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Fulltext Solubility of drugs in aqueous polymeric solution: effect of ovalbumin on microencapsulation process

Aziz HA, Tan YT, Peh KK

AAPS PharmSciTech, 2012 Mar;13(1):35-45.
PMID: 22101965 DOI: 10.1208/s12249-011-9707-x

Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

Matched MeSH terms: Ovalbumin/metabolism; Ovalbumin/chemistry*
Ovalbumin causes impairment of preimplantation embryonic growth in asthma-induced mice

Wafriy CI, Kamsani YS, Nor-Ashikin MNK, Nasir NAA, Hanafiah M

J Reprod Immunol, 2021 02;143:103240.
PMID: 33166807 DOI: 10.1016/j.jri.2020.103240

Insufficient experimental studies have reported the effect of ovalbumin (OVA) as an allergen towards embryonic growth in asthma mouse model. The impact of 10 μg/200 μL OVA on maternal inflammatory and oxidative stress (OS) responses, and preimplantation embryonic development was investigated in this study. We first established OVA-induced asthma mouse model, and following superovulation, mated the females and challenged them with Methacholine (Mch) test. Upon embryo retrieval, only those with the highest implantation potential were cultured in vitro. Significant reduction in the number of embryos at each preimplantation stage was noted in the treated group. Uneven sized blastomeres at 2-, 4- and 8-cell stages were also evident in this group. Embryo fragmentation was significant at only 2-, 4- and 8-cell stages. We also found that OVA tended to raise maternal inflammatory and OS biomarker levels as well as to cause inappropriate levels of pregnancy hormones progesterone (P4) and estrogen (E2) although insignificant. The combined results indicate that 10 μg/200 μL OVA had altered both quality and quantity of the embryos in asthma mouse model although its effect on pregnancy hormones, inflammatory and OS responses were non-pathological.

Matched MeSH terms: Ovalbumin/administration & dosage; Ovalbumin/immunology
Fulltext Evaluation of functional properties of egg white obtained from pasteurized shell egg as ingredient in angel food cake

Tan, T.C., Kanyarat, K., Azhar, M.E.

International Food Research Journal, 2012;19(1):303-308.
MyJurnal

Pasteurized shell eggs are eggs that have been thermally treated to eliminate harmful bacteria, however the treatment may also denature some of the egg white proteins. In this study the degree of denaturation and functional properties (emulsifying, foaming, and gelling properties) of egg white obtained from pasteurized eggs (EWP) were compared with those of unpasteurized eggs (EWUP). Data from differential scanning calorimeter showed that the EWP (ovotransferin, lysozyme, and ovalbumin) denatured at lower temperatures and required lower denaturation enthalpies than EWUP, indicating a partial loss of protein structure during the pasteurization process in the pasteurized eggs. The emulsion and foam stability formed from EWP were significantly (P < 0.05) lower than those of EWUP, however the EWP formed stronger gels than EWUP. To assess suitability of EWP as a cake ingredient, angel food cake was prepared using both egg whites. As compared to EWUP-cake, EWP-cake was significantly (P < 0.05) lower in volume, cohesiveness and springiness values, but significantly (P < 0.05) higher in hardness, gumminess and chewiness. Overall, the sensory panelists gave significantly (P < 0.05) higher scores for angel food cake prepared with EWUP. The differences in functional properties of egg white proteins and the quality of cake were due mainly to the higher levels of denaturation attained by EWP as a result of the pasteurization process.

Matched MeSH terms: Ovalbumin
Targeting chemical and thermal stability of ovalbumin by simulated honey sugar cocktail

Wong YH, Kadir HA, Tayyab S

Int J Biol Macromol, 2015 Feb;73:207-14.
PMID: 25434804 DOI: 10.1016/j.ijbiomac.2014.11.015

Effect of simulated honey sugar cocktail (SHSC) on chemical and thermal stability of ovalbumin (OVA) was investigated using multiple-spectroscopic techniques. Urea-induced denaturation of OVA produced a transition, characterized by the start-, the mid- and the end-points at 3.2 M, 5.9/5.6 M and 8.5/8.0 M urea, respectively, when studied by MRE222nm and tryptophan fluorescence measurements. Presence of 10% or 20% (w/v) SHSC in the incubation mixture shifted the transition curve towards higher urea concentration in a concentration dependent manner. A comparison of far- and near-UV CD, UV-difference, ANS fluorescence and 3-D fluorescence spectral results of native OVA and 5.9 M urea-denatured OVA (U-OVA), obtained in the absence and the presence of 20% (w/v) SHSC suggested SHSC-induced stabilization of U-OVA. Furthermore, a significant shift towards higher denaturant concentration was also noticed in the GdnHCl and thermal transition curves of OVA in the presence of 20% (w/v) SHSC. Taken together, all these results suggested stabilization of OVA against chemical and thermal denaturations by SHSC.

