title: Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer.
abstract: A growing body of research suggests daily low-dose aspirin (ASA) reduces heart diseases and colorectal cancers. However, the major limitation to the use of aspirin is its side effect to cause ulceration and bleeding in the gastrointestinal tract. Preclinical studies have shown that ginger constituents ameliorate ASA-induced gastric ulceration. We here report the design and synthesis of a novel prodrug of aspirin, [6]-gingerol aspirinate (GAS). Our data show that GAS exerts enhanced anti-cancer properties in vitro and superior gastroprotective effects in mice. GAS was also able to survive stomach acid and decomposed in intestinal linings or after absorption to simultaneously release ASA and [6]-gingerol. We further present that GAS inactivates both COX-1 and COX-2 equally. Our results demonstrate the enhanced anticancer properties along with gastroprotective effects of GAS, suggesting that GAS can be a therapeutic equivalent for ASA in inflammatory and proliferative diseases without the deleterious effects on stomach mucosa.
authors.affiliation: Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.|Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750004, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, USA.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000138:chemical synthesis; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002396:Catechols / Q000008:administration & dosage* / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005233:Fatty Alcohols / Q000008:administration & dosage* / Q000138:chemical synthesis; D005260:Female; D006801:Humans; D051379:Mice; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002396:Catechols; D005233:Fatty Alcohols; D011355:Prodrugs; C007845:gingerol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin