curcumin and xanthorrhizol

Xanthorrhizol (XTZ), a bisabolene sesquiterpenoid, is abundantly found in the plant Curcuma xanthorrhiza Roxb. Traditionally, C. xanthorrhiza is widely used for the treatment of different health conditions, including common fever, infection, lack of appetite, fatigue, liver complaints, and gastrointestinal disorders. XTZ exhibits wide-ranging pharmacological activities, including anticancer, antioxidative, anti-inflammatory, antimicrobial, and antidiabetic activities, in addition to a protective effect on multiple organs. The present review provides detailed findings on the anticancer activities of XTZ and the underlying cellular and molecular mechanisms.. Literature was searched systematically in main databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with keywords "tumor AND xanthorrhizol" or "cancer AND xanthorrhizol".. Studies show that XTZ has preventive and therapeutic activities against different types of cancer, including breast, cervical, colon, liver, lung, oral and esophageal, and skin cancers. XTZ regulates multiple signaling pathways that block carcinogenesis and proliferation. In vitro and in vivo studies showed that XTZ targets different kinases, inflammatory cytokines, apoptosis proteins, and transcription factors, leading to the suppression of angiogenesis, metastasis, and the activation of apoptosis and cell cycle arrest.. The potential anticancer benefits of XTZ recommend further in vivo studies against different types of cancer. Further, XTZ needs to be confirmed for its toxicity, bioavailability, protective, antifatigue, and energy booster activities. Future studies for the therapeutic development of XTZ may be directed to cancer-related fatigue.

Topics: Antineoplastic Agents; Curcuma; Fatigue; Humans; Phenols

Xanthorrhizol (XNT), is a bioactive compound found in Curcuma xanthorrhiza Roxb. This study aimed to determine the potential targets of the XNT via computational target fishing method. This compound obeyed Lipinski's and Veber's rules where it has a molecular weight (MW) of 218.37 gmol

Topics: Binding Sites; Blood-Brain Barrier; Computational Biology; Curcuma; Cyclin-Dependent Kinase 2; Gene Expression; Half-Life; Humans; Molecular Docking Simulation; Molecular Weight; Phenols; Protein Interaction Maps; Proteins

Topics: Animals; Cell Adhesion Molecules; Curcuma; Female; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Mice; Neovascularization, Pathologic; NF-kappa B; Nitric Oxide Synthase Type III; Phenols; Phosphatidylinositol 3-Kinases; Phytotherapy; Proto-Oncogene Proteins c-akt; Signal Transduction; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Xanthorrhizol (XTZ), isolated from Curcuma xanthorrhiza, has potent antifungal and antibacterial activity. It shows very strong activity against Gram-positive bacteria, such as Streptococcus mutans and Staphylococcus aureus, but is generally not active against Gram-negative bacteria. In this study, we explored the possibility of using a combination strategy for expanding the antimicrobial spectrum of XTZ against Gram-negative bacteria. To take advantage of XTZ being a food-grade material, 10 food-grade or generally recognized as safe (GRAS) antimicrobial compounds with low toxicities were selected for combination therapy. In addition, polymyxin B nonapeptide (PMBN), which is less toxic than polymyxin B, was also selected as an outer membrane permeabilizer. The antibacterial activity of various double or triple combinations with or without XTZ were assayed in vitro against four Gram-negative bacterial species (Escherichia coli, Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Vibrio cholerae), with synergistic combinations exhibiting clear activity subjected to further screening. The combinations with the greatest synergism were XTZ + PMBN + nisin, XTZ + PMBN + carvacrol, and XTZ + PMBN + thymol. These combinations also showed potent antimicrobial activity against Shigella spp., Yersinia enterocolitica, and Acinetobacter baumannii. In time-kill assays, the three combinations achieved complete killing of E. coli within 2 h, and S. Typhi and V. cholera within 15 min. This is the first report on expanding the activity spectrum of XTZ against Gram-negative bacteria through combination with PMBN and food-grade or GRAS substances, with the resulting findings being particularly useful for increasing the industrial and medical applications of XTZ.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Curcuma; Cymenes; Drug Combinations; Drug Synergism; Escherichia coli; Gram-Negative Bacteria; Microbial Sensitivity Tests; Monoterpenes; Nisin; Phenols; Polymyxin B; Salmonella typhi; Salmonella typhimurium; Vibrio cholerae; Yersinia enterocolitica

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Curcuma; Fibroblasts; Gene Expression; Humans; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Molecular Structure; Osteoclasts; Osteogenesis; Phenols; Plant Extracts; RANK Ligand; RAW 264.7 Cells

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone.

