6-Gingerdiols as the Major Metabolites of 6-Gingerol in Cancer Cells and in Mice and Their Cytotoxic Effects on Human Cancer Cells

Abstract

6-Gingerol, a major pungent component of ginger (Zingiber officinale Roscoe, Zingiberaceae), has been reported to have anti-tumor activities. However, the metabolic fate of 6-gingerol and the contribution of its metabolites to the observed activities are still unclear. In the present study, we investigated the biotransformation of 6-gingerol in different cancer cells and in mice, purified and identified the major metabolites from human lung cancer cells, and determined the effects of the major metabolites on the proliferation of human cancer cells. Our results show that 6-gingerol is extensively metabolized in H-1299 human lung cancer cells, CL-13 mouse lung cancer cells, HCT-116 and HT-29 human colon cancer cells, and in mice. The two major metabolites in H-1299 cells were purified and identified as (3R,5S)-6-gingerdiol (M1) and (3S,5S)-6-gingerdiol (M2) based on the analysis of their 1D and 2D NMR data. Both metabolites induced cytotoxicity in cancer cells after 24 hours, with M1 having a comparable effect to 6-gingerol in H-1299 cells.

Therapeutic Effects of 6‐Gingerol, 8‐Gingerol, and 10‐Gingerol on Dextran Sulfate Sodium‐Induced Acute Ulcerative Colitis in Rats

“…In particular, clinical studies have provided evidence that patients with IBD are at a higher risk of developing colorectal cancer (Itzkowitz and Yio, 2004;Samadder et al, 2017). It is worth noting the anticancer activity of gingerols (Lv et al, 2012;Zhu et al, 2017) may provide insight into potential prevention of colorectal cancer. Hence, 6-gingerol, 8-gingerol, and 10-gingerol represent promising alternative drug candidates in the therapy of colitis and prevention of IBD-related colorectal cancer.…”

“…It is well acknowledged that gingerols consist of 6‐gingerol, 8‐gingerol, 10‐gingerol, and 6‐shogaol, which share analogous structural features. Several studies have revealed that gingerols are effective in the treatment of chronic inflammatory diseases and cancer (Fuzer et al ., ; Huang et al ., ; Li et al ., ; Tripathi et al ., ). More recently, it has been reported that 6‐gingerol can suppress the induction of UC in mice, via antioxidant and antiinflammatory activities (Ajayi et al ., ).…”

Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer

“…5). The presence of gingerdiols, ( 3R,5S )-[6]-gingerdiol (M1) and ( 3S,5S )-[6]-gingerdiol (M2), in mice was evidenced by comparing MS/MS fragmentation patterns with published data in our previous studies (Table 1)2425. Under positive ESI mode, GAS was found to be almost intact in the stomach, partly hydrolyzed in the proximal intestine and then fully decomposed in the distal intestine to release 6G and ASA in 2 h after oral administration (Fig.…”

Stereoselective Approach towards the Synthesis of 3R, 5 S Gingerdiol and 3 S, 5 S Gingerdiol

“…These gingerdiols 1 and 2 were also isolated from the seeds of Aframomum Melegueta . Shang and co‐workers reported that, 6‐gingerol undergoes several metabolisms in cancer cells and in mice out of which 3 R , 5 S gingerdiol 1 and 3 S , 5 S gingerdiol 2 isolated as major metabolites . Gingerdiols 1 and 2 are lesser cytotoxic than gingerol but more potent for other biological activities ,…”