet achieved complete inhibition of both bacteria at a minimum inhibitory concentration of 7000 ppm. An extensive peptidomics analysis was conducted to characterize these rennet samples and correlate their antimicrobial activity with the data on endogenous peptides. Moreover, a prediction of the potential antimicrobial activity of the peptides was carried out with specific bioinformatic tools available online, proving that the isolated peptides did have the tested biological activity. Lamb rennet was found to contain 73 antimicrobial peptides with bioactivity scores between 1 and 0.52, including casocidin-I, known for its broad-spectrum antibacterial activity. Further research is ongoing to explore the applications of artisanal rennet in cheese production.

AVPI analogs and conjugates: Molecular docking studies and in vitro biological evaluation

In recent years, small peptide and non-peptide AVPI-/Smac-mimetics have been developed as IAP antagonists and are in clinical trials to overcome resistance to apoptosis in various cancer types. In this study, we present molecular modeling studies and in vitro biological evaluation of a set of AVPI-mimetics, including parent AVPI, tetrapeptide AVPI-mimetics and AVPI-conjugates.Combined molecular modeling studies and HYDE analyses provided valuable information regarding the protein–ligand interactions within the binding site of cIAP1-BIR3 and XIAP-BIR3 domain, showing that the binding part of both domains (cIAP1- and XIAP-BIR3) are formed from 22 amino acid residues, and their active part of 11 AAs. Moreover, 5 amino acids are defined common for both targets, namely Lys299, Gly306, Leu307, Trp310, and Trp323. Based on the observed docking models, six amino acid residues for cIAP1-BIR3 and five amino acids for XIAP-BIR3 are recognized actively involved in the formation of H-bonds with the respective ligand. The amino acid sequence 308 (Arg308 in cIAP1-BIR3, Thr308 in XIAP-BIR3), simultaneously forming two H-hydrogen bonds, seems to plays a key role in improvement of binding affinity.Apart from docking results the synthesized set of AVPI-mimetics was tested in vitro using cell biology (MTT assay) and parallel artificial membrane permeability assay (PAMPA). The results showed that the double modification of AVPI via substitution of Pro3 with Hyp3, as well as elongation of AVPI’s C-terminus by its conjugation with RGD-analogs, significantly increase the antiproliferative effects of AVPI-conjugates on all tested cancer cell lines (MDA-MB-231, MCF-7, HepG2 and HT-29 cells) compared to the parent AVPI peptide. SARs analysis defined this modification beneficial for the overall biological activity of the AVPI-mimetics and pointed out AVHypI-AgbGD as the most active conjugate with an IC50 of 348 µM for MDA-MB-231, 457 µM for MCF-7, 399 µM for HepG2, and 578 µM for HT-29 cells. Though the calculated IC50 values were still high, we consider AVHypI-AgbGD peptide as a good basis for further modifications. In addition, PAMPA results showed that substitution of Pro with Hyp improved the BBB permeability of AVHypI peptide compared to its parent molecule.

The role and mechanism of action of miR‑92a in endothelial cell autophagy.

Although microRNAs (miRNAs/miRs) serve a significant role in the autophagy of vascular endothelial cells (ECs), the effect of miR‑92a on the autophagy of ECs is currently unclear. Therefore, the present study aimed to investigate the impact of miR‑92a on autophagy in ECs and the underlying molecular processes that control this biological activity. Firstly, an autophagy model of EA.hy926 cells was generated via treatment with the autophagy inducer rapamycin (rapa‑EA.hy926 cells). The expression levels of miR‑92a were then detected by reverse transcription‑quantitative PCR, and the effect of miR‑92a expression on the autophagic activity of rapa‑EA.hy926 cells was studied by overexpressing or inhibiting miR‑92a. The level of autophagy was evaluated by western blot analysis, immunofluorescence staining and transmission electron microscopy. Dual‑luciferase reporter assays were used to confirm the interaction between miR‑92a and FOXO3. The results demonstrated that the expression levels of miR‑92a were decreased in the rapa‑EA.hy926 cell autophagy model. Furthermore, overexpression and inhibition of miR‑92a revealed that upregulation of miR‑92a in these cells inhibited autophagy, whereas miR‑92a knockdown promoted it. It was also confirmed that miR‑92a directly bound to the 3'‑untranslated region of the autophagy‑related gene FOXO3 and reduced its expression. In conclusion, the present study suggested that miR‑92a inhibits autophagy activity in EA.hy926 cells by targeting FOXO3.

