五苓散对高尿酸血症小鼠降尿酸及肾保护机制的研究（英文）

目的：研究五苓散对高尿酸血症小鼠降尿酸和肾保护作用并探索其可能的作用机制。方法：在氧嗪酸钾连续7天诱导小鼠产生高尿酸血症模型同时每天灌胃给予不同剂量五苓散（每组10只）,并以别嘌呤醇作为阳性药对照。分别测定每组动物血清尿酸、肌酐及尿液尿酸、肌酐等水平并计算其尿酸排泄分数。采用RT-PCR和Westernblot方法分别测定小鼠肾脏尿酸盐重吸收转运体1（mURAT1）、葡萄糖转运体9（mGLUT9）、有机阴离子转运体1（mOAT1）、有机阳离子转运体1和2（mOCT1、mOCT2）及肉毒碱转运体2（mOCTN2）mRNA及蛋白表达水平。结果：与模型组比较,五苓散显著降低高尿酸血症小鼠血清尿酸与肌酐水平,促进尿酸和肌酐排泄,提高尿酸排泄分数,呈现出促进肾脏尿酸排泄与肾保护作用。五苓散显著下调高尿酸血症动物肾脏mURAT1、mGLUT9mRNA及蛋白表达水平,并上调mOAT1、mOCT1、mOCT2以及mOCTN2mRNA及蛋白表达水平。结论：这些结果表明五苓散可介导肾脏有机离子转运体表达以促进高尿酸血症和肾功能异常动物尿酸排泄并发挥其肾保护作用。     

Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice

Ethnopharmacological relevance

Modified Simiao Decoction (MSD), based on clinical experience, has been used for decades and famous for its efficiency in treating hyperuricemic and gouty diseases.

Aim of the study

To investigate the effects of MSD on anti-hyperuricemic and nephroprotective effects are involved in potassium oxonate-induced hyperuricemic mice.

Materials and methods

The effects of MSD were investigated in hyperuricemic mice induced by potassium oxonate. MSD were fed to hyperuricemic mice daily at a dose of 0.45, 0.90, 1.80 g/kg for 10 days, and allopurinol (5 mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were determined by colorimetric method. Its nephroprotective effects were evaluated by determining a panel of oxidative stress markers after the intervention in hyperuricemic mice. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blotting.

Results

MSD could inhibit XOD activities in serum and liver, decrease levels of serum uric acid, serum creatinine and BUN, and increased levels of urine uric acid, urine creatinine, FEUA dose-dependently through down-regulation of URAT1 and up-regulation of OAT1 protein expressions in the renal tissue of hyperuricemic mice. It also effectively reversed oxonate-induced alterations on renal MDA levels and SOD activities in this model.

Conclusion

MSD processes uricosuric and nephroprotective actions by regulating renal urate transporters and enhancing antioxidant enzymes activities to improve renal dysfunction in hyperuricemic mice.     

The dual actions of Sanmiao wan as a hypouricemic agent: Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice

Ethnopharmacological relevance

Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.

Aim of the study

The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.

Materials and methods

SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5 mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.

Results

SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.

Conclusion

These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.     

车前子醇提物降低急性高尿酸血症小鼠血尿酸水平及机制研究

目的:探讨车前子醇提物对高尿酸血症小鼠血清尿酸水平的影响及降尿酸作用机制.方法:车前子低、中、高剂量(1.17,2.34,4.68 g·kg-1)和别嘌呤醇(10 mg·kg-1)ig连续7d,建立小鼠高尿酸血症模型,观测对氧嗪酸钾盐诱导的急性高尿酸血症小鼠血清尿酸与肌酐含量、肝脏黄嘌呤氧化酶(XOD)与腺苷脱氨酶(ADA)的活性、肾脏尿酸转运体(mURAT1)mRNA表达的影响.结果:与正常组比,模型组小鼠血清尿酸与肌酐含量和肝脏XOD与ADA活性显著增高,并上调肾脏尿酸转运体mURAT1 mRNA的表达.提取物低、中、高剂量组血清尿酸分别为(178.32±10.26),(148.77±13.59),(160.28±14.65)μmol·L-1,明显低于模型组(235.65±19.38) μmol·L-1(P ＜0.01).血清肌酐分别为(56.12±4.58),(50.97±3.27),(52.45±4.66) μmol·L-1,明显低于模型组(107.59±8.32) μmol·L-1(P ＜0.01).肝脏XOD活性分别为(23.18±3.72),(16.96±2.45),(14.62±3.43) U·g-1,明显低于模型组(24.39±3.58) U·g-1 (P ＜0.05).ADA活性分别为(4.70±0.44),(3.89±0.24),(4.08±0.58) U·mg-1,明显低于模型组(5.92±0.84) U·mg-1 (P ＜0.05,P＜0.oi).肾尿酸转运体mURAT1 mRNA的表达分别为1.83±0.12,1.52±0.13,1.72±0.11,明显低于模型组2.22 ±0.1(P ＜0.05,P＜0.01).结论:车前子醇提物能够降低高尿酸血症模型小鼠的血尿酸,改善高尿酸血症小鼠肾脏功能.抑制XOD与ADA活性并下调肾脏尿酸转运体mURAT1 mRNA的表达,是其降低高尿酸血症小鼠血清尿酸水平的可能机制.     

