Aucubin, a natural iridoid glucoside, attenuates oxidative stress-induced testis injury by inhibiting JNK and CHOP activation via Nrf2 up-regulation

Ma, Bo; Zhang, Jie; Zhu, Zhiming; Bao, Xiaowen; Zhang, Mingya; Ren, Chaoxing; Zhang, Qi

doi:10.1016/j.phymed.2019.153057

Cited by 49 publications

(20 citation statements)

References 27 publications

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“…In the model, the deteriorated sperm quality, altered testicle histomorphology, disordered hormone levels, the decreased activity of testicular marker enzyme, and the triggered testis oxidative stress and germ cells apoptosis were observed. The observed altered sperm quality and testicle histomorphology in this study is consistent with the previous reports [ 8 , 13 , 30 ]. Gastric administration of appropriate dose of OPs could reverse these abnormalities.…”

Section: Discussionsupporting

confidence: 94%

“…Spermatogenesis occurs in the seminiferous tubules and is strictly dependent on the structure of the testis. Therefore, the integrity of testicular morphological structure and the maintenance of physiological function play important roles in spermatogenesis [ 8 ]. Abnormal testicular tissue structure, changes in reproductive hormones, oxidative damage, and cell apoptosis may be the mechanisms of male reproductive dysfunction [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice

et al. 2021

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Peptides from oyster hydrolysate (OPs) have a variety of biological activities. However, its protective effect and exact mechanism on testicular injury remain poorly understood. This study aimed to evaluate the protective effect of OPs on triptolide (TP)-induced testis damage and spermatogenesis dysfunction and investigate its underlying mechanism. In this work, the TP-induced testis injury model was created while OPs were gavaged in mice for 4 weeks. The results showed that OPs significantly improved the sperm count and motility of mice, and alleviated the seminiferous tubule injury. Further study showed that OPs decreased malonaldehyde (MDA) level and increased antioxidant enzyme (SOD and GPH-Px) activities, attenuating oxidative stress and thereby reducing the number of apoptotic cells in the testis. In addition, OPs improved the activities of enzymes (LDH, ALP and ACP) related to energy metabolism in the testis and restored the serum hormone level of mice to normal. Furthermore, OPs promoted the expression of Nrf2 protein, and then increased the expression of antioxidant enzyme regulatory protein (HO-1 and NQO1) in the testis. OPs inhibited JNK phosphorylation and Bcl-2/Bax-mediated apoptosis. In conclusion, OPs have a protective effect on testicular injury and spermatogenesis disorders caused by TP, suggesting the potential protection of OPs on male reproduction.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice

et al. 2021

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“…Glycosylated iridoid compounds such as aucubin 55 , catalposide and verproside (the main compounds found in the ethyl acetate fraction of Veronica ciliata) 56 showed a protective effect mediated by Nrf2, increasing the expression levels of the gene and the antioxidant protein NQO1. Ma et al reported that aucubin positively regulates Nrf2 translocation and induces the response of phase II antioxidant enzymes such as HMOX-1, NQO1 and SOD, considering aucubin a promising candidate to prevent oxidative stress that induces testicular damage 57 . Moon et al evaluated the ability of catalposide to induce the expression of HMOX-1 and its protein in a concentration-and time-dependent manner and found that exposure of neuro-2A cells to catalposide generates a protective effect against H 2 O 2 -induced oxidative stress, increasing the levels of the enzyme HMOX-1 58 .…”

Section: Discussionmentioning

confidence: 99%

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

Garzón-Castaño¹,

Jiménez-González²,

Veloza³

et al. 2020

F1000Res

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Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H2O2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 μM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H2O2-induced oxidative stress in HepG2 cells.

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“…For instance, the main active ingredient of traditional Chinese medicines Eucommia ulmoides , Rehmannia glutinosa , and plantain is the iridoid glucoside aucubin (AU), whose chemical name is β- d -glucopyranoside ( Figure 1 ). AU provides moist heat, analgesic, antihypertensive, liver protection, and antitumor effects ( Park, 2013 ; Ma et al., 2019 ). In the carbon-tetrachloride-mediated acute liver injury model ( Chang et al., 1983 ) and nonalcoholic fatty liver model ( Shen et al., 2019 ), AU improves liver injury through its anti-inflammatory and antioxidative effects.…”

Section: Introductionmentioning

confidence: 99%

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

et al. 2020

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Liver ischemia-reperfusion injury (IRI) is a common clinical event with high morbidity in patients undergoing complex liver surgery or having abdominal trauma. Inflammatory and oxidative stress responses are the main contributing factors in liver IRI. The iridoid glucoside aucubin (AU) has good anti-inflammatory and antioxidative effects; however, there are no relevant reports on the protective effect of glucosides on hepatic IRI. The purpose of this study was to determine whether AU pretreatment could prevent liver IRI and to explore the mechanism. Sprague-Dawley rats were randomly divided into five groups. The sham operation and IRI control groups were given intraperitoneal injections of normal saline, while the AU low-dose (AU-L) group, AU medium-dose (AU-M) group, and AU high-dose (AU-H) group were given intraperitoneal injections of AU at doses of 1, 5, and 10 mg/kg/day, respectively. After 10 d, liver IRI (70% liver ischemia for 1 h, reperfusion for 6 h) was surgically established in all groups except the sham group. Our results confirmed that liver injury was significantly aggravated after hepatic ischemia-reperfusion. AU alleviated the increase of transaminase and pathological changes induced by ischemia-reperfusion and improved liver damage. AU could also ameliorate the inflammatory and oxidative stress responses induced by ischemia-reperfusion and reduced expression of high mobility group protein (HMG)B1, receptor for advanced glycation end-products (RAGE), tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and reactive oxygen species (ROS). Moreover, AU reduced ischemia-reperfusion-induced mitochondrial dysfunction and cells apoptosis, increased peroxisome proliferatoractivated receptor g coactivator (PGC)-1a and uncoupling (UCP)2 protein expression, and reduced caspase-3, cleaved caspase-3, and Cytochrome P450 proteins (CYP) expression. To determine expression levels of the Toll-like receptor (TLR)-4/ nuclear factor-kB (NF-kB) pathway-related proteins in vitro and in vivo, we also measured TLR-4, myeloid differentiation factor88 (MyD88), NF-kB P65, p-P65, Ikappa-B-alpha (IkB-a), and p-IkB-a levels. The results showed that AU effectively

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Aucubin, a natural iridoid glucoside, attenuates oxidative stress-induced testis injury by inhibiting JNK and CHOP activation via Nrf2 up-regulation

Cited by 49 publications

References 27 publications

The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice

The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

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