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.

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.

Dietary Ziziphus jujuba Fruit Influence on Aberrant Crypt Formation and Blood Cells in Colitis-Associated Colorectal Cancer in Mice.

Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary complaints. However, dietary effects with regard to chemoprevention of colon cancer have not been studied. The present study was performed to evaluate the protective effects of dietary ZJ against colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between were administered to induce colitis-associated colon cancer. ZJ fruit was supplemented into feed at levels of 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation and also decreased the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation may delay the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leukocytes, main regulators of cancer inflammation. Dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

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.

Sesame oil mitigates nutritional steatohepatitis via attenuation of oxidative stress and inflammation: a tale of two-hit hypothesis.

Nonalcoholic fatty liver disease, the most common chronic liver disorder worldwide, comprises conditions from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma. Sesame oil, a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. We investigated the protective effect of sesame oil against nutritional steatohepatitis in mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 28 days to induce NASH. Sesame oil (1 and 2 ml/kg) was treated from 22nd to 28th day. Body weight, steatosis, triglycerides, aspartate transaminase, alanine transaminase, nitric oxide, malondialdehyde, tumor necrosis factor-α, interlukin-6, interleukin-1ß, leptin, and transforming growth factor-ß1 (TGF-ß1) were assessed after 28 days. All tested parameters were higher in MCD-fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, oxidative stress, and necrotic inflammation. In sesame-oil-treated mice, all tested parameters were significantly attenuated compared with MCD-alone mice. Sesame oil inhibited oxidative stress, inflammatory cytokines, leptin, and TGF-ß1 in MCD-fed mice. In addition, histological analysis showed that sesame oil provided significant protection against fibrotic collagen. We conclude that sesame oil protects against steatohepatitic fibrosis by decreasing oxidative stress, inflammatory cytokines, leptin and TGF-ß1.

Sesame oil attenuates nutritional fibrosing steatohepatitis by modulating matrix metalloproteinases-2, 9 and PPAR-γ.

Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its improved liver function in various animal model studies. However, its effect on nutritional fibrosing steatohepatitis is unclear. We investigated therapeutic sesame oil on matrix metalloproteinases-2, 9 (MMP-2, 9) in nutritional fibrosing steatohepatitic mice. C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 35 days to induce fibrosing steatohepatitis. Sesame oil was treated from 29-35th day. Body weight, steatosis, aspartate transaminase, alanine transaminase, peroxisome proliferator-activated receptor (PPAR)-γ, α-smooth muscle actin (α-SMA), MMP-2, 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed after 35 days. All tested parameters except TIMP-1 and PPAR-γ were higher in MCD fed mice than in normal control mice. Mice fed with MCD diet for 4 weeks showed severe liver injury with steatosis, necrotic-inflammation, and fibrosis. In sesame-oil (4 ml)-treated mice, all tested parameters except TIMP-1, α-SMA, and PPAR-γ were significantly attenuated compared with MCD fed mice. Sesame oil inhibited MMP-2, 9 activities, but up-regulated TIMP-1 expression in MCD fed mice. In addition, a histological analysis of liver tissue samples showed that sesame oil provided significant protection against fibrosis. We conclude that therapeutic sesame oil protects against fibrosing steatohepatitis by inhibiting MMP-2, 9 activities, up-regulating TIMP-1 expression, and PPAR-γ.

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.

Prophylactic sesame oil attenuates sinusoidal obstruction syndrome by inhibiting matrix metalloproteinase-9 and oxidative stress.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) occurs in patients undergoing hematopoietic cell transplantation and chemotherapy. The chemotherapeutic drugs oxaliplatin and cyclophosphamide cause SOS. Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the protective effect of prophylactic sesame oil against monocrotaline-induced SOS in rats. METHODS: Male Sprague-Dawley rats were gavaged with a single dose of sesame oil (0.5, 1, 2, or 4 mL/kg). One hour later, those rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only. Aspartate transaminase, alanine transaminase, laminin, collagen, myeloperoxidase, nitrate content, lipid peroxidation, glutathione levels, matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed 48 hours after the monocrotaline gavage. RESULTS: All tested parameters except TIMP-1, laminin, collagen, and glutathione were higher in monocrotaline-treated rats than in saline-only-treated control rats. In sesame oil-treated rats, all tested parameters except TIMP-1, laminin, collagen, and glutathione were significantly attenuated compared with monocrotaline-only-treated rats. Sesame oil downregulated MMP-9 expression but upregulated TIMP-1 expression in monocrotaline-only-treated rats. In addition, a histological analysis of liver tissue samples showed that sesame oil showed significant protection. CONCLUSION: A single prophylactic dose of sesame oil protects against SOS by downregulating MMP-9 expression, upregulating TIMP-1 expression, and inhibiting oxidative stress.

