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Planta medica [journal]
- The Endothelial Protective Properties of Essential Oil from Fructus Alpiniae zerumbet via the Akt/NOS-NO Signaling Pathway In Vitro. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 28.
Oxidized low-density lipoprotein has been demonstrated to induce vascular injury, at least partly, through the nitric oxide-dependent pathway. Our previous studies showed that the essential oil from Fructus Alpiniae zerumbet had a capacity of antioxidation to ameliorate endothelial function and vasodilatation on aortic rings ex vivo. The present study aims to confirm the hypothesis that Fructus Alpiniae zerumbet protects against oxidized low-density lipoprotein-induced endothelial dysfunction in human aortic endothelial cells, and the role nitric oxide synthase plays in the process. Human aortic endothelial cells were pretreated with one of three different doses of Fructus Alpiniae zerumbet (1, 2, or 4 µg/mL), simvastatin (10 µM), or vehicle,followed by coincubation with oxidized low-density lipoprotein (150 µg/mL), for designed time periods. Exposure to oxidized low-density lipoprotein resulted in cytotoxicity accompanied by mitochondrial membrane potential collapse, excessive reactive oxygen species generation, and a decrease of nitric oxide production. The upregulation of inducible nitric oxide synthase mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Furthermore, oxidized low-density lipoprotein inhibited Akt phosphorylation and downregulated endothelial nitric oxide synthase and soluble guanylatecyclase in mRNA expression and the protein level. However, cytotoxicity and aberrant reactive oxygen species and nitric oxide generation caused by oxidized low-density lipoprotein could be significantly inhibited by Fructus Alpiniae zerumbet or Sim pretreatment. Results from this study confirmed that Fructus Alpiniae zerumbet could protect against oxidized low-density lipoprotein-induced endothelial dysfunction by antioxidation and modulating the Akt/nitric oxide synthase-nitric oxide signaling pathway.
- Xanthine Oxidase Inhibitors from Garcinia esculenta Twigs. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 23.
The EtOAc-soluble portion of the 80 % (v/v) EtOH extract from the twigs of Garcinia esculenta exhibited strong xanthine oxidase inhibition in vitro. Bioassay-guided purification led to the isolation of 1,3,6,7-tetrahydroxyxanthone (3) and griffipavixanthone (8) as the main xanthine oxidase inhibitors, along with six additional compounds (1, 2, 4-7), including two new compounds (1 and 2). This enzyme inhibition was dose dependent with an IC50 value of approximately 1.2 µM for 3 and 6.3 µM for 8. The inhibitory activity of 3 was stronger than the control allopurinol (IC50 value: 5.3 µM). To our knowledge, compound 8 is the first bixanthone that demonstrated potent XO inhibitory activity in vitro. The structures of the new compounds were established by spectroscopic analysis, and the optical properties and absolute stereochemistry of racemic (±) esculentin A (2) were further determined by the calculation of the DP4 probability and analysis of its MTPA ester derivatives.
- Neuroprotection of Total Steroid Saponins from Dioscorea zingiberensis against Transient Focal Cerebral Ischemia-Reperfusion Injury in Rats via Anti-Inflammatory and Antiapoptotic Effects. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 23.
