Project description:Four hitherto unknown polysubstituted isoflavonoids, including three isoflavans: 7,4'-dihydroxy-8,2',3'-trimethoxyisoflavan (1), 7,2',4'-trihydroxy-8,3'-dimethoxyisoflavan (2), and 7,2',4'-trihydroxy-5-methoxyisoflavan (3), and one prenylated isoflavone cudraisoflavone M (4) were isolated from the ethanol extracts of Spatholobus suberectus (for 1 and 2), Flemingia macrophylla (for 3), and Cudrania cochinchinensis (for 4), respectively. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 1 and 4 exhibited weak cytotoxic activity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW-480).
Project description:A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1-9 and flavonoids 10-16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1-9 and 13-16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9-13.6 ?M. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.
Project description:The composition and content of the active constituents and their biological activity vary according to diverse factors including their maturation stages. A previous study showed that the fruits of Cudrania tricuspidata inhibited pancreatic lipase activity, a key enzyme in fat absorption. In this study, we investigated the chemical composition and pancreatic lipase inhibitory activity of unripe and ripe fruits of C. tricuspidata. Unripe fruits of C. tricuspidata have a higher content of total phenolic and flavonoids and exhibited stronger pancreatic lipase inhibition compared to ripe fruits. HPLC analysis revealed the different chemical compositions of the unripe and ripe fruits. Further fractionation resulted in the isolation of 30 compounds including two new isoflavonoids. Analysis of the chemical constituents of the unripe and ripe fruits revealed that a 2,2-dimethylpyran ring, a cyclized prenyl, was the predominant side chain in the unripe fruits, whereas it was a linear prenyl group in the ripe fruits. In addition, a new isoflavonoid (19) from the unripe fruits showed the most potent inhibition on pancreatic lipase. Taken together, the maturation stage is an important factor for maximum efficacy and that unripe fruits of C. tricuspidata are a good source of new bioactive constituents for the regulation of obesity.
Project description:Green-synthesized silver nanoparticles (SNPs) have great potential for biomedical applications, due to their distinctive optical, chemical, and catalytic properties. In this study, we aimed to develop green-synthesized SNPs from extracts of Cudrania tricuspidata (CT) roots (CTR), stems (CTS), leaves (CTL), and fruit (CTF) and to evaluate their physicochemical, photocatalytic, and biological properties. CTR, CTS, CTL, and CTF extracts were evaluated and compared for their total phenol and flavonoid content, reducing capacity, and antioxidant activity. The results revealed that CTR, CTS, CTL, and CTF extracts have high phenol and flavonoid content, as well as a powerful antioxidant and reducing capacity. CTR and CTS extracts showed the strongest effects. The results from UV-Vis spectra analysis, dynamic light scattering, high-resolution transmission electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy showed the successful formation of CT-SNPs with surface morphology, crystallinity, reduction capacity, capsulation, and stabilization. Synthesized CT-SNPs successfully photocatalyzed methylene blue, methyl orange, rhodamine B, and Reactive Black 5 within 20 min. The CTR- and CTS-SNPs showed better antibacterial properties against different pathogenic microbes (Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Salmonella enteritidis) than the CTL- and CTF-SNPs. CTS- and CTR-SNPs showed the most effective cytotoxicity and antiapoptosis properties in human hepatocellular carcinoma cells (HepG2 and SK-Hep-1). CT-SNPs also seemed to be more biologically active than the CT extracts. The results of this study provide evidence of the establishment of CT extract SNPs and their physicochemical, photocatalytic, and biological properties.
Project description:Obesity, which is characterized by excessive fat accumulation, is associated with several pathological disorders, including metabolic diseases. In this study, the anti-obesity effect of 6,8-diprenylgenistein (DPG), a major isoflavonoid of Cudrania tricuspidata fruits was investigated using high fat-diet (HFD)-induced obese mice at the doses of 10 and 30 mg/kg for six week. The body weight of the DPG-treated groups was significantly lower compared to the HFD-treated group. In addition, fat accumulation in epididymal adipose tissue and liver was dramatically decreased in the HFD + DPG groups. The food efficiency ratios of the HFD + DPG groups were also lower compared to the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD + DPG groups. Further studies demonstrate that DPG efficiently reduces lipogenic genes by regulation of transcription factors, such as peroxisome proliferator-activated receptor ? (PPAR?) and CCAAT/enhancer-binding protein ? (C/EBP?), and hormones, such as leptin and adiponection. DPG also regulates acetyl-CoA carboxylase (ACC) and hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) by AMP-activated protein kinase (AMPK) activation. Taken together, DPG is beneficial for the regulation of obesity, especially resulting from high fat intake.
Project description:Prenylated flavonoids are attractive specialized metabolites with a wide range of biological activities and are distributed in several plant families. The prenylation catalyzed by prenyltransferases represents a Friedel-Crafts alkylation of the flavonoid skeleton in the biosynthesis of natural prenylated flavonoids and contributes to the structural diversity and biological activities of these compounds. To date, all identified plant flavonoid prenyltransferases (FPTs) have been identified in Leguminosae. In the present study two new FPTs, Morus alba isoliquiritigenin 3'-dimethylallyltransferase (MaIDT) and Cudrania tricuspidata isoliquiritigenin 3'-dimethylallyltransferase (CtIDT), were identified from moraceous plants M. alba and C. tricuspidata, respectively. MaIDT and CtIDT shared low levels of homology with the leguminous FPTs. MaIDT and CtIDT are predicted to be membrane-bound proteins with predicted transit peptides, seven transmembrane regions, and conserved functional domains that are similar to other homogentisate prenyltransferases. Recombinant MaIDT and CtIDT were able to regioselectively introduce dimethylallyl diphosphate into the A ring of three flavonoids with different skeleton types (chalcones, isoflavones, and flavones). Phylogenetic analysis revealed that MaIDT and CtIDT are distantly related to their homologs in Leguminosae, which suggests that FPTs in Moraceae and Leguminosae might have evolved independently. MaIDT and CtIDT represent the first two non-Leguminosae FPTs to be identified in plants and could thus lead to the identification of additional evolutionarily varied FPTs in other non-Leguminosae plants and could elucidate the biosyntheses of prenylated flavonoids in various plants. Furthermore, MaIDT and CtIDT might be used for regiospecific prenylation of flavonoids to produce bioactive compounds for potential therapeutic applications due to their high efficiency and catalytic promiscuity.
Project description:In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE? in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE? in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF-?, IL-12, and IL-1? production, blocked nuclear translocation of NF-?B heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of I?B-?, and inhibited NF-?B binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation.
Project description:The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125-0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer.