Intestinal Absorption of Berberine and 8-Hydroxy Dihydroberberine and Their Effects on Sugar Absorption in Rat Small Intestine

The intestinal absorption ofberberine （Ber） and its structural modified compound 8-hydroxy dihydroberberine （Hdber） was compared, and their effects on the intestinal absorption of sugar by per- fusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography （HPLC） was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than I0%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 ~tg/mL. However, Hdber presented stronger activity than Bet （P〈0.01）. It is suggested that Hdber is ab- sorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9:A Novel Mechanism of Berberine and 8-hydroxy Dihydroberberine against Hyperlipidemia

Objective： To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine （Hdber） for the treatment of hyperlipidemia in rats. Methods： A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups： a model group （MOD）; a berberine group [BBR, 156 mg/（kg.day）]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/（kg.day）]; and a simvastatin group [SIM, 4 mg/（kg.day）]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycarides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid （FFA）, apolipoprotein A I （Apo-A I ） and apolipoprotein B （APO-B） were examined. The protein expressions of low-density lipoprotein receptor （LDL-R）, sterol regulatory element-binding protein 2 （SREBP-2）, 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR） and proprotein convertase subtilisin/kexin type 9 （PCSK-9） in liver tissues were determined by Western blot analysis. Results： Compared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues （P〈0.01）. In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes （P〈0.05 or P〈0.01）, decreased the expression levels of PCSK-9 proteins （P〈0.01）, and increased the expression levels of LDL-R proteins in the hyperlipidemic rats （P〈0.01）. These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats. Conclusions： Hdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.

蛇足石杉中一个新的Phlegmariurine型生物碱

目的 研究石杉科植物蛇足石杉Huperziaserrata (Thunb .)Trev .的生物碱成分。方法 应用各种色谱技术进行分离纯化 ,经衍生物制备和光谱数据分析鉴定其结构。结果 从蛇足石杉中分离得到 1个新生物碱。 结论该化合物为一新的phlegmariurine型生物碱 ,命名为 8β 羟基马尾杉碱乙 ( 8β hydroxyphlegmariurineB)。

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

To investigate the malondialdehyde（MDA） levels,paraoxonase1（PON1） activity and 8-hydroxy 2-deoxyguanosine（8-OHd G） levels in the primary open angle glaucoma（POAG） patient.Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHd G by high-performance liquid chromatography（HPLC） and PON1 by spectrophotometry.The data obtained were analyzed statistically.MDA levels were 10.46±8.4 and 4.70±1.79 μmol; PON1 levels were 121 ±39.55 and 161.62 ±60.22 U/m L; and 8-OHd G values were1.32 ±0.53/10~6 d G and 0.47 ±0.27/10~6 d G in the POAG patients and the control group,respectively.The difference was significant in MDA levels,8-OHd G levels and PON1 activity in POAG patients in comparison with controls（P 〈0.001）.We concluded that the observed increase in MDA and 8-OHd G levels may be correlated with decreased PON1 activity.Oxidative stress plays an important role in glaucoma development.

Sulforaphane Protects Astrocytes Against Oxidative Stress and Delayed Death Caused by Oxygen and Glucose Deprivation

氧化应激是缺血再灌注后星形胶质细胞损伤和死亡的重要分子机制之一,可能成为有效的干预靶点。下述治疗策略可减轻缺血再灌注条件下产生的多种反应性氮氧化合物损伤。这种方法可通过使用化学试剂或适当条件促进转录活化因子NRF2从细胞浆转入细胞核,并与抗氧化基因反应位点结合,来诱导缺血再灌注后损伤细胞的Ⅱ期基因反应。本研究将验证如下假说:NRF2基因表达通路激活剂sulforaphane能对体外无氧无糖环境处理的培养皮质星形胶质细胞起神经保护作用。将皮质星形胶质细胞暴露于无氧无糖环境(OGD)4 h,于干预前48 h或干预后给予5μMsulforaphane(NRF2基因表达通路激活剂)培养48 h,两种培育条件下细胞死亡均明显减少。免疫细胞化学结果表明干预前给予sulforaphane处理,细胞中DNA/RNA氧化标志物8-hydroxy-2-deox-yguanosine的表达在恢复给氧4 h后降低,两种培育条件下胞浆内及胞核内NRF2的免疫反应均增强且NQO1(NRF2转录活化基因产物)的表达和酶活性均增强。本研究提示sulforaphane可通过激活NRF2抗氧化基因表达通路,减少体外缺氧再灌注后星形胶质细胞的死亡。