Comparative effects of traditional Chinese medicines (dai-saiko-to, hatimi-zio-gan and byakko-ka-ninzin-to) on experimental diabetes and hyperlipidemia

In order to clarify the anti-hyperglycemic and anti-hyperlipidemic actions of traditional Chinese medicines, experiments were carried out with experimentally diabetic rats induced by cyproheptadine treatment. The following results were obtained: 1) Dai-saiko-to decreased the blood glucose level at 30, 60 and 120 min after glucose loading in the tolerance test; and the drug tended to increase serum insulin level and increased the ratio (glucose/insulin) at 120 min after the glucose loading. A significant decrease in serum total cholesterol was observed in the high fat diet-treated rats. 2) Hatimi-zio-gan also decreased the blood glucose level at 30 and 120 min after glucose loading. The drug did not lower the serum insulin, but rather increased the glucagon level at 120 min after the loading. The serum lipid level was not reduced by the drug. 3) Byakko-ka-ninzin-to also increased serum glucagon at 120 min, but no change of glucose and lipid in the sera under the above experimental conditions was observed. Such experimental results suggest that Dai-saiko-to might exert an effect that can improve the pathological conditions of diabetes mellitus.     

Effect of mexiletine on spontaneous sensory afferent activity in spontaneous diabetic rats (WBN/Kob rats)

In this study, we investigated the hypothesis that mexiletine has an inhibitory action on spontaneous sensory afferent activity caused by small fiber neuropathy in diabetic rats (WBN/Kob rats). Gastric administrations of mexiletine (10 mg in 0.3 ml saline) and the local anesthetic agent lidocaine (10 mg in 0.3 ml saline) were made in urethane-anesthetized rats. In 6 of 7 WBN/Kob rats (57-62 weeks of age), spontaneous afferent activity was observed and was significantly inhibited after administration of mexiletine, whereas it was not seen in either WBN/Kob rats (54 weeks of age) or Wistar SLC rats (31 and 35 weeks of age). This inhibitory action of mexiletine was sustained for more than 2 h after the administration. In contrast, lidocaine administration also inhibited the spontaneous nerve activity, but the magnitude of the inhibitory action was less than that of mexiletine. In another experiment, the afferent conductance velocity of the sural nerve was not affected after mexiletine was administrated in the WBN/Kob rats (62 weeks of age). The results suggest that pain mitigation of a diabetic prescribed with mexiletine may depend on the inhibitory effect of mexiletine on the generation of the spontaneous afferent action potentials by mexiletine in aged WBN/Kob rats, whereas mexiletine has no effect on the autonomic function of the afferent nerve.     

Pharmacological studies of some traditional Chinese medicines on gastric functions. (2) The effects of oren-gedoku-to (OGT), san'o-syasin-to (SST), antyu-san (AS) and dai-saiko-to (DST) on gastric acid secretion in rats

The effects of OGT, SST, AS and DST on gastric acid secretion stimulated by histamine, pentagastrin, carbachol and 2-deoxy-D-glucose (2-DG) were studied in the perfused stomach of anesthetized rats, and these effects were compared with those of cimetidine, 16,16-dimethyl-prostaglandin E2(DMPGE2) and atropine. OGT and SST showed little or no effect on the acid secretion induced by histamine or carbachol at doses of 100 mg/kg, whereas the former showed a moderate inhibition and the latter showed a marked one against pentagastrin-stimulation. AS and DST had no effect on the acid secretion induced by carbachol at doses of 100 mg/kg, whereas they showed a moderate inhibition against histamine-stimulation, and the latter showed a significant inhibition against pentagastrin-stimulation. Further, each of the above four drugs showed a significant effect on 2-DG-stimulation. Cimetidine (1-10 mg/kg) inhibited gastric acid secretion stimulated by histamine, pentagastrin, carbachol or 2-DG in a dose-dependent manner. Similarly, DMPGE2 (10 micrograms/kg) strongly inhibited acid secretion induced by the four secretagogues. Atropine (50 micrograms/kg) inhibited acid secretion induced by carbachol or 2-DG, but not that by histamine or pentagastrin. These results suggest that OGT, SST, AS and DST clearly affect the mechanism of gastric acid secretion, and the site of action of OGT may differ from those of SST, AS and DST.     

Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats

This study was carried out to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the effects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko-to was significantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho-saiko-to, and there were significant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to significantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory effect on the function of gastric emptying in rats. The reduced gastric emptying could affect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but affect neither the intragastric dissolution nor the gastric absorption of tolbutamide.     

Pharmacological studies on the effects of some traditional Chinese medicines on gastric functions. (3) The effects of oren-gedoku-to (OGT), san'o-syasin-to (SST), antyu-san (AS) and dai-saiko-to (DST) on ethanol- and aspirin-induced gastric lesions in rats

The effects of OGT, SST, AS and DST on ethanol- and aspirin-induced gastric hemorrhagic lesions in rats were studied in comparison with those of sucralfate, 16,16-dimethyl-prostaglandin E2 (DMPGE2) and cimetidine. 1) OGT given orally at doses of 25-250 mg/kg protected gastric mucosa from injury induced by ethanol or aspirin. 2) SST prevented the appearance of aspirin-induced lesions at doses more than 25 mg/kg, and ethanol-induced lesions at 250 and 500 mg/kg. 3) AS and DST inhibited aspirin-induced lesions at more than 250 mg/kg and inhibited ethanol-induced lesions at 500 mg/kg. 4) Sucralfate (500 mg/kg) significantly prevented ethanol- and aspirin-induced lesions. DMPGE2 significantly inhibited ethanol-induced lesions at doses more than 0.1 micrograms/kg, and it inhibited aspirin-induced lesions dose-dependently at doses ranging from 0.1 to 5 micrograms/kg. Cimetidine significantly inhibited aspirin-induced lesions at doses of 10-250 mg/kg and inhibited ethanol-induced lesions at doses of 100 and 250 mg/kg. These results suggest that OGT, SST, AS and DST have a prophylactic effect on ulcerogenics, and the potency of OGT may be superior to those of SST, AS and DST.     

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.     

壳聚糖合并中药对实验性大鼠脂肪肝的治疗作用

目的；研究壳聚糖合并中药对脂肪肝的治疗作用。方法：采用小剂量四氯化碳合并高脂饮食建立大鼠脂肪肝模型。给予壳聚糖合并中药治疗，以肝脏的脂质含量及组织形态学变化为衡量标准。观察其治疗效果。结果：四氯化碳合并高脂饮食可引起大鼠肝脏明显的脂肪变性，表现为肝组织甘油三酯（TG），总胆固醇（TC），游离脂肪酸（FFA）含量显著增加，病理检查显示；肝细胞肿胀，内部充满大小不等的脂滴；壳聚糖加中药治疗组大鼠肝脏TG，TC，FFA含量显著降低。肝细胞脂变程度明显减轻。结论：壳聚糖合并中药可明显降低肝脂肪含量，对脂肪肝有明显的治疗作用。     

Pharmacological studies of some blended traditional Chinese medicines on gastric functions. (1). The effects of oren-gedoku-to (OGT), san'o-syasin-to (SST), antyu-san (AS) and dai-saiko-to (DST) on ethanol- and aspirin-induced injury of gastric mucosal barrier

We studied the effects of OGT, SST, AS and DST on ethanol- and aspirin-induced reduction of gastric transmucosal potential difference (PD) in rats as an index of gastric mucosal damage, and these effects were compared with those of sucralfate, 16,16-dimethyl-prostaglandin E2 (DMPGE2), cimetidine and proglumide. 1) OGT and SST as well as sucralfate and DMPGE2 significantly inhibited the PD reduction induced by ethanol and aspirin. 2) AS and DST as well as cimetidine significantly inhibited the PD reduction induced by aspirin, but not by ethanol. 3) Proglumide did not influence the PD reduction induced by ethanol and aspirin. 4) OGT alone, like sucralfate and proglumide, showed no influence on the basal PD, while SST, AS and DST, like DMPGE2 and cimetidine, increased the basal PD. These results suggest that OGT, SST, AS and DST protect the gastric mucosal barrier, and this effect of OGT differs from that of SST, AS and DST.     

