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The aim of the present study was to make a polyherbal formulation of three herbs that would offset the negative effects of the high-fat cafeteria diet on rats and the beneficial effects of exercise. The ingredients for this herbal remedy included a water extract of Garcinia cambogia fruit, Trigonella foenum-graecum seed, and Glycyrrhiza glabra root in a 1:1:1 ratio. Nine groups of six male Wistar albino rats were chosen. Animals in Group I were normal and fed a standard diet; animals in Group II were given HFCD to prevent disease; animals in Group III were given HFCD plus exercise; while animals in Groups IV and V were given PHF at doses of 400 and 200 mg/kg p. o. Daily, respectively, in addition to HFCD; while animals in Groups VI and VII were exercised obese rats prevented from gaining more weight had their serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels lowered. HDL cholesterol was raised. Further, the liver biopsy showed increased mononuclear cells; fat globules numbered less; and the enzymes and cells that are regenerating were at lower levels. The polyherbal formulation plus exercise exhibited significant anti-obesity efficacy at 400 mg/kg p. o.; the effect was equivalent to orlistat plus exercise. The research employed HFCD-induced obese rats as a model to investigate the joint effects of PHF and exercise against obesity.

Gut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts ( e.g ., strain LF82) are associated with Crohn's disease. E. coli -LF82 causes fragmentation of the epithelial mitochondrial network, leading to increased epithelial permeability. We hypothesized that butyrate would limit the epithelial mitochondrial disruption caused by E. coli -LF82. Human colonic organoids and the T84 epithelial cell line infected with E. coli -LF82 (MOI = 100, 4 h) showed a significant increase in mitochondrial network fission that was reduced by butyrate (10 mM) co-treatment. Butyrate reduced the loss of mitochondrial membrane potential caused by E. coli -LF82 and increased expression of PGC-1 α mRNA, the master regulator of mitochondrial biogenesis. Metabolomics revealed that butyrate significantly altered E. coli -LF82 central carbon metabolism leading to diminished glucose uptake and increased succinate secretion. Correlating with preservation of mitochondrial network form/function, butyrate reduced E. coli -LF82 transcytosis across T84-cell monolayers. The use of the G-protein inhibitor, pertussis toxin, implicated GPCR signaling as critical to the effect of butyrate, and the free fatty acid receptor three (FFAR3, GPR41) agonist, AR420626, reproduced butyrate's effect in terms of ameliorating the loss of barrier function and reducing the mitochondrial fragmentation observed in E. coli -LF82 infected T84-cells and organoids. These data indicate that butyrate helps maintain epithelial mitochondrial form/function when challenged by E. coli -LF82 and that this occurs, at least in part, via FFAR3. Thus, loss of butyrate-producing bacteria in IBD in the context of pathobionts would contribute to loss of epithelial mitochondrial and barrier functions that could evoke disease and/or exaggerate a low-grade inflammation.

Mitochondrial dysfunction as defined by transcriptomic and proteomic analysis of biopsies or ultra-structure in transmission electron microscopy occurs in inflammatory bowel disease (IBD); however, mitochondrial dynamics in IBD have received minimal attention, with most investigations relying on cell-based in vitro models. We build on these studies by adapting the epithelial cell immunofluorescence workflow to imaging mitochondrial networks in normal and inflamed colonic tissue (i.e., murine di-nitrobenzene sulphonic acid (DNBS)-induced colitis, human ulcerative colitis). Using antibodies directed to TOMM20 (translocase of outer mitochondrial membrane 20) and cytochrome-C, we have translated the cell-based protocol for high-fidelity imaging to examine epithelial mitochondria networks in intact intestine. In epithelia of non-inflamed small or large intestinal tissue, the mitochondrial networks were dense and compact. This pattern was more pronounced in the basal region of the cell compared to that between the nucleus and apical surface facing the gut lumen. In comparison, mitochondrial networks in inflamed tissue displayed substantial loss of TOMM20 + staining. The remaining networks were less dense and fragmented, and contained isolated spherical mitochondrial fragments. The degree of mitochondrial network fragmentation mirrored the severity of inflammation, as assessed by blinded semi-quantitative scoring. As an indication of poor cell 'health' or viability, cytosolic cytochrome-C was observed in enterocytes with highly fragmented mitochondria. Thus, high-resolution and detailed visualization of mitochondrial networks in tissue is a feasible and valuable approach to assess disease, suited to characterizing mitochondrial abnormalities in tissue. We speculate that drugs that maintain a functional remodelling mitochondrial network and limit excess fragmentation could be a valuable addition to current therapies for IBD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)