Inhibition Of Histamine Release Research Articles

Anti-allergic Inflammatory Activities of Compounds of Amomi Fructus

Activity-guided isolation of compounds from the fruits of Amomum xanthioides resulted in the purification of fourteen phenolic compounds, 4-hydroxy-benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4-methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o-vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12), 1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (14). To evaluate the anti-allergic inflammatory activities of these compounds, we examined the inhibitory effects of the isolates (1-14) on histamine release and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6 genes by using human mast cells. Of the tested compounds, 9, 11, and 13 suppressed histamine release from mast cells, and all isolates attenuated the expressions of the pro-inflammatory cytokines, TNF-α and IL-6 genes in human mast cells.

Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats.

Background:Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats.Materials and Methods:Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg).Results:Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study.Conclusion:These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release.

Adenosine A1 receptor activation inhibits histamine release in gastric enterochromaffin-like cells

Adenosine acts as a gastroprotective factor decreasing inflammation and reducing gastric acid secretion. Quantitative RT-PCR was used to determine the expression of the adenosine receptor genes (A1AR, A2AAR, A2BAR and A3AR) and that of the gastrin receptor B gene (CCKBR) in isolated, short-term cultured enterochromaffin-like (ECL) cells. Both the A1AR and the CCKBR genes were expressed at a level higher than the other genes. Also, the effect of 2-chloroadenosine, a stable agonist of A1 and A2A receptors, was explored on ECL cells, with a resulting inhibition of both basal and gastrin-stimulated histamine release. Also, dipropylcyclopentylxanthine (DPCPX), a selective A1 antagonist, prevented the inhibitory effects of 2-chloroadenosine, suggesting the effect of 2-chloroadenosine is mediated by A1 receptors. It is concluded that isolated, short-term cultured ECL cells are a suitable model for studies relating gene expression and function, and that the gastroprotective actions of adenosine are at least partly mediated through A1 receptors.

고욤(Diospyros lotus)잎 유래 Ethyl Acetate 분획물의 항산화 및 항가려움 활성

Diospyros lotus has been cultivated for its edible fruits, which are considered to have medicinal importance. The aim of this study was to evaluate the antioxidant and antipruritic activities of water-soluble, methanol extract, and ethyl acetate (EA) fractions from D. lotus leaves. The EA fraction showed the lowest IC50 vale (DPPH: 5.3 μg/mL, ABTS: 53.8 μg/mL). Therefore, we further investigated anti-inflammatory and antipruritic effects of the EA fraction. TNF-α production increased by PMA plus A23187 treatment was significantly inhibited by the EA fraction in a dose-dependent manner. The EA fraction also inhibited histamine release from rat peritoneal mast cells stimulated by compound 48/80, which promotes histamine release. Furthermore, EA fraction had inhibitory effects on scratching behavior induced by compound 48/80 in Balb/c mice. These results suggest that the EA fraction from D. lotus leaves has potential as ameliorative agent against oxidative stress and pruritus-related disease.

SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines.

In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.

Identification of anti-allergic lactic acid bacteria that suppress Ca2+ influx and histamine release in human basophilic cells

Many anti-allergic foods or food-derived factors have so far been reported. In this study, we screened for anti-allergic lactic acid bacteria (LABs) using the human basophilic cell line, KU812F. IgE crosslinking induced Ca2+ influx and subsequent histamine release in KU812F cells. The abilities of LAB strains to suppress the increase in [Ca2+]i level triggered by IgE crosslinking and to suppress histamine release triggered by the increased [Ca2+]i level was subsequently examined. Among the LAB strains tested, five (i.e., T2101, C0102, H1001, C1103, and H0709) suppressed both the increase in [Ca2+]i and histamine release. Thus, these five LAB strains may be candidate anti-allergic LABs. Elucidation of common structures and cell content in these LAB strains may provide a molecular basis for the anti-allergic properties of specific foods and facilitate the development of novel anti-allergic foods.