Pharmacological basis for use of Lychnophora trichocarpha in gouty arthritis: anti-hyperuricemic and anti-inflammatory effects of its extract, fraction and constituents

Ethnopharmacological relevance

The ethanolic extract of Lychnophora trichocarpha Spreng. is used in Brazilian folk medicine to treat bruise, pain and inflammatory diseases.

Aim of the study

The present study aimed at investigating whether ethanolic extract of L. trichocarpha, its ethyl acetate fraction and its main bioactive compounds could be useful to treat gouty arthritis by countering hyperuricemia and inflammation.

Materials and methods

L. trichocarpha ethanolic extract (LTE), ethyl acetate fraction from ethanolic extract (LTA) and isolated compounds were evaluated for urate-lowering activity and liver xanthine oxidase (XOD) inhibition in oxonate-induced hyperuricemic mice. Anti-inflammatory activity in monosodium urate crystal-induced paw oedema, an experimental model of gouty arthritis, was also investigated.

Results

Crude ethanolic extract and its ethyl acetate fraction showed significant urate-lowering effects. LTE was also able to significantly inhibit liver xantine oxidase (XOD) activity in vivo at the dose of 250 mg/kg. Luteolin, apigenin, lupeol, lychnopholide and eremantholide C showed the anti-hyperuricemic activities among tested compounds. Apigenin also showed XOD inhibitory activity in vivo. Luteolin, lychnopholide, lupeol and eremantholide C, in turn, did not shown significant inhibitory activity towards this enzyme, indicating that this mechanism is not likely to be involved in urate-lowering effects of those compounds. LTE, LTA, lupeol, β-sitosterol, lychnopholide, eremantholide, luteolin and apigenin were also found to inhibit monosodium urate crystals-induced paw oedema in mice.

Conclusions

Ethanolic extract of Lychnophora trichocarpha and some of its bioactive compounds may be promising agents for the treatment of gouty arthritis since they possesses both anti-hiperuricemic and anti-inflammatory properties.     

3,5,2′,4′-四羟基查尔酮对小鼠血尿酸及肝脏XOD/XDH的影响

 目的 研究3,5,2′,4′-四羟基查尔酮(P40)对氧嗪酸钾诱导的高尿酸血症小鼠尿酸水平及肝脏黄嘌呤氧化还原酶的影响(量效及时效关系)。方法 腹腔注射尿酸酶抑制剂氧嗪酸钾(450 mg·kg ^-1体重)复制高尿酸血症小鼠模型。用磷钨酸法测定血尿酸(uric acid,UA)水平;用Elisa方法测定肝脏黄嘌呤氧化酶(XOD)及黄嘌呤脱氢酶(XDH)的含量。结果 灌胃给予3,5,2′,4′-四羟基查尔酮(0.5~4.0 mg·kg ^-1)后,显著降低高尿酸血症小鼠的血清尿酸水平和肝脏中黄嘌呤氧化酶的含量,与模型组相比,差异有统计学意义(P<0.05,P<0.01)。灌胃给予别嘌醇30 min、3,5,2′,4′-四羟基查尔酮 60 min时即能显著降低高尿酸小鼠血清尿酸水平;给予3,5,2′,4′-四羟基查尔酮/别嘌醇15、30、60、90 min后,均能降低肝脏中黄嘌呤氧化酶及黄嘌呤脱氢酶的含量,与模型组相比,差异有统计学意义(P<0.05,P<0.01)。结论 ①3,5,2′,4′-四羟基查尔酮可降低氧嗪酸钾所致高尿酸血症小鼠的尿酸水平,起效时间慢于别嘌醇;② 3,5,2′,4′-四羟基查尔酮的降尿酸作用与抑制黄嘌呤氧化还原酶活性有关。     

