Extract matrix composition does not affect in vitro leukotriene inhibitory effects of the Petasites hybridus extract Ze 339.

It has been shown that a lipophilic CO2-extract prepared from the leaves of Petasites hybridus (Ze 339) inhibited leukotriene synthesis in vitro and ex vivo. The inhibition of the leukotriene synthesis was solely attributed to the sum of the petasins, namely petasin and its isomers isopetasin and neopetasin. To further investigate the influence of the extract matrix on leukotriene synthesis inhibition, we compared twelve selected batches of Ze 339 that differed significantly in the composition of the extract matrix. Quantitative analysis of the twelve extract batches revealed high contents of petasins [28.8-41.9%], fatty acids [17.1-27.2%] and crude oil and fat [17.7-44.2%]. The amount of sterols ranged between 3.0 and 4.9% and that of essential oils between 1.3 and 10.5%. Based on the quantitative analysis, 97-100% of the extract mass could be attributed to the above mentioned groups of ingredients. Despite significant differences in extract matrix composition, only the content of petasins was critical for the dose-dependent inhibition of leukotriene synthesis. However, at equal concentrations of petasins, no significant differences in 5-LOX, LTC4 synthase and LTA4 hydrolase inhibition were detected between the selected extract batches, despite differences in the composition of the petasin isomers. Our data suggest that the extract matrix of Ze 339 has no effect on leukotriene inhibitory effects of the petasins.

Therapeutic Potential of Antileukotriene Drug-Camellia sinensis Extract Co-Formulation on Histamine Induced Asthma in Guinea Pigs.

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

In vivo modulation of LPS induced leukotrienes generation and oxidative stress by sesame lignans.

The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA2 (61 and 56%), 5-LOX (44 and 51%), BLT-1(32 and 35%) and LTC4 synthase (49 and 50%), respectively, in liver homogenate. The diminished serum LTB4 (53 and 64%) and LTC4 (67 and 44%) levels in sesamol and sesamin administered groups, respectively, were found to be concurrent with the observed decrease in the expression of cPLA2 and 5-LOX. The serum levels of TNF-α (29 and 19%), MCP-1 (44 and 57%) and IL-1ß (43 and 42%) were found to be reduced in sesamol and sesamin group, respectively, as given in parentheses, compared to LPS group. Sesamol and sesamin offered protection against LPS induced lipid peroxidation in both serum and liver. Sesamol, but not sesamin, significantly restored the loss of catalase and glutathione reductase activity due to LPS (P<.05). However, both sesamol and sesamin reverted SOD activities by 92 and 98%, respectively. Thus, oral supplementation of sesamol and sesamin beneficially modulated the inflammatory and oxidative stress markers, as observed in the present study, in LPS injected rats. Our report further advocates the potential use of sesamol and sesamin as an adjunct therapy wherein, inflammatory and oxidative stress is of major concern.

[Method for screening cysteinyl leukotriene receptor 2 antagonists and preliminary screening of compounds].

OBJECTIVE: To establish a method for screening cysteinyl leukotriene receptor 2 (CysLT(2)) antagonists and to preliminarily screen a series of synthetic compounds. METHODS: Rat glioma cell line (C6 cells) highly expressing CysLT(2) receptor was used. Intracellular calcium concentration was measured after stimulation with the agonist LTD(4),which was used to screen compounds with antagonist activity for CysLT(2) receptor. Bay u9773, a CysLT1/CysLT(2) receptor non-selective antagonist, and AP-100984, a CysLT(2) receptor antagonist, were used as control. RESULT: PT-PCR showed a higher expression of CysLT(2) receptor in C6 cells. LTD(4) at 1 mumol/L significantly increased intracellular calcium in C6 cells; the maximal effect was about 37.5% of ATP, a positive stimulus.LTD(4)-induced increase of intracellular calcium was blocked by CysLT(2) receptor antagonists, but not by CysLT(1) receptor antagonists. Among the synthetic compounds, D(XW-)1,2,13,23,29 and 30 inhibited LTD(4)-induced increase of intracellular calcium. CONCLUSION: LTD(4)-induced change in intracellular calcium in C6 cells can be used as a screening method for CysLT(2) receptor antagonists. The compounds, D(XW-)1,2,13,23,29 and 30, possess antagonist activity for CysLT(2) receptor.

Antiallergic agent from natural sources. 2. Structures and leukotriene release-inhibitory effect of torososide B and torosachrysone 8-O-6"-malonyl beta-gentiobioside from Cassia torosa Cav.

Two new anti-allergic compounds, torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were isolated from the seeds of Cassia torosa Cav., and their structures were established as physcion 8-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl- (1-->3)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and torosachrysone 8-O-beta-D-glucopyranosyl-(1-->6)-6-malonyl beta-D-glucopyranoside on the basis of spectral and chemical evidence. Torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were found to inhibit the release of leucotrienes from rat peritoneal mast cells induced by calcium ionophore A 23187.

Cyclodextrin solubilization of ETH-615, a zwitterionic drug.

Therapeutic usefulness of many zwitterionic drugs is hampered by their very low aqueous solubility. The purpose of this work was to investigate the effects of cyclodextrins on the solubility of the zwitterionic drug ETH-615, the role that charge might play in the cyclodextrin complexation, and the influence of polymers and ion-pairing agents on the cyclodextrin solubilization. The effects of five different beta-cyclodextrin derivatives were evaluated, i.e., the anionic beta-cyclodextrin sulfobutyl ether sodium salt and carboxymethyl-beta-cyclodextrin sodium salt, the uncharged 2-hydroxypropyl-beta-cyclodextrin and randomly methylated beta-cyclodextrin, and the cationic 2-hydroxy-3-trimethyl-ammoniopropyl-beta-cyclodextrin. The uncharged cyclodextrins had much larger solubilizing effect on ETH-615 than the charged ones. However, due to the highly polar zwitterionic structure of ETH-615 the stability constants of its cyclodextrin complexes were several orders of magnitude smaller than those commonly observed for uncharged lipophilic compounds. Cyclodextrin solubilization of ETH-615 was enhanced by water-soluble polymers and ion-pairing agents.