Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2–related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo

Zhu, Daocheng; Wang, Yihan; Lin, Jiahao; Miao, Zhimin; Xu, Jiajing; Wu, Yaosen

doi:10.1039/d0fo02325f

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…Interestingly, Sha and coworkers demonstrated that maltol supplementation could reduce the levels of OS and restain apoptosis via promoting the Nrf2/HO-1 signaling axis in the brain tissue alleviating D-Gal-induced neurological impairment [ 21 ]. A pioneering research reports that maltol administration attenuates the aggravation of osteoarthritis via enhancing the Nrf2/HO-1 signaling pathway [ 36 ]. Our study is consistent with the above analysis that maltol can activate the Nrf2 signal pathway.…”

Section: Discussionmentioning

confidence: 99%

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

Mao

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Spinal cord injury (SCI), a fatal disease in the central nervous system, is characteristic of weak neuronal regeneration ability and complex pathological progress. Activation of oxidative stress (OS) and apoptosis-mediated cell death significantly contributes to the progression of SCI. Current evidence suggests that maltol exerts natural antioxidative properties via obstructing OS and apoptosis. However, the significant effect of maltol on SCI treatment has never been evaluated yet. In our current study, we explored maltol administration that could trigger the expression of Nrf2 and promote the retranslocation of Nrf2 from the cytosol to the nucleus, which can subsequently obstruct OS signal and apoptosis-mediated neuronal cell death after SCI. Furthermore, we found that maltol treatment enhances PINK1/Parkin-mediated mitophagy in PC12 cells, facilitating the recovery of mitochondrial functions. Our findings propose that maltol could be a promising therapeutic candidate for the treatment and management of SCI.

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Section: Discussionmentioning

confidence: 99%

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

Mao

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Previous studies have identified several signaling pathways involving the action mechanism of IL-1β in OA progression, such as p38 MAPK signaling pathway (Wang 2021 ), PI3K/Akt/mTOR signaling pathway (Xu 2021 ), nuclear factor erythroid 2-related factor-2/heme oxygenase-1 signaling pathway (Zhu 2021 ), JAK2/STAT3 signaling pathway (Liu et al 2020 ), and Wnt/β-catenin signaling pathway (Miyatake and Kumagai 2020 ). Among them, NF-κB signaling is a widely studied pathway participating in IL-1β-induced inflammatory response during OA development (Jimi et al 2019 ; Choi et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

Zhang

et al. 2021

Mol Med

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Purpose Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA. Methods IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. Results DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. Conclusions Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

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“…In the present study, it was found that maltol markedly prevented OGD-induced λ-H2AX formation and phosphorylation of ATM, as well as effectively inhibited ROS accumulation. Another study revealed that maltol not only upregulates the expression of Nrf2, but also promotes its translocation into nuclei (12). Within nuclei, Nrf2 acts as a transcription factor accounting for upregulating the expression of inducible antioxidant enzymes (47).…”

Section: Discussionmentioning

confidence: 99%

“…Although being widely used as a food flavoring agent, it has multiple bio-activities including anti-oxidative stress, anti-inflammatory and anti-apoptotic (9)(10)(11). Moreover, it effectively inhibits several pathological processes including osteoarthritis, diabetic peripheral neuropathy and liver fibrosis (12)(13)(14). In mice, maltol has neuroprotective effects against hypoxia-induced damage in neurons (15,16).…”

Section: Introductionmentioning

confidence: 99%

Maltol inhibits oxygen glucose deprivation‑induced chromatinolysis in SH‑SY5Y cells by maintaining pyruvate level

Zhang

Wang

et al. 2023

Mol Med Rep

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Maltol, a chemical isolated from ginseng root, has shown treatment effects on several pathological processes including osteoarthritis, diabetic peripheral neuropathy and liver fibrosis. Nevertheless, its effect on ischemia-induced neuron death remains elusive. In the present study, the treatment effect of maltol on ischemia-induced neuron damage was investigated by using oxygen and glucose deprivation (OGD) model in SH-SY5Y cells. In vitro studies revealed that maltol protected SH-SY5Y cells against OGD-induced chromatinolysis by inhibiting two reactive oxygen species (ROS)-regulated pathways. One was DNA double-strand breaks and the other was nuclear translocation of apoptosis inducing factor. Mechanistically, maltol not only inhibited OGD-induced depletion of glutathione and cysteine by maintaining cystine/glutamate antiporter (xCT) level, but also abrogated OGD-induced catalase downregulation. Meanwhile, maltol also alleviated OGD-induced inactivation of mTOR by attenuating OGD-induced depletion of adenosine triphosphate and pyruvate and downregulation of pyruvate kinase M2, indicating that maltol inhibited the glycolysis dysfunction caused by OGD. Considering that activated mammalian target of the rapamycin (mTOR) could lead to enhanced xCT expression and decreased catalase degradation by autophagy, these findings indicated that maltol attenuated OGD-induced ROS via inhibition of mTOR inactivation by maintaining pyruvate level. Taken together, it was demonstrated that maltol prevented OGD-induced chromatinolysis in SH-SY5Y cells via inhibiting pyruvate depletion.

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Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2–related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo

Abstract: Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation.

Cited by 16 publications

References 39 publications

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

Maltol inhibits oxygen glucose deprivation‑induced chromatinolysis in SH‑SY5Y cells by maintaining pyruvate level

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