Bisdemethoxycurcumin

Molecules. 2015 Jan 14;20(1):1277-92.

Bisdemethoxycurcumin Induces apoptosis in activated hepatic stellate cells via cannabinoid receptor 2.[Pubmed: 25594342]

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC in hepatic fibrosis has not been studied thus far in the context of the apoptosis in activated HSCs.
METHODS AND RESULTS:
In the current study, we compared the activities of BDMC and curcumin in the HSC-T6 cell line and demonstrated that BDMC relatively induced a potent apoptosis. BDMC-induced apoptosis was mediated by a combinatory inhibition of cytoprotective proteins, such as Bcl2 and heme oxygenase-1 and increased generation of reactive oxygen species. Intriguingly, BDMC-induced apoptosis was reversed with co-treatment of sr144528, a cannabinoid receptor (CBR) 2 antagonist, which was confirmed with genetic downregulation of the receptor using siCBR2. Additionally, incubation with BDMC increased the formation of death-induced signaling complex in HSC-T6 cells. Treatment with BDMC significantly diminished total intracellular ATP levels and upregulated ATP inhibitory factor-1.
CONCLUSIONS:
Collectively, the results demonstrate that BDMC induces apoptosis in activated HSCs, but not in hepatocytes, by impairing cellular energetics and causing a downregulation of cytoprotective proteins, likely through a mechanism that involves CBR2.

Oncol Lett. 2015 Jan;9(1):270-274. Epub 2014 Nov 7.

Bisdemethoxycurcumin attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction.[Pubmed: 25435973]

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC in hepatic fibrosis has not been studied thus far in the context of the apoptosis in activated HSCs.
METHODS AND RESULTS:
In the current study, we compared the activities of BDMC and curcumin in the HSC-T6 cell line and demonstrated that BDMC relatively induced a potent apoptosis. BDMC-induced apoptosis was mediated by a combinatory inhibition of cytoprotective proteins, such as Bcl2 and heme oxygenase-1 and increased generation of reactive oxygen species. Intriguingly, BDMC-induced apoptosis was reversed with co-treatment of sr144528, a cannabinoid receptor (CBR) 2 antagonist, which was confirmed with genetic downregulation of the receptor using siCBR2. Additionally, incubation with BDMC increased the formation of death-induced signaling complex in HSC-T6 cells. Treatment with BDMC significantly diminished total intracellular ATP levels and upregulated ATP inhibitory factor-1.
CONCLUSIONS:
Collectively, the results demonstrate that BDMC induces apoptosis in activated HSCs, but not in hepatocytes, by impairing cellular energetics and causing a downregulation of cytoprotective proteins, likely through a mechanism that involves CBR2.

Mol Nutr Food Res. 2013 Sep;57(9):1611-8.

Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation.[Pubmed: 23554078]

A key event in the development of plaque in the arteries is the migration and proliferation of smooth muscle cells (SMCs) from the media to the intima of the blood vessel. This study was conducted to evaluate the effects of Bisdemethoxycurcumin (BC), a naturally occurring structural analog of curcumin (CC), on platelet-derived growth factor (PDGF)-stimulated migration and proliferation of SMCs.
METHODS AND RESULTS:
CC and BC were synthesized by condensing acetyl acetone with vanillin and 4-hydroxybenzaldehyde, respectively. SMCs isolated from adult rat aorta were stimulated with PDGF in the presence or absence of CC or BC following which, cell migration and proliferation were assessed by monolayer wound healing assay and [(3) H]-thymidine incorporation respectively. PDGF-stimulated phosphorylation of PDGF receptor-β and its downstream effectors Akt and ERK were assessed by Western blotting. Intracellular reactive oxygen species was assessed using the fluorescent dye 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. BC elicited a concentration-dependent inhibition of PDGF-stimulated phosphorylation of PDGF receptor-β, Akt and Erk as well as the PDGF-stimulated SMC migration and proliferation. BC was more potent than CC in inhibiting migration and proliferation and suppressing PDGF-signaling in SMCs. Both compounds were equipotent in inhibiting PDGF-stimulated generation of intracellular reactive oxygen species.
CONCLUSIONS:
BC may be of potential use in the prevention or treatment of vascular disease.

Phytomedicine. 2009 Apr;16(4):342-51.

