<p>Methyl Jasmonate Protects Microglial Cells Against β-Amyloid-Induced Oxidative Stress and Inflammation via Nrf2-Dependent HO-1 Pathway</p>

Abstract

Background: β-Amyloid (Aβ) induces oxidative stress and inflammation of microglial cells, thus leading to Alzheimer's disease. Methyl jasmonate (MeJA) is reported to have antiinflammatory and anti-oxidant effects. However, the potential roles of MeJA in Aβ-induced cell activities and the underlying mechanism are unclear. Methods: Microglial cell line BV-2 was stimulated by 20 μM Aβ and/or 20 μM MeJA and then divided into four groups (control, Aβ, MeJA, and Aβ+MeJA). Cell viability was detected by MTT assay. MDA, SOD activity, and ROS were detected by fluorescence spectrophotometry and immunofluorescence assay. Nrf2 and HO-1 were detected by qRT-PCR and Western blot. Furthermore, inflammatory cytokines (p-NFκB, TLR4, TNF-α, IL-1β, and IL-6) and apoptosis factors (Bcl-2, Bax, and cl-casp-3) were detected by Western blot. TUNEL assay was applied to investigate apoptosis rate. Moreover, the mechanism of how MeJA played anti-oxidative stress and anti-inflammatory roles was investigated by silencing of Nrf2 via siRNA. Results: The result of MTT assay showed that MeJA improved the decreased viability of BV-2 cells induced by Aβ. The detection of MDA, SOD activity, and ROS showed the oxidative stress levels were decreased in Aβ+MeJA group compared with Aβ group. Nrf2, HO-1, and SOD were significantly up-regulated in Aβ+MeJA group compared with Aβ group (p<0.01). In contrast, inflammatory cytokines were significantly down-regulated in Aβ +MeJA group compared with Aβ group (p<0.05). Similarly, the expressions of apoptosis cytokines and TUNEL assay suggested a decreased apoptosis rate in Aβ+MeJA group compared to Aβ group (p<0.01). Finally, results of Nrf2 knockdown experiment showed down-regulations of anti-oxidative stress factors (Nrf2, HO-1 and SOD), up-regulations of inflammatory cytokines, and increased ratio of Bax to Bcl in Aβ+MeJA+si-Nrf2 group compared with Aβ+MeJA group (p<0.01). Conclusion: MeJA could relieve Aβ-induced oxidative stress and inflammatory response in microglial cells by activating Nrf2/HO-1 pathway.

Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling

“…Although evidence of increased ROS has been identified in AD, several studies demonstrate that this endogenous protective pathway is down-regulated in AD models and patients ( Ramsey et al, 2007 ; Tian et al, 2019 ; Sharma et al, 2020 ), which may be explained by different stage of AD ( Fao et al, 2019 ). In this study (see Figures 6 , 7 ) we found that the mRNA and protein levels of Nrf2, HO-1, and NQO1 and nuclear translocation of Nrf2 significantly decreased under AβO stimulation, which was consistent with previous studies ( Ali et al, 2018 ; Chiang et al, 2018 ; Li et al, 2020 ). However, ISL pre-treatment notably promoted the expression of Nrf2, HO-1, and NQO1 at both the transcription and translation levels as well as promoted the nuclear translocation of Nrf2 (see Figures 6 , 7 ).…”

Novel small molecules inhibit proteotoxicity and inflammation: Mechanistic and therapeutic implications for Alzheimer’s Disease, healthspan and lifespan- Aging as a consequence of glycolysis

“…BV2 cells were exposed to 5ug/ml of LPS for 24 hours, followed by exposure to 8 uM of the test compound which in our first screen inhibited Abeta-induced proteotoxicity. After supernatant was removed to measure cytokine release, cell viability was assessed using the MTT assay [111]. in our hands stimulating inflammation by adding LPS (1.25-5ug/mL) was a more reliable stimulus of inflammation than hAbeta1-42 [99].…”

Methyl jasmonate reduces the inflammation and apoptosis of HK-2 cells induced by LPS by regulating the NF-κB pathway

“…Moreover, oxidative stress and apoptosis have been considered to be the main mechanisms for the pathogenesis of TIN [14], and enhanced oxidative stress was found in patients with TIN through up-regulation of IL-6, IL-10 and TNF-α [23]. Methyl jasmonate was shown to alter antioxidative defense system and lipid peroxidation in soybean under drought [24], and demonstrated anti-oxidant effect in βamyloid-induced microglial cells [25]. Additionally, methyl jasmonate ameliorated oxidative stress [26] and reduced the oxidative stress in arthritic rats [27].…”