Anti-Asthmatic and Cardioprotective Efficacy of Curcumin-A Review

Curcumin is a natural yellow pigment of turmeric. It is used for the treatment of diseases like Alzheimer's disease, chronic obstructive pulmonary disease, asthma, neuropathic pain, psoriasis, cancer and atherosclerosis. The present review aims to encompass the studies of curcumin as anti-asthmatic and cardioprotective. It has shown antiallergic properties by inhibiting histamine release from mast cells. It has been evidenced to have anti-inflammatory properties through inhibition of the NF-κB pathway. By its good radical scavenging activity, it has proved to be potent in treating cardiovascular diseases. However, its combination with other asthma and cardio medicines needs to be evaluated, especially; combination of herbal medicines or curcumin along with synthetic drugs can lead to positive outcomes. Moreover, derivatives of the drug can also show some promising results and more derivatives, like CNB001, must be synthesized and investigated to control airway epithelial cell function and asthma. Only little work has been done so far showing its effects on the pulmonary functions of smokers, so this area needs to be explored by further clinical trials.

Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation

Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation

A series of NSAID-induced anaphylactic response to immunotherapy and a proposal to include NSAIDS avoidance in future immunotherapy guidelines

A review of anaphylaxis in a clinic over three years was performed. A co-factor for anaphylaxis stood out as a commonality to all reactions. All five patients had a non steroidal anti-inflammatory drug (NSAID) 24 hours prior to immunotherapy. Among symptoms, urticaria was the commonest; others included cough, angioedema, dyspnea, nausea, vomiting, hypotension and tachycardia. The symptoms appeared within 5 minutes to two hours post-injection. All reactions resolved after few hours. In all cases, NSAID use pre-injection was the only common factor. Two patients also had moderate exercise post-injection, but previous immunotherapy was without incident. All but one patient were administered epinephrine in clinic and recovered without significant morbidity, some were also given cetirizine as adjunct treatment and all were observed until symptoms resolved. While two patients stopped immunotherapy, three patients continued without incident and are now on maintenance dose. The one patient who did not receive epinephrine presented to a walk in clinic for her reaction and received antihistamine treatment alone. NSAID use, although overlooked in the literature, is a common cofactor in anaphylaxis in response to immunotherapy. At Torontoallergists™, a clinic with three allergists in practice, 5 such cases among approximately 3 600 injections in the last three years were noted after extensive chart review. Therefore an NSAID was associated with anaphylaxis in 0.0014% of the immunotherapy injections, whereas two cases of anaphylaxis involved NSAID and exercise involvement. No cases implicating other risk factors or co-factors for anaphylaxis during immunotherapy, such as dosage errors, or injection during asthma exacerbation were present [1]. It is speculated that aspirin and other NSAIDS lower the threshold for anaphylaxis after allergen injections through their COX-inhibiting mechanism of action [2]. The COX pathway synthesizes, from arachidonic acids, prostaglandin D2 and E2, are repressors of inflammatory mediator release from basophils and mast cells [3]. Therefore, NSAIDS increases the likelihood of anaphylaxis after immunotherapy by suppression of prostaglandin D2 and E2, which would normally inhibit histamine release. Supporting this mechanism is Marone et al’s study where higher concentration of NSAIDS and more inhibition of COX activity correlated with higher release of histamine [2]. However, in spite of the data about NSAID acting as a co-factor for anaphylaxis, NSAID avoidance around immunotherapy cannot be found in practice parameters from the AAAAI, ACAAI, and CSACI [4,5]. Therefore, as a patient safety precaution, we highly encourage NSAIDS avoidance to be included for future immunotherapy practice guidelines. We welcome other centers to corroborate.

CheonggukjangEthanol Extracts Inhibit a Murine Allergic Asthma via Suppression of Mast Cell-Dependent Anaphylactic Reactions

Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts immunomodulatory effects. Asthma is the most common chronic allergic disease to be associated with immune response to environmental allergens. In the pathogenesis of asthma, histamine is one of the important inflammatory mediators released from granules of mast cells. In this study, we evaluated the therapeutic effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal injection of OVA or a phosphate-buffered saline (PBS) control and then challenged with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol-extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. To elucidate the mechanisms of asthma inhibition by CGJE treatment, we also examined degranulation and histamine release of compound 48/80-induced rat peritoneal mast cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and monocytes in the lungs of mice challenged with OVA and suppressed histopathological changes, such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated compound 48/80-induced mast cell degranulation and histamine release from RPMCs through inhibition of calcium (Ca²⁺) uptake as well as ear swelling by infiltration of inflammatory cells. These findings demonstrated that CGJE can be used as an antiasthmatic dietary supplements candidate for histamine-mediated asthma.

