Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats

ObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.MethodsIn addition to a normal control (group 1), drugs or vehicles were administered orally to seven groups (n = 5) of rats that had already received 4-weeks of pre-treatment with CP (5 mg/[kg·d], per oral administration); group 2 received CP + distilled water (10 mL/[kg·d]); group 3 received CP + 5% tween 80 (10 mL/[kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/[kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/[kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/[kg·d]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated.ResultsThe CP-treated group showed a significant reduction (P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated (P < 0.001) sperm morphological abnormalities and testicular structure alterations, compared to the control group. Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts. For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count (P < 0.001), sperm motility (AE, 50 mg/kg, P < 0.05; ME, 50 and 100 mg/kg, P < 0.05) and sperm viability (AE, 50 mg/kg, P < 0.001; ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes.ConclusionH. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.     

Inhibition of aldose reductase by Aegle marmelos and its protective role in diabetic cataract

Ethnopharmacological relevance

Aegle marmelos (L.) Corr. Serr. (Aegle marmelos) leaves were extensively used in the Ayurvedic, Unani and Siddha systems of Indian medicine as an anti-diabetic agent, which serves as hypoglycemic agent. However, the significance of this plant on secondary complications of diabetes such as cataract remained unknown. The aim of the study was to investigate the possible anti-cataractous activity of Aegle marmelos against streptozotocin (STZ) induced diabetic cataract in rats.

Materials and methods

Aegle marmelos leaf extract was prepared using three different solvents (petroleum ether, ethyl acetate and methanol) and tested for inhibition against rat lens aldose reductase (AR), a key enzyme of polyol pathway. Furthermore, the pharmacological potential of Aegle marmelos extract was investigated against osmotic stress induced opacification of lens in ex vivo organ culture and streptozotocin (STZ) induced diabetic cataract in rats.

Results

Ethyl acetate extract of Aegle marmelos inhibited rat lens AR in vitro with an IC₅₀ value of ∼15 µg/ml. This extract also prevented the hyperglycemia induced increase in AR activity, sorbitol accumulation and opacification of rat lens in ex vivo lens organ culture. Supplementation of ethyl acetate extract of Aegle marmelos to STZ-induced diabetic rats decreased the blood glucose levels due to hyperglycemia and inhibited the AR activity and delayed cataract progression in dose dependent manner. α-crystallin isolated from diabetic rats fed with Aegle marmelos showed improved chaperone activity than that of isolated from rats naïve to Aegle marmelos.

Conclusion

This study indicates that ethyl acetate extract of Aegle marmelos has pharmacologically active components with a potential to inhibit rat lens AR and consequential decrease in osmotic stress. Besides this, the present study also demonstrates that the extract prevented loss of antioxidants contributing to the integrity of α-crystallin's chaperone activity and thereby delaying cataract.     

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress,inflammation and apoptosis in rats

ObjectiveSalvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.MethodsIn a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5′-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.ResultsLiver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.ConclusionThis study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.     

Chemopreventive and remediation effect of Hydrocotyl bonariensis Comm. Ex Lam (Apiaceae) leave extract in galactose-induced cataract

Ethnopharmacological relevance

Hydrocotyl bonariensis Comm. Ex Lam (Apiaceae) is being widely used in Western Nigeria in treating various symptoms of ophthalmic diseases; however scientific data in support of this medicinal use have not been reported.

Aim of the study

This study, investigated the efficacy of Hydrocotyl bonariensis leave extract in offering protection against experimental cataract and also examined its remediation effect when administered after cataract onset.

Materials and methods

Weanling albino rats fed with 30% galactose diet were used in the study. Mechanisms of action of the extract were investigated by measuring the degree of lens peroxidation, lens antioxidant status and lens protein concentration. Severity of cataract was determined by measuring the cataract index.

