Protective effects of catalpol on diabetes mellitus-induced male reproductive damage via suppression of the AGEs/RAGE/Nox4 signaling pathway

Jiao, Ni; Chen, Yuping; Zhu, Yihui; Wang, Wei; Liu, Mengxue; Ding, Wangli; Lv, Gaohong; Lu, Jianhua; Yu, Bin; Xu, Hao

doi:10.1016/j.lfs.2019.116736

Cited by 28 publications

(17 citation statements)

References 42 publications

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“…4,5 The kidney and testes are two organs that are grossly affected by diabetes and several reports have shown that more than 40% of diabetic patients eventually develop complications of the kidney or testicular dysfunction during their lifetime. [6][7][8] Although, testicular dysfunction in diabetes is not life threatening, the psychological and emotional problems associated with it is huge. Whereas, complications of the kidney arising from diabetes can be fatal and can result in end stage kidney disease, kidney failure or even death.…”

Section: Introductionmentioning

confidence: 99%

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Song

Sun²,

et al. 2020

J Sci Food Agric

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BACKGROUND Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats. METHODS Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg−1 body weight) and its major component, 5,7‐dihydroxy‐6‐oxoheptadecanoic acid (DHA, 25 mg kg−1 body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle‐stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro‐inflammation were analysed along with histology. RESULTS The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non‐diabetic normal rats. The 28‐day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro‐inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes‐mediated histopathological damage was alleviated in the kidney and testis. CONCLUSION The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti‐inflammatory activities. © 2020 Society of Chemical Industry

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Section: Introductionmentioning

confidence: 99%

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Song

Sun²,

et al. 2020

J Sci Food Agric

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“…Preliminary studies have shown that the leading causes of reproductive damage caused by DM are induction of inflammation and oxidative stress ( Amaral et al, 2008 ; Khosravi et al, 2019 ; Chen Y. et al, 2020 ). We previously reported the deposition of AGEs in the testis, and that inflammation and oxidative stress were secondary to the activation of the AGEs-RAGE signaling pathway that plays an essential role in the reproductive malfunction induced by diabetes ( Jiao et al, 2020 ). Some recent studies ( Meneses et al, 2016 ; Yang et al, 2019 ) have also shown the vital role of metabolic factors that regulate normal spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

Combination of the Herbs Radix Rehmanniae and Cornus Officinalis Mitigated Testicular Damage From Diabetes Mellitus by Enhancing Glycolysis via the AGEs/RAGE/HIF-1α Axis

Chen

Shu

et al. 2021

Front. Pharmacol.

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Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as “nourishing Yin and tonifying kidney” herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of “kidney governing reproduction” in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

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“…Then it changes the biological characteristics of cells in the inflammatory environment and eventually differentiated into tumor cells abnormally. TNF acts as an inflammatory mediator, including TNF-α secreted by macrophages and TNF-β secreted by T lymphocytes (Jiao et al, 2020). It is often used as an indicator of some infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

Chen

et al. 2020

Front. Pharmacol.

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Objective: To investigate the mechanism of Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson (SC) and Patrinia scabiosifolia (PS) against Pelvic Inflammatory Disease with Dampness-Heat Stasis Syndrome via network pharmacological approach and experimental validation.Methods: The active compounds with OB ≥ 30% and DL ≥ 0.18 were obtained from TCMSP database and further confirmed by literature research. The targets of the compounds and disease were acquired from multiple databases, such as GeneCards, CTD and TCMSP database. The intersection targets were identified by Venny software. Cytoscape 3.7.0 was employed to construct the protein-protein interaction (PPI) network and compound-target network. Moreover, GO enrichment and KEGG pathway analysis were analyzed by DAVID database. Finally, CCK-8, Griess assay and a cytometric bead array (CBA) immunoassay were used for experimental validation by detecting the influence of the active compounds on proliferation of macrophage, release of NO and TNF-α after LPS treatment.Results: 9 bioactive compounds were identified from SC and PS. Those compounds corresponded to 134 targets of pelvic inflammatory disease with dampness-heat stasis syndrome. The targets include vascular endothelial growth factor A (VEGFA), von willebrand factor (VWF), interleukin 6 (IL6), tumor necrosis factor (TNF) and nuclear transcription factor 1 (NFκB1). They act on the signaling pathways like advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE), focal adhesion (FA), Toll-like receptor (TLR) and nuclear transcription factor κB (NF-κB). In addition, by in vitro validation, the selected active components of SC and PS such as acacetin, kaempferol, linarin, isovitexin, sinoacutine could significantly inhibit the release of NO induced by LPS, respectively. Moreover, different dose of acacetin, kaempferol, isovitexin and sinoacutine significantly inhibits the TNF-α production.Conclusion: This study provides solid evidence for the anti-inflammatory mechanism of SC and PS against pelvic inflammatory disease with dampness-heat stasis syndrome, which will provide a preliminary evidence and novelty ideas for future research on the two herbs.

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Protective effects of catalpol on diabetes mellitus-induced male reproductive damage via suppression of the AGEs/RAGE/Nox4 signaling pathway

Cited by 28 publications

References 42 publications

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

Combination of the Herbs Radix Rehmanniae and Cornus Officinalis Mitigated Testicular Damage From Diabetes Mellitus by Enhancing Glycolysis via the AGEs/RAGE/HIF-1α Axis

A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

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