Search Results (13)

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2–5) named albaphenol A–E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7–16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1–16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC₅₀ 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC₅₀ 2.5–32.8 μM) than the positive control galantamine (IC₅₀ 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure–activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor–enzyme complex. Full article

Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds. Full article

Fermented wheatgrass juice was prepared using a two-stage fermentation process by employing Saccharomyces cerevisiae and recombinant Pediococcus acidilactici BD16 (alaD⁺). During fermentation, a reddish-brown hue appeared in wheatgrass juice due to production of different types of red pigments. The fermented wheatgrass juice has considerably higher content of anthocyanins, total phenols and beta-carotenes as compared to unfermented wheatgrass juice. It has low ethanol content, which might be ascribed to the presence of certain phytolignans in wheatgrass juice. Several yeast-mediated phenolic transformations (such as bioconversion of coumaric acid, hydroxybenzoic acid, hydroxycinnamic acid and quinic acid into respective derivatives; glycosylation and prenylation of flavonoids; glycosylation of lignans; sulphonation of phenols; synthesis of carotenoids, diarylnonanoids, flavanones, stilbenes, steroids, quinolones, di- and tri-terpenoids and tannin) were identified in fermented wheatgrass juice using an untargeted liquid chromatography (LC)-mass spectrometry (MS)-matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)/time-of-flight (TOF) technique. The recombinant P. acidilactici BD16 (alaD⁺) also supported flavonoid and lignin glycosylation; benzoic acid, hydroxycoumaric acid and quinic acid derivatization; and synthesis of anthraquinones, sterols and triterpenes with therapeutic benefits. The information presented in this manuscript may be utilized to elucidate the importance of Saccharomyces cerevisiae and P. acidilactici BD16 (alaD⁺) mediated phenolic biotransformations in developing functional food supplements such as fermented wheatgrass juice. Full article

Morus bombycis has a long history of usage as a treatment for metabolic diseases, especially, diabetes mellitus (DM). Thus, we aimed to isolate and evaluate bioactive constituents derived from M. bombycis leaves for the treatment of DM. According to bioassay-guided isolation by column chromatography, eight compounds were obtained from M. bombycis leaves: two phenolic compounds, p-coumaric acid (1) and chlorogenic acid methyl ester (2), one stilbene, oxyresveratrol (3), two stilbene dimers, macrourin B (4) and austrafuran C (6), one 2-arylbenzofuran, moracin M (5), and two Diels–Alder type adducts, mulberrofuran F (7) and chalcomoracin (8). Among the eight isolated compounds, the anti-DM activity of 3–8 (which possess chemotaxonomic significance in Morus species) was evaluated by inhibition of α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation as well as by scavenging peroxynitrite (ONOO⁻), which are crucial therapeutic targets of DM and its complications. Compounds 4 and 6–8 significantly inhibited α-glucosidase, PTP1B, and HRAR enzymes with mixed-type and non-competitive-type inhibition modes. Furthermore, the four compounds had low negative binding energies in both enzymes according to molecular docking simulation, and compounds 3–8 exhibited strong antioxidant capacity by inhibiting AGE formation and ONOO⁻ scavenging. Overall results suggested that the most active stilbene-dimer-type compounds (4 and 6) along with Diels–Alder type adducts (7 and 8) could be promising therapeutic and preventive resources against DM and have the potential to be used as antioxidants, anti-diabetic agents, and anti-diabetic complication agents. Full article

Stilbene and benzofuran derivatives isolated from the root of white mulberry (Morus alba) have shown various biological activities, including anti-inflammatory, antioxidant, and antimicrobial properties. The objectives of this study were to develop hairy root cultures and assess the effect of multiple elicitors combinations including (I) methyl-β-cyclodextrin (CD), MgCl₂, methyl jasmonate (MeJA), and H₂O₂, (II) CD, MgCl₂, and MeJA and (III) CD, MgCl_2, and H₂O₂, on the production of these bioactive compounds. The highest yields of stilbenes and benzofurans were obtained upon co-treatment with 18 g/L CD, 3 mM H₂O₂ and 1 mM MgCl₂. The stilbenes oxyresveratrol, resveratrol, and 3′-prenylresveratrol accumulated up to 6.27, 0.61, and 5.00 mg/g DW root, respectively. Meanwhile, the aryl benzofurans moracin M and moracin C accumulated up to 7.82 and 1.82 mg/g DW root, respectively. These stilbenes and benzofurans accumulated in the culture medium of the elicited hairy root cultures. They were not detected in the root tissue. However, the oxyresveratrol diglucoside mulberroside A was only detected in the root tissue with yields up to 10.01 mg/g DW. The results demonstrated that co-treatment of white mulberry hairy root cultures with multiple elicitors can significantly enhance production and secretion of stilbenes and benzofurans in this controlled and sustainable axenic culture system. Full article

Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1−17), among which three steroids (1−3), one triterpene (4), four flavonoids (5−8), two stilbenoids (9 and 10) four ellagic acid derivatives (11−14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 μg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 μg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 μg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 μg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a–c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper. Full article

Prenylated stilbenoids such as arachidin-1 and arachidin-3 are stilbene derivatives that exhibit multiple pharmacological activities. We report an elicitation strategy using different combinations of cyclodextrin, hydrogen peroxide, methyl jasmonate and magnesium chloride to increase arachidin-1 and arachidin-3 production in peanut hairy root cultures. The treatment of hairy root cultures with cyclodextrin with hydrogen peroxide selectively enhanced arachidin-1 yield (132.6 ± 20.4 mg/L), which was 1.8-fold higher than arachidin-3. Similarly, cyclodextrin combined with methyl jasmonate selectively enhanced arachidin-3 yield (178.2 ± 6.8 mg/L), which was 5.5-fold higher than arachidin-1. Re-elicitation of the hairy root cultures further increased the levels of arachidin-1 and arachidin-3 by 24% and 42%, respectively. The ethyl acetate extract of the culture medium was consecutively fractionated by normal- and reversed-phase column chromatography, followed by semi-preparative HPLC purification on a C18 column to yield arachidin-1 with a recovery rate of 32% and arachidin-3 with a recovery rate of 39%, both at higher than 95% purity. This study provided a sustainable strategy to produce high-purity arachidin-1 and arachidin-3 using hairy root cultures of peanuts combined with column chromatography and semi-preparative HPLC. Full article

Previously, we reported the anti-diabetic effect of Morus alba root bark and the compounds therein. In our continuous study of other parts of this plant, the ability of the branch of Morus alba to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and advanced glycation end products (AGEs) formation was evaluated. Moreover, there are no previous studies that have performed enzyme kinetics and molecular docking analyses, along with assessments of peroxynitrite (ONOO⁻) inhibitory activities. Since the Morus alba branch exhibited favorable inhibitory effects, repeated column chromatography was performed to obtain eight compounds, including four flavonoids (1, 3, 6, 8), one arylbenzofuran (2), one stilbene (5), one Diels–Alder-type adduct (7), and one sterol (4). Among them, compounds 1–3 and 5–7 were mixed-type inhibitors of α-glucosidase, sharing the same catalytic residues with acarbose and the same allosteric sites with (Z)-3-bytylidenephthalide. On the other hand, kuwanon C (1) and oxyresveratrol (5) interacted with residues of the allosteric site (α3 and α6 helices) of PTP1B, indicating their use as non-competitive inhibitors. Interestingly, kuwanon G (7) directly bound the catalytic site, or interrupted the binding between the substrate and the active site, as a mixed-type inhibitor. Moreover, most of the compounds exhibited greater activity against AGE formation and ONOO⁻ than positive controls. The IC₅₀ values required to inhibit ONOO⁻ using compounds 1, 3, 5, 6, and 7 were reported for the first time, and range from 1.08 to 12.92 μM. Based on the structure–activity relationship, the presence of hydroxyl, resorcinol, and prenyl moieties was important in the prevention of diabetes’ pathological mechanisms, and these findings have been further supported by molecular docking analysis. These computational and experimental results will be useful in the development of therapeutic candidates to prevent/treat diabetes and its complications. Full article

