Bingru Ren

Hypoglycemic effect of the total flavonoid fraction from Folium Eriobotryae

The antidiabetic effect of the total flavonoids fraction from leaves of Eriobotrya japonica (EJF) was evaluated through normal and streptozotocin-induced diabetic mice with graded oral doses of 150, 300, 450 mg/kg for 7 days or 14 days. The result showed that the dose of 300 mg/kg and 450 mg/kg resulted significant hypoglycemic effect on normal mice, the dose of 300 mg/kg induced significant decrease in plasma glucose concentration (PGC), glycosylated serum protein (GSP), total cholesterol (TC) and triglyceride (TG), and significant increase in superoxide dismutase (SOD) activity and serum insulin level in streptozotocin-diabetic mice. These results suggested that EJF has hypoglycemic potential.

Total sesquiterpene glycosides from Loquat (Eriobotrya japonica) leaf alleviate high-fat diet induced non-alcoholic fatty liver disease through cytochrome P450 2E1 inhibition

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, which affects 20-40% of the population in the world. Loquat (Eriobotrya japonica) Leaf possesses several pharmacological actions. Many sesquiterpene glycosides were reported to be isolated exclusively from the Loquat Leaf, however, their biological activity has been rarely investigated. The present study was designed to evaluate the pharmacological effect of total sesquiterpene glycosides (TSG) in high-fat diet (HFD) induced NAFLD mice with its related mechanisms of action. Mice were fed with a normal diet or HFD for 8 weeks. TSG (25 and 100mg/kg/day), simvastatin (10mg/kg/day) or vehicle were orally administered for last 4 weeks of the 8-week HFD feeding period. From the result, it was showed that TSG significantly reduced the body weight and fat deposition in the liver of NAFLD mice. It also decreased total cholesterol (TC) and triglyceride (TG) contents in the serum. Compared with NAFLD mice, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased and decreased after the administration of TSG in a dose of 100mg/kg, respectively. TSG reduced alanine aminotransferase (ALT) activity as well. Finally, TSG was found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) in NAFLD mice. In summary, this study demonstrates that TSG reduces oxidative stress by downregulating of CYP2E1 expression and JNK phosphorylation in NAFLD, and alleviates NAFLD ultimately. TSG potentially serves as bioactive compounds for the treatment of NAFLD.

A novel sesquiterpene glycoside from Loquat leaf alleviates oleic acid-induced steatosis and oxidative stress in HepG2 cells

Loquat (Eriobotrya japonica) leaf has displayed beneficial effect on metabolic syndrome. In our previously study, total sesquiterpene glycosides (TSG) isolated from Loquat leaf exhibited therapeutic effect on Non-alcoholic fatty liver disease (NAFLD) in vivo, but the accurate active compound remains unknown. Sesquiterpene glycoside 1 (SG1) is a novel compound, which is exclusively isolated from Loquat leaf, but its biological activity has been rarely reported. The present study was designed to evaluate the pharmacological effect of SG1, the main component of TSG, in oleic acid (OA)-induced HepG2 cell model of NAFLD with its related mechanisms of action. In this study, both SG1 and TSG were found to significantly reduce the lipid deposition in the cell model. They could also decrease total cholesterol (TC), triglyceride (TG) and intracellular free fatty acid (FFA) contents. Compared with OA-treated cells, the superoxide dismutase (SOD) level increased, and the malondialdehyde (MDA) and 4-hydroxynonenal levels respectively decreased after the administration of SG1 or TSG. The high dose of SG1 (140 μg/mL) displayed a similar therapeutic effect as TSG at 200 μg/mL. Both SG1 and TSG were found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) and its downstream target c-Jun in OA-treated cell. These results demonstrate again that TSG are probably the main responsible chemical profiles of Loquat leaf for the treatment of NAFLD, for which it can effectively improve OA-induced steatosis and reduce oxidative stress, probably by downregulating of CYP2E1 expression and JNK/c-Jun phosphorylation, while SG1 may be the principle compound.

