Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion

Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum® gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen

Contribution of a1-adrenoceptor subtypes in renal hemodynamics and functions of rats with renal impairment : alteration of g-protien linked to shift in the functionality And expression of renal a1-adrenoceptor subtypes.

This study investigated the role of a 1-adrenoceptors subtypes in the regulation of renal haeamodynamics at the level of renal resistance vasculature. It is hypothesized that a 1- adrenoceptor subtype(s) distribution depends on pathophysiological states of animal. Thus, the functional role of a 1-adrenoceptor subtype(s) on renal haeamodynamics of rats with renal failure, diabetic nephropathy and cardiac hypertrophy was investigated along with the Go proteins expression in the kidney and heart of normal rats and that of rats with impairments. Kajian ini menyiasat peranan adrenoseptor subjenis a1 dalam pengawalaturan hemodinamik ginjal di peringkat rintangan vaskulatur ginjal. Adalah dihipotesis bahawa distribusi adrenoseptor subjenis a1 bergantung kepada keadaan patofisiologi haiwan. Oleh itu, peranan fungsi adrenoseptor subjenisa 1 ke atas hemodinamik ginjaJ telah dikaji dalam tikus dengan kegagalan buah pinggang, nefropati diabetes dan hipertropi jantung bersama-sama dengan ungkapan protein Go dalam buah pinggang dan hati tikus biasa dan tikus dengan kecacatan

Withaferin A inhibits adipogenesis in 3T3-F442A cell line, improves insulin sensitivity and promotes weight loss in high fat diet-induced obese mice.

The increased prevalence of obesity and associated insulin resistance calls for effective therapeutic treatment of metabolic diseases. The current PPARγ-targeting antidiabetic drugs have undesirable side effects. The present study investigated the anti-diabetic and anti-obesity effects of withaferin A (WFA) in diet-induced obese (DIO) C57BL/6J mice and also the anti-adipogenic effect of WFA in differentiating 3T3- F442A cells. DIO mice were treated with WFA (6 mg/kg) or rosiglitazone (10 mg/kg) for 8 weeks. At the end of the treatment period, metabolic profile, liver function and inflammatory parameters were obtained. Expression of selective genes controlling insulin signaling, inflammation, adipogenesis, energy expenditure and PPARγ phosphorylation-regulated genes in epididymal fats were analyzed. Furthermore, the anti-adipogenic effect of WFA was evaluated in 3T3- F442A cell line. WFA treatment prevented weight gain without affecting food or caloric intake in DIO mice. WFA-treated group also exhibited lower epididymal and mesenteric fat pad mass, an improvement in lipid profile and hepatic steatosis and a reduction in serum inflammatory cytokines. Insulin resistance was reduced as shown by an improvement in glucose and insulin tolerance and serum adiponectin. WFA treatment upregulated selective insulin signaling (insr, irs1, slc2a4 and pi3k) and PPARγ phosphorylation-regulated (car3, selenbp1, aplp2, txnip, and adipoq) genes, downregulated inflammatory (tnf-α and il-6) genes and altered energy expenditure controlling (tph2 and adrb3) genes. In 3T3- F442A cell line, withaferin A inhibited adipogenesis as indicated by a decrease in lipid accumulation in differentiating adipocytes and protein expression of PPARγ and C/EBPα. The effect of rosiglitazone on physiological and lipid profiles, insulin resistance, some genes expression and differentiating adipocytes were markedly different. Our data suggest that WFA is a promising therapeutic agent for both diabetes and obesity

Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen

Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P=0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted P=0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk

Chronic Administration of Oil Palm (Elaeis guineensis) Leaves Extract Attenuates Hyperglycaemic-Induced Oxidative Stress and Improves Renal Histopathology and Function in Experimental Diabetes

Oil palm (Elaeis guineensis) leaves extract (OPLE) has antioxidant properties and because oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN), we tested the hypothesis that OPLE prevents diabetes renal oxidative stress, attenuating injury. Sprague-Dawley rats received OPLE (200 and 500 mg kg−1) for 4 and 12 weeks after diabetes induction (streptozotocin 60 mg kg−1). Blood glucose level, body and kidney weights, urine flow rate (UFR), glomerular filtration rate (GFR), and proteinuria were assessed. Oxidative stress variables such as 8-hydroxy-2′-deoxyguanosine (8-OHdG), glutathione (GSH), and lipid peroxides (LPO) were quantified. Renal morphology was analysed, and plasma transforming growth factor-beta1 (TGF-β1) was measured. Diabetic rats demonstrated increase in blood glucose and decreased body and increased kidney weights. Renal dysfunction (proteinuria, elevations in UFR and GFR) was observed in association with increases in LPO, 8-OHdG, and TGF-β1 and a decrease in GSH. Histological evaluation of diabetic kidney demonstrated glomerulosclerosis and tubulointerstitial fibrosis. OPLE attenuated renal dysfunction, improved oxidative stress markers, and reduced renal pathology in diabetic animals. These results suggest OPLE improves renal dysfunction and pathology in diabetes by reducing oxidative stress; furthermore, the protective effect of OPLE against renal damage in diabetes depends on the dose of OPLE as well as progression of DN

