Glucuronidated curcumin is completely biologically inactive.
"everybody's competing for the amount of um glucuronidated curcumin because it's completely inactive." (said at 1:14:05)
In direct cellular and molecular assays, glucuronidated curcumin is widely documented to lack the primary antiproliferative, anti-inflammatory, and signaling-inhibition activities seen with free (aglycone) curcumin. However, stating that it is 'completely inactive' requires context: while intrinsically inactive or markedly attenuated at target cellular receptors, curcumin glucuronide serves in vivo as a transport form or prodrug that can undergo deglucuronidation by tissue beta-glucuronidases (e.g., in bone marrow, inflamed sites, or tumor microenvironments) to regenerate active free curcumin.
- supports: Curcumin glucuronides: assessing the proliferative activity against human cell lines. (Bioorganic & medicinal chemistry 2014)
"Biological data revealed that as much as 1 μM curcumin 1 exhibited anticancer activity and almost 100% cell kill was noted at 10 μM on two out of four cell lines; while curcumin mono-glucuronide 2 as well as di-glucuronide 3 displayed no suppression of cell proliferation." (abstract, results, passage verified)
pubmedfull study (doi) - context: Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin… (Biological & pharmaceutical bulletin 2017)
"The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone met… (The Journal of nutritional biochemistry 2019)
"While curcumin inhibited TGFβ-receptor-mediated Smad2/3 phosphorylation in all BCa cells studied (human MDA-SA, MDA-1833, MDA-2287 and murine 4T1 cells), curcumin-glucuronide did not. Similarly, curcumin, but not curcumin-glucuronide, blocked TGFβ-stimulated secretion of PTHrP from MDA-SA and 4T1 cells. Because the predominant serum metabolite, curcumin-glucuronide, lacked bioactivity, we examined tissue-specific metabolism of curcumin in mice." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. (Journal of natural products 2019)
"Consistent with this postulate, aglycone, but not glucuronidated, curcumin inhibited RANKL-stimulated osteoclastogenesis, a key curcumin target in bone." (abstract, results, passage verified)
pubmedfull study (doi)