Flavonoids isolated from the flowers of Limonium bicolor and their in vitro antitumor evaluation

Background: Limonium bicolor, a halophytic species, can grow in saline or saline-alkali soil, is well known as a traditional Chinese medicine. Recently it attracted much attention for its treatment for cancer. Objective: The present study was performed to evaluate this species from the phytochemical standpoint and the possible relationship between the antitumor activity and its natural products. Materials and methods: The chemical constituents from the flowers of L. bicolor were investigated through bioassay-guided fractionation and isolation. All the individual compounds were characterized by spectroscopic analysis and their potential antitumor activity was tested against three different human tumor cell lines by MTT assays. Results: The EtOAc extract was proven as the most potent fraction and further fractionation led to the isolation of 15 natural flavonoids, which were characterized as luteolin (1), acacetin (2), quercetin (3), isorhamnetin (4), kaempferol (5), eriodictyol (6), kaempferol-3-O-α-L-rhamnoside (7), kaempferol-3-O-β-D-glucoside (8), quercetin-3-O-α-L-rhamnoside (9), quercetin-3-O-β-D-glucoside (10), quercetin-3-O-β-D-galactoside (11), myricetin-3-O-α-L-rhamnoside (12), kaempferol-3-O-(6″-O-galloyl)-β-D-glucoside (13), hesperidin (14) and rutin (15). The biotesting results demonstrated that both compounds 1 and 3 showed good cytotoxicity against human colon cancer cells (LOVO). Compound 5 exhibited relative greater growth inhibition against both human breast cancer cells (MCF-7) and osteosarcoma cell lines (U2-OS) at the concentration of 100 μg/mL. Conclusion: On the basis of these findings, the flavonoids were deduced to be potentially responsible for the antitumor activity of L. bicolor. The preliminary structure–activity relationship analysis suggests that the 3-O-glycosylation moiety in natural flavonoids was not essential for the antiproliferative activity on LOVO and U2-OS cells. Abbreviation used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, EtOAc: Ethyl acetate; LOVO: human colon cancer; MCF-7: human breast, cancer; U2-OS: human osteosarcoma; 5-FU: 5-Fluorouracil; DMSO: dimethyl sulfoxide, NMR: nuclear magnetic resonance; HR-ESI-MS: high resolution electrospray ionization mass chromatography, HPLC: high performance liquid chromatography, EtOH: ethanol; n-BuOH: n-butanol; CC: column chromatography, TLC: thin layer chromatography; PBS: phosphate-buffered saline.

Hepatoprotective Effect of Loquat Leaf Flavonoids in PM2.5-Induced Non-Alcoholic Fatty Liver Disease via Regulation of IRs-1/Akt and CYP2E1/JNK Pathways

Ambient air particulate matter (PM) represents a class of heterogeneous substances present in polluted air, which contains many harmful components. Exposure to ambient particulate matter in fine rages (PM2.5) is associated with non-alcoholic fatty liver disease (NAFLD). Loquat Leaf possesses pharmacological actions on NAFLD. As the main biological active ingredients, the potential therapeutic role of total flavonoids (TF) isolated from Loquat Leaf in PM2.5-induced NAFLD model remains unclear. The present study was designed to explore the hepatoprotective effect of TF in PM2.5-induced NAFLD mice with its related mechanisms of action. Mice were exposed to PM2.5 to induce NAFLD, and body weight, the ratio of liver to body weight, and blood lipids increased significantly compared with the control group. It was found that TF significantly reduced the above parameters in PM2.5-induced NAFLD mice. TF treatment alleviated oxidative stress by preventing the accumulation of oxidative product malondialdehyde (MDA) and by strengthening the anti-oxidative capacity of superoxide dismutase (SOD). TF was also found to reduce the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the PM2.5 group. In addition, TF repaired the PM2.5-induced decline of insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. Meanwhile, the data showed TF suppressed the expression of cytochrome P450 2E1(CYP2E1) and the phosphorylation of c-jun N-terminal kinase (JNK) in PM2.5-induced NAFLD. Taken together, these findings show that TF alleviate PM2.5-induced NAFLD via regulation of IRs-1/Akt and CYP2E1/JNK pathways, which may have potential for further development as novel therapeutic agents for NAFLD.

A New Sesquiterpene Glycoside from the Leaves of Eriobotrya japonica

A new sesquiterpene glycoside, namely β-monocyclonerolidol-3-O-α-L-rhamnopyranosyl-(1→4)-α-Lrhamnopyranosyl-( 1→2)-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (1), was isolated from the leaves of Eriobotrya japonica. Its structure was characterized by chemical and spectroscopic methods.