Written by Joyce Smith, BS. In a 5xFAD mouse model of Alzheimer’s disease, treatment with solid lipid curcumin particles demonstrated greater permeability across the blood brain and provided more anti-amyloid, anti-inflammatory, and neuroprotective effects than regular curcumin.
Alzheimer’s disease (AD), one of the most common age-related neurodegenerative diseases worldwide, is characterized by loss of neurons and ultimately memory loss and cognitive impairment . 1 The aggregation of miss-folded amyloid beta protein(Aß)plaques and hyper-phosphorylated tau (p-tau) are the key players responsible for the neuroinflammation and neurodegeneration seen in AD 2 While several studies have demonstrated benefits of anti-inflammatory drugs in AD treatment 3, curcumin, a potential therapeutic polyphenol with anti-amyloid 4, anti-oxidant 5 , and anti-inflammatory properties 6 has shown promise as a compound that can inhibit the misfolded Aß aggregation and reduce the neuroinflammation present in AD.
Different lipid formulations of curcumin have been developed to enhance its therapeutic potential such as solid lipid curcumin particles (SLCP) with potentially greater permeability, stability, bioavailability and neuroprotection than natural Curcumin (Cur) 7. The present study by Maiti et al 8 was designed to achieve the following: compare the permeability of Cur [65% pure curcumin] and SLCP [26% curcumin] in the brain; compare anti-inflammatory activities of Cur with those of SLCP after acute treatment in 5xFAD mice; and to determine which short-term treatment protocol (2 or 5 days ) with Cur or SLCP would most effectively decrease Aß plaque loads and reduce aberrant neuronal pathology in different brain regions of 5xFAD mice.
One –year-old 5xFAD mice and age-matched wild-type mice were given intraperitoneal injections of SLCP or Cur [50 mg/kg body weight] for 2 or 5 days, then sacrificed, and the brain sections collected and immunolabled for lba-1 and GFAP. The anti-amyloid and anti-inflammatory responses and Aß aggregation inhibition of SLCP and Cur in both in vitro and in vivo models of AD were analyzed.
Both Cur and SLCP permeated the brain in therapeutically significant amounts, decreased Aß plaque loads, and improved neuronal morphology after 5 days of treatment; however, when comparing the permeability of curcumin in different cells of the brain such as 7-DIV primary hippocampal neurons and N2a cells, SLCP appeared to deliver more free curcumin into cells than did the unformulated curcumin. SLCP also tended to confer greater neuroprotective effects compared to the unformulated curcumin in 5xFAD mice. For example, the 5-day treatment saw a significant reduction (≈ 50%) of Aß plaques in prefrontal cortex (PFC) and dentate gyrus (DG) areas in all SLCP and Cur treated mice (p<0.01 and p<0.05 respectively) compared to the untreated 5xFAD mice. There was also a significant decrease (30%) in the number of pyknotic or tangle-like neurons in PDC, CA1 and CA3 subfields of hippocampus for both SLCP and Cur treatments (p<0.01 and p<0.05 respectively).
Evidence of a more impactful 5-day treatment versus a two-day treatment for both SLCP and Cur groups of mice suggests that a longer treatment duration could better optimize the tangible health benefits seen. Evidence of SLCP treatment also suggests that the permeability of SLCP across the blood brain barrier (BBB) is superior to regular curcumin in that it provided more anti-amyloid, anti-inflammatory, and neuroprotection than did Cur in the 5xFAD mouse model of AD; and, therefore, may provide a more efficient and effective treatment for AD.
Source: Maiti, Panchanan, Leela Paladugu, and Gary L. Dunbar. “Solid lipid curcumin particles provide greater anti-amyloid, anti-inflammatory and neuroprotective effects than curcumin in the 5xFAD mouse model of Alzheimer’s disease.” BMC neuroscience 19, no. 1 (2018): 7.
© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). The Creative Commons Public Domain Dedication waiver . (http:/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Posted March 18, 2019.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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