Identification of novel saponins from edible seeds of Japanese horse chestnut (Aesculus turbinata Blume) after treatment with wooden ashes and their nutraceutical activity

Natural seeds of Japanese horse chestnut (Aesculus turbinata Blume) contain large amounts of mixed triterpenoidal saponins called escins. Recent studies have shown that escins have several biological activities including anti-inflammatory action and inhibitory effects on the absorption of ethanol and glucose. For the edible utilization of the seeds, natural seeds are usually treated with wooden ashes to remove harshness. Here, we found the novel compounds derived from escins in the edible seeds after the food processing with wooden ashes. The instrumental analyses revealed the chemical structures of escins and the derivatives. These compounds are identified as four types of deacetylescins Ia, IIa, Ib, and IIb as well as two types of desacylescins I and II. To determine their biological activity, the purified compounds were tested for their potential nutraceutical activity. The oral glucose tolerance test in mice revealed that a single oral administration of the isolated components of deacetylescins at a dose of 100 mg/kg was clearly effective in attenuating the elevation of blood glucose levels. The inhibitory effects of escins and their derivatives were in the order of escins>deacetylescins>desacylescins. Moreover, we found the inhibitory activity of those compounds on pancreatic lipase. Escins were the most potent in inhibiting the enzyme activity, and followed by desacylescins and then deacetylescins. Taken together, our results suggest the potential usefulness of novel saponins including deacetylescins and desacylescins from edible seeds as novel sources for nutraceutical foods with anti-obese effects.     

毛冬青中有效成分的分离及其对两种主要口腔致病菌的抑制作用

目的 观察、追踪毛冬青抑制口腔常见致龋菌（变形链球菌和具核梭杆菌）的有效部位和成分。方法 通过系统溶剂萃取、大孔树脂及硅胶柱色谱分离等方法以及质谱和核磁共振等鉴定技术,结合液体二倍稀释法,研究毛冬青不同部位及单体对变形链球菌和具核梭杆菌的最低抑菌浓度（MIC）,1%玉洁纯作为阳性对照药。结果 毛冬青三萜总皂苷和冬青素对两种主要口腔致病菌均具有一定的抑制作用,特别对变形链球菌具有显著地抑制效果。结论 毛冬青三萜总皂苷和冬青素对变形链球菌具有很强的抑制作用,具有开发成为抗龋齿的保健牙膏或药品的潜力。     

Gastroprotections of escins Ia, Ib, IIa, and IIb on ethanol-induced gastric mucosal lesions in rats.

Effects of escins Ia, Ib, IIa, and IIb isolated from horse chestnuts on ethanol-induced gastric mucosal lesions and the roles of capsaicin-sensitive afferent neurons, endogenous nitric oxide (NO), sulfhydryls, prostaglandins, as well as gastric secretion and the sympathetic nervous system, were investigated in rats. Test samples were given orally to fasted rats 1 h before ethanol (1.5 ml/rat, p.o.) treatment or ligation of the pylorus. Escins Ia-IIb (10-50 mg/kg) potently inhibited ethanol-induced gastric mucosal lesions, whereas desacylescins I and II (50 mg/kg) showed no such effect. These active saponins (10 and 20 mg/kg) did not decrease the gastric secretion. The gastroprotections of escins Ia-IIb were attenuated by the pretreatment with capsaicin, N(G)-nitro-L-arginine methyl ester, and indomethacin, but not by N-ethylmaleimide. The effects of escins Ia-IIb were also attenuated in streptozotocin-induced diabetic rats, in which the activity of the sympathetic nervous system was abnormal. These results suggest that the gastroprotections of escins Ia-IIb on ethanol-induced gastric mucosal lesions are acid-independent, whereas endogenous prostaglandins, NO, capsaicin-sensitive afferent neurons, and the sympathetic nervous system participate.     

