Integrated adrenal and testicular metabolomics revealed the protective effects of Guilingji on the Kidney-Yang deficiency syndrome rats

Du, Ke; Gao, Xiaoxia; Feng, Yan; Li, Jing; Wang, Hui; Lv, Silin; PeiYi, Wang; Zhang, Bin; Qin, Xuemei

doi:10.1016/j.jep.2020.112734

Cited by 17 publications

(21 citation statements)

References 47 publications

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“…In order to test this hypothesis, we selected Immp2l mutant mice as our animal model. Inner mitochondrial membrane peptidase 2-like (IMMP2L) is a functional domain of mitochondrial intima proteina that plays a crucial role in cleaving space-sorting signal peptide sequences of cytochrome c1 (CYC1) and mitochondrial glycerol phosphate dehydrogenase 2 (GPD2) ( Lu et al, 2008 ; Yang et al, 2016 ; Du et al, 2020 ). Therefore, it is an oxidative stress state in the Immp2l mutant mice.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, it is an oxidative stress state in the Immp2l mutant mice. Some studies have shown that oxidative stress mediates age-dependent spermatogenesis damage in Immp2l mutant mice ( Yang et al, 2016 ; Du et al, 2020 ). Thus, we employed the Immp2l mutant mice to investigate the protective effects of Guilingji on oligospermia induced by oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

et al. 2022

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Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Oxidative stress (OS) is one of the main causes of male infertility, which is characterized by excessive reactive oxygen species (ROS) or lack of antioxidants. Meanwhile, it is reported that oxidative stress plays an important role in the spermatogenic impairment in Inner mitochondrial membrane peptidase 2-like (Immp2l) mutant mice. In this study, we focused on the potential mechanism of Guilingji in protecting the spermatogenic functions in Immp2l mutant mice. The results revealed that Immp2l mutant mice exhibit impaired spermatogenesis and histology shows seminiferous tubules with reduced spermatogenic cells. After administration of Guilingji [150 mg/kg per day intragastric gavage], however, alleviated spermatogenesis impairment and reversed testis histopathological damage and reduced apoptosis. What’s more, western blotting and the levels of redox classic markers revealed that Guilingji can markedly reduce reactive oxygen species. Moreover, Guilingji treatment led to inhibition of the phosphorylation of mitogen-activated protein kinase (MAPK), regulated apoptosis in the cells. In summary, Guilingji can improve spermatogenesis in Immp2l mutant mice by regulating oxidation-antioxidant balance and MAPK pathway. Our data suggests that Guilingji may be a promising and effective antioxidant candidate for the treatment of male infertility.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

et al. 2022

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“…Researchers have found that testicular dysfunction induced by excessive HCT is characterized by disrupted testicular morphology and suppressed ability of the testes to produce testosterone [ 28 , 29 ]. Regarding testicular morphology, the present study first demonstrated that DP1 effectively alleviated the HCT-induced decreases in testicular and epididymal index, seminiferous tubule atrophy, and reduced germ cell layer thickness in testicular tissue.…”

Section: Discussionmentioning

confidence: 99%

A Protein from Dioscorea polystachya (Chinese Yam) Improves Hydrocortisone‐Induced Testicular Dysfunction by Alleviating Leydig Cell Injury via Upregulation of the Nrf2 Pathway

Han

Xing

et al. 2021

Oxidative Medicine and Cellular Longevity

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Leydig cell injury has been described as a primary driver of testicular dysfunction and is affected by oxidative stress. Dioscorea polystachya (Chinese yam) is used to improve testicular dysfunction in clinical and pharmacological research via its antioxidative activity, but the mechanisms underlying the beneficial effect of Chinese yam on testicular dysfunction and its suppression of Leydig cell oxidative damage remain unclear. In this study, we obtained a Chinese yam protein (DP1) and explored its effectiveness and possible mechanism in improving testicular dysfunction in vivo and in vitro. We established a testicular dysfunction model in rats using hydrocortisone (HCT). DP1 increased body weight and organ index, improved the deterioration in testicular morphology (including increasing the diameter of seminiferous tubules and thickness of germinal cell layers, inhibiting testicular cell apoptosis by increasing the Bcl-2/Bax ratio, and impeding collagen leakage by downregulating TGF-β1 and p-SMAD2/3 expression), and restored the testosterone content. In addition, DP1 enhanced the number of Leydig cells in rats and H2O2-induced TM3 Leydig cells, and the effect of DP1 on the apoptosis, fibrosis, and testosterone content of TM3 cells was similar to that observed in vivo. These changes were dependent on the regulation of oxidative stress, including significantly reduced intracellular 8-hydroxy-2-deoxyguanosine levels, enhanced superoxide dismutase activities, and decreased superoxide anion levels, which were confirmed via a superoxide overexpression system. Furthermore, we observed that DP1 promoted Nrf2 nuclear import and upregulated antioxidant factor expression in vivo and in vitro. However, Nrf2 silencing eliminated the ability of DP1 to increase the Bcl-2/Bax ratio, reduce the expression levels of TGF-β1 and p-SMAD2/3, and increase testosterone contents in H2O2-induced TM3 cells. In conclusion, DP1 reversed the HCT-induced testicular apoptosis and fibrosis and decreased testosterone contents by alleviating Leydig cell oxidative damage via upregulation of the Nrf2 pathway.

