Search Results (20)

Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba’s compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = −8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = −7.84 kcal/mol; Ki = 7.96µM). From ashitaba’s compounds, it was found that 4′-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3′-carboxymethyl-4,2′-dihydroxy-4′-methoxychalcone have low ΔG of below −6 kcal/mol. The lowest ΔG value was found in 3′-carboxymethyl-4,2′-dihydroxy-4′-methoxy chalcone with a ΔG of −6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = −5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = −6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity. Full article

Blister blight (BB) disease is caused by the obligate biotrophic fungal pathogen Exobasidium vexans Massee and seriously affects the yield and quality of Camellia sinensis. The use of chemical pesticides on tea leaves substantially increases the toxic risks of tea consumption. Botanic fungicide isobavachalcone (IBC) has the potential to control fungal diseases on many crops but has not been used on tea plants. In this study, the field control effects of IBC were evaluated by comparison and in combination with natural elicitor chitosan oligosaccharides (COSs) and the chemical pesticide pyraclostrobin (Py), and the preliminary action mode of IBC was also investigated. The bioassay results for IBC or its combination with COSs showed a remarkable control effect against BB (61.72% and 70.46%). IBC, like COSs, could improve the disease resistance of tea plants by enhancing the activity of tea-plant-related defense enzymes, including polyphenol oxidase (PPO), catalase (CAT), phenylalanine aminolase (PAL), peroxidase (POD), superoxide dismutase (SOD), β-1,3-glucanase (Glu), and chitinase enzymes. The fungal community structure and diversity of the diseased tea leaves were examined using Illumina MiSeq sequencing of the internal transcribed spacer (ITS) region of the ribosomal rDNA genes. It was obvious that IBC could significantly alter the species’ richness and the diversity of the fungal community in affected plant sites. This study broadens the application range of IBC and provides an important strategy for the control of BB disease. Full article

In this paper, the natural chalcones: 2′-hydroxy-4,4′,6′-trimethoxychalcone (HCH), cardamonin (CA), xanthohumol (XN), isobavachalcone (IBC) and licochalcone A (LIC) are studied using spectroscopic techniques such as UV–vis, fluorescence spectroscopy, scanning electron microscopy (SEM) and single-crystal X-ray diffraction (XRD). For the first time, the spectroscopic and structural features of naturally occurring chalcones with varying numbers and positions of hydroxyl groups in rings A and B were investigated to prove the presence of the aggregation-induced emission enhancement (AIEE) effect. The fluorescence studies were carried out in the aggregate form in a solution and in a solid state. As to the results of spectroscopic analyses conducted in the solvent media, the selected mixtures (CH₃OH:H₂O and CH₃OH:ethylene glycol), as well as the fluorescence quantum yield (ϕ_F) and SEM, confirmed that two of the tested chalcones (CA and HCH) exhibited effective AIEE behaviour. On the other hand, LIC showed a large fluorescence quantum yield and Stokes shift in the polar solvents and in the solid state. Moreover, all studied compounds were tested for their promising antioxidant activities via the utilisation of 1,1- diphenyl-2-picrylhydrazyl as a free-radical scavenging reagent as well as potential anti-neurodegenerative agents via their ability to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Finally, the results demonstrated that licochalcone A, with the most desirable emission properties, showed the most effective antioxidant (DPPH IC₅₀ 29%) and neuroprotective properties (AChE IC₅₀ 23.41 ± 0.02 μM, BuChE IC₅₀ 42.28 ± 0.06 μM). The substitution pattern and the biological assay findings establish some relation between photophysical properties and biological activity that might apply in designing AIEE molecules with the specified characteristics for biological application. Full article

Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans. Full article

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity. Full article

The review presents prenylated flavonoids as potential therapeutic agents for the treatment of topical skin infections and wounds, as they can restore the balance in the wound microenvironment. A thorough two-stage search of scientific papers published between 2000 and 2022 was conducted, with independent assessment of results by two reviewers. The main criteria were an MIC (minimum inhibitory concentration) of up to 32 µg/mL, a microdilution/macrodilution broth method according to CLSI (Clinical and Laboratory Standards Institute) or EUCAST (European Committee on Antimicrobial Susceptibility Testing), pathogens responsible for skin infections, and additional antioxidant, anti-inflammatory, and low cytotoxic effects. A total of 127 structurally diverse flavonoids showed promising antimicrobial activity against pathogens affecting wound healing, predominantly Staphylococcus aureus strains, but only artocarpin, diplacone, isobavachalcone, licochalcone A, sophoraflavanone G, and xanthohumol showed multiple activity, including antimicrobial, antioxidant, and anti-inflammatory along with low cytotoxicity important for wound healing. Although prenylated flavonoids appear to be promising in wound therapy of humans, and also animals, their activity was measured only in vitro and in vivo. Future studies are, therefore, needed to establish rational dosing according to MIC and MBC (minimum bactericidal concentration) values, test potential toxicity to human cells, measure healing kinetics, and consider formulation in smart drug release systems and/or delivery technologies to increase their bioavailability. Full article