Effects of high‐sodium intake on systemic blood pressure and vascular responses in spontaneously diabetic WBN/Kob‐Leprfa/fa rats

The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high‐salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob‐Lepr^fa/fa (WBKDF) rats, a new spontaneous animal model of T2DM. Male WBKDF rats and age‐matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal‐sodium (NS, 0.26%) diet or high‐sodium (HS, 8%) diet for 14 weeks: (i) Wistar rats on NS diet (Wistar‐NS); (ii) Wistar rats on HS diet (Wistar‐HS); (iii) WBKDF rats on NS diet (WBKDF‐NS); (iv) WBKDF rats on HS diets (WBKDF‐HS). Neither WBKDF‐NS nor Wistar‐NS rats showed significant changes in SBP throughout the experiment, but both WBKDF‐HS and Wistar‐HS exhibited significant elevation of SBP, which was more prominent (P<.01) in WBKDF‐HS than in Wistar‐HS. Phenylephrine‐induced contractions of isolated thoracic aortic rings were significantly (P<.01) enhanced in WBKDF‐HS and Wistar‐HS compared with the respective strain of rats on the NS diet. In contrast, acetylcholine‐ and nitroprusside‐induced relaxation were significantly (P<.01) diminished in both WBKDF‐HS and Wistar‐HS, and these HS diet‐induced changes were more profound (P<.01) in WBKDF rats than in Wistar rats. Significantly (P<.05) higher plasma concentrations of 8‐iso‐prostaglandin F_2α and sodium ions were observed in WBKDF‐HS than in Wistar‐HS. The current study demonstrated that WBKDF‐HS rats developed salt‐sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2DM.     

中西医结合治疗糖尿病肾病48例临床观察

目的观察黄芪注射液静点及同时应用胰岛素治疗糖尿病肾病的疗效。方法随机选取我院糖尿病肾病病人70例,其中48例糖尿病病人,采用黄芪注射液静点,同时应用胰岛素皮下注射治疗。22例糖尿病肾病病人单用胰岛素治疗。治疗前后的尿微量白蛋白、血肌酐、尿蛋白检测结果的变化情况。结果中西医结合治疗后,尿微量白蛋白、血肌酐、尿蛋白均明显下降(P<0.01)。结论黄芪注射液同时应用胰岛素治疗糖尿病肾病有很好疗效。     

Effects of sodium hyaluronate on the nociceptive response of rats with experimentally induced arthritis]

Antinociceptive effects of sodium hyaluronate (Na-HA) were studied on the basis of improvement in the graded abnormal gait elicited by arthritis induced by intra-articular administration of monosodium urate crystal (MSU) to rats. One hour before MSU injection, intra-articular administration of a 1.0% solution of Na-HA with different molecular weights, ranging from 4.70 x 10(5) to 2.02 x 10(6) (HA-200), improved the score of abnormal gait in a molecular weight-dependent manner in the experimental arthritis model. Similarly, administrations of HA-200 at concentrations ranging from 0.1 to 1.0% prior to MSU treatment resulted in improvement of the score in abnormal gait in a dose-dependent manner. To elucidate the antinociceptive mechanisms of Na-HA, effects of pretreatment with Na-HA (1.0%) of different molecular weights on prostaglandin E2 (PGE2) and bradykinin (BK) releases in synovial fluid 3 hr after MSU injection were studied. Increases in PGE2 and BK concentration in the synovial fluid were depressed in a molecular weight-dependent manner by Na-HA (1.0%) pretreatment. These results indicate that Na-HA attenuates the nociceptive responses inflicted by the MSU-induced arthritis. Such an antinociceptive effect may be due to the inhibition of PGE2 and BK synthesis in the synovial joint of rats.     