Results

The extract at 500 mg kg⁻¹ reduced cataract index significantly and also reduced cataract progression when administered after cataract onset. Administration of this dosage also significantly reduced the degree of lens peroxidation, increased the level of reduced glutathione (GSH) and the lens catalase and superoxide dismutase activity. The extract also prevents protein insolubilization. Administration of the extract at 1000 mg kg⁻¹ reduced cataract index and lens peroxidation but did not increase the antioxidant status significantly. Administration of the extract after cataract onset reduced cataract index, moderately increased percentage soluble protein above the value prior to the arrest of hypergalactosemia but did not increase the antioxidant status.

Conclusion

Our study suggests that Hydrocotyl bonariensis protects against galactose-induced cataract, and that administration of the extract after cataract onset reduced cataract progression but did not reverse cataractogenesis.     

Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don: A comparative review on traditional uses,phytochemistry and pharmacology

Ethnopharmacological relevance

Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don are two vital medicinal plant species (family: Apocynaceae). In India, the therapeutic use of Alstonia scholaris has been described in both codified and non-codified drug systems for the treatment of malaria, jaundice, gastrointestinal troubles, cancer and in many other ailments. Other species, Alstonia macrophylla has been used in conventional medicines in Thailand, Malaysia and Philippines as a general tonic, aphrodisiac, anticholeric, antidysentery, antipyretic, emmenagogue, and vulnerary agents. In India, Alstonia macrophylla is used as a substitute for Alstonia scholaris in various herbal pharmaceutical preparations. However, one certainly cannot evaluate the truthfulness of a practice (i.e. in scientific terms). In this article we discuss and summarize comparative data about traditional uses, phytochemistry, pharmacology and toxicity of Alstonia scholaris and Alstonia macrophylla. Moreover, in order to unfold future research opportunities, lacunae in the present knowledge are also highlighted.

Materials and methods

Literature about Alstonia scholaris and Alstonia macrophylla was collected by using electronic and library search. Additionally, referred books on traditional medicine and ethnopharmacology were also utilized for receiving traditional records about both the plant species.

Results

Both Alstonia scholaris and Alstonia macrophylla are rich in different types of bioactive alkaloids. So far, broad spectrum of in vitro and in vivo biological and pharmacological activities have been reported to both the species. Amongst them, antimicrobial and anticancer activities were promising.

Conclusions

The use of Alstonia macrophylla as a substitute for Alstonia scholaris is not at all justifiable as both the species are distinct from each other in their phytochemistry and pharmacology. Further detail chemical fingerprinting and metabolic studies of these two species are warranted to prevent their mutual adulteration most importantly in the context of commercial preparations.     

明目地黄丸对白内障大鼠晶状体内SOD、MDA影响的实验研究

[目的] 研究明目地黄丸对白内障大鼠晶状体中超氧化物歧化酶(SOD) 活性和丙二醛(MDA)含量的影响。[方法] 建立大鼠白内障模型, 采用黄嘌呤氧化酶法和硫代巴比妥酸(TBA)法对模型组、治疗组及对照组大鼠晶状体中SOD活性和MDA含量进行检测。[结果] 明目地黄丸高、中剂量组大鼠晶状体中MDA含量明显低于模型组, 高、中剂量组大鼠晶状体中SOD活性明显高于模型组, 差异具有显着性(P<0.05).[结论] 明目地黄丸能明显降低白内障大鼠晶状体中MDA含量, 且能明显升高白内障大鼠晶状体中SOD活性。     

Pharmacological evaluation of Alstonia scholaris: Anti-tussive,anti-asthmatic and expectorant activities

Ethnopharmacological relevance

Alstonia scholaris (Apocynaceae) was documented as an effective herb for the treatment of chronic respiratory diseases in “dai” ethnopharmacy historically, and its leaf crude extract, used for releasing tracheitis and cold symptom, was approved to be a commercial formulation by State Food and Drugs Administration of China (SFDA).

Aim of the study

The investigation evaluates the anti-tussive and anti-asthmatic activities of the ethanolic extract, fractions and main alkaloids of Alstonia scholaris leaf to provide experimental evidence for its traditional and modern clinical use. For our most interesting, is to reveal the active components for further new drug development.

