Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors

This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3–10 mg/kg) and PGL (1–20 mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated.Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3 mg/kg) with increasing doses of PGL (1–10 mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized.These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.     

Adverse Drug Events and Surgical Patients: Need for Pharmacovigilance Urgency

Hellenic Journal of Surgery -     

Antipyretic,anti-inflammatory and analgesic activity of <Emphasis Type="Italic">Acacia hydaspica</Emphasis> R. Parker and its phytochemical analysis

Background

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.

Methods

Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, ¹H NMR, ¹³C NMR and ²D NMR spectroscopic analyses, and also by comparison with reported literature.

Results

Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p?<?0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E₂ (PGE₂) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.

Conclusion

These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

     

Regression to the mean for the bivariate binomial distribution

Regression to the mean (RTM) occurs when subjects having relatively high or low measurements are remeasured and found closer to the population mean. This phenomenon can potentially lead to an inaccurate conclusion in a pre-post study design. Expressions are available for quantifying RTM when the distribution of pre and post observations are bivariate normal and bivariate Poisson. However, situations exist where the response variables are the number of successes in a fixed number of trials and follow the bivariate binomial distribution. In this article, expressions for quantifying RTM effects are derived when the underlying distribution is the bivariate binomial. Unlike the normal and Poisson distributions, the correlation between pre and post observations can be either negative or positive under the bivariate binomial distribution and the severity of RTM is greater in the former case. The percentage relative difference is used to highlight the differences in quantifying RTM under the bivariate binomial distribution and normal and Poisson approximations to the bivariate binomial distribution. Expressions for estimating RTM using the method of maximum likelihood along with its asymptotic distribution are derived. A simulation study is conducted to empirically assess the statistical properties of the RTM estimator and its asymptotic distribution. Data examples using the number of obese individuals and the number of nonconforming cardboard cans are discussed.     

Phylloquinone content of herbs,spices and seasonings

Culinary herbs and spices contain a variety of bioactive compounds including phylloquinone, the most common dietary form of vitamin K. In this study, we analyzed the phylloquinone content of a large number of commonly available culinary herbs, spices, and seasonings. Samples of fresh herbs (n = 19), dried herbs (n = 28), spices and seeds (n = 26), seasoning blends (n = 9), and other flavor enhancers (n = 11) were purchased in Montreal (Quebec, Canada) and Washington (DC, USA). All samples were analyzed in quadruplicate using standardized HPLC procedures. Most fresh herbs contained between 450 and 1200 μg of phylloquinone/100 g. Dried herbs were even richer with some (cilantro, marjoram, parsley) showing concentrations of ≈3000 μg/100 g. Phylloquinone content of spices and seeds was relatively low (5–250 μg/100 g), while being highly variable among seasoning blends (2.3–1878 μg/100 g). According to our results, portions of only 3 g of herbs can increase daily intakes of phylloquinone by up to 100 μg, contributing significantly to the daily vitamin K intake. Herbs can thus be important food sources of phylloquinone and should be accounted for when assessing vitamin K intakes in research or in patients treated with vitamin K antagonists. Future research should focus on the bioavailability of phylloquinone in these products.