Anti-inflammatory coumarins from Paramignya trimera

Abstract

Context:Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.Objective: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds.Materials and methods: Cytotoxicity of isolated compounds (5–40 μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 μM) on nitrite and PGE2 concentrations were determined using Griess reaction and PGE2 ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS).Results: Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6′,7′-dihydroxy-3′,7′-dimethylocta-2′-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1–4 and 7 inhibited NO and PGE2 production in LPS-stimulated BV2 cells, with IC50 values ranging from 9.8 to 46.8 and from 9.4 to 52.8 μM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression.Discussion and conclusion: The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.

A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and Biological Activity

“…Nuclear factor- κ B (NF- κ B) activation has been playing a central role in inflammatory reactions [ 4 , 37 ], while macrophages played an important role in regulating inflammatory responses via production of various proinflammatory cytokines and proinflammatory mediators, such as nitric oxide (NO), prostaglandins, tumor necrosis factor- α (TNF- α ), and interleukin-1 β (IL-1 β ) [ 4 , 37 , 43 ]. Additionally, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions also conducted production levels of NO and prostaglandin PGE2 [ 61 ]. Normally, lipopolysaccharide (LPS) was used as an inflammatory stimulant in the anti-inflammatory experiments as it induces NF- κ B activation through phosphorylation of I κ B inhibitor [ 4 , 37 , 61 ].…”

“…Additionally, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions also conducted production levels of NO and prostaglandin PGE2 [ 61 ]. Normally, lipopolysaccharide (LPS) was used as an inflammatory stimulant in the anti-inflammatory experiments as it induces NF- κ B activation through phosphorylation of I κ B inhibitor [ 4 , 37 , 61 ]. Hemeoxygenase-1 (HO-1) was an enzyme that catalyzed the degradation of heme to generate carbon monoxide, biliverdin, and free iron, and it also has been involved in the reduction of proneuroinflammatory mediators and inflammatory expressions [ 4 , 5 , 37 , 43 ].…”

“…Therefore, HO-1 and its related by-products can be seen as the critical regulators of inflammation with macrophages acting as the critical targets [ 44 ]. Diseases related to inflammation include arthritis, hepatitis, septic shock syndrome, neuronal disorders caused by extensive and uncontrolled injuries, or irregular inflammatory responses [ 37 , 61 ]. Among them, neurodegenerative diseases such as Alzheimer's, Parkinson's, or Huntington's disease have been increasing in recent decades, which was closely related to the activity of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE 2 ) in microglia [ 61 ].…”

“…Diseases related to inflammation include arthritis, hepatitis, septic shock syndrome, neuronal disorders caused by extensive and uncontrolled injuries, or irregular inflammatory responses [ 37 , 61 ]. Among them, neurodegenerative diseases such as Alzheimer's, Parkinson's, or Huntington's disease have been increasing in recent decades, which was closely related to the activity of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE 2 ) in microglia [ 61 ]. Consequently, anti-inflammatory drugs of medicinal plants have been receiving much more attention from researchers.…”

Xao tam phan (Paramignya trimera) methanol extract induced apoptosis in hepatocellular carcinoma HepG2 cell line in vitro

“…According to some analyzes, P. trimera extract contains saponin (267.15 mg EE/g dry sample), proanthocyanidin (3.98 mg CE/g dry sample), phenolic (11.27 mg GAE/g dry sample), flavonoid (19.88 mg RE/g dry sample) 9 . Besides, P. trimera extract has also been shown to contain coumarins with potent anti-inflammatory properties, including ostruthin and ninhvanin 10 . Moreover, there are also studies proving P. trimera has many antioxidants.…”