Anti-allergic Inflammatory Effects of Cyanogenic and Phenolic Glycosides from the Seed of Prunus persica

A methanol extract of the seed of Prunus persica (Rosaceae) was found to inhibit histamine release in human mast cells. Activity-guided fractionation of the methanol extract yielded three cyanogenic glycosides (1-3) and other phenolic compounds (4-8). To evaluate their anti-allergic and anti-inflammatory activities, the isolates (1-8) were tested for their inhibitory effects on histamine release and on the gene expressions of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in human mast cells. Of these, phenolic glycosides 7 and 8 suppressed histamine release and inhibited the pro-inflammatory cytokines TNF-alpha and IL-6. These results suggest that isolates from P. persica are among the anti-allergic inflammatory principles in this medicinal plant.

Regulation of human skin mast cell histamine release by PDE inhibitors

BackgroundMast cell and basophiles are thought to be central to inflammation that has an allergic basis as allergens activate these cells in an IgE-dependent manner to generate mediators such as histamine, eicosanoids and cytokines. Phosphodiesterase (PDE) is known to exist as multiple molecular forms of enzyme that metabolise the second messengers. Studies of our own have shown that, of a variety of isoform-selective drugs, the PDE4-selective inhibitors, such as rolipram, attenuate the IgE-mediated release of histamine from human basophiles but not from human lung mast cells (HLMC).The main aim of the present study was to characterise the type and role of PDEs regulating human skin mast cells by using selective and non-selective PDE inhibitors. MethodsCells were pre-treated for 15min with these agents and then challenged with an optimal releasing concentration of anti IgE (1:300) for a further 25min for the release of histamine. ResultsThe data show that all the selective PDE-inhibitor compounds (10−5M) were ineffective whereas the non-selective PDE inhibitor, theophylline (10−3M), inhibited histamine release from HSMC (74±4% inhibition; p<0.05). None of the selective PDE inhibitors had any effect on histamine release from HLMC whereas, in basophiles, compounds with activity at PDE 4 (rolipram, denbufylline, Ro-2017, Org 30029) were effective inhibitors of histamine release. ConclusionThe data suggest that unlike most inflammatory cells, PDE-selective inhibitors are ineffective stabilisers of HSMC activity which is similar to HLMC.

비타민 나무 Seed 추출물의 항산화 활성 및 항염증에 관한 연구

This study aimed to observe the effects of Sea Buckthorn seed extracts (SEB) on anti-oxidation and anti-inflammation. SEB were found to strongly depress ROS production depending on concentration, and 46.5% anti-oxidation effects were found in the top concentration of 100 μg/mL. Histamine and arachidonic acid release were measured to observe the effects of SEB on anti-inflammation. SEB inhibited histamine release and arachidonic acid release on dose dependent manner. Based on the results above, the conclusion is drawn that SEB have the potential to be used as natural materials that are effective for anti-oxidation and anti-inflammation.

The antiallergic mechanisms ofCitrus sunkiand bamboo salt (K-ALL) in an allergic rhinitis model

The antiallergic effects of traditional medicines have long been studied. Traditional Korean medicine, Citrus sunki and bamboo salt, has been used for the treatment of allergic diseases in Korea. K-ALL, composed of Citrus sunki and bamboo salt, is a newly prepared prescription for allergic patients. To develop the new antiallergic agent, we examined the effects of K-ALL through invivo and invitro models. K-ALL and naringin (an active compound of K-ALL) significantly inhibited histamine release from rat peritoneal mast cells. This inhibitory effect of K-ALL on histamine release was higher than effects from other known histamine inhibitors such as bamboo salt, Citrus sunki or disodium cromoglycate. K-ALL significantly inhibited systemic anaphylactic shock induced by the compound 48/80 and passive cutaneous anaphylaxis induced by the IgE. K-ALL also inhibited production and mRNA expression of inflammatory cytokines induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 on HMC-1 cells (a human mast cell line). In the ovalbumin-induced allergic rhinitis animal model, rub scores, histamine, IgE, inflammatory cytokines and inflammatory cell counts were all reduced by the oral or nasal administration of K-ALL (pre and posttreatment). These results indicate the great potential of K-ALL as an active immune modulator for the treatment of mast cell-mediated allergic diseases.

