Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, Nω- nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensin II, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensin II levels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Anti-tumor activity of rice bran hydrolysates on migration, invasion and angiogenesis

Objective: To investigate anti-tumor effect of rice bran hydrolysates (RBH) on proliferation, migration, invasion, and angiogenesis of cholangiocarcinoma (CCA) cells, and elucidate the underlying mechanisms. Methods: RBH was prepared from Tubtim Chumprae rice (Oryza sativa L.) by hydrothermolysis followed by protease digestion. Phenolic content in RBH was analyzed by high-performance liquid chromatography. Human CCA cells, KKU-156, KKU-452, and KKU-100, were used to study the effects of RBH on proliferation, migration, invasion, and adhesion by wound healing, Transwell chamber, and fibronectin cell adhesion assays. Angiogenesis was evaluated using human umbilical vein endothelial cells. Proteins associated with cancer progression were analyzed by immunobloting assays. Results: RBH contained carbohydrates, proteins, lipids, and various phenolic compounds and flavonoids. RBH did not inhibit CCA proliferation, but strongly suppressed migration, invasion, adhesion of CCA cells, and the formation of tube-like capillary structures of human umbilical vein endothelial cells. Moreover, RBH down-regulated phosphorylation of FAK, PI3K, and Akt, suppressed NF-κB nuclear translocation, decreased the expression of ICAM-1, vimentin and vascular endothelium growth factor (VEGF), and increased the expression of E-cadherin. Conclusions: RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis. RBH is a potential food supplement for cancer prevention.

Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, Nω- nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensin II, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensin II levels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Anti-tumor activity of rice bran hydrolysates on migration, invasion and angiogenesis

Objective: To investigate anti-tumor effect of rice bran hydrolysates (RBH) on proliferation, migration, invasion, and angiogenesis of cholangiocarcinoma (CCA) cells, and elucidate the underlying mechanisms. Methods: RBH was prepared from Tubtim Chumprae rice (Oryza sativa L.) by hydrothermolysis followed by protease digestion. Phenolic content in RBH was analyzed by high-performance liquid chromatography. Human CCA cells, KKU-156, KKU-452, and KKU-100, were used to study the effects of RBH on proliferation, migration, invasion, and adhesion by wound healing, Transwell chamber, and fibronectin cell adhesion assays. Angiogenesis was evaluated using human umbilical vein endothelial cells. Proteins associated with cancer progression were analyzed by immunobloting assays. Results: RBH contained carbohydrates, proteins, lipids, and various phenolic compounds and flavonoids. RBH did not inhibit CCA proliferation, but strongly suppressed migration, invasion, adhesion of CCA cells, and the formation of tube-like capillary structures of human umbilical vein endothelial cells. Moreover, RBH down-regulated phosphorylation of FAK, PI3K, and Akt, suppressed NF-κB nuclear translocation, decreased the expression of ICAM-1, vimentin and vascular endothelium growth factor (VEGF), and increased the expression of E-cadherin. Conclusions: RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis. RBH is a potential food supplement for cancer prevention.

Rice bran hydrolysates induce immunomodulatory effects by suppression of chemotaxis, and modulation of cytokine release and cell-mediated cytotoxicity

Objective: To evaluate the immunomodulatory effects of rice bran hydrolysates on cultured immune cells and their underlying mechanism. Methods: Rice bran hydrolysates were prepared from pigmented rice (Oryza sativa L.) by hydrothermolysis and protease digestion. Rice bran hydrolysates were assayed for phenolic content and antioxidant activity. Cell proliferation of Jurkat, THP-1 and peripheral blood mononuclear cells (PBMC) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Chemotaxis was evaluated by transwell chamber methods. Immunoadherence of THP-1 was performed on cultured human umbilical vein endothelial cells (HUVEC). Cytokine released from PBMC was measured by ELISA assay kits. Lymphocyte-mediated cytotoxicity was carried out on KKU-452 cells. Proteins associated with immunomodulation were analyzed by Western immunoblotting assay. Results: Rice bran hydrolysates were rich in phenolic compounds, such as ferulic acid, catechin, quercetin, and quercetin glycosides. Rice bran hydrolysates suppressed phytohemagglutinin (PHA)- stimulated proliferation of PBMC and Jurkat cells, chemotaxis of Jurkat and THP-1 cells, and immunoadherence of THP-1 on HUVEC cultured cells. The cellular mechanism of rice bran hydrolysates involved the activation of AMPK as well as suppression of mTOR, NF-κB and VCAM-1. Rice bran hydrolysates potentiated PBMC on the PHA-stimulated release of IL-2, TNF-α, and IL-4, and enhanced PHA-induced non-MHC-restricted cytotoxicity on KKU-452 cancer cells. Conclusions: The immunomodulatory effect of phytochemicals derived from rice bran hydrolysates suggests its therapeutic potential for further investigation.