Isobavachalcone (IBC) is a natural prenylated chalcone with a broad spectrum of pharmacological properties. In this work, we newly synthesized and investigated the antibacterial activity of IBC against Gram-positive, Gram-negative and mycobacterial species. IBC was active against Gram-positive bacteria, mainly against Methicillin-Susceptible Staphylococcus aureus (MSSA) and Methicillin-Resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) values of 1.56 and 3.12 µg/mL, respectively. On the other hand, IBC was not able to act against Gram-negative species (MIC > 400 µg/mL). IBC displayed activity against mycobacterial species (MIC = 64 µg/mL), including Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii. IBC was able to inhibit more than 50% of MSSA and MRSA biofilm formation at 0.78 µg/mL. Its antibiofilm activity was similar to vancomycin, which was active at 0.74 µg/mL. In order to study the mechanism of the action by fluorescence microscopy, the propidium iodide (PI) and SYTO9 fluorophores indicated that IBC disrupted the membrane of Bacillus subtilis. Toxicity assays using human keratinocytes (HaCaT cell line) showed that IBC did not have the capacity to reduce the cell viability. These results suggested that IBC is a promising antibacterial agent with an elucidated mode of action and potential applications as an antibacterial drug and a medical device coating. Full article

Microbial transformation is an alternative method for structural modification. The current study aimed at application of microbial transformation for discovering new derivatives and investigating the structure-activity relationship of isobavachalcone (1), 4-hydroxyderricin (2), and xanthoangelol (3) isolated from the herb Angelica keiskei. In the initial screening process, 1–3 were incubated with microbes using a two-stage fermentation method and analyzed through TLC monitoring. The screening results showed that Rhizopus oryzae and Mucor hiemalis were able to transform 1 and 2, respectively. Additionally, M. hiemalis and Mortierella ramanniana var. angulispora were able to transform 3. Following scale-up fermentation, four new (4, 5, 7, and 10) and five known (6, 8, 9, 11, and 12) metabolites were produced. Cytotoxicity of all the compounds (1–12) was investigated using three human cancer cell lines including A375P, HT-29, and MCF-7 by MTT method. Meanwhile, the tyrosinase inhibitory activity of 1–12 was evaluated using l-tyrosine as a substrate. Overall, 1 and 3 displayed the highest cytotoxicity, and 5 and 7 exhibited the most potent tyrosinase inhibitory activity with relatively low cytotoxicity. This allowed us to postulate that the introduction of 4′-O-glucopyranosyl group led to the reduction in cytotoxicity and improvement in tyrosinase inhibitory activity. Full article

The aging process is concurrently shaped by genetic and extrinsic factors. In this work, we screened a small library of natural compounds, many of marine origin, to identify novel possible anti-aging interventions in Caenorhabditis elegans, a powerful model organism for aging studies. To this aim, we exploited a high-content microscopy platform to search for interventions able to induce phenotypes associated with mild mitochondrial stress, which is known to promote animal’s health- and lifespan. Worms were initially exposed to three different concentrations of the drugs in liquid culture, in search of those affecting animal size and expression of mitochondrial stress response genes. This was followed by a validation step with nine compounds on solid media to refine compounds concentration, which led to the identification of four compounds (namely isobavachalcone, manzamine A, kahalalide F and lutein) consistently affecting development, fertility, size and lipid content of the nematodes. Treatment of Drosophila cells with the four hits confirmed their effects on mitochondria activity and lipid content. Out of these four, two were specifically chosen for analysis of age-related parameters, kahalalide F and lutein, which conferred increased resistance to heat and oxidative stress and extended animals’ healthspan. We also found that, out of different mitochondrial stress response genes, only the C. elegans ortholog of the synaptic regulatory proteins neuroligins, nlg-1, was consistently induced by the two compounds and mediated lutein healthspan effects. Full article