Pretreatment with Jieduxiezhuo decoction impedes elevations in serum uric acid levels in mice

Objective

To investigate whether Jieduxiezhuo decoction (JDXZD) can prevent serum uric acid elevations in mice.

Methods

Hyperuricemia in mice was induced by intraperitoneally administering uric acid (250 mg/kg). Concentrations of uric acid in serum were determined using the uric acid enzyme method. Mice were treated with JDXZD for 4 days before uric acid was administered.

Results

After intraperitoneal injection of uric acid, serum uric acid concentrations in mice significantly increased. However, the levels of uric acid in groups pretreated with 16.25 or 4.06 g/kg of JDXZD were significantly lower than those in the model and normal groups.

Conclusion

Pretreatment with JDXZD slowed increases in serum uric acid levels in mice intraperitoneally administered uric acid.     

Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents

Ethnopharmacological relevance

Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.

Aim of the study

The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.

Material and methods

The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.

Results

Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC₅₀ of 39.39 μg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10 mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.

Conclusions

The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.     

Study on the correlation between constituents detected in serum from Rhizoma Smilacis Glabrae and the reduction of uric acid levels in hyperuricemia

Ethnopharmacological relevance

Rhizoma Smilacis Glabrae (RSG) has been used in the clinical treatment of gout and hyperuricemia in China for thousands of years. Modern pharmacological studies have shown that RSG exhibits hypouricemic effects because of its significant inhibitory effect on the activity of xanthine oxidase.

Materials and methods

The Rhizoma Smilacis Glabrae extract (RSGE) at 1 mL/100 g oral administration was demonstrated to possess in vivo potent hypouricemic effects in hyperuricemic rats pretreated with oxonic acid potassium salt (200 mg/kg, 2 mL/kg). UPLC–MS was used to identify the constituents absorbed in the serum. In addition, a bivariate correlation analysis between the changes in the relative contents of the constituents from RSGE detected by HPLC and the serum uric acid levels in hyperuricemic rats at different points in time was used to calculate their correlation coefficients.

Results

A total of 14 constituents were observed in the RSGE-treated rat serum, and 11 of these were inferred. An RSGE constituent was considered correlated with the hypouricemic effects if its correlation coefficient was above 0.5. The results suggested that only seven of the constituents absorbed in the serum of the hyperuricemic rats were correlated with hypouricemic effects, namely, palmitic acid, 3′-O-methyltaxifolin glucuronide, 3′-O-methyiastilbin glucuronide, astilbin glucuronide, 5-O-caffeoylshikimic acid glucuronide, resveratrol glucuronide, and dihydrokaempferol.

Conclusion

These findings provide potent evidence for the study on RSG as a pharmacodynamic material basis and for developing RSG as a safe and promising natural drug to prevent hyperuricemia and gout instead of allopurinol.     

桂枝汤对高尿酸血症小鼠肾保护作用的研究

目的：研究桂枝汤对高尿酸血症小鼠肾保护作用及其机制。方法：用氧嗪酸钾诱导小鼠产生高尿酸血症模型,并随机分为6组：空白对照组、模型对照组、别嘌呤醇组（5 mg·kg^-1）、桂枝汤组（900、1 799和3 598 mg·kg^-1）。苏木精-伊红染色观察小鼠肾脏组织病理学变化;商品化试剂盒测定小鼠血清和尿液中尿酸、肌酐和尿素氮水平以及肝脏黄嘌呤氧化（XOD）活性。采用Western blot方法检测动物肾脏尿酸盐转运子（URAT1）、葡萄糖转运子9（GLUT9）、三磷酸腺苷结合转运蛋白G超家族成员2（ABCG2）、有机阳离子转运子1（OCT1）、OCT2、有机阳离子/肉毒碱转运子1（OCTN1）和OCTN2。结果：与模型对照组比较,桂枝汤可明显降低高尿酸血症小鼠血清尿酸、肌酐和尿素氮水平,增加尿液尿酸和肌酐浓度,提高尿酸排泄分数。另外,桂枝汤可有效抑制高尿酸血症小鼠肝脏XOD活性,下调模型动物肾脏URAT1和GLUT9蛋白水平,上调肾脏ABCG2、OCT1、OCT2、OCTN1和OCTN2蛋白水平。结论：桂枝汤可能通过抑制高尿酸血症小鼠肝脏XOD活性以减少尿酸生成、调节肾脏有机离子转运子蛋白水平以促进尿酸及其他有机离子排泄,从而发挥其降尿酸和肾保护作用。     

