An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome.

Inulin-type fructan CP-A, a predominant polysaccharide in Codonopsis pilosula, demonstrates regulatory effects on immune activity and anti-inflammation. The efficacy of CP-A in treating ulcerative colitis (UC) is, however, not well-established. This study employed an in vitro lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) and an in vivo dextran sulfate sodium (DSS)-induced colitis mouse model to explore CP-A's protective effects against experimental colitis and its underlying mechanisms. We monitored the clinical symptoms in mice using various parameters: body weight, disease activity index (DAI), colon length, spleen weight, and histopathological scores. Additionally, molecular markers were assessed through enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays. Results showed that CP-A significantly reduced reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-1ß, IL-18) in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1, ZO-1, and occludin proteins in NCM460 cells. Correspondingly, in vivo findings revealed that CP-A administration markedly improved DAI, reduced colon shortening, and decreased the production of myeloperoxidase (MPO), malondialdehyde (MDA), ROS, IL-1ß, IL-18, and NOD-like receptor protein 3 (NLRP3) inflammasome-associated genes/proteins in UC mice. CP-A treatment also elevated glutathione (GSH) and superoxide dismutase (SOD) levels, stimulated autophagy (LC3B, P62, Beclin-1, and ATG5), and reinforced Claudin-1 and ZO-1 expression, thereby aiding in intestinal epithelial barrier repair in colitis mice. Notably, the inhibition of autophagy via chloroquine (CQ) diminished CP-A's protective impact against colitis in vivo. These findings elucidate that CP-A's therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagy-mediated NLRP3 inflammasome inactivation. Consequently, inulin-type fructan CP-A emerges as a promising drug candidate for UC treatment.

Assessment of reporting quality of randomized controlled trials investigating the effects of inulin-type fructans supplementation on cardiovascular disease risk factors: A systematic survey.

BACKGROUND: Transparent and detailed reporting of randomized controlled trials (RCTs) is essential to judge its validity and generalizability. We assessed the reporting quality of RCTs examining the effects of inulin-type fructans supplementation on cardiovascular risk factors, before and after the publication of the Consolidated Standards of Reporting Trials (CONSORT) in 2010. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, the Cochrane Library, and CINAHL from inception to May 15, 2022, including the reference lists of selected RCTs. We screened titles and abstracts and extracted the data independently and in duplicate. We included RCTs that investigated the effects of inulin-type fructans on cardiovascular disease risk factors (e.g., low-density lipoprotein cholesterol, triglycerides, fasting blood glucose) in adults (18 years or older). The primary outcomes of this study were: the overall reporting quality of RCTs (defined as the total number of items [0 to 36] present from the CONSORT checklist) published before and after CONSORT; and the study characteristics (e.g., sample size, significance of primary outcome) predictive of the CONSORT score. The secondary outcome was the reporting of each specific item of the CONSORT checklist during pre- and post-CONSORT periods. The mean difference in the total number of reported items in studies published before and after CONSORT were compared using a t-test and Poisson regression to explore the factors associated with overall reporting quality of RCTs. We used Fisher's exact test to compare the adherence to each of the 36 items during pre- and post-CONSORT periods. RESULTS: We identified 1,767 citations from our systematic search, of which 55 were eligible. There was a significant increase in the reporting of CONSORT items (mean difference 8.5, 95% confidence interval [CI] 5.24 to 11.71) between studies published before and after publication of CONSORT. The sole variable that was predictive of better reporting quality of RCTs was whether the study was published before or after CONSORT (incidence rate ratio 1.67, 95% CI 1.40 to 2.02). Completeness of reporting of RCTs only improved in 15 out of 36 items (41.6%) after the publication of CONSORT. CONCLUSION: The completeness of reporting in RCTs investigating inulin-type fructans supplementation on cardiovascular disease risk factors remains inadequate after the publication of CONSORT. Greater adherence to CONSORT by authors and enforcement of CONSORT by journals may improve the quality of reporting among RCTs.

Structural characterization of an inulin neoseries-type fructan from Ophiopogonis Radix and the therapeutic effect on liver fibrosis in vivo.

