Effects of Compounds Isolated from Lindera erythrocarpa on Anti-Inflammatory and Anti-Neuroinflammatory Action in BV2 Microglia and RAW264.7 Macrophage

Abstract

Lindera erythrocarpa contains various constituents such as cyclopentenedione-, flavonoid-, and chalcone-type components. In this study, a novel bi-linderone derivative and 17 known compounds were isolated from the leaves of L. erythrocarpa by using various chromatographic methods. The structures of the components were determined from nuclear magnetic resonance and mass spectrometry data. All isolated compounds were tested for anti-inflammatory and anti-neuroinflammatory activities in lipopolysaccharide (LPS)-induced BV2 and RAW264.7 cells. Some of these compounds showed anti-inflammatory effects by inhibiting the nitric oxide (NO) produced by LPS. In particular, linderaspirone A (16), bi-linderone (17) and novel compound demethoxy-bi-linderone (18) showed significant inhibitory effects on the production of prostaglandin E2 (PGE2), tumor necrosis factor-α, and interleukin-6. The three compounds also inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are pro-inflammatory proteins, and the activation of nuclear factor κB (NF-κB). Therefore, linderaspirone A (16), bi-linderone (17), and demethoxy-bi-linderone (18) isolated from the leaves of L. erythrocarpa have therapeutic potential in neuroinflammatory diseases.

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

“…In our previous report, the isolation of 18 compounds from L . erythrocarpa extract was described [ 17 ]. The 18 compounds are as follows: kanakugiol ( 1 ), 2′-hydroxy-3′,4′,6′-trimethoxychalcone ( 2 ), pashanone ( 3 ), kanakugin ( 4 ), 5-hydroxy-7,8-dimethoxyflavanone ( 5 ), onysilin ( 6 ), dihydropashanone ( 7 ), 2-hydroxy-3′,4′,6′-trimethoxydihydrochalcone ( 8 ), avicularin ( 9 ), afzelin ( 10 ), avicularin-acetate ( 11 ), quercitrin ( 12 ), linderone ( 13 ), methyllinderone ( 14 ), methyllucidone ( 15 ), linderaspirone A ( 16 ), bi-linderone ( 17 ) and demethoxy-bi-linderone ( 18 ).…”

“…L. erythrocarpa is a common plant species in eastern Asia. An earlier investigation revealed the isolation of various chemicals from L. erythrocarpa that may have anti-neuroinflammatory properties [ 17 ]. However, there has been little research into these substances’ neuroprotective properties.…”

“…The hexane fraction was further fractionated by silica gel and C18 column chromatography and purified by HPLC to obtain dihydropashanone (33 mg, yield 0.000022%). Detailed purification steps are described in our previous literature [ 17 ]. LPS and glutamate were obtained from Sigma-Aldrich (St. Louis, MO, USA).…”

“…Lindera erythrocarpa (Lauraceae) is widespread in South Korea, Japan, and China. 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 ].…”

Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin

“…Afzelin was shown to act as an inhibitor of NO production with an IC 50 value of 42.8 µg/mL with comparable efficacy to nitric oxide inhibitor L-NMMA used in the experiment as a positive control (IC 50 of 42.1 µg/mL) [ 100 ]. Furthermore, interleukin-1 beta (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) production were shown to be down-regulated by afzelin treatment suggesting that this compound can dampen the inflammation in the human skin for effective prevention of skin cancers [ 101 , 102 ]. The administration of flavonoids, specifically quercitrin, isoquercitrin, and afzelin, to human neuroblastoma SH-SY5Y cells have demonstrated advantageous outcomes via modulating inflammation, apoptosis (through inhibition of caspase activation), and ROS-scavenging [ 103 , 104 ].…”