The Discovery of Selective Protein Arginine Methyltransferase 5 Inhibitors in the Management of ß-Thalassemia through Computational Methods.

ß-Thalassemia is an inherited genetic disorder associated with ß-globin chain synthesis, which ultimately becomes anemia. Adenosine-2,3-dialdehyde, by inhibiting arginine methyl transferase 5 (PRMT5), can induce fetal hemoglobin (HbF) levels. Hence, the materialization of PRMT5 inhibitors is considered a promising therapy in the management of ß-thalassemia. This study conducted a virtual screening of certain compounds similar to 5'-deoxy-5'methyladenosine (3XV) using the PubChem database. The top 10 compounds were chosen based on the best docking scores, while their interactions with the PRMT5 active site were analyzed. Further, the top two compounds demonstrating the lowest binding energy were subjected to drug-likeness analysis and pharmacokinetic property predictions, followed by molecular dynamics simulation studies. Based on the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) score and molecular interactions, (3R,4S)-2-(6-aminopurin-9-yl)-5-[(4-ethylcyclohexyl)sulfanylmethyl]oxolane-3,4-diol (TOP1) and 2-(6-Aminopurin-9-yl)-5-[(6-aminopurin-9-yl)methylsulfanylmethyl]oxolane-3,4-diol (TOP2) were identified as potential hit compounds, while TOP1 exhibited higher binding affinity and stabler binding capabilities than TOP2 during molecular dynamics simulation (MDS) analysis. Taken together, the outcomes of our study could aid researchers in identifying promising PRMT5 inhibitors. Moreover, further investigations through in vivo and in vitro experiments would unquestionably confirm that this compound could be employed as a therapeutic drug in the management of ß-thalassemia.

Gamma-Oryzanol-Rich Fraction from Purple Rice Extract Attenuates Lipopolysaccharide-Stimulated Inflammatory Responses, Migration and VEGFA Production in SW480 Cells via Modulation of TLR4 and NF-κB Pathways.

Inflammatory response facilitating colorectal cancer (CRC) progression is a serious event following operative infection, which can occur in CRC patients. This event is mainly mediated by bacterial lipopolysaccharide (LPS), via a toll like receptor 4 (TLR4) and NF-κB. Hexane soluble fraction (HSF) from purple rice extract (PRE) has been identified as a γ-oryzanol (OR)-rich fraction. Recently, HSF possessed inhibitory effect of LPS-stimulated metastasis of human colon cancer SW480 cells, however the related mechanism was unknown. Thus, this study aimed to investigate the effect of HSF on inflammatory response-associated cancer progression of LPS-stimulated SW480 cells. The various inflammatory mediators, vascular endothelial growth factor-A (VEGFA) and related pathways were evaluated by Western blot and ELISA. Furthermore, cell migration was also determined by migration assays. Of all, HSF seemed to be stronger than OR to attenuate the responsiveness of LPS on various inflammatory mediators, which was related to an obvious reduction of cancer cell migration as well as indistinct disruption on VEGFA production in SW480 cells, via downregulation of TLR4 and NF-κB. Therefore, OR-rich fraction from PRE, against the subsequent inflammatory response and CRC progression following surgery, which could be combined with conventional treatments to increase the survival rate.

Safety and bioactivity assessment of aqueous extract of Thai Henna (Lawsonia inermis Linn.) Leaf.

The worldwide demand for a natural dye by the cosmetic and food industry has recently gained interest. To provide scientific data supporting the usage of Thai henna leaf as a natural colorant, the phytochemical constituents, safety, and bioactivity of aqueous extract of the henna leaf by autoclave (HAE) and hot water (HHE) were determined. HAE contained a higher amount of total phenolic and flavonoid contents than HHE. The major constituents in both extracts were ferulic acid, gallic acid, and luteolin. The extracts displayed no marked mutagenic activity both in vitro and in vivo mammalian-like biotransformation. HAE and HHE also exhibited non-cytotoxicity to human immortalized keratinocyte cells (HaCaT), peripheral blood mononuclear cells (PBMCs), and murine macrophage RAW 264.7 cell line with IC20 and IC50 > 200 µg/ml. The extracts exhibited antioxidant and anti-inflammatory activity as evidenced by significant scavenging of ABTS and DPPH radicals and decreasing NO levels in LPS-induced RAW 264.7 cells. The antioxidant and anti-inflammatory properties of the extracts might be attributed to their phenolic and flavonoid contents. In conclusion, the traditional use of henna as a natural dye appears not to exert toxic effects and seems biosecure. Regarding safety, antioxidant, and anti-inflammatory properties, the aqueous extract of Thai henna leaf might thus serve as a readily available source for utilization in commercial health industries.