Total steroid saponins isolated from Dioscorea zingiberensis have shown a variety of beneficial bioactivities. However, there are no reports about their neuroprotective effects, until now. Therefore, in the present study, we explored the neuroprotective effects of the total steroid saponins from D. zingiberensis on rats against transient focal cerebral ischemia-reperfusion and their underlying mechanisms. Healthy adult Sprague-Dawley rats were randomly assigned to six groups. After pretreatment with D. zingiberensis total steroid saponins intragastrically for six days, the rats were subjected to an ischemia injury by surgery on the middle cerebral artery occlusion for 90 min. Compared to the ischemia-reperfusion group, the D. zingiberensis total steroid saponin group of rats, especially those given a 30-mg/kg dose, showed not only a marked reduction in neurological deficit scores, cerebral infarct volume, and brain edema, but also an increase in neuron survival (Nissl bodies) in the hippocampal cornuammons 1 and cortex hemisphere of the ipsilateral ischemia. At the same time, the inflammatory cytokines in serum induced by the middle cerebral artery occlusion were significantly decreased by the preadministration of D. zingiberensis total steroid saponins. Furthermore, the increase of caspase-3 was evidently reduced in the hippocampal cornuammons 1 and cortex of the hemisphere injured brain. Finally, the downregulating antiapoptotic Bcl-2 and upregulating proapoptotic Bax proteins were obviously suppressed. Taken together, the current findings suggest that D. zingiberensis total steroid saponins played a potential neuroprotective role against a severe injury induced by transient focal cerebral ischemic reperfusion in a rat experimental model, and this role may be mediated by its anti-inflammatory and antiapoptotic actions.
- Antagonism of Ca2+ Influx via L-Type Ca2+ Channels Mediates the Vasorelaxant Effect of Catharanthus roseus-Derived Vindorosine in Rat Renal Artery. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 23.
Catharanthus roseus is a traditional herbal medicine used in Asian and African countries for the treatment of various diseases including hypertension. The present study examined possible cellular mechanisms for the relaxation of rat renal arteries induced by vindorosine extracted from C. roseus. Intrarenal arteries were isolated from 200-300 g male Sprague-Dawley rats and treated with different pharmacological blockers and inhibitors for the measurement of vascular reactivity on a Multi Myograph System. Fluorescence imaging by laser scanning confocal microscopy was utilized to determine the intracellular Ca(2+) level in the vascular smooth muscles of the renal arteries. Vindorosine in micromolar concentrations relaxes renal arteries precontracted by KCl, phenylephrine, 11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α, and serotonin. Vindorosine-induced relaxations were unaffected by endothelium denudation or by treatment with the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester hydrochloride, the guanylyl cyclase inhibitor 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, the cyclooxygenase inhibitor indomethacin, or K(+) channel blockers such as tetraethylammonium ions, glibenclamide, and BaCl2. Vindorosine-induced relaxations were attenuated in the presence of 0.1 µM nifedipine (an L-type Ca(2+) channel blocker). Vindorosine also concentration-dependently suppressed contractions induced by CaCl2 (0.01-5 mM) in Ca-free 60 mM KCl solution. Furthermore, fluorescence imaging using fluo-4 demonstrated that 30 min incubation with 100 µM vindorosine reduced the 60 mM KCl-stimulated Ca(2+) influx in the smooth muscles of rat renal arteries. The present study is probably the first report of blood vessel relaxation by vindorosine and the possible underlying mechanisms involving the inhibition of Ca(2+) entry via L-type Ca(2+) channels in vascular smooth muscles.
- Pharmacological Activities of Cilantro's Aliphatic Aldehydes against Leishmania donovani. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 23.
Leishmaniasis is a chronic infectious disease caused by different Leishmania species. Global occurrences of this disease are primarily limited to tropical and subtropical regions. Treatments are available; however, patients complain of side effects. Different species of plants have been screened as a potential source of new drugs against leishmaniasis. In this study, we investigated the antileishmanial activity of cilantro (Coriandrum sativum) essential oil and its main components: (E)-2-undecenal, (E)-2-decenal, (E)-2-dodecenal, decanal, dodecanal, and tetradecanal. The essential oil of C. sativum leaves inhibits growth of Leishmani donovani promastigotes in culture with an IC50 of 26.58 ± 6.11 µg/mL. The aliphatic aldehydes (E)-2-decenal (7.85 ± 0.28 µg/mL), (E)-2-undecenal (2.81 ± 0.21 µg/mL), and (E)-2-dodecenal (4.35 ± 0.15 µg/mL), all isolated from C. sativum essential oil, are effective inhibitors of in vitro cultures of L. donovani promastigotes. Aldehydes (E)-2-decenal, (E)-2-undecenal, and (E)-2-dodecenal were also evaluated against axenic amastigotes and IC50 values were determined to be 2.47 ± 0.25 µg/mL, 1.25 ± 0.11 µg/mL, and 4.78 ± 1.12 µg/mL, respectively. (E)-2-Undecenal and (E)-2-dodecenal demonstrated IC50 values of 5.65 ± 0.19 µg/mL and 9.60 ± 0.89 µg/mL, respectively, against macrophage amastigotes. These cilantro compounds showed no cytotoxicity against THP-1 macrophages.
