Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.

BACKGROUND: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. METHOD: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. RESULTS: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. CONCLUSION: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

Polyphenolic enriched extract of Cassia glauca Lamk, improves streptozotocin-induced type-1 diabetes linked with partial insulin resistance in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Cassia glauca (CG) has been used to treat diabetes. AIM OF THE STUDY: The study was undertaken to evaluate anti-diabetic and antioxidant activity of polyphenolic enriched extract of CG in standardized streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The effect of ethanol (CGE) and water (CGW) extracts of CG (200 and 400mg/kg) treatment were evaluated in STZ (50mg/kg, iv) induced diabetic rats. On 10th day, oral glucose tolerance test and degree of insulin resistance was calculated. On 13th day, insulin tolerance test was performed to know the peripheral utilization of glucose. On 15th day, blood glucose, lipid profiles and endogenous antioxidant levels were estimated. In addition, the effects on oral glucose/sucrose tolerance test in normal rats. Further, HPLC fingerprinting profile of CGE and simultaneous quantification of biomarkers were carried out. RESULTS: Supplementation with CGE and CGW significantly reduced STZ-induced deleterious effects and improved glucose tolerance, and insulin tolerance. In addition, supplementation also decreased oxidative stress by improving endogenous antioxidant levels. Furthermore, administration significantly improves sucrose tolerance suggesting that extract possess inhibition of α-glucosidase enzyme. Further, HPLC studies revealed that CGE contains three bioactive polyphenolic compounds viz., rutin (0.10±0.01mg/g), luteolin-7-glucoside (0.06±0.01mg/g) and isorhoifolin (0.7±0.05mg/g). CONCLUSION: Observed beneficial outcome of CG might be attributed to the presence of polyphenolic compounds and mediated by interacting with multiple targets of diabetes and oxidative stress. Taken together, this study provided the scientific evidence for the traditional use of CG.

Bilateral single-session retrograde intra-renal surgery: A safe option for renal stones up to 1.5 cm.

INTRODUCTION: Assessment of treatment outcomes in patients undergoing bilateral single-session retrograde intra-renal surgery (RIRS) for bilateral renal stones up to 1.5 cm. MATERIALS AND METHODS: Retrospective analysis of 74 patients was done with bilateral renal calculi, who underwent bilateral single-session RIRS at our stone referral hospital from December 2011 to May 2014. The selection criteria for this intervention were patient's preference, failure of other treatments and stone up to 1.5 cm. Patients with creatinine more than 2, pyonephrosis sepsis, bilateral impacted pelviureteric junction calculi were excluded from study. All patients were evaluated with serum biochemistry, urinalysis, urine culture, plain radiography of kidney-ureter-bladder, intravenous urography, renal ultrasonography (USG) and/or computed tomography (CT). Follow-up evaluation included serum biochemistry and postoperative plain film and renal USG. The success rate was defined as patients who were stone-free or only had a residual fragment of less than 4 mm. CT was conducted only in patients with residual stones, which were present in seven patients. RESULTS: A total of 74 patients (50 male, 24 female) with a mean age 39.2 ± 15.2 were included in the present study. The mean stone size was 11.7 ± 2.4 mm. The stone-free rates were 86.84% and 97.29% after the first and second procedures, respectively. In eight patients (10.8%), minor complications were observed, whereas no major complications were noted in the studied group. There was no significant difference in pre- and post-operative serum creatinine levels. CONCLUSION: In patients with bilateral renal stones up to 1.5 cm bilateral single-session RIRS with flexible ureteroscope can be safely performed with low complication rate.

The surgical management of urogenital tuberculosis our experience and long-term follow-up.

