MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats
It is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: <i>Morinda officinalis</i>...
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MDPI AG
2020-07-01
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| author | Keshab Kumar Karna Kiran Kumar Soni Jae Hyung You Na Young Choi Hye Kyung Kim Chul Young Kim Sung Won Lee Yu Seob Shin Jong Kwan Park |
| author_facet | Keshab Kumar Karna Kiran Kumar Soni Jae Hyung You Na Young Choi Hye Kyung Kim Chul Young Kim Sung Won Lee Yu Seob Shin Jong Kwan Park |
| author_sort | Keshab Kumar Karna |
| collection | DOAJ |
| description | It is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: <i>Morinda officinalis</i> How (Rubiaceae) roots, <i>Allium cepa</i> L. (Liliaceae) outer scales, and <i>Cuscuta chinensis</i> Lamark (convolvulaceae) seeds. The present study aimed to investigate the possible mechanisms responsible for the effects of MOTILIPERM on testicular dysfunction induced by immobilization stress. Fifty male Sprague Dawley rats were divided into five groups (10 rats each): a normal control group (CTR), a control group administered MOTILIPERM 200 mg/kg (M 200), an immobilization-induced stress control group (S), an immobilization-induced stress group administered MOTILIPERM 100 mg/kg (S + M 100), and MOTILIPERM 200 mg/kg (S + M 200). Stressed rats (<i>n</i> = 30) were subjected to stress by immobilization for 6 h by placing them in a Perspex restraint cage, while controls (<i>n</i> = 20) were maintained without disturbance. Rats were administrated 100 or 200 mg/kg MOTILIPERM once daily for 30 days 1 h prior to immobilization. At the end of the treatment period, we measured body and reproductive organ weight; sperm parameters; histopathological damage; reproductive hormone levels; steroidogenic acute regulatory protein (StAR); biomarkers of oxidative stress; and apoptosis markers. MOTILIPERM treatment improved testicular dysfunction by up-regulating (<i>p</i> < 0.05) sperm count, sperm motility, serum testosterone level, StAR protein level, Johnsen score, and spermatogenic cell density in stressed rats. MOTILIPERM decreased oxidative stress by increasing (<i>p</i> < 0.05) testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione peroxidase-4 (GPx 4), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) levels and decreasing (<i>p</i> < 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (<i>p</i> < 0.05) cleaved caspase 3 and BCL2 associated X protein (Bax) levels; increased pro caspase-3 and B-cell lymphoma 2 (Bcl-2) levels; and upregulated testicular germ cell proliferation in stressed rats. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels also significantly (<i>p</i> < 0.05) decreased after pretreatment with MOTILIPERM in stressed rats. Collectively, our results suggest that, in immobilization-mediated stress-induced testicular dysfunction, MOTILIPERM sustains normal spermatogenesis via antioxidant and anti-apoptotic activities by activating the NRF/HO-1 signaling pathway. |
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| spelling | doaj.art-096724c127044f48a29ef4f2de26f1662023-11-20T05:48:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012113475010.3390/ijms21134750MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD RatsKeshab Kumar Karna0Kiran Kumar Soni1Jae Hyung You2Na Young Choi3Hye Kyung Kim4Chul Young Kim5Sung Won Lee6Yu Seob Shin7Jong Kwan Park8Department of Urology and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Clinical Trial Center for Medical Device, Jeonbuk National University Hospital, Jeonju 54907, KoreaDepartment of Biological Sciences, Kent State University, Kent, OH 44242, USADepartment of Urology and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Clinical Trial Center for Medical Device, Jeonbuk National University Hospital, Jeonju 54907, KoreaDepartment of Urology and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Clinical Trial Center for Medical Device, Jeonbuk National University Hospital, Jeonju 54907, KoreaCollege of Pharmacy, Kyungsung University, Busan 48434, KoreaCollege of Pharmacy, Hanyang University, Ansan 426791, KoreaDepartment of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaDepartment of Urology and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Clinical Trial Center for Medical Device, Jeonbuk National University Hospital, Jeonju 54907, KoreaDepartment of Urology and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute and Clinical Trial Center for Medical Device, Jeonbuk National University Hospital, Jeonju 54907, KoreaIt is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: <i>Morinda officinalis</i> How (Rubiaceae) roots, <i>Allium cepa</i> L. (Liliaceae) outer scales, and <i>Cuscuta chinensis</i> Lamark (convolvulaceae) seeds. The present study aimed to investigate the possible mechanisms responsible for the effects of MOTILIPERM on testicular dysfunction induced by immobilization stress. Fifty male Sprague Dawley rats were divided into five groups (10 rats each): a normal control group (CTR), a control group administered MOTILIPERM 200 mg/kg (M 200), an immobilization-induced stress control group (S), an immobilization-induced stress group administered MOTILIPERM 100 mg/kg (S + M 100), and MOTILIPERM 200 mg/kg (S + M 200). Stressed rats (<i>n</i> = 30) were subjected to stress by immobilization for 6 h by placing them in a Perspex restraint cage, while controls (<i>n</i> = 20) were maintained without disturbance. Rats were administrated 100 or 200 mg/kg MOTILIPERM once daily for 30 days 1 h prior to immobilization. At the end of the treatment period, we measured body and reproductive organ weight; sperm parameters; histopathological damage; reproductive hormone levels; steroidogenic acute regulatory protein (StAR); biomarkers of oxidative stress; and apoptosis markers. MOTILIPERM treatment improved testicular dysfunction by up-regulating (<i>p</i> < 0.05) sperm count, sperm motility, serum testosterone level, StAR protein level, Johnsen score, and spermatogenic cell density in stressed rats. MOTILIPERM decreased oxidative stress by increasing (<i>p</i> < 0.05) testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione peroxidase-4 (GPx 4), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) levels and decreasing (<i>p</i> < 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (<i>p</i> < 0.05) cleaved caspase 3 and BCL2 associated X protein (Bax) levels; increased pro caspase-3 and B-cell lymphoma 2 (Bcl-2) levels; and upregulated testicular germ cell proliferation in stressed rats. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels also significantly (<i>p</i> < 0.05) decreased after pretreatment with MOTILIPERM in stressed rats. Collectively, our results suggest that, in immobilization-mediated stress-induced testicular dysfunction, MOTILIPERM sustains normal spermatogenesis via antioxidant and anti-apoptotic activities by activating the NRF/HO-1 signaling pathway.https://www.mdpi.com/1422-0067/21/13/4750stress by immobilizationMOTILIPERMtestisoxidative stressapoptosis |
| spellingShingle | Keshab Kumar Karna Kiran Kumar Soni Jae Hyung You Na Young Choi Hye Kyung Kim Chul Young Kim Sung Won Lee Yu Seob Shin Jong Kwan Park MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats International Journal of Molecular Sciences stress by immobilization MOTILIPERM testis oxidative stress apoptosis |
| title | MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats |
| title_full | MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats |
| title_fullStr | MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats |
| title_full_unstemmed | MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats |
| title_short | MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats |
| title_sort | motiliperm ameliorates immobilization stress induced testicular dysfunction via inhibition of oxidative stress and modulation of the nrf2 ho 1 pathway in sd rats |
| topic | stress by immobilization MOTILIPERM testis oxidative stress apoptosis |
| url | https://www.mdpi.com/1422-0067/21/13/4750 |
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