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1.
Molecules ; 29(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39274884

ABSTRACT

Prion diseases, known as a group of fatal neurodegenerative disorders caused by prions, remain incurable despite extensive research efforts. In a recent study, crude extract from Curcuma phaeocaulis Valeton (Cp) showed promising anti-prion efficacy in in vitro and in vivo models, prompting further investigation into their active compounds. We endeavored to identify the chemical constituents of the Cp extract and discover potential anti-prion agents. With the use of centrifugal partition chromatography (CPC), major constituents were isolated from the n-hexane (HX) fraction of the extract in a single step. Spectroscopic analysis confirmed the presence of curcumenone, curcumenol, and furanodienone. Subsequent efficacy testing in a cell culture model of prion disease identified curcumenol and furanodienone as active compounds. This study underscores the potential of natural products in the search for effective treatments against prion diseases.


Subject(s)
Curcuma , Plant Extracts , Curcuma/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Animals , Prions/antagonists & inhibitors , Prion Diseases/drug therapy , Mice , Humans , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification
2.
Phytomedicine ; 133: 155922, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39126921

ABSTRACT

BACKGROUND: Cartilage metabolism dysregulation is a crucial driver in knee osteoarthritis (KOA). Modulating the homeostasis can mitigate the cartilage degeneration in KOA. Curcumenol, derived from traditional Chinese medicine Curcuma Longa L., has demonstrated potential in enhancing chondrocyte proliferation and reducing apoptosis. However, the specific mechanism of Curcumenol in treating KOA remains unclear. This study aimed to demonstrate the molecular mechanism of Curcumenol in treating KOA based on the transcriptomics and metabolomics, and both in vivo and in vitro experimental validations. MATERIALS AND METHODS: In this study, a destabilization medial meniscus (DMM)-induced KOA mouse model was established. And the mice were intraperitoneally injected with Curcumenol at 4 and 8 mg/kg concentrations. The effects of Curcumenol on KOA cartilage and subchondral was evaluated using micro-CT, histopathology, and immunohistochemistry (IHC). In vitro, OA chondrocytes were induced with 10 µg/mL lipopolysaccharide (LPS) and treated with Curcumenol to evaluate the proliferation, apoptosis, and extracellular matrix (ECM) metabolism through CCK8 assay, flow cytometry, and chondrocyte staining. Furthermore, transcriptomics and metabolomics were utilized to identify differentially expressed genes (DEGs) and metabolites. Finally, integrating multi-omics analysis, virtual molecular docking (VMD), and molecular dynamics simulation (MDS), IHC, immunofluorescence (IF), PCR, and Western blot (WB) validation were conducted to elucidate the mechanism by which Curcumenol ameliorates KOA cartilage degeneration. RESULTS: Curcumenol ameliorated cartilage destruction and subchondral bone loss in KOA mice, promoted cartilage repair, upregulated the expression of COL2 while downregulated MMP3, and improved ECM synthesis metabolism. Additionally, Curcumenol also alleviated the damage of LPS on the proliferation activity and suppressed apoptosis, promoted ECM synthesis. Transcriptomic analysis combined with weighted gene co-expression network analysis (WGCNA) identified a significant downregulation of 19 key genes in KOA. Metabolomic profiling showed that Curcumenol downregulates the expression of d-Alanyl-d-alanine, 17a-Estradiol, Glutathione, and Succinic acid, while upregulating Sterculic acid and Azelaic acid. The integrated multi-omics analysis suggested that Curcumenol targeted KDM6B to regulate downstream protein H3K27me3 expression, which inhibited methylation at the histone H3K27, consequently reducing Succinic acid levels and improving KOA cartilage metabolism homeostasis. Finally, both in vivo and in vitro findings indicated that Curcumenol upregulated KDM6B, suppressed H3K27me3 expression, and stimulated collagen II expression and ECM synthesis, thus maintaining cartilage metabolism homeostasis and alleviating KOA cartilage degeneration. CONCLUSION: Curcumenol promotes cartilage repair and ameliorates cartilage degeneration in KOA by upregulating KDM6B expression, thereby reducing H3K27 methylation and downregulating Succinic Acid, restoring metabolic stability and ECM synthesis.