- Tingenone, a Pentacyclic Triterpene, Induces Peripheral Antinociception Due to Opioidergic Activation. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 22.
Plants belonging to the genus Maytenus are routinely used in folk medicine for the treatment of pain diseases. Our previous phytochemical study of the roots of Maytenus imbricata resulted in the isolation and characterization of tingenone, a pentacyclic triterpene. Natural triterpenoids are of growing interest because they have several biological activities, including analgesic properties. The present study assessed the involvement of the opiodergic pathway in the tingenone-induced antinociceptive effect against hyperalgesia induced by prostaglandin E2 (2 µg) in the peripheral pathway. We evaluated the effect of several antagonists to opioid receptors using the mouse paw pressure test. Tingenone administered into the right hind paw induced a local antinociceptive effect that was antagonized by naloxone, a nonselective antagonist to opioid receptors. Clocinnamox, naltrindole, and nor-binaltorphimine are selective antagonists to µ, δ, and κ receptors, respectively, which reverted the peripheral antinociception induced by tingenone. Bestatine acts as an inhibitor of aminopeptidase, an enzyme that degrades endogenous opioid peptides, and was shown to intensify the antinociceptive effect of tingenone. The results suggest that the opioidergic system participates in the peripheral antinociception induced by tingenone.
- Sucrose Esters from Physalis peruviana Calyces with Anti-Inflammatory Activity. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 22.
Physalis peruviana is a native plant from the South American Andes and is widely used in traditional Colombian medicine of as an anti-inflammatory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Previous studies performed by our group on P. peruviana calyces showed potent anti-inflammatory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the active compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vitro. The enriched fraction of P. peruviana was purified by several chromatographic methods to obtain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were elucidated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macrophages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation induced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demonstrated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. peruviana that showed a potent anti-inflammatory effect. These results suggest the potential of sucrose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases.
- Protective Role of Cupressuflavone from Cupressus macrocarpa against Carbon Tetrachloride-Induced Hepato- and Nephrotoxicity in Mice. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 22.
The hepatoprotective and nephroprotective activity of cupressuflavone isolated from Cupressus macrocarpa was investigated against CCl4-induced toxicity in mice. Cupressuflavone was administered (40, 80, and 160 mg/kg/day) for five days. CCl4 was administered (0.5 mL/kg intraperitoneally) at the end of the experiment. A substantial increase (p < 0.001) in the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, cholesterol, creatinine, uric acid, urea, and malondialdehyde was observed in the CCl4-treated group compared to the normal control group. In contrast, a significant reduction (p < 0.001) in glutathione and superoxide dismutase contents as well as the total protein level was evident in the CCl4-intoxicated mice. Cupressuflavone pretreatment markedly inhibited the CCl4-induced increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, creatinine, uric acid, urea, and malondialdehyde levels in a dose-dependent manner (p < 0.001 at all the tested doses). In addition, a significant (p < 0.001) and dose-dependent decrease in the total bilirubin levels was evident by cupressuflavone pretreatment (80 and 160 mg/kg/day) when compared to the CCl4-intoxicated group. Furthermore, cupressuflavone administration significantly increased the activity of antioxidant parameters glutathione and superoxide dismutase as well as the serum protein levels (p < 0.001 at all the tested doses) in a dose-dependent manner. Histological observations confirmed the strong hepato- and nephroprotective activity. These findings suggest that cupressuflavone could exert a beneficial effect against oxidative stress by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes induced by CCl4 in the liver and kidney tissues. The structure of cupressuflavone was identified by NMR, UV, and HRESI-MS/MS spectral data.