Materials and methods

The leaf of Alstonia scholaris was extracted with ethanol and then separated into different fractions. Furthermore, alkaloids were isolated by phytochemical method. The anti-tussive activity was evaluated using three different models including ammonia or sulfur dioxide induced mice coughing, and citric acid induced guinea pigs coughing. The anti-asthmatic activity was investigated on guinea pigs bronchoconstraction induced by histamine. The expectorant activity was evaluated by volume of phenol red in mice's tracheas.

Results

The alkaloids fraction significantly inhibited mice's frequency of cough induced by ammonia, increased mice's latent period of cough induced by sulfur dioxide, and increased guinea pigs’ latent period of cough and inhibited frequency of cough. Besides, the alkaloids fraction increased delitescence of convulsion, and tumble of guinea pigs in anti-asthmatic test, and enhanced tracheal phenol red output in expectorant evaluation. Moreover, the main alkaloid, picrinine exhibited anti-tussive and anti-asthmatic activities in vivo.

Conclusions

The alkaloids fraction was anti-tussive, anti-asthmatic and expectorant activities component of Alstonia scholaris leaf, and it may also be a valuable lead material for respiratory diseases drug development. Picrinine, the main anti-tussive and anti-asthmatic compound, could be applied in quality control of products from Alstonia scholaris leaf.     

Pharmacological evaluation of Alstonia scholaris: Anti-inflammatory and analgesic effects

Ethnopharmacological relevance

Alstonia scholaris (Apocynaceae) has been historically used in “dai” ethnopharmacy to treat chronic respiratory diseases. The leaf extract, developed as a commercially available traditional Chinese medicine, used to release tracheitis and cold symptom, has also been prescribed in hospitals and sold over the counter in drug stores.

Aim of the study

The investigation evaluated the anti-inflammatory and analgesic activities of the ethanolic extract, fractions and main alkaloids of Alstonia scholaris leaf to provide experimental evidence for its traditional and modern clinical use. Besides, to discover the active fraction and components for further better use in Chinese medicine is hopeful.

Materials and methods

The leaf of Alstonia scholaris was extracted with ethanol and then separated into different fractions. Furthermore, alkaloids were isolated by phytochemical method. The analgesic activities were investigated using acetic acid-induced writhing, hot-plate and formalin tests in mice. The anti-inflammatory activities were carried out in vivo and in vitro, including xylene-induced ear edema and carrageenan-induced air pouch formation in mice, and COX-1, -2 and 5-LOX inhibition.

Results

It has been exhibited that the EtOAc and alkaloid fractions reduced acetic acid-induced writhing response in mice, significantly. The ethanolic extract, EtOAc and alkaloid fractions remarkably inhibited xylene-induced ear edema. Further investigation was focused on the alkaloids fraction and three main alkaloids isolated from the alkaloids fraction, in different animal models. Alkaloids reduced acetic acid-induced writhing response, and xylene-induced ear edema in mice. In the hot-plate test, alkaloids did not increase the latency period of mice obviously. In the formalin test, alkaloids did not inhibit the licking time in first phase, but significantly inhibited the licking time in second phase of mice. Alkaloids increased significantly SOD activity and decreased levels of NO, PGE2 and MDA significantly, in air pouch mice model. Moreover, some alkaloids isolated from the leaf of Alstonia scholaris exhibited inhibition of COX-1, COX-2 and 5-LOX in vitro anti-inflammatory assay, which supported alkaloids as the bioactive fraction.

Conclusions

The alkaloids fraction of Alstonia scholaris leaf, three main alkaloids, picrinine, vallesamine and scholaricine, may produce the anti-inflammatory and analgesic effect peripherally based on several in vivo assays. In in vitro tests, alkaloids exhibited inhibition of inflammatory mediators (COX-1, COX-2 and 5-LOX), which is accordant with results on animal models. Besides, COX-2/5-LOX dual inhibitors found in the experiment, such as 16-formyl-5α-methoxystrictamine, picralinal, and tubotaiwine might be valuable for further attention.     

