Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A-L (1-12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B-C (2-3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D-F (4-6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model.

Hypolipidemic and Hepatoprotective Effects of Polysaccharides Extracted from Liriope spicata Var. Prolifera in C57BL/6J Mice with High-Fat Diet-Induced Hyperlipidemia.

In this study, C57BL/6J mice with high-fat diet- (HFD-) induced hyperlipidemia were treated with total Liriope spicata var. prolifera polysaccharides (TLSP: 200, 400, and 800 mg/kg body weight), simvastatin (3 mg/kg body weight), or saline for 8 weeks, respectively. The results showed that TLSP had strong lipid-lowering and hepatoprotective effects on C57BL/6J mice with HFD-induced hyperlipidemia. TLSP administration significantly reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels and downregulated the expressions of peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase (FAS) in the adipose and liver tissues of the mice. TLSP exerted hypolipidemic and hepatoprotective effects by activating lipid/bile acid metabolism via the FXH-SHP/CYP7A1 and SEBP-1c/FAC/ACC signaling pathways. Thus, TLPS is a promising natural polymer with hepatoprotective and hypolipidemic properties.

Buxus alkaloid compound destabilizes mutant p53 through inhibition of the HSF1 chaperone axis.

BACKGROUND: P53 is the most frequently mutated gene in most tumour types, and the mutant p53 protein accumulates at high levels in tumours to promote tumour development and progression. Thus, targeting mutant p53 for degradation is one of the therapeutic strategies used to manage tumours that depend on mutant p53 for survival. Buxus alkaloids are traditionally used in the treatment of cardiovascular diseases. We found that triterpenoid alkaloids extracted from Buxus sinica found in the Yunnan Province exhibit anticancer activity by depleting mutant p53 levels in colon cancer cells. PURPOSE: To explore the anticancer mechanism of action of the triterpenoid alkaloid KBA01 compound by targeting mutant p53 degradation. STUDY DESIGN AND METHODS: Different mutant p53 cell lines were used to evaluate the anticancer activity of KBA01. MTT assay, colony formation assay and cell cycle analysis were performed to examine the effect of KBA01 on cancer cell proliferation. Western blotting and qPCR were used to investigate effects of depleting mutant p53, and a ubiquitination assay was used to determine mutant p53 ubiquitin levels after cells were treated with the compound. Co-IP and small interfering RNA assays were used to explore the effects of KBA01 on the interaction of Hsp90 with mutant p53. RESULTS: The triterpenoid alkaloid KBA01 can induce G2/M cell cycle arrest and the apoptosis of HT29 colon cancer cells. KBA01 decreases the stability of DNA contact mutant p53 proteins through the proteasomal pathway with minimal effects on p53 mutant protein conformation. Moreover, KBA01 enhances the interaction of mutant p53 with Hsp70, CHIP and MDM2, and knocking down CHIP and MDM2 stabilizes mutant p53 levels in KBA01-treated cells. In addition, KBA01 disrupts the HSF1-mutant p53-Hsp90 complex and releases mutant p53 to enable its MDM2- and CHIP-mediated degradation. CONCLUSION: Our study reveals that KBA01 depletes mutant p53 protein in a chaperone-assisted ubiquitin/proteasome degradation pathway in cancer cells, providing insights into potential strategies to target mutant p53 tumours.

A new bile acid from the traditional chinese medicine shedan.

A new bile acid tauro-16ß-hydroxy-12α-sulfate-5ß-cholenoic acid (1), along with six known ones (2-7), was isolated from the snake bile. Its planar structure and relative configuration were elucidated based on extensive spectroscopic analyses. Moreover, compound 2 showed inhibitory effect on NO production in RAW 264.7 macrophages at non-cytotoxic concentration (20 µM) with inhibitory rate of 69.7%. [Formula: see text].

Pepluanols C-D, Two Diterpenoids with Two Skeletons from Euphorbia peplus.

Pepluanols C and D (1 and 2), featuring unprecedented 5/5/10 with out,out-[7.2.1]bicylcododecane core and 6/6/7/3 fused-ring skeletons, respectively, were isolated from Euphorbia peplus. Their chemical structures and absolute configurations were determined by a series of extensive spectroscopic methods, and X-ray diffraction analysis. In addition, pepluanols C and D showed 31.6 ± 8.3% and 30.5 ± 2.8% peak current inhibition on the Kv1.3 potassium channel at 30 µM.

