Total Flavonoids of Glycyrrhiza uralensis Alleviates Irinotecan-Induced Colitis via Modification of Gut Microbiota and Fecal Metabolism

Irinotecan (CPT-11)-induced gastrointestinal toxicity strongly limits its anticancer efficacy. Glycyrrhiza uralensis Fisch., especially flavonoids, has strong anti-inflammatory and immunomodulatory activities. Herein, we investigate the protective effect of the total flavonoids of G. uralensis (TFGU) on CPT-11–induced colitis mice from the perspective of gut microbiota and fecal metabolism. The body weight and colon length of mice were measured. Our results showed that oral administration of TFGU significantly attenuated the loss of body weight and the shortening of colon length induced by CPT-11. The elevated disease activity index and histological score of colon as well as the up-regulated mRNA and protein levels of TNF-α, IL-1β, and IL-6 in the colonic tissue of CPT-11–treated mice were significantly decreased by TFGU. Meanwhile, TFGU restored the perturbed gut microbial structure and function in CPT-11–treated mice to near normal level. TFGU also effectively reversed the CPT-11–induced fecal metabolic disorders in mice, mainly call backing the hypoxanthine and uric acid in purine metabolism. Spearman’s correlation analysis further revealed that Lactobacillus abundance negatively correlated with fecal uric acid concentration, suggesting the pivotal role of gut microbiota in CPT-11–induced colitis. Since uric acid is a ligand of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, TFGU was further validated to inhibit the activation of NLRP3 inflammasome by CPT-11. Our findings suggest TFGU can correct the overall gut microbial dysbiosis and fecal metabolic disorders in the CPT-11–induced colitis mice, underscoring the potential of using dietary G. uralensis as a chemotherapeutic adjuvant.

Download Full-text

Influence of testosterone on purine metabolism and gout

Andrology and Genital Surgery ◽

10.17650/1726-9784-2021-22-3-11-17 ◽

2021 ◽

Vol 22 (3) ◽

pp. 11-17

Author(s):

T. S. Panevin

Keyword(s):

Uric Acid ◽

Sex Hormones ◽

Metabolic Disorders ◽

Purine Metabolism ◽

The Body ◽

Uric Acid Concentration ◽

Androgen Deficiency ◽

Inflammatory Processes ◽

High Concentrations ◽

Pro Inflammatory Cytokines

Many different factors are involved in the regulation of purine metabolism. An important role is played by the level of sex hormones: high concentrations of androgens lead to a higher, and estrogen – to a lower level of uric acid. However, according to the results of numerous studies, it has been shown that the effect of sex hormones is not limited only to the uric acid concentration. Sex hormones affect inflammatory processes in the body by modulating the production of pro-inflammatory cytokines and regulating the corresponding signaling pathways. Androgen deficiency can lead to obesity and metabolic disorders, which can contribute to the development and course of gout. This review examines the effect of testosterone, as well as the effect of changes in its concentration on the dynamics of purine metabolism and gout.

Download Full-text

Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0005 ◽

2013 ◽

Vol 16 (2) ◽

Cited By ~ 1

Author(s):

Pablo A. Scacchi Bernasconi ◽

Nancy P. Cardoso ◽

Roxana Reynoso ◽

Pablo Scacchi ◽

Daniel P. Cardinali

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

Uric Acid ◽

Plasma Levels ◽

Density Lipoprotein ◽

The Body ◽

High Fat ◽

Testosterone Secretion ◽

Diet Manipulation ◽

The Impact

AbstractCombinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.

Download Full-text

Contributions of Lactobacillus plantarum PC170 administration on the recovery of gut microbiota after short-term ceftriaxone exposure in mice

Beneficial Microbes ◽

10.3920/bm2019.0191 ◽

2020 ◽

Vol 11 (5) ◽

pp. 489-509

Author(s):

