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Effect of Polygonum viviparum (PV) on endothelial nitric oxide (NO) synthase (eNOS) phosphorylation, cytosolic nuclear factor E2-related factor 2 (Nrf2) degradation, and heme oxygenase (HO)-1 activation. (A) Human umbilical vein endothelial cells (HUVECs) were treated with PV (at the indicated concentrations) for 0.5 or 24 h. Total proteins (30 μg) were analyzed on an 8% SDS-PAGE with an antibody specific of eNOS Ser-1177; and analyzed on 10% SDS-PAGE with an antibody specific of Nrf2 and HO-1. (B) The relative density was calculated as the ratio of eNOS (phosphor form) expression to eNOS (total form) expression. In addition, the relative density was calculated as the ratio of Nrf2 degradation and HO-1 expression to β-actin expression. Each electrophoretogram is representative of the results from more than 5 individual experiments. * p < 0.05, #p <0.05, ξξp < 0.01, significantly different from the control.
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Background
In the past several decades, Polygonum viviparum L. (PV) was reported to have antibacterial, antiulcer, antioxidant, antitumor, anti-inflammatory, and antiarthritic properties. The anti-inflammatory pathway was recently elucidated through cytosolic nuclear factor E2-related factor 2 (Nrf2) activation and heme oxygenase (HO)-1 protein exp...
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Traditional Tibetan medicine (TTM) is major component of traditional Chinese medicine (TCM). Over thousands of years, the Tibetan people have gradually established a comprehensive theoretical system for Tibetan medicine and obtained rich clinical experience in the snow-covered plateau. The history of TTM has developed rapidly, especially since the...
Citations
... Modern studies have shown that PV contains a variety of chemical components including flavonoids, flavonoid glycosides, organic acids, volatile oils, tannins, polysaccharides, and trace elements [8]. In addition, due to its various pharmacological activities such as antioxidant, anti-tumor, and antibacterial properties, PV has shown promising effects in the treatment of diseases including bronchitis, hemorrhoids, ulcers, and vomiting [10,11]. However, only a few studies have been reported on the chemical composition and pharmacological activity of PV, and further studies are urgently needed. ...
Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. Polygonum viviparum L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats’ own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against H2O2-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.
... Confluent cells were treated with ACh (30 μM) alone, MOE (3-30 μg/mL) alone, and MOE (30 μg/mL) plus L-NAME (100 μM), for 30 or 60 min. Acetylcholine, a well-known endotheliumderived NO inducer, was used as a positive control [18]. In the case of experiments with eNOS inhibitor L-NAME, the cells were pre-incubated the inhibitor for 30 min prior to the MOE administration [19,20]. ...
A mass of evidence has identified a promoting of nitric oxide (NO) production in endothelial cells using natural products as a potential strategy to prevent and treat hypertension. This study investigated whether the aqueous extract of Moringa oleifera leaves (MOE) could lower mean arterial pressure (MAP) and relax mesenteric arterial beds in rats via stimulating endothelium-derived NO production. Intravenous administration of MOE (1-30 mg/ kg) caused a dose-dependent reduction in MAP in anesthetized rats. In rats pretreated with the NO-synthase inhibitor, N ω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, i.v.), the effect of MOE on MAP was significantly reduced. MOE (0.001-3 mg) induced relaxation in methoxamine (10 μM) pre-contracted mesenteric arterial beds, which was abolished by endothelium denudation. This endothelium-dependent vasorelaxation was reduced by L-NAME (100 μM) or the NO-sensitive guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 μM). In primary human pulmonary artery endothelial cells, MOE (3-30 μg/mL) induced NO production, which was inhibited by L-NAME (100 μM) pretreatment. These findings show that MOE stimulates the endothelium-derived NO release for driving its vasorelaxation to lower arterial blood pressure. These suggest the development of MOE as a natural antihypertensive supplement.
... The 5 mM H 2 O 2 treatment significantly promoted the generation of the reduced NBT (formazan) in isolated rat aortic rings, while the 50 μM RA almost entirely abolished the effect of H 2 O 2 (Figure 2(d)). that NO is the most potent vasodilator and the modulator of intracellular oxidative status, and it is produced by the eNOS in endothelium [19], we explored the effect of eNOS activation in RA's protection against the endothelial dysfunction induced by H 2 O 2 . The pretreatment with the NOS inhibitor L-NAME alone significantly decreased the vasodilation induced by ACh (Figure 3(a)), while increased the NBT reduction (Figure 3(b)) in rat aortic rings. ...
Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H 2 O 2 ). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H 2 O 2 . H 2 O 2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H 2 O 2 . The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H 2 O 2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.
... Anti-inflammatory, antibacterial, antiulcer, antioxidant, antitumor, antiarthritic, cure bronchitis, piles, wounds, ulcers, vomiting and biliousness (Hui et al., 2013;Chang et al., 2014) Volatile oil, flavonoids, flavone glycosides, gallic acid, saponins and tannins (Chang et al., 2014) Plantago lanceolata L., Plantaginaceae Febrifuge, demulcent, treat diarrhea, dysentery, piles, constipation, whooping cough, bronchitis, neck rashes, sores, boils, blisters, jaundice and inflammation (Singh and Kumar, 2000;Prajapati et al., 2003;Kayani et al., 2014;Rana and Masoodi, 2014;Abbasi et al., 2015) Iridoid glucoside aucubin, phenylpropanoid glycoside verbascoside and tannins (Stewart, 1996). ...
