Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivati...Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.展开更多
Objective To investigate the effects of bisdemethoxycurcumin(BDMC) on non-small cell lung cancer(NSCLC) cell line, A549, and the highly metastatic lung cancer 95 D cells. Methods CCK-8 assay was used to assess the eff...Objective To investigate the effects of bisdemethoxycurcumin(BDMC) on non-small cell lung cancer(NSCLC) cell line, A549, and the highly metastatic lung cancer 95 D cells. Methods CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells. Results BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells(SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine(3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened(SMO) and the transcription factor glioma-associated oncogene 1(Gli1) expression. Furthermore, depletion of Gli1 by si RNA and cyclopamine(a specific SMO inhibitor) induced autophagy. Conclusion Aberrant activation of Hedgehog(Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.展开更多
Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic ...Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic studies of these three curcuminoids are still limited.Objective: To identify the metabolites of curcumin, DMC and BDMC in rats after oral administration of solid lipid nanoparticles(SLNs).Methods: Male Sprague-Dawley rats(250 ± 20 g, body weight) were randomly divided into 4 groups(n=3), and were orally administered with curcumin-SLN, DMC-SLN, BDMC-SLN, or blank-SLN, respectively. Plasma samples(500 μL) via the angular vein were collected at 1, 2 and 4 h post dosing, and the urine and feces samples were collected at 0–12 h and 12–24 h post-intake. An HPLC-DAD-ESI-MSnmethod was developed to identify the metabolites. The structures of phase II metabolites were further confirmed by enzyme hydrolysis.Results: A total of 34 metabolites were identified in rats plasma, urine, and feces. Most of them were phase II metabolites, including glucuronide conjugates and sulfate conjugates. Among them, the glucuronide conjugates were the major metabolites in rats plasma. In the meanwhile, the three parent curcuminoids were detected in high amounts in the urine and feces samples.Conclusion: The possible metabolic pathways of curcuminoids in rats were proposed.展开更多
基金supported by the National Natural Science Foundation of China,No.82002400(to GJZ)Scientific Research Project of Hu nan Health Committee,No.20201911and No.20200469(both to ZJX)+2 种基金Scientific Research Project of Hunan Health Committee,No.20211411761(to HMW)the Natural Science Foundation of Hunan Province,No.2020JJ5512(to GJZ)a grant from Clinical Medical Technology Innovation Guidance Project in Hunan Province,No.2020SK51822(to ZJX)。
文摘Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.
基金supported by a grant from the National Science Foundation(Grant number 81102857)
文摘Objective To investigate the effects of bisdemethoxycurcumin(BDMC) on non-small cell lung cancer(NSCLC) cell line, A549, and the highly metastatic lung cancer 95 D cells. Methods CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells. Results BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells(SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine(3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened(SMO) and the transcription factor glioma-associated oncogene 1(Gli1) expression. Furthermore, depletion of Gli1 by si RNA and cyclopamine(a specific SMO inhibitor) induced autophagy. Conclusion Aberrant activation of Hedgehog(Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.
基金supported by the National Natural Science Foundation of China(Grant No.81222054 and 81302742)State Administration of Traditional Chinese Medicine(No.201307002)the Key Research Project of Department of Education of Sichuan(11ZA005)
文摘Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin(DMC) and bisdemethoxycurcumin(BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic studies of these three curcuminoids are still limited.Objective: To identify the metabolites of curcumin, DMC and BDMC in rats after oral administration of solid lipid nanoparticles(SLNs).Methods: Male Sprague-Dawley rats(250 ± 20 g, body weight) were randomly divided into 4 groups(n=3), and were orally administered with curcumin-SLN, DMC-SLN, BDMC-SLN, or blank-SLN, respectively. Plasma samples(500 μL) via the angular vein were collected at 1, 2 and 4 h post dosing, and the urine and feces samples were collected at 0–12 h and 12–24 h post-intake. An HPLC-DAD-ESI-MSnmethod was developed to identify the metabolites. The structures of phase II metabolites were further confirmed by enzyme hydrolysis.Results: A total of 34 metabolites were identified in rats plasma, urine, and feces. Most of them were phase II metabolites, including glucuronide conjugates and sulfate conjugates. Among them, the glucuronide conjugates were the major metabolites in rats plasma. In the meanwhile, the three parent curcuminoids were detected in high amounts in the urine and feces samples.Conclusion: The possible metabolic pathways of curcuminoids in rats were proposed.
