Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress.

PMID: 

Apoptosis. 2019 Dec ;24(11-12):905-920. PMID: 31538267

Abstract Title: 

Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress.

Abstract: 

Hepatic stellate cell (HSC) activation plays an indispensable role in hepatic fibrosis. Inducing apoptosis of activated HSCs can attenuate or reverse fibrogenesis. In this study, we initially found that oroxylin A (OA) protected CCl-induced liver injury accompanied by endoplasmic reticulum stress (ERS) activation of HSCs in mice. In vitro, OA treatment markedly reduced fibrogenesis by modulating extracellular matrix synthesis and degradation. OA inhibited cell proliferation and induced cell cycle arrest of HSCs at S phase. Further, OA was observed to induce HSC apoptosis, as indicated by caspase activation. Using the eIF2α dephosphorylation inhibitor salubrinal, we found that ERS pathway activation was required for OA to induce HSC apoptosis. ERS-related proteins were significantly upregulated by OA treatment, and salubrinal abrogated the effects of OA on HSCs. Thus, we inferred that OA attenuated HSC activation bypromoting ERS. In vivo, inhibition of ERS by salubrinal partly abrogated the hepatoprotective effect of OA in CCl-treated mice. In conclusion, our findings suggest a role for ERS in the mechanism underlying amelioration of hepatic fibrosis by OA.

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Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human hepatocellular carcinoma.

PMID: 

Cancer Chemother Pharmacol. 2010 Feb ;65(3):481-9. Epub 2009 Jul 8. PMID: 19585117

Abstract Title: 

Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human hepatocellular carcinoma and on H22 transplanted mice.

Abstract: 

AIM: To investigate the synergistic inhibitory effects of the combination of 5-fluorouracil (5-FU) with the natural flavanoid oroxylin A on human hepatocellular carcinoma cells HepG2 in vitro and on transplanted murine hepatoma 22 (H22) tumors in vivo and the preliminary mechanisms.METHODS: The inhibitory effects of 5-FU combined with the natural flavanoid oroxylin A in vitro were detected by MTT assay and the effects in vivo were investigated by transplanted H22 mice model. DAPI staining and Annexin V/propidium iodide (PI) double staining were used to detect the cell morphological changes and apoptosis. The mRNA levels of thymidine synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in HepG2 cells after oroxylin A and 5-FU combination treatment were observed by quantitative real-time PCR. Western blotting assay was used to reveal the expressions of apoptotic-inducing proteins P53, cleaved PARP, COX-2, Bcl-2, and pro-caspase3.RESULTS: Oroxylin A in combination with 5-FU presented synergistic effect (CI

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Superhongmi extract diet supplementation significantly suppressed hyperglycemia, oxidative stress, and bone resorption.

PMID: 

Prev Nutr Food Sci. 2019 Jun ;24(2):144-149. Epub 2019 Jun 30. PMID: 31328118

Abstract Title: 

Effects of 'Superhongmi' Rice Bran Extracts on Biochemical Markers of Glycolysis and Bone Metabolism in Ovariectomized Rats.

Abstract: 

Middle aged women naturally enter menopause, which increases the risk of several metabolic diseases. The objective of this research was to investigate the regulatory effects of bioactive natural product"Superhongmi"rice bran on hyperglycemia, oxidative stress, and bone metabolism. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n=10): ovariectomized (OVX)-AIN93M diet (OVX-AIN93M) and OVX-AIN93M diet supplemented with either low dose Superhongmi extract (1 g/kg, OVX-LSH) or high dose Superhongmi extract (5 g/kg, OVXHSH). Body weight, activities of glucose regulatory, antioxidant enzymes, and bone metabolism biochemical markers of rats were measured. After eight weeks of feeding, the OVX-AIN93M group showed a significant increase in body weight gain relative to the sham-operated group. Superhongmi extract diet supplementation (OVX-HSH group) significantly suppressed hyperglycemia, oxidative stress, and bone resorption. These findings indicated that OVX-HSH has a potential therapeutic effect on menopause women.

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Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection.

PMID: 

Int J Immunopathol Pharmacol. 2016 Dec ;29(4):647-653. Epub 2016 Oct 31. PMID: 27799299

Abstract Title: 

Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial.

Abstract: 

Current treatments for Hepatitis C virus (HCV) have severe side effects and are very expensive. There is a need to explore effective natural therapies against HCV that are less toxic and more cost-effective. In the current study, 37 chronic HCV patients were randomized into two groups and treated with either pegylated interferon (PEG IFN) plus ribavirin (n = 21) or Biobran, an arabinoxylan from rice bran (1 g/day) (n = 16). We examined viremia, liver enzymes, interferon-γ (IFN-γ) levels in serum, and toxicity before and three months after treatment. Both groups showed a significant and similar reduction in viral load after three months of treatment relative to the baseline viral load (P

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Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects.

PMID: 

Exp Ther Med. 2018 Mar ;15(3):2313-2320. Epub 2018 Jan 8. PMID: 29456638

Abstract Title: 

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double-blind, placebo-controlled clinical trial.

Abstract: 

Aging is associated with a decline in natural killer (NK) and natural killer T (NKT) cell function that may contribute to increased susceptibility to malignancy and infection. A preliminary investigation was conducted examining the hypothesis that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known immunomodulatory activity, could counteract this decline in NK/NKT cell activity in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56 years old, participated in a randomized, double-blind, placebo-controlled clinical trial. A total of six subjects served as control and six subjects ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3 supplementation on NK/NKT cell activity was assessed using the degranulation assay. All study subjects were monitored for the development of any inadvertent side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood cell components and liver and kidney functions were also assessed. Results demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK cells, however it enhanced the cytotoxic activity of induced NK cell expression of cluster of differentiation 107a, when compared with baseline values and with the placebo group (P

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Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance.