Subject(s)
Chondrocytes , Curcuma , Disease Models, Animal , Mice, Inbred C57BL , Osteoarthritis, Knee , Succinic Acid , Animals , Chondrocytes/drug effects , Chondrocytes/metabolism , Mice , Male , Curcuma/chemistry , Osteoarthritis, Knee/drug therapy , Osteoarthritis, Knee/metabolism , Succinic Acid/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Cell Proliferation/drug effects , Apoptosis/drug effects , Sesquiterpenes/pharmacology , Molecular Docking Simulation , Cartilage, Articular/drug effects , Cartilage, Articular/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Humans
3.
Molecules ; 29(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38338400

ABSTRACT

Curcuma wenyujin is a member of the Curcuma zedoaria (zedoary, Zingiberaceae) family, which has a long history in traditional Chinese medicine (TCM) due to its abundant biologically active constituents. Curcumenol, a component of Curcuma wenyujin, has several biological activities. At present, despite different pharmacological activities being reported, the clinical usage of curcumenol remains under investigation. To further determine the characteristics of curcumenol, the extraction, determination, and bioactivity of the compound are summarized in this review. Existing research has reported that curcumenol exerts different pharmacological effects in regard to a variety of diseases, including anti-inflammatory, anti-oxidant, anti-bactericidal, anti-diabetic, and anti-cancer activity, and also ameliorates osteoporosis. This review of curcumenol provides a theoretical basis for further research and clinical applications.


Subject(s)
Sesquiterpenes , Sesquiterpenes/pharmacology , Curcuma
4.
Anat Rec (Hoboken) ; 306(12): 3189-3198, 2023 12.
Article in English | MEDLINE | ID: mdl-36495299

ABSTRACT

The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy-induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF-κB, MCP-1 and IL-1ß were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT-PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF-κB, MCP-1, IL-1ß, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down-regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up-regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy-induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF-κB signaling pathways.


Subject(s)
Kidney Failure, Chronic , NF-kappa B , Rats , Animals , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha/therapeutic use , Sirtuin 1/metabolism , Kidney Failure, Chronic/drug therapy , Kidney/metabolism , Nephrectomy , RNA, Messenger/metabolism
5.
Front Pharmacol ; 13: 905966, 2022.
Article in English | MEDLINE | ID: mdl-35795557

ABSTRACT

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats' primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.

6.
Pharmacol Res ; 182: 106339, 2022 08.
Article in English | MEDLINE | ID: mdl-35792297

ABSTRACT

Internal organs fibrosis (IOF) is the leading cause of morbidity and mortality in most chronic inflammatory diseases, which is responsible for 45% of deaths due to disease. However, there is a paucity of drugs used to treat IOF, making it urgent to find medicine with good efficacy, low toxic side effects and good prognosis. Essential oils (EOs) extracted from natural herbs with a wide range of pharmacological components, multiple therapeutic targets, low toxicity, and broad sources have unique advantages and great potential in the treatment of IOF. In this review, we summarized EOs and their monomeric components with anti-IOF, and found that they work mainly through inhibiting TGF-ß-related signaling pathways, modulating inflammatory cytokines, suppressing NF-κB, and anti-oxidative stress. The prognostic improvement of natural EOs on IOF was further discussed, as well as the quality and safety issues in the current development of natural EOs. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in anti-IOF.


Subject(s)
Oils, Volatile , Fibrosis , Humans , NF-kappa B , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use
7.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1739-1753, 2022 Apr.
Article in Chinese | MEDLINE | ID: mdl-35534245

ABSTRACT

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and ß-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.