石斛酚与丁香酸联合抗白内障作用及其机制研究

目的:探讨石斛酚和丁香酸联合对抗白内障作用并探讨其作用机制。方法:H2O2致离体培养的氧化损伤大鼠晶状体模型,解剖显微镜下观察石斛酚和丁香酸联合对晶状体的透明度的影响;D-半乳糖致糖性白内障大鼠模型,裂隙灯观察石斛酚和丁香酸联合对在体大鼠晶状体透明度的影响;采用紫外分光光度法表征石斛酚和丁香酸联合对醛糖还原酶(AR)的抑制活性;采用分子对接考察石斛酚和丁香酸联合抑制AR的结合位点、结合方式及其药效团。结果:离体及在体实验均表明石斛酚和丁香酸组合具有良好的抗糖性白内障活性,且优于单一组分石斛酚和丁香酸及阳性对照药物白内停,表现良好的协同效果;分子对接及动力学模拟表明二者协同抑制AR的氨基酸残基为Asn160,主要作用力为范德华力,形成共同药效团。结论:石斛酚与丁香酸联合具有良好的抗白内障活性,其作用机制在于二者对AR呈现良好的协同抑制性。     

明目地黄丸合并莎普爱思滴眼液治疗早期老年性白内障的疗效观察

[目的]观察明目地黄丸合并莎普爱思滴眼液治疗早期老年性白内障的疗效。[方法]将124例早期老年性白内障患者,随机分为治疗组62例(115眼),对照组62例(108眼),对照组局部莎普爱思滴眼液滴眼,治疗组在对照组的基础上,服用明目地黄丸,进行90 d的临床观察。对其视力、晶体混浊程度进行观察。[结果]2组患者视力在治疗后与治疗前相比差异均有统计学意义(P<0.05),2组患者在治疗后视力、晶体混浊程度等指标相比,差异有统计学意义(P<0.05),治疗组总有效率显著高于对照组(P<0.05)。[结论]明目地黄丸合并莎普爱思滴眼液治疗早期老年性白内障安全,疗效显著,具有推广价值。     

Antidiarrhoeal and spasmolytic activities of the methanolic crude extract of Alstonia scholaris L. are mediated through calcium channel blockade

This study was aimed to provide a pharmacological basis to the medicinal use of Alstonia scholaris as an antidiarrhoeal and antispasmodic by using in vivo and in vitro techniques. In the in vivo study the crude extract of Alstonia scholaris (As.Cr), which tested positive for the presence of alkaloids, provided 31–84% protection against castor oil‐induced diarrhoea in mice at 100–1000 mg/kg doses, similar to loperamide. In isolated rabbit jejunum preparation, the As.Cr caused inhibition of spontaneous and high K⁺ (80 mm )‐induced contractions, with respective EC₅₀ values of 1.04 (0.73–1.48) and 1.02 mg/mL (0.56–1.84; 95% CI), thus showing spasmolytic activity mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with the As.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca⁺⁺ concentration‐response curves similar to verapamil, a standard calcium channel blocker. Loperamide also inhibited spontaneous and high K⁺ precontractions as well as shifted the Ca⁺⁺ CRCs to the right. These results indicate that the crude extract of Alstonia scholaris possesses antidiarrhoeal and spasmolytic effects, mediated possibly through the presence of CCB‐like constituent(s) and this study provides a mechanistic base for its medicinal use in diarrhoea and colic. Copyright © 2009 John Wiley & Sons, Ltd.     

