ISRN Pharmacology最新文献

We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) were determined. PEP (100 mM) significantly prevented an increase in LDH leakage, histological changes, such as tubulonecrosis and vacuolization, and changes in oxidative stress parameters during 72 h of cold preservation in mouse liver. Although glucose (100 mM) partly prevented LDH leakage and histological changes, no effects against oxidative stress were observed. By contrast, NAC inhibited oxidative stress in the liver and did not prevent LDH leakage or histological changes. PEP also significantly prevented kidney damage during cold preservation in a dose-dependent manner, and the protective effects were superior to those of glucose and NAC. We suggest that PEP, a functional carbohydrate with organ protective and antioxidative activities, may be useful as an organ preservation agent in clinical transplantation.

A variety of active constituents with wide range of pharmacological actions have been reported with Centella asiatica. The present study was undertaken to assess analgesic and anti-inflammatory properties of its leaf extracts. Dried leaves were defatted with petroleum ether and extracted with chloroform and methanol. Both chloroform and methanol extracts were evaluated for analgesic activity through tail clip, tail flick, tail immersion, and writhing assay tests at doses of 50, 100, and 200 mg/kg using Swiss albino mice. On the other hand, anti-inflammatory assay was performed by carrageenan induced paw edema of methanol extract at 100 and 200 mg doses in Wistar albino rat. Dextropropoxyphene and indomethacin were employed as a standard for analgesic and anti-inflammatory studies, respectively. Our present study demonstrated that Centella asiatica bears significant analgesic and anti-inflammatory activities in those models.

104 samples from 27 accessions belonging to 12 species of genus Epimedium were studied on the basis of cytology observation, POD (i.e., peroxide) isozyme, high performance liquid chromatography (i.e., HPLC) fingerprint, and interspecific hybridization. The cytology observation showed karyotypes of twelve species studied; all are 2A symmetry type of Stebbins standard and similar to each other, and except for karyotype of E. leptorrhizum which is 2n = 2x = 8m (2SAT) + 4sm, the rest are 2n = 2x = 6m (2SAT) + 6sm. Chromosomes C-banding of barrenwort species varies, with 15 to 22 bands, consisting of centromeric bands, intercalary bands, terminal bands, and middle satellite bands. Results of POD isozyme showed that the zymographs vary greatly and sixteen bands were detected in the eleven species, and each species has its own characteristic bands different from the others. Studies on the HPLC fingerprint showed that the HPLC fingerprint of different species has characteristic peaks, divided into two regions (retention time < 10 min and retention time > 10 min). Results of interspecific hybridization showed that crosses of any combination among seven species studied are successful and the rates of grain set vary greatly. Based on these results, the system and phylogeny of this genus were inferred.

Sericin-derived oligopeptides obtained from silk cocoons were investigated for the in vivo hypotensive effect and investigated for the underlying mechanism involved in vasodilation in isolated rat thoracic aorta. In normotensive anesthetized rats, oligopeptides induced an immediate and transient hypotensive activity. In rat aortic rings, oligopeptides induced a concentration-dependent vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with endothelium-intact or endothelium-denuded rings. In endothelium-intact rings, pretreatment with N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 µM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM), a selective inhibitor of the guanylyl cyclase enzyme, significantly reduced the relaxant effect of oligopeptides. However, indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides-induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5 mM) reduced the maximal relaxant effect induced by oligopeptides. By contrast, relaxation was not affected by 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 µM), or barium chloride (BaCl2, 1 mM). In depolarization Ca(2+)-free solution, oligopeptides inhibited calcium chloride- (CaCl2-) induced contraction in endothelium-denuded rings in a concentration-dependent manner. Nevertheless, oligopeptides attenuated transient contractions in Ca(2+)-free medium containing EGTA (1 mM) induced by 1 µM PE, but they were not affected by 20 mM caffeine. It is obvious that potent vasodilation effect of oligopeptides is mediated through both the endothelium and the vascular smooth muscle.

Objective. The objective of this study was to investigate the inotropic mechanisms and the related muscarinic receptor subtype of acetylcholine (ACh) in canine cardiac Purkinje fibers. Materials and Methods. Isolated Purkinje fiber bundles were used for the measurement of contraction. The receptor subtype was determined using PCR and real-time PCR methods. Results. ACh evoked a biphasic response with a transient negative inotropic effect followed by a positive inotropic effect in a concentration-dependent manner. The biphasic inotropic actions of ACh were inhibited by the pretreatment with atropine. Caffeine inhibited the positive inotropic effect of ACh. ACh increased inositol-1,4,5-trisphosphate content in the Purkinje fibers, which was abolished by atropine. Muscarinic subtypes 2 (M2) and 3 (M3) mRNAs were detected in the canine Purkinje fibers albeit the amount of M3 mRNA was smaller than M2 mRNA. M1 mRNA was not detected. Conclusion. These results suggest that the positive inotropic action of ACh may be mediated by the activation of IP3 receptors through the stimulation of M3 receptors in the canine cardiac Purkinje fibers.