Metabolic profile of the bioactive compounds of burdock (Arctium lappa) seeds, roots and leaves

In this work the bioactive metabolic profile, the antioxidant activity and total phenolic content of burdock (Arctium lappa) seeds, leaves and roots were obtained. TEAC values and total phenolic content for hydro-alcoholic extracts of burdock ranged from 67.39 to 1.63 μmol Trolox equivalent/100 g dry weight (DW), and from 2.87 to 45 g of gallic acid equivalent/100 g DW, respectively. Phytochemical compounds were analyzed by liquid chromatography coupled to electrospray tandem mass spectrometry (LC/MS/MS) in negative mode. The main compounds of burdock extracts were caffeoylquinic acid derivatives, lignans (mainly arctiin) and various flavonoids.The occurrence of some phenolic acids (caffeic acid, chlorogenic acid and cynarin) in burdock seeds; arctiin, luteolin and quercetin rhamnoside in burdock roots; phenolic acids, quercetin, quercitrin and luteolin in burdock leaves was reported for the first time.     

Suppressive effects of novel derivatives prepared from <Emphasis Type="Italic">Aconitum</Emphasis> alkaloids on tumor growth

Summary  Little information has so far been reported regarding the antiproliferative properties of Aconitum alkaloids against human tumor cells despite of their intense toxicities. In the present study, the antitumor properties and radiation sensitizing effects were investigated by various types of novel derivatives prepared from Aconitum alkaloids. The antitumor properties were investigated against human tumor cell lines, A172, A549, HeLa and Raji, respectively, by a cell growth, a clonogenic assay, cell cycle distribution, cell cycle related molecules and γH2AX expression. The novel compounds derived from C₂₀-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C₁₉-norditerpenoid alkaloids and their derivatives showed either no effect or only a slight effect. One of the compounds also showed radiosensitizing properties on A549 cells. These effects are not related to either the cell cycle distribution, the enhancement of apoptosis or the γH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.     

Synthesis,Evaluation and Molecular Docking of Prolyl‐Fluoropyrrolidine Derivatives as Dipeptidyl Peptidase IV Inhibitors

A series of prolyl‐fluoropyrrolidine derivatives were designed, synthesized and screened for in vitro inhibition of dipeptidyl peptidase IV. The SAR study revealed the influence of substituted chemical modifications on dipeptidyl peptidase IV inhibitory activity. Among all the compounds screened, compound 9 (IC₅₀ = 0.83 μm ) and 10 (IC₅₀ = 0.43 μm ) possessing aryl substituted piperazine with acetamide linker resulted as most potent dipeptidyl peptidase IV inhibitors. Both the compounds 9 and 10 resulted significant reduction in glucose excursion during oral glucose tolerance test in streptozotocin‐induced diabetic rat model at single dose of 10 mg/kg. Molecular docking studies were performed to illustrate the probable binding mode and interactions of prolyl‐fluoropyrrolidine nucleus and its derivatives at binding site of receptor. The fluoropyrrolidine moiety of prolyl‐fluoropyrrolidine derivatives occupied S1 pocket as observed in the crystal structure (PDB id: 2FJP). The compounds 9 and 10 were observed to occupy S2 binding pocket and were observed to have interaction with Arg125, Tyr547 and Ser630 acquired through hydrogen bond. The aryl moiety at piperazine ring was found to extend into the cavity and interacted with Arg358. The observed interactions signalled that occupancy of the highly hydrophobic S2 pocket is very crucial for dipeptidyl peptidase IV inhibitory activity.     

Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin

Catechins and quercetin are major polyphenols in many plant foods that have been related to health promotion. In the human organism they are largely metabolized to different metabolites, which are further found in plasma and should contribute to the biological effects associated to the intake of the parent compounds. An important step in quercetin and catechins metabolism is the O-methylation of the catechol group, which can be expected to have an effect on their antioxidant and scavenging properties. In the present work, the 3′- and 4′-methylethers of catechin and epicatechin have been prepared and characterised and their antioxidant activity evaluated and compared to that of the corresponding quercetin derivatives. The antioxidant activity was assessed using the ferric reducing power (FRAP) assay and two methods based on the ability to scavenge the ABTS⁺ radical cation at different pH values. In these assays the three flavonoids behave as better radical scavengers and reducing compounds than usually recognised antioxidants like α-tocopherol. The O-methylation of the hydroxyls of the catechol B-ring resulted in a decrease of the antioxidant activity with regard to the parent compounds. However, the methylated metabolites still retain significant radical scavenging activity at pH 7.4, suggesting that they could act as potential antioxidants in physiological conditions. Quercetin and its methylated metabolites showed, in general, greater activity than (epi)catechin and their O-methyl derivatives, although a relatively high antioxidant activity was found in the case of 3′-O-methyl catechin at pH 7.4, comparable to those of its parent compound and the quercetin metabolites. It was confirmed that the antioxidant activity of the flavonoids assayed was strongly dependent on the pH of the medium, showing higher activity at greater pH values. The results obtained are expected to contribute to the understanding of the mechanisms involved in the biological effects attributed to the intake of flavonoid-rich diets.     

Structure-function relationship of the saponins from the roots of Platycodon grandiflorum for hemolytic and adjuvant activity

To assess the contribution of the aglycone and sugar chain to the biological activity of saponins from Platycodon grandiflorum, seven structurally consecutive saponins, platycodin D (PD), D2 (PD2), D3 (PD3), platycoside A (PA), E (PE), deapioplatycoside E (DPE), and polygalacin D2 (PGD) were compared for their hemolytic activities and adjuvant potentials on the immune responses to Newcastle disease virus-based recombinant avian influenza vaccine (rL-H5) in mice. Among seven compounds, the order of the hemolytic activity was PGD ≈ PD > PD2 > PA > PD3 > PE > DPE. PD, PD2, PA, and PGD significantly not only promoted concanavalin A (Con A)-, lipopolysaccharide (LPS)- and antigen-induced splenocyte proliferation, but enhanced the NK cell activity in mice immunized with rL-H5. PD and PD2 increased the antigen specific IgG, IgG1, IgG2a, and IgG2b antibody titers, while PA and PGD only induce the IgG and IgG1 antibody responses in the immunized mice. However, the other three saponins were not observed for adjuvant activity. The results suggested that the sugar chains attached to C-3, the glycidic moiety at C-28 of aglycone, as well as aglycone affect their biological activities. Interestingly, their hemolytic and adjuvant activities increased with the retention time by reverse phase HPLC analysis. The retention time may be useful for primary estimation of fundamental adjuvanticity of saponin with the same aglycone.     

In vitro antioxidant and free radical scavenging activities of Garcinia kola seeds

Garcinia kola Heckel – a tropical plant which grows in moist forest, has found wide applications in traditional medicine especially in the West and Central African sub-region. The seeds have been demonstrated to possess numerous bioactivities but research is highly limited on the link between its fractions and the bioactivities. In this work, the methanolic extract of Garcinia kola seeds was subjected to silica gel column chromatography into five fractions ME1–ME5 and the free radical scavenging activities and antioxidant potentials were determined for each fraction using various in vitro models. The ME4 fraction possessed the greatest activities. It was also demonstrated that the ME4 fraction strongly inhibited nitric oxide production in lipopolysaccharide activated macrophage U937 cells. Chromatographic fractionation and spectroscopic analysis of the ME4 fraction revealed the presence of four compounds namely garcinia biflavonoids GB1 and GB2, garcinal and garcinoic acid. These findings show that these four compounds are partly responsible for the great antioxidant potential of Garcinia kola seeds. This gives further evidence to the nutraceutical and pharmaceutical potential of Garcinia kola.     

芳杂基哌嗪基脒类化合物的设计、合成及5-HT和NE重摄取双重抑制活性

本文基于药效团模型的指导和课题组前期的研究结果,设计合成了一类全新结构类型的芳杂基哌嗪基脒类化合物,通过¹H NMR、HRMS对化合物结构进行了确证,并完成了初步的体外药理活性评价。结果表明这些化合物显示不同程度的5-HT和NE重摄取抑制活性,值得进一步研究。     

Design,synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease

Twenty‐two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC₅₀ value of 218 nm . Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β‐protein 1–42 (Aβ_1–42). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).     