- In Vitro Anti-Inflammatory and Wound-Healing Potential of a Phyllostachys edulis Leaf Extract - Identification of Isoorientin as an Active Compound. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 15.
Extracts prepared from the leaves of Phyllostachys edulis (bamboo) have received attention in pharmacological research due to their potent antitumor, anti-inflammatory, antimicrobial, and anti-ulcerogenic activities. In this study, anti-inflammatory effects of a bamboo leaf extract on tumor necrosis factor alpha-induced overproduction of interleukin 8, vascular endothelial growth factor, and interleukin 6 in immortalized human keratinocytes were investigated for the first time. In addition, wound-healing effects were evaluated in 3T3-swiss albino mouse fibroblasts. Bamboo leaf extract and isoorientin inhibited the tumor necrosis factor alpha-induced release of interleukin 8 and vascular endothelial growth factor. Furthermore, isoorientin dose-dependently reduced levels of interleukin 6 in tumor necrosis factor alpha-α-treated immortalized human keratinocytes cells. Wound healing was evaluated using a modification of the classical scratch assay. For evaluation of the wound gap, a new computerized method based on time-lapse microscopy was developed. It was shown that bamboo leaf extract (10 µg/mL) improved wound closure by 28 % (12 h) and 54 % (24 h), respectively. In concentrations of 50 µg/mL and above, bamboo leaf extract inhibited cell migration without affecting cell viability. Isoorientin (10 µM) improved wound closure by 29 % (12 h) and 56 % (24 h), respectively. Comparable to bamboo leaf extract, higher concentrations of isoorientin prevented cell migration. It is suggested that bamboo leaf extract as well as isoorientin have a dual activity - in higher doses, they show anti-inflammatory effects, and in lower concentrations, they exert anti-angiogenic activities.
- Antimicrobial, Antioxidative, and Insect Repellent Effects of Artemisia absinthium Essential Oil. [JOURNAL ARTICLE]
- Planta Med 2014 Oct 15.
In this paper, the chemical composition and biological activity of the essential oil of Artemisia absinthium was studied. The aim of this study was to investigate the potential of ethnopharmacological uses of this plant species in the treatment of gastrointestinal diseases and wounds, and as an insect repellent. The aerial part of the plant was hydrodistilled, and the chemical composition of the essential oil was analyzed by gas chromatography and gas chromatography/mass spectrometry. Forty-seven compounds, corresponding to 94.65 % of the total oil, were identified, with the main constituents being sabinene (24.49 %), sabinyl acetate (13.64 %), and α-phellandrene (10.29 %). The oil yield was 0.23 % (v/w). The antimicrobial activity of the oil was investigated against ten bacterial isolates (from patients wounds and stools) and seven American Type Culture Collection strains using a microwell dilution assay. The minimal inhibitory/bactericidal concentration of the oil ranged from < 0.08 to 2.43 mg/mL and from 0.08 to 38.80 mg/mL, respectively. The antioxidant activity of the essential oil was evaluated using 2,2-diphenyl-1-picrylhydrazil and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical-scavenging methods and assessed as significant. Skin irritation potential and acute toxicity of the oil were also investigated. Results of the skin irritant reaction showed that none of the 30 volunteers developed a positive skin irritant reaction to undiluted A. absinthium essential oil. Acute oral exposure to the essential oil did not cause mortality in the treated mice, but it did cause neurological, muscle, and gastrointestinal problems. A subchronic toxicity test on Drosophila melanogaster showed that the essential oil of A. absinthium is toxic for developing insect larvae. Starting with the concentration of 0.38 % of essential oil in medium, significant mortality of larvae exposed to the oil was noted when compared to the control. Probit analysis revealed that the LC50 value of A. absinthium essential oil for D. melanogaster larvae after 15 days of exposure was 6.31 % (49 mg/mL). The essential oil also affected the development of D. melanogaster larvae and significantly delayed achievement of the pupa stadium.