补青颗粒防治大鼠D-乳糖性白内障的研究

目的:观察补青颗粒对大鼠半乳糖性白内障的防治作用.方法:用SD大鼠复制半乳糖白内障模型.实验分为6组:空白对照组无特殊处理;模型对照组每日ip注射50％ D-半乳糖溶液(10g·kg-1),连续15d,制成白内障动物模型;阳性对照组同模型组处理的同时每天给予障眼明片混悬液0.02g·kg-1 ig至实验结束;补青颗粒高、中、低剂量组处理同模型组且每天分别给予0.8,0.4,0.2 g·kg-1的剂量ig至实验结束.分别记录实验前及造模起第3,7,14天晶状体的混浊程度,实验结束时检测各组晶体超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量.结果:对照组晶状体始终透明,模型组第3天晶体开始发生混浊,补青颗粒3个剂量组晶体混浊的速度及程度在3,7,14天均明显低于模型组(P＜0.05),SOD活性显著高于模型组(P＜0.05),MDA含量显著低于模型组(P＜0.05).结论:补青颗粒具有较好的防治大鼠半乳糖性白内障的作用.     

姜黄素眼用脂质体的制备及晶状体抗氧化作用考察

目的：制备N-三甲基壳聚糖（TMC）包覆姜黄素眼用脂质体并考察其抑制大鼠硒性白内障晶状体氧化作用。方法：采用乙醇注入法制备姜黄素脂质体（Cur-TCL）,通过星点设计-效应面法优化脂质体处方工艺;采用过膜法、透射电镜、粒径电位测定仪测定Cur-TCL的理化性质;建立大鼠硒性白内障模型,考察Cur-TCL对白内障形成过程中晶状体氧化的抑制作用。结果：最佳处方为姜黄素1.41 mg,磷脂质量分数4%,胆固醇-磷脂（1：5.44）。经0.5%TMC溶液包覆后脂质体呈球形,粒径增大,电位显著提高,药物包封率基本不变。与未包覆脂质体相比,Cur-TCL组大鼠晶状体中SOD活力提高30.3%,MDA摩尔浓度减少52.4%,GSH含量增加1.29倍。结论：Cur-TCL可显著抑制硒性白内障导致的晶状体氧化过程,为该制剂治疗白内障提供参考。     

Protection of Water Extract from Paeoniae Radix Rubra against Myocardial Ischemia in Mice Induced by Isoproterenol

Objective To study the protective effect of the water extract from Paeoniae Radix Rubra(WEPRR)against myocardial ischemia in mice induced by isoproterenol(ISO).Methods The mice were randomly divided into six groups:positive control,normal control,model,low-,mid-,and high-dose[0.3,0.6,and 1.2 g/(kg·d)]WEPRR groups.The mice in WEPRR groups were ig administered with WEPRR,the mice in the positive control group were ig administered with 0.98%Di’ao Xinxue Kang[(0.195 g/(kg·d)],and the mice in normal and model groups were ig administered with the same volume of physiological saline once daily for consecutive 11 d.On the day 7 from the beginning of the ig administration,the mice in the model and WEPRR groups were ip perfused with 0.02 g/(kg·d)ISO.After 15 min of the last medication,the mice were anesthetized with isoflurane gas,the blood was collected through venous sinus of eye orbit,then the mice were killed.The heart tissues were rapidly removed from the mice,washed in physiological saline,soaked in filter paper,and stored in 80℃until use.The activities of lactate dehydrogenase(LDH),creatine kinase-MB(CK-MB),creatine kinase(CK)in serum,superoxide dismutase(SOD),and the contents of malondialdehyde(MDA)in the heart of mice were determined,respectively.Results Compared with the model group,the activities of LDH,CK-MB,and CK in serum,and the SOD of mice in the positive control and WEPRR groups were increased and the content of MDA in heart was decreased.Conclusion The WEPRR has the cardioprotective activities on ISO-induced myocardial ischemia.     

