Jatrophane Diterpenoids with Kv1.3 Ion Channel Inhibitory Effects from Euphorbia helioscopia.

Chemical investigation of bioactive components from the whole plant of Euphorbia helioscopia resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D (1) and helioscopids A-P (2-17), along with 11 known analogues (18-28). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D (1) is the fourth natural diterpenoid with a rare bicyclo[8.3.0]tridecane skeleton. The inhibitory effect of the isolated diterpenoids against Kv1.3 ion channels was evaluated in a human embryonic kidney 293 cell model transfected with plasmid encoding Kv1.3, resulting in the identification of a series of potent Kv1.3 ion channel inhibitors, with the most active ones (2 and 15) showing IC50 values of 0.9 µM.

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.

Buxaustroines A-N, a Series of 17(13→18)abeo-Cycloartenol Triterpenoidal Alkaloids from Buxus austro-yunnanensis and Their Cardioprotective Activities.

Buxaustroines A-N (1-14), a series of triterpenoidal alkaloids featuring a novel 17(13→18)abeo motif, were obtained from the extract of Buxus austro-yunnanensis. Their structures were assigned based on NMR data analysis and X-ray diffraction crystallography. A putative biosynthetic pathway for one of the alkaloids from a co-isolate 15 is proposed. In the assessment of their bioactivities, some of the compounds displayed protective effects against doxorubicin-induced injury of myocardial cells. Preliminary structure-activity relationship studies of 1-14, which are based on the same skeleton, were conducted.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Two new compounds with anti-inflammatory activity from Alangium chinense.

A new phenolic glycoside, chinenside A (1), and a new megastigmane glycoside, chinenionside A (2), together with twelve known compounds (3-14), were isolated from the roots of Alangium chinense. Their structures were deduced on the basis of extensive spectroscopic analyses and comparison with data reported in the literature. The anti-inflammatory activity in vitro of all 13 phenolic glycosides was evaluated against lipopolysaccharide-induced mouse macrophage RAW264.7 cells. The compounds 1, 9, and 10 potentially inhibited the productions of nitric oxide (NO), prostaglandin (PEG2), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 6 (IL-6). Compound 1 (50 µM) showed stronger anti-inflammatory activity than Triptolide (TPL, 20 nm).

Diterpenoids with Rearranged 9(10→11)-abeo-10,12-Cyclojatrophane Skeleton and the First (15S)-Jatrophane from Euphorbia helioscopia: Structural Elucidation, Biomimetic Conversion, and Their Immunosuppressive Effects.

Two novel diterpenoids, one with a rearranged trans,trans-fused tricyclo[10.3.0.04,6]pentadecane framework (1) and the other with an unprecedented 15S configuration (2), were isolated from Euphorbia helioscopia. Their structures were elucidated by extensive analysis of HR-ESI-MS, NMR, quantum-chemical calculation, and X-ray crystallographic data. Biosynthetically, 1 has a unique "cyclopropane-shift-like" biogenesis involving an oxa-di-π-methane (ODPM) rearrangement, which inspired us to accomplish the biomimetic conversion of 3 to 1. Moreover, compound 1 displayed a potent immunosuppressive effect by inhibiting Kv1.3 voltage-gated channels.

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.