Buffer-Free High Performance Liquid Chromatography Method for the Determination of Theophylline in Pharmaceutical Dosage Forms

Purpose: To develop and validate a simple, economical and reproducible high performance liquid chromatographic (HPLC) method for the determination of theophylline in pharmaceutical dosage forms. Method: Caffeine was used as the internal standard and reversed phase C-18 column was used to elute the drug and standard. The mobile phase was prepared by mixing water:acetonitrile:methanol at the ratio of 90:03:07 and the pH set at 4.6. Flow rate and ultraviolet (UV) detector were set at 1.0 mLmin-1 and 271 nm, respectively. The method was validated for linearity, recovery, accuracy, precision, specificity, and also for inter-day stability under laboratory conditions. Results: Retention time was 5.5 min. The limits of detection and quantification were 12.5 ngmL-1 and 100 ngmL-1, respectively. Recovery accuracy (%) for different concentrations ranged from 100.05 to 102.43; regression coefficient (R2) of 0.994; precision RSD < 2.0, and negligible interference from common excipients. Conclusion: The method is simple, rapid, highly specific and suitable for the determination of theophylline. Absence of buffer and use of small quantity of organic solvents increase the life span of the column and reduce the cost of routine analysis of theophylline in industry

Preclinical safety assessment and mutagenicity of the hydroethanolic extract of Syzygium campanulatum leaves.

Syzygium campanulatum (Myrtaceae) is a species indigenous to Southeast Asia, a widely consumed medicinal herb and rich in phytochemical content and notable antiangiogenic and anti-colon cancer. Safety reports of administration of S. campanulatum are however lacking.In this study, we investigated the quality of dried leaves, chemical composition analyzed by FTIR and HPLC, phytochemicals content and repeated doses toxicity and mutagenicity effect of the hydroethanolic extract of S.campanulatum leaves (HESCL). The rats were divided into experimental and control groups and fed with 500, 1000, 2000 mg/kg/day of the hydroethanolic extract of S. campanulatum leaves for 28 and 90 days and with a single dose of 5000 mg/kg in acute study.The obtained results showed the dry leaves of S. campanulatum were devoid of any heavy metal and microbial contamination. The major components of HESCL were, respectively betulinic acid (60.43 mg/g.), total glycol saponins, total phenolics, total proteins, total tannins, and total flavonoids. No mutagenicity was detected in S. typhimurium auxotroph and no signs of clinical toxicity and mortality were observed in the experimental groups after 28 and 90-day experiment. However, significant (p &amp;lt; 0.05) statistical deviations were observed in hematological, and biochemical parameters but they were within the normal clinical range for rat, therefore not considered treatment-related.Based on these findings the fifty percent lethal dose was &amp;gt; 5000 mg/kg and the NOAEL was up to 2000 mg/kg for 90 days, as such HESCL is a relatively safe herb

Alterations of haemodynamic parameters in spontaneously hypertensive rats by Aristolochia ringens Vahl. (Aristolochiaceae)

Aristolochia ringens Vahl. (Aristolochiaceae (AR); 馬兜鈴 mǎ dōu líng) is used traditionally in Nigeria for the management of various disorders including oedema. Preliminary investigation revealed its modulatory effect on the cardiovascular system. This study was aimed at investigating the effect of the aqueous root extract of A. ringens (AR) on haemodynamic parameters of spontaneously hypertensive rats (SHRs). The effect of oral subacute (21 days) and intravenous acute exposure of SHRs to the extract were assessed using tail cuff and carotid artery canulation methods respectively. In the latter, the effect of chloroform, butanol and aqueous fractions of AR were also evaluated. The extract significantly reduced systolic and diastolic blood pressures in SHRs, with peak reductions of 20.3% and 26.7% respectively at 50 mg/kg by the 21st day of oral subacute exposure. Upon intravenous exposure, AR (50 mg/kg) reduced systolic and diastolic blood pressure by as much as 53.4 ± 2.2 and 49.2 ± 2.8 mmHg respectively. A dose-dependent reduction in heart rate, significant at 25 and 50 mg/kg was also observed. Hexamethonium (20 mg/kg) and atropine (1 mg/kg) inhibited the extract's reduction of systolic blood pressure, diastolic blood pressure and heart rate significantly. The extract's butanol fraction produced the greatest systolic and diastolic blood pressures reduction of 67.0 ± 3.8 and 68.4 mmHg respectively at 25 mg/kg and heart rate reduction of 40 ± 7 beats per minute at 50 mg/kg. HPLC analysis revealed the presence of 4-hydroxybenzoic acid and quercetin in AR. The extract's alterations of haemodynamic parameters in this study show that it has hypotensive effect on spontaneously hypertensive rats