中药对原发性肾病综合征糖皮质激素治疗的增效减毒作用分析

目的 探讨中药对原发性肾病综合征(PNS)糖皮质激素治疗的增效减毒效果,为临床治疗提供参考.方法 选取收治的80例PNS患者,随机分为糖皮质激素组和中药组,每组40例.糖皮质激素组给予泼尼松片治疗,中药组在糖皮质激素组治疗的基础上给予分阶段辩证治疗.治疗6个月后,比较2组患者的临床疗效、肾功能、纤维蛋白原(Fib)、血脂代谢及免疫功能和不良反应发生率.结果 治疗6个月后,中药组总有效率为92.50%明显高于糖皮质激素组的72.50%(P<0.05);中药组24 h尿蛋白定量(UTP)、Fib均明显低于糖皮质激素组,低密度脂蛋白胆固醇(HDL-C)、IgG、白蛋白(ALB)均明显高于糖皮质激素组(P<0.05);中药组肝功能受损、血糖升高、痤疮、向心性肥胖发生率均明显低于糖皮质激素组(P<0.05).结论 对PNS的治疗在不同糖皮质激素用药治疗阶段,同时给予中药辨证用药可明显提高PNS治疗效果,且明显改善患者肾功能、血脂代谢和免疫功能,并减少不良反应的发生,增效减毒作用显著.     

中药复骨方对糖皮质激素致骨质疏松骨折大鼠骨代谢及骨密度的影响

目的 观察中药复骨方对糖皮质激素致骨质疏松骨折模型大鼠骨代谢及骨密度的影响.方法 将48只SD大鼠随机分为基础组、模型组及治疗组各16只.基础组仅给予肌内注射生理盐水1 mg/kg,模型组和治疗组予肌内注射地塞米松1 mg/kg,1次/d,3次/周,用药8周建立糖皮质激素性骨质疏松（GIOP）模型.第8周末对3组大鼠手术造成单侧股骨闭合性骨折,骨折处采用金属内固定,复制GIOP骨折模型.术后第2天开始治疗组中药复骨方药液灌胃,持续8周.检测大鼠血清钙（Ca）、磷（P）、碱性磷酸酶（ALP）、骨钙素（BGP）指标,采用双能X线吸收法（DXA）测量大鼠股骨骨密度.结果 骨折术前,模型组大鼠骨密度值为（0.219±0.013）g/cm2,基础组骨密度值为（0.283±0.015）g/cm2,模型组骨密度值明显低于基础组（t=12.8970,P＜0.05）.实验16周末,治疗组股骨全长骨骨密度为（0.265±0.014）g/cm2,高于模型组（t=9.8403,P＜0.05）.实验12周末,治疗组大鼠血清Ca为（2.35±0.19） mmol/L、P为（2.47±0.23） mmol/L、ALP为（196.74±25.38） U/L及BGP为（1.33±0.25） μg/L,与模型组比较均显著升高,差异有统计学意义（P＜0.05）.结论 中药复骨方可显著提高GIOP骨折大鼠股骨骨密度,升高GIOP骨折大鼠血清Ca、P、ALP及BGP活性,促进骨形成,有助于GIOP骨折的愈合.     

The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man

The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.     

Effects of Gomishi and Shosaiko-to on lipid peroxidation of rat brain]

Gomishi and Shosaiko-to were administered to the rats at a dose of 10-100 mg/kg daily for 2 weeks, and their effects on lipid peroxidation of rat brain were compared with that of alpha-tocopherol. Administration of Gomishi and Shosaiko-to showed almost the same suppressive action on the lipid peroxidation. Gomishi and Shosaiko-to exhibited a radical-trapping action on a stable free radical, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), which was estimated photometrically. The effects of Gomishi or Shosaiko-to at concentrations of 10(-3) to 10(-5)g/ml on lipid peroxidation of rat brain homogenates were investigated. The lipid peroxidation was inhibited by the addition of these drugs, and the suppressive effect was also dependent on the concentration. These suppressive effects with Shosaiko-to were stronger than those of Gomishi. These results suggest that the radical trapping action of Gomishi or Shosaiko-to is the likely mechanism suppressing brain lipid peroxidation; Particularly, the suppressive effect on the brain's lipid peroxidation by Shosaiko-to is at least in part due to its radical trapping action and inhibition of O2-. production.     