A Study of Antidiarrheal Effects of Guava Leaf (Psidium guajava Linn.) in Experimental Animals

Background : Diarrheal diseases are caused by several agents including infections or chemical agents that induced irritation of the gut wall, decrease electrolyte and water absorption or increase secretion. Much of interest is now focused on indigenous plants as herbal medicine. Our work will be on plants with antidiarrheal actions.Objective : To study of the antidiarrheal effects and the possible mechanism of actions of guava leaf and pomegranate fruit bark extracts in experimental animals.Design : Experimental animal.Setting : Department of Pharmacology, Faculty of Medicine, Khon Kaen University.Subjects : Swiss albino mice were used in the in vivo studies. Animals were divided into control group (20 animals), and treatment (80 animals). They were given with extracts at two doses levels (high and low), then animals were induced to develop diarrhea with several agents. For in vitro studies, isolated Guinea pig ileum segments were used. Ileum was induced to contract with electrical stimuli or chemical spasmogens Ach. or BaCl2Measurement : Number of defecation, texture of stool, and time to onset of diarrhea were recorded. Amplitude of contraction was recorded for in vitro studies.Results : In this study, the extracts of guava leaf and pomegranate fruit bark, at either 0.5 or 1 g/kg body weight, were tested for antidiarrheal effects. In in vivo experiments, mice were treated with either 0.5 ml of castor oil or 2 g/kg body weight of MgSO4 in order to induce loosening of stool. It was found that both extracts, at concentration tested, could reduce the loosening of stool induced by either castor oil or MgSO4 significantly. With isolated guinea pig ileum, both extracts also inhibited the contraction induced by either acetylcholine, BaCl2 or electrical stimulation at frequency 0.2 and 10 HZ.Conclusion : The results suggest that the extracts might act through cholinergic or non-cholinergic nerve in ileum wall and/or directly on ileum smooth muscles.

Bioequivalence Study of Ceftazidime by Intramuscular Administration in Healthy Thai Volunteers

Background : Ceftazidime is a third generation cephalosporin that has been commercially available through several manufacturers and distributors in Thailand because of its widely clinical use. However, there is no bioequivalent study of this drug in Thais.\  The present study was conducted to compare the in vivo bioequivalent of ceftazidime obtained from an original (reference), and a local (tested) manufacturer in healthy Thai volunteers.Objective: To determine if two ceftazidime preparations (Fortum and Forzid) of different manufacturers are bioequivalent when administered intramuscularly.Design: Double-blind single-dose, two-period, randomized crossover study.Subjects: Fourteen Healthy Thai Volunteers.Methods and Interventions: Ceftazidime 1 g was administered intramuscularly to subjects. Blood samples were collected at predetermined intervals and assayed for ceftazidime concentration with HPLC. Pharmacokinetic parameters were calculated from the observed plasma-concentration time profiles. Maximum plasma concentration (Cmax), time to peak concentration (Tmax), areas under the concentration-time curve from 0 to 12 h (AUC0-12) and 0 to infinity (AUC0-) were the primary parameters considered in the determination of bioequivalence.Results: The two ceftazidime preparations were generally well tolerated by all volunteers. Administration of both preparations resulted in similar mean values for every pharmacokinetic parameters. Statistical analysis revealed no significant difference between the two preparations in any parameter, indicating that the two preparations are statistically bioequivalent (p\<0.05). The 90% confident interval (CI) for the ratio of the means for the Cmax (0.9281-1.1272) and AUC0- (0.9311-1.0184), are within the Food and Drug Administration Guideline range of bioequivalence (0.80 to 1.25).Conclusions: These results demonstrated that the tested ceftazidime preparation (Forzid) is bioequivalent to the reference ceftazidime preparation (Fortum) when administered intramuscularly.