Matched MeSH terms: Ovalbumin/chemistry*
Precipitation of Hevea brasiliensis latex proteins with trichloroacetic acid and phosphotungstic acid in preparation for the Lowry protein assay

Yeang HY, Yusof F, Abdullah L

Anal Biochem, 1995 Mar 20;226(1):35-43.
PMID: 7785777

Many proteins derived from the latex of Hevea brasiliensis that remain soluble in trichloroacetic acid (TCA) can be precipitated by phosphotungstic acid (PTA). A combination of 5% TCA and 0.2% PTA precipitates a wide range of proteins effectively even when they are present in low concentrations (below 1 microgram ml-1). In addition to its protein purification function, acid precipitation also increases the sensitivity of the subsequent protein assay by allowing the test sample to be concentrated. Another advantage of protein precipitation by TCA and PTA is that very small amounts of protein (of the order of 10 micrograms) can be repeatably recovered without the use of precipitate-bulking agents such as sodium deoxycholate. This general procedure of protein purification and concentration is simple and rapid, but the use of PTA may not be fully compatible with the Bradford protein assay. A modified Lowry microassay is described which enables about 3 micrograms ml-1 to be quantitated at the photometric absorbance of 0.05. When used in conjunction with protein concentration by precipitating with TCA/PTA, approximately 0.4 microgram ml-1 protein present in 6 ml of solution can be assayed.

Matched MeSH terms: Ovalbumin/analysis
Fulltext Effects of Palm Oil Tocotrienol-Rich Fraction (TRF) and Carotenes in Ovalbumin (OVA)-Challenged Asthmatic Brown Norway Rats

Zainal Z, Abdul Rahim A, Khaza'ai H, Chang SK

Int J Mol Sci, 2019 Apr 10;20(7).
PMID: 30974772 DOI: 10.3390/ijms20071764

Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and carotene, may be beneficial for alleviating asthma. Here, we determined the therapeutic efficacy of TRF, carotene, and dexamethasone in ovalbumin-challenged allergic asthma in Brown Norway rats. Asthmatic symptoms fully developed within 8 days after the second sensitization, and were preserved throughout the time course via intranasal ovalbumin re-challenge. Asthmatic rats were then orally administered 30 mg/kg body weight TRF or carotene. TRF-treated animals exhibited reduced inflammatory cells in bronchial alveolar lavage fluid. TRF- and carotene-treated rats exhibited notable white blood cell reduction comparable to that from dexamethasone. TRF- and carotene-treatment also downregulated pro-inflammatory markers (IL-β, IL-6, TNF-α), coincident with anti-inflammatory marker IL-4 and IL-13 upregulation. Treatment significantly reduced asthmatic rat plasma CRP and IgE, signifying improved systemic inflammation. Asthmatic lung histology displayed severe edema and inflammatory cell infiltration in the bronchial wall, whereas treated animals retained healthy, normal-appearing lungs. The phytonutrients tocotrienol and carotene thus exhibit potential benefits for consumption as nutritional adjuncts in asthmatic disease.

Matched MeSH terms: Ovalbumin/toxicity
Enhanced paracellular delivery of vaccine by hydrogel microparticles-mediated reversible tight junction opening for effective oral immunization

Chen XY, Butt AM, Mohd Amin MCI

J Control Release, 2019 10;311-312:50-64.
PMID: 31465827 DOI: 10.1016/j.jconrel.2019.08.031

The current conventional injectable vaccines face several drawbacks such as inconvenience and ineffectiveness in mucosal immunization. Therefore, the current development of effective oral vaccines is vital to enable the generation of dual systemic and mucosal immunity. In the present study, we examine the potential of pH-responsive bacterial nanocellulose/polyacrylic acid (BNC/PAA) hydrogel microparticles (MPs) as an oral vaccine carrier. In-vitro entrapment efficiency and release study of Ovalbumin (Ova) demonstrated that as high as 72% of Ova were entrapped in the hydrogel, and the release of loaded Ova was pH-dependent. The released Ova remained structurally conserved as evident by Western blot and circular dichroism. Hydrogel MPs reduced the TEER measurement of HT29MTX/Caco2/Raji B triple co-culture monolayer by reversibly opening the tight junctions (TJs) as shown in the TEM images. The ligated ileal loop assay revealed that hydrogel MPs could facilitate the penetration of FITC-Ova into the Peyer's patches in small intestine. Ova and cholera toxin B (CTB) were utilized in in-vivo oral immunization as model antigen and mucosal adjuvant. The in-vivo immunization revealed mice orally administered with Ova and CTB-loaded hydrogel MPs generated significantly higher level of serum anti-Ova IgG and mucosal anti-Ova IgA in the intestinal washes, compared to intramuscular administrated Ova. These results conclude that BNC/PAA hydrogel MPs is a potential oral vaccine carrier for effective oral immunization.