The present study reports the antioxidant and membrane protective activities of Calotropis procera aqueous root extract using several in vitro assays along with the determination of phenolic as well as flavonoid contents. Total phenol and flavonoid contents in extract were 15.67 ± 1.52 mg propyl gallate equivalent/g and 1.62 ± 0.05 mg quercetin equivalent/g, respectively. UV-visual spectroscopic scanning of the extract indicated the presence of glycoside-linked tannins or flavonoids. The extract exhibited appreciable reducing power signifying hydrogen donating potential. DPPH radical scavenging assay revealed substantial free radical scavenging activity (42-90%) in the extracts. Concentration dependent response was observed in the metal ion chelating activity (16-95%). Extracts also provided protection against iron induced lipid peroxidation in rat tissue (liver, brain, and kidney) homogenates. Comparatively better protective efficacy against peroxidative damage was observed in liver (71%) followed by kidney (65%) and brain (60%) tissues. Positive correlation (r (2) = 0.756) was observed between DPPH free radical scavenging activity and reducing power of extract. Similarly strong positive correlation (r (2) ≈ 0.756) was observed between metal ion chelating ability and percentage lipid peroxidation inhibition in different tissues. The study demonstrated considerable protective efficacy in C. procera root aqueous extracts against free radical and metal ion mediated oxidative damage.

The genetic models in Drosophila provide a platform to understand the mechanism associated with degenerative diseases. The model for Parkinson's disease (PD) based on normal human alpha-synuclein ( α S) expression was used in the present study. The aggregation of α S in brain leads to the formation of Lewy bodies and selective loss of dopaminergic neurons due to oxidative stress. Polyphenols generally have the reduced oral bioavailability, increased metabolic turnover, and lower permeability through the blood brain barrier. In the present study, the effect of synthesized alginate-curcumin nanocomposite was studied on the climbing ability of the PD model flies, lipid peroxidation, and apoptosis in the brain of PD model flies. The alginate-curcumin nanocomposite at final doses of 10(-5), 10(-3), and 10(-1) g/mL was supplemented with diet, and the flies were allowed to feed for 24 days. A significant dose-dependent delay in the loss of climbing ability and reduction in the oxidative stress and apoptosis in the brain of PD model flies were observed. The results suggest that alginate-curcumin nanocomposite is potent in delaying the climbing disability of PD model flies and also reduced the oxidative stress as well as apoptosis in the brain of PD model flies.

Antiaris toxicaria (Moraceae) was evaluated for anticonvulsant activity in rodents. Animal models used include maximal electroshock test (MEST); pentylenetetrazole-induced (PTZ) convulsions; picrotoxin-induced (PCT) convulsions; strychnine- (STR-) and 4-aminopyridine-induced convulsions. Increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity. The extract was more effective in all models used except the maximal electroshock test and strychnine-induced convulsions. Antiaris toxicaria aqueous extract (200, 400, and 800 mg kg(-1)) significantly (P < 0.05 - 0.01) shortened the duration of convulsions in PTZ- and PCT-induced seizures. Delay in the onset of convulsions in the two tests was significant (P < 0.001). Reduction in the frequency of seizures was also significant (P < 0.05 - 0.001) in both tests. Antiaris further delayed the onset of seizures in 4-aminopyridine model while producing 75% protection against death in mice. Diazepam (0.1, 0.3, and 1 mg kg(-1)), carbamazepine (3, 10, and 30 mg kg(-1)), and sodium valproate (100-400 mg kg(-1)) were used as reference anticonvulsant drugs for various models. Flumazenil blocked the effect of the extract in the PTZ test significantly suggesting that Antiaris toxicaria may be acting by enhancing the effects of the GABAergic system. Antiaris toxicaria aqueous extract therefore possesses anticonvulsant activity.

Background. Various parts of Glyphaea brevis (Spreng) Monachino (Tiliaceae) find a use in traditional medicine in the treatment of pain and oedema among others. This study evaluates the anti-inflammatory, antiallergic, and antiarthritic effects of a 70% (v/v) aqueous ethanol extract of the stem bark of Glyphaea brevis in murine models. Materials and Methods. The effect of the aqueous ethanol extract of Glyphaea brevis extract (GBE) was assessed on the maximal and total oedema responses in the carrageenan-induced paw oedema in mice to evaluate the acute anti-inflammatory actions of the extract. Systemic anaphylaxis was induced with compound 48/80 and survival rates monitored for 1 h in mice with prior treatment with GBE to assess the anti-allergic action of the extract. The indirect antihistamine effect of GBE was evaluated on clonidine-induced catalepsy. Rat adjuvant-induced arthritis model was used to study GBE's antiarthritic action. Results. GBE significantly suppressed the mean maximal swelling and the total paw swellings over 6 h in the carrageenan-induced paw oedema when administered either prophylactically or therapeutically. GBE dose dependently increased the time for compound 48/80-induced mortality. Administered either prophylactically or therapeutically, GBE inhibited clonidine-induced catalepsy while it had no effect on haloperidol-induced catalepsy. GBE caused a significant dose-dependent suppression of Freund's adjuvant-induced arthritis. Conclusion. Glyphaea brevis inhibits the in vivo degranulation of mast cells and thereby suppress allergy. In addition it exhibits anti-inflammatory action and attenuates Freund's adjuvant-induced arthritis. The results of this work contribute to validate the traditional use of Glyphaea brevis in the management of inflammatory disorders.