With the aim of finding a better xanthine oxidase inhibitor with potential anti-gout properties, the studies on the fruit of Stauntonia brachyanthera were carried out, which led to the isolation of 12 glycosides, including 4 new nor-oleanane triterpenoids. Their structures were determined by comprehensive spectroscopic (NMR and HR MS) analysis. Two compounds (4 and 11) exhibited significant inhibitory activities on xanthine oxidase with IC50 values of 5.22 and 1.60 µM, respectively. Another five compounds (1, 2, 3, 8 and 10) showed qualified activities. The results suggested that the existences of nor-oleanane triterpenoids and flavonoids in the fruits were responsible for the inhibitory activity on xanthine oxidase that could cut off the production of uric acid. Nor-oleanane triterpenoids, a new leading XO inhibitor, is worthy of further studies on molecular biology level for its mechanisms.Download high-res image (135KB)Download full-size image

With the aim of finding a better kidney-type glutaminase (KGA) inhibitor with potential anti-cancer properties, 18 nor-oleanane triterpenoids from Stauntonia brachyanthera, including 2 new ones, were screened against KGA. The structure-based virtual ligand screening identified 8 compounds, which might have more chance to become inhibitors of KGA with low binding energy. Glutaminase inhibition experiments and a series of cellular level assays, including cytotoxicity, wound healing, transwell invasion, western blot, and cell apoptosis, further confirmed the inhibitory effect of 5 (brachyantheraoside A8). These provided the possibility for 5 to become an inhibitor.

•4 new nor-oleanane triterpenoids were got from the leaves of S. brachyanthera.•3 compounds exhibited inhibitory activities on xanthine oxidase.•A primary structure–activity relationship was summarized.•Nor-oleanane glycosides as a potential candidate drug for the treatment of gout.With the aim of finding more potential anti-gout compounds from natural resources, a phytochemical study on the leaves of Stauntonia brachyanthera was carried out, which led to the isolation of 11 nor-oleanane triterpenoids, including 4 new ones. Their structures were determined by the comprehensive 1D, 2D NMR, HRMS, and HPLC analysis after acid hydrolysis. Brachyantheraoside B4 (3) and 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl-30-norolean-12,20(29)-dien-28-oic acid (8) exhibited significant inhibitory activities on xanthine oxidase with IC50 values of 0.20 and 18.5 μM, respectively. Brachyantheraoside C2 (2) also showed moderate effects on XO. A primary structure–activity relationship was also summarized, which revealed the anti-gout abilities of three nor-oleanane triterpenoids and their potential possibilities as the candidate compounds for the treatment of gout. The discovery of nor-oleanane triterpenoids also widens people’s idea for the study of anti-gout agents and promotes the comprehensive development of S. brachyanthera.

Ten ent-abietane diterpenoids (1–10), including four new (1–4) and six known ones (5–10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88 μM, respectively. A primary structure–activity relationship was also discussed.

•The fruits of Stauntonia brachyanthera provided a potential resource of hepatic protectant.•Eight new nor-oleanane type triterpenoid saponins and nine known compounds were isolated.•Nine compounds showed hepatoprotective activities against DL-galactosamine-induced toxicity.•Compound 15 might be a new safe leading compound for further investigation as hepatoprotectants.Stauntonia brachyanthera Hand-Mazz., an evergreen shrub belonging to the family of Lardizabalaceae, is traditionally used in China to treat various diseases. Its fruit, zhuyaozi, is extremely popular in the southwest of China because of its fresh taste and abundant nutrients. The chemical study on this fruit resulted in the isolation of eight new nor-oleanane type triterpenoid saponins, brachyanthera acid A, brachyantheraoside A1–A5 and brachyantheraoside B6, B9, along with nine known compounds. Their structures were determined by extensive 1D and 2D NMR experiments along with HRESIMS analysis. Nine compounds including four new ones showed hepatoprotective activities against DL-galactosamine-induced toxicity in WB-F344 cells, with their survival rates being very close to that of bicyclol. Additionally, the results of the inhibitory study of brachyantheraoside A5 (15) on 4-MU glucuronidation indicated its less probability leading to drug–drug interaction, which revealed that brachyantheraoside A5 and its analogues might be new safe leading compounds for further investigation as hepatoprotectants.