Topics: Alveolar Bone Loss; Animals; Anti-Inflammatory Agents; Bone Remodeling; Curcuma; Disease Models, Animal; Gene Expression; Gingiva; Inflammation; Lipopolysaccharides; Male; Osteoblasts; Osteogenesis; Periodontitis; Phenols; Plant Extracts; Rats; Rats, Sprague-Dawley

The purpose of this study was to investigate the activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. on Candida albicans biofilms at adherent, intermediate, and mature phase of growth. C. albicans biofilms were formed in flat-bottom 96-well microtiter plates. The biofilms of C. albicans at different phases of development were exposed to xanthorrhizol at different concentrations (0.5 µg/mL-256 µg/mL) for 24 h. The metabolic activity of cells within the biofilms was quantified using the XTT reduction assay. Sessile minimum inhibitory concentrations (SMICs) were determined at 50% and 80% reduction in the biofilm OD₄₉₀ compared to the control wells. The SMIC₅₀ and SMIC₈₀ of xanthorrhizol against 18 C. albicans biofilms were 4--16 µg/mL and 8--32 µg/mL, respectively. The results demonstrated that the activity of xanthorrhizol in reducing C. albicans biofilms OD₄₉₀ was dependent on the concentration and the phase of growth of biofilm. Xanthorrhizol at concentration of 8 µg/mL completely reduced in biofilm referring to XTT-colorimetric readings at adherent phase, whereas 32 µg/mL of xanthorrhizol reduced 87.95% and 67.48 % of biofilm referring to XTT-colorimetric readings at intermediate and mature phases, respectively. Xanthorrhizol displayed potent activity against C. albicans biofilms in vitro and therefore might have potential therapeutic implication for biofilm-associated candidal infections.

Topics: Antifungal Agents; Biofilms; Candida albicans; Curcuma; Microbial Sensitivity Tests; Phenols; Plant Extracts; Rhizome

The aim of this study was to investigate the effects of xanthorrhizol (5-(1,5-dimethyl-4-hexenyl)-2-methylphenol, XA) in a mouse model of dextran sulfate sodium (DSS)-induced colitis.. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7days. XA (10 or 100mg/kg) was administered orally once a day, together with the DSS. We evaluated body weight, colon length, histological changes, and myeloperoxidase (MPO) activity. A cDNA microarray was used to assess the gene expression profiles that were affected by XA and DSS treatment and a co-citation analysis was used to examine the biological relationship between XA-responsive genes and colitis.. Decreased body weight, shortened colon length, and damaged colon were observed in the group that was exposed to DSS. Oral administration of XA (10 or 100mg/kg) rescued these symptomatic and histopathological features. The DSS-induced increase in MPO activity, which was used as an index of neutrophil infiltration, was significantly decreased after treatment with XA. Microarray analysis revealed that XA treatment regulated the expression of 34 genes that were altered by exposure to DSS, and that these XA-responsive genes were associated with colonic inflammation. Furthermore, co-citation analysis and graphing of XA-responsive genes revealed a network associated with the gene that encodes for MPO.. These results suggest that XA attenuates acute DSS-induced colitis, possibly by modulating the expression of genes mostly associated with colonic inflammation.

