Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C. The results suggested that compounds A-C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A-C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) were also suppressed by wortmannin. Western blot results indicated that compounds A-C-induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A-C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A-C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.

The known compounds cappariloside A and stachydrin, an adenosine nucleoside, and for the first time from plants of the Capparidaceae family the known compounds hypoxanthine and uracil were isolated from Capparis spinosa (Capparidaceae) fruit.Capparis spinosa (Capparidaceae) is widely distributed throughout the whole world. Information on alkaloids, flavonoids, and glycosides [1][2][3][4][5] in addition to lipids and carbohydrates [6] from this plant has been published.Herein we report a study of alkaloids from fruit of C. spinosa growing in Xinjiang Autonomy Region of China. The alcohol extract of ground and defatted ripe fruit of C. spinosa produced total extracted substances containing also water-soluble alkaloids of the betaine type. The lipophilic components were removed by washing the acidic solution of extracted substances with ether. The total alkaloids were obtained by treatment of the acidic solution with conc. ammonia to adjust the pH to 9 and extraction with n-butanol (fraction A). The dried alkaloidal fraction A was chromatographed over a silica-gel column with elution by CHCl 3 , CHCl 3 :CH 3 OH, and CH 3 OH. Work up with CH 3 OH of the CHCl 3 :CH 3 OH (12:1) fractions isolated amorphous hypoxanthine (1) and uracil (2) [7,8], which were identified using PMR and 13 C NMR spectral data and authentic samples (spectral properties are given in Experimental).Crystalline 3, mp 228-229°C, was isolated from CHCl 3 :CH 3 OH (10:1) fractions. The UV spectrum of 3 had absorption maxima at 206.4 and 259.6 nm. The IR spectrum had absorption bands for active H at 3425, 3370 (NH 2 ), 3320, and 3143 (OH) cm −1 ; lactone ring (tetrahydrofuran), 1680; ether, 1100 and 1030; and tri-and disubstituted aromatic rings, 1600, 1577, 870, 822, 795, and 765. The mass spectrum of 3 gave a peak for the molecular ion with m/z 267 and fragments with m/z 148 and 119 produced by cleavage of the tetrahydrofuran ring. Peaks for ions with m/z 134 and 133 corresponded to fragments formed by cleavage of the C-N bond between the main part of the molecule and the tetrahydrofuran ring. NMR data ( 1 H and 13 C) are given in Experimental.The spectral data (UV, IR, mass, NMR) were reminiscent of those of adenosine (3) [9]. However, the lack of an authentic sample prohibited reliable identification of 3 as adenosine. As a result, a single-crystal x-ray structure analysis (XSA) of 3 showed that the isolated base was in fact the known nucleoside adenosine (C 10 H 13 N 5 O 4 ), which is constructed from D-ribose and a purine base in which the N-9 atom of the purine base adenine is bonded to C-1 of D-ribose [10][11][12][13]. Adenosine

Ligularia cymbulifera is one of the predominant species in the Hengduan Mountains, China, and has led to a decrease in the amount of forage grass in this area. However, little is known about the mechanism behind its predominance. In this study, two novel eremophilane sesquiterpenes, ligulacymirin A and B (1 and 2), together with seven other known terpenoids (3–9), were isolated from the roots of L. cymbulifera. The structures of 1 and 2 were determined by spectroscopic methods and single-crystal X-ray diffraction. Each compound showed phytotoxic activities against Arabidopsis thaliana, and each was detected and identified in rhizosphere soil by UHPLC-MS. Compound 3 was the most potent phytotoxin, showing remarkable inhibition against both seedling growth (EC50 = 30.33 ± 0.94 μg/mL) and seed germination (EC50 = 155.13 ± 0.52 μg/mL), with an average content in rhizosphere soil of 3.44 μg/g. These results indicate that terpenoids in L. cymbulifera roots might be released as phytotoxins in rhizosphere soil to interfere with neighboring plants.