Subject(s)
Curcuma , Neoplasms , China , Curcuma/chemistry , Humans , Liver , Terpenes/pharmacology
8.
Pharmacol Res ; 178: 106154, 2022 04.
Article in English | MEDLINE | ID: mdl-35248698

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease associated with aging, and the number of people affected is rapidly increasing. Abnormally hyperphosphorylated tau filaments and extracellular deposits of amyloid ß-peptides (Aß) fibrils are two important pathological hallmarks of AD. Currently, stopping the production of Aß and blocking its aggregation is the main strategy for the treatment of AD. Turmeric is effective in treating neurodegenerative diseases, but there is no effective way to identify active compounds from their complicated chemical compositions. Instead of using conventional extraction and separation methods with low efficiency and time-consuming, our group tried to use atomic materials in high-throughput chemical screening due to their structural characteristics and the unique advantages of surface atomic. Herein, a novel atomic zinc sites with hierarchical porous carbon (Zn-HPC) was synthesized to quickly screen potential inhibitors of Aß aggregation in turmeric. As-combined Aß@Zn-HPC demonstrates superior storage stability and high selectivity, outperforming the most reported supporters for ligand fishing. Five compounds with strong affinity on Aß@Zn-HPC were selected by high-performance liquid chromatography-hybrid linear ion trap/orbitrap mass spectrometer after incubation with turmeric extract. Finally, it was shown that curcumin and bisdemethoxycurcumin can inhibit Aß aggregation by using thioflavin-T fluorescence assay and biolayer interferometry. A new application for the accurate identification of Aß aggregation inhibitors from turmeric were developed based on the active compounds possessing binding affinity to Aß to inhibit its aggregation. The developed method could provide a promising tool for efficient drug discovery from natural product resources.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Carbon , Humans , Porosity , Zinc/therapeutic use
9.
Bioact Mater ; 13: 23-36, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35224289

ABSTRACT

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-928171

ABSTRACT

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and β-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.


Subject(s)
Humans , China , Curcuma/chemistry , Liver , Neoplasms , Terpenes/pharmacology
11.
Int J Mol Med ; 48(4)2021 10.
Article in English | MEDLINE | ID: mdl-34435650

ABSTRACT

At present, an increasing number of individuals are affected by osteoarthritis (OA), resulting in a heavy socioeconomic burden. OA in knee joints is caused by the release of inflammatory cytokines and subsequent biomechanical and structural deterioration. To determine its anti­inflammatory function, the current study investigated the use of the plant­derived medicine, curcumenol, in OA treatment. Curcumenol was not cytotoxic to ATDC5 chondrocytes and primary chondrocytes, as determined using a cell viability test. When these cells were treated with TNF­α and IL­1ß to induce inflammation, curcumenol treatment inhibited the progression of inflammation by inactivating the NF­κB and MAPK signaling pathways, as well as decreasing the expression levels of MMP3 (as indicated by reverse transcription­quantitative PCR and western blotting). Moreover, to analyze metabolic and catabolic status in high­density and pellet culture, catalytic changes and the degradation of the extracellular matrix induced by TNF­α and IL­1ß, were evaluated by alcian blue staining. These catalytic deteriorations were ameliorated by curcumenol. Using curcumenol in disease management, the mechanical and metabolic disruption of cartilage caused in the destabilization of medial meniscus (DMM) model was prevented in vivo. Thus, curcumenol mitigated inflammation in ATDC5 chondrocytes and primary mice chondrocytes, and also ameliorated OA in a DMM­induced mouse model.


Subject(s)
Chondrocytes/drug effects , Inflammation/drug therapy , Menisci, Tibial/pathology , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Sesquiterpenes/pharmacology , Animals , Cartilage, Articular/drug effects , Cartilage, Articular/metabolism , Cell Survival/drug effects , Chondrocytes/metabolism , Disease Models, Animal , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Inflammation/metabolism , Interleukin-1beta/metabolism , Matrix Metalloproteinase 3/metabolism , Menisci, Tibial/metabolism , Mice , Osteoarthritis/chemically induced , Osteoarthritis/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolism
12.
J Bone Miner Res ; 36(9): 1850-1865, 2021 09.
Article in English | MEDLINE | ID: mdl-33956362