INTRODUCTION: Urogenital tuberculosis (TB) is common in developing countries. We present our experience of surgically managed cases of genitourinary TB (GUTB). MATERIALS AND METHODS: We retrospectively reviewed 60 cases GUTB who underwent surgery at our center from January 2003 to January 2010. Mode of presentation, organ involvement, investigation, surgical treatment and follow-up were studied. RESULTS: There were 38 males and 22 females with a mean age of 32.5 years. The most common symptom was irritative voiding symptoms. The most common organ involved was bladder in 33 cases, and next most common was kidney in 30 cases. Preoperative bacteriologic diagnosis was confirmed in only 19 cases. A total of 66 procedures were performed as some patients needed more than one procedure. These included 35 ablative procedures and 31 reconstructive procedures. All the patients were followed-up with renal function test (RFT) at 3, 6 and 12 months. The intravenous urography and diethylenetriamine pentaacetic acid scan were performed at 3 months when indicated. Then the patients were followed with RFT and ultrasonography 6 monthly for 3 years and then annual RFT. CONCLUSION: Many patients of urogenital TB present late with cicatrisation sequelae. Multidrug chemotherapy with judicious surgery as and when indicated is the ideal treatment. The results of reconstructive surgery are good and should be done when possible. Rigorous and long term follow-up is necessary in patients undergoing reconstructive surgery.

Synthesis, characterization, and preclinical evaluation of new thiazolidin-4-ones substituted with p-chlorophenoxy acetic acid and clofibric acid against insulin resistance and metabolic disorder.

We synthesized twenty thiazolidin-4-one derivatives, which were then characterized by standard chromatographic and spectroscopic methods. From the in vitro glucose uptake assay, two compounds behaved as insulin sensitizers, where they enhanced glucose uptake in isolated rat diaphragm. In high-carbohydrate diet-induced insulin resistant mice, these two thiazolidin-4-ones attenuated hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and glucose intolerance. They raised the plasma leptin but did not reverse the diabetes-induced hypoadiponectinemia. Additionally, compound 3a reduced adiposity. The test compounds were also able to reverse the disturbed liver antioxidant milieu. To conclude, these two novel thiazolidin-4-ones modulated multiple mechanisms involved in metabolic disorders, reversing insulin resistance and thus preventing the development of type-2 diabetes.

Evaluation of in vitro antioxidant and in vivo analgesic potential of Terminalia paniculata aqueous bark extract.

The Terminalia genus includes plants that are used in a variety of food, nutritional products, and traditional medicines. Aqueous bark extract of Terminalia paniculata (TPW) was screened for its antioxidant and analgesic potential. The major polyphenols were identified by high-performance liquid chromatography. In vitro antioxidant potential of TPW was investigated by 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(2-)) radical assay, nitric oxide (NO) scavenging, superoxide scavenging (O(2-)), Fe(2+) chelating (O-phenanthroline), and ferric reducing/antioxidant power (FRAP) assay. We evaluated the effects of TPW on cell viability, lipopolysaccharide (LPS)-stimulated reactive oxygen species (ROS), nitrite, and cytokines (interleukin [IL] 6 and tumor necrosis factor alpha [TNF-α]) in RAW 264.7 murine macrophages. Evaluation of analgesic activity of TPW was performed using acetic acid-induced writhing and hot plate test in mice. Phytochemical analysis showed the presence of four polyphenols, namely, gallic acid, ellagic acid, rutin, and quercetin. TPW showed maximum superoxide, ABTS(2-), NO, DPPH inhibition, and Fe(2+-)chelating property at 400 µg/mL, respectively. FRAP value was 4.5±0.25 µg Fe(II)/g. TPW, per se, did not affect RAW 264.7 cell viability. In LPS-induced RAW 264.7 cells, TPW attenuated the elevation in ROS, nitrite, IL-6, and TNF-α levels. TPW (100-400 mg/kg, orally) significantly reduced the number of writhes in a dose-dependent manner compared with the control. Similarly, TPW (400 mg/kg, orally) evoked a significant increase in the maximum percentage effect in the hot plate test. The study suggests the efficacy of aqueous bark extract of T. paniculata as a potential antioxidant and analgesic agent.

Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents.

BACKGROUND: Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. METHODS: Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. RESULTS: TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. CONCLUSION: The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.

Sesamol prevents doxorubicin-induced oxidative damage and toxicity on H9c2 cardiomyoblasts.

