Search Results (42)

Bibenzyls are now recognized as compounds for use in cancer therapy, and many molecules from the bibenzyl group have shown promising anticancer activity; therefore, the characterization of new bibenzyls with strong biological activity is important for developing new anticancer drugs. In this study, we compared the effects of three bibenzyls (3,3′-dihydroxy-4,5-dimethoxybibenzyl, 3,5-dihydroxy-4-methoxybibenzyl and 3,5,3′-trihydroxy-4-methoxybibenzyl) isolated from Empetrum nigrum and erianin on platelets and the MOLT-3 T-lymphoblast cell line. Among the studied bibenzyls, 3,3′-dihydroxy-4,5-dimethoxybibenzyl significantly reduced the viability of MOLT-3 cells and platelets and induced strong phosphatidylserine (PS) surface exposure. We showed that 3,3′-dihydroxy-4,5-dimethoxybibenzyl induced the death of MOLT-3 cells and platelets, which was not mediated by apoptosis, pyroptosis, necroptosis, autophagy, or calpain-dependent pathways, and that the p38 MAP kinase pathways are at least partly involved in the activity of 3,3′-dihydroxy-4,5-dimethoxybibenzyl. In conclusion, our data show that 3,3′-dihydroxy-4,5-dimethoxybibenzyl could be a promising candidate for future analysis as an anticancer drug. Full article

Background: Phytochemicals possess diverse therapeutic potential; however, the impact of arene substitutions on the pharmacological properties of the bibenzyl compounds batatasin III and gigantol, derived from Dendrobium venustum, remains unexplored. Objectives: This study examines how structural differences between these compounds affect cellular glucose uptake and lipid metabolism during adipocyte differentiation. Methods: The effects of both bibenzyl compounds on cytotoxicity and glucose uptake were assessed in mouse and human pre-adipocytes and rat skeletal muscle myoblasts using colorimetric assays. Lipid metabolism was evaluated through Oil Red O staining and quantification of triglyceride and glycerol levels, while protein and gene expression during adipocyte differentiation were analyzed via western blotting and RT-qPCR. Results: At the highest non-cytotoxic concentration (25 µM), gigantol significantly enhanced glucose uptake (up to 2-fold) under both basal and insulin-stimulated conditions, whereas batatasin III showed a similar effect only under basal conditions. Gigantol upregulated GLUT1 and GLUT4 in myotubes but downregulated them in adipocytes, whereas batatasin III had minimal impact on these transporters. Both compounds suppressed lipid accumulation in mouse and human adipocytes by decreasing intracellular triglyceride content and promoting extracellular glycerol release. However, batatasin III did not affect extracellular glycerol release during early adipocyte differentiation, as evidenced by the marked downregulation of key lipogenic proteins (PLIN1, LPL, FABP4) observed only with gigantol. Molecular docking analyses suggest that gigantol’s greater bioactivity may result from its higher number of arene substitutions. Conclusions: This study provides the first evidence that differences in arene substitutions among orchid-derived bibenzyls influence their pharmacological properties. Our findings support the strategic modification of natural products as a potential approach for managing metabolic disorders. Full article

Berbamine (BBM) is a bibenzyl isoquinoline present in the traditional Chinese herbal medicine Berberis amurensisis Rupr. The present study demonstrates that BBM exerts strong antiviral efficacy against influenza A virus (IAV) infection. We examined the anti-IAV effect of BBM using green fluorescent protein (GFP)-expressing influenza A and H1N1 IAV. The fluorescence microscopy, fluorescence-activated cell sorting analysis, and plaque assay showed that BBM significantly hinders IAV infection. The immunofluorescence analysis confirmed the anti-influenza activity of BBM. From the time-of-addition and hemagglutination inhibition results, it is elucidated that the antiviral effect of BBM is closely related to its inhibitory effect against viral binding and entry at an early infection stage. Our findings imply that BBM has the potential to be developed as a potent antiviral drug against influenza viral infection. Full article

