• Title, Summary, Keyword: Tetrahydrocurcumin

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Subchronic and Reproductive/Developmental Toxicity Studies of Tetrahydrocurcumin in Rats

  • Majeed, Muhammed;Natarajan, Sankaran;Pandey, Anjali;Bani, Sarang;Mundkur, Lakshmi
    • Toxicological Research
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    • v.35 no.1
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    • pp.65-74
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    • 2019
  • Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

Antiproliferative Effects of Curcumin Analogues;Comparative antiproliferative activities of curcumin, tetrahydrocurcumin, dimethoxycurcumin and bis-demethoxycurcumin in human leukemia HL-60 cells

  • Jeong, Seon-Choong;Chong, Myong-Soo;Koo, Bon-Soon;Pae, Hyun-Ock;Chung, Hun-Taeg;Lee, Ki-Nam
    • Journal of Society of Preventive Korean Medicine
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    • v.11 no.1
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    • pp.1-8
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    • 2007
  • Curcumin and its analogues(Tetrahydrocurcumin THC, demethoxycurcumin ; BDMC and dimethoxycurcumin DiMC) were compared for their ability to inhibit the growth of human leukemia HL-60 cells. The growth of HL-60 cells was inhibited by curcumin, DeMC and DiMC, but not by THC lacking ${\alpha},{\beta}-unsaturated$ carbonyl groups thus suggesting that ${\alpha},{\beta}-unsaturated$ carbonyl groups are crucial for antiproliferative activity. The order of antiproliferative activity was DiMC, curcumin and BDMC indicating that the number of methoxy groups on the aromatic rings of the active compounds plays an important role in enhancing anti-proliferating activity. In comparison with cellular uptake of the active compounds, uptake capacity was found to be highest with DiMC, followed by curcumin and BDMC. Therefore, it is most likely that the differential antiproliferative activities of DiMC, curcumin and BDMC are associated with their capacities of cellular uptake resulting in building up of enough concentration inside the cells.

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Effects of Curcumin Analogues and Metabolite on Oxidative Stress-induced Cytotoxicity in HepG2 Cells (Curcumin 유도체 및 대사체가 산화스트레스에 의한 HepG2 세포 독성에 미치는 영향)

  • Kim, Ki-Byoung;Lee, Su-Kyung;Kwon, Young-Dal;Yeom, Seung-Ryong;Song, Yung-Sun
    • Journal of Korean Medicine Rehabilitation
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    • v.20 no.2
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    • pp.51-61
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    • 2010
  • Objectives : The purpose of this study was to investigate antioxidant effects of curcumin from Curcumae Longae Radix. Methods : Using HepG2 Iiver-like cells, the antioxidant effects of curcumin, one of main components from Curcumae Longae Radix, and its analogues have been evaluated by measuring their effects on cytotoxicity induced by $H_2O_2$. Results : The pre-incubation for 6 hours with curcumin, bis-demethoxycurcumin, or dimethoxycurcumin protected HepG2 cells from $H_2O_2$-induced toxicity in a dose-dependent manner. However, tetrahydrocurcumin, one of curcumin metabolites, did not protect HepG2 cells from $H_2O_2$-induced toxicity. Interestingly, curcumin, bis-demethoxycurcumin, and dimethoxycurcumin were increased in the protein levels of heme oxygenase-1(HO-1) at concentrations that were also effective in cellular protection. In contrast, tetrahydrocurcumin did not induce HO-1 expression. Tin protoporphyrin-IX, an inhibitor of HO-1 activity, significantly abolished cytoprotection afforded by curcumin, bis-demethoxycurcumin and dimethoxycurcumin. Conclusions : These results demonstrate that curcumin, bis-demethoxycurcumin, and dimethoxycurcumin with two conjugated doble bonds on their structures may reduce $H_2O_2$-induced oxidative stress through HO-1 expression. HO-1 induction may be one of antioxidant pathways by which curcumin protects from oxidative stress-induced cytotoxicity.

Suppression of Protein Kinase C and Nuclear Oncogene Expression as Possible Action Mechanisms of Cancer Chemoprevention by Curcumin

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.683-692
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    • 2004
  • Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

Effects of Dimethoxycurcumin, a Synthetic Curcumin Analogue, on Nitric Oxide Production in RAW264.7 Macrophage (Dimethoxycurcumin 및 curcumin 합성유도체가 RAW264.7 대식세포의 nitric oxide 생성에 미치는 효과)

  • Park, Seong-Heak;Shin, Byung-Cheul;Kwon, Young-Dal;Song, Yung-Sun
    • Journal of Korean Medicine Rehabilitation
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    • v.18 no.1
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    • pp.95-110
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    • 2008
  • 목 적 : 급성 및 만성 염증 질환은 iNOS에 의해서 생성된 과량의 NO와 관련이 있다. 따라서 이러한 질병 치료를 목적으로 NO 생성 억제물질 또는 iNOS 발현 차단물질을 개발할 가치가 있다. 본 연구는 대사 안정성을 개선시킨 dimethoxycurcumin (DiMC)이 활성화된 대식세포에서 NO 생성 및 iNOS 발현을 제어할 수 있는지 조사하였다. 방 법 : RAW264.7 세포를 DiMC (양쪽 방향성 고리에 각각 2개의 methoxy group을 가짐), curcumin (양쪽 방향성 고리에 각각 1개의 methoxy group을 가짐), bis-demethoxycurcumin (양쪽 방향성 고리에 methoxy group이 없음; BDMC) 및 tetrahydrocurcumin (양쪽 방향성 고리에 각각 1개의 methoxy group을 가지고 있지만 중앙 7개 탄소 사슬에 이중결합이 없음; THC)로 각각 전처리한 후에 LPS로 자극하였다. 이들 전처리 물질의 효과를 비교하기 위하여, NO 생성, iNOS 발현, NF-kB p65 인산화 및 p65 DNA-binding 활성을 조사하였다. 결 과 : DiMC, curcumin 및 BDMC는 NO 생성, iNOS 발현 및 NF-kB 활성을 억제하였으며, 그 세기에 있어서 DiMC가 가장 크게 관찰되었고 그 다음 curcumin 그리고 BDMC 순으로 관찰되었다. THC는 어떠한 활성도 보이지 못했다. 결 론 :DiMC는 NO 생성 억제, iNOS 발현 차단 및 NF-kB 비활성을 유도할 수 있음을 알 수 있었다. 이러한 효과는 연속된 이중결합 및 methoxy group의 증가와 관련이 있는 것으로 판단된다.

Effect of Curcumin Derivatives on Heme Oxygenase-1 Expression in HT22 Cells (HT22 세포에서 Curcumin 유도체가 Heme Oxygenase-1 발현에 미치는 효과)

  • Cheong, Yong-Kwan;Lee, Yun-Jung;Chun, Hyun-Ja;Ryu, Il-Hwan;Jee, Yeon-Ju;Chae, Gwon-U;Kim, Young-Sook;Shon, Ji-Ue;Kang, Hyun-Gyu;Lee, Sung-Hee;An, Ren-Bo;Chung, Hun-Taeg;Pae, Hyun-Ock
    • YAKHAK HOEJI
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    • v.55 no.4
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    • pp.319-323
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    • 2011
  • Curcumin, of which a critical characteristic is the capacity of crossing the blood-brain barrier, has been reported to induce the expression of neuroprotective heme oxygenase (HO)-1. The aim of this study is to compare HO-1-inducing capacity and neuroprotective activity of curcumin, its demethoxy (demethoxycurcumin, DMC; bis-demethoxycurcumin, BDMC) and hydrogenated derivatives (tetrahydrocurcumin, THC) in mouse hippocampal HT22 cells. Curcumin attenuated glutamate-induced cell death through HO-1 expression. DMC lacking a methoxy group on one of the aromatic rings possessed slightly lower activity in HO-1 expression and neuroprotection than curcumin. Similarly, BDMC, which lacks two methoxy groups on both of the aromatic rings, showed less activity than curcumin. These findings suggest that the presence of methoxy groups on the aromatic ring is required to enhance neuroprotective HO-1 expression. The reduction of the diarylheptadienone chain of curcumin by hydrogen, as in THC, was accompanied by a complete loss of ability to induce HO-1 expression and neuroprotection, suggesting that the conjugated double bonds of the central seven-carbon chain of curcumin may be essential for its ability to induce neuroprotective HO-1 expression. Our findings may provide useful information for further development of neuroprotective HO-1 inducers.