Inhibitory effects of constituents of <Emphasis Type="Italic">Morinda citrifolia</Emphasis> seeds on elastase and tyrosinase

A 50% ethanolic extract (MCS-ext) from seeds of Morinda citrifolia (“noni” seeds) showed more potent in vitro inhibition of elastase and tyrosinase, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than extracts of M. citrifolia leaves or flesh. Activity-guided fractionation of MCS-ext using in vitro assays led to the isolation of ursolic acid as an active constituent of elastase inhibitory activity. 3,3′-Bisdemethylpinoresinol, americanin A, and quercetin were isolated as active constituents having both tyrosinase inhibitory and radical scavenging activities. Americanin A and quercetin also showed superoxide dismutase (SOD)-like activity. These active compounds were isolated from noni seeds for the first time.     

Inhibitory effect of the rhizomes of<Emphasis Type="Italic"> Alpinia officinarum</Emphasis> on TPA-induced inflammation and tumor promotion in two-stage carcinogenesis in mouse skin

The methanol extract of galangal (the rhizomes of Alpinia officinarum L.) exhibited remarkable antitumor-promoting activity on an in vivo two-stage carcinogenesis test of mice using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. Seven diarylheptanoids (1–7) were isolated and identified from the active fraction of the methanol extracts of the galangal. These compounds, 1–7, were evaluated for their inhibitory effects on TPA-induced inflammation (1 μg/ear) in mice. These compounds (1–7) tested showed marked anti-inflammatory effects, with a 50% inhibitory dose of 0.8–2.7 μmol/ear.     

药食同源植物-葱（Allium fistulosum）种植物的研究进展

药食同源植物葱（Allium fistulosum）的化学成分复杂,主要的化学成分主要集中在黄酮类、甾体皂苷类、含硫类化合物等几部分。有较好的消除亚硝酸盐、抑制肿瘤细胞增殖、降血脂、防治非酒精性脂肪肝等作用。本文综述近年关于葱的化学成分及药理活性,为其进一步开发利用提供依据。     

Design,synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring

A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure–activity relationship studies resulted in compounds 11b , 13b , and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration = 0.0625–0.125 μg/mL). The binding of compounds 11b , 13b , and 14a to the E. coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.     

Evaluation of Perylenediimide Derivatives for Potential Therapeutic Benefits on Cancer Chemotherapy

Perylene derivatives, known to have potential therapeutic benefits on particular cancer types as photosensitizers, may also function as small‐molecule inhibitors with promising therapeutic value for diverse diseases. This recently recognized biological activity was attributed to their capacity to modulate the function of various enzymes as biological targets in vitro. Although the inhibitory activity on glutathione transferase and Src tyrosine kinase is important in determining the anticancer potential of compounds for target‐specific drug design and development, to date, there are no successful inhibitors of this kind. Moreover, there are only a few studies about the effects of perylene derivatives on glutathione transferase and various kinases. In this study, four novel perylene compounds, N,N′‐disubstituted perylenediimides and their 1,7‐dibromo derivatives, were synthesized and evaluated for their biological activities. Here, among the compounds analyzed, one of them was identified with strong glutathione transferase inhibition and two with dual activity for both glutathione transferase and c‐src inhibition. These results revealed that perylene derivatives may be employed as potential chemosensitizers to prevent chemotherapy‐dependent drug resistance and identified as prospective anticancer agents with dual activity on both glutathione transferase and c‐src enzymes.     

Design,synthesis, and biological evaluation of some novel naphthoquinone-glycine/β-alanine anilide derivatives as noncovalent proteasome inhibitors

