Antihyperglycemic activity of Selaginella tamariscina (Beauv.) Spring

Aim of the study

The present study was designed to investigate the effects of the EtOH and H₂O extracts of Selaginella tamariscina (Beauv.) Spring on hyperglycemia in diabetic rats and HepG2 cells, and to confirm the active fractions of EtOH extract in HepG2 cells.

Materials and methods

HepG2 cells and type II diabetic rats induced by low-dose streptozotocin (STZ) and high-fat diet (HFD) were used to evaluate the hypoglycemic effect of EtOH and H₂O extracts of Selaginella tamariscina. HepG2 cells were used to evaluate the promotive effect of different fractions of EtOH extract obtained from a polyamide column on glucose utilization.

Results

The results in HepG2 cells indicated that the EtOH extract had a better hypoglycemic effect than the H₂O extract. The results in diabetic rats indicated that both EtOH extract and H₂O extract were able to ameliorate the fasting blood glucose (FBG) level and improve oral glucose tolerance (OGTT). Total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels in serum were lowered. High density lipoprotein (HDL-c), insulin and superoxide dismutase (SOD) levels in serum were elevated as well as the hepatic glycogen content in diabetic rats. Compared with H₂O extract, the effects of EtOH extract were more marked. The 80% ethanol fraction exhibited a stronger hypoglycemic effect than the aqueous and 50% ethanol fractions, but the 95% ethanol fraction did not show any appreciable effects in HepG2 cells.

Conclusions

The results suggested that the EtOH extract had a better hypoglycemic effect than the H₂O extract; the 80% ethanol fraction from polyamide column had a strong hypoglycemic activity in HepG2 cells.     

Effects of total glucosides from paeony (Paeonia lactiflora Pall) roots on experimental atherosclerosis in rats

Ethnopharmacological relevance

Total glucosides of paeony (TGP), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China. Inflammation plays a critical role in the development of atherosclerotic vascular disease. Risk of cardiovascular diseases is significantly higher in patients with RA than in normal population. It has a great significance to study the effects of TGP on atherosclerosis.

Aim of the study

To investigate the effects of TGP on atherosclerosis induced by excessive administration of vitamin D and cholesterol in rats and study the mechanisms involved.

Materials and methods

Atherosclerosis was induced by excessive administration of vitamin D and cholesterol in rats. TGP was intragastrically administered for 15 weeks. The serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer. Apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy.

Results

Compared to controls, TGP significantly lowered the serum level of TC, TG, LDL-C, ApoB, TNF-alpha, IL-6 and CRP, increased the ratios of HDL-C/LDL-C and ApoA1/ApoB, decreased the intima-media thickness (IMT) of abdominal aortal wall and improved the morphological change of the aorta.

Conclusions

TGP may attenuate the development of atherosclerotic disease. The beneficial effects are associated with its lowering blood lipids and inhibiting the expression of inflammatory cytokines.     

司他夫定、拉米夫定、奈韦拉平联合治疗AIDS效果

目的了解应用司他夫定（d4T）、拉米夫定（3TC）、奈韦拉平（NVP）方案治疗艾滋病患者的效果。方法42例艾滋病患者用d4T、3TC、NVP方案治疗1年,所有患者于治疗前和治疗后每月随访1次,并分别在治疗0个月、6个月及12个月检测病毒载量、CD4＋绝对计数和耐药情况。结果42例艾滋病患者治疗0个月、6个月、12月病毒载量平均值为5．00、2．54、2．03log10拷贝／ml,其中治疗6个月、12月后分别有24例、36例达到检测不到水平（〈50拷贝,1111）。CD4＋绝对计数治疗0个月、6个月、12月平均值分别为147、247、274个／mm^3。42例患者在治疗后发现有1例患者对ABC、AZT、d4T、DDI有潜在低度耐药突变。结论艾滋病人规范使用抗病毒治疗效果满意。     

血脂康治疗高脂血症的疗效和安全性的观察

高脂血症是引起动脉粥样硬化及导致心脑血管疾病的危险因素之一,纠正高脂血症已成为防治心脑血管疾病的重要环节,国际上大型临床试验证明,调脂干预对冠心病的一级和二级预防均有显著意义。调脂治疗可使致命性和非致命性急性心肌梗死的发生率和病死率都明显下降。     

Pharmacokinetics of lamivudine in subjects receiving peritoneal dialysis in end-stage renal failure

What is already known about this subject

• Prior to the conduct of this study, information on the pharmacokinetics of lamivudine in subjects with renal impairment was limited to patients on haemodialysis. (Br J Clin Pharmacol 1998; 46: 21–7).
• No pharmacokinetic data were available on subjects receiving lamivudine who were concurrently receiving peritoneal dialysis.
• With increasing numbers of individuals opting for peritoneal dialysis, the need to establish if dose modification was necessary in this setting was important to ensure efficacious and safe drug exposures were being obtained.

What this study adds

• This study demonstrated that similar to patients receiving haemodialysis, dose modifications based on reductions in renal function (i.e. decreased CL_CR), also applied to subjects on peritoneal dialysis.

Aims

To establish whether peritoneal dialysis (PD) requires dosing modification from the CL_CR-corrected lamivudine dose in end-stage renal failure subjects.

