Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL-4 production in peripheral blood from asthmatic patients.

Asthma, a major non-communicable disease, affects both adults and children and is associated with high morbidity compared with other chronic diseases. The glycolysis-associated activation of type 2 helper T (Th2) cells is the critical immunopathological mechanism involved in asthma deterioration. Long-term use of steroids as a medical treatment for asthma induces side effects and resistance. Pterostilbene (PS), a stilbenoid compound found in blueberry and vines, exhibits antihyperglycemic and anti-inflammatory properties. Thus, we hypothesized that the modulation of T cell immunity by PS may be an applicable intervention to treat asthma. Airway hyperresponsiveness, interleukin (IL)-4 and IL-13 levels, IgE, IgG, pulmonary infiltrated monocytes and eosinophils, and mucosubstances were measured in house dust mite (HDM)-induced asthmatic mice under PS treatment. Bioenergetic metabolism, PI3K-mTOR signalling, GATA3 expression and histone acetylation in PS-treated Th2 cells were investigated. PS improved HDM-induced pulmonary allergic airway inflammation by inhibiting Th2 cell and eosinophil accumulation in HDM asthmatic mice both in the preventive and therapeutic models. Targeting glycolysis resulted in IL-4 inhibition via the downregulation of mTOR, GATA3 and histone acetylation in PS-treated Th2 cells. Glucose supplementation reversed the inhibitory effect of PS on Th2 cells in vitro. Adoptive transfer with glucose-treated Th2 cells enhanced Th2 activation and eosinophilic accumulation in PS-treated asthmatic mice. Furthermore, PS significantly inhibited IL-4 production of CD4+ T cells from the peripheral blood mononuclear cells of patients with asthma. PS attenuates HDM-induced asthma via the inhibition of the Glut1/mTOR/GATA3 axis in Th2 cells, which supports the potential pharmaceutical application of PS treatment for asthma.

Adoptive transfer of IL-4 reprogrammed Tc17 cells elicits anti-tumour immunity through functional plasticity.

Ability of IL-17-producing CD8+ T cells (Tc17) to transform into cytotoxic anti-tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17-based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL-4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN-γ-producing IECs, an effect dependent on Eomes expression. IL-4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN-γ-producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL-4/AKT signalling drove the upregulation of the T-cell receptor-associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL-4-induced T-cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL-4 in Tc17 reprogramming. Collectively, these results document a novel IL-4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL-4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti-tumour responses.

The protective effect of muscimol against systemic inflammatory response in endotoxemic mice is independent of GABAergic and cholinergic receptors.

Systemic inflammatory response syndrome plays an important role in the development of sepsis. GABAergic and cholinergic pathways activation are considered important for inflammatory response regulation. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-12, IL-10, as well as inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) are important inflammatory mediators involved in the pathogenesis of sepsis. Muscimol, an active compound from the mushroom Amanita muscaria (L.) Lam., is a potent GABAA agonist, inhibits inflammatory response via activating GABAA receptor and vagus nerve. However, the effect of muscimol on lipopolysaccharide (LPS)-induced systemic inflammatory response is still unclear. Therefore, we studied the effects of muscimol on systemic inflammatory response and survival rate in endotoxemic mice. Mice endotoxemia was induced by LPS. Muscimol was given to mice or RAW264.7 cells 30 min before LPS (10 mg/kg, i.p., or 10 ng/mL, respectively). Mice received GABAergic and cholinergic receptor antagonists 30 min before muscimol and LPS. Muscimol decreased TNF-α, IL-1ß, IL-12, iNOS-derived NO, and increased IL-10 levels and survival rate after LPS treatment. Muscimol significantly decreased nuclear factor kappa B (NF-κB) activity, increased IκB expression, and decreased pIKK expression in LPS-treated RAW264.7 cells. GABAergic and cholinergic antagonists failed to reverse muscimol's protection in LPS-treated mice. In conclusion, muscimol protected against systemic inflammatory response in endotoxemic mice may be partially independent of GABAergic and cholinergic receptors.

Dietary Ziziphus jujuba Fruit Attenuates Colitis-Associated Tumorigenesis: A Pivotal Role of the NF-κB/IL-6/JAK1/STAT3 Pathway.

