Anti-Diabetic Effects and Molecular Mechanisms of Amide Alkaloids from Piper longum Based on Network Pharmacology Integrated with Cellular Assays.

Piper longum is a well-known spice and traditional medicine. It was revealed to possess anti-diabetic activity, but few information about its active component and underlying mechanism could be available. In this study, retrofractamides A (1) and C (2) isolated from P. longum showed potent inhibitory activity against PTP1B. Therefore, the potential mechanism was predicted by network pharmacology and molecular docking. PI3K/AKT was obtained as the most remarkable pathway against type 2 diabetes mellitus (T2DM), and AKT1 and GSK3ß were yielded as the top two core targets of retrofractamides A (1) and C (2). Molecular docking of compounds with AKT1 and GSK3ß showed strong binding affinity between them. Additionally, cellular experiments with a L6 cell model was conducted to further verify the above predictions. Results indicated that retrofractamides A (1) and C (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they promoted glucose consumption, glucose uptake, glycogen synthesis and glycolysis.

Chemical profiling of spermidines in goji berry by strong cation exchange solid-phase extraction (SCX-SPE) combined with ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS/MS).

Lycium barbarum fruit (Goji berry) have been used as a traditional Chinese medicine (TCM) with its outstanding biological and pharmacological activities. Spermidine alkaloids are a major class of bioactive constituents in goji berry, nevertheless, detailed information related to its identification remains scarce. In this study, chemical profiling of spermidines in goji berry was carried out by ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Four structure types of standards were used to study the comprehensive fragmentation rules of spermidines. Different types of spermidines were identified by distinctive MS/MS fragment ions. Noticeably, it was first proposed that the co-existence of fragment ions at m/z 220 and 222 was the key characteristic for distinguishing spermidine isomers. According to the structural feature of spermidines, a quick, convenient, highly selective strong cation exchange solid-phase extraction (SCX-SPE) combined with RP-LC procedure was developed for selective enrichment and the MS detection compatibility. A total of 41 out of 58 spermidines were tentatively characterized using the established method, of which 26 were reported for the first time from goji berry. This study provides guidelines and references for the identification of spermidines in natural products.

The estrogenic activity of isoflavones extracted from chickpea Cicer arietinum L sprouts in vitro.

Isoflavones have drawn attention due to their potential therapeutic use. Isoflavones are the important chemical components of the seeds and sprouts of chickpea and higher isoflavones in sprouts than in seeds. However, there have been no previous reports of the estrogenic activity of isoflavones extracted from chickpea Cicer arietinum L sprouts (ICS) in vitro. In this study, which incorporated several in vitro bioassays methods, we systematically evaluated the estrogenic properties of ICS. MTT assay showed that ICS at the low concentration ranges (10(-3)-1 mg/L) promoted MCF-7 cell growth, while at high concentrations, (>1 mg/L) inhibited cell proliferation, indicating ICS worked at a diphasic mechanism. Flow cytometric analysis further calculated the proliferation rate of ICS at low concentration (1 mg/L). ERα/Luc trans-activation assay and then semi-quantitative RT-PCR analysis indicated that ICS at low concentrations induced ERα-mediated luciferase activity in MCF-7 cells and promoted the ER downstream target gene pS2 and PR trans-activation. These effects were inhibited by ICI 182,780, a special antagonist of ER, indicating that an ER-mediating pathway was involved. Alkaline phosphatase (AP) expression in Ishikawa cells showed that ICS at low concentrations stimulated AP expression. Our current study is the first to demonstrate that ICS has significant estrogenic activity in vitro. ICS may be useful as a supplement to hormone replacement therapy and in dietary supplements.

Effects of pomegranate flowers polyphenols on liver PON expression of diabetes combining non-alcoholic fat liver diseases rats / 药学学报

To investigate the protective effects and possible mechanism of pomegranate flowers polyphenols (PFP) on liver function of rats with diabetes combining non-alcoholic fat liver diseases, diabetes combining nonalcoholic fat liver disease model rats were established with high calorie feeding and small dose intraperitoneal injection of streptozotocin (STZ). Model rats were randomly divided into: model group, metformin group, pomegranate flowers polyphenols low, medium and high dose group (75, 150 and 300 mg x kg(-1)). After four weeks treatment, the levels of FPG, blood fat profiles and serum insulin, ALT, AST levels, SOD and MDA in the liver and serum separately were analyzed with biochemical methods. Paraoxonase (PON1 and PON3) mRNA and protein expression in liver were checked by RT-PCR and immunohistochemical method. Pathological changes of the liver were observed. FPG, IRI, non-HDL-C and transaminase significantly reduced and HDL-C raised in the each PFP dose group; Furthermore, compared with model group, fat drops in liver cells significantly reduced, antioxidant ability enhanced, PON1 mRNA and protein expression level in liver increased significantly. The protective effects of PFP against diabetes combining non-alcoholic fat liver diseases rats might through the increase liver PON1 mRNA and protein expression further enhanced the body antioxidant capacity and reduced IRI so as to ameliorate the rat hepatic steatosis.

Effects of two different extracts of total saponins from Cicer arietinum on kidney of T2DM rats / 药学学报

Protective effects of two different extracts of TSCA (total saponins from Cicer arietinum) were studied on kidney of T2DM rats. The diabetic model group was established with high calorie feeding and small dose injection of streptozotocin (STZ, 45 mg x kg(-1)). DM rats were randomly assigned to model group (feed with propylene glycol 1 mL/100 g), TSCA high dose group (300 mg x kg(-1)), TSCA low dose group (100 mg x kg(-1)) and normal control group (feed with propylene glycol 1 mL/100 g). After four weeks treatment with TSCA I and II, the levels of FPG FIns, BUN, Scr, ATII, ET-1, TXB2 and 6-keto-PGF1alpha in blood and the activities of SOD, GSH-PX and MDA in kidney were analyzed by biochemical methods. After four weeks treatment with TSCA II, the levels of FPG FIns, BUN, Scr, ATII and ET-1 were reduced significantly; and the ratios of TXB2 to 6-keto-PGF1alpha and SOD were effectively alleviated in TSCA II group. While there is no significant change on FPG and BUN in comparison to the rats treated with TSCA I, Scr, ATII, ET-I, GSH-PX and SOD were alleviated. The results suggest that TSCA II could be used to reduce FPG and FIns. According to the result of vasoactive substances index, TSCA II is more effective than TSCA I on renal protection of DM rats.

New phthalide glycosides from Helichrysum arenarium (L.) Moench.

Two new prenylated phthalide glycosides 1 and 2 were isolated from the whole plant of Helichrysum arenarium, and their structures were elucidated on the basis of spectral data.