Cancer Chemoprevention from Dietary Phytochemical

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Screening for Analgesic and Anti-inflammatory Activities of Extracts from Local Vegetables in Northeast Thailand

Background: Northeast region of Thailand is one of the rich source of vegetables, the favorite Thai food in daily diet. There are very few pharmacological studies in folk vegetables.Objectives: This study described screening tests for the analgesic and anti-inflammatory activities of 10 local vegetables inhabitated in the Northeast region of Thailand.Method: Analgesic activity was assessed by writhing test and tail flick test. Anti-inflammatory activity was assessed by rat hind paw edema model.Results: The water extract of vegetables at 1 g/kg administered orally in Swiss albino male mice was used to test for analgesic activity in the acetic acid-induced writhing test model. The extracts from Coccinia grandis (L.) Voigt., Tiliacora triandra Diels., Barringtonia acutangula Gaerth., Brassica juncea (Linn.) Czern\&Coss., Limnophila aromatica (Lomk) Merr., Piper samentosum Roxb. Ex. Hunter and Anethum graveolens Linn. elicited significant inhibition of writhing reflex by 35-64% (p

Sensitivity of Cholangiocarcinoma Cells to Chemotherapeutic Agents and Curcumin

Background: Chemotherapeutic treatment of cholangiocarcinoma is largely ineffective, because it is due to non-responsive for the obscured reason of the cancer to anticancer agents. Study was to investigate the cytotoxicity effects of chemotherapeutic agents and curcumin in vitro.Objective: To test sensitivity of cholangiocarcinoma cell lines to chemotherapeutic agents and curcumin Material and Methods: Three cholangiocarcinoma (CCA) cell lines, including KKU-100, KKU-M214 and KKU-OCA17 were used in the study. All cell lines were treated with three chemotherapeutic agents (5-fluorouracil, doxorubicin and carboplatin) or curcumin. The cell viability was determined under a fluorescence microscope by counting the number of living and dead cells after treatment.Results: KKU-100 and KKU-M214 were the very sensitive cell lines to doxorubicin (IC50 values ranging from 0.4 to 0.7 nmol/l), whereas KKU-OCA17 was relatively more resistant cell line. Interestingly, all cell lines were sensitive to curcumin (IC50 values ranging from 3 to 17 μmol/l). Conclusion: This study showed different degrees of semsitivity of CCA cell lines to various chemotherapeutic agents. The data could serve as basic information for chemotherapeutic selection for the treatment in CCA patients. Moreover curcumin exhibits the cytotoxicity on CCA cell lines; thereby it is suggested to be very beneficial in the development of strategy for chemotherapy of CCA cancer.Keywords: cholangiocarcinoma, curcumin, chemotherapeutic agent

New Strategy of Cancer Targeting Chemotherapy

Cancer is the disease that mutilates patient life and family. Cancer chemotherapy is one of treatment modalities for some cancers and cancers in some stages. Current advances in chemotherapeutic drugs involve with the targeted drug therapy where it is distinct from the classical cytotoxic drugs which damage rapidly dividing cancer as well as normal cells. Target molecules of the new drugs include molecules in signaling pathways which confer advantages for growth, survival, metastasis, and resistance to dead signals from normal tissues or chemotherapeutic drugs. The target molecules of interest which undergo new drug development pipelines comprise various protein tyrosine kinases, i.e. epidermal growth factor family and vascular epidermal growth factor receptors; mitogen-activated protein kinases, and molecules involving in broad metabolic pathways, such as proteasomes, histone deacetylase and transcription factor proteins such as nuclear factor kappa B. The target molecules are derived from basic studies of cancer and evolved to be potential anticancer drugs. This new generation of targeting drugs offers an alternative of cancer chemotherapy and is also employed as potential research tools in cancer biology.

Individualized Therapy and Pharmacogenetic Test

Variability of drug response and toxic adverse effects are primarily responsible for the failure of drug therapy. Individual variation in genetic composition in regulating pharmacokinetic and pharmacodynamic processes, such as genes of drug metabolizing enzymes and genes of receptor or enzyme of drug response is critically important in determining drug efficacy. Pharmacogenetic testing will enable selection of appropriate drugs from the beginning, avoiding the drugs that could cause serious adverse events and assortment of alternative drugs to enhance therapeutic efficacy and minimize the illness.