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Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells
Azizah Ugusman, Zaiton Zakaria, Chua Hui, Nor Megat Mohd Nordin
BMC Complementary and Alternative Medicine , 2011, DOI: 10.1186/1472-6882-11-31
Abstract: HUVECs were divided into four groups:- control; treatment with 180 μM hydrogen peroxide (H2O2); treatment with 150 μg/mL AEPS and concomitant treatment with AEPS and H2O2 for 24 hours. Total RNA was extracted from all the groups of HUVEC using TRI reagent. Subsequently, qPCR was carried out to determine the mRNA expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx. The specificity of the reactions was verified using melting curve analysis and agarose gel electrophoresis.When stimulated with H2O2, HUVECs expressed higher level of ICAM-1 (1.3-fold) and Nox4 (1.2-fold) mRNA expression. However, AEPS treatment led to a reduction in the mRNA expression of ICAM-1 (p < 0.01) and Nox4 (p < 0.05) in the H2O2-induced HUVECs. AEPS also upregulated the mRNA expression of SOD1 (p < 0.05), CAT (p < 0.01) and GPx (p < 0.05) in oxidative stress-induced HUVECs. There was no significant change in the mRNA expression of VCAM-1 and E-selectin.The expressional suppression of ICAM-1 and Nox4 and induction of antioxidant enzymes might be an important component of the vascular protective effect of AEPS.Atherosclerosis has been recognized as a chronic inflammatory disease and oxidative stress plays a pivotal role in its initiation and progression [1]. Endothelial dysfunction is considered to be an early marker for atherosclerosis [2]. Evidence suggests that increased production of reactive oxygen species (ROS) and vascular inflammation play important roles in endothelial dysfunction.Vascular disorders, through over expression of adhesion molecules and cytokines are involved in the development of atherosclerosis. Endothelial cells in human atherosclerotic lesions have increased cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) [3,4]. The adhesion of monocytes to the arterial wall and their subsequent infiltration and differentiation into macrophages are th
Allelopathic Activity of Piper sarmentosum Roxb.  [PDF]
Piyatida Pukclai,Hisashi Kato-Noguchi
Asian Journal of Plant Sciences , 2011,
Abstract: The allelopathic effect of medicinal plant, Piper sarmentosum Roxb., against 12 test plant species was evaluated. Four different concentrations of 0.01, 0.03, 0.1 and 0.3 g dry weight equivalent extract mL-1 were used in the study. The hypocotyl and root length were measured compared with control treatments. It was observed that the aqueous methanol extracts of P. sarmentosum plants inhibited all test plant species with different inhibition values. The variation may result, in part, from the different test plant species with different sensitivity to allelochemicals. The shoot and root growth of test plants were inhibited at the concentration greater than 0.03 g dry weight equivalent extract mL-1 and increasing the extract concentration increased inhibition. These results suggesting that P. sarmentosum may contain growth inhibitory substances and possess allelopathic activity. The concentrations required for 50% growth inhibition of test plants were 0.001-0.210 g dry weight equivalent extract mL-1 and alfalfa seedling were most sensitive to the extract. P. sarmentosum may be good candidate for isolation and identification of allelochemicals. The information obtained could be utilized in the development of bioherbicide for future weed management.
The role of nitric oxide on rosuvastatin-mediated S-nitrosylation and translational proteomes in human umbilical vein endothelial cells
Bin Huang, Fu An Li, Chien Hsing Wu, Danny Ling Wang
Proteome Science , 2012, DOI: 10.1186/1477-5956-10-43
Abstract: Rosuvastatin treatment of human umbilical vein endothelial cells (ECs) enhanced the enzymatic activity of endothelial nitric oxide synthase (eNOS) and the expression of 78 S-nitrosoproteins. Among these S-nitrosoproteins, we identified 17 proteins, including protein disulfide bond isomerase, phospholipase C, transaldolase and heat shock proteins. Furthermore, a hydrophobic Cys66 was determined as the S-nitrosylation site of the mitochondrial HSP70. In addition to the statin-modulated posttranslational S-nitrosylation, changes in the NO-mediated translational proteome were also observed. Seventeen major proteins were significantly upregulated after rosuvastatin treatment. However, 12 of these proteins were downregulated after pretreating ECs with an eNOS inhibitor (L-NAME), which indicated that their expression was modulated by NO.ECs treated with rosuvastatin increase eNOS activation. The increased NO production is involved in modulating S-nitrosylation and translation of proteins. We provide further evidence of the pleiotropic effect of rosuvastatin on endothelial physiology.