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) is one of the risk factors for the development of colitis-associated colon cancer (CAC). CAC is a type of colorectal cancer (CRC), the third leading cause of cancer death. Ziziphus jujuba (ZJ) fruit contains bioactive components such as polysaccharides, triterpenoid acid, and flavonoids, and it has shown anti-inflammatory property. The aim of the study was to investigate the protective effect of dietary ZJ on colitis-associated colorectal tumorigenesis in mice. Mice (n = 42, two sets) were injected with azoxymethane (AOM) followed by three cycles of 2% (w/v) dextran sulfate sodium (DSS) in drinking water to induce CAC. Simultaneously, those mice were fed with ZJ diet for 70 days (5% or 10% w/w). Data were analyzed by ANOVA followed by LSD Bonferroni test. Dietary ZJ decreased fecal blood, diarrhea, disease activity index (DAI), spleen weight (P < 0.001), and the number of tumors (P < 0.001). In addition, dietary ZJ increased colon length (P < 0.001) and suppressed the activation of NF-кB/IL-6/JAK1/STAT3 signaling pathway. In conclusion, we suggest that dietary ZJ attenuates inflammation by interfering NF-κB/IL-6/JAK1/STAT3 signaling pathway, thereby inhibits AOM/DSS-induced colon tumorigenesis in mice.

Curative effect of sesame oil in a rat model of chronic kidney disease.

AIM: Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. METHODS: Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. RESULTS: Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. CONCLUSION: We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats.

Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis.

BACKGROUND: An effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown. METHODS: Seventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method. RESULTS: We observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability. CONCLUSION: This study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.

Targeting Nrf2 with 3 H-1,2-dithiole-3-thione to moderate OXPHOS-driven oxidative stress attenuates IL-17A-induced psoriasis.

Psoriasis, a chronic autoimmune disease characterized by the hyperproliferation of keratinocytes in the epidermis and parakeratosis, significantly impacts quality of life. Interleukin (IL)- 17A dominates the pathogenesis of psoriasis and facilitates reactive oxygen species (ROS) accumulation, which exacerbates local psoriatic lesions. Biologic treatment provides remarkable clinical efficacy, but its high cost and unignorable side effects limit its applications. 3 H-1,2-Dithiole-3-thione (D3T) possesses compelling antioxidative capacities against several diseases through the nuclear factor erythroid 2-related factor 2 (Nrf2) cascade. Hence, we aimed to evaluate the effect and mechanism of D3T in psoriasis. We found that D3T attenuates skin thickening and scaling by inhibiting IL-17A-secreting γδT cells in imiquimod (IMQ)-induced psoriatic mice. Interleukin-17A markedly enhanced IL-6 and IL-8 expression, lipid peroxidation, the contents of nitric oxide and hydrogen peroxide, oxidative phosphorylation and the MAPK/NF-κB pathways in keratinocytes. IL-17A also inhibited the Nrf2-NQO1-HO-1 axis and the activities of superoxide dismutase and glutathione peroxidase. D3T significantly reversed these parameters in IL-17A-treated keratinocytes. ML-385, a Nrf2 neutralizer, failed to improve D3T-induced anti-inflammatory and antioxidative effects in IL-17A-treated keratinocytes. We conclude that targeting Nrf2 with D3T to diminish oxidative and inflammatory damage in keratinocytes may attenuate psoriasis.

Cordycepin prevents and ameliorates experimental autoimmune encephalomyelitis by inhibiting leukocyte infiltration and reducing neuroinflammation.

Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease characterized by multifocal perivascular infiltration of immune cells in the central nervous system (CNS). Cordycepin (3'-deoxyadenosine), an adenosine analogue initially extracted from the fungus Cordyceps militarisa, is one of the candidates that has multiple actions. We investigated that cordycepin attenuated the activation of LPS-induced mouse bone marrow-derived dendritic cells (BMDCs) and human monocyte-derived dendritic cells (MoDCs) through the inhibition of the AKT, ERK, NFκB, and ROS pathways and impaired the migration of BMDCs through the downregulation of adhesion molecules and chemokine receptors in vitro. In experimental autoimmune encephalomyelitis (EAE) model, preventive treatment with cordycepin decreased the expression of trafficking factors in the CNS, inhibited the secretion of inflammatory cytokines (IFN-γ, IL-6, TNF-α, and IL-17), and attenuated disease symptoms. A chemokine array indicated that cordycepin treatment reversed the high levels of CCL6, PARRES2, IL-16, CXCL10, and CCL12 in the brain and spinal cord of EAE mice, consistent with the RNA-seq data. Moreover, cordycepin suppressed the release of neuroinflammatory cytokines by activated microglial cells, macrophages, Th17 cells, Tc1 cells, and Th1 cells in vitro. Furthermore, cordycepin treatment exerted therapeutic effects on attenuating the disease severity in the early disease onset stage and late disease progression stage. Our study suggests that cordycepin treatment may not only prevent the occurrence of MS by inhibiting DC activation and migration but also potentially ameliorates the progression of MS by reducing neuroinflammation, which may provide insights into the development of new approaches for the treatment of MS.