The combination of natural products with standard chemotherapeutic agents offers a promising strategy to enhance the efficacy or reduce the side effects of standard chemotherapy. Doxorubicin (DOX), a standard drug for breast cancer, has several disadvantages, including severe side effects and the development of drug resistance. Recently, we reported the potential bioactive markers of Australian propolis extract (AP-1) and their broad spectrum of pharmacological activities. In the present study, we explored the synergistic interactions between AP-1 and DOX in the MCF7 breast adenocarcinoma cells using different synergy quantitation models. Biochemometric and metabolomics-driven analysis was performed to identify the potential anticancer metabolites in AP-1. The molecular mechanisms of synergy were studied by analysing the apoptotic profile via flow cytometry, apoptotic proteome array and measuring the oxidative status of the MCF7 cells treated with the most synergistic combination. Furthermore, label-free quantification proteomics analysis was performed to decipher the underlying synergistic mechanisms. Five prenylated stilbenes were identified as the key metabolites in the most active AP-1 fraction. Strong synergy was observed when AP-1 was combined with DOX in the ratio of 100:0.29 (w/w) as validated by different synergy quantitation models implemented. AP-1 significantly enhanced the inhibitory effect of DOX against MCF7 cell proliferation in a dose-dependent manner with significant inhibition of the reactive oxygen species (p < 0.0001) compared to DOX alone. AP-1 enabled the reversal of DOX-mediated necrosis to programmed cell death, which may be advantageous to decline DOX-related side effects. AP-1 also significantly enhanced the apoptotic effect of DOX after 24 h of treatment with significant upregulation of catalase, HTRA2/Omi, FADD together with DR5 and DR4 TRAIL-mediated apoptosis (p < 0.05), contributing to the antiproliferative activity of AP-1. Significant upregulation of pro-apoptotic p27, PON2 and catalase with downregulated anti-apoptotic XIAP, HSP60 and HIF-1α, and increased antioxidant proteins (catalase and PON2) may be associated with the improved apoptosis and oxidative status of the synergistic combination-treated MCF7 cells compared to the mono treatments. Shotgun proteomics identified 21 significantly dysregulated proteins in the synergistic combination-treated cells versus the mono treatments. These proteins were involved in the TP53/ATM-regulated non-homologous end-joining pathway and double-strand breaks repairs, recruiting the overexpressed BRCA1 and suppressed RIF1 encoded proteins. The overexpression of UPF2 was noticed in the synergistic combination treatment, which could assist in overcoming doxorubicin resistance-associated long non-coding RNA and metastasis of the MCF7 cells. In conclusion, we identified the significant synergy and highlighted the key molecular pathways in the interaction between AP-1 and DOX in the MCF7 cells together with the AP-1 anticancer metabolites. Further in vivo and clinical studies are warranted on this synergistic combination. Full article

Fusarium is one of the most toxigenic phytopathogens causing diseases and reduced agricultural productivity worldwide. Current chemical fungicides exhibit toxicity against non-target organisms, triggering negative environmental impact, and are a danger to consumers. In order to explore the chemical diversity of plants for potential antifungal applications, crude extract and fractions from Monotes kerstingii were screened for their activity against two multi-resistant Fusarium oxysporum strains: Fo32931 and Fo4287. Antifungal activity was evaluated by the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts using kinetic OD_{600 nm} reading by a spectrophotometer. The n-butanol fraction showed the best activity against Fo4287. We screened eleven previously reported natural compounds isolated from different fractions, and a stilbene–coumarin 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-4,7-dimethoxy-3-methyl-2H-1-benzopyran-2-one (1) was the most active compound against both strains. Compound 1 was employed as a nucleophile with a selection of electrophilic derivatizing agents to synthesize five novel stilbene–coumarin analogues. These semisynthetic derivatives showed moderate activity against Fo32931 with only prenylated derivative exhibiting activity comparable to the natural stilbene–coumarin (1), demonstrating the key role of the phenolic group. Full article

Traditional medicine is especially important in the treatment of neglected tropical diseases because it is the way the majority of populations of affected countries manage primary healthcare. We present a case study that can serve as an example that can be replicated by others in the same situation. It is about the validation of a local remedy for myasis in Amazonian Ecuador, which is contrasted by bibliographic chemical reviews and in silico activity tests. We look for scientific arguments to demonstrate the reason for using extracts of Lonchocarpus utilis against south American myasis (tupe). We provide a summary of the isoflavonoids, prenylated flavonoids, chalcones, and stilbenes that justify the action. We make modeling predictions on the affinity of eight chemical components and enzyme targets using Swiss Target Prediction software. We conclude that the effects of this extract can be reasonably attributed to an effect of the parasite that causes the disease, similar to the one produced by synthetic drugs used by conventional medicine (e.g., Ivermectine). Full article

Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species. Full article

Separation of the extract of the tubers of Scirpus holoschoenus L. (family Cyperaceae), a species easily confused with Juncus plants, afforded 2-prenyl-3,5,4'-trimethoxystilbene, 2-prenyl-3-hydroxy-5,4'-dimethoxystilbene, 2-prenyl-3,4'-dihydroxy-5-methoxy-stilbene and 3,5,4'-trimethoxystilbene, in addition to a new acetophenone derivative. The isolated compounds were identified on the basis of spectral measurements. Full article