Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: Involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway

Chen, Yuping; Wu, Yunhao; Gan, Xiaoyang; Liu, Kai; Lv, Xing; Shen, Hongsheng; Guoying, Dai; Xu, Hao

doi:10.1016/j.jep.2016.10.079

Cited by 59 publications

(47 citation statements)

References 41 publications

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“…[32,33] The persistent high blood glucose level is due to low level of serum insulin observed in this study and also reported by other. [34] Our data showed that STZinduced diabetic rats have severe loss in body weight which is consistent with the findings of other investigators. [35,36] This marked reduction in body weight may be breakdown of structural tissue protein in diabetic state.…”

Section: Discussionsupporting

confidence: 93%

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Maiti¹

2017

IJGP

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Background: Tamarindus indica Linn. (Caesalpiniaceae) is a well-known traditional plant used by the tribes as well as rural sectors of tropical countries. Locally, it is named as Tantul and recognized as therapeutic uses of different diseases. Aim: The present study aimed to evaluate the efficacy of hydromethanolic extract of T. indica Linn. seed in streptozotocin (STZ)-induced diabetic testicular dysfunction correction. Materials and Methods: STZ-induced diabetic state has been established here by single intramuscular injection of STZ (6 mg/100 g body weight in citrate buffer, pH 4.5) resulted hyperglycemia. STZ-induced experimental diabetes resulted testicular dysfunctions evaluated by sperm count, sperm motility, viability, and seminal vesicle fructose content as well as by the level of serum testosterone. Testicular oxidative stress has been observed by the monitoring of catalase, peroxidase, superoxide dismutase, and glutathione-S-transferase activities. Quantification of thiobarbituric acid reactive substances and conjugated diene in testicular tissue was assessed. General and metabolic toxicity assessment parameters were studied. Results: Administration of hydromethanolic extract to STZ-induced diabetic rat at the dose of 80 mg/100 g body weight/day for 28 days resulted a significant protection in fasting blood glucose, serum insulin, and serum testosterone levels (P < 0.05) along with the correction of testicular above-mentioned parameters as well as semen analysis parameters toward the control level (P < 0.05). This extract has no general toxic effect on the body weight, along with no metabolic toxicity that was reflected here by the assessment of serum glutamate oxaloacetate transaminase and pyruvate transaminase activities. Conclusion: These data demonstrated that T. indica significantly improved STZ-induced diabetic complication in rat testis. This study suggested that hydromethanolic extract might have a protective role against oxidative stress-induced impairment in testicular functions in diabetic rats.

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Section: Discussionsupporting

confidence: 93%

Untitled

Maiti¹

2017

IJGP

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“…There are conflicting reports on the impact of DM on gonadotropic hormones. For example, significant decreases in serum gonadotropin‐releasing hormone (GnRH), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) have been reported (Chen et al ., ), while others reported increases in FSH and LH levels in diabetic rats (Himabindu et al ., ; Sönmez et al ., ). DM increases testicular concentration of cholesterol, the precursor for androgen synthesis (Saumya & Basha, ).…”

Section: Introductionmentioning

confidence: 91%

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

et al. 2018

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Background: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged. Objectives: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats. Materials and methods: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks. Results: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3b-hydroxysteroid dehydrogenase (HSD), and 17b-HSD, as well as the level of StAR protein and activities of CYP11A1, 3b-HSD, and 17b-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre-and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome. Discussion and conclusion: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state. Research has shown that DM impairs several aspects of the male reproductive function (Nna et al., 2017a). Decreased daily sperm production, sperm count, motility and viability, increased 110

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“…31 It has also been demonstrated that MAPK p38 signalling might be involved in downstream signalling of RAGE activity connecting the AGE/RAGE signalling with pro-inflammatory response. 32,33 To summarize, NADPH-oxidase activity is enhanced by AGE-RAGE interaction and MAPK p38 signalling is activated, which contributes to the excessive inflammatory response. In atherosclerotic lesions, VECs and inflammatory cells can produce inflammatory cytokines including IL-1β and IL-6 in response to the initial injury of the vascular wall because of mechanical stress and deposition of ox-LDL.…”

Section: Discussionmentioning

confidence: 99%

miR‐21‐3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis

Shao

Zhao

et al. 2020

Cell Biochemistry & Function

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To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose. We also observed that the introduction of miR-21-3p mimic significantly increased the expression of ADAM10 in the VECs. Similarly, significantly higher levels of sRAGE were found in the cultured supernatant after administration of miR-21-3p mimic in human vein endothelial cells. The production of reactive oxygen species and expression of inflammatory cytokines in VECs induced by LPS and high-concentration glucose were significantly decreased after administration of miR-21-3p. in vivo studies revealed that intravenous injection of miR-21-3p at regular intervals would reduce the area of atherosclerotic lesion and elevate the serum levels of sRAGE in atherosclerotic diabetic mice. miR-21-3p may be beneficial in diabetic atherosclerosis by promoting the cleaved form of sRAGE and inhibition of RAGE/NADPH oxidase signalling depending on the increased expression of ADAM10. Significance of the Study: We identified a novel microRNA, miR-21-3p, which is characteristically at elevated levels in serum derived from diabetic patients and responsible for target degradation of ADAM10 mRNA. Further, we show that miR-21-3p aggravates the atherosclerotic lesion via dysfunction of the ectodomain shedding of molecular binding RAGE in the diabetic atherosclerotic mice.

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Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: Involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway

Cited by 59 publications

References 41 publications

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Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

miR‐21‐3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis

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