Effects of supplemental Bacillus subtilis, injectable vitamin E plus selenium, or both on health parameters during the transition period in dairy cows in a tropical environment.

The objective of this study was to determine the effects of supplemental Bacillus subtilis (BS, 0.5 × 1011 CFU/day), injectable vitamin E and selenium (ES, 1000 mg α-tocopherol acetate and 10 mg sodium selenite), or both during the transition period on health parameters and the incidence of retained fetal membranes (RFM) of dairy cows under tropical conditions (average temperature humidity index = 77.0). Thirty-two crossbred Holstein-Friesian cows were used in a randomized design trial with a 2 × 2 factorial arrangement of treatments. Cows were randomly assigned to one of four treatments, including no supplementation (CON), single intramuscular injection of ES on day - 21 before the expected calving date (ES), daily oral supplementation of BS between day - 21 and day 21 relative to calving, or both ES and BS. Body condition score (BCS) and blood samples were collected on days - 28, - 14, 0, 14, and 28 relative to calving. Mean concentrations of corpuscular hemoglobin were higher (33.12 vs 34.03 g/dL, p = 0.06) and platelets were lower (380.97 vs 302.32 × 103/µL, p = 0.10) with ES than without ES. Cows fed supplemental BS had lower concentrations of creatinine and albumin and tended to have lower AST and ß-hydroxybutyrate (BHBA) levels. However, concentrations of glucose were higher for cows fed BS than for those without BS. No differences in the incidence of RFM were observed. In summary, supplemental B. subtilis could reduce indicators of negative energy balance by increasing glucose and lowering BHBA and improve health parameters by keeping WBCs and monocytes in a healthy range during the transition period.

The Effects of Houttuynia cordata Thunb and Piper ribesioides Wall Extracts on Breast Carcinoma Cell Proliferation, Migration, Invasion and Apoptosis.

Houttuynia cordata Thunb. (HCT) and Piper ribesioides Wall. (PR) are common herbs that are widely distributed throughout East Asia and possess various biological properties including anti-cancer effects. However, in breast cancer, their mechanisms responsible for anti-carcinogenic effects have not been clarified yet. In this study, the inhibitory effects of HCT and PR ethanolic extracts on breast cancer cell proliferation, migration, invasion and apoptosis were examined. In MCF-7 and MDA-MB-231 cells, HCT and PR extracts at low concentrations can inhibit colony formation and induce G1 cell cycle arrest by downregulating cyclinD1 and CDK4 expression. Additionally, HCT and PR extracts also decreased the migration and invasion of both breast cancer cell lines through inhibition of MMP-2 and MMP-9 secretion. Moreover, the induction of apoptosis was observed in breast cancer cells treated with high concentrations of HCT and PR extracts. Not only stimulated caspases activity, but HCT and PR extracts also upregulated the expression of caspases and pro-apoptotic Bcl-2 family proteins in breast cancer cells. Altogether, these findings provide the rationale to further investigate the potential actions of HCT and PR extracts against breast cancer in vivo.

Augmentation of diethylnitrosamine-induced early stages of rat hepatocarcinogenesis by 1,2-dimethylhydrazine.

Diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) are classical carcinogens used in experimental rodent carcinogenesis. However, the interaction effects of these carcinogens on biochemical and molecular changes during carcinogenesis have not been investigated. Therefore, the effect of DEN and DMH co-administration on preneoplastic lesion formation and its molecular mechanism in rats were determined. Triple intraperitoneal administrations of DEN were made before, during or after double subcutaneous injections of DMH. At week 8 of the experiment, the preneoplastic hepatic glutathione-S-transferase placental form (GST-P) positive foci and colonic aberrant crypt foci (ACF) were analyzed. The combined treatment of these carcinogens increased toxicity to rats. Administration of DMH alone did not induce hepatic GST-P positive foci, while co-treatment with DMH enhanced hepatic GST-P positive foci formation. However, DEN did not influence the size or number of colonic ACF. The treatment with DMH alone induced CYP2E1 and P450 reductase, demonstrating that DMH enhanced DEN metabolism in DEN- and DMH-treated rats. These findings were related to increases in hepatic O6-methylguanine DNA adducts and hepatotoxicity, which are associated with the induction of cell proliferation and liver cancer development. DEN-induced early stages of rat hepatocarcinogenesis were synergistically promoted by DMH via metabolic enzyme induction leading to enhanced DNA mutation and hepatocarcinogenicity.

Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis.

BACKGROUND: Ellagic acid (EA), a component of pomegranate fruit juice (PFJ), is a plant-derived polyphenol and has antioxidant properties. PFJ and EA have been reported to suppress various cancers, including prostate cancer. However, their chemopreventive effects on development and progression of prostate cancer using in vivo models have not been established yet. METHODS: The transgenic rat for adenocarcinoma of prostate (TRAP) model was used to investigate the modulating effects of PFJ and EA on prostate carcinogenesis. Three-week-old male transgenic rats were treated with EA or PFJ for 10 weeks. In vitro assays for cell growth, apoptosis, and Western blot were performed using the human prostate cancer cell lines, LNCaP (androgen-dependent), PC-3 and DU145 (androgen-independent). RESULTS: PFJ decreased the incidence of adenocarcinoma in lateral prostate, and both EA and PFJ suppressed the progression of prostate carcinogenesis and induced apoptosis by caspase 3 activation in the TRAP model. In addition, the level of lipid peroxidation in ventral prostate was significantly decreased by EA treatment. EA was able to inhibit cell proliferation of LNCaP, whereas this effect was not observed in PC-3 and DU145. As with the in vivo data, EA induced apoptosis in LNCaP by increasing Bax/Bcl-2 ratio and caspase 3 activation. Cell-cycle related proteins, p21(WAF) , p27(Kip) , cdk2, and cyclin E, were increased while cyclin D1 and cdk1 were decreased by EA treatment. CONCLUSIONS: The results indicate that PFJ and EA are potential chemopreventive agents for prostate cancer, and EA may be the active component of PFJ that exerts these anti-cancer effects.

Apoptosis induction in colon cancer cell lines and alteration of aberrant crypt foci in rat colon by purple rice (Oryza sativa L. var. glutinosa) extracts.

Crude ethanol extracts (CEE) of purple rice was fractionated to obtain hexane soluble (HSF) and ethyl acetate soluble fractions (EASF). Total antioxidant capacity was higher in CEE than the HSF and EASF. However, HSF exhibited strong antiproliferation and apoptosis induction against colon cancer cell lines, both p53 wild-type (RKO) and mutant (SW620) strains. Then, the CEE was used to determine the effects on the progression of aberrant crypt foci (ACF), a preneoplastic lesion seen in colon carcinogenesis in rats. Male Wistar rats were subcutaneously injected of 40 mg/kg body weight dimethylhydrazin (DMH) once weekly for 2 wk. After 2 wk, rats were orally administered ethanol extract at 100 and 1000 mg/kg body weight, for 4 wk. Rats fed with only the high dose of CEE had significantly decreased numbers of ACF per rat (45.56%) and crypt multiplicity (AC/focus) (16.67%) compared to rats that received DMH alone. The result also demonstrated that CEE induced apoptosis in colonic epithelium cells of rat received colon carcinogen as detected the increasing of caspase-3 activity. This finding could be concluded that purple rice extracts inhibited aberrant colonic epithelial cell progression via apoptosis induction.

Hexane insoluble fraction from purple rice extract improves steatohepatitis and fibrosis via inhibition of NF-κB and JNK signaling.

Nonalcoholic fatty liver disease (NAFLD) is fatty liver mainly related to metabolic syndrome. NAFLD with inflammation and hepatocellular damage is defined as nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. We have previously reported that a hexane insoluble fraction from an anthocyanin-rich purple rice ethanolic extract (PRE-HIF) can suppress prostate carcinogenesis. However, the extract's effect on NASH has not yet been established. In the present study, we investigated the chemopreventive effect of a PRE-HIF on NASH and liver fibrosis using a connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rat NASH model. Seven-week-old male Cx32ΔTg rats were fed a control diet, a high-fat diet (HFD), or an HFD with 1% PRE-HIF and intraperitoneal administration of dimethylnitrosamine for 17 weeks. Histological findings of NASH such as fat deposition, lobular inflammation, hepatocyte ballooning injury, and bridging fibrosis were observed in the HFD group but not in the control group, and all histological parameters were significantly improved by PRE-HIF treatment. Corresponding to the histological changes, increased expression of inflammatory cytokine mRNAs (TNF-α, IL-6, IL-18, IFN-γ, IL-1ß, TGF-ß1, TIMP1, TIMP2, COL1A1), along with and activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling were observed in the HFD group, which was significantly decreased by PRE-HIF. The number and area of hepatic precancerous glutathione S-transferase placental form-positive foci tended to be decreased by PRE-HIF. These results indicate that intake of purple rice as a dietary supplement may reduce steatohepatitis, liver injury, and fibrosis in NASH by inactivation of NF-κB or JNK.

