Study on therapeutic targets networks of xuefu-zhuyu decoction and gualou-xiebai-banxia decoction for the treatment of coronary artery disease

Aim This work is to provide a network approach to identify the potential therapeutic targets in molecular level for xuefu-zhuyu decoction （XZD） and gualou-xiebai-banxia decoction （GXBD） in treating Coronary artery dis- ease （CAD）. Methods The networks between the ingredients/drugs and relevant target proteins for XZD, GXBD, and modern anti-CAD drugs were constructed, respectively. A master network based on the three established networks was further generated. By comparing the similarities and the differences of the targets containing in the master net- work between the individual formula and the modern drugs, the potential anti-CAD targets for XZD and GXBD were i- dentified for further pharmacological investigations. Results Although the herbal formulations and the chemical con- stituents of XZD and GXBD were significant different, both formulas presented the great similarity on target proteins and with the Tanimoto coefficient of 0. 7225. Comparison the formula-specific targets to modem drugs targets, 50 mu- tual targets with higher possibility were modulated. Moreover, a total amount of 114 mutual targets between formulas derived from the master network were identified to be not yet related to those of the approved anti-CAD drugs. Among them, the top 10 targets were identified to be NOS3, PTPN1, GABRA1, PRKACA, CDK2, MAOB, ESR1, ADH1C, ADH1B and AKR1B1. The formula-specific targets of XZD or GXBD which were not yet covered by the current anti- CAD drugs provided the potential opportunities to discovery of the new drug candidates from the two formulas for CAD treatment. Conclusion The established method of network analysis provides a novel approach for screening of the potential therapeutic targets based on the chemical constituents in traditional Chinese medicines or formulas. It is cru- cial for this work to select relatively favorable therapeutic areas of traditional Chinese medicines, syndrome-oriented formulas and syndrome differentiation of same diseases. Meanwhile, this kind of work is helpful for unveiling the mo- lecular mechanism of TCM formulas.

益肾泄浊方治疗糖尿病肾病气阴两虚、肾络瘀阻证临床研究

目的:观察益肾泄浊方辨治气阴两虚、肾络瘀阻型糖尿病肾病的临床疗效,并观察其对患者肾功能、血液流变学指标及血清因子水平的影响。方法:98例气阴两虚、肾络瘀阻型糖尿病肾病患者按照随机数字表法分为对照组和观察组患者各49例。对照组患者给予盐酸贝那普利片治疗,观察组患者则给予自拟益肾泄浊方,2周为1个疗程,两组均连续治疗6个疗程。比较两组患者临床疗效,观察糖脂代谢、肾功能、血液流变改善情况,监测治疗前后血清胱抑素C(cystatinc,CysC)、视黄醇结合蛋白(retinol-binding protein,RBP)、血浆同型半胱氨酸(homocysteine,Hcy)水平变化。结果:对照组有效率为77.6%,观察组有效率为93.9%,两组有效率比较,差异有统计学意义(P<0.05);治疗后观察组的糖脂代谢、肾功能及血液流变水平改善更为明显,各指标较对照组显著降低(P<0.05);治疗后观察组患者的血清Cys C、RBP、Hcy水平与对照组比较,差异有显著统计学意义(P<0.05)。结论:自拟益肾泄浊方能显著改善气阴两虚、肾络瘀阻型糖尿病肾病患者的糖脂代谢,提高肾脏功能,疗效肯定,其机制可能是改善血液微循环、调控CysC、RBP、Hcy等因子水平以减少肾功能损害。

Effect of Lingguizhugan decoction on myocardial Nuclear factor kappa B protein expression in rats with chronic heart failure

OBJECTIVE: To investigate the effect of Lingguizhugan decoction (LGZGD) on changes of cardiac structure and function, and its putative mechanism of action, by investigating mRNA and protein expression of myocardial nuclear factor kappa B(NF-κB), and the plasma content of NF-κB in rats with chronic heart failure.METHODS: The chronic heart failure (CHF) model in rats was induced by coronary artery ligation.Sham operation was performed in control rats. Six weeks after the procedure, rats were randomly classified into the various treatment groups: model CHF, Captopril (4.4 mg/kg), low LGZGD dose (2.1 g/kg), medium LGZGD dose (4.2 g/kg), and high LG-ZGD dose (8.4 g/kg). Treatments continued for 4 consecutive weeks. Changes of hemodynamic indices were observed by the PowerLab data acquisition and analysis system. Morphological changes of myocardium were observed by hematoxylin and eosin staining, and Masson staining. The mRNA and protein expression of myocardial NF-κB were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. The plasma content of NF-κB was detected by enzyme-linked immuno-sorbent assay.RESULTS: CHF rats showed significant dysfunction in hemodynamic indices and in cardiac structure.Compared with the sham operation group, mRNA expression of myocardial NF-κB and plasma content of NF-κB of the model group was significantly increased. All three doses of LGZGD, and Captopril,improved the hemodynamic dysfunction, and inhibited the change of cardiac structure while significantly improving the survival rate. Furthermore,compared with the model group, mRNA expression of myocardial NF-κB and plasma content of NF-κB were significantly reduced by all dosage groups of LGZGD as well as the\Captopril group.CONCLUSION: In CHF rats, LGZGD improves changes of cardiac structure and function via its inhibition of NF-κB.