Matched MeSH terms: Ovalbumin/administration & dosage*; Ovalbumin/chemistry
Enhancement of ovalbumin-specific IgA responses via oral boosting with antigen co-administered with an aqueous Solanum torvum extract

Israf DA, Lajis NH, Somchit MN, Sulaiman MR

Life Sci, 2004 Jun 11;75(4):397-406.
PMID: 15147827

An experiment was conducted with the objective to enhance mucosal immunity against ovalbumin (OVA) by co-administration of OVA with an aqueous extract from the fruit of Solanum torvum (STE). Five groups of female ICR mice aged approximately 8 weeks at the commencement of the experiment were caged in groups of eight and received various treatments. The treatments included OVA alone, OVA with cholera toxin (CT), and OVA with various doses of STE. Mice were primed intraperitoneally with 500 microg of OVA alone or co-administered with 0.1 microg CT, or with 1 microg STE. All mice were boosted orally via gastric intubation 14 days after priming with 10 mg OVA alone, or co-administered with 10 microg CT or with 10 mg, 1 mg or 0.1 mg STE. One week later all mice were killed and organs obtained for analysis of the immune response. Intestinal, faecal and pulmonary OVA-specific sIgA concentration was significantly increased (p<0.05) in mice that received booster combinations of OVA/CT and OVA with all extract doses (p<0.05). Specific serum IgG titres did not differ significantly between groups. It is concluded that STE can significantly enhance secretory immunity in the intestine to OVA with mucosal homing to the lungs. The adjuvant effect of STE is comparable to that of CT.

Matched MeSH terms: Ovalbumin/administration & dosage; Ovalbumin/immunology*
Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model

Yang X, Guo G, Dang M, Yan L, Kang X, Jia K, et al.

J Environ Pathol Toxicol Oncol, 2019;38(3):229-238.
PMID: 31679310 DOI: 10.1615/JEnvironPatholToxicolOncol.2019030154

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.

Matched MeSH terms: Ovalbumin/toxicity
Fulltext Inhalation of honey reduces airway inflammation and histopathological changes in a rabbit model of ovalbumin-induced chronic asthma

Kamaruzaman NA, Sulaiman SA, Kaur G, Yahaya B

BMC Complement Altern Med, 2014;14:176.
PMID: 24886260 DOI: 10.1186/1472-6882-14-176

Honey is widely used in folk medicine to treat cough, fever, and inflammation. In this study, the effect of aerosolised honey on airway tissues in a rabbit model of ovalbumin (OVA)-induced asthma was investigated. The ability of honey to act either as a rescuing agent in alleviating asthma-related symptoms or as a preventive agent to preclude the occurrence of asthma was also assessed.

Matched MeSH terms: Ovalbumin
Fulltext A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice

Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA

Mediators Inflamm, 2021;2021:9725903.
PMID: 33883974 DOI: 10.1155/2021/9725903

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Matched MeSH terms: Ovalbumin
Biocompatible ionic liquids assisted transdermal co-delivery of antigenic protein and adjuvant for cancer immunotherapy

Chowdhury MR, Moshikur RM, Wakabayashi R, Moniruzzaman M, Goto M

Int J Pharm, 2021 May 15;601:120582.
PMID: 33872711 DOI: 10.1016/j.ijpharm.2021.120582

Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin-the stratum corneum-acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVA-specific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.

Matched MeSH terms: Ovalbumin
Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair

Halim NSS, Ch'ng ES, Kardia E, Ali SA, Radzi R, Yahaya BH

Stem Cell Rev Rep, 2019 02;15(1):112-125.
PMID: 30178289 DOI: 10.1007/s12015-018-9844-7

BACKGROUND: The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model.
METHODS: Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments.
RESULT(S): Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p

Matched MeSH terms: Ovalbumin
Fulltext Intranasal administration of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) extract attenuates airway inflammation in murine model of allergic asthma

Muhamad SA, Muhammad NS, Ismail NDA, Mohamud R, Safuan S, Nurul AA

Exp Ther Med, 2019 May;17(5):3867-3876.
PMID: 30988772 DOI: 10.3892/etm.2019.7416

