Nobiletin: efficient and large quantity isolation from orange peel extract

Abstract

It is known that nobiletin possesses anticancer, antiviral and anti-inflammatory activities. Recently, the demand for nobiletin in large quantities and high purity has increased. However, conventional normal-phase silica gel chromatography and C 18 -reverse-phase separation methods cannot satisfy the requirement of pure and gram scale nobiletin in a timely manner. In exploring the composition and the biological activities of polymethoxyflavones from sweet orange (Citrus sinensis) peel, we developed an efficient isolation method for nobiletin. By employing this methodology, pure nobiletin, in gram quantities, was obtained in only one purification cycle. The orange peel extract was loaded onto a silica gel flash column and eluted by a mixed solvent system of ethyl acetate and hexanes, and the fractions collected. Upon combination of the eluted fractions, mainly containing nobiletin and 5,6,7,4′-tetramethoxyflavone, and concentration under reduced pressure, the resultant residue was loaded onto a Regis chiral column. Gram amounts of nobiletin and 5,6,7,4′-tetramethoxyflavone were then eluted with ethanol and hexanes, respectively.

Polymethoxy flavones are responsible for the anti-inflammatory activity of citrus fruit peel

“…Indeed, the fact that the hydrophobic nature of the polymethoxy flavones enables them to cross the intestinal membrane easily, and makes them absorbed more readily into the human body (Li, Wang, Sang, Huang, & Ho, 2006). These results indicate polymethoxy flavones to be promising therapeutic phytochemicals of citrus by-products (Li, Yu, & Ho, 2006).…”

Nobiletin Relaxes Isolated Mesenteric Arteries by Activating the Endothelial Ca²⁺-eNOS Pathway in Rats

“…Polymethoxylated flavones play a role in anticancer and anti-inflammation, as well as in atherosclerosis, cardiovascular dysfunction, and Alzheimer's disease in rats and humans [3,4,31]. Nobiletin is a well-known traditional Chinese medicine or food, and has antitumor, immune stimulation, anti-inflammation, antioxidant, and cardiovascular disease-mitigating properties [3,4].…”

“…Nobiletin is a well-known traditional Chinese medicine or food, and has antitumor, immune stimulation, anti-inflammation, antioxidant, and cardiovascular disease-mitigating properties [3,4]. Recent studies revealed that nobiletin, a clock-enhancing natural polymethoxylated compound, activates ROR nuclear receptors and protects against metabolic syndrome in a clock-dependent manner [32].…”

“…Nobiletin has been widely used as a folk medicine herb for centuries and plays an important role in tumor suppression, immune stimulation, anti-inflammation, antioxidation, and some cardiovascular disease mitigation [3,4]. Nobiletin is a polymethoxylated flavonoid compound (Fig.…”

Preparation of a polymethoxyflavone-rich fraction (PRF) of Citrus sunki Hort. ex Tanaka and its antiproliferative effects

“…Given their biological properties, a rapid, large-scale procedure for separating PMFs is needed (Li, Yu, & Ho, 2006;Raman, Jayaprakasha, Cho, Brodbelt, & Patil, 2005;Wang et al, 2005). It has been reported that Citrus sunki Hort.…”