Immunomodulators for conjunctivitis

Allergic conjunctivitis is an IgE-mediated inflammatory of conjunctiva. Despite the fact that histamine is a major mediator in this condition, use of topical antihistamines often gives only temporarily relief. Therapeutic agents aiming at inflammatory cascades of the disease are desirable particularly in cases with prolonged and severe allergic conjunctivitis. The article reviews these new treatment armamentariums with regard to their mechanism of actions and clinical efficacy. Some second generation of antihistamines demonstrated anti-inflammatory properties such as inhibition of histamine release from mast cells as well as interference with the production cytokines and adhesion molecules from cord blood and conjunctival mast cells. Among these agents, ketotifen, epinastine and olopatadine are agents of major interest and are thus reviewed. Cromolyn, nedocromil, topical corticosteroids and immunotherapy, especially sublingual immunotherapy, are among other modes of therapy examined. Finally, the review focuses on cyclosporine A and tacrolimus, immunomodulators that have been extensively studied in the therapy of severe conjunctivitis such as atopic and vernal keratoconjunctivitis with promising results. Several immunomodulatory options are currently available for treatment of allergic conjunctivitis. These therapeutic availabilities bring about a better therapeutic outcome for patients with allergic conjunctivitis, particularly those on the severe end of the spectrum.

Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE‐dependent secretion from human lung mast cells

Prostaglandin E2 (PGE2 ) has been shown to inhibit IgE-dependent histamine release from human lung mast cells. This effect of PGE2 is believed to be mediated by EP2 receptors. However, definitive evidence that this is the case has been lacking in the absence of EP2 -selective antagonists. Moreover, recent evidence has suggested that PGE2 activates EP4 receptors to inhibit respiratory cell function. The aim of this study was to determine the receptor by which PGE2 inhibits human lung mast cell responses by using recently developed potent and selective EP2 and EP4 receptor antagonists alongside other established EP receptor ligands. The effects of non-selective (PGE2 , misoprostol), EP2 -selective (ONO-AE1-259, AH13205, butaprost-free acid) and EP4 -selective (L-902,688, TCS251) agonists on IgE-dependent histamine release and cyclic-AMP generation in mast cells were determined. The effects of EP2 -selective (PF-04418948, PF-04852946) and EP4 -selective (CJ-042794, L-161,982) antagonists on PGE2 responses of mast cells were studied. The expression of EP receptor subtypes was determined by RT-PCR. Prostaglandin E2 , EP2 agonists and EP4 agonists inhibited IgE-dependent histamine release from mast cells. PGE2 and EP2 agonists, but not EP4 agonists, increased cyclic-AMP levels in mast cells. EP4 -selective antagonists did not affect the PGE2 inhibition of histamine release, whereas EP2 -selective antagonists caused rightward shifts in the PGE2 concentration-response curves. RT-PCR studies indicated that mast cells expressed EP2 and EP4 receptors. Although human lung mast cells may express both EP2 and EP4 receptors, the principal mechanism by which PGE2 inhibits mediator release in mast cells is by activating EP2 receptors.

Aqueous ethanol extract of the fruit of Xylopia aethiopica (Annonaceae) exhibits anti-anaphylactic and anti-inflammatory actions in mice

