Icariin protects mouse Leydig cell testosterone synthesis from the adverse effects of di(2-ethylhexyl) phthalate

Sun, Jiandong; Wang, Dongdi; Lin, Jianbo; Liu, Yue; Xu, Lixuan; Lv, Ruimin; Mo, Kaien; Lian, Xiuli; Xie, Min; Xu, Shunqing; Wang, Shie

doi:10.1016/j.taap.2019.114612

Cited by 34 publications

(29 citation statements)

References 32 publications

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“…Therefore, we consider that ICA may attenuate tubulointerstitial fibrosis by activating autophagy. It has been reported that ICA promoted androgen production and upregulated the expression of transcription factor SF-1 (adrenal 4-binding protein) and steroid-producing enzymes Chen et al (2014) , Sun et al (2019) , and ICA improves the physiological state of the testicles and increases the circulating levels of testosterone ( Zhang and Yang, 2006 ). Thence, ICA has androgen-like effects and can ameliorate sexual dysfunction ( Koizumi et al, 2010 ; Liu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

et al. 2021

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Tubulointerstitial fibrosis is one of the most common pathological features of diabetic nephropathy. Autophagy, an intracellular mechanism to remove damaged or dysfunctional cell parts and maintain metabolic homeostasis, is inhibited in diabetic neuropathy. Icariin is a traditional Chinese medicine extract known for nourishing the kidney and reinforcing Yang. In this study, we investigated the effects and mechanism of Icariin on renal function, autophagy, and fibrosis in type 2 diabetic nephropathic rats and in high-glucose-incubated human renal tubular epithelial cells and rat renal fibroblasts (in vitro). Icariin improved diabetes, renal function, restored autophagy, and alleviated fibrosis in type 2 diabetic neuropathic rats and in vitro. After we applied autophagy-related gene 5-small interfering RNA, we found that fibrosis improvement by Icariin was related to autophagy restoration. By detecting serum sex hormone levels, and using dihydrotestosterone, siRNA for androgen receptor, and the androgen receptor antagonist Apalutamide (ARN-509), we found that Icariin had an androgen-like effect and restored autophagy and reduced fibrosis by regulating the androgen receptor. In addition, miR-192-5p levels were increased under high glucose but reduced after dihydrotestosterone and Icariin treatment. Furthermore, dihydrotestosterone and Icariin inhibited miR-192-5p overexpression-induced fibrosis production and autophagy limitation. Glucagon-like peptide-1 receptor (GLP-1R) was downregulated by high glucose and overexpression of miR-192-5p and could be restored by dihydrotestosterone and Icariin. By using ARN-509, we found that Icariin increased GLP-1R expression by regulating the androgen receptor. GLP-1R-siRNA transfection weakened the effects of Icariin on autophagy and fibrosis. These findings indicate that Icariin alleviates tubulointerstitial fibrosis by restoring autophagy through the miR-192-5p/GLP-1R pathway and is a novel therapeutic option for diabetic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

et al. 2021

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“…Icariin (11) is a prenylated flavonol glycoside ( Figure 6) derived from kaempferol (10) and isolated from several species of plant belonging to the genus Epimedium, such as the horny goat weed. Icariin (11) has been shown to reverse the adverse effects of di(2-ethylhexyl) phtalate (DEHP) on primary Leydig cell proliferation and testosterone synthesis [70]. Specifically, icariin (11) allowed to recover from the inhibitory effects of DEHP on the expression of steroidogenic enzymes (Cyp11a1, Hsd3b1, and Hsd17b3) and the transcription factor Nr5a1 (Sf-1), known to regulate steroidogenic gene expression.…”

Section: Flavonolsmentioning

confidence: 99%

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Martin

Touaibia

2020

Antioxidants

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Androgen production, being important for male fertility, is mainly accomplished by the Leydig cells from the interstitial compartment of the testis. Testosterone plays a critical role in testis development, normal masculinization, and the maintenance of spermatogenesis. Within seminiferous tubules, appropriate Sertoli cell function is highly dependent on testicular androgen levels and is essential to initiate and maintain spermatogenesis. During aging, testosterone production by the testicular Leydig cells declines from the 30s in humans at a rate of 1% per year. This review outlines the recent findings regarding the use of flavonoids and isoflavonoids to improve testosterone production, contributing to normal spermatogenesis and preventing age-related degenerative diseases associated with testosterone deficiency. With the cumulation of information on the actions of different flavonoids and isoflavonoids on steroidogenesis in Leydig cells, we can now draw conclusions regarding the structure-activity relationship on androgen production. Indeed, flavonoids having a 5,7-dihydroxychromen-4-one backbone tend to increase the expression of the steroidogenic acute regulatory protein (StAR), being critical for the entry of cholesterol into the mitochondria, leading to increased testosterone production from testis Leydig cells. Therefore, flavonoids and isoflavonoids such as chrysin, apigenin, luteolin, quercetin, and daidzein may be effective in delaying the initiation of late-onset hypogonadism associated with aging in males.