In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes.

In spite of the fact that many medicinal plants have been truly utilized for the management of diabetes all through the world, very few of them have been reported scientifically. Recently, a diverse variety of animal models have been established to better understand the pathophysiology of diabetes mellitus, and new medications to treat the condition have been introduced in the market. Flavonoids are naturally occurring substances that can be found in plants and various foods and may have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable novel therapy option for macrovasular complications in preclinical models; however, human clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques and animal models. Natural compounds, mostly derived from plants, have been studied in diabetes models generated by chemical agents in the majority of research. The aim of this work was to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic agents. This review contributes to the scientist's design of new methodologies for the development of novel therapeutic agents having potential antihyperglycemic activity.

Transplanting network pharmacology technology into food science research: A comprehensive review on uncovering food-sourced functional factors and their health benefits.

Network pharmacology is an emerging interdisciplinary research method. The application of network pharmacology to reveal the nutritional effects and mechanisms of active ingredients in food is of great significance in promoting the development of functional food, facilitating personalized nutrition, and exploring the mechanisms of food health effects. This article systematically reviews the application of network pharmacology in the field of food science using a literature review method. The application progress of network pharmacology in food science is discussed, and the mechanisms of functional factors in food on the basis of network pharmacology are explored. Additionally, the limitations and challenges of network pharmacology are discussed, and future directions and application prospects are proposed. Network pharmacology serves as an important tool to reveal the mechanisms of action and health benefits of functional factors in food. It helps to conduct in-depth research on the biological activities of individual ingredients, composite foods, and compounds in food, and assessment of the potential health effects of food components. Moreover, it can help to control and enhance their functionality through relevant information during the production and processing of samples to guarantee food safety. The application of network pharmacology in exploring the mechanisms of functional factors in food is further analyzed and summarized. Combining machine learning, artificial intelligence, clinical experiments, and in vitro validation, the achievement transformation of functional factor in food driven by network pharmacology is of great significance for the future development of network pharmacology research.

Comprehensive phytochemical profiling and biological activities of Hodgsonia heteroclita subsp. indochinensis seed extracts

Hodgsonia heteroclita subsp. indochinensis, a member of the Cucurbitaceae family, is utilized in traditional medicinal remedies based on indigenous wisdom. This study aimed to comprehensively identify and analyze the bioactive phytoconstituents within H. heteroclita subsp. indochinensis seeds. Seeds were sequentially extracted with n-hexane, ethyl acetate, and methanol. Liquid chromatography-mass spectrometry analysis detected ferulic acid, salicylic acid, cucurbitacin E, stigmasterol glucoside, and ß-sitosterol glucoside in all extracts. The total phenolic content in the HH(S)-EtOAc and HH(S)-MeOH was 14.22 ± 1.58 and 12.98 ± 1.03 mg gallic acid equivalent/g, respectively. Consequently, the HH(S)-EtOAc demonstrated antioxidant activity with an IC50 of 1.10 ± 0.28 mg/mL, while the HH(S)-MeOH displayed strong antioxidant potential with an IC50 of 0.04 ± 0.00 mg/mL according to an ABTS assay. Antibacterial evaluations of both the HH(S)-hexane and HH(S)-EtOAc revealed significant activity against Staphylococcus aureus (zone of inhibition (ZOI): 13.67 ± 2.31 and 11.67 ± 1.53 mm, respectively) but limited activity against Escherichia coli (ZOI: 7.33 ± 0.58 and 7.67 ± 0.58 mm, respectively). Additionally, the extracts exhibited low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, ranging from 62.50 to 250 mg/mL. The antiproliferative activity of seed extracts was assessed against two breast cancer cell lines (MCF-7 and MDA-MB-231), normal breast cells (MCF10A), and human embryonic kidney (HEK) 293T cells, through MTT and clonogenic assays. The results revealed IC50 values exceeding 400 μg/mL, indicating that the extracts are safe. Furthermore, all seed extracts (50 μg/mL) exhibited potent anti-inflammatory activity, evident by their substantial inhibition of nitric oxide production (p < 0.001) and inducible nitric oxide synthase (iNOS) gene expression (p < 0.05) in LPS-induced RAW264.7. These findings demonstrate the potential for H. heteroclita subsp. indochinensis seed extracts in the development of functional foods, nutraceuticals, and dietary supplements due to their diverse bioactive compounds and substantial biological activities, particularly their anti-inflammatory effects.

