Suppression of MAPK/NF‐kB and activation of Nrf2 signaling by Ajugarin‐I in EAE model of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamateinduced HT22 cells and hydrogen peroxide (H 2 O 2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/ NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.

Isoorientin ameliorates H2O2-induced apoptosis and oxidative stress in chondrocytes by regulating MAPK and PI3K/Akt pathways

“…In brief, these findings suggest that ISO inhibits chondrocyte apoptosis induced by H2O2, which may be mediated by the MAPK signaling pathway. ISO has been shown in numerous studies to prevent apoptosis caused by the MAPK signaling pathway [27,[45][46][47]. This phenomenon is also confirmed in our current study, which provides a theoretical foundation for ISO osteoarthritis treatment.…”

An active peptide from yak inhibits hypoxia-induced lung injury via suppressing VEGF/MAPK/inflammatory signaling

“…Thus, our study has revealed a previously unidentified feedback loop that triggers the activation of Nrf2 by LV in response to MAPK/NF-κB and HIF-1α coordination, inhibiting BEAS-2B damage during hypoxic stress. Additionally, the anti-hypoxia capability of LV towards BEAS-2B cells and lung tissue may also be attributed to its anti-apoptotic activity, as the coupling between MAPK/NF-κB and HIF-1α during stress induces nuclear senescence prior to apoptosis [ 55 , 56 ]. MAPK/NF-κB regulates local O 2 levels by modulating HIF-1α activation in BEAS-2B and lung tissue during hypoxia, potentially playing a role in chronic lung diseases.…”