PMID: 

Sci Rep. 2019 Aug 26 ;9(1):12339. Epub 2019 Aug 26. PMID: 31451704

Abstract Title: 

Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study.

Abstract: 

We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine Hreceptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double-blinded, placebo-controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, includingdecreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.

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Rice bran reduces weight gain and modulates lipid metabolism in rats with high-energy-diet-induced obesity.

PMID: 

Nutrients. 2019 Aug 30 ;11(9). Epub 2019 Aug 30. PMID: 31480353

Abstract Title: 

Rice Bran Reduces Weight Gain and Modulates Lipid Metabolism in Rats with High-Energy-Diet-Induced Obesity.

Abstract: 

Obesity has become an epidemic worldwide. It is a complex metabolic disorder associated with many serious complications and high morbidity. Rice bran is a nutrient-dense by product of the rice milling process. Asia has the world's highest rice production (90% of the world's rice production); therefore, rice bran is inexpensive in Asian countries. Moreover, the high nutritional value of the rice bran suggests its potential as a food supplement promoting health improvements, such as enhancing brain function, lowering blood pressure, and regulating pancreatic secretion. The present study evaluated the anti-obesity effect of rice bran in rats with high-energy diet (HED)-induced obesity. Male Sprague-Dawley rats were randomly divided into one of five diet groups (= 10 per group) and fed the following for eight weeks: Normal diet with vehicle treatment, HED with vehicle, rice bran-0.5X (RB-0.5X) (2% wt/wt rice bran), RB-1.0X (4% wt/wt rice bran), and RB-2.0X (8% wt/wt rice bran). Rice bran (RB-1.0X and RB-2.0X groups) markedly reduced obesity, including body weight and adipocyte size. In addition, treating rats with HED-induced obesity using rice bran significantly reduced the serum uric acid and glucose as well as the liver triglyceride (TG) and total cholesterol (TC). Furthermore, administration of an HED to obese rats significantly affected hepatic lipid homeostasis by increasing phosphotidylcholine (PC; 18:2/22:6), diacylglycerol (DG; 18:2/16:0), DG (18:2/18:1), DG (18:1/16:0), cholesteryl ester (CE; 20:5), CE (28:2), TG (18:0/16:0/18:3), and glycerol-1-2-hexadecanoate 3-octadecanoate. However, the rice bran treatment demonstrated an anti-adiposity effect by partially reducing the HED-induced DG (18:2/18:1) and TG (18:0/16:0/18:3) increases in obese rats. In conclusion, rice bran could act as an anti-obesity supplement in rats, as demonstrated by partially reducing the HED-induced DG and TG increases in obese rats, and thus limit the metabolic diseases associated with obesity and the accumulation of body fat and hepatic lipids in rats.

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Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma.

PMID: 

J Radiat Res. 2019 Aug 29. Epub 2019 Aug 29. PMID: 31504707

Abstract Title: 

Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma†.

Abstract: 

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.

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Habitual mushroom intake might help to prevent prostate cancer.

PMID: 

Int J Cancer. 2019 Sep 4. Epub 2019 Sep 4. PMID: 31486077

Abstract Title: 

Mushroom consumption and incident risk of prostate cancer in Japan: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

Abstract: 

In vivo and in vitro evidence has shown that mushrooms have the potential to prevent prostate cancer. However, the relationship between mushroom consumption and incident prostate cancer in humans has never been investigated. In the present study, a total of 36,499 men, aged 40-79 years, who participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994 were followed for a median of 13.2 years. Data on mushroom consumption (categorized as

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Virgin rice bran oil alleviates hypertension.

PMID: 

Nutrition. 2019 Aug 26 ;69:110575. Epub 2019 Aug 26. PMID: 31585258

Abstract Title: 

Virgin rice bran oil alleviates hypertension through the upregulation of eNOS and reduction of oxidative stress and inflammation in L-NAME-induced hypertensive rats.

Abstract: 

OBJECTIVE: Endothelial dysfunction associated with reduction in nitric oxide (NO) bioavailability plays an important role in development of hypertension. Consumption of a diet rich in antioxidants appears to lower the risk for hypertension. Virgin rice bran oil (VRBO) possesses antioxidant, anti-inflammatory, and hypocholesterolemic activities. However, to our knowledge, the antihypertensive effect of VRBO has not been investigated. The aim of this study was to examine the antihypertensive effect of VRBO in N-nitro-l-arginine methyl ester (L-NAME)-induced hypertensive rats and its underlying mechanisms.METHODS: Hypertension was induced in rats by administration of L-NAME, after which VRBO, lisinopril (Lis), or VRBO + Lis was administered. Studies were then conducted on the hemodynamics of vascular responses to vasoactive substances, plasma angiotensin-converting enzyme (ACE), plasma nitrate/nitrite, oxidative stress, and inflammatory markers.RESULTS: L-NAME administration induced hemodynamic changes including elevation of blood pressure, increased peripheral vascular resistance, and endothelial dysfunction. Reduction in plasma nitrate/nitrite, overproduction of vascular superoxide, and increases in plasma ACE, malondialdehyde, protein carbonyl, and plasma tumor necrosis factor-α were observed in L-NAME hypertensive rats. The changes were associated with a marked decrease in endothelial NO synthase expression, increased expression of gp91and vascular cell adhesion molecule-1, and activation of nuclear factor-κB in aortic tissues. Administration of either VRBO or Lis significantly mitigated all of these deleterious effects. The combination of VRBO and Lis was more effective than either treatment alone.CONCLUSIONS: The antihypertensive effect of VRBO may be mediated by restoration of hemodynamics, increased NO bioavailability, and alleviation of oxidative stress and inflammation. VRBO has an additive effect on antihypertensive medication.

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