Influence of extraction solvents on the chemical constituents and biological activities of Astragalus aduncusfrom Turkey flora: In vitro and in silico insights.

The n-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of Astragalus aduncus aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE],antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line[HT-29], gastric cancer cell line[HGC-27], prostate carcinoma cell line[DU-145], breast adenocarcinoma cell line[MDA-MB-231],and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopymethods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents. Our findings indicated that the ethyl acetate extract was the most potent BChE inhibitor (11.44 mg galantamine equivalents [GALAE]/g) followed by the ethanol extract (8.51 mg GALAE/g), while the ethanol extract was the most promising AChE inhibitor (3.42 mg GALAE/g) followed by the ethanol/water extract (3.17 mg GALAE/g).Excellent tyrosinase inhibitory activity (66.25 mg kojic acid equivalent/g) was observed in ethanol/water extracts of the aerial part of A. aduncus. Тhese results showed that the most cytotoxic effects were exhibited by the ethyl acetate extract against HGC-27 cells (IC50: 36.76 µg/mL), the ethanol extract against HT-29 cells (IC50: 30.79 µg/mL), and the water extract against DU-145 cells (IC50: 37.01 µg/mL). A strong correlation was observed between the highest total flavonoid content and the highest content of individual compounds in the ethanol extract, including rutin, hyperoside, isoquercitrin, delphinidin-3,5-diglucoside (delphinidin-3,5-O-diglucoside), and kaempferol-3-glucoside (kaempferol-3-O-glucoside). In the present study, the A. aduncus plant was considered a new source of antioxidants, enzyme inhibitors, and anticancer agents and could be used as a future health-benefit natural product.

A new perspective of sediment layering scour and migration under the coupled effects of particle distribution and bio-viscosity–cavitation erosion

The scouring and migration of sediments in sewer systems are the key contributors to overflow pollution. Both physical and biological factors affect the erosion and migration of layered sediments. However, the functional characteristics of these factors and their quantification process still need to be further explored. In this study, the physical form and biological metabolism of the sediment are coupled, and the suspension mechanism under the dual action is proposed systematically and deeply. The influence coefficient of scour initiation was redefined as A^/prime, where the physical factors were particle size and mass, and the biological factors were bio-viscosity and internal cavitation. The bio-viscosity of layered sediment particles is provided by Extracellular Polymeric Substances (EPS). The slope value of |ΔD/−Δf| (ΔD: Dissipation; Δf: frequency) of surface EPS decreased from 0.489 to 0.315 when Quartz Crystal Microbalance with Dissipation (QCM-D) was used to analyse EPS viscosity, indicating that biological activities formed a dense biofilm on the sediment surface and enhanced the bond between particles. Meanwhile, by monitoring the accumulation density of sediments at different depths, it was found that the packing density of the bottom layer decreased from 1.50 to 1.45 g/cm3, which was mainly due to the internal cavitation caused by microorganism consuming organic matrix and releasing H2S and CH4. The delamination difference of EPS results in the uneven change of adhesion between different layers. This, combined with the internal erosion characteristics triggered by microbial stratified metabolism, collectively constitutes the biological effects on the sediment structure. Finally, the coupling mechanism of particle distribution and bio-viscous-cavitation erosion was formed, and the correctness of the formula was verified by repeated experiments, which proved the agreement between the theory and the practice and provided a scientific method for systematically analysing the erosion and migration law of sediment in the sewer system.

