scholarly journals The Protective Effects of Orthosiphon stamineus Extract Against Intestinal Barrier Injury in High-Fat Diet-Induced Mouse and Oxidative Stress Cell Models

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098534
Author(s):  
Xuan Cai ◽  
Lihui Zhu ◽  
Xiaofeng Yin ◽  
Huiqin Xue ◽  
Changfeng Xiao ◽  
...  

Orthosiphon stamineus Benth. (Lamiaceae) is commonly used for the treatment of kidney diseases, but its role in intestinal barrier function remains unknown. The present study investigated the protective effects of O. stamineus extract (OE) against oxidative stress-induced injury to the small intestinal epithelium and the possible mechanism. High-performance liquid chromatography fingerprinting was used to analyze OE. Oxidative stress was induced by hydrogen peroxide (1 mM for 1 hour) in an IPEC-J2 cell monolayer model and a high-fat diet in C57BL/6 mice (8 weeks). The malondialdehyde (MDA) content was tested in both models. To evaluate permeability, transepithelial electrical resistance (TEER) was tested in a cell model. Serum diamine oxidase (DAO) and endotoxin contents were determined in a mouse model, and histological sections were analyzed. The messenger ribonucleic acid expression of tight junction proteins was measured by quantitative real-time polymerase chain reaction. Pretreatment with OE (50 µg/mL) increased the IPEC-J2 cell monolayer TEER (12.4%) and decreased MDA (from 6.1 to 4.7 mmol/mg prot). Oral administration of OE (100 mg/kg) decreased serum DAO (34.2%), endotoxin (13.4%), and MDA (from 21.3 to 11.0 mmol/mL) in mice. OE upregulated ZO-1 (42.8% in the cell model and 125.0% in mice) and occluding (127.0% in the cell model and 120.3% in mice) gene expression. These results confirmed the protective effect of OE on the intestinal barrier, which was associated with the antioxidant effect of OE; thus, OE is suitable for the prevention and treatment of intestinal barrier injury.

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-ru Su ◽  
Yu-pu Hong ◽  
Fang-chao Mei ◽  
Chen-yang Wang ◽  
Man Li ◽  
...  

Objective. For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. Methods. A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. Result. Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. Conclusion. High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.


2020 ◽  
Vol 75 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Sen Li ◽  
Furong Xian ◽  
Xiao Guan ◽  
Kai Huang ◽  
Wenwen Yu ◽  
...  

2019 ◽  
Author(s):  
Lulu Deng ◽  
Zihao Ou ◽  
Dongquan Huang ◽  
Chong Li ◽  
Zhi Lu ◽  
...  

Abstract Background The study aimed to investigate the differences of different Akkermansia muciniphila (A.muciniphila) genotypes on metabolic protective effects in mice with high-fat diet and explore possible mechanisms. Methods Male C57BL/6 mice were randomly divided into 6 groups, including high-fat diet (HFD)+ A.muciniphila I/II/PBS group, normal chow diet (NCD)+A.muciniphila I/ II /PBS group, respectively. Dietary intervention and A.muciniphila gavage were performed simultaneously. Blood glucose and lipid metabolism, brown adipose morphology and activities, and intestinal barrier function were examined after the mice were sacrificed. Results A.muciniphila gavage improved the impaired glucose tolerance, hyperlipidemia and liver steatosis in HFD mice, and that A.muciniphila II was not as effective as A.muciniphila I. This phenomenon might be because A.muciniphila I intervention significantly inhibited brown adipose tissue whitening and inflammation induced by HFD, by repairing the intestinal barrier and relieving endotoxemia. A.muciniphila II did not display the same results as A.muciniphila I in HFD mice, but had stronger effects in the NCD mice. Conclusions This study mainly reveals the distinct functions of different A.muciniphila genotypes on diet-induced obesity, suggesting that different A.muciniphila genotypes may play inequitable roles in pathological conditions through distinct action pathways.


Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1139 ◽  
Author(s):  
Qihui Luo ◽  
Dongjing Cheng ◽  
Chao Huang ◽  
Yifan Li ◽  
Chengjie Lao ◽  
...  

Background: The damage to intestinal barrier function plays an important role in the development of obesity and associated diseases. Soy isoflavones are effective natural active components for controlling obesity and reducing the level of blood lipid. Here, we explored whether these effects of soy isoflavones were associated with the intestinal barrier function. Methods and Results: The obese rat models were established by high fat diet feeding. Then, those obese rats were supplemented with soy isoflavones at different doses for 4 weeks. Our results showed that obesity induced the expressions of pro-inflammatory cytokines, decreased the anti-inflammatory cytokine (IL-10) expression, elevated intestinal permeability, altered gut microbiota and exacerbated oxidative damages in colon. The administration of soy isoflavones reversed these changes in obese rats, presenting as the improvement of intestinal immune function and permeability, attenuation of oxidative damage, increase in the fraction of beneficial bacteria producing short-chain fatty acids and short-chain fatty acid production, and reduction in harmful bacteria. Furthermore, soy isoflavones blocked the expressions of TLR4 and NF-κB in the colons of the obese rats. Conclusions: Soy isoflavones could improve obesity through the attenuation of intestinal oxidative stress, recovery of immune and mucosal barrier, as well as re-balance of intestinal gut microbiota.


2019 ◽  
Vol 2 (1) ◽  
pp. 9-31 ◽  
Author(s):  
Auroma Ghosh ◽  
Gargi Bose ◽  
Tiyasa Dey ◽  
Palash Kumar Pal ◽  
Sanatan Mishra ◽  
...  

In the current study, it was found that high fat diet (60% of total kCal) (H) or/and isoproterenol (I) exacerbated oxidative stress and caused myocardial damage. This was indicated by increased levels of LPO, PCO, abnormal mitochondria and altered activities of metabolic as well as antioxidant enzymes in myocardium of rats. Melatonin at different doses (10, 20 and 40 mg/kg) effectively protected against myocardial damage induced by H or/and I and preserved all of these altered parameters. Morphological analyses showed that combination of H and I treatment led to the extensive myofibril disintegration and neutrophil infiltration. Melatonin at the dose of 40 mg/kg almost completely prevented these pathological alterations. The mechanistical studies have uncovered that the protective effects of melatonin on the myocardial damage induced by H and I are attributed to its direct and indirect antioxidative capacity, i.e., it directly scavenges free radicals and also regulates the gene expression of antioxidant enzymes. Collectively, based on the evidences gathered from the current study, it will not be unwise to suggest that melatonin can serve as an ideal therapeutic agent for those cardiovascular diseases caused by oxidative stress. 


2011 ◽  
Vol 300 (6) ◽  
pp. E1047-E1058 ◽  
Author(s):  
Christine Ruggiero ◽  
Marilyn Ehrenshaft ◽  
Ellen Cleland ◽  
Krisztian Stadler

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases.


2020 ◽  
Vol 11 (4) ◽  
pp. 3167-3179 ◽  
Author(s):  
Yuxin Cheng ◽  
Ting Wu ◽  
Shuxin Tang ◽  
Fuqiang Liang ◽  
Yajing Fang ◽  
...  

The barrier-improving functions of fermented blueberry pomace (FBP) and its potential mechanism were investigated in this study.


Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2701 ◽  
Author(s):  
Xiao-yu Zhang ◽  
Kang Yi ◽  
Jiang Chen ◽  
Rui-ping Li ◽  
Jie Xie ◽  
...  

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.


Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 55
Author(s):  
Tingyi Du ◽  
Qin Fang ◽  
Zhihao Zhang ◽  
Chuanmeng Zhu ◽  
Renfan Xu ◽  
...  

Aim: Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. Methods: C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). Results: After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. Conclusion: In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.


Sign in / Sign up

Export Citation Format

Share Document