OBJECTIVES: Exposure to toxicants like doxorubicin (Dox) damages cellular components by generating reactive oxygen species (ROS). This can be attenuated using free radical scavengers and/or antioxidants. METHODS: Dox-exposed cardiac myoblasts (H9c2 cells) were treated with sesamol (12.5, 25 and 50 µm), a natural phenolic compound. Intracellular ROS inhibition, cell viability and analysis of antioxidant and biochemical markers such as superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, reduced/oxidized glutathione, lipid peroxidation and protein carbonyl content were performed. The effect of sesamol treatment on the cytotoxic and genotoxic parameters was studied by monitoring the signalling proteins involved in the apoptotic pathway. KEY FINDINGS: Dox triggered cellular and genetic damage by increasing levels of intracellular ROS, thereby decreasing cell viability and increasing apoptosis. Sesamol reversed the cytotoxic and genotoxic effects of Dox. In addition, sesamol attenuated the pro-apoptotic proteins and improved the anti-apoptotic status. Sesamol pre-treatment also alleviated the disturbed antioxidant milieu by preventing ROS production and improving endogenous enzyme levels. CONCLUSIONS: Among the different doses tested, 50 µm of sesamol showed maximum protection against Dox-induced oxidative damage. This reflects the significance of sesamol in ameliorating the deleterious effects associated with cancer chemotherapy.

Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington's disease in rats.

Oxidative stress (OS) and nitric oxide mechanisms have been recently proposed in 3-nitropropionic acid (3-NP)-induced neurotoxicity. The compounds, having antioxidant, anti-inflammatory and estrogenic effects, have been suggested for neuroprotection in different experimental models. Calendula officinalis Linn. flower extract (COE) is known for its potent antioxidant, anti-inflammatory, estrogenic and neuroprotective activities. Hence, the present study was designed to evaluate the neuroprotective effect of COE on 3-NP-induced neurotoxicity in rats by observing behavioral changes, OS and striatal damage in rat brain. Adult female Wistar rats were pretreated with vehicle or COE (100 and 200 mg/kg) for 7 days, followed by cotreatment with 3-NP (15 mg/kg, intraperitoneally) for the next 7 days. At the end of the treatment schedule, rats were evaluated for alterations in sensory motor functions and short-term memory. Animals were sacrificed and brain homogenates were used for the estimation of lipid peroxidation (LPO), glutathione, total thiols, glutathione S-transferase, catalase and nitrite. A set of brain slices was used for the evaluation of neuronal damage in the striatal region of the brain. 3-NP caused significant alterations in animal behavior, oxidative defense system evidenced by raised levels of LPO and nitrite concentration, and depletion of antioxidant levels. It also produced a loss of neuronal cells in the striatal region. Treatment with COE significantly attenuated behavioral alterations, oxidative damage and striatal neuronal loss in 3-NP-treated animals. The present study shows that COE is protective against 3-NP-induced neurotoxicity in rats. The antioxidant, anti-inflammatory and estrogenic properties of COE may be responsible for its neuroprotective action.

Buccal mucosal graft urethroplasty in long segment anterior urethral stricture - is it gold standard?

To assess the success of dorsal onlay buccal mucosal graft (BMG) urethroplasty in long segment anterior urethral stricture extending from external meatus to bulbar urethra). We studied 40 patients with long segment anterior urethral stricture, who underwent substitution urethroplasty using dorsal onlay BMG from January 2002 to December 2007. The patients were in the age range of 15-65 years (mean 35 years) in the LS group and 16-63 years (mean 34 years) in the non-lichen sclerosus (NLS) group. The cause of stricture was LS in 20 and NLS (inflammatory and idiopathic) in the other 20 patients. The mean stricture length was 14.5 cm (range 12-17 cm) in the LS group while it was 14.0 cm (range 12-16 cm) in the NLS group. The patients were evaluated with antegrade, retrograde urethrograms and sono-urethrograms and they were followed- up with uroflometery at three months for one year, then six- monthly for two years and then annually. The contrast studies were repeated at six-monthly intervals for one year and then annually for one year. Success was defined as normal voiding pattern without any intervention post-operatively. Median follow-up was 48 months (18-72 months) in the LS group, while it was 42 months (12-72 months) in the NLS group. Among the NLS group patients, three patients developed restricture on follow-up, while seven patients among the LS group developed restricture. We conclude that the high percentage of recurrence of strictures (35%) among the LS group renders BMG urethroplasty in long segment anterior urethral stricture an unacceptable solution, and it needs further study.