The Ameliorative Effect of Litsea martabanica (Kurz) Hook. f. Leaf Water Extract on Chlorpyrifos-Induced Toxicity in Rats and Its Antioxidant Potentials.

Litsea martabanica root's antioxidant and acetylcholinesterase (AChE) activity showed promise as a pesticide detoxification agent in our previous study. In addition to its root, leaves can help alleviate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in several countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally used leaves instead of roots. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extract from L. martabanica leaves through in vitro and in vivo investigations. In the in vitro study, L. martabanica water extract and its fractions demonstrated antioxidant activity and induced apoptosis in hepatic satellite cells. In the in vivo study, treatment with the leaf extract led to increased AChE activity, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) levels, and reduced glutathione in chlorpyrifos-exposed rats. Histopathological examination revealed that chlorpyrifos-treated rats exhibited liver cell damage, while treatment with the water extract of L. martabanica exhibited a protective effect on the liver. In conclusion, L. martabanica water extract exhibited antioxidant activity, enhanced AChE activity, and improved histopathological abnormalities in the liver.

The Safety Assessment of Mutagenicity, Acute and Chronic Toxicity of the Litsea martabanica (Kurz) Hook.f. Water Leaf Extract.

Litsea martabanica (Kurz) Hook.f. has traditionally been used as an anti-insecticidal agent and as a medication due to its hepatoprotective properties by highland communities in Thailand. This study examined the mutagenicity, as well as the acute and chronic toxicity, of the L. martabanica water leaf extract in Sprague-Dawley rats. The pharmacognostic evaluation of L. martabanica was performed in this study to ensure its authenticity and purity. Then, the sample was extracted using decoction with water to obtain the crude water extract. The assessment of acute toxicity involved a single oral administration of 5000 mg/kg, whereas the chronic toxicity assessment comprised daily oral doses of 250, 750, and 2250 mg/kg over 270 days. Various physiological and behavioral parameters, as well as body and organ weights, were systematically monitored. The endpoint assessments involved hematological and biochemical analyses plus gross and histopathological assessments of the internal organs. Our results exhibited no mutagenic activation by the L. martabanica water leaf extract in the Ames test, and no acute toxicity was observed. In the chronic toxicity tests, no abnormalities were found in rats receiving the L. martabanica water leaf extract across multiple measures, comprising behavioral, physiological, and hematological indices. Crucially, the histopathological assessment corroborated previous studies, reporting an absence of any tissue abnormalities. The results revealed that the L. martabanica water leaf extract had no adverse effects on rats over 270 days of oral administration. This demonstrates its safety and crucial scientific evidence for informing public policy and enabling its potential future commercial use in both highland and lowland communities.

Inhibitory Effects of Chlorogenic Acid Containing Green Coffee Bean Extract on Lipopolysaccharide-Induced Inflammatory Responses and Progression of Colon Cancer Cell Line.

An inflammatory response, related to colorectal cancer (CRC) progression, is a major subsequent result of bacterial infection following CRC surgery and should be of serious concern. Lipopolysaccharide (LPS), from the bacterial membrane, is a vital mediator of this event through binding with a Toll-like receptor 4 (TLR4) and activating through NF-κB in CRC. To identify a novel inhibitor of LPS-induced colon cancer cells (SW480), green coffee bean extract (GBE) was investigated. Ethyl acetate insoluble fraction (EIF) was mainly collected from GBE and classified as chlorogenic acid (CGA)-rich fractions. EIF and CGA inhibited TLR4 expression in LPS-induced SW480 cells. However, EIF was more dominant than CGA, via inhibition of expression and secretion of several associated mediators in inflammatory responses and CRC metastasis through NF-κB inactivation, which resulted in the abrogation of CRC migration and invasion. Thus, CGA-rich fraction from GBE can be further developed as an alternative treatment, coupled with CRC surgical treatment, to increase therapeutic efficiency and survival rate.