Structural analysis and biological activity of cell wall polysaccharides and enzyme-extracted polysaccharides from pomelo (Citrus maxima (Burm.) Merr.)

Pomelo peel is a valuable source of pectin, but research on its cell wall polysaccharides is limited. This study compared the cell wall polysaccharides of pomelo peel, enzyme-extracted polysaccharides of pomelo peel, and enzyme-extracted polysaccharides of whole pomelo fruit. Cell wall polysaccharides, including water-soluble pectin (WSP), chelator-soluble pectin (CSP), sodium carbonate-soluble pectin (NSP), 1 mol/L KOH soluble hemicellulose (KSH-1), and 4 mol/L KOH soluble hemicellulose (KSH-2), were obtained by sequence-extraction method. Total polysaccharides from whole pomelo fruit (TP) and peel-polysaccharides from pomelo pericarps (PP) were obtained using enzyme-extraction method. The structural, thermal, rheological, antioxidant properties, and wound healing effect in vitro were described for each polysaccharide. WSP had a uniform molecular weight distribution and high uronic acid (UA) content, suitable for commercial pectin. NSP had the highest Rhamnose (Rha)/UA ratio and a rich side chain with highest viscosity and water retention. PP displayed the highest DPPH radical scavenging activity and reducing capacity at 0.1 to 2.0 mg/mL concentration range, with an IC50 of 1.05 mg/mL for DPPH free radicals. NSP also demonstrated the highest hydroxyl radical scavenging activity and promoted Human dermal keratinocyte proliferation and migration at 10 μg/mL, suggesting potential applications in daily chemical and pharmaceutical industries.

Diphenyl Ethers: Isolation, Bioactivities and Biosynthesis

Abstract: Diphenyl ethers (DPEs) are mainly produced by microorganisms and plants. The chemical structure of DPEs is relatively simple, and all of these compounds have the structure of biphenyl ethers in their chemical structure, the difference being the difference in the substituents on the benzene ring. Several recent studies have shown antibacterial, antioxidant, antitumor, antitumor, antihemolytic, neuroprotective, and anti-Alzheimer effects. DPEs could be candidate compounds for the treatment of Alzheimer's disease, by inhibiting the aggregation of Aβ42. Many DPEs from natural products exhibit good biological activity and they play an important role in the control of microbial infections. Diphenyl ethers have a wide range of applications and research value in the fields of pesticides, pharmaceuticals, textiles, household products, and public health. In this paper, we review the research progress of diphenyl ethers isolated from marine and plant endophytic sources in recent years, including their biosynthesis, and lay the foundation for further utilization and development.

Assessment on Functionalized Conjugated Acetylide and Its Designated Acetylide-Imine Moieties towards Acanthamoeba sp.: An in vitro Bioindicator Study

The demand for developing bioindicators to assess environmental pollution has increased significantly due to the awareness of potential threats of diseases. Herein, the eukaryotic ubiquitous microorganism Acanthamoeba sp. was used as a bioindicator to explore further the influence of functionalized organic molecules containing -C≡C- and -CH=N- moieties prior application in the potential electronic components. The acetylide and hybrid acetylide-imine derivatives (FYD3A, FYD4B, and FYD4C) were tested for their cytotoxicity potentials based on dose-response analysis, morphological observation, and mode of cell death assessment on Acanthamoeba sp. (environmental-isolate). The biological activities of optimized compounds were evaluated by HOMO-LUMO energy gap and MEP analysis. The determination of the IC50 value through the MTT assay showed functionalized organic molecules of FYD3A, FYD4B, and FYD4C, revealing the inhibition growth of Acanthamoeba sp. with IC50 values in the 3.515 - 3.845 μg/mL range. Morphological observation displayed encystment with cellular agglutination and overall cell shrinkage. AO/PI-stained moieties-treated Acanthamoeba sp. cells appeared with shades of red to orange in necrotic Acanthamoeba cells whilst green to yellow apoptotic Acanthamoeba cells when compared to entirely green fluorescence untreated cells. Moreover, the results of the mitochondrial membrane potential (MMP) assay demonstrate the integrity and functionality potential of the mitochondrial membrane in cells, where a decrease in the MMP assay is linked to apoptosis. This study confirmed that the functionalized organic molecule featuring acetylide and its designated acetylide-imine moieties exhibit cytotoxicity towards the Acanthamoeba sp. by apoptotic and necrotic mode of cell death. This indicates that seeping these derivatives as electronic components can lead to the leaching of hazardous chemicals and contribute to environmental pollution that negatively affects the ecosystem. This study proposes the selection of efficient systems and elements for functionalized organic molecules that are safe to be released into the environment.

