Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/ß-Catenin Signaling Pathway Components.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/ß-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, ß-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/ß-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.

Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide.

Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. ß-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance ß-glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of ß-glucuronidase could be increased by 2.66-fold via the addition of ISL to a ß-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the Km and Ea of ß-glucuronidase reacting with GL. This study sheds new light on the mechanism of ß-glucuronidase and helps to make industrial production of GAMG through fermentation feasible.

Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model.

Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin (1), glycyrrhetic acid-3-O-mono-ß-d-glucuronide (2), and glycyrrhetinic acid (3); and the selected major flavonoids, licochalcone A (4), licochalcone B (5), licochalcone C (6), echinatin (7), isoliquiritin apioside (8), liquiritigenin (9), liquiritin apioside (10) isolated from Glycyrrhizae radix et rhizoma, were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3, 5-7, and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1, 8, and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application.

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes.

Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling.

[Study on chemical constituents in seeds of Helicia nilagirica (II)].

OBJECTIVE: To study the chemical constituents in seeds of Helicia nilagirica. METHOD: The ethanol extract was seperated by petroleum ether, dichloromethane, n-butanol in sequence, then isolated by silica gel column chromatography. The structures were identified and elucidated by physicochemical properties and spectral analysis. RESULT: Five compounds were isolated from the dichloromethane and n-butanol extracts, identified as p-hydroxybenzaldehyde (1), p-hydroxybenzoic acid (2), gallic acid (3), helicide (4), 4-formylpymyl-O-beta-D-glucopyranoside (5). CONCLUSION: All the compounds except IV were isolated from the plant for the first time. The compounds I, II and III were isolated from the genus Helicia for the first time.

[Study on sterols and triterpenes from the stems of Akebia quinata].

The ethanol extract from Akebia quinata was seperated by dichloromethane, n-butanol in sequence. Six compounds were isolated and identified as beta-sitosterol (I), delta(5,22) stigmasterol (II), oleanolic acid (III), hederagenin (IV), daucosterol (V), delta(5,22) stigmasterol-3-O-beta-D-glycopyranoside (VI). Compound VI was isolated from Akebia plants for the first time.