Shear stress effect on endothelial nitric oxide synthase in cultured human umbilical vein endothelial cells  [PDF]
Qiuying Gu, Dean O. Smith, Karlene A. Hoo
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.610122
Abstract: Background: Low shear stress caused by disturbed or turbulent flow at arterial branch points is known to associate with atherosclerosis. However, shear stress at the venous valve location and its association with deep vein thrombosis are less understood due to the complex and poorly understood bi-directional flow in the valve pocket region. We investigated how venous endothelial cells respond to flow shear stress around the venous valve region using a novel in vitro system that mimics venous flow. Results: Human umbilical vein EAhy. 926 cells were cultured on a flexible silastic membrane that mimicked venous tissue. Confluent cells were exposed to sinusoidal uni-and bi-directional pulsatile shear stress (0.1 to 1 dyne/cm2) for up to 6 h. Western-blot analyses indicated that endothelial nitric oxide (eNOS) expression levels decreased regardless of all tested flow patterns, stress magnitude, and shearing time. In contrast, the expression levels of inhibitor of κB (kappa B) and α (alpha)-tubulin were unaffected by the shear stress. Conclusions: Our results indicate that shear stress causes a decrease specifically in eNOS expression, suggesting that it may play a significant role in regulating inflammation related protein expression in endothelial cells.
Histological Changes in the Fracture Callus Following the Administration of Water Extract of Piper Sarmentosum (Daun Kadok) in Estrogen-Deficient Rats
Mohamed Abdalla Estai,Ima Nirwana Soelaiman,Ahmad Nazrun Shuid,Srijit Das
Iranian Journal of Medical Sciences , 2011,
Abstract: Background: The fracture healing is impaired in osteoporosis. Piper sarmentosum is a plant, which contains potent antioxidant, naringenin that may enhance fracture healing. The present histological study aimed to determine the effects of water extract of Piper sarmentosum on the late phase of frac-ture healing in estrogen-deficient rats. Methods: Twenty four female Sprague-Dawley rats (200-250 gm) were obtained. Six rats underwent sham operation and the rest were ovariectomized. Six weeks post-ovariectomy all the rats were fractured at the mid-diaphysis of the right femur and a K-wire was inserted for internal fixation. The sham group was given vehicle (normal saline) and the ovariectomized group was randomly subdivided into three groups: (i) ovariectomized-control group supplemented with vehicle; (ii) ovariectomized+estrogen replacement therapy group treated with es-trogen (100 μg/kg/day) and (iii) ovariectomized+Piper sarmentosum group treated with Piper sarmentosum water extract (125 mg/kg). Following six weeks of treatment, the rats were sacrificed and the right femora were harvested for histological assessment of fracture callus. Results: The ovariectomized-control group showed a significant delay in fracture healing compared to the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups. The median callus score for the ovariectomized-Piper sarmentosum group was 4.50 (range, 4-5), which was significantly higher than the median callus score 3.50 (range, 3-4) for the ovariectomized-control group (P=0.019). However, there was no significant (P>0.05) difference in the callus score among the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups groups. Conclusion: Treatment with water extract of Piper sarmentosum proved beneficial in the fracture healing in estrogen-deficient rats.
Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study
Estai, Mohamed Abdalla;Suhaimi, Farihah Haji;Das, Srijit;Fadzilah, Fazalina Mohd;Alhabshi, Sharifah Majedah Idrus;Shuid, Ahmad Nazrun;Soelaiman, Ima-Nirwana;
Clinics , 2011, DOI: 10.1590/S1807-59322011000500025
Abstract: introduction: osteoporotic fractures are common during osteoporotic states. piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. objectives: to observe the radiological changes in fracture calluses following administration of a piper sarmentosum extract during an estrogen-deficient state. methods: a total of 24 female sprague-dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + piper sarmentosum (ovariectomized + piper sarmentosum) group, which was supplemented with a water-based piper sarmentosum extract (125 mg/kg). six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a k-wire was inserted. each group of rats received their respective treatment for 6 weeks. following sacrifice, the right femora were subjected to radiological assessment. results: the mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 + 11.74 mm3) than in the sham-operated, estrogen-replacement-therapy and piper sarmentosum groups (20.4 + 4.05, 22.4 + 4.14 and 17.5 + 3.68 mm3, respectively). the median callus scores for the sham-operated, estrogen-replacement-therapy and piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). the median fracture scores for the sham-operated, estrogen-replacement-therapy and piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). conclusion: the piper sarmentosum extract improved fracture h
The Effects of Piper Sarmentosum Water Extract on the Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 1 in the Bones with Excessive Glucocorticoids
Elvy Suhana Mohd Ramli,Ima Nirwana Soelaiman,Faizah Othman,Fairus Ahmad
Iranian Journal of Medical Sciences , 2012,
Abstract: Background: Long-term glucocorticoid therapy causes secondary osteoporosis leading to pathological fractures. Glucocorticoid action in bone is dependant upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Piper sarmentosum is a local herb that possesses the ability to inhibit 11-βHSD1 enzyme activity. We aimed to determine the effects of Piper sarmentosum water extract on 11-βHSD1 expressions and activity in the bones of glucocorticoid-treated adrenalectomized rats. Methods: Forty male Sprague–Dawley rats (200-250 g) were used. Twenty-four animals were adrenalectomized and received intramuscular injection of dexamethasone (120 μg/kg/day). They were simultaneously administered with either Piper sarmentosum water extract (125 mg/kg/day), GCA (120 mg/kg/day) or distilled water as vehicle by oral gavage for two months. Eight animals were sham-operated and given vehicle daily, i.e. intramuscular olive oil and oral distilled water. Results: Following two months treatment, dexamethasone-treated adrenalectomized rats had significantly lower 11β-HSD1 dehydrogenase activity and higher 11β-HSD1 expression in the femoral bones compared to the sham-operated and baseline group. The rats supplemented with Piper sarmentosum water extract had significantly higher 11β-HSD1 dehydrogenase activity and lower 11β-HSD1 expression in the bones. Conclusion: The results showed that Piper sarmentosum water extract had the ability to prevent glucocorcoticoid excess in the bones of glucocorticoid-treated adrenalectomized rats through the local modulation of 11β-HSD1 expression and activity, and may be used as prophylaxis for osteoporosis in patients on long-term glucocorticoid treatment.
Studies of the anti-inflammatory and antipyretic activities of the methanolic extract of Piper sarmentosum Roxb. leaves in rats
Wibool Ridtitid,Peerati Ruangsang,Wantana Reanmongkol,Malinee Wongnawa
Songklanakarin Journal of Science and Technology , 2007,
Abstract: The methanolic extract of Piper sarmentosum Roxb. leaves at doses of 50, 100 and 200 mg/kg was investigated for anti-inflammatory and antipyretic activities on carrageenan-induced rat paw edema and brewer's yeast-induced pyrexia in rats. The results revealed that the extract at test doses produced a significant anti-inflammatory activity at 3 h with an inhibition of paw edema of 8.6% (P<0.05), 18.6% (P<0.01) and 24.7% (P<0.01), respectively, compared to the reference drug aspirin 200 mg/kg p.o. with an inhibition of 33.3% (P<0.01). Only the extract at the dose of 200 mg/kg p.o. showed a significant inhibition ofcarrageenan-induced rat paw edema beginning at 2 h of 11.8% (P<0.01) and at 3, 4 and 5 h of 24.7% (P< 0.01), 14.1% (P<0.01) and 11.9% (P<0.01), respectively, whereas the reference drug aspirin 200 mg/kg p.o. exhibited a significant inhibition of edema beginning at 1 h of 15.6% (P<0.05) and at 2, 3, 4 and 5 h of 31.8% (P<0.01), 33.3% (P<0.01), 30.4% (P<0.01) and 30.2% (P<0.01), respectively. The methanolic extract of P. sarmentosum leaves (50, 100 and 200 mg/kg p.o.) did not decrease brewerís yeast-induced pyrexia in rats, whereas aspirin at the dose of 200 mg/kg p.o. showed a significant antipyretic activity by reducing fever in this animal model. In acute toxicity test, the methanolic extract of P. sarmentosum leaves at the dose of 5g/kg did not produce any abnormal symptoms or mortality in rats.
