Korean Red Ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress–induced testicular damage in rats via multifunctional approach

Kopalli, Spandana Rajendra; Cha, Kyu-Min; Hwang, Seock-Yeon; Jeong, Manbok; Kim, Si-Kwan

doi:10.1016/j.jgr.2018.06.004

Cited by 20 publications

(16 citation statements)

References 46 publications

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“…Ginsenosides are abundant in ginseng stems and leaves (GSLS), belong to nontraditional medicine parts, but are considered the most important medicinal resources (Wang, Yang, Yu, Yao, & Ren, 2013; Zhuo et al, 2017). Prior to the present study, Kopalli et al (Kopalli et al, 2019) have confirmed that KRG extract (enriched ginsenoside Rg3) protects the scrotal from chronic intermittent HS‐induced spermatogenic damage and help to recover testicular function by restoring intrinsic anti‐oxidant defenses. Recent research suggests that HS‐induced testicular damage may be related to apoptosis, oxidative stress, and autophagy (Li, Li, Zhou, Dai, & Li, 2018; Park et al, 2017).…”

Section: Discussionsupporting

confidence: 74%

“…Prior to the present study, Kopalli et al (Kopalli et al, 2019) have confirmed that KRG extract (enriched ginsenoside Rg3) protects the scrotal from chronic intermittent HS-induced spermatogenic damage and help to recover testicular function by restoring intrinsic anti-oxidant defenses. Recent research suggests that HS-induced testicular damage may be related to apoptosis, oxidative stress, and autophagy (Li, Li, Zhou, Dai, & Li, 2018;Park et al, 2017).…”

Section: Discussionsupporting

confidence: 65%

“…From previous results, long‐term administration of Korean red ginseng (KRG, P. ginseng Meyer) significantly delayed the aging‐induced testicular dysfunction (Kopalli et al, 2017). And KRG with enriched Rg3 ameliorated chronic intermittent HS‐induced testicular damage in rats (Kopalli, Cha, Hwang, Jeong, & Kim, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Saponins derived from the stems and leaves of Panax ginseng attenuate scrotal heat‐induced spermatogenic damage via inhibiting the MAPK mediated oxidative stress and apoptosis in mice

Liu

Leng

Hou

et al. 2020

Phytotherapy Research

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Heat stress (HS) reaction is a stress response caused by adverse conditions. Currently, the incidence of reproductive malignancies particularly in males has been constantly increasing. This work investigated the effects of saponins derived from the stems and leaves of Panax ginseng (GSLS) on testicular injury induced by scrotal hyperthermia in mice. GSLS (150, 300 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43°C for 18 min on seventh day. HS induced a significant loss of multinucleate giant cells, desquamation of germ cells in destructive seminiferous tubules. Moreover, HS reduced the serum testosterone, testicular tissue superoxide dismutase activity and glutathione (GSH) content, while significantly enhanced the production of malondialdehyde (p < .05). GSLS exhibited the protective potential against HS‐induced injury not only by modulating Bcl‐2 family and caspase protease family, but also by suppressing the protein levels of heme oxygenase‐1 (HO‐1), heat shock protein 70 (HSP70), hypoxia inducible factor‐1α (HIF‐1α) and activation of Mitogen‐activated protein kinase (MAPK) signaling pathways (p < .05). In conclusion, we clearly demonstrated that GSLS exhibited a significant protective effect against HS‐induced testicular dysfunction, mainly the inhibition of oxidative stress associated apoptosis partly via regulation of the MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 65%

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Saponins derived from the stems and leaves of Panax ginseng attenuate scrotal heat‐induced spermatogenic damage via inhibiting the MAPK mediated oxidative stress and apoptosis in mice

Liu

Leng

Hou

et al. 2020

Phytotherapy Research

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“…Moreover, Rg3 could reverse TP-induced apoptosis in MLTC-1 cells via downregulating the levels of Bax, active caspase 3, Cyto c and active caspase 9, and upregulating the level of Bcl-2. Kopalli et al indicated that Rg3 could alleviate hyperthermia-mediated male infertility 38. Ginseng could protect fertility factors and testicular damage in immobilization stress-induced rats 39.…”

Section: Discussionmentioning

confidence: 99%

<p>Ginsenoside Rg3 protects mouse leydig cells against triptolide by downregulation of miR-26a</p>

