Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement.
Piceatannol (PCT), an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT) were compared with PCT in a gelatin capsule (conventional PCT) in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products.
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Soohwan
S
Yum
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Seongkeun
S
Jeong
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Sunyoung
S
Lee
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Joon
J
Nam
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Wooseong
W
Kim
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Jin-Wook
JW
Yoo
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Min-Soo
MS
Kim
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Bok Luel
BL
Lee
College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Yunjin
Y
Jung
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D014162:Transfection; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002214:Capsules; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D014302:Trinitrobenzenesulfonic Acid; D005780:Gelatin
colitis; colon-targeted delivery; multitarget; piceatannol; polypharmacology