Effects of Piper sarmentosum Water Extract on 11-β Hydroxysteroid Dehydrogenase Type 1 Bioactivity in Ovariectomy-Induced Obese Rats  [PDF]
A. Aida Azlina,H.S. Farihah,H.M.S. Qodriyah,M.F. Nur Azlina
International Journal of Pharmacology , 2009,
Abstract: The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) convert inactive circulating 11-keto steroids into active glucocorticoids, amplifying local glucocorticoid action. It is elevated in adipose tissue in obese humans and rodents, suggesting that adipose tissue glucocorticoid excess may be the causative factor for obesity. This study was conducted to evaluate the effects of Piper sarmentosum (PS) water extract and glycyrrhizic acid (GCA) on 11β-HSD1 bioactivity in ovariectomized induced obese rats. Fourty-two female Sprague-Dawley rats were randomly divided into six groups; four treatments (PS, GCA, CTRL and SHM) and two basal (B-CTRL and B-SHM). All groups underwent ovariectomy excluding SHM and B-SHM which underwent sham operation. Basal groups were sacrificed on the first day of treatment, while ovariectomized groups were given PS extract (0.125 g kg-1), GCA (0.120 g kg-1) and water (CTRL), respectively, while SHM received only water. Blood pressure was measured monthly while body weight weekly. After five months, rats were sacrificed and liver, heart and visceral adipose tissues were taken for analysis. Piper sarmentosum (PS) and GCA group showed a significant reduction in enzyme activity but no difference in body weight compared to CTRL group. Meanwhile only the blood pressure in GCA group was significantly higher after three months of treatment as compared to CTRL group but no difference after five months. In conclusion, both PS water extract and GCA have the ability to reduce 11β-HSD1 enzyme activity but only GCA cause an increased in blood pressure.
Intrinsic anticarcinogenic effects of Piper sarmentosum ethanolic extract on a human hepatoma cell line
Shahrul Hisham Zainal Ariffin, Wan Haifa Haryani Wan Omar, Zaidah Zainal Ariffin, Muhd Fauzi Safian, Sahidan Senafi, Rohaya Megat Abdul Wahab
Cancer Cell International , 2009, DOI: 10.1186/1475-2867-9-6
Abstract: The anticarcinogenic activity of an ethanolic extract from Piper sarmentosum in HepG2 and non-malignant Chang's liver cell lines has been previously determined using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) (MTT) assays, where the IC50 value was used as a parameter for cytotoxicity. The ethanolic extract that showed anticarcinogenic properties in HepG2 cells had an IC50 of 12.5 μg mL-1, while IC50 values in the non-malignant Chang's liver cell line were greater than 30 μg mL-1. Apoptotic morphological changes in HepG2 cells were observed using an inverted microscope and showed chromatin condensation, cell shrinkage and apoptotic bodies following May-Grunwald-Giemsa's staining. The percentage of apoptotic cells in the overall population (apoptotic index) showed a continuously significant increase (p < 0.05) in 12.5 μg mL-1 ethanolic extract-treated cells at 24, 48 and 72 hours compared to controls (untreated cells). Following acridine orange and ethidium bromide staining, treatment with 10, 12 and 14 μg mL-1 of ethanolic extracts caused typical apoptotic morphological changes in HepG2 cells. Molecular analysis of DNA fragmentation was used to examine intrinsic apoptosis induced by the ethanolic extracts. These results showed a typical intrinsic apoptotic characterisation, which included fragmentation of nuclear DNA in ethanolic extract-treated HepG2 cells. However, the non-malignant Chang's liver cell line produced no DNA fragmentation. In addition, the DNA genome was similarly intact for both the untreated non-malignant Chang's liver and HepG2 cell lines.Therefore, our results suggest that the ethanolic extract from P. sarmentosum induced anticarcinogenic activity through an intrinsic apoptosis pathway in HepG2 cells in vitro.Human hepatocellular carcinoma is the fifth most common cancer in the world and the fourth most common cause of cancer-associated mortality [1]. Surgical resection and local treatment are frequently limited due to metasta
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