Renal pleomorphic undifferentiated sarcoma: a rarity.

A 70-year-old male presented with progressive weight loss for eight months. Radiological imaging showed a large tumor in the right kidney. The patient underwent right open radical nephrectomy and histopathology revealed pleomorphic undifferentiated sarcoma (PUS) earlier known as malignant fibrous histiocytoma (MFH). One year after surgery, the patient developed pulmonary metastasis. Unfortunately, the patient died after six months.

Synchronous primary cancers of urinary bladder and kidney and prostate.

Synchronous occurrence of two or more than two primary cancers of the urinary tract is quite rare, and poses a difficult treatment challenge. Here, we present a case of synchronous renal cell carcinoma, transitional cell carcinoma of urinary bladder and adenocarcinoma of prostate diagnosed within a short period. To the best of our knowledge, this is the first case reported from India and the youngest patient reported in the literature having this combination of urinary cancers.

Collecting duct carcinoma: a rare renal tumor.

The most common primary malignant renal tumor is renal cell carcinoma (RCC), which accounts for 3% of all adult malignancies. Bellini duct carcinoma or collecting duct carcinoma is an unusual rare variant of RCC. This histologically distinct tumor is very rare, with less than 100 cases reported in the literature, and accounts for approximately 1% of all malignant renal epithelial tumors. We report two cases of collecting duct carcinoma and highlight the rarity of these tumors and their similarity to RCC.

Protective effect of hydroalcoholic extract of Mimusops elengi Linn. flowers against middle cerebral artery occlusion induced brain injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional Indian and Thai system of medicine, Mimusops elengi Linn., flower is used as brain tonic and to calm anxiety and panic attacks. AIM OF THE STUDY: The present study was designed to investigate the neuroprotective effect of hydroalcoholic extract of Mimusops elengi (ME) against cerebral ischemic reperfusion injury in rats. MATERIALS AND METHODS: Male rats were pretreated with ME (100 and 200mg/kg) for seven days and focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) method. After 60min of MCAO and 24h of reperfusion, a battery of behavioral tests assessed the extent of neurological deficits. Infarct volume and brain edema were measured in TTC stained brain sections and the extent of blood brain barrier (BBB) disruption was observed by Evan's blue extravasation. Oxidative and nitrative stress parameters were estimated in the brain homogenates. Further, simultaneous quantification of five polyphenolic biomarkers were done using HPLC. RESULTS: Pretreatment with ME at doses of 100 and 200mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema and extent of BBB disruption induced by ischemia reperfusion injury. It also prevented the alteration in the antioxidant status and reduced the nitrite levels when compared to ischemic animals. Further, HPLC studies revealed that ME contains five bioactive polyphenolic compounds. CONCLUSIONS: These results clearly indicate the neuroprotective effect of ME against stroke like injury. The observed protective effect might be attributed to the polyphenolic compounds and their antioxidant and anti-inflammatory property.

Squamous cell carcinoma in exstrophic unreconstructed urinary bladder in an adult.

Bladder exstrophy is rare and associated with an increased incidence of bladder cancer. Unreconstructed bladder extrophy presenting in an adult is very rare as most of the patients undergo repair in childhood. Most of the cancers are adenocarcinomas. We report a rare case of squamous cell carcinoma occurring in exstrophic unreconstructed bladder in a 58-year-old male patient.

Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice.