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“…16,22 For the AS rats yang deficiency, rats were placed in a refrigerator at 2°C for 2 h every day according to the previous studies. 20,23 A total of 30 SD rats were randomly divided into a normal group (CON), AS with damp-heat syndrome group (AS + DH), AS with yang deficiency group (AS + YX), AS with damp-heat syndrome treated with BBR (Shanghai Sangon Biological Co., Ltd.; Shanghai, China) group (AS + DH + BBR), AS with yang deficiency syndrome treated with BBR (AS + YX + BBR), AS with damp-heat syndrome treated with BBR and 3-methyl adenine (3-MA; an autophagy inhibitor; Lanzhou Day State Biological Technology Co., Ltd., Lanzhou, China) group (AS + DH + BBR + 3-MA) group. For the AS + DH + BBR and AS + YX + BBR groups, rats were orally administered BBR (150 mg/kg) daily for four weeks.…”

Section: Animal Models and Drug Treatmentsmentioning

confidence: 99%

“…19 In addition, Integrated adrenal and testicular metabolomics revealed the protective effects of Guilingji on the Yang deficiency syndrome rats. 20 In this study, we established an AS rat model with the characteristics of damp-heat syndrome or yang deficiency syndrome and examined the pathological morphology and degree of the inflammatory response in aortic tissue sections following BBR intervention. Further mechanistic studies were also performed to explore the effects of BBR on the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency.…”

Section: Introductionmentioning

confidence: 99%

<p>Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy</p>

Xiao

Huang

Li³

et al. 2020

DDDT

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Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency. Methods: Thirty SD rats were randomly divided into (1) control (CON); (2) damp-heat syndrome atherosclerosis (AS + DH); (3) yang deficiency syndrome atherosclerosis (AS + YX); (4) dampheat syndrome atherosclerosis + BBR (AS + DH + BBR); (5) yang deficiency syndrome, atherosclerosis + BBR (AS + YX + BBR); and (6) damp-heat syndrome, atherosclerosis + BBR + 3-methyladenine (AS + DH + BBR + 3-MA) (n = 5/group) groups. Pathological morphology, macrophage plaque infiltration, inflammation, and LC3-II and P62 expression were assessed. Results: Compared with the CON group, the AS + DH and AS + YX groups had an increased plaque area in the aortic tissue with substantial foam cell and macrophage infiltration, and increased levels of IL-1β and TNF-α (P < 0.01). After four weeks of BBR intervention, the plaque area in the AS + DH + BBR group was reduced with decreased foam cells and macrophage infiltration, and decreased levels of TNF-α and IL-1β, whereas LC3-II protein expression was increased and P62 protein expression was decreased in the AS + DH + BBR group when compared to AS + DH group. In addition, the AS + DH + BBR + 3-MA group exhibited a significantly enlarged plaque, substantial foam cell and macrophage infiltration, increased levels of IL-1β and TNF-α, and decreased LC3-II and P62 (P < 0.01) expression when compared to the AS + DH + BBR group. Conclusion: Our results indicated that the BBR could inhibit arterial plaque formation and alleviate the inflammatory response in the aortic tissues in the AS rats with damp-heat syndrome possibly via promoting autophagy. The molecular mechanisms of BBR-mediated protective effects in this animal model still require further investigation.

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Integrated adrenal and testicular metabolomics revealed the protective effects of Guilingji on the Kidney-Yang deficiency syndrome rats

Cited by 17 publications

References 47 publications

Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

A Protein from Dioscorea polystachya (Chinese Yam) Improves Hydrocortisone‐Induced Testicular Dysfunction by Alleviating Leydig Cell Injury via Upregulation of the Nrf2 Pathway

<p>Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy</p>

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