Asthma is a chronic inflammatory disorder in the airways that involves the activation of cells and mediators. Lignosus rhinocerotis (Cooke) Ryvardan or Tiger Milk mushroom is a medicinal mushroom that is traditionally used to treat inflammatory diseases including asthma. In this study, the protective effects of intranasal administration of L. rhinocerotis extract (LRE) in ovalbumin (OVA)-induced airway inflammation mouse model were investigated. Mice were sensitized by intraperitoneal (i.p) injection on days 0 and 14, followed by a daily challenge with 1% OVA from days 21 to 27. Following OVA challenge, LRE and dexamethasone were administered via intranasal and i.p. injection respectively. On day 28, the level of serum immunoglobulin (Ig)E, differential cell counts and T-helper (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) fluid, cell subset population in lung-draining lymph nodes (LNs), leukocytes infiltration and mucus production in the lungs of the animals was measured. Results demonstrated that intranasal administration of LRE significantly suppressed the level of inflammatory cell counts in BALF as well as populations of CD4+ T-cells in lung draining LNs. Apart from that, LRE also significantly reduced the level of Th2 cytokines in BALF and IgE in the serum in OVA-induced asthma. Histological analysis also demonstrated the amelioration of leukocytes infiltration and mucus production in the lungs. Overall, these findings demonstrated the attenuation of airway inflammation in the LRE-treated mice therefore suggesting a promising alternative for the management of allergic airway inflammation.

Matched MeSH terms: Ovalbumin
Plasma and urine metabolite profiling reveals the protective effect of Clinacanthus nutans in an ovalbumin-induced anaphylaxis model: 1H-NMR metabolomics approach

Khoo LW, Audrey Kow SF, Maulidiani M, Lee MT, Tan CP, Shaari K, et al.

J Pharm Biomed Anal, 2018 Sep 05;158:438-450.
PMID: 29957507 DOI: 10.1016/j.jpba.2018.06.038

The present study sought to identify the key biomarkers and pathways involved in the induction of allergic sensitization to ovalbumin and to elucidate the potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key requisites for the induction of anaphylaxis reaction. Sensitized rats treated with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive correlation with the normal group and was negatively related to the induced group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and Genomes (KEGG) reveals the protective effect of C. nutans extract against ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism (choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2-propanediol), amino acid metabolism (betaine, N,N-dimethylglycine, methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In summary, this study reports for the first time, C. nutans water extract is a potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative analytical tool to explicate the mechanism of action of anaphylaxis.

Matched MeSH terms: Ovalbumin/immunology
An orally active geranyl acetophenone attenuates airway remodeling in a murine model of chronic asthma

Lee YZ, Shaari K, Cheema MS, Tham CL, Sulaiman MR, Israf DA

Eur J Pharmacol, 2017 Feb 15;797:53-64.
PMID: 28089919 DOI: 10.1016/j.ejphar.2017.01.011

2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a synthetic compound that is naturally found in Melicope ptelefolia. We had previously demonstrated that parenteral administration of tHGA reduces pulmonary inflammation in OVA-sensitized mice. In this study, we evaluated the effect of orally administered tHGA upon airway remodeling in a murine model of chronic asthma. Female BALB/C mice were sensitized intraperitoneally with ovalbumin (OVA) on day 0, 7 and 14, followed by aerosolized 1% OVA 3 times per week for 6 weeks. Control groups were sensitized with saline. OVA sensitized animals were either treated orally with vehicle (saline with 1% DMSO and Tween 80), tHGA (80, 40, 20mg/kg) or zileuton (30mg/kg) 1h prior to each aerosolized OVA sensitization. On day 61, mice underwent methacholine challenge to determine airway hyperresponsiveness prior to collection of bronchoalveolar lavage (BAL) fluid and lung samples. BAL fluid inflammatory cell counts and cytokine concentrations were evaluated while histological analysis and extracellular matrix protein concentrations were determined on collected lung samples. Oral tHGA treatment attenuated airway hyperresponsiveness and inhibited airway remodeling in a dose-dependent fashion. tHGA's effect on airway remodeling could be attributed to the reduction of inflammatory cell infiltration and decreased expression of cytokines associated with airway remodeling. Oral administration of tHGA attenuates airway hyperresponsiveness and remodeling in OVA-induced BALB/c mice. tHGA is an interesting compound that should be evaluated further for its possible role as an alternative non-steroidal pharmacological approach in the management of asthma.

Matched MeSH terms: Ovalbumin/immunology
Clinacanthus nutans aqueous leaves extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway

Kow ASF, Khoo LW, Tan JW, Abas F, Lee MT, Israf DA, et al.

J Ethnopharmacol, 2023 Mar 01;303:116003.
PMID: 36464074 DOI: 10.1016/j.jep.2022.116003

ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach.
AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.
MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.
RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.
CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

Matched MeSH terms: Ovalbumin
A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model

Lim JC, Goh FY, Sagineedu SR, Yong AC, Sidik SM, Lajis NH, et al.

Toxicol Appl Pharmacol, 2016 07 01;302:10-22.
PMID: 27089844 DOI: 10.1016/j.taap.2016.04.004

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6-8weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1h before and 11h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model.

Matched MeSH terms: Ovalbumin

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