Caffeic Acid Phenethyl Ester (CAPE) Improves Boar Sperm Quality and Antioxidant Capacity in Liquid Preservation (17°C) Linked to AMPK Activity Maintenance

Lan, Qun; Xue, Li'e; Cao, Jiacheng; Xie, Yingyu; Xiao, Tianfang; Fang, Shouguo

doi:10.3389/fvets.2022.904886

Cited by 5 publications

(5 citation statements)

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“…CAPE, one of the main bioactive components of propolis, has been reported to effectively repress tumor migration [ 45 ], relieve inflammatory responses [ 46 ], inhibit oxidation, and protect neurons from apoptosis [ 28 , 47 ]. Although there have been many studies of the pharmacological effects of CAPE, there are few reports of its anti-inflammatory and anti-oxidative stress effects after SCI.…”

Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

Zhang,

Deng,

Hong

et al. 2024

J Transl Med

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Background The treatment of spinal cord injury (SCI) has always been a significant research focus of clinical neuroscience, with inhibition of microglia-mediated neuro-inflammation as well as oxidative stress key to successful SCI patient treatment. Caffeic acid phenethyl ester (CAPE), a compound extracted from propolis, has both anti-inflammatory and anti-oxidative effects, but its SCI therapeutic effects have rarely been reported. Methods We constructed a mouse spinal cord contusion model and administered CAPE intraperitoneally for 7 consecutive days after injury, and methylprednisolone (MP) was used as a positive control. Hematoxylin–eosin, Nissl, and Luxol Fast Blue staining were used to assess the effect of CAPE on the structures of nervous tissue after SCI. Basso Mouse Scale scores and footprint analysis were used to explore the effect of CAPE on the recovery of motor function by SCI mice. Western blot analysis and immunofluorescence staining assessed levels of inflammatory mediators and oxidative stress-related proteins both in vivo and in vitro after CAPE treatment. Further, reactive oxygen species (ROS) within the cytoplasm were detected using an ROS kit. Changes in mitochondrial membrane potential after CAPE treatment were detected with 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide. Mechanistically, western blot analysis and immunofluorescence staining were used to examine the effect of CAPE on the SIRT1/PGC1α/DRP1 signaling pathway. Results CAPE-treated SCI mice showed less neuronal tissue loss, more neuronal survival, and reduced demyelination. Interestingly, SCI mice treated with CAPE showed better recovery of motor function. CAPE treatment reduced the expression of inflammatory and oxidative mediators, including iNOS, COX-2, TNF-α, IL-1β, 1L-6, NOX-2, and NOX-4, as well as the positive control MP both in vitro and in vivo. In addition, molecular docking experiments showed that CAPE had a high affinity for SIRT1, and that CAPE treatment significantly activated SIRT1 and PGC1α, with down-regulation of DRP1. Further, CAPE treatment significantly reduced the level of ROS in cellular cytoplasm and increased the mitochondrial membrane potential, which improved normal mitochondrial function. After administering the SIRT1 inhibitor nicotinamide, the effect of CAPE on neuro-inflammation and oxidative stress was reversed.On the contrary, SIRT1 agonist SRT2183 further enhanced the anti-inflammatory and antioxidant effects of CAPE, indicating that the anti-inflammatory and anti-oxidative stress effects of CAPE after SCI were dependent on SIRT1. Conclusion CAPE inhibits microglia-mediated neuro-inflammation and oxidative stress and supports mitochondrial function by regulating the SIRT1/PGC1α/DRP1 signaling pathway after SCI. These effects demonstrate that CAPE reduces nerve tissue damage. Therefore, CAPE is a potential drug for the treatment of SCI through production of anti-inflammatory and anti-oxidative stress effects. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

Zhang,

Deng,

Hong

et al. 2024

J Transl Med

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“…To overcome the detrimental effects of OS on semen storage, various antioxidants were added into the semen extender, and their protective effect on sperm quality was observed [ 11 , 33 , 34 ]. Furthermore, our previous investigation demonstrated that antioxidants in seminal plasma are directly involved in cryotolerance of boar spermatozoa by playing against OS induced by the freezing and thawing process [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…After four days of storage, the sperm AMPK was significantly activated. The increase in sperm SOD-like activity after four days of storage may be due to the activation of the sperm AMPK, which is suggested to promote the antioxidants in boar spermatozoa [ 33 ]. SOD scavenges O 2-• [ 12 ], and its supplementation into freezing medium was demonstrated to be beneficial to the cryosurvival of Black Bengal buck spermatozoa [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…The final question regarding how the activated AMPK influences sperm quality remains. It has been reported that the addition of caffeic acid phenethyl ester and rosmarinic acid in boar semen improves sperm quality and promotes antioxidant capacity, possibly through affecting AMPK activity [ 33 , 52 ]. Further evidence in mouse embryonic fibroblasts and skeletal muscle suggests that the activation of the AMPK induces a peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)-dependent antioxidant response [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

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Antioxidants and Oxidants in Boar Spermatozoa and Their Surrounding Environment Are Associated with AMPK Activation during Liquid Storage

