Effects of Hydroxy Pentacyclic Triterpene Acids from Forsythia viridissima on Asthmatic Responses to Ovalbumin Challenge in Conscious Guinea Pigs

Abstract

Bronchial asthma is considered to be a chronic inflammatory disease of the airways. Thus, anti-inflammatory therapy is considered central for its long-term asthma management. 1)Inhaled corticosteroids are highly effective chronic treatments, and are capable of suppressing the underlying inflammatory process. Furthermore, combination inhalers containing corticosteroids and long-acting b 2 -agonists are the principle approach to asthma therapy, and are being increasingly used in patients with persistent symptoms.2-3) However, concern persists regarding the use of inhaled corticosteroids, because the fear is irrational long-term side effects, such as, osteoporosis and growth stunting in children.3) Although these effective medications are delivered by inhalation, compliance is surprisingly poor.3,4) But dichromone flavonoid derivative, cromolyn sodium (CRO), which is a similar chemical structure to flavonoids, inhibits the release of chemical mediators, and has been used as anti-asthmatic agent, especially the prophylactic treatment of both allergic and exercise-induced asthma via the first dry-powder inhaler. 5)Forsythiae fructus (FF), the dried fruits of Forsythia viridissima LINDLE (Oleaceae), which are known as Yeon Kyo in Korea, had been reported to have the anti-inflammatory ingredients such as triterpenoids, lignans, flavonoids, and their glycosides, 6,7) and so are used as a herbal medicine due to their anti-inflammatory, diuretic, antidote, extrusion of pus, and antibacterial effects in Korea, China, and Japan. 8) In a previous study, we found that the natural lignans and flavonoids of FF inhibit inflammatory and asthmatic responses. 9,10) In the present study, we isolated three hydroxyl pentacyclic triterpene acids (HTAs), namely, oleanolic acid (OA), ursolic acid (UA), and betulinic acid (BA), from an ethylacetate fraction of FF, and sought to determine their effects and the underlying mechanisms involved on immunoglobulin E (IgE)-mediated asthmatic response induced by an aerosolized ovalbumin (AOVA) challenge in ovalbumin-sensitized guinea pigs. Their anti-asthmatic effects, which were investigated by measuring sRaw during immediate-phase response (IAR) and late-phase response (LAR) in a double-chambered plethysmograph, [10][11][12] were compared with those elicited by the authorized anti-asthmatic drugs, salbutamol (SAL), dexamethasone (DEX), and CRO. In addition, the chemical mediators of inflammation, histamine, eosinophil peroxidase (EPO), phospholipase A 2 (PLA 2 ), and leukocytosis, were quantified in bronchoalveolar lavage fluid (BALF), and accompanying histopathological changes in lung tissues were monitored. For the identification of anti-inflammatory ingredients from Forsythiae fructus (FF), we isolated three hydroxyl pentacyclic triterpene acids (HTAs), namely, oleanolic acid, ursolic acid, and betulinic acid, from an ethylacetate fraction of FF, and evaluated the effect of these triterpene acids on asthmatic guinea pigs by measuring specific airway resistance (sRaw) during both immediate-pha...

Dibenzylbutyrolactone Lignans from Forsythia koreana Fruits Attenuate Lipopolysaccharide-Induced Inducible Nitric Oxide Synthetase and Cyclooxygenase-2 Expressions through Activation of Nuclear Factor-.KAPPA.B and Mitogen-Activated Protein Kinase in RAW264.7 Cells

“…Measurement of Cell Viability Cell viability was assessed using the MTT assay. 21) RAW264.7 cells were seeded in a 96-well plate at a density of 5ϫ10 5 cell/ml and were treated with various concentrations of DBLLs for 24 h. MTT (final concentration of 200 mg/ml) was added and incubated for another 4 h at 37°C. The culture medium was removed, and cells were dissolved in 0.04 N HCl/isopropyl alcohol.…”

“…4) Previous chemical studies of these DBLLcontaining plant materials have reported the presence of biological activity as well as anti-inflammatory and antitumor activities. [4][5][6][7] However, the effects of these DBLLs on the NF-kB signaling pathway are still poorly understood.…”

Protective effects of phillyrin against influenza A virus in vivo

“…Moreover, arctigenin, a lignin found in Oleaceae Fructus Forsythiae, has been shown to exhibit anti-inflammatory activity through inhibition of both exudate production and leukocyte recruitment to inflamed tissues (Kang et al 2008). Recently, hydroxyl pentacyclic triterpene acids have been reported to have anti-asthmatic activity through reduction of specific airway resistance (sRaw) and inhibition of both eosinophil recruitment and inflammatory mediator release in the lungs (Lee et al 2010). In addition, alkaloids from Oleaceae Fructus Forsythiae have been reported to show anti-inflammatory activity (Dai et al 2009).…”

De Novo Transcriptomes of Forsythia koreana Using a Novel Assembly Method: Insight into Tissue- and Species-Specific Expression of Lignan Biosynthesis-Related Gene

“…These results are compatible with a previous study demonstrating the identification of 3 β -acetoxy-20 α -hydroxyursan-28-oic acid, β -amyrin acetate, taraxasterol acetate, 3 β -acetyl-20,25-epoxy-dammarane-24 α -ol, acetyl oleanolic acid, betulinic acid, labda-8(17),13E-dien-15,18-dioic acid 15-methyl ester, and other tri- and di-terpenes specifically in F . suspensa [ 36 , 37 ]. Particularly, 3 β -acetoxy-20 α -hydroxyursan-28-oic acid was a newly identified compound in Forsythia [ 36 ].…”