Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone

Nilesh M. Kalariya, Mohammad Shoeb, Aramati B M Reddy, Min Zhang, Frederik J G M van Kuijk, Kota Ramana

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To investigate the anti-inflammatory effects of guggulsterone, an antioxidant and antitumor agent, in endotoxininduced uveitis (EIU) in rats and to elucidate the underlying molecular mechanism or mechanisms related to ocular inflammation. METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS; 150 μg) into Lewis rats treated with guggulsterone (30 mg/kg body weight, intraperitoneally) or its carrier. After 24 hours the rats were killed, eyes were enucleated, and aqueous humor (AqH) was collected. Numbers of infiltrating cells and levels of matrix metalloproteinase-2 (MMP-2), nitric oxide (NO), and prostaglandin E2 (PGE2) were determined in AqH by specific ELISAs. An antibody array was used to measure the expression of various inflammatory cytokines in AqH. The expression of MMP-2, iNOS, Cox-2, phospho-IκB, and phospho-NF-κB was determined immunohistochemically. Human primary nonpigment ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of guggulsterone on the LPS-induced inflammatory response. RESULTS. Compared with control, the EIU rat eye AqH had a significantly higher number of infiltrating cells, total protein, and inflammatory markers, such as MMP-2, NO, and PGE2, and the treatment of guggulsterone prevented EIU-induced increases. Guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins and of IκB and NF-κB in various eye tissues. Moreover, in cultured HNPECs, guggulsterone inhibited LPS-induced expression of inflammatory proteins. CONCLUSIONS. These results for the first time demonstrate that the plant sterol guggulsterone suppresses ocular inflammation in EIU, suggesting that the supplementation of guggulsterone could be a novel approach for the treatment of ocular inflammation.

Original languageEnglish (US)
Pages (from-to)5105-5113
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number10
DOIs
StatePublished - Oct 2010

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Phytosterols
Uveitis
Endotoxins
Aqueous Humor
Matrix Metalloproteinase 2
Inflammation
Dinoprostone
Nitric Oxide
Cell Count
Epithelial Cells
Proteins
pregna-4,17-diene-3,16-dione
Subcutaneous Injections
Antineoplastic Agents
Lipopolysaccharides
Anti-Inflammatory Agents
Antioxidants
Enzyme-Linked Immunosorbent Assay
Body Weight
Cytokines

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone. / Kalariya, Nilesh M.; Shoeb, Mohammad; Reddy, Aramati B M; Zhang, Min; van Kuijk, Frederik J G M; Ramana, Kota.

In: Investigative Ophthalmology and Visual Science, Vol. 51, No. 10, 10.2010, p. 5105-5113.

Research output: Contribution to journalArticle

Kalariya, Nilesh M. ; Shoeb, Mohammad ; Reddy, Aramati B M ; Zhang, Min ; van Kuijk, Frederik J G M ; Ramana, Kota. / Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone. In: Investigative Ophthalmology and Visual Science. 2010 ; Vol. 51, No. 10. pp. 5105-5113.
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T1 - Prevention of endotoxin-induced uveitis in rats by plant sterol guggulsterone

AU - Kalariya, Nilesh M.

AU - Shoeb, Mohammad

AU - Reddy, Aramati B M

AU - Zhang, Min

AU - van Kuijk, Frederik J G M

AU - Ramana, Kota

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N2 - PURPOSE. To investigate the anti-inflammatory effects of guggulsterone, an antioxidant and antitumor agent, in endotoxininduced uveitis (EIU) in rats and to elucidate the underlying molecular mechanism or mechanisms related to ocular inflammation. METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS; 150 μg) into Lewis rats treated with guggulsterone (30 mg/kg body weight, intraperitoneally) or its carrier. After 24 hours the rats were killed, eyes were enucleated, and aqueous humor (AqH) was collected. Numbers of infiltrating cells and levels of matrix metalloproteinase-2 (MMP-2), nitric oxide (NO), and prostaglandin E2 (PGE2) were determined in AqH by specific ELISAs. An antibody array was used to measure the expression of various inflammatory cytokines in AqH. The expression of MMP-2, iNOS, Cox-2, phospho-IκB, and phospho-NF-κB was determined immunohistochemically. Human primary nonpigment ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of guggulsterone on the LPS-induced inflammatory response. RESULTS. Compared with control, the EIU rat eye AqH had a significantly higher number of infiltrating cells, total protein, and inflammatory markers, such as MMP-2, NO, and PGE2, and the treatment of guggulsterone prevented EIU-induced increases. Guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins and of IκB and NF-κB in various eye tissues. Moreover, in cultured HNPECs, guggulsterone inhibited LPS-induced expression of inflammatory proteins. CONCLUSIONS. These results for the first time demonstrate that the plant sterol guggulsterone suppresses ocular inflammation in EIU, suggesting that the supplementation of guggulsterone could be a novel approach for the treatment of ocular inflammation.

AB - PURPOSE. To investigate the anti-inflammatory effects of guggulsterone, an antioxidant and antitumor agent, in endotoxininduced uveitis (EIU) in rats and to elucidate the underlying molecular mechanism or mechanisms related to ocular inflammation. METHODS. EIU was induced by subcutaneous injection of lipopolysaccharide (LPS; 150 μg) into Lewis rats treated with guggulsterone (30 mg/kg body weight, intraperitoneally) or its carrier. After 24 hours the rats were killed, eyes were enucleated, and aqueous humor (AqH) was collected. Numbers of infiltrating cells and levels of matrix metalloproteinase-2 (MMP-2), nitric oxide (NO), and prostaglandin E2 (PGE2) were determined in AqH by specific ELISAs. An antibody array was used to measure the expression of various inflammatory cytokines in AqH. The expression of MMP-2, iNOS, Cox-2, phospho-IκB, and phospho-NF-κB was determined immunohistochemically. Human primary nonpigment ciliary epithelial cells (HNPECs) were used to determine the in vitro efficacy of guggulsterone on the LPS-induced inflammatory response. RESULTS. Compared with control, the EIU rat eye AqH had a significantly higher number of infiltrating cells, total protein, and inflammatory markers, such as MMP-2, NO, and PGE2, and the treatment of guggulsterone prevented EIU-induced increases. Guggulsterone also prevented the expression of MMP-2, iNOS, and Cox-2 proteins and of IκB and NF-κB in various eye tissues. Moreover, in cultured HNPECs, guggulsterone inhibited LPS-induced expression of inflammatory proteins. CONCLUSIONS. These results for the first time demonstrate that the plant sterol guggulsterone suppresses ocular inflammation in EIU, suggesting that the supplementation of guggulsterone could be a novel approach for the treatment of ocular inflammation.

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