A series of novel noncovalent glycine/β-alanine anilide derivatives possessing 2-chloronaphthoquinone structure as a pharmacophoric unit were designed, synthesized, and evaluated for their antiproliferative and antiproteasomal activities against MCF-7 cell line, in vitro. According to biological activity results, all the target compounds showed antiproliferative activity in the range of IC₅₀ = 7.10 ± 0.10–41.08 ± 0.14 μM and most of them exhibited inhibitory efficacy with varying ratios against the three catalytic subunits (β1, β2, and β5) presenting caspase-like (C-L), trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities of proteasome. The antiproteasomal activity evaluations revealed that compounds preferentially inhibited the β5 subunit compared with β1 and β2 subunits of the proteasome. Among the compounds, compounds 7 and 9 showed the highest antiproliferative activity with an IC₅₀ value of 7.10 ± 0.10 and 7.43 ± 0.25 μM, respectively. Additionally, compound 7 displayed comparable potency to PI-083 lead compound in terms of β5 antiproteasomal activity with an inhibition percentage of 34.67 at 10 μM. This compound showed an IC₅₀ value of 32.30 ± 0.45 μM against β5 subunit. Furthermore, molecular modeling studies of the most active compound 7 revealed key interactions with β5 subunit. The results suggest that this class of compounds may be beneficial for the development of new potent proteasome inhibitors.     

Targeted metabolite analysis of Catharanthus roseus and its biological potential

Catharanthus roseus is nowadays one of the most studied medicinal plants. In this work, further knowledge on different parts of this species (leaves, stems, seeds and petals) was achieved, namely phenolics by HPLC-DAD and organic acids and amino acids by HPLC-UV. Also, the biological potential, expressed as acetylcholinesterase inhibitory activity was accessed and, in some parts, an acetylcholinesterase inhibitory capacity higher than 85% was found (IC₅₀ at 422, 442 and 2683 μg/mL in leaves, stems and petals, respectively). C. roseus aqueous extract revealed to be a rich source of phenolics, namely caffeoylquinic acids and flavonoids derivatives (up to 4127 mg/kg in stems, 4484 mg/kg in seeds, 8688 mg/kg in leaves and 41125 mg/kg in petals), organic acids (962, 6678, 25972 and 12463 mg/kg in seeds, petals, stems and leaves, respectively), such as citric acid (over 85% in some plant parts), and amino acids (31557, 39327, 50540 and 159697 mg/kg in stems, petals, seeds and leaves, respectively), of which arginine was a major compound.     

Synthesis and biological activities of Schiff bases of gabapentin with different aldehydes and ketones: a structure–activity relationship study

A series of novel gabapentin derivatives 6a–k and 7a–f were synthesized, and their biological activities were determined. The chemical structures were confirmed by elemental analyses, UV–visible, FT-IR, and ¹H NMR spectral studies. The structure–activity relationships (SAR) for anticonvulsant and antioxidant activities were discussed. Compounds 7a–f were evaluated for their possible anticonvulsant activity by Maximal Electroshock Seizure (MES) test, and their neurotoxic effects were determined by rotorod test. Majority of the compounds were active in MES tests. Compounds 7b and 7e showed good protective effect from seizure when compared to standard drug, phenytoin (100 mg/kg). The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). Most of the novel compounds showed DPPH radical scavenging activity, where compounds 6f, 6j, and 7a were the best radical scavengers (IC₅₀ was about 60 μg/ml).     

Antioxidant and antilisterial effect of seed essential oil and organic extracts from Zizyphus jujuba

Hydrodistilled volatile oil from the seeds of Zizyphus jujuba was analyzed by GC–MS. Twenty three compounds representing 91.59% of the total oil was identified. The oil and organic extracts revealed a great potential of antilisterial effect against all five strains of Listeria monocytogenes ATCC 19111, 19116, 19118, 19166 and 15313. Also the oil had strong detrimental effect on the viable count of the tested bacteria. The samples were also subjected to screening for the antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals scavenging activities assay. In the first case, the IC₅₀ value of the Z. jujuba essential oil was determined to be 5.21 ± 0.01 μg/ml. Among the extracts, the strongest activity was exhibited by the methanol extract with an IC₅₀ value of 20.44 ± 0.18 μg/ml. In the superoxide radicals scavenging activities assay, methanol extract was superior to all other extracts (IC₅₀ = 18.60 ± 0.3 μg/ml). Furthermore, the amount of total phenolic compounds was determined. The results indicate that the essential oil and extracts of Z. jujuba could serve as natural antimicrobial and antioxidant agents for the food industry.