Ophiopogonis Radix is a well-known Traditional Chinese Medicine and functional food that is rich in polysaccharides and has fructan as a characteristic component. In this study, an inulin neoseries-type fructan designated as OJP-W2 was obtained and characterized from Ophiopogonis Radix, and its potential therapeutic effect on liver fibrosis in vivo were investigated. Structural studies revealed that OJP-W2 had a molecular weight of 5.76 kDa and was composed of glucose and fructose with a molar ratio of 1.00:30.87. Further analysis revealed OJP-W2 has a predominantly lineal (1-2)-linked ß-D-fructosyl units linked to the glucose moiety of the sucrose molecule with (2-6)-linked ß-D-fructosyl side chains. Pharmacological studies revealed that OJP-W2 exerted a marked hepatoprotective effect against liver fibrosis, the mechanism of action was involved in regulating collagen deposition (α-SMA, COL1A1 and liver Hyp contents) and TGF-ß/Smads signaling pathway, alleviating liver inflammation (IL-1ß, IL-6, CCL5 and F4/80) and MAPK signaling pathway, and inhibiting hepatic apoptosis (Bax, Bcl-2, ATF4 and Caspase 3). These data provide evidence for expanding Ophiopogonis Radix-acquired fructan types and advancing our understanding of the specific role of inulin neoseries-type fructan in liver fibrosis therapy.

Effects of inulin-type fructans with different degrees of polymerization on inflammation, oxidative stress and endothelial dysfunction in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with several cardiovascular risk factors. Prebiotics were proposed to beneficially affect risk factors associated with metabolic disorders. The aim of this study was to investigate and compare the effects of inulin-type fructans (ITFs), as well-studied prebiotics, with different degrees of polymerization, on markers of inflammation, oxidative stress and endothelial dysfunction in PCOS patients. DESIGN: A randomized, double-blind, placebo-controlled trial. PATIENTS: Seventy-five PCOS women were randomly assigned to receive 10 g/day of either high-performance inulin (HPI) or oligofructose-enriched inulin (OEI) or placebo for 12 weeks. MEASUREMENTS: Biochemical indices and blood pressure levelswere assessed before and after the intervention. RESULTS: In the intent-to-treat analysis, high-sensitive C-reactive protein (hs-CRP) decreased in HPI and OEI groups, over the 12 weeks, and the changes were significant in the HPI group, compared to placebo (changes from baseline in the HPI group: -0.11 vs. placebo group: 0.004 mg/L [conversion factor to SI units (nmol/L): 9/5238]; p = .007). Serum levels of nitric oxide (NO) increased, and endothelin-1 and total oxidant status decreased in HPI and OEI groups, at the end of the trial; however, these changes were not significantly compared to placebo (p = .07, .36 and .22, respectively). No differences in systolic and diastolic blood pressure were found. Per-protocol analysis (n = 68) yielded consistent results for all endpoints, with the exception that the significant effect of ITFs on serum hs-CRP levels in the unadjusted ITT analysis became nonsignificant in the per-protocol analysis (p = .06). CONCLUSION: A 12-week supplementation with long-chain ITFs had favourable effects on inflammatory status among PCOS patients.

Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

BACKGROUND: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control. METHODS: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation. RESULTS: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF. CONCLUSIONS: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

Clinical Efficacy of Oligofructans from Ophiopogon japonicus in Reducing Atopic Dermatitis Flare-ups in Caucasian Patients.

Atopic dermatitis is a chronic relapsing inflammatory skin disease affecting 15-20% children and 2-10% adults worldwide. Topical treatments include corticosteroids and calcineurin inhibitors, despite frequently observed adverse events such as skin atrophy, itching and burning sensations. Good alternatives that can prolong disease relief in between flare-ups are therefore needed. We conducted a randomized, single-blind, placebo-controlled, multicenter clinical trial in a Caucasian cohort of 90 children and 144 adults with mild-to-moderate atopic dermatitis that applied tested products twice daily for 60 days. A natural active from Ophiopogon japonicus, that improves atopic dermatitis symptoms in vivo, was successful in reducing the SCORing of Atopic Dermatitis (SCORAD), including erythema, pruritus and body surface area in both cohorts. The active also improved patient's quality of life and significantly reduced the number of patients relapsing compared to placebo. We conclude that this treatment could be an effective solution to help control the disease in between flare-ups.

Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: A randomized controlled trial.