The Extract of Perilla frutescens Seed Residue Attenuated the Progression of Aberrant Crypt Foci in Rat Colon by Reducing Inflammatory Processes and Altered Gut Microbiota.

Perilla frutescens (PF) seed residue is a waste from perilla oil production that still contains nutrients and phytochemicals. This study aimed to investigate the chemoprotective action of PF seed residue crude ethanolic extract (PCE) on the inflammatory-induced promotion stage of rat colon carcinogenesis and cell culture models. PCE 0.1 and 1 g/kg body weight were administered by oral gavage to rats after receiving dimethylhydrazine (DMH) with one week of dextran sulfate sodium (DSS) supplementation. PCE at high dose exhibited a reduction in aberrant crypt foci (ACF) number (66.46%) and decreased pro-inflammatory cytokines compared to the DMH + DSS group (p < 0.01). Additionally, PCE could either modulate the inflammation induced in murine macrophage cells by bacterial toxins or suppress the proliferation of cancer cell lines, which was induced by the inflammatory process. These results demonstrate that the active components in PF seed residue showed a preventive effect on the aberrant colonic epithelial cell progression by modulating inflammatory microenvironments from the infiltrated macrophage or inflammatory response of aberrant cells. Moreover, consumption of PCE could alter rat microbiota, which might be related to health benefits. However, the mechanisms of PCE on the microbiota, which are related to inflammation and inflammatory-induced colon cancer progression, need to be further investigated.

The Toxicological Assessment of Anoectochilus burmannicus Ethanolic-Extract-Synthesized Selenium Nanoparticles Using Cell Culture, Bacteria, and Drosophila melanogaster as Suitable Models.

Selenium nanoparticles (SeNPs) are worthy of attention and development for nutritional supplementation due to their health benefits in both animals and humans with low toxicity, improved bioavailability, and controlled release, being greater than the Se inorganic and organic forms. Our previous study reported that Anoectochilus burmannicus extract (ABE)-synthesized SeNPs (ABE-SeNPs) exerted antioxidant and anti-inflammatory activities. Furthermore, ABE could stabilize and preserve the biological activities of SeNPs. To promote the ABE-SeNPs as supplementary and functional foods, it was necessary to carry out a safety assessment. Cytotoxicity testing showed that SeNPs and ABE-SeNPs were harmless with no killing effect on Caco2 (intestinal epithelial cells), MRC-5 (lung fibroblasts), HEK293 (kidney cells), LX-2 (hepatic stellate cells), and 3T3-L1 (adipocytes), and were not toxic to isolated human PBMCs and RBCs. Genotoxicity assessments found that SeNPs and ABE-SeNPs did not induce mutations in Salmonella typhimurium TA98 and TA100 (Ames test) as well as in Drosophila melanogaster (somatic mutation and recombination test). Noticeably, ABE-SeNPs inhibited mutation in TA98 and TA100 induced by AF-2, and in Drosophila induced by urethane, ethyl methanesulfonate, and mitomycin c, suggesting their anti-mutagenicity ability. This study provides data that support the safety and anti-genotoxicity properties of ABE-SeNPs for the further development of SeNPs-based food supplements.

Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells.

To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly-metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control-siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors.

Ficus dubia Latex Extract Induces Cell Cycle Arrest and Apoptosis by Regulating the NF-κB Pathway in Inflammatory Human Colorectal Cancer Cell Lines.

Colorectal cancer is one of the most diagnosed cancers that is associated with inflammation. Ficus dubia latex is recognized as a remedy with various therapeutic effects in traditional medicine, including anti-inflammatory and antioxidant activity. The present study aims to compare the anti-tumor activity of Ficus dubia latex extract (FDLE) against HCT-116 and HT-29 human colorectal cancer cell lines in normal and inflammatory condition and explore its mechanism of action. FDLE exhibited remarkable antiproliferative activity against HCT-116 and HT-29 colorectal cancer cell lines in both conditions using MTT and colony formation assays and more effective anti-proliferation was observed in inflammatory condition. Mechanistically, FDLE induced cell cycle arrest at G0/G1 phase by down-regulating NF-κB, cyclin D1, CDK4 and up-regulatingp21 in both cell in normal condition. In inflammatory condition, FDLE not only exhibited stronger induction of cell cycle arrest in both cells by down-regulating NF-κB, cyclin D1, CDK4 and down-regulating p21, but also selectively induced apoptosis in HCT-116 cells by down-regulating NF-κB and Bcl-xl and up-regulating Bid, Bak, cleaved caspase-7 and caspase-3 through stronger ability to regulate these proteins. Our results demonstrated that the phytochemical agent in the latex of Ficus dubia could potential be used for treatment and prevention of human colorectal cancer, especially in inflammation-induced hyperproliferation progression.

Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.

Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and ß-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.

Impact of Green Extraction on Curcuminoid Content, Antioxidant Activities and Anti-Cancer Efficiency (In Vitro) from Turmeric Rhizomes (Curcuma longa L.).

Turmeric (Curcuma longa L.) powder is widely used as a spice and seasoning in Asian countries. This study investigated the effect of turmeric extracts on the anticancer activity of Huh7 and HCT 116 cells. The curcumin bioactive compounds were extracted using various methods such as microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and traditional extraction (TDE). The yield of dried extracts from MAE was found to be the highest at 17.89%, followed by UAE and TDE, with 11.34% and 5.54%, respectively. Antioxidant activities such as TPC, DPPH and FRAP from MAE were higher than those of UAE and TDE. The total curcuminoid contents from the novel extractions were higher than those from traditional extraction methods. For instance, curcuminoid contents from MAE, UAE and TDE were 326.79, 241.17 and 215.83 mg/g, respectively. Due to having the highest bioactive compounds and extraction yield, turmeric extract from MAE was used to investigate the potential anticancer properties. The extract showed significant cytotoxic potential against the human liver (Huh7) and human colon (HCT116) cell lines, in concentrations ranging from 31.25 to 1000.00 µg/mL. Turmeric extracts using MAE have potential anticancer effects on Huh7 and HCT116 cells. This study serves as scientific data for the chemotherapeutic properties of turmeric extracts and their use as functional ingredients.

Effects of nobiletin on PhIP-induced prostate and colon carcinogenesis in F344 rats.

The current study was designed to investigate the effects of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced prostate and colon carcinogenesis. PhIP was administered to 6-wk-old F344 male rats intragastrically (100 mg/kg) twice a wk for 10 wk. The animals were given 0.05% nobiletin or the basal diet for 50 wk. At the end of the experiment, serum testosterone, estrogen, and leptin did not differ between the 2 groups. The body weights of nobiletin-treated rats were significantly higher than controls (P<0.05), and feeding of nobiletin significantly reduced the relative prostate (P<0.05) and testes (P<0.05) weights as well as the Ki67 labeling index in the normal epithelium in the ventral prostate (P<0.01). The incidence and multiplicity of adenocarcinomas in nobiletin-treated ventral prostate were 50% and 36%, respectively, of controls, but the differences were not statistically significant. However, nobiletin did significantly reduce the total number of colonic aberrant crypt foci (ACF) compared to the control value (P<0.05). Nobiletin, therefore, may have potential for chemoprevention of early changes associated with carcinogenesis in both the prostate and colon.

Effects of Fermented Houttuynia cordata Thunb. on Diabetic Rats Induced by a High-Fat Diet with Streptozotocin and on Insulin Resistance in 3T3-L1 Adipocytes.

Houttuynia cordata Thunb. (plukaow in Thai language) exhibits several biological properties, and many products of H. cordata are therefore commercially available for human consumption, such as fermented juice or tablets as food supplements. This study aimed to investigate the antidiabetic effects of fermented H. cordata (HC) in high-fat diets and streptozotocin-induced diabetic rats. Oral administration of HC at a dose of 100 mg/kg.bw not only maintained bodyweight, food intake, and water consumption but also reduced blood glucose levels and improved glucose tolerance ability in the diabetic rats. Moreover, HC also decreased oxidative stress markers in serum and inflammatory-related mediators in pancreas tissues, indicating the improvement of pancreatic beta-cell function in the diabetic rats. In order to clarify the mechanism of HC, the effects of ethanolic extract of HC (HCE) on insulin resistance were determined in 3T3-L1 adipocytes. FHE could recover glucose uptake and decrease lipolysis in palmitate-treated 3T3-L1 adipocytes. Taken together, these results demonstrate that HC can improve diabetic symptoms by enhancing insulin sensitivity, reducing oxidative stress, and suppressing inflammation.