Isolation and evaluation of anti-inflammatory constituents from lichen Dirinaria applanata and Lasia spinosa leaves

Dirinaria applanate葉およびLasia spinosa葉に含まれる抗炎症物質の単離と評価

2020-09-24

2020-09-24

Natural products or traditional medicines play essential roles in therapeutic agents as well as a resource for the discovery of new drugs. Lichen Dirinaria applanata and Lasia spinosa (L.) Thwaites were used as traditional medicines to treat many diseases for centuries. However, chemical components and their effects on inflammatory response are not yet characterized. Thus, the goal of this dissertation is to explore chemical positions and investigate the anti-inflammatory activities of these extracts in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Chemical investigation of the lichen Dirinaria applanata methanol extract led to isolating two hopane derivatives including 1β-acetoxy-21α,3β-hydroxyhopane-29-oic acid (1), hopane-3β,6β,21α-triol (2) and a depside namely 2-O′-methylnordivaricatic acid (3). Their structures were elucidated by spectroscopic data in combination with published literature. Notably, compound 2 was isolated from this lichen species for the first time. Unfortunately, only compound 1 shows the anti-inflammatory effect by reducing nitric oxide (NO) production in LPS-induced inflammation response. Besides, ethanol extracts of L. spinosa leaves showed antioxidant activity due to the presence of high levels of polyphenolic compounds. Therefore, L. spinosa leaves may exhibit anti-inflammatory properties. In particular, treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW264.7 cells. Moreover, pretreatment of L. spinosa leaf extract prevented activation of the nuclear factor-kappa B (NF-κB) pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase (MAPK) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also promoted the activated nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 (Nrf2/HO-1) pathway. Taken together, the significant findings of these herbs will be highlighted and discussed throughout this dissertation. Result obtained highlights critical findings in assessing the potential of anti-inflammatory constituents. Thereby, we propose to further develop them as novel pharmacological strategies in order to defeat inflammation diseases.

博士(学術)

京都工芸繊維大学

14303甲第972号

http://hdl.handle.net/10212/2601

eng

ETD

Thesis or Dissertation

Thesis