Auraptene Enhances Junction Assembly in Cerebrovascular Endothelial Cells by Promoting Resilience to Mitochondrial Stress through Activation of Antioxidant Enzymes and mtUPR

Lee, Min Joung; Jang, Yunseon; Zhu, Jiebo; Namgung, Eunji; Go, Dahyun; Seo, Changjun; Ju, Xianshu; Cui, Jianchen; Lee, Yu Lim; Kang, Hyoeun; Kim, Hyeongseok; Chung, Woosuk; Heo, Jun Young

doi:10.3390/antiox10030475

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…The anti-inflammatory and antioxidative effects of AUR also increased oocyte maturation and the fertilization rates of oocytes in an in vivo polycystic ovarian syndrome (PCOS) model [27]. AUR inhibited ROS generation and enhanced mitochondrial respiration through induction of NRF2 in a Parkinson's disease mouse model [28] and activated antioxidant enzymes and the mitochondrial unfolded protein response, which improves junction assembly in cerebrovascular endothelial cells [29]. AUR also induced hepatic GST and NQO1 by activating the antioxidant response in Nrf2 knockout mice [30].…”

Section: Discussionmentioning

confidence: 99%

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

et al. 2022

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Decrease in quality of postovulatory aged oocytes occurs due to oxidative stress and leads to low fertilization and development competence. It is one of the main causes that exerting detrimental effect on the success rate in assisted reproductive technology (ART). Auraptene (AUR), a citrus coumarin, has been reported to possess an antioxidant effects in other tissues. In this study, we aimed to confirm the potential of AUR to delay the oocyte aging process by alleviating oxidative stress. Superovulated mouse oocytes in metaphase of second meiosis (MII) were exposed to 0, 1 or 10 μM AUR for 12 h of in vitro aging. AUR addition to the culture medium recovered abnormal spindle and chromosome morphology and mitigated mitochondrial distribution and mitochondrial membrane potential (ΔΨ) in aged oocytes. AUR-treated aged oocytes also showed suppressed oxidative stress, with lower reactive oxygen species (ROS) levels, higher glutathione (GSH) levels and increased expression of several genes involved in antioxidation. Furthermore, AUR significantly elevated the fertilization and embryo developmental rates. Oocytes aged with 1 μM AUR exhibited morphokinetics that were very similar to those of the control group. Altogether, these data allowed us to conclude that AUR improved the quality of aged oocytes and suggest AUR as an effective clinical supplement candidate to prevent postovulatory aging.

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Section: Discussionmentioning

confidence: 99%

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

et al. 2022

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“…Furthermore, these components exert various effects. HMF exhibits anti-inflammatory activity, inhibits neuronal cell death, promotes BDNF production, stimulates neurogenesis, improves memory impairment, and exerts antidepressant effects [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]; AUR exhibits anti-inflammatory activity, inhibits neuronal cell death, promotes neurogenesis, and suppresses tau phosphorylation [ 25 , 26 , 27 , 28 , 29 ]. NGI also exhibits anti-inflammatory activity, inhibits neuronal cell death, promotes neurogenesis, suppresses tau phosphorylation, and exerts antioxidant effects [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Citrus kawachiensis Peel in Frailty-like Model Mice Induced by Low Protein Nutrition Disorders

et al. 2023

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“Frailty” caused by a decline in physiological reserve capacity, chronic inflammation, and oxidative stress in the elderly has recently become a major social issue. The present study examined the effects of the peel of Citrus kawachiensis (CK), which exhibits anti-inflammatory, antioxidant, and pro-neurogenesis activities in frailty-like model mice. Male C57BL/6 mice (15 weeks old) were fed an 18% protein diet (CON), a 2.5% protein diet (PM), and PM mixed with 1% dried CK peel powder for approximately 1 month. Mice were euthanized 2 or 8 days after a single intraperitoneal administration of lipopolysaccharide (LPS) and tissues were dissected. Among peripheral tissues, muscle weight, liver weight, and blood glucose levels were significantly higher in the PM–LPS–CK group than in the PM–LPS group. In the behavioral analysis, locomotive activity was significantly lower in the PM–LPS group than in the PM group. The reduction in locomotive activity in the PM–LPS–CK group was significantly smaller than that in the PM–LPS group. The quantification of microglia in the hippocampal stratum lacunosum-moleculare revealed that increases in the PM–LPS group were significantly suppressed by the dried CK peel powder. Furthermore, the quantification of synaptic vesicle membrane proteins in the hippocampal CA3 region showed down-regulated expression in the PM–LPS group, which was significantly ameliorated by the administration of the dried CK peel powder. Collectively, these results suggest that CK inhibits inflammation and oxidative stress induced by PM and LPS in the central nervous system and peripheral tissue. Therefore, C. kawachiensis is highly effective against “frailty”.

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“…Likewise, it was demonstrated that caloric restriction could activate the mtUPR via a miRNA-dependent pathway [ 95 ], and the treatment with statins, such as fluvastatin and rosuvastatin, that inhibit the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the mevalonate pathway, activate the mtUPR since they interfere with mitochondrial electron carriers [ 96 ]. Other compounds that were reported as mtUPR activators are chlorprothixene, an antagonist of the D2 dopamine receptor, auranofin, an antirheumatic agent [ 86 ], as well as auraptene, a natural compound from citrus fruits [ 97 ]. Finally, another antioxidant compound that activates the mtUPR is choline, which promotes the SIRT3-AMPK pathway [ 98 ] ( Table 1 ).…”

Section: Mitochondrial Proteostasismentioning

confidence: 99%

mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases

Cilleros-Holgado

Gómez-Fernández

Piñero-Pérez

et al. 2023

IJMS

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Mitochondrial dysfunction is a key pathological event in many diseases. Its role in energy production, calcium homeostasis, apoptosis regulation, and reactive oxygen species (ROS) balance render mitochondria essential for cell survival and fitness. However, there are no effective treatments for most primary and secondary mitochondrial diseases to this day. Therefore, new therapeutic approaches, such as the modulation of the mitochondrial unfolded protein response (mtUPR), are being explored. mtUPRs englobe several compensatory processes related to proteostasis and antioxidant system mechanisms. mtUPR activation, through an overcompensation for mild intracellular stress, promotes cell homeostasis and improves lifespan and disease alterations in biological models of mitochondrial dysfunction in age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases. Although mtUPR activation is a promising therapeutic option for many pathological conditions, its activation could promote tumor progression in cancer patients, and its overactivation could lead to non-desired side effects, such as the increased heteroplasmy of mitochondrial DNA mutations. In this review, we present the most recent data about mtUPR modulation as a therapeutic approach, its role in diseases, and its potential negative consequences in specific pathological situations.

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Auraptene Enhances Junction Assembly in Cerebrovascular Endothelial Cells by Promoting Resilience to Mitochondrial Stress through Activation of Antioxidant Enzymes and mtUPR

Cited by 9 publications

References 45 publications

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

Effects of Citrus kawachiensis Peel in Frailty-like Model Mice Induced by Low Protein Nutrition Disorders

mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases

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