Topics: Animals; Colitis; Curcuma; Dextran Sulfate; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Male; Mice; Mice, Inbred BALB C; Phenols; Plant Extracts

Matrix metalloproteinases (MMPs) are key regulators of the skin photoaging process that is set in motion by exposure to ultraviolet (UV) irradiation. This skin damage results from UV-induced generation of reactive oxygen species, which are associated with upregulation of MMPs and decreased collagen synthesis. We investigated the effects of xanthorrhizol, isolated from Curcuma xanthorrhiza, on the expression of MMP-1 and type-I procollagen in UV-irradiated human skin fibroblasts. Fibroblasts cultured in the presence or absence of purified xanthorrhizol or C. xanthorrhiza extract were irradiated with UV (20 mJ/cm(2)), and MMP-1 and type-I procollagen levels were measured using Western blot analysis. Xanthorrhizol (0.001-0.1 microM) and C. xanthorrhiza extract (0.01-0.5 microg/mL) induced a significant, dose-dependent decrease in the expression of MMP-1 protein, and increased the expression of type-1 procollagen. At a concentration of 0.1 microM, xanthorrhizol nearly completely abrogated MMP-1 expression. The MMP-1-suppressing and type-1 procollagen-inducing effects of xanthorrhizol treatment were greater than those of epigallocatechin 3-O-gallate (EGCG), which is known to be a natural anti-aging agent. These results suggest that xanthorrhizol is a potential candidate for the prevention and treatment of skin aging.

Topics: Cell Survival; Cells, Cultured; Collagen Type I; Curcuma; Dose-Response Relationship, Drug; Fibroblasts; Humans; Matrix Metalloproteinase 1; Molecular Structure; Phenols; Skin; Ultraviolet Rays

Candida species are responsible for the fourth most common nosocominal bloodstream infection. Xanthorrhizol, a sesquiterpene compound isolated from Curcuma xanthorrhiza Roxb. has been reported to have anticandidal activity. The aim of this study is to investigate the synergistic anticandidal effect of xanthorrhizol in combination with ketoconazole or amphotericin B against Candida albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis, and Candida tropicalis. Mostly, xanthorrhizol in combination with ketoconazole or amphotericin B exhibited the synergistic anticandidal effects against all species of Candida tested. In combination with xanthorrhizol, the concentration of ketoconazole or amphotericin B for inhibiting the growth of the tested Candida species could be reduced by >/=50%. Time-kill curves showed that 1/2 minimum inhibitory concentration (MIC) dose of xanthorrhizol, amphotericin B, or ketoconazole alone against each of the six Candida species did not inhibit the growth of all Candida species tested. However, 1/2 MIC dose of xanthorrhizol in combination with 1/2 MIC dose of ketoconazole or 1/2 MIC dose of amphotericin B exhibited growth inhibition of all Candida species tested and reduced viable cells by several logs within 4 h. These results support the potential use of xanthorrhizol as an anticandidal agent, and it can be used complementarily with other conventional antifungal agents.

Topics: Amphotericin B; Antifungal Agents; Candida; Colony Count, Microbial; Curcuma; Drug Synergism; Ketoconazole; Microbial Sensitivity Tests; Microbial Viability; Molecular Structure; Phenols; Time Factors

Plant-derived estrogen-like compounds, or phytoestrogens, are given much attention due to their potential therapeutic use. In this study, xanthorrhizol, a natural sesquiterpenoid isolated from the rhizome of Curcuma xanthorrhiza ROXB. (Zingiberaceae), was evaluated for its estrogenic activity. It has been known that compounds acting as ligands for estrogen receptors (ERs) are considered to possess estrogenic activity. Therefore, the Gal-4/ER transactivation assay in transiently transfected African green monkey kidney (COS-7) cells was used to examine the estrogenic activity of xanthorrhizol. Both subtypes of ERs, ERalpha and ERbeta, were involved in this assay. Further transactivation assays and pS2 mRNA analysis were also conducted in estrogen receptor-positive human breast cancer (MCF-7). Our results showed that xanthorrhizol significantly increased Gal-4/ER luciferase activity in a dose-dependent manner and induced the endogenous ER-estrogen response element (ERE) interaction in MCF-7 cells. Xanthorrhizol also significantly enhanced the expression of the pS2 gene in MCF-7 cells. In contrast, treatment using ICI 182780, an ER antagonist, suppressed all activities induced by xanthorrhizol, indicating ER-dependant activities were involved. These results suggest that xanthorrhizol possesses estrogenic activity and its estrogenic effects are mediated by estrogen-induced gene expression.