... Anti-inflammatory, antibacterial, antiulcer, antioxidant, antitumor, antiarthritic, cure bronchitis, piles, wounds, ulcers, vomiting and biliousness (Hui et al., 2013;Chang et al., 2014) Volatile oil, flavonoids, flavone glycosides, gallic acid, saponins and tannins (Chang et al., 2014) Plantago lanceolata L., Plantaginaceae Febrifuge, demulcent, treat diarrhea, dysentery, piles, constipation, whooping cough, bronchitis, neck rashes, sores, boils, blisters, jaundice and inflammation (Singh and Kumar, 2000;Prajapati et al., 2003;Kayani et al., 2014;Rana and Masoodi, 2014;Abbasi et al., 2015) Iridoid glucoside aucubin, phenylpropanoid glycoside verbascoside and tannins (Stewart, 1996). ...
Prenatal hypoxia can affect vascular functions in young offspring. However, there is limited knowledge regarding whether and how prenatal hypoxia influences vascular functions in aged offspring. This study compared the effects of prenatal hypoxia on the mesenteric arteries (MA) between a young adult and aged offspring and investigated the underlying mechanisms. Pregnant rats were randomly divided into the control and prenatal hypoxia groups. The vascular functions and molecular levels were assessed in 5-month-old (5 M) or 20-month-old (20 M) offspring. Prenatal hypoxia decreased acetylcholine-mediated vascular relaxations in 20-M but not 5-M offspring. Sodium nitroprusside-mediated relaxation curves were not altered by prenatal hypoxia in 5- and 20-M offspring. Prenatal hypoxia enhanced the contractile responses caused by phenylephrine, phorbol 12,13-dibutyrate, and 5-hydroxytryptamine only in 5-M offspring. The endothelial NO synthase (eNOS) activities were decreased along with downregulated eNOS mRNA expression and phosphorylated eNOS/total eNOS protein expression in 20-M offspring with prenatal hypoxia. The NADPH oxidase (NOX) inhibitor apocynin and superoxide dismutase (SOD) mimetic tempol restored the acetylcholine-mediated weaker relaxations in 20-M offspring with prenatal hypoxia. Enzyme-linked immunosorbent and dihydroethidium assay showed that prenatal hypoxia enhanced oxidative stress in 20-M offspring. Transmission electron microscopy showed that prenatal hypoxia damaged mitochondrial structures in the MA endothelial cells of 20-M offspring. Increased NOX2 protein expression and decreased SOD3 expression were found in 20-M offspring. The results demonstrated that endothelial dysfunction induced by intrauterine hypoxia occurred with aging via enhanced oxidative stress and decreased nitric oxide activities in aged offspring.
The present research aimed to isolate the non-polar secondary metabolites that produce the vasodilator effects induced by the dichloromethane extract of Prunus serotina (P. serotina) fruits and to determine whether the NO/cGMP and the H2S/KATP channel pathways are involved in their mechanism of action. A bioactivity-directed fractionation of the dichloromethane extract of P. serotina fruits led to the isolation of ursolic acid and uvaol as the main non-polar vasodilator compounds. These compounds showed significant relaxant effect on rat aortic rings in an endothelium- and concentration-dependent manner, which was inhibited by NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG) and glibenclamide (Gli). Additionally, both triterpenes increased NO and H2S production in aortic tissue. Molecular docking studies showed that ursolic acid and uvaol are able to bind to endothelial NOS and CSE with high affinity for residues that form the oligomeric interface of both enzymes. These results suggest that the vasodilator effect produced by ursolic acid and uvaol contained in P. serotina fruits, involves activation of the NO/cGMP and H2S/KATP channel pathways, possibly through direct activation of NOS and CSE.
Medicinal Plants: Chemistry, Biology and Omics reviews the phytochemistry, chemotaxonomy, molecular biology, and phylogeny of selected medicinal plant tribes and genera, and their relevance to drug efficacy. Medicinal plants provide a myriad of pharmaceutically active components, which have been commonly used in traditional Chinese medicine and worldwide for thousands of years. Increasing interest in plant-based medicinal resources has led to additional discoveries of many novel compounds, in various angiosperm and gymnosperm species, and investigations on their chemotaxonomy, molecular phylogeny and pharmacology. Chapters in this book explore the interrelationship within traditional Chinese medicinal plant groups and between Chinese species and species outside of China. Chapters also discuss the incongruence between chemotaxonomy and molecular phylogeny, concluding with chapters on systems biology and "-omics? technologies (genomics, transcriptomics, proteomics, and metabolomics), and how they will play an increasingly important role in future pharmaceutical research.
This chapter synthesizes current knowledge on phytochemistry, bioactivity, molecular phylogeny, and omics of Polygoneae medicinal resources. Many species in the seven genera of Polygoneae are traditional and popular medicinal herbs. Anthraquinones and stilbenes are characteristic medicinal compounds of Polygoneae, while other useful constituents, such as alkaloids, glycosides, flavonoids, volatile oils, tannins, resins, coumarins, and lignans, have also been isolated from Polygoneae species. Among versatile bioactivities of Polygoneae compounds, their effects on the cardiovascular and nervous systems and their anti-inflammatory, antimicrobial, antiparasitic, insecticidal, anticancer, and antioxidant activities are highlighted. Interspecific hybridization and the following polyploidization play a major role in Polygoneae diversification. Nuclear ITS and chloroplast DNA sequences are retrieved to resolve the interspecific relationship and reassign some taxa to the appropriate genus. Omics study of Polygoneae is at the budding stage, which will revolutionize the sustainable utilization of Polygoneae medicinal resources.
