Anti-Inflammatory Activities of Isogosferol, a Furanocoumarin Isolated from Citrus junos Seed Shells through Bioactivity-Guided Fractionation

Abstract

Citrus junos Tanaka is a traditional medicine for treating coughs, dyspepsia, diabetes, asthma, neuralgia, and inflammatory disorders, and is distributed in Asia, especially in Korea, Japan, and China. This study aimed to use bioactivity-guided fractionation to find therapeutic phytochemicals from C. junos seeds, which can attenuate inflammatory responses. Nine coumarins (1–9) were isolated from the methanolic extract of C. junos seed shells and the inhibitory effects against inflammatory mediators were investigated using murine macrophages. Among the coumarins, compound 3, isogosferol (ISO), more potently attenuated the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. ISO also inhibited the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Additionally, the phosphorylation of extracellular-regulated kinases (pERK)1/2 was reduced by ISO. We confirmed that ISO attenuated the release of interleukin-1 beta (IL-1β), which is a central mediator of the inflammatory response. These results demonstrate that ISO from C. junos seed shells may be a potent therapeutic candidate for the treatment of inflammatory diseases.

Neopapillarine, an Unusual Coumarino-Alkaloid from the Root Extract of Neocryptodiscus papillaris with Cytotoxic Activity on Renal Cancer Cells

“…senecioyloxyosthol (5) [8], psoralen (6), bergapten (7), isoimperatorin (8) [9], oxypeucedanin (9) [10], oxypeucedanin hydrate (10) [10,11], pranferol (11) [12], scopoletin (12), and scoparone (13) [13]; the fractionation of the dichloromethane extract of the root of N. papillaris yielded several novel osthol derivatives, i.e., 4′-hydroxyosthol (2), 4′-acetoxyosthol (3) and neopapillarine (4) ( Figure 1). In addition to their cytotoxic and anticancer activities [14,15], natural and semi-synthetic coumarins possess many biological activities properties [16] such as antiviral [17][18][19], antifungal, antioxidative [20,21], antibacterial [22] and anti-inflammatory activities [23]. It should be noted that aflatoxins, potent hepatotoxic, carcinogenic, mutagenic and teratogenic mycotoxins isolated from Aspergillus species, also contain a coumarin nucleus as part of their polycylic heterocyclic structure [24].…”

“…2.55 ppm) indicating a molecular formula of C15H16O4 for 2 which that is in agreement with the hydoxylated isoprenyl side chain added to the osthol structure. Although this compound has previously been reported as a rat metabolite of osthol [25], both the 1 H-NMR and 13 C-NMR spectra In addition to their cytotoxic and anticancer activities [14,15], natural and semi-synthetic coumarins possess many biological activities properties [16] such as antiviral [17][18][19], antifungal, antioxidative [20,21], antibacterial [22] and anti-inflammatory activities [23]. It should be noted that aflatoxins, potent hepatotoxic, carcinogenic, mutagenic and teratogenic mycotoxins isolated from Aspergillus species, also contain a coumarin nucleus as part of their polycylic heterocyclic structure [24].…”

“…In addition to their cytotoxic and anticancer activities [ 14 , 15 ], natural and semi-synthetic coumarins possess many biological activities properties [ 16 ] such as antiviral [ 17 , 18 , 19 ], antifungal, antioxidative [ 20 , 21 ], antibacterial [ 22 ] and anti-inflammatory activities [ 23 ]. It should be noted that aflatoxins, potent hepatotoxic, carcinogenic, mutagenic and teratogenic mycotoxins isolated from Aspergillus species, also contain a coumarin nucleus as part of their polycylic heterocyclic structure [ 24 ].…”

Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

“…Membranes were then blocked with 5% skim milk power in platin buffer [4 M NaCl and 1 M Tris-HCl (PH 7.5)] for one hour at RT. Primary antibodies against iNOS, COX-2, NF-κB , ERK1/2, and pERK1/2 were incubated with the membrane for 24 h at 4 • C. Membranes were then washed with wash buffer (4 M NaCl, Tween-20, 1 M Tris-HCl (PH 7.5)) in DW and then incubated with a second antibody (1:2000 dilution) at RT for 2 h. Protein signals were detected with a bio image system (Microchemi 4.2 Chemilumineszenz-System, Neve Yamin, Israel) using ECL solution (Thermo Fisher Scientific, Waltham, MA, USA) [36].…”

Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

“…Previously, we identified extracts with anti-inflammatory activity and fractions of coumarins using Citrus junos seeds. Additionally, we also attempted to discover novel anti-inflammatory phytochemicals from extracts that contain limonoids as their bitter constituents [ 12 ]. It was reported that some limonoids, such as obacunone, a limonoid abundantly distributed in citrus fruits, have anti-inflammatory activities [ 13 ].…”