基于叶绿体全基因组的贝母属特异性DNA条形码的筛选

本研究通过对贝母属4个物种叶绿体基因组进行全局分析,分别查找基因区域和基因间区的高变异区域,筛选用于高效鉴别贝母属植物的新DNA条形码序列。相关研究发现贝母属植物的基因区域序列相似度极高,不适用于DNA条形码鉴定研究;共有7个基因间区可以作为潜在的贝母属植物鉴定的特异性DNA条形码。本研究所构建的DNA条形码筛选方法,为筛选用于难鉴定科属的新的DNA条形码提供了通用的方法体系。     

基于肠道尿酸转运体ABCG2的芒果苷降尿酸作用机制分析

目的:探讨芒果苷对尿酸诱导的高尿酸血症小鼠血尿酸、肠道尿酸转运体三磷酸腺苷结合盒转运蛋白G2[ATP-binding cassette superfamily G(White)member 2,ABCG2]mRNA及蛋白表达的影响,初步探讨芒果苷降尿酸的作用机制。方法:昆明种小鼠60只,随机分为6组,每组10只,分为正常组,模型组组,芒果苷(1.5,3.0,6.0 mg·kg~(-1))组和阳性药苯溴马隆(25.0 mg·kg~(-1))组,除正常组外,以腹腔注射的方式给予小鼠尿酸,诱导形成高尿酸血症模型,同时灌胃给予芒果苷及苯溴马隆,2周后磷钨酸法检测小鼠血尿酸,逆转录聚合酶链式反应(RT-PCR)及蛋白免疫印迹法(Western blot)检测小鼠空肠、回肠部ABCG2 mRNA和蛋白的表达,并采用苏木素-伊红(HE)染色观察小鼠回肠病理学变化。结果:与正常组比较,模型组小鼠血尿酸显著升高,小鼠的空部、回肠部ABCG2 mRNA明显降低,小鼠的空部、回肠部ABCG2蛋白明显升高(P0.05,P0.01),病理变化不明显;灌胃给药2周后,与模型组比较,芒果苷(3.0,6.0 mg·kg~(-1))组小鼠血尿酸明显下降(P0.05,P0.01),芒果苷(1.5,3.0,6.0 mg·kg~(-1))组小鼠的空部、回肠部ABCG2 mRNA表达均明显的上调,芒果苷(6.0 mg·kg~(-1))组小鼠空肠部ABCG2蛋白明显下调,而在小鼠回肠部,芒果苷(3.0,6.0 mg·kg~(-1))组的ABCG2蛋白表达明显下调(P0.05)。结论:芒果苷可明显降低高尿酸血症小鼠的血尿酸水平,并能使小鼠肠道ABCG2 mRNA和蛋白表达改变恢复至正常水平。     

Anti-urolithiatic effects of Punica granatum in male rats

Ethnopharmacological relevance

The traditional use of Punica granatum has been reported to regulate urine discharge and controls the burning sensation of urine.

Materials and methods

Animals model of calcium oxalate urolithiasis was developed in male rats by adding ethylene glycol 0.75% in drinking water. The Punica granatum chloroform extract (PGCE) and Punica grantum methanol extract (PGME) orally at 100, 200 and 400 mg/kg, respectively, were administered along with ethylene glycol for 28 days. On 28 day, 24 h urine was collected from individual rats and used for estimation of urine calcium, phosphate and oxalate. The serum creatinine, urea and uric acid levels were estimated in each animal. The kidney homogenate was used for the estimation of renal oxalate contents. The paraffin kidney sections were prepared to observe the CaOx deposits.

