[10]-Gingerdiols as the Major Metabolites of [10]-Gingerol in Zebrafish Embryos and in Humans and Their Hematopoietic Effects in Zebrafish Embryos

Abstract

Gingerols are a series of major constituents in fresh ginger with the most abundant being [6]-, [8]-, and [10]-gingerols (6G, 8G, and 10G). We previously found that ginger extract and its purified components, especially 10G, potentially stimulate both the primitive and definitive waves of hematopoiesis (blood cell formation) in zebrafish embryos. However, it is still unclear if the metabolites of 10G retain the efficacy of the parent compound towards pathological anemia treatment. In the present study, we first investigated the metabolism of 10G in zebrafish embryos, and then explored the biotransformation of 10G in humans. Our results show that 10G was extensively metabolized in both zebrafish embryos and in humans, in which two major metabolites, (3S,5S)-[10]-gingerdiol and (3R,5S)-[10]-gingerdiol, were identified by analysis of the MSn spectra and comparison to authentic standards that we synthesized. After 24 hours of treatment of zebrafish embryos, 10G was mostly converted to its metabolites. Our results clearly indicate the reductive pathway is a major metabolic route for 10G in both zebrafish embryos and in humans. Furthermore, we investigated the hematopoietic effect of 10G and its two metabolites, which show similar hematopoietic effects as 10G in zebrafish embryos.

Gingerols and shogaols: Important nutraceutical principles from ginger

“…The abilities of both 6-and 8-GN to reduce the levels of intracellular reactive species and ROS imply that these compounds could be used as a skin-whitening agent (Huang et al, 2013). Complete metabolism of 10-GN to (3S,5S)-10-gingerdiol and (3R,5S)-10-gingerdiol was observed in zebrafish embryos and humans after 24 h of treatment (Chen et al, 2013). Both metabolites, as well as 10-GN, displayed hematopoietic effects on zebrafish embryos.…”

The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells

“…Among polyphenolic compounds, zerumbone, a gingerol-related compound, has been shown to inhibit osteoclastogenesis induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) ( 15 ). Recent research has reported that 10-gingerol induces the bone morphogenetic protein signaling pathway in a model of zebra fish ( 16 ). Ginger has been demonstrated to be effective against bone-related disorders such as osteoarthritis ( 17 , 18 ).…”

Targeted therapy of human leukemia xenografts in immunodeficient zebrafish

“…In zebrafish, as in other vertebrates and humans, blood cells are formed from the mesoderm near the aorta, later at the posterior blood island (primitive hematopoiesis) and the caudal hematopoietic tissues (CHT) (definitive hematopoiesis), which forms a transient site of hematopoiesis; blood cells finally migrate to the thymus and pronephros (kidney marrow) 3 – 5 . The development of the hematopoietic stem/progenitor cells (HSPC) is readily accessible by genetic manipulation or chemical modulation in zebrafish 6 – 8 . The conserved mechanism 9 , 10 of HSPC development makes it possible to develop a zebrafish model that supports human hematopoietic and leukemia cells in vivo.…”