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“…ICA is a flavonoid that can protect the synthesis of testosterone in mouse Leydig cells (by the effects of 2ethylhexyl phthalate). It protects mouse testes from the damage induced by DEHP by blocking ROS and promoting the secretion of testosterone (Sun et al, 2019). It can be concluded that icariin- zinc may promote testosterone secretion by protecting rat testicular cells from damage.…”

Section: Discussionmentioning

confidence: 92%

Synthesis of Icariin-Zinc and its Protective Effect on Exercise Fatigue and Reproductive System Related Glands in Male Rats

Zhang

Liu

et al. 2021

Front. Pharmacol.

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Background: Icariin, a traditional Chinese medicine, plays a protective role in the treatment of exercise fatigue. Zinc, a trace element, plays an important role in the reproductive system. Therefore, we aimed to synthesize an Icariin-Zinc complex (by chemical means) and verify its protective effect on exercise fatigue and the reproductive system using animal experiments.Methods: The icariin-zinc complex was prepared by the reaction of icariin carbonyl and zinc ions (molar ratio 1:3). The molecular formula and structural formula of the complex were identified and tested. Fifty-six rats selected by swimming training were randomly divided into six groups: static control, exercise control, icariin, gluconate zinc (G-Zn group), icariin glucose zinc and icariin-zinc exercise ( low, high dose/L-E group, H-E group) groups. These groups respectively received the following doses: 1 ml/100 g, daily gavage with NS (for the first two groups), 45 mg/kg icariin, 110 mg/kg Gluconate Zinc, Icariin glucose zinc (45 mg/kg Icariin and 110 mg/kg Gluconate Zinc), 60 mg/kg icariin zinc and 180 mg/kg icariin zinc. After 3 weeks of gavage, we conducted 6 weeks of exhaustive swimming training. Test indices such as exhaustive swimming time of rats and body weight were evaluated after the last training exercise. The seminal vesicles, testes, and prostate gland were weighed, and their indices were calculated. The levels of testosterone (in the plasma) and glycogen (in the liver and muscle homogenates) were also evaluated using ELISA.Results: Compared with the static control group, the exhaustive swimming time of the rats in each group was prolonged. Compared with the other groups, the exhaustive swimming time of the L-E and H-E groups was significantly longer (p < 0.01); the Icariin-Zinc complex significantly increased the exhaustive swimming time of the rats. Compared with the static control group, the plasma testosterone content of the L-E and H-E groups increased significantly (p < 0.05). Compared with the exercise control group and G-Zn group, the plasma testosterone content of the H-E group also increased significantly (p < 0.01). The Icariin-Zinc complex significantly increased the serum levels of testosterone in rats. Compared with the control group, the muscle glycogen reserves of each group decreased, indicating that the muscle glycogen reserves of the rats decreased after swimming. Compared with other groups, the Icariin-Zinc complex can reduce the level of glycogen in the muscles, indicating that it can increase the utilization efficiency of glycogen in muscles. Compared with the static control and exercise control groups, the testicular weight of rats in the administration groups increased slightly. The Icariin-Zinc complex increased the testicular weight, indicating that the function of the reproductive system was improved to some extent.Conclusion: Icariin-Zinc can significantly prolong the exhaustive swimming time, improve exercise ability, and increase the plasma testosterone level (which is beneficial for improving the reproductive ability of male rats). Moreover, the beneficial effect of Icariin-Zinc on the glycogen content, testis index, and other reproductive system glands is dose-dependent.

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Icariin protects mouse Leydig cell testosterone synthesis from the adverse effects of di(2-ethylhexyl) phthalate

Cited by 34 publications

References 32 publications

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

Improvement of Testicular Steroidogenesis Using Flavonoids and Isoflavonoids for Prevention of Late-Onset Male Hypogonadism

Synthesis of Icariin-Zinc and its Protective Effect on Exercise Fatigue and Reproductive System Related Glands in Male Rats

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