Results

The ethylene glycol control (Gr.-II) had significant (P < 0.001 vs. normal) increase in levels of urine oxalate, calcium and phosphate, serum creatinine, urea and uric acid and renal tissues oxalates, as compared to normal (Gr.-I). The paraffin kidney sections show significant histopathological changes. The treatment of PGCE and PGME at 100, 200 and 400 mg/kg doses, significantly (P < 0.001 vs. control) decreased the urine oxalate, calcium and phosphate, renal tissue oxalates and serum creatinine, urea and uric acid, in EG induced urolithiasis after 28 days.

Conclusions

The PGCE and PGME at the doses of 400 mg/kg, found to be more effective in decreasing the urolithiasis and regeneration of renal tissues in male rats.     

Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components

Ethnopharmacological relevance

Panax notoginseng (Burk) F.H. Chen (Araliaceae) is a well-known and commonly used traditional Chinese herb for treatment of various diseases, such as hemostasis, edema and odynolysis.

Aim of study

Our aim was to investigate the mechanisms of anti-hyperglycemic and anti-obese effects of Panax notoginseng saponins (PNS) in KK-Ay mice, and explore the components in PNS for such effects.

Materials and methods

KK-Ay mice received daily intraperitoneal injections of PNS 200 mg/kg or vehicle for 30 days while ginsenoside Re 14 mg/kg, Rd 15 mg/kg, Rg1 40 mg/kg, Rb1 60 mg/kg and notoginsenoside R1 6 mg/kg for 12 days. Fasting blood glucose levels (FBGL), glucose tolerance (GT), serum insulin, leptin levels, body weight changes, food intake, adipose tissues and blood fat levels were measured at different time points.

Results

The PNS group had significantly lower FBGL, improved GT and smaller body weight incremental percentage after the 30-day treatment. Additionally, Rb1 exhibited significant reduction of FBGL on day 12, and Re also exhibited a decreasing trend after the 12-day treatment.

Conclusions

PNS possess anti-hyperglycemic and anti-obese activities by improving insulin- and leptin sensitivity, and Rb1 is responsible for the anti-hyperglycemic effect among the five saponins in KK-Ay mice.     

Effects of Smilaxchinoside A and Smilaxchinoside C,Two Steroidal Glycosides from Smilax riparia,on Hyperuricemia in a Mouse Model

The roots and rhizomes of Smilax riparia, called ‘Niu‐Wei‐Cai’ in traditional Chinese medicine, are believed to be effective in treating the symptoms of gout. However, the active constituents and their uricosuric mechanisms are unknown. In this study, we isolated two steroidal glycosides, named smilaxchinoside A and smilaxchinoside C, from the total saponins obtained from the ethanol extract of the roots of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We observed that these two steroidal glycosides possess potent uricosuric activities, and the observed effects accompanied the reduction of renal mURAT1 and the inhibition of xanthine oxidase, which contribute to the enhancement of uric acid excretion and the reduction of hyperuricemia‐induced renal dysfunction. Smilaxchinoside A and smilaxchinoside C may have a clinical utility in treating gout and other medical conditions caused by hyperuricemia. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of water extract and crude polysaccharides from Liriope spicata var. prolifera on InsR/IRS-1/PI3K pathway and glucose metabolism in mice

Aim of the study

The present study was designed to investigate the effects of water extract (WE) and crude polysaccharides (CPs) from the tuberous root of Liriope spicata var. prolifer on the InsR/IRS-1/PI3K pathway and glucose metabolism in type 2 diabetic mice.

Materials and methods

WE and CPs were administered orally at different doses (200 and 100 mg/kg body weight) to streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice, respectively. After 4 weeks of administration, immunohistochemistry and western blot were applied to detect the expression levels of insulin receptor-α (InsR-α), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) in renal tissues of mice. Moreover, the hepatic glycogen content, glucokinase (GK) and glucose-6-phosphatase (G6Pase) activities were measured to investigate the effect of WE and CPs on glucose metabolism.

Results

Compared with diabetic control, greater immunostaining for InsR-α, IRS-1 and PI3K was present in the tubulointerstitial regions of WE and CPS groups in renal tissues and the expression levels of these three signal molecules from WE and CPs groups were significantly increased; the glycogen content and GK activity from WE and CPs groups in liver were significantly increased, yet the G6Pase activity was significantly lower.

