Diarylheptanoids with In Vitro Inducible Nitric Oxide Synthesis Inhibitory Activity from Alnus hirsuta

Abstract

Four diarylheptanoids were isolated from the leaf of Alnus hirsuta (Betulaceae) and have been assessed for nitric oxide (NO) production inhibitory effects in vitro. Oregonin (1) and hirsutanonol (2) were found to be potent inducible nitric oxide synthase (iNOS) inhibitors. Compounds 1 and 2 showed inhibition of NO synthesis in dose-dependent manners by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). Their 50% inhibitory concentrations (IC50) were 3.8 and 14.3 microM, respectively. The inhibitory effects of these compounds on NO synthesis were due to suppression of iNOS mRNA expression as determined by Northern blotting.

Diarylheptanoids from Alnus hirsuta Inhibit the NF-kB Activation and NO and TNF-.ALPHA. Production

“…It is a broad-leaved deciduous tree that grows in damp places. The bark of this species has been used in Chinese and Korean traditional medicine as a remedy for fever, hemorrhage, diarrhea, and alcoholism.3) Previous studies on the chemical constituents of A. hirsuta have led to the isolation of various natural products such as tannins, 4,5) flavonoids, 6,7) diarylheptanoids, [8][9][10] and triterpenoids.11) It has also been reported to exhibit a variety of bioactivities such as antioxidant activity, 12,13) antiinflammation, 14) cytotoxicity, and antitumor effects. [15][16][17][18] Here we describe the isolation and effects of six diarylheptanoids (1-6) from the stem bark of A. hirsuta on LPS-induced NFkB activation, on nitric oxide (NO) production, and on tumor necrosis factor-a (TNF-a) production in LPS-stimulated RAW264.7 cells.…”

“…11) It has also been reported to exhibit a variety of bioactivities such as antioxidant activity, 12,13) antiinflammation, 14) cytotoxicity, and antitumor effects. [15][16][17][18] Here we describe the isolation and effects of six diarylheptanoids (1-6) from the stem bark of A. hirsuta on LPS-induced NFkB activation, on nitric oxide (NO) production, and on tumor necrosis factor-a (TNF-a) production in LPS-stimulated RAW264.7 cells.…”

Facilitated Skin Permeation of Oregonin by Elastic Liposomal Formulations and Suppression of Atopic Dermatitis in NC/Nga Mice

“…9,10) As shown in Fig. 4, in the control group, immunohistochemical observation revealed the abundant expression of iNOS as well as COX-2 in dermis or epidermis of NC/Nga mice bearing AD symptoms.…”

“…6) Oregonin (ORG) is a diarylheptanoid derivative, (5S)-1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-beta-D-xylopyranoside, isolated from the bark of Alnus japonica. 7) Various biological activities of ORG including an anti-oxidative effect, 8) inhibitory effects on nitric oxide synthesis and COX-2 expression, 9,10) and an immunomodulatory effect 11) have been reported. Recently, it has been further investigated as a natural remedy for the treatment of autoimmune diseases, including AD.…”

Quantitative Analysis and Preformulation of Extracts from Alnus Japonica

“…Also, it was shown to exert antioxidative activity (Masanori et al, 2005), nitric oxide synthase inhibitory activity (Choi et al, 2009), inhibitory activity of cyclooxygenase-2 expression (Lee et al, 2000), inhibitory activity of melanogenesis (Cho et al, 2002) and anti-inflammatory effects (Kang et al, 2004). On the other hand, it was known that oregonin exerted several anti-inflammatory activities (Lee et al, 2000;Lee et al, 2000;Kim et al, 2005) and anti-apoptotic properties in vitro, which were inhibitory effect on the production of cytokine, the formation of reactive oxygen species and nitric oxide as well as the change in intracellular Ca 2+ levels in dendritic cells of bone marrow and spleen exposed to microbial products and IL-1B (Choi et al, 2008). Therefore, the amount of hirsutanone and oregonin extracted from Alnus japonica might be important for biological activity.…”