title: Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo: Impact on oxidative stress and RANKL/OPG signals.
abstract: Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on the modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt; Chapman University, Irvine 92618, CA, USA.
authors.forename: Mai F
authors.initials: MF
authors.lastname: Tolba
authors.affiliation: Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: Ahmed T
authors.initials: AT
authors.lastname: El-Serafi
authors.affiliation: Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: hanyomar@sharjah.ac.ae.
authors.forename: Hany A
authors.initials: HA
authors.lastname: Omar
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000633:toxicity*; D005938:Glucocorticoids / Q000633:toxicity*; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D053244:Osteoprotegerin / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000633:toxicity; D053245:RANK Ligand / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002109:Caffeic Acids; D005938:Glucocorticoids; D053244:Osteoprotegerin; D053245:RANK Ligand; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Apoptosis; Caffeic acid phenethyl ester; Dexamethasone; GSH; Osteoporosis; SOD