Comparative antiulcer effect of bisdemethoxycurcumin and curcumin in a gastric ulcer model system.[Pubmed: 19188055 ]

The antiulcer effect of Bisdemethoxycurcumin, a yellow pigment found mainly in rhizomes of Curcuma longa, was compared with curcumin in gastric ulcer model systems to validate its clinical application as a remedy for peptic ulcer.
METHODS AND RESULTS:
Western blot analysis of mouse macrophage cell line RAW 264.7 activated with lipopolysaccharide showed that Bisdemethoxycurcumin inhibited inducible nitric oxide synthase (iNOS) production significantly but had no effect on tumor necrosis factor-alpha (TNF-alpha) production, whereas curcumin showed stronger suppression of iNOS protein production and inhibited TNF-alpha protein production significantly. However, Bisdemethoxycurcumin and curcumin possessed similar potency in scavenging nitric oxide generated from mouse macrophage cell line RAW 264.7. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that both curcuminoids inhibited the induction of iNOS dose-dependently at the transcriptional level and curcumin also appeared to inhibit the induction of TNF-alpha at post-transcriptional level. In an animal model, intraduodenal administration of Bisdemethoxycurcumin (5-80 mg/kg body wt.) showed a strong inhibitory effect on gastric acid secretion in pylorus-ligated rats whereas curcumin (5-20 mg/kg body wt.) showed a less inhibitory effect, with maximum potency at a dose of 20mg/kg body wt. Moreover, oral administration of Bisdemethoxycurcumin at doses of 20-80 mg/kg body wt. twice daily for 10 days showed a significant curative efficacy in accelerating the healing of acetic acid-induced chronic gastric ulcer and promotion of mucosal regeneration in the ulcerated portion in a dose-related manner with potency equal to curcumin. In contrast, the curative potency of curcumin tended to decrease at doses over 160 mg/kg body wt./day. Western blot analysis in ulcerated gastric mucosa showed that Bisdemethoxycurcumin dose-dependently reduced the increased protein expression level of iNOS but not TNF-alpha.
CONCLUSIONS:
These results indicated that Bisdemethoxycurcumin directly accelerates gastric ulcer healing with potency equal to curcumin. Its antiulcer effect might be due to its properties of decreasing gastric acid secretion and enhancing the mucosal defensive mechanism through suppression of iNOS-mediated inflammation.

Pharmacol Rep. 2013;65(3):700-9.

Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways.[Pubmed: 23950593]

Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin present in the phenolic components extracted from the dried rhizome of Curcuma longa L. BDMC demonstrated potential chemotherapeutic activities but the underlying mechanisms have not been fully clarified. In the present study, the role of reactive oxidative species (ROS) in the anti-cancer effects of BDMC was investigated.
METHODS AND RESULTS:
MCF-7 cells were exposed to BDMC, and then the cell proliferation, colony formation ability and cell cycle profile were analyzed. Cellular ROS level was determined by flow cytometry and fluorescent microscope observation using specific fluorescent probes. Mitochondrial membrane potential (ψm) was assessed using JC-1. In addition, effects of BDMC on senescence-related molecules were analyzed by western blot assay. BDMC significantly inhibited MCF-7 breast cancer cell proliferation, while a rapid rise of the intracellular ROS level accompanied with a reduction of Dym were observed. In addition, BDMC activated the pro-apoptotic protein p53 and its downstream effector p21 as well as the cell cycle regulatory proteins p16 and its downstream effector retinoblastoma protein (Rb). All of these BDMC-induced effects were counteracted with the pre-incubation of the antioxidant N-acetylcysteine (NAC).
CONCLUSIONS:
These results suggested that BDMC-induced ROS accumulation may contribute to its inhibitory effect on MCF-7 cell viability through regulation of p53/p21 and p16/Rb pathways.

Carcinogenesis, 2007, 28(8):1765-73.

Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism[Pubmed: 17522064]

Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs of curcumin (Cur), such as demethoxycurcumin (DMC), Bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones, modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin was investigated. The results indicate that the relative potency for suppression of tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-kappaB) activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-kappaB activation. The suppression of NF-kappaB activity correlated with inhibition of NF-kappaB reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC and BDMC was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-kappaB or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production.
CONCLUSIONS:
Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.