Topics: Animals; Base Sequence; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; Curcuma; DNA Primers; Estradiol; Estrogen Receptor Modulators; Estrogens; Fulvestrant; Humans; Phenols; Reverse Transcriptase Polymerase Chain Reaction

Xanthorrhizol, isolated from the ethanol extract of Curcuma xanthorrhiza Roxb., is a sesquiterpene compound with a molecular weight of 218. The aim of this study was to investigate the antibacterial activity of xanthorrhizol against foodborne pathogens. The antibacterial activity of xanthorrhizol was measured in terms of the MIC and the MBC. MICs and MBCs of xanthorrhizol against Bacillus cereus, Clostridium perfringens, Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium, and Vibrio parahaemolyticus were 8, 16, 8, 8, 16, 8 microg/ml and 16, 32, 16, 16, 16, 16 microg/ml, respectively. The bactericidal study, as determined by the viable cell count method, revealed that xanthorrhizol treatment at 4 x MIC reduced viable cells by at least 6 to 8 log for all six foodborne pathogens in 4 h. Xanthorrhizol maintained its antibacterial activity after thermal treatments (121 degrees C, 15 min) under various pH ranges (pH 3.0, 7.0, and 11.0). These results strongly suggest that xanthorrhizol, conferring strong antibacterial activity with thermal and pH stability, can be effectively used as a natural preservative to prevent the growth of foodborne pathogens.

Topics: Anti-Bacterial Agents; Bacteria; Colony Count, Microbial; Curcuma; Dose-Response Relationship, Drug; Food Preservation; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Molecular Weight; Phenols; Plant Extracts

Solvolysis reaction of methyl (4S,5S)-4-(4'-methoxyphenyl)-5-tosyloxy-2(E)-hexenoate 5 in water-saturated MeNO(2) gave the 1,2-migration product, (4S,5S)-5-hydroxy-4-(4'-methoxyphenyl)-2-(E)-hexenoate 6 (55% yield), which was converted to methyl (R)-(4'-methylphenyl)hexanoate 11 in 25% overall yield (5 steps). Treatment of (R)-11 with MeLi gave tertiary alcohol congener 12, which was subjected to dehydration to afford (R)-(-)-curcumene 1. An introduction of hydroxyl group at meta-position of the aromatic ring in (R)-11 was achieved based on consecutive treatment [1) selective iodination, 2) conversion of aryl iodide to aryl boronate, 3) conversion of aryl boronate to phenol]. Thus obtained phenol (R)-16 was treated with MeLi to give tertiary alcohol congener 17, which was subjected to dehydration to afford (R)-(-)-xanthorrizol 2.

Topics: Boronic Acids; Cations; Chromatography, Thin Layer; Curcumin; Indicators and Reagents; Iodides; Magnetic Resonance Spectroscopy; Phenols; Sesquiterpenes; Solvents

Xanthorrhizol was isolated from the rhizome of Curcuma xanthorrhiza (Zingiberaceae) and its in vitro activity against opportunistic filamentous fungi was evaluated using the NCCLS (M38-A) standard method. Xanthorrhizol was found to be active against all the species tested, namely Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium oxysporum, Rhizopus oryzae and Trichophyton mentagrophytes: the MICs being 2.0, 2.0, 2.0, 4.0, 1.0 and 1.0 microg/mL, while the MFCs were 4.0, 4.0, 4.0, 8.0, 2.0 and 2.0 microg/mL, respectively. The susceptibility of six species of filamentous fungi to xanthorrhizol was comparable to that of the commercial antifungal, amphotericin B. Xanthorrhizol also has activity to inhibit the conidial germination of all tested species. The results strongly suggest that xanthorrhizol can be developed as a natural antifungal agent.