SCOPE: Independently, prebiotics and dietary protein have been shown to improve weight loss and/or alter appetite. Our objective was to determine the effect of combined prebiotic and whey protein on appetite, body composition and gut microbiota in adults with overweight/obesity. METHODS AND RESULTS: In a 12 week, placebo-controlled, double-blind study, 125 adults with overweight/obesity were randomly assigned to receive isocaloric snack bars of: (1) Control; (2) Inulin-type fructans (ITF); (3) Whey protein; (4) ITF + Whey protein. Appetite, body composition and gut microbiota composition/genetic potential were assessed. Compared to Control, body fat was significantly reduced in the Whey protein group at 12 wks. Hunger, desire to eat and prospective food consumption were all lower with ITF, Whey protein and ITF + Whey protein compared to Control at 12 wks. Microbial community structure differed from 0 to 12 wks in the ITF and ITF +Whey Protein groups (i.e. increased Bifidobacterium) but not Whey Protein or Control. Changes in microbial genetic potential were seen between Control and ITF-containing treatments. CONCLUSION: Adding ITF, whey protein or both to snack bars improved several aspects of appetite control. Changes in gut microbiota may explain in part the effects of ITF but likely not whey protein.

Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury.

BACKGROUND: Infusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PURPOSE: Evaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). STUDY DESIGN: The hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. METHODS: A. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: VI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. CONCLUSION: VI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.

Effect of prebiotics of Agave salmiana fed to healthy Wistar rats.

BACKGROUND: Inulin and other fructans are synthesized and stored in mezcal agave (Agave salmiana). Fructans provide several health benefits and have excellent technological properties, but only few data report their physiological effect when added in the diet. RESULTS: Here, we studied the physiological effects of fructans obtained from A. salmiana when added in the diet of Wistar rats. Results showed favorable changes on Wistar rats when the fructans was added to their diet, including the decrease of the pH in the feces and the increase of the number of lactic acid bacteria (CFU g-1 ) (Lactobacillus spp. and Bifidobacterium spp.), even these changes were enhanced with the synbiotic diet (fructans plus B. animalis subsp. lactis). Synbiotic diet, developed changes in the reduction of cholesterol and triglycerides concentrations in serum, with statistical differences (P < 0.05). Histological analysis of colon sections showed that synbiotic diet promoted colon cells growth suggesting that fructans from A. salmiana confer beneficial health effects through gut microbiota modulation. CONCLUSION: Our data underline the advantage of targeting the gut microbiota by colonic nutrients like specific structure of fructans from A. salmiana, with their beneficial effects. More studies are necessary to define the role of fructans to develop more solid therapeutic solutions in humans. © 2016 Society of Chemical Industry.

Protective effect ofAgave salmiana fructans in azoxymethane- induced colon cancer in Wistar rats.

Colon cancer is a world concerning disease; it shows a high mortality rate and may be related to eating habits. Studies using inulin-like fructans, which are produced as energy supplies by several plants, have demonstrated a chemo-protective effect of these fructans in colon cancer. However, agavins a structurally different type of fructans from the Agave genus with demonstrated prebiotic effects, have been poorly studied for their possible protective effects in cancer. The aim of the present study was to evaluate the effect ofAgave fructan-rich diets in colon cancer progress using a rat model and "Agave mezcalero potosino" A. salmiana Otto ex Salm Dick, which is widely distributed in Mexico. Results showed a significant decrease (p<0.05) in early lesions of colon cancer (aberrant crypt foci) compared with the control group. These data suggest that fructans from A. salmiana may contribute to a reduction in the risk of colon cancer as well as inulin-like compounds.

Effect of oligofructose supplementation on body weight in overweight and obese children: a randomised, double-blind, placebo-controlled trial.

Limited evidence suggests that the dietary inclusion of oligofructose, an inulin-type fructan with prebiotic properties, may increase satiety and, thus, reduce energy intake and body weight in overweight and obese adults. The aim of the present study was to assess the effect of oligofructose supplementation for 12 weeks on the BMI of overweight and obese children. A total of ninety-seven children aged 7-18 years who were overweight and obese (BMI >85th percentile) were randomly assigned to receive placebo (maltodextrin) or oligofructose (both at an age-dependent dose: 8 g/d for children aged 7-11 years and 15 g/d for children aged 12-18 years) for 12 weeks. Before the intervention, all children received dietetic advice and they were encouraged to engage in physical activity. The primary outcome measure was the BMI-for-age z-score difference between the groups at the end of the intervention. Data from seventy-nine (81%) children were available for analysis. At 12 weeks, the BMI-for-age z-score difference did not differ between the experimental (n 40) and control (n 39) groups (mean difference 0.002, 95% CI - 0.11, 0.1). There were also no significant differences between the groups with regard to any of the secondary outcomes, such as the mean BMI-for-age z-score, percentage of body weight reduction and the difference in total body fat. Adverse effects were similar in both groups. In conclusion, oligofructose supplementation for 12 weeks has no effect on body weight in overweight and obese children.

