Linderone Isolated from Lindera erythrocarpa Exerts Antioxidant and Anti-Neuroinflammatory Effects via NF-κB and Nrf2 Pathways in BV2 and HT22 Cells

Abstract

Linderone is a major compound in Lindera erythrocarpa and exhibits anti-inflammatory effects in BV2 cells. This study investigated the neuroprotective effects and mechanisms of linderone action in BV2 and HT22 cells. Linderone suppressed lipopolysaccharide (LPS)-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines (e.g., tumor necrosis factor alpha, interleukin-6, and prostaglandin E-2) in BV2 cells. Linderone treatment also inhibited the LPS-induced activation of p65 nuclear factor-kappa B, protecting against oxidative stress in glutamate-stimulated HT22 cells. Furthermore, linderone activated the translocation of nuclear factor E2-related factor 2 and induces the expression of heme oxygenase-1. These findings provided a mechanistic explanation of the antioxidant and anti-neuroinflammatory effects of linderone. In conclusion, our study demonstrated the therapeutic potential of linderone in neuronal diseases.

Dihydropashanone Isolated from Lindera erythrocarpa, a Potential Natural Product for the Treatment of Neurodegenerative Diseases

“…The results show that only compounds 7 (dihydropashanone) and 13 (linderone) exhibited neuroprotective effects in the neural cells. Previous studies have demonstrated the anti-neuroinflammatory effects of linderone [ 18 ]. Therefore, we chose to focus on dihydropashanone for this study.…”

“…In our earlier study, 18 compounds were identified in L. erythrocarpa , including dihydropashanone [ 17 ]. Dihydropashanone was found to inhibit the excessive production of LPS-induced NO in both BV2 and RAW264.7 cells [ 18 ]. However, dihydropashanone has only been confirmed to inhibit NO production in BV2 cells [ 18 ] and no additional mechanistic studies related to inflammation regulation have been conducted.…”

“…Dihydropashanone was found to inhibit the excessive production of LPS-induced NO in both BV2 and RAW264.7 cells [ 18 ]. However, dihydropashanone has only been confirmed to inhibit NO production in BV2 cells [ 18 ] and no additional mechanistic studies related to inflammation regulation have been conducted. Furthermore, the primary aim of this study is to show, for the first time, the neuroprotective effects of 18 compounds in hippocampal HT22 cells.…”

Fissistigma oldhamii (Hemsl.) Merr.: Ethnomedicinal, Phytochemistry, and Pharmacological Aspects

“…To our knowledge, these two products have not been found in any other plants. They bear a structural similarity to the anti-neuroinflammatory agent linderone, a cyclo-pentenedione from Lindera erythrocarpa [ 92 ]. The related furanone derivative designated fissohamione ( 70 ) has also been found in F. oldhamii seed extract, but its bioactivity, if any, is unknown at present ( Figure 5 ) [ 27 ].…”

“…To our knowledge, these two products have not been found in any other plants. They bear a structural similarity to the anti-neuroinflammatory agent linderone, a cyclo-pentenedione from Lindera erythrocarpa [92]. The related furanone derivative designated fissohamione Two main steroids were identified in the methanolic fruit extract: β-sitosterol (64) (cupreol) and a glucoside derivative (65) [25,86].…”