Topics: Antifungal Agents; Aspergillus; Curcuma; Fusarium; Microbial Sensitivity Tests; Phenols; Rhizome; Rhizopus; Trichophyton

This study aimed at investigating the anti-Malassezia activity of xanthorrhizol (XTZ) isolated from Curcuma xanthorrhiza Roxb. against Malassezia furfur ATCC 14521 and Malassezia pachydermatis ATCC 14522.. The in vitro susceptibility tests for XTZ were carried out in terms of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), using broth microdilution method with endpoint after 48 h. Time-kill curves were determined at concentrations ranging from 0 to 25 microg ml(-1). The MIC values of XTZ against M. furfur and M. pachydermatis were 1.25 and 0.25 mug ml(-1), respectively. The MFC of XTZ was 5 microg ml(-1) for M. furfur and 2.5 microg ml(-1) for M. pachydermatis. Time-kill curves demonstrated that treatment with 25 microg ml(-1) of XTZ for 5 h was able to kill 100% of M. furfur, while 20 microg ml(-1) of XTZ for 15 min killed M. pachydermatis completely.. XTZ shows potential as an anti-Malassezia agent for inhibiting the growth of M. furfur ATCC 14521 and M. pachydermatis ATCC 14522 in vitro.. XTZ may be a useful alternative for treating Malassezia-associated diseases.

Topics: Antifungal Agents; Curcuma; Malassezia; Microbial Sensitivity Tests; Phenols

Xanthorrhizol, isolated from the methanol extract of Curcuma xanthorrhiza Roxb., was investigated for its anticandidal activity using six Candida species.. The in vitro susceptibility tests for xanthorrhizol were carried out in terms of MIC and minimal fungicidal concentration (MFC) using the NCCLS M27-A2 broth microdilution method. Time-kill curves were determined to assess the correlation between MIC and fungicidal activity of xanthorrhizol at concentrations ranging from 0 MIC to 4x MIC.. All Candida species showed susceptibility to xanthorrhizol in the MIC range 1.0-15.0 mg/L for Candida albicans, 1.0-10 mg/L for Candida glabrata, 2.0-8.0 mg/L for Candida guilliermondii, 2.5-7.5 mg/L for Candida krusei, 2.5-25 mg/L for Candida parapsilosis and 2.0-8.0 mg/L for Candida tropicalis. Time-kill curves demonstrated that xanthorrhizol was able to kill the Candida strains with MFCs of 20 mg/mL, 15 mg/mL, 12.5 mg/mL, 10 mg/L, 30 mg/mL and 10 mg/L for C. albicans, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis and C. tropicalis, respectively.. The potent anticandidal activity of xanthorrhizol may support the use of C. xanthorriza for the treatment of candidiasis.

Topics: Antifungal Agents; Candida; Colony Count, Microbial; Curcuma; Microbial Sensitivity Tests; Phenols; Plant Extracts

Colonization on the surface of tooth by Streptococcus mutans is an important step in the initiation of dental plaque. Polystyrene microtiter plates have been employed to study bacterial colonization and biofilm formation of periodontal bacteria. The objective of this work was to evaluate the effect of coating the wells of a polystyrene microtiter plate with xanthorrhizol isolated from java turmeric (Curcuma xanthorrhiza Roxb.) on Strep. mutans biofilm formation. Our studies demonstrated that coating of a polystyrene microtiter plate with 5 microg/ml of xanthorrhizol resulted in significant (up to 60%) reduction of adherent cells compared to that of cells in uncoated wells. This result suggests that xanthorrhizol displays potent activity in preventing Strep. mutans biofilm formation.

Topics: Animals; Biofilms; Curcuma; Microbial Sensitivity Tests; Mucins; Phenols; Polystyrenes; Streptococcus mutans; Swine

Cisplatin is a potent anti-cancer chemotherapeutic agent but has the undesirable side effect of hepatotoxicity at high doses. In a previous study, abrogation of cisplatin-induced hepatotoxicity by pretreatment with xanthorrhizol was observed in mice, but the mechanism has not yet been studied. We therefore investigated whether the protective effect of xanthorrhizol on cisplatin-induced hepatotoxicity is associated with the mitogen-activated protein (MAP) kinase-signaling pathway. Cisplatin caused phosphorylation of both c-Jun N-terminal kinases 1/2 (JNK1/2) and the extracellular signal-regulated kinase 1/2 (ERK1/2), but not that of p38. However, cisplatin-induced phosphorylation of JNKs, especially JNK1, was highly attenuated by pretreatment with xanthorrhizol in a dose-dependent manner. This study suggested that the phosphorylation of JNKs could be involved in the protective effect of xanthorrhizol on cisplatin-induced hepatotoxicity and it also affects gene transcription by regulating the expression of transcription factor subunits such as c-fos and p50 in part. In addition, considering that the expression of both cytochrome c and caspase-9 were not changed in this model, its mechanism might be independent of mitochondria-related apoptosis. This is the first report giving evidence that the physiological function of xanthorrhizol is linked to regulation of the phosphorylation of JNK(s).

