New advances in understanding why ginger/turmeric affect our health Shobha Ghosh, PhD, FAHA Department of Internal Medicine, VCU Medical Center Hunter McGuire VA Medical Center, Richmond, VA
Gut Barrier: Our body’s “ADT” Sign (Prevents invasion of unwanted things)
Consequences of “leaky gut”
Consequences of “leaky gut”
Oral supplementation with Curcumin (the active ingredient of Turmeric) restores the intestinal barrier function • By Increasing IAP – an enzyme that breaks down bacterial endotoxin in the gut (Ghosh SS, Bie J, Wang J, Ghosh S. Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice-- role of intestinal permeability and macrophage activation. PLoS One. 2014;9(9):e108577) • By improving tight junctions between intestinal cells ( Wang J, Ghosh SS, Ghosh S. Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. Am J Physiol Cell Physiol. 2017;312(4):C438-C445 )
Directly Testing the role of IAP Necessary to define the mechanism of action of curcumin • Developed disease prone mice expressing human IAP in the intestine • Fed these mice high fat high cholesterol containing Western Diet for 16 weeks • These IAP expressing mice show the following beneficial effects: Increase in the protective mucin layer o Reduced plasma endotoxin levels o Reduced plasma lipids o Reduced heart disease o Unpublished results from Ghosh Lab
• Our studies with oral curcumin supplementation led us to IAP • Now, using mice expressing high IAP in the intestine, we have the proof that Curcumin, via IAP, prevents metabolic diseases • Are there other “ways” by which dietary components affect the functions of other organs in the body?
Role of Extracellular Vesicles (EV) • EV are released by all cells, including intestinal cells • EV from the intestine can reach the circulation via the lymphatic system • High fat high cholesterol diet increases the number of circulating EV • Increase in IAP expression reduces EV and deficiency of IAP increases it • EV represent a novel means of “communication” between different organs and may be even diet and the body!!
Biological Effects of Plant derived EV Sophie Rome: Biological properties of plant-derived extracellular vesicles. Food Funct., 2019, 10, 529-538
Ginger derived EV improve barrier function Ginger-derived EV Taken up by intestinal bacteria (Lactobacillaceae) Changes the genes in Lactobacillaceae Production of “beneficial” compounds that increase production of anti-inflammatory mediators IMPROVED GUT BARRIER FUNCTION Teng Y et al. Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota. Cell Host Microbe. 24:637-652, 2018
Ginger derived EV reduce alcohol induced liver disease Zhuang et al. Ginger-derived nanoparticles protect against alcohol- induced liver damage. J Extracellular Vesicles, 4:28713, 2015
Ginger derived EV Inhibit Inflammation Chen et al. Exosome-like Nanoparticles from Ginger Rhizome inhibit NLRP3 inflammasome activation. Mol. Pharmaceutics, 16:2690-2699, 2019.
Ginger supplementation increase energy utilization Increase in Brown Adipose tissue Ginger = 500mg/kg fresh ginger/day Wang J et al. Ginger prevents obesity through regulation of energy metabolism and activation of browning in high-fat diet-induced obese mice. J Nutr Biochem. 70:105-115, 2019
Diverse beneficial effects of Ginger
Active compounds in Ginger
Studied targets of active components of Ginger
Summary • Both turmeric and ginger have well known health benefits – extensively demonstrated in ancient Indian and Chinese civilizations • Curcumin is water insoluble and very poorly absorbed – hence the controversy regarding its actions on distant visceral tissues • Our data provides evidence for gut-focused benefits of curcumin – it does not need to be absorbed to provide health benefits!! • Active compounds in ginger are water soluble and very readily absorbed • Number of mechanisms have already been established to demonstrate biological activity – mechanisms defined • More targeted studies needed to establish the role in disease prevention • Novel discovery of plant-derived EV and their systemic effects provide another likely mechanism for modulation of distant organ functions • Plant or Ginger-derived EV are currently being evaluated as a vehicle to deliver drugs – a very exciting area of investigation!!
Thank you for your attention Any Questions???
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