R. Cheng ◽

H. Liang ◽

Y. Zhang ◽

J. Guo ◽

Z. Miao ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Lactobacillus Plantarum ◽

Antibiotic Treatment ◽

Recovery Phase ◽

The Body ◽

Faecal Microbiota ◽

Short Term ◽

Host Animal ◽

The Impact

This study aimed to determine the impact of Lactobacillus plantarum PC170 concurrent with antibiotic treatment and/or during the recovery phase after antibiotic treatment on the body weight, faecal bacterial composition, short-chain fatty acids (SCFAs) concentration, and splenic cytokine mRNA expression of mice. Orally administrated ceftriaxone quantitatively and significantly decreased body weight, faecal total bacteria, Akkermansia muciniphila, and Lactobacillus plantarum, and faecal SCFAs concentration. Ceftriaxone treatment also dramatically altered the faecal microbiota with an increased Chao1 index, decreased species diversities and Bacteroidetes, and more Firmicutes and Proteobacteria. After ceftriaxone intervention, these changes all gradually started to recover. However, faecal microbiota diversities were still totally different from control by significantly increased α- and β-diversities. Bacteroidetes all flourished and became dominant during the recovery process. However, mice treated with PC170 both in parallel with and after ceftriaxone treatment encouraged more Bacteroidetes, Verrucomicrobia, and Actinobacteria, and the diversity by which to make faecal microbiota was very much closer to control. Furthermore, the expression of splenic pro-inflammatory cytokine tumour necrosis factor-α mRNA in mice supplemented with PC170 during the recovery phase was significantly lower than natural recovery. These results indicated that antibiotics, such as ceftriaxone, even with short-term intervention, could dramatically damage the structure of gut microbiota and their abilities to produce SCFAs with loss of body weight. Although such damages could be partly recovered with the cessation of antibiotics, the implication of antibiotics to gut microbiota might remain even after antibiotic treatment. The selected strain PC170 might be a potential probiotic because of its contributions in helping the host animal to remodel or stabilise its gut microbiome and enhancing the anti-inflammatory response as protection from the side effects of antibiotic therapy when it was administered in parallel with and after antibiotic treatment.

Download Full-text

ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i3.16485 ◽

2017 ◽

Vol 9 (3) ◽

pp. 282

Author(s):

P. Geetha ◽

B. Lakshman Kumar ◽

U. Indra ◽

B. Pavithra Sheetal

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Antioxidant Status ◽

Activity Index ◽

Disease Activity Index ◽

The Body ◽

Unknown Etiology ◽

Steady Increase ◽

Tissue Samples ◽

Significant Change

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.

Download Full-text

Evaluation of Anti-Obesity Activity, Acute Toxicity, and Subacute Toxicity of Probiotic Dark Tea

Biomolecules ◽

10.3390/biom8040099 ◽

2018 ◽

Vol 8 (4) ◽

pp. 99 ◽

Cited By ~ 2

Author(s):

Wang Ling ◽

Shungeng Li ◽

Xingcai Zhang ◽

Yongquan Xu ◽

Ying Gao ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Metabolic Disorders ◽

The Body ◽

High Fat ◽

Water Group ◽

Subacute Toxicity ◽

Infusion Group ◽

Sd Rats ◽

Group Ii

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.

Download Full-text

Jiaweishaoyao Decoction Alleviates DSS-Induced Ulcerative Colitis via Inhibiting Inflammation

Gastroenterology Research and Practice ◽

10.1155/2020/7182874 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Huixia Qiao ◽

Yahui Huang ◽

Xiaoyan Chen ◽

Long Yang ◽

Yue Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Nlrp3 Inflammasome ◽

Activity Index ◽

Raw264.7 Cells ◽

Spleen Weight ◽

Associated Proteins ◽

Histopathological Score

Purpose. Jiaweishaoyao decoction (JWSYD) is a traditional prescription of Chinese medicine that is initially used for the treatment of diarrhea. This study is aimed at investigating the effects of JWSYD on DSS-induced ulcerative colitis (UC). Methods. DSS-induced UC mice and LPS-induced RAW264.7 cells were used as the UC model in vivo and in vitro. UC was assessed by body weight, disease activity index (DAI), colon length, spleen weight, and histopathological score (HE staining). The levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA and qRT-PCR. The levels of NLRP3 inflammasome- and NF-κB pathway-associated proteins were measured by western blot. Results. JWSYD alleviated DSS-induced UC in respect to body weight, DAI, colon length, spleen weight, and histopathological score. JWSYD reduced the levels of TNF-α, IL-1β, and IL-6 in DSS-induced UC mice and the supernatants of LPS-induced RAW264.7 cells. JWSYD suppressed the protein levels of inflammasome-associated proteins, including NLRP3, ASC1, Procaspase-1, Cleaved caspase-1, and Cleaved IL-1β in DSS-induced UC mice and LPS-induced RAW264.7 cells. In addition, JWSYD suppressed the NF-κB pathway in vitro and in vivo. Conclusion. JWSYD alleviated DSS-induced UC via inhibiting the NLRP3 inflammasome and NF-κB pathway.