Bibenzyl compounds are one of the most important bioactive components of natural medicine. However, Dendrobium officinale as a traditional herbal medicine is rich in bibenzyl compounds and performs functions such as acting as an antioxidant, inhibiting cancer cell growth, and assisting in neuro-protection. The biosynthesis of bibenzyl products is regulated by bibenzyl synthase (BBS). In this study, we have cloned the cDNA gene of the bibenzyl synthase (DoBS1) from D. officinale using PCR with degenerate primers, and we have identified a novel type III polyketide synthase (PKS) gene by phylogenetic analyses. In a series of perfect experiments, DoBS1 was expressed in Escherichia coli, purified and some catalytic properties of the recombinant protein were investigated. The molecular weight of the recombinant protein was verified to be approximately 42.7 kDa. An enzyme activity analysis indicated that the recombinant DoBS1-HisTag protein was capable of using 4-coumaryol-CoA and 3 malonyl-CoA as substrates for dihydroresveratrol (DHR) in vitro. The Vmax and Km of the recombinant protein for DHR were 3.57 ± 0.23 nmol·min⁻¹·mg⁻¹ and 0.30 ± 0.08 mmol, respectively. The present study provides further insights into the catalytic mechanism of the active site in the biosynthetic pathway for the catalytic production of dihydroresveratrol by bibenzylase in D. officinale. The results can be used to optimize a novel biosynthetic pathway for the industrial synthesis of DHR. Full article

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyl compounds. However, few studies have explored the molecular mechanisms of bibenzyl biosynthesis. This study presents a comprehensive analysis of DsBBS1 and DsBBS2 function in D. sinense. A molecular docking simulation revealed high-resolution three-dimensional structural models with minor domain orientation differences. Expression analyses of DsBBS1 and DsBBS2 across various tissues indicated a consistent pattern, with the highest expression being found in the roots, implying that they play a pivotal role in bibenzyl biosynthesis. Protein expression studies identified optimal conditions for DsBBS2-HisTag expression and purification, resulting in a soluble protein with a molecular weight of approximately 45 kDa. Enzyme activity assays confirmed DsBBS2’s capacity to synthesize resveratrol, exhibiting higher V_max and lower K_m values than DsBBS1. Functional analyses in transgenic Arabidopsis demonstrated that both DsBBS1 and DsBBS2 could complement the Atchs mutant phenotype. The total flavonoid content in the DsBBS1 and DsBBS2 transgenic lines was restored to wild-type levels, while the total bibenzyl content increased. DsBBS1 and DsBBS2 are capable of catalyzing both bibenzyl and flavonoid biosynthesis in Arabidopsis. This study provides valuable insights into the molecular mechanisms underlying the biosynthesis of bibenzyl compounds in D. sinense. Full article

Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients’ tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial–mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment. Full article

The waterways adjacent to Washington DC, USA have a history of contamination from heavy metals, nutrients, pesticides, and industrial chemicals. Among the chemicals of concern are PAHs, which are a historical contaminant but also have modern pyrogenic and petrogenic sources in the area’s waterways. Another group of contaminants that are of emerging interest are siloxanes (silicones), which are widely used as lubricants, sealants, and cosmetics. Some lower-molecular-weight siloxanes are regulated by the EU in recognition of harm to aquatic life, but there are no restrictions in the United States. In fact, studies examining water pollutants do not typically test for siloxanes. Here, we present the concentrations of specific PAHs and siloxanes from surface sediments in the Potomac and Anacostia Rivers (including the Anacostia’s tributaries) collected between 2018 and 2023. Both D5 (decamethylcyclopentasiloxane) and D6 (dodecamethylcyclohexasiloxane) were found in most locations, with concentrations averaging 0.13 and 0.006 mg/g (dry mass), respectively. Pyrene, fluoranthene, bibenzyl, and phenanthrene were also found in the Anacostia and some of its tributaries, with concentrations increasing downstream. In the Potomac, concentrations were generally lower than those observed in the Anacostia. Based on ratios of pyrene to fluoranthene + pyrene, the likely source of PAHs was petrogenic. Full article

Bletilla striata is the dried tuber of B. striata (Thund.) Reichb.f., which has antibacterial, anti-inflammatory, anti-tumor, antioxidant and wound healing effects. Traditionally, it has been used for hemostasis therapy, as well as to treat sores, swelling and chapped skin. In this study, we used the ultraviolet (UV) absorbance rate of B. striata extracts as the index, and the extraction was varied with respect to the solid–liquid ratio, ethanol concentration, ultrasonic time and temperature in order to optimize the extraction process for its sunscreen components. The main compounds in the sunscreen ingredients of Baiji (B. striata) were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry. The sunscreen properties were subsequently evaluated in vitro using the 3M tape method. The results show that the optimal extraction conditions for the sunscreen components of B. striata were a solid–liquid ratio of 1:40 (g/mL), an ethanol concentration of 50%, an ultrasonic time of 50 min and a temperature of 60 °C. A power of 100 W and an ultrasonic frequency of 40 Hz were used throughout the experiments. Under these optimized conditions, the UV absorption rate of the isolated sunscreen components in the UVB region reached 84.38%, and the RSD was 0.11%. Eighteen compounds were identified, including eleven 2-isobutyl malic acid glucose oxybenzyl esters, four phenanthrenes, two bibenzyl and one α-isobutylmalic acid. An evaluation of the sunscreen properties showed that the average UVB absorption values for the sunscreen samples from different batches of B. striata ranged from 0.727 to 1.201. The sunscreen ingredients of the extracts from B. striata had a good UV absorption capacity in the UVB area, and they were effective in their sunscreen effects under medium-intensity sunlight. Therefore, this study will be an experimental reference for the extraction of sunscreen ingredients from the B. striata plant, and it provides evidence for the future development of B. striata as a candidate cosmetic raw material with UVB protection properties. Full article