•The antioxidants in Stauntonia brachyanthera might confer many health protective benefits.•13 compounds isolated from S. brachyanthera were investigated for their antioxidant and cytotoxic activities.•Six compounds revealed strong antioxidant activities using three antioxidant assays.•Some compounds displayed qualified antioxidant and significant cytotoxicity activities.•Six new compounds were obtained from S. brachyanthera.Stauntonia brachyanthera Hand-Mazz., known as zhuyaozi or north banana by Dong Ethnicity in the southwest of China, is widely accepted as a delicious fruit with high economic value because of the presence of health-promoting components and the delivery of new tastes. In search for antioxidant compounds, the activity-guided fractionation and purification processes were performed on the stems and roots of S. brachyanthera, which resulted in the isolation of six new compounds, brachyanin A–F (1–6), and seven known compounds (7–13). Their structures were elucidated by 1D and 2D NMR, and HR-ESI-MS. Brachyanin A (1) exhibited significant cytotoxicity against HepG2 and K562 cell lines with IC50 values of 6.93 and 7.89 µM, respectively, and possessed antioxidant activity. Six compounds presented stronger antioxidant activities than those of vitamin C and quercetin in three tests (DPPH, ABTS, and FRAP). Among them, calceolarioside B (9) exhibited strongest activity and was present in higher amounts in the plant, which could be designated as characteristic component for the pharmacognostic identification and the quality control of S. brachyanthera. These findings laid solid theoretical references for the exploration of traditional usage of S. brachyanthera.

Psidium guajava (Myrtaceae) is an evergreen shrub growing extensively throughout the tropical and subtropical areas. Four new compounds, guavinoside C, D, E and F (1–3, 10) were isolated from the leaves of P. guajava, along with six known ones (4–9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 4 and 10 showed significant cytotoxic activities on HeLa, SGC-7901 and A549 cell lines, respectively. Compounds 1 and 4–10 showed antioxidant activities in DPPH, ABTS and FRAP assays, and five of them (1, 4–6, 10) exhibited stronger activities than that of vitamin C.Four new compounds, guavinoside C, D, E and F (1–3, 10) were isolated from the leaves of Psidium guajava, along with six known compounds. The isolated compounds were evaluated for cytotoxic and antioxidant activities, for the purpose of finding safe antitumor and antioxidant constituents from natural resource.

•28 compounds were isolated from Euphorbia fischeriana and Euphorbia ebracteolata Hayata.•Acetophenone derivatives and diterpenes are the basis compounds of two plants.•The plants of Euphorbia have similar biosynthesis system and genetic relationship.•Three compounds can be designated as characteristics for plants identification.•It provided evidences to support two plants as the origin of the same Chinese Langdu.The phytochemical investigation of two plants from genus Euphorbia, Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata led to the isolation of 28 compounds. Among them, 1–3, 12–13, 20–21, 23–25, and 28 were obtained from E. fischeriana. 14–19, and 22 were acquired from E. ebracteolata. 4–11, and 26–27 were found in both of species, and 20 and 28 are isolated from E. fischeriana for the first time. In addition, acetophenone derivatives (7–9) and diterpenes (10–25) are the basis of E. fischeriana and E. ebracteolata. The abietane, atisane, and kaurane types of diterpenes and acetophenone derivatives could be regarded as good taxonomic markers for two medicinal plants, while lupane type triterpenoids，tigliane type diterpenoids and rosane diterpenes demonstrated differences of the two species.

The inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb-drug interaction (HDI). The inhibitory effects on UGTs via nor-oleanane triterpenoid saponins, which were the bioactive ingredients from Stauntonia brachyanthera, a traditional Chinese folk medicines with highly biological values, were evaluated comprehensively with recombinant UGT isoforms as enzyme source and a nonspecific substrate 4-methylumbelliferone (4-MU) as substrate. The results showed that there are seven compounds, 2, 3, 4, 8, 9, 13 and 14, respectively, exhibited potential inhibitions towards UGT1A1, UGT1A3 and UGT1A10 among all 23 compounds isolated from the plants. The IC50 values were 17.1 μM, 13.5 μM, 9.5 μM, 15.7 μM, 16.3 μM, 1.1 μM, and 0.3 μM, respectively. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A10, UGT1A1 and UGT1A3 was best fit to noncompetitive type and competitive, respectively. The inhibition kinetic parameter (Ki) was calculated to be 39 μM, 17 μM, 3.3 μM, 10 μM, 9.3 μM, 0.19 μM, and 0.016 μM, respectively. All these experimental data suggested that HDI might occur when compounds containing herbs were co-administered with drugs which mainly undergo UGTs-mediated metabolism.Download high-res image (116KB)Download full-size image

A new steroidal saponin, furotrilliumoside (FT) was isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Its structure was elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. FT showed superior activity of inhibiting NO production of RAW264.7 cells induced by lipopolysaccharide (LPS) in the preliminary biological screening. In order to develop novel therapeutic drug for acute and chronic inflammatory disorders, the anti-inflammatory activity and underlying mechanism of FT were investigated in LPS-induced RAW264.7 cells. The results showed that FT could reduce LPS-induced expression of inducible nitric oxide synthase (iNOS) and then resulted in the decrement of NO production. More meaningful, FT could down-regulate the expression of cyclooxygenase-2 (COX-2) and decrease the expressions of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), in both gene and protein levels. In mechanism study, FT blocked the LPS-induced upregulation of phosphorylated phosphoinositide-3-kinase and Akt (PI3K/Akt). Furthermore, FT inhibited the translocation of nuclear factor-kappa B (NF-κB) through the prevention of inhibitory factor kappa B alpha (IκBα) phosphorylation and degradation and also suppressed the mitogen-activated protein kinases (MAPK) signaling pathway in LPS-stimulated RAW264.7 macrophages. In addition, FT upregulated heme oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2). Taken together, FT might act as a natural agent to treat some inflammatory diseases by targeting PI3K/Akt, MARK and Nrf2/HO-1 pathways.Download high-res image (113KB)Download full-size image

Xanthoceras sorbifolia Bunge is a medicinal plant and also a valuable cash crop used for production of edible oil and biofuels in China. In our previous research, systematical phytochemical and bioactive profiles of different parts from X. sorbifolia have been obtained. Here we describe the effective phenols from the leaves of X. sorbifolia, which could function as natural neuroinflammation inhibitors. As a result, 23 compounds were characterized as the phenols from the leaves of X. sorbifolia by means of chromatographical methods and spectroscopic analysis. Among them, flavonoids quercetin3-O-β-d-glucopyarnoside (IC50 13.39 ± 1.27 μM), catechin (IC50 9.52 ± 2.18 μM), and phenylpropanoids syringaresinol-4-O-β-d-glucopyranoside (IC50 3.08 ± 1.77 μM), 4-O-β-d-glucopyranosyl-trans-p-coumaric acid (IC50 9.08 ± 1.23 μM) exhibited much stronger inhibiting effect on NO production than that of the positive control minocycline (IC50 37.04 ± 2.09 μM) in LPS-induced BV2 cells.To enrich the phytochemical profile and bioassay of different parts from X. sorbifolia, effective phenols from the leaves, function as natural neuroinflammation inhibitors were described in this manuscript.

