July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Identification of Botanical Extracts with PPARγ Receptor Activity for Improving Meibomian Gland Health and Function.
Author Affiliations & Notes
  • James V Jester
    Gavin Herbert Eye Institute, University of California, Irvine, Irvine, California, United States
  • Sun Woong Kim
    Gavin Herbert Eye Institute, University of California, Irvine, Irvine, California, United States
    Ophthalmology, Yonsei University Wonju College of Medicine, Korea (the Republic of)
  • Yilu Xie
    Gavin Herbert Eye Institute, University of California, Irvine, Irvine, California, United States
  • Dawna Venzon
    Amway Research & Development, Amway Corporation, California, United States
  • Becky L. Bender
    Amway Research & Development, Amway Corporation, California, United States
  • Mary A. Murray
    Amway Research & Development, Amway Corporation, California, United States
  • John F. Rebhun
    Amway Research & Development, Amway Corporation, California, United States
  • Rohit P. Dugar
    Amway Research & Development, Amway Corporation, California, United States
  • Kevin W. Gellenbeck
    Amway Research & Development, Amway Corporation, California, United States
  • Kelly M. Glynn
    Amway Research & Development, Amway Corporation, California, United States
  • Footnotes
    Commercial Relationships   James Jester, None; Sun Woong Kim, None; Yilu Xie, None; Dawna Venzon, Amway Company (E); Becky Bender, Amway Corporation (E); Mary Murray, Amway Corporation (E); John Rebhun, Amway Corporation (E); Rohit Dugar, Amway Corporation (E); Kevin Gellenbeck, Amway Corporation (E); Kelly Glynn, Amway Corporation (E)
  • Footnotes
    Support  NEI R01 EY021510, unrestricted grant from Research to Prevent Blindness, Inc., gift from Amway Corporation.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 280. doi:
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      James V Jester, Sun Woong Kim, Yilu Xie, Dawna Venzon, Becky L. Bender, Mary A. Murray, John F. Rebhun, Rohit P. Dugar, Kevin W. Gellenbeck, Kelly M. Glynn; Identification of Botanical Extracts with PPARγ Receptor Activity for Improving Meibomian Gland Health and Function.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):280.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Peroxisome proliferator activated receptor gamma (PPARγ) has been shown to regulate meibomian gland (MG) differentiation and lipid synthesis. Importantly, PPARγ is down regulated with age suggesting that receptor signaling plays an important role in the development of MG associated evaporative dry eye. While PPARγ is a validated pharmacological target for Diabetes, there are currently no natural PPARγ agonists known to target MG function. The purpose of this study was to screen botanical extracts for PPARγ agonist activity.

Methods : A botanical extract library was screened for PPARγ ligand binding domain activity using a GAL4/UAS luciferase reporter assay in Chinese Hamster Ovary cells. Extracts were screened at 100 µg/mL concentrations, then titered if active. Results were compared to vehicle-control treated cells. Twenty-four extracts from at least 13 species were tested for their effect on lipid synthesis and PPARγ receptor activation using human meibomian gland epithelial cells (gift of D. Sullivan). Cells were plated on collagen coated glass cover slips and treated with extracts or 30 μM rosiglitazone (Rosi) or media alone containing DMEM/F12, 10 ng/ml EGF and 150 μg/ml albumin. After 6 days, cells were fixed and stained with LipidTox and the area of neutral lipid staining quantified. Positive extracts and their phytochemical components were then tested by real-time PCR to identify expression of PPARγ response genes (ADFP, ANGPTL4, PPARγ, ELOVL4).

Results : Five extracts were identified that increased lipid synthesis equal to or greater than that obtained with Rosi, including Loquat Leaf (2 different extracts), Ginger (2 different extracts) and Black Cumin. Further testing showed that Loquat leaf, the most potent inducer (1575% of Rosi), consistently increased gene expression of ADFP, ELOVL4, ANGPTL4, and PPARγ, and that this effect was blocked by the PPARγ antagonist. Testing of known phytochemical components of Loquat leaf (maslinic acid, oleanolic acid and ursolic acid) showed no effect of these phytochemicals on lipid synthesis or PPARγ response gene expression.

Conclusions : Loquat leaf was shown to have specific PPARγ agonist activity that appeared unrelated to major known phytochemical components. Future studies will evaluate these natural materials for their long-term effect on meibomian gland health and function.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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