Identification of mangiferin as a potential Glucokinase activator by structure-based virtual ligand screening.

The natural product mangiferin (compound 7) has been identified as a potential glucokinase activator by structure-based virtual ligand screening. It was proved by enzyme activation experiment and cell-based assays in vitro, with potency in micromolar range. Meanwhile, this compound showed good antihyperglycemic activity in db/db mice without obvious side effects such as excessive hypoglycaemia.

Pepluane and Paraliane Diterpenoids from Euphorbia peplus with Potential Anti-inflammatory Activity.

Twelve new diterpenoids based on two rare skeletal types, namely, paralianones A-D (1-4) and pepluanols A-H (5-12), along with five known compounds, were isolated from an acetone extract of Euphorbia peplus. Their structures were proposed based on 1D and 2D NMR spectroscopic data analysis. These diterpenoids were evaluated for potential anti-inflammatory activity in a lipopolysaccharide-stimulated mouse macrophage cellular model. Compounds 3, 4, 11, 13, and 16 displayed moderate inhibitory effects on NO inhibition, with IC50 values ranging from 29.9 to 38.3 µM.

Three Minor Diterpenoids with Three Carbon Skeletons from Euphorbia peplus.

Euphorbia peplus has been used in traditional medicine to treat asthma and psoriasis. Three highly modified diterpenoids, namely, pepluacetal (1) and pepluanol A-B (2-3), have been isolated and identified from this plant. Compounds 1-3 exhibit unprecedented 5/4/7/3, 5/6/7/3, and 5/5/8/3 ring systems, respectively. Their structures with absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and electronic circular dichroism calculations. Since Kv1.3 is a validated target for the treatment of autoimmune diseases, such as multiple sclerosis, type-1 diabetes, asthma, and psoriasis, Kv1.3 was studied in terms of its response to the new compounds. All three compounds inhibit Kv1.3, with compound 3 being the most effective with an IC50 value of 9.50 µM.

Xanthone glycosides from Swertia bimaculata with α-glucosidase inhibitory activity.

Seven new xanthone glycosides (1-7) were isolated from the n-butanol extract of Swertia bimaculata, together with six known compounds (8-13). Their structures were elucidated on the basis of extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. All the compounds were evaluated for their α-glucosidase inhibitory activities in vitro, and compounds 3, 4, and 7 exhibited significant activities to inhibit α-glucosidase. Meanwhile the effects of different substitutions on the α-glucosidase inhibitory activity of xanthone glycosides from S. bimaculata are also discussed.

Characterization of diterpenoid glucosides in roasted puer coffee beans.

Five new diterpenoid glucosides, named mascaroside I (1), mascaroside II (2), paniculoside VI (3), cofaryloside I (4), and villanovane I (5), along with seven known ent-kaurane diterpenoid glucosides (6-12) were isolated from acetone extracts of the roasted coffee beans of Coffea arabica var. yunnanensis. Their structures were established by extensive spectroscopic analysis including 1D and 2D NMR (HSQC, HMBC, COSY, and ROESY) and by comparison with published data. Cytotoxicities evaluation of the isolates showed that they were inactive against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells.