Effect of Xixin decoction on O-linked N-acetylglucosamine Glycosylation of tau proteins in rat brain with sporadic Alzheimer disease

OBJECTIVE： To study the effects of Xixin decoction （XXD） on O-linked N-acetylglucosamine （O-GIcNAc） glycosylation of tau proteins in rat brain with spo- radic Alzheimer disease （SAD）, and discuss its possi- ble mechanism on prevention and treatment of SAD. METHODS： The rat model of SAD was established by intracerebroventricular injection of streptozoto- cin. The specific pathogen free male Sprague-Daw- ley rats were randomly divided into sham-opera- tion group （S）, model group （M）, donepezil group （D）, XXD at a low dose group （XL）, XXD at a medium dose group （XM） and XXD at a high dose group （XH）. After treatment and praxiology test, immuno- histochemistry and western blotting were used to detect O-GIcNAc glycosylation level of tau proteins in rat brain with SAD. O-GIcNAc glycosylation and expression of tau proteins were detected by O-GIcNAc-specific antibodies RL2 and CTD110.6. RESULTS： O-GIcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significant- ly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups （P〈0.05, P〈0.01）, while no obvious dif- ferences were observed between D group and M group （P〉0.05）. CONCLUSION： XXD can significantly improve O-GIcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hy- perphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological pro- cess of SAD.

Effects of Chaiyuwendan decoction on endocannabinoids levels in adipose tissue of rats with chronic stress-induced depression

OBJECTIVE:To investigate how Chaiyuwendan decoction(CWD)affects endocannabinoid levels in the adipose tissue of depressed rats.METHODS:Twenty-four male Sprague-Dawley rats were randomly divided into four groups with six rats in each.One group was randomly selected as the control group.The remaining three groups were subjected to chronic stress to induce depression.Groups were randomly assigned as a model group,CWD group,and amitriptyline group.CWD was given to the CWD group once a day from the second day of modeling.The amitriptyline group was administered amitriptyline intragastrically(10 mg/kg)once a day.After treatment for 21 days,body weight and fat weight were measured and the levels of N-arachidonoylethanolamine(AEA),2-arachidonoylglycerol(2-AG),and N-palmitoylethanolamine(PEA)in adipose tissue were determined with liquid chromatography-mass spectrometry.RESULTS:Compared with the control group,body weight,fat weight,AEA,and PEA were significantly lower,and 2-AG was higher,in the model group(P<0.05,P<0.01).Compared with the model group,body weight,fat weight,the AEA,and PEA levels were significantly higher,and 2-AG level was significantly lower in the CWD group(P<0.05).However,the levels did not differ significantly between the CWD group and the amitriptyline group.CONCLUSION:CWD could regulate the levels of AEA,2-AG,and PEA in rats with depression induced by chronic stress.

Clinical Study on Zhengan xifeng（镇肝熄风）Decoction in Preventing and Treating Hypertensive Nephropathy

Seventeen cases of hypertensive nephropathy with azotemia (test group) treated with Zhen-gan Xifeng Decoction (ZGXFD) and a routine regimen of Western Medicine were observed. The result wascompared with that of 15 cases treated with routine regimen alone(control. group) . After 3 months of treat-ment, the blood pressure, sodium excretion, blood urea nitrogen and creatinine were all reduced, while cre-atinine clearance rate (CCr) and residual renal function index(RRFI) were improved significantly in bothgroups. Compared with the control group, the treatment on the test group showed a more prominent effect onlowering of diastolic blood pressure, elevating the hemoglobin, reducing the blood level of triglyceride andcreatinine as well as improving on CCr and RRFI , suggesting the deterioration of residual renal function couldbe restrained by ZGXFD , through improving the disorder of lipid metabolism, osmolality gradient and creati-nine kinetics.