病理和正常生理状态下淫藤骨痹康方总萜体内指纹图谱差异性研究

目的 研究病理和正常生理状态下淫藤骨痹康方总萜体内代谢指纹图谱差异,阐明其活血作用的药效物质基础。方法 采用HPLC法建立藤骨痹康方总萜在正常生理状态与急性血瘀病理状态下的代谢特征指纹图谱,并对共有峰的数与量进行对比分析。结果 在正常生理状态下,5个批次的含药血浆样品中有21个共有峰,其中3个峰来自于空白血浆,4个峰为总萜的原型成分,14个峰为其代谢产物峰或产生的新成分峰;在急性血瘀病理状态下,含药血浆样品中有21个共有峰,其中6个峰来自于空白血浆,3个峰为总萜的原型成分,12个峰为其代谢产物峰或产生的新成分峰;经对照品对照,52 min处的峰为丹参酮II_A。总萜在正常生理状态与病理状态下的色谱峰的数目、峰形及峰的大小存在一定的差异;病理状态下的色谱峰峰面积明显强于正常生理状态下的色谱峰峰面积,其中有7个共有峰的峰面积具有显著性差异（P＜0.05）。结论 淫藤骨痹康方总萜体内代谢指纹图谱的建立方法可行;不同生理状态下的大多数共有峰的峰面积存在显著性差异;其入血原型成分与代谢新成分可能为其活血作用的药效物质。     

针刺阻抑幼鼠白内障形成及晶体谷胱甘肽耗竭的研究

本文观察了针刺对白内障形成和晶状体内谷胱甘肽 (GSH、GSSG)耗竭的阻抑作用 ,并为临床针刺防治早期白内障提供科学的依据。采用L Buthionine (S·R) Sulfoximine(BSO)药物诱发新生幼鼠晶状体GSH的耗竭 ,形成双侧白内障。并随机分成空白对照组、药物致障组、针刺治疗组 ,同步进行研究及探索其新生鼠白内障的形成与晶状体GSH、GSSG水平的相关性。结果 :新生鼠诞生后第 9天加上第 1 7天全部致障率综合统计数据提示 ,空白对照组的致障率为 0 % (0 / 1 8) ;药物致障组的致障率为 88 89% (1 6 / 1 8) ,其第 9天的GSH含量水平比空白对照组显著下降 (P <0 0 0 1 ) ;针刺治疗组的致障率为 2 1 4% (3/ 1 4) ,其中第 9天新生鼠的致障率为 0 % (0 / 5 ) ,第 1 7天的致障率为 33 3% (3/ 9) ,与药物致障组比较有显著差异 (P <0 0 5 ) ,其晶体内的GSH含量 ,第 1 7天也比第 9天极度升高 (P <0 0 0 1 ) ,同时也与空白对照组及药物致障组有显著差异 (P <0 0 5 )。其氧化型谷胱甘肽GSSG含量 ,除空白组第 1 7天比第 9天有显著差异 (P <0 0 5 )外 ,另外两组并无显著差异。说明针刺确实可以提高晶体内GSH含量 ,具有阻抑BSO药物对晶体内GSH水平的耗竭和临床防治早期白内障形成的作用     

决明子提取物对链脲佐菌素诱发糖尿病小鼠 晶状体氧化应激状态的影响

目的:研究决明子提取物Cassia obtusifolia extract(COE)对链脲佐菌素(STZ)诱发糖尿病小鼠晶状体氧化应激状态的改善作用。方法:雄性昆明种小鼠尾静脉注射STZ 130 mg·kg-1造成糖尿病模型后,分成STZ模型组、二甲双胍组(300 mg·kg-1,ig)、决明子提取物低、中、高给药组(50,150,450 mg·kg-1,ig),每组10只,每天ig 1次,连续给药10 d后。检测小鼠血糖浓度和晶状体氧化应激状态相关指标抗氧化能力指数(ORAC)、丙二醛(MDA)、一氧化氮(NO)、谷胱甘肽(GSH)、超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)的改善作用。结果:小鼠尾静脉注射STZ 7 d后,诱发小鼠血糖值明显增高(P<0.01),同时造成晶状体的氧化损伤。同时与模型组相比,决明子提取物没有显示有效的降血糖作用(P>0.01),但决明子给药均能显著降低小鼠晶状体的氧化应激产物NO和MDA含量(P<0.01),同时提高晶状体的抗氧化能力指数ORAC和GSH水平(P<0.01),并提高小鼠晶状体组织内抗氧化的自由基清除系统相关酶(T-SOD和GSH-Px)的活性(P<0.01)。结论:决明子提取物可以改善STZ诱导糖尿病小鼠晶状体内的过氧化状态,其作用机制可能通过清除自由基和抑制脂质过氧化过程实现的。     