芪苓汤、八味地黄丸、柴苓汤抗糖尿病发病和降血糖的探讨

目的探讨中草药抗糖尿病发病和降血糖的机制.方法将大白鼠分成5组,芪苓汤组、八味地黄丸组、柴苓汤组,分别接受相应药物治疗;模型组接受自来水治疗.各组从实验的 d 8 起腹腔内注射链脲霉素 30 mg*kg-1,每天1次,连续 5 d.另设正常对照组,不作任何处理.检测大白鼠的体重、血糖、果糖胺、胰岛素及T淋巴细胞(W3/25和OX8)的百分率,取胰腺组织作组织学检查.结果用药各组的糖尿病发病率比模型组低(P<0.05).d 26 八味地黄丸组和柴苓汤组的血糖分别比 d 15 下降25%和18%(P<0.05).芪苓汤组和八味地黄丸组的W3/25细胞比率明显高于对照组.用药各组的平均胰岛面积和平均β细胞面积较模型组大.结论八味地黄丸、柴苓汤方剂具有降血糖作用;3方剂不同程度降低糖尿病发病率可能与提高细胞免疫功能有关.     

红景天苷对链脲佐菌素诱导糖尿病大鼠血糖、血脂和抗氧化能力的影响

目的研究红景天苷对链脲佐菌素诱导糖尿病大鼠血糖、血脂和抗氧化能力的影响。方法采用ip链脲佐菌素(60mg/kg)制备糖尿病大鼠模型;取造模成功的糖尿病大鼠50只,根据血糖值水平随机分为模型组、二甲双胍(25 mg/kg)组和红景天苷(25、50、100 mg/kg)组,每组10只,并另设对照组。ig给药体积均为1 m L/kg,1次/d,连续给药12周。分别于给药前和治疗后第4、8、12周测定各组大鼠空腹血糖和胰岛素水平。给药治疗12周后,分别称量各组大鼠体质量。测定血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)的水平以及血清中总抗氧化能力(T-AOC)水平,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)的活性和丙二醛(MDA)含量。结果与模型组比较,红景天苷50、100 mg/kg组糖尿病大鼠体质量明显增加,血清中TC水平和MDA含量显著降低(P0.05、0.01);与模型组比较,红景天苷25、50、100 mg/kg组糖尿病大鼠血清中TG、LDL-C水平显著降低且HDL-C水平显著升高(P0.05、0.01),T-AOC水平和SOD、CAT活性均显著升高(P0.05、0.01);与模型组比较,红景天苷100 mg/kg组糖尿病大鼠空腹血糖水平显著降低且胰岛素水平显著升高(P0.01),GSH-Px活性显著升高(P0.05)。结论红景天苷能够有效降低链脲佐菌素诱导糖尿病大鼠的血糖和血脂,并提高机体抗氧化能力。     

中药中蒽醌类的肝毒性及其分离分析技术研究进展

目的概述含有蒽醌类化合物的中药肝毒性研究现状,总结中药中蒽醌类化合物现有的分离分析方法及其存在的问题,为该类物质的质量控制方法发展提供参考。方法查阅国内外关于蒽醌类化合物肝毒性及分离分析方法的文献并加以总结。结果蒽醌类化合物是大黄、何首乌等多种常用中药的主要活性成分,有一定的肝毒性,现常用的分离分析方法也存在着选择性差、灵敏度低和操作时间长等问题。结论随着新型分离分析技术的发展,蒽醌类化合物的测定方法不断完善,有望实现对含有蒽醌类化合物的药品全面准确地质量控制。