Combined Effects of Tanshinone IIA and an Autophagy Inhibitor on the Apoptosis of Leukemia Cells via p53, Apoptosis-Related Proteins and Oxidative Stress Pathways.

BACKGROUND: Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy with limited response and acquired resistance to therapy. Inducing apoptosis and inhibiting autophagy in tumor cells is a combinational strategy for the development of anticancer therapeutics. Tanshinone IIA (TAIIA) is one of the major ingredients in Salvia miltiorrhiza, which is the most prescribed herb for the treatment of AML in Taiwan. Therefore, this study aimed to delineate the anticancer effects of TAIIA and its effect when combined with an autophagy inhibitor to treat AML. METHODS: The anticancer effects of a combination of TAIIA and the autophagy inhibitor 3-methladenine (3MA) on the human monocytic leukemia cell line THP-1 were explored. The apoptosis and cell cycle of the leukemia cells were examined by Annexin V and propidium iodide staining and analyzed by flow cytometry. The oxidative stress level was determined by a malondialdehyde (MDA) colorimetric assay, nitric oxide colorimetric assay and glutathione peroxidase (GPx) colorimetric assay. The expression of apoptosis-related proteins was determined by western blotting. RESULTS: TAIIA treatment significantly induced apoptosis via increased p53, Bax/Bcl, PARP, and caspase-3 signals and oxidative stress by enhancing MDA and nitrate/nitrite production and reducing GPx activity in THP-1 cells in a dose-dependent and time-dependent manner. The combination of the autophagy inhibitor 3MA enhanced TAIIA-induced apoptosis via the p53, Bax/Bcl, PARP, caspase-3, and oxidative stress pathways in THP-1 cells. CONCLUSION: The results suggest that TAIIA and autophagy inhibitors have combined effects on the apoptosis of leukemia cells, thus representing a novel and effective combination with the potential for application as a clinical therapy for AML.

Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells.

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22-49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

Sesame oil accelerates kidney healing following gentamicin-induced kidney injury in rats.

BACKGROUND/AIMS: We investigated the therapeutic effect of a single dose of sesame oil against gentamicin-induced renal damage in rats. METHODS: Experimental rats were subcutaneously injected with gentamicin (100 mg/kg/day for 7 days) to induce renal injury. Sesame oil (1, 2 or 4 ml/kg) was given orally 24 h after the last dose of gentamicin. Control rats were treated with saline only. Renal injury, histopathological examination, histochemical staining, osteopontin expression, superoxide anion, nitric oxide, peroxynitrite radical and lipid peroxidation were assessed 24 h after sesame oil administration. RESULTS: Serum blood urea nitrogen and creatinine as well as renal osteopontin expression, superoxide anion, nitric oxide, peroxynitrite radical and lipid peroxidation levels were higher in gentamicin-treated rats than in control rats. Sesame oil significantly decreased all the tested parameters compared with gentamicin-alone rats. Furthermore, histopathological and histochemical staining showed that renal tubules had recovered and regenerated in the sesame oil-treated rats. CONCLUSION: We hypothesize that a single dose of sesame oil inhibits oxidative stress to shorten the recovery period and allow the regeneration of renal tubules after the onset of gentamicin-induced renal injury in rats.

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses.

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Daily sesame oil supplementation attenuates local renin-angiotensin system via inhibiting MAPK activation and oxidative stress in cardiac hypertrophy.

The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was gavaged (0.5 or 1 ml/kg/day for 7 days) after 4 weeks of DOCA/salt treatment. Cardiac histopathology, RAS parameters, expression of MAPKs, reactive oxygen species and lipid peroxidation were assessed 24 h after the last dose of sesame oil. Sesame oil significantly decreased the size of cardiomyocytes and the levels of cardiac renin, angiotensin-converting enzyme and angiotensin II. In addition, sesame oil down-regulated the expression of angiotensin type 1 receptor, JNK and p38 MAPK and apoptosis signal regulating kinase 1, c-Fos and c-Jun in rats receiving DOCA/salt. Furthermore, the induction of nicotinamide adenine dinucleotide phosphate oxidase, superoxide anion and hydroxyl radical and lipid peroxidation by DOCA/salt were inhibited by sesame oil. Sesame oil modulates cardiac RAS to ameliorate LVH by inhibiting MAPK activation and lowering oxidative stress.