Conclusions

It is demonstrated that WE and CPs can ameliorate insulin signaling transduction and glucose metabolism, as a result, lessen IR and hyperglycemia eventually. So, this study has provided more powerful evidences for Liriope spicata var. prolifer to be a potential hypoglycemic agent and insulin sensitizer.     

复方土茯苓颗粒对HUA痰湿体质大鼠模型相关理化指标及蛋白水平的影响

目的:观察复方土茯苓颗粒对高尿酸血症(HUA)痰湿体质大鼠模型的相关理化指标及蛋白水平的影响,并探讨其相关的作用机制。方法:48只大鼠随机分为正常组,模型组,西药组(非布司他,4 mg·kg-1),复方土茯苓颗粒低、中、高剂量组(1,2,4 g·kg-1),除正常组外,其余各组用高脂饲料联合次黄嘌呤ig,氧嗪酸钾ip制备HUA痰湿体质大鼠模型,并给予相应药物干预;30 d后测定各组大鼠行为学变化及血清中尿酸(UA),丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),甘油三脂(TG),低密度脂蛋白(LDL)和肾脏尿酸盐重吸收转运体1(m URAT1)蛋白的水平及肝脏病理变化。结果:模型组大鼠血清中UA,ALT,AST,TG,LDL和m URAT1蛋白的水平均较正常组显著升高(P0.05),同时,复方土茯苓颗粒高剂量组大鼠血清中的UA,ALT,AST,TG,LDL和m URAT1蛋白的水平均比模型组要显著降低(P0.05),并且痰湿证评分明显改善(P0.05),复方土茯苓颗粒中剂量组大鼠血清中仅AST,TG,LDL水平与模型组比差异不大,余结果同复方土茯苓颗粒高剂量组,而复方土茯苓颗粒低剂量组与模型组无明显差别;而非布司他组仅血清UA水平与模型组比较显著降低(P0.05),其中血清UA水平与复方土茯苓颗粒高剂量组比较无明显差异;模型组肝脏病理显示一定的肝损害。结论:复方土茯苓颗粒能降低高尿酸血症痰湿证血清UA水平,与非布司他比较更能改善痰湿型体质、肝功能和血脂,其机制可能与抑制m URAT1蛋白表达水平有关。     

Korean red ginseng (Panax ginseng) ameliorates type 1 diabetes and restores immune cell compartments

Ethnopharmacological relevance

Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential.

Aim

This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D).

Materials and methods

The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed.

Results

KRG extract significantly lowered blood glucose levels to an average of 250 mg/dl from 350 mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis.

Conclusion

This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects.     

Bidirectional effects of methanol extract of Wei-Chang-An pill on gastrointestinal transit and the spasmolytic activity on isolated rat jejunum

Ethnopharmacological relevance

Wei-Chang-An pill (WCA pill), a traditional Chinese medicine, has been used for treating various gastrointestinal diseases for several decades. Despite the popular medicinal use of WCA pill, less data was available to its activity and mechanism in gastrointestinal disorders. To examine the effects of the methanol extract of WCA pill (ME) on gastrointestinal tract so as to assess some of the possible mechanisms involved in the clinical treatment.

Materials and methods

ME was studied on gastrointestinal transit in vivo including gastric emptying and small intestinal motility in normal and neostigmine-induced mice, as well as on the isolated tissue preparations of rat jejunum in vitro.

Results

In vivo, the gastric emptying decreased and intestinal transit increased after administration of ME in normal mice. However, administration of ME accelerated the intestinal transit ranging from 0.01 to 0.8 mg/mL and reduced it at the concentration of 1.6 and 3.2 mg/mL, while the gastric emptying was inhibited throughout the concentrations in neostigmine-induced mice. in vitro, ME caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in dose-dependent manner ranging from 0.01 to 6 mg/mL and also relaxed the acetylcholine chloride (Ach, 10⁻⁶ M)-induced and K⁺ (60 mM)-induced contractions. ME shifted the Ca²⁺ concentration–response curves to right, similar to that caused by verapamil (0.025 mM).

Conclusions

These results indicated that ME might play a bidirectional role in gastrointestinal transit modulation and the effects on isolated tissue are probably mediated through calcium influx and muscarinic receptors, which provides pharmacological basis for the clinical use of WCA pill in gastrointestinal tract disorders.