p,p-hydroxy-curucumin

Dietary Turmeric Bisdemethoxycurcumin Suppresses Wilms' Tumor 1 and CD34 Protein Expressions in KG-1a Leukemic Stem Cells.[Pubmed:30955364]

Nutr Cancer. 2019 Apr 7:1-12.

Leukemic cells remaining in the body is the main problem for cancer patients, and these cells are called Leukemic Stem Cells (LSCs). Many studies have revealed that the overexpression of the Wilms' tumor 1 (WT1) protein is related to leukemogenesis. Curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) from Thai turmeric (Curcuma longa Linn.) are the focus of this study because they have been previously been reported to show potent antileukemic activity. This study aims to investigate the cytotoxic effect of in-house curcuminoids on the human leukemic stem cell line (KG-1a) when compared to other leukemic cell lines (KG-1 and K562). MTT assays were used to determine the cytotoxicity of curcuminoids at various concentrations. Curcumin exhibited the strongest cytotoxic activity on KG-1a cells with IC50 values of 13.6 +/- 1.9 microM. To determine the effect of curcuminoids on WT1 and CD34 protein expressions by Western blotting, KG-1a cells were treated with noncytotoxic concentrations (IC20 value). Bisdemethoxycurcumin showed the strongest suppression of WT1 and CD34 protein expressions with 73.3 +/- 1.4 and 82.9 +/- 2.0%, respectively. In summary, curcuminoids, especially bisdemethoxycurcumin, could inhibit WT1 and CD34 protein expressions. Thus, bisdemethoxycurcumin is a compound that calls for further studies of its process in the inhibition of WT1 and CD34 expressions in LSCs for the leukemia treatment.

Bisdemethoxycurcumin protects against renal fibrosis via activation of fibroblast apoptosis.[Pubmed:30660576]

Eur J Pharmacol. 2019 Mar 15;847:26-31.

Renal fibrosis is the common final outcome of nearly all progressive chronic kidney diseases (CKD) that eventually develop into end-stage renal failure, which threatens the lives of patients. Currently, there are no effective drugs for the treatment of renal fibrosis. However, studies have shown that certain plant natural products have a fibrosis-alleviating effect. Thus, we have screened a large number of natural products for their ability to protect against renal fibrosis and found that bisdemethoxycurcumin has a good therapeutic effect in renal fibrosis according to the data obtained in a mouse model of unilateral ureteral obstruction (UUO). The results indicate that bisdemethoxycurcumin can efficiently attenuate renal fibrosis induced by UUO. Additional studies of the bisdemethoxycurcumin mechanism of action in the treatment of renal fibrosis demonstrated that the therapeutic effect of bisdemethoxycurcumin is mediated by the specific induction of fibroblast apoptosis at a concentration of 20muM. bisdemethoxycurcumin can efficiently protect against renal fibrosis both in vitro and in vivo. This discovery will provide new ideas for renal fibrosis treatment in clinics and a new direction for the development of effective drug therapy of renal fibrosis.

Efflux excretion of bisdemethoxycurcumin-O-glucuronide in UGT1A1-overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 (MRP1) as the glucuronide transporters.[Pubmed:30334318]

Biofactors. 2018 Nov;44(6):558-569.

Bisdemethoxycurcumin (BDMC) was a natural curcuminoid with many bioactivities present in turmeric (Curcuma longa L.). However, the disposition mechanisms of BDMC via uridine 5'-diphospho-glucuronosyltransferase (UGT) metabolism still remain unclear. Therefore, we aimed to determine the potential efflux transporters for the excretion of BDMC-O-glucuronide. Herein, chemical inhibition assays (Ko143, MK571, dipyridamole, and leukotriene C4) and biological inhibition experiments including stable knocked-down of breast cancer resistance protein (BCRP), multidrug resistance-associated proteins (MRPs) transporters were both performed in a HeLa cell line stably overexpressing UGT1A1 established previously. The results indicated that Ko143 (5 and 20 muM) caused a marked reduction in excretion rate (18.4-55.6%) and elevation of intracellular BDMC-O-glucuronide (28.8-48.1%), whereas MK-571 (5 and 20 muM) resulted in a significant decrease in excretion rate (6.2-61.6%) and increase of intracellular BDMC-O-glucuronide (maximal 27.1-32.6%). Furthermore, shRNA-mediated silencing of BCRP transporter led to a marked reduction in the excretion rate (21.1-36.9%) and an obvious elevation of intracellular glucuronide (24.9%). Similar results were observed when MRP1 was partially silenced. In addition, MRP3 and MRP4 silencing both displayed no obvious changes on the excretion rate and intracellular levels of glucuronide. In conclusion, chemical inhibition and gene silencing results both indicated that generated BDMC-O-glucoside were excreted primarily by the BCRP and MRP1 transporters. (c) 2018 BioFactors, 44(6):558-569, 2018.

Inhibitory effects of bisdemethoxycurcumin on mast cell-mediated allergic diseases.[Pubmed:30316076]

Int Immunopharmacol. 2018 Dec;65:182-189.

Most allergic reactions are induced by mast cell activation. Mast cells play vital roles in the pathogenesis of allergic diseases. Bisdemethoxycurcumin (BDMC), a natural curcuminoid, has potential anti-allergic effects. Hence, we explored the effect of BDMC on mast cell-mediated allergic diseases. The study proved that BDMC suppresses beta-hexosaminidase release, granule release, and membrane ruffling in monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukaemia cells (RBL-2H3 cells), and BDMC suppressed ovalbumin (OVA)-induced allergic rhinitis (AR) symptoms and OVA-specific IgE levels in AR mice. Furthermore, BDMC increased the survival of compound 48/80 anaphylaxis shock mice and elevated the decreased rectal temperature in OVA-induced active systemic anaphylaxis mice. These findings indicate that BDMC regulates the degranulation of mast cells, demonstrating its potential in the treatment of mast cell-induced allergic reactions.