A novel coupled fermentation system for low-molecular-weight xanthan gum with diverse biological activities

Xanthan gum (XG) is a bacterial exopolysaccharide widely used in various industries due to its stability and rheological properties. Low-molecular-weight xanthan gum (LXG) exhibits enhanced properties and broader applications, but current degradation methods are limited. This study introduces an innovative coupled fermentation system for the efficient production of LXG. Endo-xanthanase from Microbacterium sp. XT11 was expressed in Pichia pastoris GS115, exhibiting optimal activity at pH 6.0 and 40 °C, with broad pH tolerance. The optimized coupled fermentation system used bean sprouts juice as nitrogen source, the inoculation quantity of X. campestris: P. pastoris was 1: 3, and the pH was controlled at 6.0. In the bioreactor, the total sugar concentration reached 12.12 g/L, the reducing sugar concentration reached 5.32 g/L, and the endo-xanthanase activity increased to 1150.26 U/L, which were 2.13, 2.3, and 3.71 times higher than those at the shake flask level, respectively. The prepared LXG had a molecular weight of 1093 Da and a monosaccharide ratio of 2.0:1.57:0.89 (glucose, mannose, and glucuronic acid). Bioactivity analysis revealed its antioxidant and prebiotic properties, promoting the growth of beneficial intestinal microbiota and metabolite production. This suggests the potential of LXG as a functional ingredient in intestinal health-focused foods and supplements.

Tailoring of apoptotic bodies for diagnostic and therapeutic applications:advances, challenges, and prospects.

Apoptotic bodies (ABs) are extracellular vesicles released during apoptosis and possess diverse biological activities. Initially, ABs were regarded as garbage bags with the main function of apoptotic cell clearance. Recent research has found that ABs carry and deliver various biological agents and are taken by surrounding and distant cells, affecting cell functions and behavior. ABs-mediated intercellular communications are involved in various physiological processes including anti-inflammation and tissue regeneration as well as the pathogenesis of a variety of diseases including cancer, cardiovascular diseases, neurodegeneration, and inflammatory diseases. ABs in biological fluids can be used as a window of altered cellular and tissue states which can be applied in the diagnosis and prognosis of various diseases. The structural and constituent versatility of ABs provides flexibility for tailoring ABs according to disease diagnostic and therapeutic needs. An in-depth understanding of ABs' constituents and biological functions is mandatory for the effective tailoring of ABs including modification of bio membrane and cargo constituents. ABs' tailoring approaches including physical, chemical, biological, and genetic have been proposed for bench-to-bed translation in disease diagnosis, prognosis, and therapy. This review summarizes the updates on ABs tailoring approaches, discusses the existing challenges, and speculates the prospects for effective diagnostic and therapeutic applications.

Functionalized Morpholine-thiazole Scaffold: Synthetic Strategies and Applications.

The thiazole derivatives as important members of heterocyclic compounds have attracted much synthetic interest due to their different biological properties. In recent years, studies on the synthesis of morpholine compounds have increased because of the properties of this core. In particular, the hybrid structures in which the thiazole ring is linked to morpholine nuclei in one molecular frame have gained popularity. The presented review is an attempt to summarize a huge volume of data on morpholinothiazoles being a widely studied class of these molecules used in modern organic and medicinal chemistry. The manuscript covers the approaches to the synthesis of the morpholinothiazoles derivatives. The synthetic strategies of the target compounds depend on one-pot or multistage reactions or the transformation of other related heterocycles. Additionally, we covered the biological activities and other applications of certain morpholinothiazoles. The information on these compounds made special consideration of medicinal chemists to yield a combinatorial library and carry out thorough efforts in the search of morpholinothiazoles.

Design, synthesis, characterization, and biological activities of novel Ag(I)-NHC complexes based on 1,3-dioxane ligand

Herein, a series of new Ag(I)-NHC complexes containing 1,3-dioxane group were synthesized by the direct reaction of Ag2O and benzimidazolium salts in light-free conditions. All Ag(I)-NHC complexes were spectrally characterized using 1H, 13C NMR, FT-IR, LC-MS, and elemental analysis. Additionally, the structures of compounds 1a and 1e were elucidated by the single X-ray diffraction techniques. Further, the synthesized Ag(I)-NHC complexes were evaluated for cytotoxicity study on the L-929 cells and the anticancer activity against the HCT 116 and MCF-7 cancer cell lines. Notably, 1a showed significant anticancer activity against HCT 116 with an IC50 of 6.37 ± 0.92 μg/mL compared to cisplatin (IC50 = 36.75 ± 1.76 μg/mL). 1c (IC50 = 3.21 ± 1.96 μg/mL) and 1e (IC50 = 3.72 ± 1.12 μg/mL) exhibited significant anticancer activity against MCF-7 cells and was similar to cisplatin (IC50 = 32.17 ± 2.85 μg/mL). Meanwhile, 1a and 1e displayed the highest selectivity index. Most importantly, the cell viability test showed that 1e induced neglectable cytotoxicity (IC50 = 36.38 ± 2.27 μg/mL) toward L-929 and was similar to cisplatin (IC50 = 36.11 ± 2.09 μg/mL). The anticancer activities of Ag(I)-NHC complexes vary depending on the substituent group of the silver complex and the cell line type. Moreover, the inhibitory mechanism of 1e was not dependent on caspase-associated apoptosis initiated by the lysosomal-mitochondrial pathway. Taken together, we conclude that this work provides a simple and rapid protocol for the synthesis of Ag(I)-NHC complexes and the featured Ag(I)-NHC complexes have an anticancer drug potential for biomedical applications.

Recent Advances in Transition Metal Catalyzed Synthesis of C3-Substitution-free 2-Oxindole Derivatives

Abstract: 2-Oxindole unit is one of the most important scaffolds found in several alkaloids, natural products, antitumor agents, pharmaceutically important compounds, etc. Molecules containing the 2- oxindole moiety were first isolated from the cat claw plant, widely distributed in the Amazon jungle. It has now been demonstrated that these molecules are present in a wide range of chemicals derived from plant sources. The capacity of 2-oxindole to be altered by various chemical groups to provide unique biological activities can be attributed to its function as a chemical framework for creating and developing biological medications. Since the development of its first synthetic methodology, several research groups have developed protocols for producing 2-oxindole core and its bioactive derivatives. These include the traditional method and the transition/non-transition metal-catalyzed pathway for the synthesis of C3-non-substituted/C3-mono-substituted/C3-di-substituted core. Among those, C3-substitution-free 2-oxindole core synthesis is quite a challenging task, as C3-centre is very reactive. Syntheses of C3-substitution-free 2-oxindole cores have been less explored compared to other substituted 2-oxindole derivatives. In this review article, we have mainly focused on showcasing the transition metal-catalyzed synthetic methodology for the synthesis of 2-oxindoles with no substitution at C3-centre.