Download Full-text

Teasaponin Ameliorates Murine Colitis by Regulating Gut Microbiota and Suppressing the Immune System Response

Frontiers in Medicine ◽

10.3389/fmed.2020.584369 ◽

2020 ◽

Vol 7 ◽

Author(s):

Huan Yang ◽

Rui Cai ◽

Ziyan Kong ◽

Ying Chen ◽

Chen Cheng ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Dietary Intervention ◽

Fecal Microbiota Transplantation ◽

Activity Index ◽

The Body ◽

System Response ◽

Murine Colitis ◽

Mucus Barrier

Background: Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). The effect of teasaponin (TS) on IBD has not been fully elucidated. Here, we aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms.Methods: We applied TS to mice with DSS-induced colitis and then monitored the body weight, disease activity index (DAI) daily. When sacrificed, the intestinal permeability was measured. The analysis of mucin and tight junction proteins was conducted. We detected the inflammatory cytokines, the immune cells and related inflammatory signaling pathways. In addition, the gut microbiota were analyzed by 16S rRNA sequencing and we also performed fecal microbiota transplantation (FMT).Results: It showed that TS ameliorated the colonic damage by lowering the DAI, prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier. Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were also decreased in TS-treated mice. Microbiota characterization showed that Campylobacteria, Proteobacteria, Helicobacter, and Enterobacteriaceae were the key bacteria associated with IBD. In addition, TS could reverse the Firmicutes/Bacteroidetes (F/B) ratio and increase the beneficial bacteria, including Akkermansia and Bacteroides. TS ameliorated DSS-induced colitis by regulating the gut microbiota, and the gut microbiota could regulate gut inflammation.Conclusions: These studies demonstrated that TS ameliorated murine colitis through the modulation of immune response, mucus barrier and gut microbiota, thus improving gut dysbiosis. In addition, the gut microbiota may play an important role in regulating the host's innate immune system, and the two coexist and are mutually beneficial. We provide a promising perspective on the clinical treatment of IBD.

Download Full-text

Effects of theabrownin on serum metabolites and gut microbiome in rats with a high-sugar diet

Food & Function ◽

10.1039/c9fo01334b ◽

2019 ◽

Vol 10 (11) ◽

pp. 7063-7080 ◽

Cited By ~ 5

Author(s):

Suijuan Yue ◽

Dan Zhao ◽

Chunxiu Peng ◽

Chao Tan ◽

Qiuping Wang ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Gut Microbiome ◽

Strong Correlation ◽

The Body ◽

Serum Metabolites ◽

High Sugar

In a high sugar diet mode, TB reduced the body weight and TG and improved HOMA-IR mainly by targeting the gut microbiota. A strong correlation between cecal microorganisms and serum metabolites, obesity and HOMA-IR was observed.

Download Full-text

Exenatide Delays the Progression of Nonalcoholic Fatty Liver Disease in C57BL/6 Mice, Which May Involve Inhibition of the NLRP3 Inflammasome through the Mitophagy Pathway

Gastroenterology Research and Practice ◽

10.1155/2018/1864307 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Ning Shao ◽

Xin-Yang Yu ◽

Xue-Fei Ma ◽

Wen-Jian Lin ◽

Ming Hao ◽

...

Keyword(s):

Body Weight ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Nlrp3 Inflammasome ◽

Fatty Liver Disease ◽

The Body ◽

Control Group ◽

Stress Injury ◽

Nonalcoholic Fatty Liver

Objective. This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. Methods. Thirty male C57BL/6 mice were randomly divided into three groups: control group (n=10), model group (n=10), and Exe (exenatide) group (n=10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. Results. The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1β proteins were suppressed after Exe treatment. Conclusion. We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.

Download Full-text