An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives.

BACKGROUND: In recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives. METHODS: Swiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia. RESULTS: Both of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice. CONCLUSIONS: It is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.

Anti-oxidant and hepatoprotective effects of Lactuca serriola and its phytochemical screening by HPLC and FTIR analysis.

Lactucaserriola (L. serriola), commonly known asprickly lettuce, is an annual and biennial herb. The plant is traditionally used as sedative, hypnotic, cough suppressant, expectorant, purgative, diuretic, vasorelaxant, demulcent, antiseptic and antispasmodic. Aim of present study was to evaluate protective effect of L. serriola in paracetamol-induced hepatotoxicity. Silymarin was used as a standard drug. Hepatoprotective effect of extract was determined by liver biochemical markers, anti-oxidant enzymes and blood lipid profile. Methanolic extract was found to be the most potent in in-vitro antioxidant assays and used for further studies. Treatment with paracetamol increased the level of hepatic biomarkers, blood lipid profile and decreased anti-oxidant enzyme levels. Pre-treatment with Lactuca serriola caused restoration of hepatic biomarkers, blood lipid profile and antioxidant enzymes. FTIR represented that L. serriola contains hydroxyl (-OH), carboxylic acid (C=O) and alkene (C=C) groups. HPLC analysis showed presence of polyphenolic compounds in the methanolic extract of L. serriola. It is concluded that the methanolic extract of Lactuca serriola possesses hepatoprotective potential that might be linked to the presence of polyphenolic compounds and their anti-oxidant activities.

Identifying the reasons for delayed presentation of Pakistani breast cancer patients at a tertiary care hospital.

BACKGROUND: Delay in seeking health care by breast cancer patients is associated with advanced stage of disease at presentation and poor survival rates. This study aimed to identify the reasons for delayed presentation and their association with various sociodemographic variables. METHODS: A total of 200 female patients with abnormal clinical findings, ie, lump or palpable mass, were consecutively invited for this study. Diagnostic delay was defined as a consultation with a health care provider more than 3 months from the appearance of the first symptoms. Sociodemographic variables, presenting symptoms, knowledge about diseases and its symptoms, time between seeking medical attention after appearance of symptoms and causes of delayed presentation were investigated. Chi-squared and logistic regression tests for significance and associations were used. RESULTS: Among 125 women with breast cancer fulfilling the inclusion criteria, aged 24-75 years, 88.8% (n=111) presented late (≥3 months) and 59% presented with advanced stage of disease (stage III/IV). The majority (65.6%) were older than 40 years of age, 99.2% were married, 60.8% had <8 years of education, 67.2% had poor social status, and 64.8% had a negative family history of any cancer type. Almost all patients (96%) complained about the presence of a painless lump in their breast. Ignorance of disease or the presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main variables associated with delayed presentation. Educational factors (P<0.001, OR 4.682) and social status (P<0.001, OR 1.8) were also associated with delayed presentation. CONCLUSION: Our study highlighted the variables associated with delayed presentation in Pakistani breast cancer patients. A significant number of patients presented late owing to misconceptions and poor knowledge about the disease and its symptoms, while illiteracy and poor social status were the major contributing factors for delayed presentation, resulting in an advanced presentation of disease and ultimately a decreased survival rate.

Tambulin is a major active compound of a methanolic extract of fruits of Zanthoxylum armatum DC causing endothelium-independent relaxations in porcine coronary artery rings via the cyclic AMP and cyclic GMP relaxing pathways.

BACKGROUND: Zanthoxylum armatum DC (Z. armatum), belonging to Rutaceae family, has been traditionally used for the treatment of various diseases such as hypertension, abdominal pain, headache, fever, high altitude sickness, diarrhea, dysentery, and as a tonic, condiment, and an anthelmintic treatment. HYPOTHESIS: The present study aims to evaluate the vasorelaxant effect of a methanolic extract of the fruits of Z. armatum, isolate the active components and characterize the underlying mechanism. STUDY DESIGN: A methanolic extract of fruits of Z. armatum was prepared and its vasorelaxant effect was studied using porcine coronary artery rings. Thereafter, the methanolic extract was analyzed, and a major compound was isolated and its structure elucidated (tambulin). Different pharmacological tools were used to characterize the vasorelaxant effect of tambulin. RESULTS: The methanolic extract and the isolated tambulin caused similar endothelium-independent relaxations of porcine coronary artery rings with and without endothelium indicating a direct relaxing effect at the vascular smooth muscle. Tambulin did not affect the relaxation curves to the endothelium-dependent vasodilators, bradykinin and the calcium ionophore A23187 in rings with endothelium. Tambulin (1 µM) slightly but significantly shifted leftwards the concentration-relaxation curve to the endothelium-independent vasodilators, sodium nitroprusside (SNP), forskolin (FC) and isoproterenol but not those to soluble guanylyl cyclase activators (YC-1 and BAY 41-2272) and K+ channel openers (levcromakalim and 1-EBIO). Pretreatment with tambulin inhibited, in a concentration-dependent manner, contractions to KCl, serotonin (5-HT), CaCl2 and U46619 in coronary artery rings without endothelium. Both the protein kinase A (H-89, 10 µM) and the protein kinase G (Rp-8-br-cyclic GMPS, 30 µM) inhibitors significantly reduced relaxations to tambulin in coronary artery rings without endothelium. CONCLUSION: The present findings indicate that tambulin isolated from Z. armatum (fruits) is a major active principle inducing vasorelaxation through a direct effect at the vascular smooth muscle and involving both the cyclic AMP and/or cyclic GMP relaxing pathways.