Topics: Animals; Antineoplastic Agents; Blotting, Western; Chemical and Drug Induced Liver Injury; Cisplatin; Curcumin; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phenols; Phosphorylation; Signal Transduction

Cisplatin is a widely used anticancer drug, but it can produce undesirable side effects such as nephrotoxicity. The present study investigated the effect of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) on cisplatin-induced nephrotoxicity in mice. A single dose of cisplatin (45 mg/kg, i.p.) significantly elevated the levels of blood urea nitrogen, serum creatinine, and the kidney to body weight ratio, but the pretreatment of xanthorrhizol (200 mg/kg/day, per os) for 4 days significantly attenuated the cisplatin-induced nephrotoxicity. The preventive effect of xanthorrhizol was more efficacious than that of curcumin with the same amount (200 mg/kg). However, this effect seemed not to be related with the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1). This is first time the preventive effect of xanthorrhizol on cisplatin-induced nephrotoxicity has been demonstrated, and these data suggest that the administration of xanthorrhizol is a promising approach in the treatment of nephrotoxicity caused by cisplatin.

Topics: Animals; Antineoplastic Agents; Blood Urea Nitrogen; Cisplatin; Creatinine; Curcumin; Kidney; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Organ Size; Phenols; Random Allocation; Transcription Factors; Transcription, Genetic

Xanthorrhizol, a natural sesquiterpenoid isolated from the rhizome of Curcuma xanthorrhiza Roxb (Zingiberaceae), has antibacterial activities and protective effects against cisplatin-induced hepatotoxicity. In this study, we investigated the activities of xanthorrhizol as an antioxidant or antiinflammatory agent using neuronal and microglial cells. Xanthorrhizol had potent neuroprotective effects on glutamate-induced neurotoxicity and reactive oxygen species (ROS) generation in the murine hippocampal HT22 cell line. Also, xanthorrhizol inhibited H(2)O(2)-induced lipid peroxidation in rat brain homogenates. The properties of xanthorrhizol as an antiinflammatory agent were investigated in microglial activation by lipopolysaccharide. It reduced the expression of cyclooxygenase-2 and the inducible nitric oxide synthase, which consequently resulted in the reduction of nitric oxide. The production of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha in activated microglial cells, was reduced by xanthorrhizol. These results suggest that xanthorrhizol could be an effective candidate for the treatment of Alzheimer's disease- and other neurological disease-related ROS and inflammation.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blotting, Western; Cell Survival; Cells, Cultured; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Glutamic Acid; Hippocampus; Hydrogen Peroxide; Interleukin-6; Lipid Peroxidation; Mice; Microglia; Neurons; Nitric Oxide; Nitric Oxide Synthase Type II; Phenols; Rats; Tumor Necrosis Factor-alpha

Xanthorrhizol is a sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza. In this study, the anti-metastatic activity of xanthorrhizol was evaluated by using an in vivo mouse lung metastasis model and a tumor mass formation assay. Interestingly, xanthorrhizol dramatically inhibited the formation of tumor nodules in the lung tissue and the intra-abdominal tumor mass formation. Next, to examine the mechanism of the anti-metastatic action of xanthorrhizol in the mouse lung metastasis, expression patterns of the several intracellular signaling molecules were evaluated using the lung tissues with tumor nodules. Higher expression levels of cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), and phosphorylated extracellular signal-regulated kinase (ERK) were observed in the metastatic group compared with control, but these were attenuated by the treatment of xanthorrhizol. In conclusion, xanthorrhizol exerts anti-metastatic activity in vivo and this effect could be highly linked to the metastasis-related multiplex signal pathway including ERK, COX-2, and MMP-9.

Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Curcuma; Dose-Response Relationship, Drug; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasms, Experimental; Phenols; Phytotherapy; Plant Extracts; Treatment Outcome