Antidiabetic effects of Swertia macrosperma extracts in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia macrosperma is a traditional folk medicine used for its anti-hepatitis, antipyretic and antidotal effects as "Dida" or "Zangyinchen" in Tibet, Yunnan and Guizhou province for a long time, and it has been reported for its anti-diabetic effects in a Chinese patent. Swertia macrosperma was reported rich in xanthones, iridoids, seco-iridoids and their glycosides, several of which had been documented as potential antidiabetic agents. The objective of this study was to investigate the antidiabetic effect of Swertia macrosperma in diabetic rats. MATERIALS AND METHODS: This study was designed firstly to evaluate the effect of Swertia macrosperma on glucose consumption in HepG2 cells. Based on the result in HepG2 cells, the antidiabetic effect of ethanol extract (EE) and n-butanol extract (BE) were investigated in diabetic rats induced by high fat fed and streptozotocin. The effects of EE and BE on fasting blood glucose, oral glucose tolerance test, serum insulin, glycosylated hemoglobin, serum lipid level, serum antioxidant parameters, glucokinase, glucose-6-phosphatase activities and glycogen content in liver tissue were measured, histology examination of pancreatic tissue was also carried out. RESULTS: After 4 weeks treatment with EE and BE, apparently decreased fasting blood glucose concentrations were observed in these treated groups, compared with the diabetic control groups. Additionally, improvement in serum antioxidant parameters and lipid profile were evidenced clearly. Moreover, EE and BE had effects of protecting the pancreatic ß-cells and stimulating insulin secretion from the remaining pancreatic ß-cells, evidenced by pancreatic histology examination. Increased glucokinase activity and decreased glucose-6-phosphatase activity were observed in liver. CONCLUSION: The results of in vivo and in vitro experiment suggested that EE and BE of Swertia macrosperma had excellent effects on controlling the hyperglycemia and hyperlipidemia in diabetic rats.

Two new chiratane-type triterpenoids from Swertia kouitchensis.

Two rare new chiratane-type triterpenoids, kouitchenoids A and B (1, 2), together with oleanolic acid (3) and ursolic acid (4), were isolated from ethanol extract of Swertia kouitchensis. The new structures were determined by the analysis of MS and NMR data. In addition, compounds 1-4 showed moderate inhibitory activity against the α-glucosidase (with IC50 values ranging from 1,812 to 2,027 µM).

Preventive effects of polysaccharides from Liriope spicata var. prolifera on diabetic nephropathy in rats.

This study was undertaken to investigate preventive effects of polysaccharides (LSP) from Liriope spicata var. prolifera on diabetic nephropathy in rats, which were induced by high fat-fed and low-dose streptozotocin (STZ). The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in diabetic rats were significantly decreased after treated with LSP for 28 days. Additional, the glucose tolerance of diabetes rats showed improvement after administration of LSP. The results also indicated that LSP were able to normalize hyperlipidemia, ameliorate oxidative stress, improve renal function parameters, inhibit the structural damages of kidney tissue and down-regulate the system of advanced glycation end products - receptor for advanced glycation end products (AGE-RAGE). In conclusion, LSP had potential preventive effects on diabetic nephropathy in diabetic rats.

Xanthone glycoside constituents of Swertia kouitchensis with α-glucosidase inhibitory activity.

Ten new xanthone glycosides, kouitchensides A-J (1-10), and 11 known analogues were isolated from an n-butanol fraction of Swertia kouitchensis. The structures of these glycosides were determined on the basis of extensive spectroscopic data interpretation and comparison with data reported in the literature. In an in vitro test, compounds 2, 4, 5, 6, 11, 12, and 13 (IC50 values in the range 126 to 451 µM) displayed more potent inhibitory effects against α-glucosidase activity than the positive control, acarbose (IC50 value of 627 µM).

In vitro and in vivo anti-diabetic activity of Swertia kouitchensis extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia kouitchensis has long been used as a folk medicine to treat hepatitis and diabetes in central-western China. Therefore, this study was aimed to evaluate the anti-diabetic activity of the plant ethanol extract. MATERIALS AND METHODS: Firstly, the extract was tested for its inhibitory activity on α-amylase and α-glucosidase in vitro. Following that, insulin secretion test in NIT-1 cell was performed. Then, oral sucrose or starch tolerance test of the extract were carried out in normal mice. After that, acute effect of the extract was executed in normal and streptozotocin-induced (60 mg/kg) diabetic mice. Eventually, long term effect of the extract was performed in diabetic mice for 4 weeks. Oral glucose tolerance test and biochemical parameters were estimated at the end of the study. RESULTS: Swertia kouitchensis extract could remarkably inhibit the activity of α-amylase and α-glucosidase and stimulate insulin secretion in vitro. And also the extract displayed anti-hyperglycemic activity, improved antioxidant capacity, ameliorated the hyperlipidemia and carbohydrate metabolism in diabetic mice. CONCLUSIONS: Swertia kouitchensis exhibits considerable anti-diabetic activity and metabolic alterations in diabetic mice. These results provide a rationale for the use of Swertia kouitchensis to treat diabetes mellitus.