Methods

This was an open-label cohort study. A total of 12 subjects undergoing PD, six continuous ambulatory peritoneal dialysis (CAPD) and six automated peritoneal dialysis (APD), for at least 3 months received lamivudine 10 mg (5 mg ml ⁻¹ × 2 ml) daily for 8 consecutive days, followed by an intensive pharmacokinetic assessment. Urine and dialysate were collected from 0 to 24 h postdose on day 8 where possible. Pharmacokinetic parameters were calculated using noncompartmental techniques.

Results

The plasma pharmacokinetic results demonstrated that peritoneal dialysis clearance (CL_D) of lamivudine was similar between APD and CAPD patients with median (range) of 0.19 l h⁻¹ (0.14–0.25) and 0.1 l h⁻¹ (0.09–0.25), respectively. CL_D was approximately 1/15th to 1/30th of plasma clearance, demonstrating that peritoneal dialysis does not contribute significantly to overall lamivudine clearance in this patient population. The AUC(0,24 h) of lamivudine given 10 mg daily to APD and CAPD patients was 3430 ng ml⁻¹ h and 3469 ng ml⁻¹ h, respectively, similar to historical data obtained in patients with normal renal function administered at the normal dose of 100 mg daily (3781 ng ml⁻¹ h). There were no clinically significant changes in any safety assessments that were attributable to lamivudine.

Conclusions

ESRD patients who receive CAPD or APD require no supplemental dosing. These patients should follow the standard dosing reduction for patients infected with HIV or HBV with renal dysfunction.     

Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile and tissue antioxidant status in rats fed a high-cholesterol diet

The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.     

Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals

Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. Previously, we have demonstrated potent hypoglycemic activity of lyophilized aqueous extract of Murraya koenigii leaves in normal and alloxan induced diabetic rabbits for short duration of 6 h. In this study, we examined the effect of 1 month oral administration of Murraya koenigii aqueous leaves extract in normal and STZ induced severe diabetic rats, at the dose of 300 mg/kg bw, on various biochemical parameters, viz., fasting blood glucose (FBG), total cholesterol (TC), HDL-cholesterol (HDL), triglyceride (TG), alkaline phosphatase (ALKP), serum glutamate oxaloacetate and pyruvate transaminases (SGOT and SGPT) and serum creatinine. In case of diabetic animals fasting blood glucose (FBG) levels of treated animals reduced by 48.2% after 30 days treatment with the aqueous leaves extract. A fall of 19.2 and 30.8% in TC and 22.97 and 37.1% in TG levels were also observed in the case of treated normal as well as diabetic rats, respectively. Feeding the extract increased the HDL-cholesterol level by 16 and 29.4% in normal and diabetic rats, respectively, as compared with their initial values. In the normal rats after 1 month of oral administration of the extract SGOT and SGPT levels were decreased by 21.7 and 25.0%. Serum alkaline phosphatase values of the treated normal animals were also reduced by 33% while negligible change was observed in the normal control animals. In the case of diabetic rats, SGOT and SGPT levels were reduced by 36.7 and 32.2%, respectively, whereas ALKP levels decreased by 39.7% after 1 month oral administration of the extract. The serum creatinine levels decrease in normal as well as in the diabetic animals by 17.75 and 18.2%, respectively, as compared to initial values. In the diabetic control animals the urinary sugar remains at +4 level but there was a decrease of 75% in urine sugar in the case of treated diabetic rats. This indicates that the aqueous extract of Murraya koenigii has favorable effect in bringing down the severity of diabetes.     

Transforming properties of TC-1 in human breast cancer: interaction with FGFR2 and beta-catenin signaling pathways

Breast cancer development is associated with gene amplification and over expression that is believed to have a causative role in oncogenesis. Previous studies have demonstrated that over expression of TC-1(C8orf4) mRNA occurs in approximately 50% of breast cancer cell lines and primary tumor specimens. Here, we show that TC-1 has transforming properties in human mammary epithelial (HME) cells and its expression is mechanistically linked to FGFR signaling cascades. In vitro experiments demonstrate that TC-1 over expression mediates both anchorage-independent and growth factor-independent proliferation of HME cells. TC-1 was down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM-52 that also has an FGFR2 gene amplification and over expression. Furthermore, forced expression of FGFR2 in HME cells increased the level of expression of endogenous TC-1 mRNA. TC-1 has been implicated as a modulator of Wnt/beta-catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of beta-catenin target genes in TC-1 over expressing cells, we did not find an association of TC-1 with global expression of beta-catenin target genes in our cells. Taken together, our data suggest that TC-1 over expression is transforming and may link with the FGFR pathway in a subset of breast cancer.     

Anti-visceral obesity and antioxidant effects of powdered sea buckthorn (Hippophae rhamnoides L.) leaf tea in diet-induced obese mice

The potential health benefits of tea have long been studied. This study examined the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six weeks. SLT suppressed body weight gain in a dose-dependent manner and significantly reduced visceral fat, plasma levels of leptin, triglyceride and total cholesterol and ALT activity compared with the high-fat-fed control mice. SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP, β-oxidation and CPT activities. However, SLT supplementation during high-fat feeding led to a significant decrease in PAP, β-oxidation and CPT activities with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and hepatic and erythrocyte lipid peroxides were significantly lowered with SLT supplements. Hepatic and erythrocyte SOD and CAT activities were also increased with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was increased in erythrocytes only. These results indicate that SLT has potential anti-visceral obesity and antioxidant effects mediated by the regulation of lipid and antioxidant metabolism in high-fat diet-induced obese mice.