Liang

Zhang

2019

DDDT

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Background Ginsenoside Rg3 has been reported to exert protection function on germ cells. However, the mechanisms by which Rg3 regulates apoptosis in mouse Leydig cells remain unclear. In addition, triptolide (TP) has been reported to induce infertility in male rats. Thus, this study aimed to investigate the protective effect of Rg3 against TP-induced toxicity in MLTC-1 cells. Methods CCK-8, immunofluorescence assay, Western blotting and flow cytometry were used to detect cell proliferation and cell apoptosis, respectively. In addition, the dual luciferase reporter system assay was used to detect the interaction between miR-26a and GSK3β in MLTC-1 cells. Results TP significantly inhibited the proliferation of MLTC-1 cells, while the inhibitory effect of TP was reversed by Rg3. In addition, TP markedly induced apoptosis in MLTC-1 cells via increasing the expressions of Bax, active caspase 3, Cyto c and active caspase 9, and decreasing the level of Bcl-2. However, Rg3 alleviated TP-induced apoptosis of MLTC-1 cells. Moreover, the level of miR-26a was obviously downregulated by Rg3 treatment. The protective effect of Rg3 against TP-induced toxicity in MLTC-1 cells was abolished by miR-26a upregulation. Meanwhile, dual-luciferase assay showed GSK3β was the direct target of miR-26a in MLTC-1 cells. Overexpression of miR-26a markedly decreased the level of GSK3β. As expected, upregulation of miR-26a could abrogate the protective effects of Rg3 against TP-induced cytotoxicity via inhibiting the expression of GSK3β. Conclusion These results indicated that Rg3 could protect MLTC-1 against TP by downregulation of miR-26a. Therefore, Rg3 might serve as a potential agent for the treatment of male hypogonadism.

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“…Over the past decades, HS research has been carried out in many species, such as humans [ 11 ], cattle [ 12 ], pigs [ 13 , 14 ], corals [ 15 ], and rats [ 16 , 17 ]. However, the regulatory mechanisms of HS are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide identification and functional prediction of long non-coding RNAs in Sprague-Dawley rats during heat stress

Dou

Schenkel

et al. 2021

BMC Genomics

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Background Heat stress (HS) is a major stress event in the life of an animal, with detrimental upshots in production and health. Long-non-coding RNAs (lncRNAs) play an important role in many biological processes by transcriptional regulation. However, no research has been reported on the characterization and functionality of lncRNAs in heat-stressed rats. Results We studied expression levels of lncRNAs in rats during HS, using strand-specific RNA sequencing. Six rats, three in each of Control (22 ± 1 °C) and H120 (42 °C for 120 min) experimental groups, were used to screen for lncRNAs in their liver and adrenal glands. Totally, 4498 and 7627 putative lncRNAs were identified in liver and adrenal glands of the Control and H120 groups, respectively. The majority of lncRNAs were relatively shorter and contained fewer exons than protein-coding transcripts. In total, 482 (174 up-regulated and 308 down-regulated) and 271 (126 up-regulated and 145 down-regulated) differentially-expressed lncRNAs (DElncRNAs, P < 0.05) were identified in the liver and adrenal glands of the Control and H120 groups, respectively. Furthermore, 1274, 121, and 73 target differentially-expressed genes (DEGs) in the liver were predicted to interact with DElncRNAs based on trans−/cis- and sequence similarity regulatory modes. Functional annotation analyses indicated that these DEGs were mostly significantly enriched in insulin signalling, myeloid leukaemia, and glucagon signalling pathways. Similarly, 437, 73 and 41 target DEGs in the adrenal glands were mostly significantly enriched in the cell cycle (trans-prediction) and lysosome pathways (cis-prediction). The DElncRNAs interacting with DEGs that encode heat shock proteins (HSPs) may play an important role in HS response, which include Hsf4, Dnaja1, Dnajb4, Hsph1 and Hspb1 in the liver, and Dnajb13 and Hspb8 in the adrenal glands. The strand-specific RNA sequencing findings were also further verified through RT-qPCR. Conclusions This study is the first to provide a detailed characterization and functional analysis of expression levels of lncRNAs in liver and adrenal glands of heat-stressed rats, which provides basis for further studies on the biological functions of lncRNAs under heat stress in rats and other mammalian species.

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Korean Red Ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress–induced testicular damage in rats via multifunctional approach

Cited by 20 publications

References 46 publications

Saponins derived from the stems and leaves of Panax ginseng attenuate scrotal heat‐induced spermatogenic damage via inhibiting the MAPK mediated oxidative stress and apoptosis in mice

Saponins derived from the stems and leaves of Panax ginseng attenuate scrotal heat‐induced spermatogenic damage via inhibiting the MAPK mediated oxidative stress and apoptosis in mice

<p>Ginsenoside Rg3 protects mouse leydig cells against triptolide by downregulation of miR-26a</p>

Genome-wide identification and functional prediction of long non-coding RNAs in Sprague-Dawley rats during heat stress

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