Zhao

Zhu

et al. 2023

Veterinary Sciences

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Activation of the AMP-activated protein kinase (AMPK) has been demonstrated to be beneficial for boar sperm quality and functionality, while the underlying mechanism of AMPK activation of boar spermatozoa remains obscure. This study aimed to explore the effect of antioxidants and oxidants in boar spermatozoa and their surrounding fluid (SF) on the activation of AMPK during the liquid storage. Ejaculates from Duroc boars, routinely used for semen production, were collected and diluted to a final concentration of 25 × 106/mL. In experiment 1, twenty-five semen samples from eighteen boars were stored at 17 °C for 7 days. In experiment 2, three pooled semen samples created from nine ejaculates of nine boars were used, and each sample was treated with 0, 0.1, 0.2, and 0.4 μM/L H2O2 and stored at 17 °C for 3 h. Sperm quality and functionality, antioxidants and oxidants in boar spermatozoa and SF, the intracellular AMP/ATP ratio, and the expression levels of the phosphorylated AMPK (Thr172) were determined. Sperm quality significantly decreased with storage time in terms of viability (p < 0.05). Antioxidant and oxidant levels were markedly affected with storage time, with a decline in the SF total antioxidant capacity (TAC) (p < 0.05), SF malondialdehyde (MDA) (p < 0.05), and the sperm’s total oxidant status (TOS), as well as a fluctuation in sperm superoxidase dismutase-like (SOD-like) activity (p < 0.05). The intracellular AMP/ATP ratio increased (p < 0.05) on day 4 and subsequently decreased to its lowest value on days 6 and 7 (p < 0.05). The phosphorylated AMPK levels increased from day 2 to day 7 (p < 0.05). Correlation analyses indicate that sperm quality during liquid storage was correlated to antioxidants and oxidants in spermatozoa and SF (p < 0.05), which were correlated to the phosphorylation of sperm AMPK (p < 0.05). Treatment with H2O2 induced damages in sperm quality (p < 0.05), a decline in antioxidant levels (SF TAC, p < 0.05; sperm SOD-like activity, p < 0.01), an increase in oxidant levels (SF MDA, p < 0.05; intracellular ROS production, p < 0.05), a higher AMP/ATP ratio (p < 0.05), and phosphorylated AMPK levels (p < 0.05) in comparison with the control. The results suggest that antioxidants and oxidants in boar spermatozoa and SF are involved in AMPK activation during liquid storage.

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“…ROS can damage sperm mitochondria, alter MMP, induce mitochondrial dysfunction, and further affect sperm energy metabolism [ 28 ]. During sperm preservation, the AMPK signaling pathway can significantly improve sperm preservation quality and antioxidant capacity [ 29 ]. After AMPK is activated, it regulates a series of energy metabolism pathways, such as glycolysis, lipid homeostasis, and mitochondrial homeostasis, by phosphorylating key proteins [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Analysis of Sodium Salicylate Improving the Preservation Quality of Ram Sperm

Bai,

Zhang,

Shen

et al. 2023

Molecules

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The aim of this study was to investigate the effects of sodium salicylate (SS) on the preservation and metabolic regulation of sheep sperm. Under 4 °C low-temperature conditions, SS (at 10 µM, 20 µM, 30 µM, and 50 µM) was added to the semen diluent to detect sperm motility, plasma membrane, and acrosome integrity. Based on the selected optimal concentration of SS (20 µM), the effects of 20 µM of SS on sperms’ antioxidant capacity and mitochondrial membrane potential (MMP) were evaluated, and metabolomics analysis was conducted. The results showed that on the 20th day of low-temperature storage, the sperm motility of the 20 µM SS group was 62.80%, and the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly higher than those of the control group (p < 0.01). The content of Ca2+, reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly lower than those of the control group (p < 0.01), and the total antioxidant capacity (T-AOC) was significantly higher than that of the control group (p < 0.05); mitochondrial activity and the total cholesterol (TC) content were significantly higher than those in the control group (p < 0.01). An ultrastructural examination showed that in the SS group, the sperm plasma membrane and acrosome were intact, the fibrous sheath and axoneme morphology of the outer dense fibers were normal, and the mitochondria were arranged neatly. In the control group, there was significant swelling of the sperm plasma membrane, rupture of the acrosome, and vacuolization of mitochondria. Using metabolomics analysis, 20 of the most significant differential metabolic markers were screened, mainly involving 6 metabolic pathways, with the amino acid biosynthesis pathway being the most abundant. In summary, 20 µM of SS significantly improved the preservation quality of sheep sperm under low-temperature conditions of 4 °C.

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Caffeic Acid Phenethyl Ester (CAPE) Improves Boar Sperm Quality and Antioxidant Capacity in Liquid Preservation (17°C) Linked to AMPK Activity Maintenance

Cited by 5 publications

References 40 publications

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

Antioxidants and Oxidants in Boar Spermatozoa and Their Surrounding Environment Are Associated with AMPK Activation during Liquid Storage

Metabolomics Analysis of Sodium Salicylate Improving the Preservation Quality of Ram Sperm

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