Ethnopharmacological relevanceXylopia aethiopica has been traditionally used in the form of the dried fruit decoction to treat bronchitis, asthma, arthritis and rheumatism in Ghana, Nigeria and Cameroon. Aim of the study is to evaluate the anti-anaphylactic and anti-inflammatory effects of a 70% aqueous ethanol extract of the fruits of Xylopia aethiopica. Materials and methodsSystemic anaphylaxis was induced by the injection of either compound 48/80 or lipopolysaccharide, LPS and survival rates of mice monitored for 1h or 7 days respectively while IgE-mediated anaphylaxis in a local allergic reaction was studied in the pinnal inflammation model in mice. Clonidine-induced catalepsy in mice was used to evaluate the indirect antihistamine effect of Xylopia aethiopica, XAE. The effects of XAE assessed on the maximal and total oedema responses in the carrageenan-induced paw oedema in mice was used to evaluate the anti-inflammatory action of the extract. ResultsAdministered at 30, 100, 300 and 1000mgkg−1 p.o., XAE dose dependently suppressed compound 48/80-induced mouse systemic anaphylactic shock and offered 63% protection to mice against LPS-induced endotoxic shock at a dose of 300mgkg−1. In addition, the extract (30–300mgkg−1) in a dose dependent manner significantly inhibited by 23–62% the mouse pinnal inflammation. Clonidine-induced catalepsy in mice was significantly suppressed in a dose and time dependent manner when administered both prophylactically and therapeutically. In the same doses, when administered before the induction of the mouse carrageenan-induced paw oedema, the mean maximal swelling attained during 6h was reduced to 41.02±6.94%, 35.61±4.30%, and 29.09±4.90% of the inflamed control response respectively and total paw swellings induced over the 6h were also dose-dependently and significantly suppressed to 74.84±14.84%, 63.95±9.37%, and 48.13±10.90% of the inflamed control response respectively. Administered after the induction of the carrageenan paw oedema the mean maximal swelling attained during 6h was suppressed to 49.84±3.95%, 43.62±1.01%, and 35.97±1.34% of the inflamed control response respectively while the total paw swellings induced over the 6h were also dose-dependently and significantly suppressed at 100 and 300mgkg−1 to 72.39±4.38% and 60.81±3.25% of the inflamed control response respectively. ConclusionThese findings suggest that XAE inhibits mast cell-dependent immediate allergic reactions and exhibit anti-inflammatory actions through the inhibition of histamine release from mast cells via stabilizing the cell membrane. Our results contribute towards validation of the traditional use of Xylopia aethiopica in the treatment of bronchitis, asthma, arthritis and rheumatism.

Inhibitory effect of unicellular green algae (Chlorella vulgaris) water extract on allergic immune response

Chlorella is used as a functional food in East Asia and has been shown to enhance immune system function. However, there has been no direct evidence of the suppressive effect of a hot water extract of Chlorella vulgaris (CVE) on histamine-mediated allergic responses. The antihistamine activity of CVE was analysed using rat peritoneal mast cells (RPMCs) stimulated by compound 48/80. For in vivo verification, ovalbumin (OVA)-immunised BALB/c mice were treated with CVE orally. Serum immunoglobulin E (IgE) levels and splenocyte cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). CVE prevented histamine release through degranulation of mast cells by blocking the uptake of extracellular Ca²⁺ into RPMCs. Moreover, CVE administration inhibited serum IgE overproduction by OVA via induction of T helper 1 (Th1) skewing that was dependent on interferon-γ (IFN-γ) and interleukin 12 (IL-12) secretion. The results of this study clearly demonstrate that CVE acts as an antiallergic dietary agent by suppressing histamine release via its enhancive effect on Th1-related responses.

Galangin attenuates mast cell-mediated allergic inflammation

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.

Phenolic Glycosides from Lindera obtusiloba and their Anti-allergic Inflammatory Activities

Eight phenolic glycosides, tachioside (1), isotachioside (2), koaburaside (3), 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-D-glucopyranoside (4), 4,6-dihydroxy-2-methoxyphenyl-1-O-beta-D-glucopyranoside (5), a mixture of erigeside C (6a) and salidroside (6b), and 6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) were isolated from the stems of Lindera obtusiloba Blume. The structures of the isolates were determined by 1H-, 13C-NMR, COSY, HMQC, and HMBC spectroscopy. To evaluate their anti-allergic inflammatory activities, the inhibitory effects of isolates (1-7) on histamine release and on the gene expressions of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were examined using human mast cells; previous studies have reported that TNF-alpha and IL-6 release from mast cells is positively related to the severity of allergic symptoms. Of the tested compounds, koaburaside (3), 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-D-glucopyranoside (4), and (6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) suppressed histamine release from mast cells as compared with gallic acid (positive control). In particular, 6-hydroxyphenyl)-1-O-beta-D-glucopyranoside (7) attenuated the gene expressions of the proinflammatory cytokines TNF-alpha and IL-6 in human mast cells. Our results support the notion that phenolic glycosides isolated from L. obtusiloba inhibit mast-cell-derived allergic inflammation, histamine, and proinflammatory cytokines.