Toxicity of Danshen Injection in Beagle’s Dogs by Repeated iv Injection

Objective To re-evaluate the potential toxicity of Danshen Injection(DI)in Beagle’s dogs by repeated iv injection.Methods DI was iv given to the dogs at the doses of 0,1.6,5.4,and 16.0 g/(kg·d)(4 per sex per group)for 13weeks.During the test period,the clinical signs,mortality,body weights,food consumption,rectal temperature,ophthalmoscopy,electrocardiography,urinalysis,hematology,serum biochemistry,organ weights,gross findings,and histopathology were examined.Results Dogs iv given with DI at the doses of 0,1.6,5.4,and 16.0 g/(kg·d)for13 weeks had no drug-related changes in mortality,body weight,food consumption,temperature,electrocardiography,ophthalmoscopy,urinalysis parameters,and organ weights.The hematological parameter data showed a significant decrease in red blood cells and hemoglobin concentration in the high-dose group and a significant increase in activated partial thromboplastin time suggesting an effect on haemopoiesis.For biochemical parameters,a significant decrease in glucose and a significant increase in total bilirubin were observed in the high-dose group,and the latter was considered to be toxicologically insignificant as lack of histopathological correlate.However,the histopathological examinations of the injection site showed that DI could cause dose-dependent focal inflammation.Conclusion That the iv injection with DI into dogs at 16 g/(kg·d)for 13 weeks could cause the decreases in red blood cell parameters and glucose,as well as the lesions of the injection site.The no observed adverse effect level is5.4 g/(kg·d),which suggests that safe clinical dosing be possible.     

五味子乙素防护晶状体氧化损伤的体外实验研究

 目的探讨五味子乙素(Sch B)对实验性晶状体氧化损伤的防护作用。方法采用Fenton反应复制兔晶状体氧化损伤模型,以吡诺克辛钠滴眼液(PS)为对照,测定晶状体SP,SOD,GSH-Px,GSH,VitC及MDA的含量,观察终浓度0.5 mmol·L^-1Sch B对晶状体氧化损伤的防护作用。结果Sch B组与Fenton对照组比较,Sch B可显著减少Fenton反应中SP的丢失,显著提高SOD和GSH-Px的活性及GSH和Vit C的水平,并降低MDA含量。Sch B组与PS组比较,Sch B组的SOD活性、GSH含量和Vit C水平分别是PS组的1.66倍,2.58倍和2.36倍,MDA含量比PS组下降24%。上述各项指标均有显著性差异(P＜0.01)。结论 Sch B对Fenton反应中晶状体的氧化损伤有明显的防护作用,且优于吡诺克辛钠滴眼液。     

Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark

ObjectiveSeveral pathologies arise from the inappropriate opening of the mitochondrial permeability transition (mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin (STZ)-induced diabetic rat liver.MethodsDifferent solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso (MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control (distilled water); B, STZ (65 mg/kg; diabetic control); C, STZ + MFFM (25 mg/kg); D, STZ + MFFM (50 mg/kg); E, STZ + glibenclamide (5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using glucometer.ResultsIn vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calcium-dependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant (P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde (MDA) levels in STZ-induced diabetes were significantly (P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiabetic drug. Also, treatment with MFFM at different doses significantly (P < 0.001) reduced high serum blood glucose compared to the diabetic control.ConclusionF. mucoso could be useful in therapeutic management of diabetes mellitus given its ability to prevent excessive tissue wastage via inhibition of pore opening, and reduction in levels of MDA and serum blood glucose.