ABSTRACT

Excessive bone resorption induced by increased osteoclast activity in postmenopausal women often causes osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, a safer and more effective treatment is still needed. Here, we found that curcumenol (CUL), an antioxidant sesquiterpene isolated from Curcuma zedoaria, impaired receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in vitro, whereas the osteoblastogenesis of MC3T3-E1 cells was not affected. We further demonstrated that CUL treatment during RANKL-induced osteoclastogenesis promotes proteasomal degradation of TRAF6 by increasing its K48-linked polyubiquitination, leading to suppression of mitogen-activated protein kinases (MAPKs) and NF-κB pathways and the production of reactive oxygen species (ROS). We also showed that inositol polyphosphate multikinase (IPMK) binds with TRAF6 to reduce its K48-linked polyubiquitination under RANKL stimulation. Concurrently, IPMK deficiency inhibits osteoclast differentiation. The binding between IPMK and TRAF6 blocked by CUL treatment was found in our study. Finally, we confirmed that CUL treatment prevented ovariectomy (OVX)-induced bone loss in mice. In summary, our study demonstrates that CUL could impair the stability of TRAF6 enhanced by IPMK and suppress excessive osteoclast activity in estrogen-deficient mice to treat osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).


Subject(s)
Bone Resorption , Osteoporosis , Sesquiterpenes , Animals , Antioxidants/pharmacology , Bone Resorption/drug therapy , Cell Differentiation , Female , Humans , Mice , NF-kappa B/metabolism , Osteoclasts/metabolism , Osteogenesis , Osteoporosis/drug therapy , Ovariectomy , Phosphotransferases (Alcohol Group Acceptor) , RANK Ligand , Sesquiterpenes/pharmacology , TNF Receptor-Associated Factor 6/metabolism
13.
China Pharmacy ; (12): 2209-2213, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-825649

ABSTRACT

OBJECTIVE:To study the analgesic effects of 4 sources of Curcumae Radix decoction pieces (Curcuma wenyujin , C. kwangsiensis ,C. phaeocaulis and C. longa ),and compare the contents of curcumenol in their water extracts. METHODS : Using aspirin as positive control ,acetic acid writhing method was used to investigate the effects of 4 sources of Curcumae Radix decoction pieces water extract on writhing latency and times of writhing in mice. The moisture contents of 4 sources of Curcumae Radix decoction pieces (10 batches of each source ,the same below )were determined according to the drying method in 2015 edition of Chinese Pharmacopoeia (part Ⅳ). The yield of water extract in 4 sources of Curcumae Radix decoction pieces were investigated by hot dipping method ,the contents of curcumenol in water extract of 4 sources of Curcumae Radix decoction pieces were determined by HPLC ,and comparison was conducted. RESULTS :Compared with model group ,aspirin and water extracts of 4 sources of Curcumae Radix decoction pieces could significantly prolong the writhing latency of model mice ,and the water extracts of C. wenyujin and C. phaeocaulis could significantly reduce the writhing times of model mice (P<0.05 or P<0.01). For C. wenyujin ,C. kwangsiensis ,C. phaeocaulis and C. longa ,the contents of moisture were 7.39%-8.80%,7.88%-9.88%,7.66%- 10.5468/ogs.2019.62.6.382 9.86% and 7.68%-10.20%;the average yield of water extract were 46.30%,60.40%,38.65%,42.99%;the average contents of curcumenol in water extract were 0.271,0.066,0.310,0.058 mg/g. Except for a few batches ,the higher the yield of water extract,the higher the content of curcuminol in the same source of Curcumae Radix decoction pieces. CONCLUSIONS :Four sources of Curcumae Radix decoction pieces have analgesic effect. The contents of curcumenol in C. wenyujin and C. phaeocaulis were similar ,and the contents of curcumenol in C. kwangsiensis and C. longa about 1/5 of that in C. phaeocaulis and C. wenyujin .