Dendrobium officinale Kimura & Migo in the genus Dendrobium of Orchidaceae is an important medicinal plant that produces various bibenzyl and phenanthrene derivatives. In some orchids, these derivatives have been reported to increase with fungal infection. Bibenzyl biosynthesis is regulated by bibenzyl synthase (BBS). Although six genes of the BBS family have been registered from D. officinale, their gene regulation mechanisms are unclear. The infection of Dendrobium with mycorrhizal fungi also reportedly increases the expression of genes involved in biosynthesis; however, the effect of mycorrhizal fungi on bibenzyl production is unknown. The present study examined the effects of three mycorrhizal fungi isolated from D. officinale on BBS gene expression and bibenzyl production over time. One of the Tulasnellaceae operational taxonomic units induced BBS gene expression and increased two representative bibenzyls, gigantol and dendrophenol, at specific time points. Furthermore, 19 BBS sequences were cloned from 12 Dendrobium species, and a phylogenetic analysis was performed. The results indicated that repeated BBS gene duplication occurred during the evolution of the genus, and further duplication occurred after speciation. These results suggest that it is possible to optimize metabolite production by selecting suitable symbiotic fungi. Full article

Research on bryophyte phytochemistry has revealed the presence of different phytochemicals like fatty acids, terpenoids, small phenolic molecules, etc. Small phenolic molecules, i.e., bibenzyls (of two aromatic rings) and bisbibenzyls (four aromatic rings), are unique signature molecules of liverworts. The first bisbibenzyls marchantin A and riccardin A were discovered in two consecutive years, i.e., 1982 and 1983, respectively, by Asakawa and coworkers. Since then, about 70 bisbibenzyls have been reported. These molecules are characterized and identified using different spectroscopic techniques and surveyed for different bioactivity and structure–activity relations. Biochemistry is determined by the season, geography, and environment. In this review, quantitative and qualitative information on bibenzyls and bisbibenzyl compounds and their distribution in different liverworts across, geographies along withtraditional to advanced extraction methods, and characterization techniques are summarized. Also, a comprehensive account of characteristic spectra of different bisbibenzyl compounds, their subtypes, and their basic skeleton patterns are compared. A comprehensive table is provided here for the first time presenting the quantity of bibenzyls, bisbenzyls, and their derivatives found in bryophytes, mentioning the spectroscopic data and mass profiles of the compounds. The significance of these compounds in different bioactivities like antibiotic, antioxidative, antitumor, antivenomous, anti-influenza, insect antifeedant, cytotoxic, and anticancerous activities are surveyed and critically enumerated. Full article

The heartwood of the Swiss Stone Pine, Pinus cembra L., has been scarcely investigated for secondary metabolites for a long period of time. Considering age and relative simplicity of heartwood investigations dating back to the 1940s to 1960s, we conducted the first investigation of P. cembra heartwood by HPLC, using UHPLC-DAD-ESI-MSⁿ and HPLC-DAD techniques in combination with isolation and NMR spectroscopy, with focus on stilbenes, bibenzyls and flavonoids. Analytical problems in the HPLC analysis of Pinus stilbenes and flavonoids on reversed stationary phases were also challenged, by comparing HPLC on pentafluorophenyl (PFP) and C18 stationary phases. Seven flavonoids (1, 2, 3, 7, 8, 11, 12), four stilbenes (4, 6, 10, 13), two bibenzyls (5, 9), three fatty acids (14, 16, 17) and one diterpenic acid (15) were detected in an ethanolic extract of Pinus cembra heartwood. HPLC comparison of reversed stationary phases in HPLC showed that the antifungal, antibacterial and chemosensitizing dihydropinosylvin monomethyl ether (9) and pinosylvin monomethyl ether (10) can be separated on PFP, but not on C18 material, when eluting with a screening gradient of 20–100% acetonitrile. Flavonoid separation showed additional benefits of combining analyses on different stationary phases, as flavonoids 7 and 8 could only be separated on one of two C18 stationary phases. Earlier phytochemical results for heartwood investigations were shown to be mostly correct, yet expandable. Substances 5 to 12 were found in alignment with these references, proving remarkable phytochemical analyses at the time. Evidence for the described presence of pinobanksin could not be found. Substances 1 to 4 and 13 have to our knowledge not yet been described for P. cembra. 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