Biotransformation of four bioactive phenolic constituents from licorice, namely licoisoflavanone (1), glycyrrhisoflavone (2), echinatin (3), and isobavachalcone (4), was performed by the selected fungal strain Aspergillus niger KCCM 60332, leading to the isolation of seventeen metabolites (5–21). Structures of the isolated compounds were determined on the basis of extensive spectroscopic methods, twelve of which (5–7, 10–17 and 19) have been previously undescribed. A series of reactions including hydroxylation, hydrogenation, epoxidation, hydrolysis, reduction, cyclization, and alkylation was observed in the biotransformation process. All compounds were tested for their cytotoxic activities against three different human cancer cell lines including A375P, MCF-7, and HT-29. Compounds 1 and 12 exhibited most considerable cytotoxic activities against all the cell lines investigated, while compounds 2 and 4 were moderately cytotoxic. These findings will contribute to expanding the chemical diversity of phenolic compounds, and compounds 1 and 12 may serve as leads for the development of potential cancer chemopreventive agents. Full article

Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial. Full article

Magnaporthe oryzae (M. oryzae) is a typical cause of rice blast in agricultural production. Isobavachalcone (IBC), an active ingredient of Psoralea corylifolia L. extract, is an effective fungicide against rice blast. To determine the mechanism of IBC against M. oryzae, the effect of IBC on the metabolic pathway of M. oryzae was explored by transcriptome profiling. In M. oryzae, the expression of pyruvate dehydrogenase E1 (PDHE1), part of the tricarboxylic acid (TCA cycle), was significantly decreased in response to treatment with IBC, which was verified by qPCR and testing of enzyme activity. To further elucidate the interactions between IBC and PDHE1, the 3D structure model of the PDHE1 from M. oryzae was established based on homology modeling. The model was utilized to analyze the molecular interactions through molecular docking and molecular dynamics simulation, revealing that IBC has π-π stacking interactions with residue TYR139 and undergoes hydrogen bonding with residue ASP217 of PDHE1. Additionally, the nonpolar residues PHE111, MET174, ILE 187, VAL188, and MET250 form strong hydrophobic interactions with IBC. The above results reveal that PDHE1 is a potential target for antifungal agents, which will be of great significance for guiding the design of new fungicides. This research clarified the mechanism of IBC against M. oryzae at the molecular level, which will underpin further studies of the inhibitory mechanism of flavonoids and the discovery of new targets. It also provides theoretical guidance for the field application of IBC. Full article

Psoralea Fructus is widely used in traditional Chinese medicine (TCM), and the content of psoralen, isopsoralen, neobavaisoflavone, bavachin, psoralidin, isobavachalcone, and bavachinin A is the main quality control index of Psoralea Fructus because of its clinical effects. Thus, a fast and environmentally-benign extraction method of seven compounds in Psoralea Fructus is necessary. In this work, an ionic liquid-based ultrasonic-assisted method (ILUAE) for the extraction of seven compounds from Psoralea Fructus was proposed. Several ILs of different types and parameters, including the concentration of ILs, concentration of ethanol (EtOH), solid–liquid ratio, particle size, ultrasonic time, centrifugal speed, and ultrasonic power, were optimized by the Placket–Burman (PB) design and Box–Behnken response surface analysis. Under this optimal condition, the total extraction yield of the seven compounds in Psoralea Fructus was 18.90 mg/g, and significantly greater than the conventional 75% EtOH solvent extraction. Full article

We isolated isobavachalcone (IBC) from Angelica keiskei (AK) as an anti-obesity component. IBC dose-dependently inhibited 3T3-L1 adipocyte differentiation by down-regulating adipogenic factors. At the mitotic clonal expansion stage (MCE), IBC caused cell cycle arrest in G0/G1 with decreased expression of cell cycle-regulating proteins. IBC also inhibited autophagic flux by inducing intracellular accumulation of LC3B and SQSTM1/p62 proteins while decreasing expression levels of regulating factors for autophagy initiation. In parallel with the inhibition of adipocyte differentiation, IBC decreased intrahepatic fat deposits and rescued the liver steatosis in high fat cholesterol diet-fed zebrafish. In this study, we found that IBC isolated from AK suppresses mitotic clonal expansion and autophagy flux of adipocytes and also shows anti-obesity activity in a high cholesterol-diet zebrafish model by decreasing intrahepatic fat deposits. These results suggest that IBC could be a leading pharmacological compound for the development of anti-obesity drugs. Full article

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloid β-peptide 42, β-secretase, glycogen synthase kinase 3β, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment. Full article