Proteinase-activated receptors

The contemporary scientific community has presently recognized flavonoids to be a unique class of therapeutic molecules due to their diverse therapeutic properties. Of these, rutin, also known as vitamin P or rutoside, has been explored for a number of pharmacological effects. Tea leaves, apples, and many more possess rutin as one of the active constituents. Today, rutin has been observed for its nutraceutical effect. The present review highlights current information and health-promoting effects of rutin. Along with this, safety pharmacology issues and SAR of the same have also been discussed.

The Pharmacological Potential of Rutin.

Composite dental restorations represent a unique class of biomaterials with severe restrictions on biocompatibility, curing behavior, esthetics, and ultimate material properties. These materials are presently limited by shrinkage and polymerization-induced shrinkage stress, limited toughness, the presence of unreacted monomer that remains following the polymerization, and several other factors. Fortunately, these materials have been the focus of a great deal of research in recent years with the goal of improving restoration performance by changing the initiation system, monomers, and fillers and their coupling agents, and by developing novel polymerization strategies. Here, we review the general characteristics of the polymerization reaction and recent approaches that have been taken to improve composite restorative performance.

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Recent Advances and Developments in Composite Dental Restorative Materials

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.

Effects of Flavonoids and other Polyphenols on Inflammation

A review on plant-based rutin extraction methods and its pharmacological activities

The effects of quercetin and rutin on the asthmatic responses were studied in ovalbumin (OA)-sensitized conscious guinea pigs challenged with aerosolized-OA. We measured the specific airway resistance (sRaw) in the double-chambered plethysmograph during the immediate-phase response (IAR) and late-phase response (LAR) at 3 approximately 10 min and 24 hr after OA challenge, respectively. We counted leukocytes in bronchoalveolar lavage fluid (BALF) using Wright's stain, as well as in lung tissue fixed with 10% formalin and stained with H & E stain. Quercetin and rutin (7.5 mg/kg, p.o.) significantly and dose-dependently inhibited both sRaw on IAR (31.60 and 26.44%) and LAR (29.87 and 28.69%) but with less efficacy than dexamethasone (3 mg/kg) and salbutamol (0.3 mg/kg), which inhibited IAR by 36.71 and 69.45%, and LAR by 67.23 and 0%, respectively, Quercetin and rutin (15 mg/kg) also inhibited production of histamine, PLA2, and EPO, and recruitment of leukocytes, particularly neutrophils and eosinophils, during LAR. respectively. Dexamethasone (3 mg/kg) also significantly reduced the recruitment of neutrophils, eosinophils, and lymphocytes in BALF, and salbutamol (0.3 mg/kg) reduced neutrophils and eosinophils with lower activity than dexamethasone. These results indicate that quercetin and rutin may be useful in the treatment of IAR and LAR in asthma via inhibition of histamine release, PLA2, and EPO, and reduced recruitment of neutrophils and eosinophils into the lung.

Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin.

Previous screening of the pharmacological action ofGastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The anti-inflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4′-hydroxybenzyloxy)benzyl methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried outin vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determinedin vitro. These phenolic compounds not only had anti-inflammatory and analgesic propertiesin vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.

Anti-inflammatory action of phenolic compounds from Gastrodia elata root.

The effect of acteoside, a phenylpropanoid glycoside isolated fromClerodendron trichotomum Thunberg, on histamine and arachidonic acid release was investigated in RBL 2H3 cells. Histamine was dose-dependently released from RBL 2H3 cells by melittin, arachidonic acid and thapsigargin. In extracellular Ca2+-free solution, basal secretion of histamine increased by two fold. The response of histamine release to melittin and thapsigargin in Ca2+-free solution was significantly decreased, whereas the response to arachidonic acid was significantly increased as compared with those in normal solution. Acteoside inhibited histamine release induced by melittin, arachidonic acid and thapsigargin in a dose-dependent manner in the presence or absence of extracellular Ca2+. However, the inhibitory activity of acteoside was more potent in normal solution than that in Ca2+-free solution. These data suggest that inhibitory mechanism of acteoside on histamine release may be related to extracellular Ca2+. On the other hand, acteoside significantly inhibited arachidonic acid release and prostaglandin E2 production induced by 0.5 μM melittin. It is possible that acteoside may be developed as an anti-inflammatory agent.

The effect of acteoside on histamine release and arachidonic acid release in RBL-2H3 mast cells.

Effects of quercetin inhalation on immediate (IAR), late-phase (LAR) and late late-phase (LLAR) asthmatic responses by exposure to aerosolized-ovalbumin (AOA) (2w/v% in saline, inhalation for 3 min) were studied in conscious guinea-pigs sensitized with AOA. We measured specific airway resistance (sRaw), and recruitment of leukocytes, histamine and protein contents and phospholipase A2 (PLA2) activity in bronchoalveolar lavage fluid (BALF). Effects of quercetin (10 mg/mL, inhalation for 2 min) compared with cromolyn sodium, salbutamol, and dexamethasone inhalations, respectively. Quercetin inhalation decreased sRaw by 57.15 ± 3.82% in IAR, 57.72 ± 7.28% in LAR, and 55.20 ± 5.69% in LLAR compared with AOA-inhaled control. Salbutamol inhalation (5 mg/mL) significantly inhibited sRaw in IAR, but inhalations of cromolyn sodium (10 mg/mL) and dexamethasone (5 mg/mL) significantly inhibited sRaw in IAR, LAR and LLAR, respectively. Inhibitory activity of quercetin inhalation on sRaw was similar to effect of its oral administration (10 mg/kg) in asthmatic responses. Quercetin (10 mg/mL, inhalation for 2 min) significantly decreased histamine and protein contents, PLA2 activity, and recruitments of leukocytes in BALF and also improved slightly infiltration of eosinophils and neutrophils in histopathological survey. Its anti-asthmatic activity was similar to cromolyn sodium and dexamethasone.

Ji Yun Lee

Papers

Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin.

Anti-inflammatory action of phenolic compounds from Gastrodia elata root.

The effect of acteoside on histamine release and arachidonic acid release in RBL-2H3 mast cells.

Quercetin Inhalation Inhibits the Asthmatic Responses by Exposure to Aerosolized-Ovalbumin in Conscious Guinea-pigs

Anti-asthmatic activity of phenolic compounds from the roots of Gastrodia elata Bl