This study aimed to systematically explore the chemical constituents of D. nobile and its hypoglycemic effect by UPLC-ESI-Q-Orbitrap, network pharmacology and in vivo experiment. The chemical constituents of D. nobile were qualitatively analyzed, and the hypoglycemic compounds were quickly identified. Network pharmacological analysis and molecular docking technique were applied to assist in the elucidation of the hypoglycemic mechanisms of D. nobile. A type 2 diabetic mellitus (T2DM) rat model was established using the HFD and STZ method for in vivo experimental verification, and these T2DM rats were treated with D. nobile extract and D. nobile polysaccharide for two months by gavage. The results showed that a total of 39 chemical constituents of D. nobile, including alkaloids, bibenzyls, phenanthrenes and other types of compounds, were identified. D. nobile extract and D. nobile polysaccharide could significantly ameliorate the body weight, hyperglycemia, insulin resistance, dyslipidemia and morphological impairment of the liver and pancreas in the T2DM rats. α-Linolenic acid, dihydroconiferyl dihydro-p-coumarate, naringenin, trans-N-feruloyltyramine, gigantol, moscatilin, 4-O-methylpinosylvic acid, venlafaxine, nordendrobin and tristin were regarded as the key hypoglycemic compounds of D. nobile, along with the hypoglycemic effect on the PI3K-AKT signaling pathway, the insulin signaling pathway, the FOXO signaling pathway, the improvement of insulin resistance and the AGE-RAGE signaling pathway. The Western blotting experiment results confirmed that D. nobile activated the PI3K/AKT pathway and insulin signaling pathway, promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β) and glucose transporter 4 (GLUT4), and inhibited liver gluconeogenesis by regulating the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6pase) in the liver. The results suggested that the hypoglycemic mechanism of D. nobile might be associated with liver glycogen synthesis and gluconeogenesis, contributing to improving insulin resistance and abnormal glucose metabolism in the T2DM rats. Full article

Three undescribed phenylpropanoid derivatives, including two new bibenzyl constituents (1–2), one new stilbene constituent (3), together with five known compounds stilbostemin F (4), dihydropinosylvin (5), 2-(4-hydroxyphenyl)ethyl benzoate (6), 1-(4-hydroxybenzoyl)ethanone (7), and 4-hydroxy-3-prenylbenzoic acid (8), were isolated from the tuber of Asparagus cochinchinensis. The structures of 1–8 were elucidated according to UV, IR, HRMS, 1D and 2D-NMR methods together with the published literature. All of the isolated compounds were assessed for anti-inflammatory activity by acting on lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells in vitro. The results showed that compounds 2 and 5 were found to inhibit the production of nitric oxide (NO) with the IC₅₀ value of 21.7 and 35.8 µM, respectively. In addition, further studies found that compound 2 demonstrated concentration-dependent suppression of the protein expression of iNOS and exerted anti-inflammatory activity via the NF-κB signalling pathway. The present data suggest that phenylpropanoid derivatives from the tuber of A. cochinchinensis might be used as a potential source of natural anti-inflammatory agents. Full article

Liverworts, considered to be the first plant type to successfully make the transition from water to land, can resist different oxidative stress. As characteristic constituents of liverworts, the bibenzyls are efficient antioxidants. In this study, spatial distributions of the bibenzyls within Marchantia polymorpha L., the model species of liverworts, were mapped using airflow-assisted desorption electrospray ionization imaging mass spectrometry. Bibenzyls were found to largely exist in the female receptacle of M. polymorpha, where lunularic acid was found to focus in the central region and bisbibenzyls were enriched in the periphery. The region-specific gene expression and antioxidant activities were characterized. In line with the spatial feature of bibenzyls, higher MpSTCS1A and Mp4CL expression levels and antioxidant ability were exhibited in the archegoniophore. The expression level of MpSTCS1A, and the content of total phenolic acid was increased after UV-B irradiation, suggesting bibenzyls play an important role in UV-B tolerance. Moreover, lunularic acid and extract of archegoniophore at a certain concentration can stimulate the spore germination under normal conditions and UV-B stress. These works broaden our understanding of the significance of bibenzyls in spore propagation and environmental adaptation. Full article