•The anti-Alzheimer’s disease effects of the roots of D. caudatum were studied.•13 compounds were obtained and 6 ones were firstly isolated from the genus.•4 compounds showed strong antioxidant and anti-amyloid-β aggregation effects.•2 compounds exhibited superior inhibitory activities on choline esterase.•The coexistence of various compounds clarified a multi-targets effect of the plant.Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and mainly initiated by the overproduction of amyloid-β (Aβ). The potential anti-AD evaluations of the roots of Desmodium caudatum, an industrial crop in the south of China with high medical and economic value, led to the isolation of 13 compounds, of which six ones were firstly obtained from the genus of Desmodium. Four compounds (1, 3, 10 and 11) showed strong free radical scavenging abilities and anti-Aβ aggregation effects, which revealed the close associations between antioxidant and anti-Aβ aggregation effects. Another two compounds (6 and 13) exhibited superior inhibitory activities on choline esterase. Therefore, the coexistence of various compounds clarified the multi-factors and multi-targets property of this industrial crop, which could act on different proteins and pathways and finally play an important role in the prevention and treatment of AD. Due to the strong biological effects in all tests and higher amount (126 mg) than the others, 8-prenylquercetin could be applied as a potential candidate agent in food and medicinal industry, and designated as a characteristic ingredient for the quality control of the plant material.Download full-size image

•9 compounds were isloated from the root of E. fischeriana including 3 new ones.•1 new compounds exhibited superior cytotoxic effects to that of positive on Hep-3B.•1 new and 1 known ones had stronger cytotoxic effects on A549 than that of 5-Fu.•Two low-polarity fractions of E. Fischeriana showed moderate cytotoxic effects.•Triterpenoid, abietane, tigliane might be the potential anti-tumor ingredients.With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1–3) and six known ones (4–9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC50 8.1 μmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC50 values of 12.5, 12.0 and 18.7 μmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC50 11.9 μmol/L) and 8 (IC50 9.4 μmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC50 values of 28.2 and 29.8 μmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects.

BackgroundX. sorbifolia is a widely cultivated ecological crop in the north of China which is used to produce biodiesel fuel. It also possesses special medicinal value and has attracted keen interests of researchers to explore its bioactivity.PurposeTo extract the total triterpenoid saponins from the husk of X. sorbifolia (TSX) and investigate its effects on Alzheimer's disease (AD).Study designTSX was prepared via modern extraction techniques. Its effects on two AD animal models, as well as the preliminary mechanism were investigated comprehensively.MethodsThe behavioral experiments including Y maze test, Morris water maze test and passive avoidance test were performed to observe the learning and memory abilities of the animals. ELISA assays, transmission electron microscope observation and Western blotting were employed in mechanism study.ResultsTSX, the main composition of X. sorbifolia, accounted for 88.77% in the plant material. It could significantly increase the spontaneous alternation in Y maze test (F (6, 65) = 3.209, P < 0.01), prolong the swimming time in the fourth quadrant in probe test of Morris water maze test (F (6, 71) = 4.019, P < 0.01), and increase the escape latency in passive avoidance test (F (6, 65) = 3.684, P < 0.01) in AD model animals. The preliminary mechanism research revealed that TSX could significantly increase the contents of hippocampal Ach and ChAT, and enhance activity of ChAT in hippocampus of quinolinic acid injected rats (F (5, 61) = 3.915, P 0.01; F (5, 61) = 3.623, P < 0.01, F (5, 61) = 4.344, P < 0.01, respectively). It could also increase the activities of T-AOC and T-SOD, and decrease the content of MDA in hippocampus of Aβ1-42 injected mice (F (5, 30) = 5.193, P < 0.01, F (5, 30) = 2.865, P < 0.05, F (5, 30) = 4.735, P < 0.01, respectively). Moreover, it significantly increased the expressions of SYP, PSD-95 and GAP-43 in hippocampus (F (4, 27) = 3.495, P < 0.05; F (4, 27) = 2.965, P < 0.05; F (4, 27) = 4.365, P < 0.01, respectively), and improved the synaptic ultra-structure damage in model rats.ConclusionTSX could significantly improve the impairments of learning and memory. The preliminary mechanism might associate with its protection effects against oxidative stress damage, cholinergic system deficiency and synaptic damage. TSX are perfectly suitable for AD patients as medicine or functional food, which would be a new candidate to treat AD.Download high-res image (156KB)Download full-size image