Daily sesame oil supplementation mitigates ketoconazole-induced oxidative stress-mediated apoptosis and hepatic injury.

Ketoconazole (KCZ) is the most commonly used systemic antifungal drug. However, long-term treatment of KCZ induces hepatic injury. Oxidative stress is involved in KCZ-induced hepatic injury. Oxidative stress plays an important role in apoptosis-associated hepatic damage. Sesame oil is rich in potent antioxidants and antifungal constituents. It attenuates hepatic injury by inhibiting oxidative stress. Thus, sesame oil may protect against KCZ-induced oxidative stress, apoptosis and hepatic damage. The aim of the present study was to investigate the protective effect of sesame oil as a nutritional supplement on KCZ-induced hepatic injury in mice. KCZ (300 mg/kg/day) was administered by gastric intubation; 30 min later, sesame oil (0, 0.0625, 0.125, 0.25 or 0.5 ml/kg/day; p.o.) was administered to mice for 14 days. Blood and liver tissue were collected. Hepatic injury was evaluated by serum biochemistry and histology. Oxidative stress was evaluated by myeloperoxidase activity, p47-phox, reactive oxygen species generation, lipid peroxidation and glutathione level. Apoptosis was evaluated by p53, caspase-3, Bcl-2, Bax and Cyto-C expression. Osteopontin was measured to assess liver healing. Sesame oil attenuated hepatic injury; it also decreased oxidative stress and apoptosis in KCZ-treated mice. Sesame oil may be used as a nutritional supplement with existing antifungal therapies to neutralize the adverse hepatotoxic nature of antifungal drugs by attenuating hepatic apoptosis through redox system to protect and heal liver injury in KCZ-treated mice.

Sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.

BACKGROUND: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long-term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. METHODS: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K(+) and Mg(2+) levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. RESULTS: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K(+) and Mg(2+) while limiting the urinary excretion of K(+) in DOCA/salt-induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. CONCLUSION: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.

Sesame oil attenuates ovalbumin-induced pulmonary edema and bronchial neutrophilic inflammation in mice.

BACKGROUND: Allergic asthma is one of the most common chronic inflammatory diseases of airways. Severe asthma may lead to hospitalization and death. Sesame oil is a natural product with anti-inflammatory property. However, the effect of sesame oil on allergic asthma has never been studied. OBJECTIVE: We investigate the effect of sesame oil on pulmonary inflammation in allergic asthma model. METHODS: Allergic airway inflammation was induced by sensitizing with two doses of 10 mg ovalbumin (OVA) and then challenged with 1% OVA nebulizer exposure (1 h/day) for 3 days. Sesame oil (0.25, 0.5, or 1 mL/kg/day) was given orally 30 min before each challenge. Samples were collected 24 h after the last challenge. RESULTS: Data showed that sesame oil inhibited pulmonary edema and decreased interleukin (IL)-1 ß and IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice. Sesame oil also decreased pulmonary nitrite level, inducible nitric oxide synthase expression, and neutrophil infiltration induced by OVA. Further, sesame oil decreased serum IgE level in OVA-treated mice. CONCLUSION: Sesame oil may attenuate pulmonary edema and bronchial neutrophilic inflammation by inhibiting systemic IgE level in allergic asthma.

Protective effect of daily sesame oil supplement on gentamicin-induced renal injury in rats.

Gentamicin, an aminoglycoside antibiotic, is widely used in the treatment of Gram-negative infections; however, dose-limiting nephrotoxicity restricts its optimal use. We investigated the effect of a daily sesame oil supplement on oxidative-stress-associated renal injury induced by a single daily dose of gentamicin in rats. Renal injury was induced by a single subcutaneous daily dose of gentamicin (100 mg kg(-1) d(-1) for 7 days), and then the effects of oral sesame oil (0.25, 0.5, and 1 mL kg(-1) d(-1) for 7 days) on renal injury, oxidative stress, hydroxyl radical, superoxide anion, and NO were assessed after treatment. Sesame oil inhibited gentamicin-induced renal injury, lipid peroxidation, hydroxyl radical, and superoxide anion, as well as NO production. In addition, sesame oil inhibited xanthine oxidase activity and inducible NOS expression in gentamicin-challenged rats. We hypothesize that a daily sesame oil supplement attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.