The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

Abstract

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.

The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer

“…Curcumin formulated in pills is therefore highly suitable for the treatment of gastrointestinal malignancies (Sharma et al, 2001;Garcea et al, 2005;Villegas et al, 2008) and for long-term chemopreventive therapy (Anto et al, 1996a;Perkins et al, 2002;Lao et al, 2006;Villegas et al, 2008), particularly in the gastrointestinal tract (Huang et al, 1994;Rao et al, 1995), but ill-suited for the treatment of cancers outside of the gastrointestinal system. For these reasons, curcumin for oral chemotherapy of nongastrointestinal cancers should at least be coadministered with uptakeenhancing agents such as piperine (Shoba et al, 1998;Singh et al, 2013) and turmerones (Yue et al, 2012) or in nanoparticle-encapsulated form (Shaikh et al, 2009) when systemic delivery by a (targeted) drug delivery system is not possible (section II.C.2.a.i). For the treatment of non-gastrointestinal cancers, curcumin is best administered via the intravenous route (Bisht and Maitra, 2009) to achieve maximal systemic concentrations and delivery to the tumor.…”

Curcumin‐free turmeric exhibits anti‐inflammatory and anticancer activities: Identification of novel components of turmeric

“…Besides these activities, turmeric oil present in turmeric has been shown to enhance the bioavailability of curcumin almost sevenfold in humans . This may be because ar‐ turmerones are known to enhance the absorption of curcumin by the cells by modulating the activity of P‐glycoprotein .…”

Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals

“…A total of 29 of the 44 herbal products identified were associated with safety‐related concerns (65.9%) (Table ) . These were grouped according to 3 predominant themes: 1) potentially harmful herb‐drug interactions with a reduction in bioavailability (and thus efficacy) of anticancer agents, or increased drug levels with increased toxicity (15 herbs; 34.1%); 2) directly toxic effects of herbal compounds and metabolites (18 herbs; 40.9%); and 3) enhanced anticancer effects of conventional treatment through either synergy with herbal components or chemosensitization of cancer cells, thereby increasing the response to treatment (7 herbs; 15.9%).…”

“…CYP induction can cause a reduction in bioavailability and subsequently the effectiveness of anticancer agents, whereas enzyme inhibition can increase the risk of toxicity, such as that observed with etoposide, paclitaxel, vinblastine, and vincristine . Additional effects on factors such as intestinal P‐glycoprotein, which inhibits drug absorption, can alter the bioavailability of anticancer drugs such as etoposide . The inhibition of boronic acid–based proteasome inhibitors (eg, bortezomib) or the transport of irinotecan and its metabolite, SN‐38, can increase biliary removal with an increase in the half‐life of the drug; a reduction in organic anion transporting polypeptides can increase the absorption of chemotherapy agents such as etoposide, irinotecan, methotrexate, and paclitaxel; gingko biloba can inhibit paclitaxel metabolism (in vitro); and an increase in the bioavailability or a decrease in the activity of tamoxifen in estrogen‐responsive tumors may occur, as well as a reduction in the drug's active metabolite levels via CYP2D6 inhibition …”