Therapeutic oral sesame oil is ineffectual against monocrotaline-induced sinusoidal obstruction syndrome in rats.

BACKGROUND: The chemotherapeutic drug oxaliplatin causes sinusoidal obstruction syndrome (SOS), which is analogous to that of monocrotaline-induced SOS. Sesame oil is a nutrient-rich antioxidant in alternative medicine. It contains phenol, sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the therapeutic effect of oral sesame oil against monocrotaline-induced SOS in rats. METHODS: Male Sprague-Dawley rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only at 0 and 24 hours. Sesame oil (0.5, 1, 2, or 4 mL/kg, orally) was given 24 hours after monocrotaline in rats. Blood samples were collected at 24 and 48 hours after monocrotaline was given to assess the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Histopathology was also assessed 48 hours after monocrotaline was given. RESULTS: AST and ALT were significantly higher in monocrotaline-treated rats than in control rats. Oral sesame oil did not decrease AST and ALT in monocrotaline-treated rats. In addition, liver pathology revealed that oral sesame oil had no therapeutic effect against SOS. CONCLUSION: Oral sesame oil is therapeutically ineffectual against monocrotaline-induced SOS.

Sesame oil accelerates healing of 2,4,6-trinitrobenzenesulfonic acid-induced acute colitis by attenuating inflammation and fibrosis.

BACKGROUND: Sesame oil is a component of traditional health food in Asian countries. Acute colitis is a form of inflammatory bowel disease (IBD) with chronic inflammatory disorder of the bowel. The precise etiology of IBD remains unknown, but it is believed that an abnormal host response to endogenous antigens causes initial tissue injury with amplification of the immune response. We investigated the protective effect of sesame oil against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in rats. METHODS: Rats were intracolonically instilled with TNBS (120 mg/kg) using a cannula to induce colitis and then orally gavaged with sesame oil (4 mL/kg for 7 days) to attenuate TNBS-induced acute colitis. The acute colitis activity index (ACAI) was assessed using the colon weight/length ratio (mg/cm), thickness, extension of lesion, diarrhea, and macroscopic and microscopic damage scores. In addition, the degree of inflammation, mucins, and fibrosis was assessed by measuring mast cells, CD68(+) cells, neutral mucin, acidic mucin, collagen, and laminin on day 8 after inducing acute colitis. RESULTS: All tested parameters except neutral mucins were significantly higher in TNBS-induced acute colitis. Sesame oil significantly decreased the degree of inflammation, fibrosis, and acidic mucin and increased neutral mucin. CONCLUSION: We conclude that sesame oil accelerates the healing of an inflamed colon by inhibiting inflammation, acidic mucin, and fibrosis in TNBS-induced acute colitis in rats.

Green tea polyphenol protection against 4-nitroquinoline 1-oxide-induced bone marrow lipid peroxidation and genotoxicity in Wistar rats.

4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer.

Sesame oil prevents acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats.

The aim of the study was to investigate the effect of sesame oil on acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats. Acute kidney injury was induced by a 5-day course of daily gentamicin injections (100 mg/kg of body weight, subcutaneously) and then iodinated contrast (4 ml/kg, intravenously) in male specific-pathogen-free Sprague-Dawley rats. Sesame oil (0.5 ml/kg, orally) was given 1 h before iodinated contrast. Renal function and oxidative stress were assessed 6 h after iodinated contrast injection. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. Renal oxidative stress was assessed by determining renal lipid peroxidation, myeloperoxidase, hydroxyl radical, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase levels. Sesame oil significantly prevented the rise of serum blood urea nitrogen and creatinine levels. Furthermore, there was a parallel inhibition of the rise in levels of expression of renal lipid peroxidation, myeloperoxidase, hydroxyl radicals, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase in rats with gentamicin-plus-iodinated contrast-induced acute kidney injury. We conclude that sesame oil may attenuate aminoglycoside-plus-iodinated contrast-induced acute kidney injury by inhibiting renal oxidative stress in rats.

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.