Twelve undescribed derivatives of ganoderic acid isolated from Ganoderma luteomarginatum and their cytotoxicity against three human cancer cell lines.

Lanostane triterpenoids are thought to be the main underlying preclinical antitumor secondary metabolites of the genus Ganoderma. To further explore the potential cytotoxic triterpenoids from Ganoderma luteomarginatum, the ethyl acetate soluble fraction of 95% ethanolic extract was systematically studied. Twelve previously undescribed lanostane-type triterpene acids were isolated from the fruiting bodies of G. luteomarginatum, and their structures were elucidated by extensive spectroscopic analyses. Among them, 11 compounds have an unusual ß-configuration for OH-15. All isolates were assessed for cytotoxic activities using three human cancer cell lines (A549, HGC-27, and SMMC-7721) and one human normal cell line (LO2). (17Z)-3ß,7ß,15ß-Trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate and (20E)-15ß-hydroxy-3,7,11,23-tetraoxolanost-20(22)-en-26-oate exhibited significant selective cytotoxicity against HGC-27 cells and A549 cells, respectively, with IC50 values of 6.82 ± 0.77 and 13.67 ± 1.04 µM, while 3ß,7ß,15ß-trihydroxy-11,23-dioxolanost-8-en-26-oate inhibited the proliferation of both A549 and SMMC-7721 cells. In addition, Hoechst fluorescence 33,258 staining and Annexin V-FITC/PI double staining proved that (17Z)-3ß,7ß,15ß-trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate could induce apoptosis in HGC-27 cells. Furthermore, a comparison of the results in this study and previous literature demonstrated that ganoderic alcohols have stronger cytotoxicity than the corresponding derivatives of ganoderic acid in the genus Ganoderma.

Lanostane triterpenoids from Ganoderma luteomarginatum and their cytotoxicity against four human cancer cell lines.

Lanostane triterpenoids are major metabolites of macrofungi from the genus Ganoderma and possess enormous substitution diversity and remarkable biological activities, especially anticancer, antioxidant, and anti-inflammatory effects. The present phytochemical investigation resulted in the isolation of nine undescribed lanostane triterpenoids and five known analogues from the fruiting bodies of Ganoderma luteomarginatum, which was first phytochemically studied by our group. Chemical structures were elucidated based on spectroscopic evidence. (5α,23E)-27-nor-lanosta-8,23-dien-3,7,25-trione and (5α,23E)-27-nor-3ß-hydroxylanosta-8,23-dien-7,25-dione are undescribed triterpenoids with an unusual 27-nor-lanostane carbon skeleton. All isolates were assayed for their cytotoxic activities using four human cancer cell lines (HGC-27, HeLa, A549, and SMMC-7721) and one human normal cell line (LO2), and the structure-cytotoxicity relationships were preliminarily explored. (5α,24E)-3ß-acetoxyl-26-hydroxylanosta-8,24-dien-7-one exhibited the highest cytotoxicity against HeLa and A549 cell lines, with IC50 values of 1.29 and 1.50 µM, respectively.

[Osteoblastic early attachment onto the surface of bioadhesive peptide modified pure titanium].

OBJECTIVE: To investigate the long-term integrity and the biological function of interface between the bioadhesive peptide modified implant surface and peri-implant tissue. METHODS: A short bioadhesive peptide containing Glycine-Tyrosine-Arginine-Glycine-Asparticacid-Serine (GYRGDS) sequence was immobilized onto the titanium implant surface by means of sol-gel coating technique and self-assembled monolayers (SAM). The chemical composition and organic functional groups on the titanium surfaces were characterized using XPS (X-ray photoelectron spectroscopy) and FTIR (Fourier transform infrared spectrometer). The adhesive strength and stability of osteoblasts on various implant surfaces were compared under flow condition. RESULTS: The results showed that alkali/hot water aging treatment could apparently improve the content of -OH functional groups of titanium surface. The chemical reactive Ti-O-Ti bonding at the surface of titanium played a vital role in inducing the formation of organosilane SAM. GYRGDS peptide can be covalently grafted onto the surface of titanium by SAM technique. The resistance of freshly adherent osteoblasts to detachment by flow was shear time dependent. When the four groups were compared under the same flow stress condition (2.05 Pa) at three specific time spans (30 min, 1 h, 2 h), the cells retention rates in GYRGDS-grafted groups were 93.0%, 54.4%, 34.4% respectively and were much higher than those in non-coated groups. CONCLUSIONS: It was suggested that GYRGDS might have positive effects on maintaining stability and adherence of cells onto the substrates under flow condition.