A Review on Synthesis and Biological Activities of 2‐Aminophenol‐Based Schiff Bases and Their Transition Metal Complexes

ABSTRACT2‐Aminophenol‐based Schiff bases and their metal complexes have drawn a lot of interest because of their wide range of biological activity and their uses in several fields. These Schiff bases are synthesized through the condensation of 2‐aminophenol and various carbonyl compounds, and metal complexes formed easily by coordinating Schiff bases with transition metal ions possess a wide range of intriguing properties that have rendered them promising candidates in biomedical research. These compounds have a diverse array of captivating biological properties including antibacterial, antifungal, anticancer, and antioxidant actions. Their versatile nature and potential for tailored modifications hold the promise for innovative biomedical applications. Compared to standard antibiotics and other studied compounds, C2, C8–C11, and C116 complexes, along with L16 and L17 ligands, exhibit the highest antibacterial activity, while C3 and C115 complexes demonstrate the highest antifungal activity. The metal chelate formation of the ligands enhanced the antimicrobial activity by increasing their lipophilic nature. C66, C76, and C112 complexes and L39 ligand showed higher anticancer activity than standard anticancer drugs. The metal complexes have higher anticancer activity than the ligand due to improved permeability and cellular uptake. The anticancer activity of the complexes is related to the substituents of the Schiff base ligands. In compounds containing an electron‐withdrawing group (e.g., Cl or Br or NO2), the activity is obviously better than others. Ligands L1–L3 and L5, L6, and L32 demonstrated the most potent antioxidant activity, surpassing both metal complexes and standard conventional antioxidants. The ligands showed greater antioxidant activity than the metal complexes due to their capability of donating free protons to scavenge free radicals. More study is needed to fully explore the potential of 2‐aminophenol‐based Schiff bases and their transition metal complexes for the development of new drugs. This review summarizes different synthetic methods, biological activities, and the structure–activity relationship. This study aims to conduct further research on 2‐aminophenol‐based Schiff bases and their metal complexes.

Bergenin protects against osteoarthritis by inhibiting STAT3, NF-κB and Jun pathways and suppressing osteoclastogenesis.

Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

Cascara Pulp: A Novel Ingredient for Healthy Kombucha by Using Honey and Brown Sugar

ABSTRACT This study investigates the effects of brown sugar and honey on microbial counts, antibacterial activity, chemical compositions, and biological activities of cascara kombucha beverages after 12 days of fermentation. Concentrations of 5, 10, and 15 g of brown sugar or equivalent volumes of honey were used per 100 mL of cascara kombucha to evaluate changes in parameters such as pH, acetic acid, sugar, alcohol content, total phenolic content, and antioxidant activity. The results indicated that the microbial composition and pH of the products remained consistent at all concentrations of honey (H) and brown sugar (BS). Cascara kombucha with 15% brown sugar had significantly lower acetic acid content and higher brix as compared with 5% and 10% honey. The alcohol concentration in cascara kombucha with 15% brown sugar was comparable to that with the same levels of honey. Increasing the amounts of brown sugar or honey significantly increased the total phenolic compounds but decreased the antioxidant capacity of cascara kombucha. Additionally, kombucha samples with honey demonstrated better inhibiting the growth of E. coli than brown sugar. Thus, the use of cascara pulp as a novel ingredient in health-promoting kombucha highlights the significant impact of honey and brown sugar on its chemical composition and biological activities.

Phytochemical Screening and Biological Activity (Antioxidant and Antibacterial) of Punica granatum Fruit peel extract Cultivated in Sa'dah Governorate-Yemen

Punica granatum (Pomegranate) is a valuable source of secondary plant metabolism compounds (SMs) that are widely used in the pharmaceutical, cosmetics, and food industries. The phytochemical screening illustrates that the Sa’dah P. granatum cultivar peel ethanol extract containsvarious beneficial components, including Flavonoids, Alkaloids, Steroids, Phenols, and Tannins. Moreover, the Sa’dah P. granatum cultivar peel ethanol extract (1.3 μg/ml) exhibited significant antioxidant activity compared to low concentrations of ascorbic acid (0.4, 0.6, 0.8, and 1 μg/ml). Furthermore, the Sa’dah P. granatum cultivar peel ethanol extract displays potent antibacterial activities against selected pathogenic bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) compared to two nominated antibiotics (Ampicillin and Gentamicin). This remarkable performance can be attributed to the presence of phenols and flavonoid compounds, which exhibit high antioxidant activity.