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在四氧嘧啶诱导的糖尿病大鼠模型中,通过山麻杆的抗氧化作用保护睾丸。

Protection of testis through antioxidant action of Mallotus roxburghianus in alloxan-induced diabetic rat model.

作者信息

Roy Vikas Kumar, Chenkual Lalramdinthara, Gurusubramanian Guruswami

机构信息

Department of Zoology, Mizoram Central University, Aizawl 796004, Mizoram, India.

Department of Zoology, Mizoram Central University, Aizawl 796004, Mizoram, India.

出版信息

J Ethnopharmacol. 2015 Dec 24;176:268-80. doi: 10.1016/j.jep.2015.11.006. Epub 2015 Nov 11.

DOI:10.1016/j.jep.2015.11.006
PMID:26549273
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Mallotus roxburghianus is used for its antihyperglycaemic properties in Southeast Asia especially in Northeast India (Mizoram) and is also recognized in traditional medicine. About 90% of diabetic patients have been associated with reproductive impairments. The primary aim of this investigation is to examine the effects of diabetes on oxidative stress, steroidogenesis, histopathology, proliferation of germ cells with proliferative cell nuclear antigen (PCNA) and antioxidant status, and alleviative effect of M. roxburghianus on the testis dysfunction.

MATERIALS AND METHODS

Methanolic leaf extract of M. roxburghianus was given to male albino Wistar rats by oral gavage to study the acute toxicity. Phyto-chemical composition of the methanol extract of M. roxburghianus was analyzed by GC-MS. Male Wistar rats were divided into six groups with seven animals in each group: untreated control; M. roxburghianus methanolic extract control (MRME, 400mg/kg); Alloxan diabetic control group (150 mg/kg); diabetic with 100mg/kg MRME treatment; diabetic with 400mg/kg MRME treatment; and diabetic with glibenclamide (0.1mg/kg) treatment. Diabetes was induced by a single intraperitoneal injection of 150 mg/kg alloxan and was confirmed by testing fasting plasma blood glucose levels 5 days after injection. MRME was administered orally for 28 days. Body and testis weights, serum testosterone, testis malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione S transferase (GST) and protein levels were measured, and testis tissue was examined histopathologically and immunohistochemically (PCNA).

RESULTS

No sign of mortality and organ toxicity was observed up to 3000 mg/kg in acute toxicity assay of MRME and inferred to be non-toxic and safe. Bergenin and betulinic acid are the major components of MRME with many biological activities. MRME treatment rendered significant increases in body weight, testis weight, testes-body weight ratio, down regulated the MDA levels, reduced the degeneration and disruption of seminiferous tubule structure, restored the antioxidant enzymes and serum testosterone levels, increased the PCNA activities and attenuated the testes injury.

CONCLUSION

MRME treatment to diabetic rats improves diabetes induced oxidative damage in testis as well as provides protection to testis. Phenols (Bergenin) and terpenes (Betulinic acid) were the main compounds of MRME that show antioxidant and antidiabetic activities and indeed validated its traditional use in the management of diabetes related testicular impairment.

摘要

民族药理学相关性

在东南亚,尤其是印度东北部(米佐拉姆邦),红背叶野桐因其降血糖特性而被使用,并且在传统医学中也得到认可。约90%的糖尿病患者伴有生殖功能障碍。本研究的主要目的是研究糖尿病对氧化应激、类固醇生成、组织病理学、增殖细胞核抗原(PCNA)标记的生殖细胞增殖及抗氧化状态的影响,以及红背叶野桐对睾丸功能障碍的缓解作用。

材料与方法

通过灌胃法给雄性白化Wistar大鼠给予红背叶野桐甲醇叶提取物以研究其急性毒性。采用气相色谱-质谱联用(GC-MS)分析法对红背叶野桐甲醇提取物的植物化学成分进行分析。将雄性Wistar大鼠分为六组,每组七只动物:未处理对照组;红背叶野桐甲醇提取物对照组(MRME,400mg/kg);四氧嘧啶糖尿病对照组(150mg/kg);100mg/kg MRME治疗的糖尿病组;400mg/kg MRME治疗的糖尿病组;以及格列本脲(0.1mg/kg)治疗的糖尿病组。通过单次腹腔注射150mg/kg四氧嘧啶诱导糖尿病,并在注射后5天通过检测空腹血浆血糖水平进行确认。口服给予MRME 28天。测量体重、睾丸重量、血清睾酮、睾丸丙二醛(MDA)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽S转移酶(GST)和蛋白质水平,并对睾丸组织进行组织病理学和免疫组织化学(PCNA)检查。

结果

在MRME的急性毒性试验中,高达3000mg/kg未观察到死亡和器官毒性迹象,推断其无毒且安全。岩白菜素和桦木酸是MRME的主要成分,具有多种生物活性。MRME治疗使体重、睾丸重量、睾丸-体重比显著增加,降低了MDA水平,减少了生精小管结构的退化和破坏,恢复了抗氧化酶和血清睾酮水平,增加了PCNA活性并减轻了睾丸损伤。

结论

对糖尿病大鼠进行MRME治疗可改善糖尿病诱导的睾丸氧化损伤,并为睾丸提供保护。酚类(岩白菜素)和萜类(桦木酸)是MRME的主要化合物,具有抗氧化和抗糖尿病活性,确实证实了其在治疗糖尿病相关睾丸损伤方面的传统用途。

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