Agave fructans: their effect on mineral absorption and bone mineral content.

In this study we investigate the effect that Agave fructans as new prebiotics have on mineral absorption improvement. Forty-eight 12-week-old C57BL/6J mice were used in this study. Forty mice were ovariectomized and eight were sham-operated controls. Mice were fed standard diets or diets supplemented with 10% Agave fructans or 10% inulin fructans. Calcium and magnesium were evaluated as well as their excretion in feces. Osteocalcin levels were also measured; femur structure was studied by scanning electron microscopy. Other parameters, such as food intake, body weight, glucose, and short-chain fatty acid content, were recorded. Calcium in plasma and bone increased in Agave fructan groups (from 53.1 to 56 and 85 mg/L and from 0.402 to 0.474 and 0.478 g/g, respectively) and osteocalcin increased in all fructan groups (>50%). Scanning electron microscopy showed that fructans were able to mitigate bone loss. In conclusion, we demonstrated that supplementation with Agave fructans prevents bone loss and improves bone formation.

Antioxidant effect of nondigestible levan and its impact on cardiovascular disease and atherosclerosis.

Levan polysaccharide, a type of fructan, has been shown to favorably affect diabetes type 2 and hypercholesterolemia. Recent reports have indicated that excessive oxidative stress contributes to the development of atherosclerosis linked metabolic syndrome. The objective of this current study was to investigate the possible protection against oxidative stress linked atherosclerosis. A group of twenty four male rats was divided into four subgroups; a normal diet group (Control), normal rats received levan (L), a high-cholesterol diet group (Chol) and a high-cholesterol diet with 5% (w/w) levan group. After the treatment period, the plasma antioxidant enzymes and lipid profiles were determined. Our results show that treatment with levan positively changed plasma antioxidant enzyme activities by increasing superoxide dismutase (SOD) and catalase (CAT) by 40% and 28%, respectively, in heart. Similarly, the treatment of Chol fed groups with levan positively changed lipid profiles by decreasing total cholesterol, triglycerides and LDL-cholesterol by 50%, 38.33% and 64%, respectively. Thus may have potential antioxidant effects and could protect against oxidative stress linked atherosclerosis.

Inhibition effect of dietary inulin and oligofructose on the growth of transplantable mouse tumor.

BACKGROUND: The influence of 15% inulin or oligofructose incorporated in to the basal diet on the growth of transplantable mouse tumor (TLT) was investigated. MATERIAL AND METHODS: This dietary treatment was performed starting at day 7 before tumor transplantation and continued until the end of observation. The results were evaluated by the mortality rates in the ascitic form of tumor, or by twice weekly solid tumor measurements, with vernier caliper. Mortality rates in ascitic tumors and mean solid tumor surface in these experimental groups was compared with those of animals from control groups fed basal diet without supplementary beta (2-1) fructans. RESULTS: The growth of both forms of transplantable mouse tumors was significantly inhibited by the supplementation of the diet with inulin or oligofructose. CONCLUSION: Such a nontoxic dietary treatment appears to be easily used ad without any risk for patients, and is applicable as an adjuvant factor to classical protocols of human cancer therapy.

Serial passage of tumors in mice in the study of tumor progression and testing of antineoplastic drugs.

AKR lymphoma cells derived from spontaneous tumors were serially transplanted at identical inocula. The degree of malignancy and sensitivity to the polysaccharide levan and methotrexate were tested at each transfer by assessing the lag of development of primary and distant tumors and survival of mice. A progressive increase in malignancy, accompanied by a loss of sensitivity to levan, were observed following serial passage of the lymphoma. Sensitivity to methotrexate was not affected. It is reasoned that, since serial passages permit a longer exposure of the tumor cells to selective forces of the internal milieu of the organism, better reflecting the situation in a long-life span animal, spontaneous and serial-passage tumors could serve as models for cancer therapy in humans.