[Changes of endothelium-dependent vasodilation in patients with impaired glucose tolerance and type 2 diabetes].

OBJECTIVE: To investigate the changes of endothelium-dependent flow-mediated dilation (FMD) in patients with impaired glucose tolerance (IGT) and Type 2 diabetes (T2DM) and its influencing factors. METHODS: The patients with IGT and T2DM were divided into IGT group (n=36), T2DM without vascular complication group (DM1;n=57), and T2DM with vascular complication group (DM2;n=31). And 25 normal subjects served as controls (NC group). The FMD was measured by high resolution ultrasound.The serum levels of tumor necrosis factor-alpha (TNF-alpha) and high sensitive C-reactive protein (hs-CRP) were detected with ELISA, and nitric oxide (NO) with Griess Reaction. The serum glucose, lipids, and other indexes were also detected. RESULTS: Compared with the NC group, the serum levels of triglyceride (TG) total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), hs-CRP, and TNF-alpha significantly increased (P<0.05), but the serum levels of high density lipoprotein-cholesterol (HDL-C), the NO, and FMD significantly decreased (P<0.05) in the IGT, DM1, and DM2 group. With the progress of diabetes, FMD level descended. Pearson correlation analysis showed a negative correlation between FMD and glycosylated hemoglobin (HbA1c), insulin resistant index (HOMA-IR),TG,TC,hs-CRP, and TNF-alpha (P<0.01), but a positive correlation between FMD and NO,HDL-C (P<0.01) in IGT and T2DM patients. In multiple linear stepwise regression with FMD as dependent variable, NO,HbA(1)c,HDL-C,HOMA-IR, TNF-alpha, and hs-CRP showed a significant association with FMD (P<0.01). CONCLUSION: Endothelium-dependent vasodilation is impaired in patients with IGT and T2DM,which is associated with hyperglycaemia, insulin-resistance, hyperlipemia, and inflammation.

[Color Doppler flow image of Budd-Chiari syndrome].

OBJECTIVE: To evaluate the diagnostic value of color Doppler flow image (CDFI) for the diagnosis of Budd-Chiari syndrome (B-CS). METHODS: CDFI findings of 35 patients with B-CS were retrospectively analyzed and compared with the findings of venography of inferior vena cava (IVC). RESULTS: Thirty-four patients were diagnosed as B-CS by CDFI, while one patient with local tunica stenosis was misdiagnosed. The correct diagnostic rate was 97.1%. In the 34 patients, CDFI displayed stenosis or occlusion in the hepatic vein and IVC in 24 patients, IVC only in 8,and hepatic vein only in 2. CONCLUSION: CDFI may be a principal non-invasive technique to diagnose B-CS.

[Effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes].

OBJECTIVE: To investigate the effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes. METHODS: Eighty-three newly diagnosed patients with Type 2 diabetes were divided into metformin group (metformin 750 mg/d), therapeutic alliance group (rosiglitazone 4 mg/d and metformin 750 mg/d), and rosiglitazone group (rosiglitazone 4 mg/d), and 25 normal subjects were as the control group. All patients were treated for 12 weeks. The height, weight, blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum nitric oxide (NO) were measured before and after the therapy. The body mass index (BMI) and homeostasis model assessment-insulin resistant index (HOMA-IR) were calculated. The flow-mediated dilatation (FMD) and endothelium independent dilatation (EID) were measured by high-resolution ultrasound. RESULTS: The BMI, TG, TC, LDL-C, FPG, HBA1c, HOMA-IR were higher (P<0.01), but HDL-C, NO, FMD were lower (P<0.01) in all diabetic groups than those in the control group before the treatment. After the 12-week treatment, TG, FPG, HBA1c, HOMA-IR decreased significantly in all the diabetic groups (P<0.01); FINS decreased, but HDL-C, NO, FMD and EID increased (P<0.01) in therapeutic alliance group and rosiglitazone groups, while HDL-C, FINS, NO, FMD had no change in metformin group compared with those before the treatment. CONCLUSION: Endothelium-dependent vasodilation function is impaired in patients with Type 2 diabetes. The therapy with rosiglitazone can increase the serum NO level, and improve endothelium-dependent vasodilation,but metformin has no influence on the above-mentioned indexes.