14.
J Ethnopharmacol ; 213: 48-55, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29102767

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds. OBJECTIVE: This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea. MATERIALS AND METHODS: Repeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the C. zedoaria MeOH extract. The cytotoxic effects of the C. zedoaria MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis. RESULTS: The MeOH extract of C. zedoaria rhizomes exerted a cytotoxic effect on AGS cells (IC50: 96.60 ± 4.87µg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (1), germacrone (2), curzerenone (3), curcumenol (4), and curcuzedoalide (5). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC50 value of 125.11±2.77µM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells. CONCLUSION: These data indicate that curcuzedoalide contributed to the cytotoxicity of C. zedoaria by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Curcuma , Sesquiterpenes/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Curcuma/chemistry , Humans , Rhizome/chemistry , Sesquiterpenes/chemistry , Stomach Neoplasms/drug therapy
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-492720

ABSTRACT

Objective To study the physical-chemical parameters of curcumenol so as to design its optimal preparations. Methods An HPLC method was established to determine the content of curcumenol. Based on the method,the equilibrium solubility, oil/water partition coefficient and stability of curcumenol were investigated. Results The equilibrium solubility in the pure water was 1.93 mg/ml(25℃)and 2.6 mg/ml(37℃),respectively. The oil/water partition coefficient was in the range of 2.2-3.0. Curcumenol solution was unstable at high temperature under light conditions,while pH value showed little effect. Conclusion The analytical method is accurate and reliable. The solubility of curcumenol can be described as strong lipotropic and slightly soluble in water. Nano-formulation and solubilization technologies could improve its bioavailability significantly. Curcumenol should be stored and operated in a dark and cool place.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-845563

ABSTRACT

Objective To study the physical- chemical parameters of curcumenol so as to design its optimal preparations. Methods An HPLC method was established to determine the content of curcumenol. Based on the method, the equilibrium solubility, oil/water partition coefficient and stability of curcumenol were investigated. Results The equilibrium solubility in the pure water was 1.93 mg/ml (25 °C) and 2.6 mg/ml (37°), respectively. The oil/water partition coefficient was in the range of 2.2-3.0. Curcumenol solution was unstable at high temperature under light conditions, while pH value showed little effect. Conclusion The analytical method is accurate and reliable. The solubility of curcumenol can be described as strong lipotropic and slightly soluble in water. Nanoformulation and solubilization technologies could improve its bioavailability significantly. Curcumenol should be stored and operated in a dark and cool place.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-854771

ABSTRACT

Objective: To investigate the chemical constituents in the roots and rhizomes of Curacuma aromtica. Methods: The chemical constituents were separated and purified by silica gel, Sephadex LH-20 column chromatography, preparative HPLC, and so on. Their structures were determined by physicochemical constants and spectral analyses. Results: Seventeen compounds were obtained and identified as curdione (1), β-sitosterol (2), stigmasterol (3), triaconatanoic acid (4), gweicurculactone (5), curcumenol (6), procurcumenol (7), eudesmane-3, 6-dione (8), lupeol (9), curcumin (10), demethoxycurcumin (11), aerugidiol (12), zedoarondiol (13), voleneol (14), uracil (15), curcumol (16), and curcumenone (17). Conclusion: Compounds 4, 5, 8, 9, 14, and 15 are isolated from the plant for the first time.

18.
China Pharmacy ; (12)2007.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-531338

ABSTRACT

OBJECTIVE: To investigate the effect and mechanism of Curcumenol against leukemia and to provide theoretical basis for the development and utilization of Curcumenol.METHODS:Curcumenol liposomes were prepared by mechanical dispersion method and ultrasonic method.MTT method was used to detect the inhibitory effects of Curcumenol and other drug on L1210 proliferation in mice with Lymphocytic leukemia.The apoptosis of L1210 cells induced by Curcumenol was observed under confocal microscope by trypan blue exclusion test and Hoechst 33258/PI double staining.RESULTS: Curcumenol significantly inhibited the proliferation of L1210 cells and induced apoptosis of L1210 cells.CONCLUSION: The anti-tumor effect of Curcumenol is possibly achieved by inducing the apoptosis of L1210 cells.

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