The present study describes the antidiabetic effect of the flavonoid rich fraction of Pilea microphylla (PM1). HPLC characterization of PM1 revealed the presence of polyphenols viz., chlorogenic acid, rutin, luteolin-7-O-glucoside, isorhoifolin, apigenin-7-O-glucoside, and quercetin. PM1 inhibited dipeptidyl peptidase IV (DPP-IV) in vitro with an IC(50) of 520.4±15.4 µg/ml. PM1, at doses of 300, 600 and 900 mg/kg i.p., also produced dose-dependent mean percent reductions of 9.9, 30.6 and 41.0 in glucose excursion (AUC(0-120 min)) respectively in lean mice. However, even the highest dose of PM1 did not alter normoglycemic condition. PM1 at dose of 100 mg/kg/day, i.p. for 28 days produced significant (p<0.05) reduction in body weight, plasma glucose (PG), triglycerides (TG) and total cholesterol (TC) content in high-fat streptozotocin-induced diabetic mice. PM1 also improved oral glucose tolerance significantly (p<0.05) with mean percentage reduction of 48.0% in glucose excursion (AUC(0-120 min)) and significantly (p<0.05) enhanced the endogenous antioxidant status in mice liver compared to diabetic control. PM1 preserved islet architecture and prevented hypertrophy of hepatocytes as evident from the histopathology of pancreas and liver. PM1 did not show any detectable hematological toxicity at therapeutic doses. In conclusion, PM1 exhibits antidiabetic effect possibly by inhibiting DPP-IV and improving antioxidant levels in high fat diet/streptozotocin (HFD/STZ) diabetic mice.

Polyphenolic fraction of Pilea microphylla (L.) protects Chinese hamster lung fibroblasts against γ-radiation-induced cytotoxicity and genotoxicity.

Present study was designed to compare cytoprotective and antigenotoxic activity of the polyphenolic fraction of Pilea microphylla (PM1) with that of its active polyphenolic constituents against γ-radiation in V79 cells. PM1 was standardized with respect to the polyphenols present by RP-HPLC. It was evaluated for its free radical scavenging potential using Fenton reaction-induced DNA damage and lipid peroxidation. Further, PM1 was subjected against γ-radiation-induced cytotoxicity and genotoxicity in V79 cells. PM1 significantly reduced free radical-mediated calf thymus DNA damage and lipid peroxidation. Among the concentrations tested (12.5, 25 and 50 µg/ml) for radioprotection, PM1 at 25 µg/ml exhibited maximum protection. Further, when compared with constituent polyphenols viz., rutin, quercetin and chlorogenic acid (concentrations equivalent to that present in PM1-25 µg/ml), a combination of polyphenols was found most effective in preventing γ-radiation-induced cytotoxicity and genotoxicity. To conclude, radioprotection is possibly a synergistic effect of the phytochemicals present in the herbal extract, rather than any single component.

Antidiabetic effect of Ficus racemosa Linn. stem bark in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats: a mechanistic study.

The present study was designed to investigate the effects of the ethanol extract of Ficus racemosa (FRE) on biochemical parameters in type 2-like diabetes, induced by a combination of standardised high-fat diet and low-dose streptozotocin (25mgkg(-1), i.p.) in rats. To elucidate the mode of action of FRE, its effects on a battery of targets involved in glucose homeostasis was evaluated. FRE (200 and 400mgkg(-1), p.o.), in a dose-dependent manner, altered the biochemical parameters and significantly improved glucose tolerance and HDL-c levels. In different bioassays, FRE showed inhibition of PTP-1B (IC50 12.1µg/mL) and DPP-IV (42.5%). FRE exhibited 82.6% binding to PPAR-γ. Furthermore FRE exhibited stimulation of glucose uptake by skeletal muscles (hemi-diaphragm). Bergenin was quantified in bioactive-FRE by high-performance liquid chromatography (0.15%w/w). This is the first report demonstrating the effectiveness of F. racemosa stem bark in type 2 diabetes and targets involved in it.

Laparoscopic versus open pyeloplasty: comparison of two surgical approaches- a single centre experience of three years.

UPJO causes hydronephrosis and progressive renal impairment may ensue if left uncorrected. Open pyeloplasty remains the standard against which new technique must be compared. We analyzed the comparison of Laparoscopic and open pyeloplasty in a randomized prospective trial. A prospective randomized study was done from January 2004 to January 2007 in which a total of 28 Laparoscopic and 34 open pyeloplasty were done. All laparoscopic pyeloplasties were performed transperitoneally. Standard open Anderson Hynes pyeloplasty, spiral flap or VY plasty was done depending on anatomic consideration. Patients were followed with DTPA scan at 3 months and IVP at 6 months. Perioperative parameters including operative time, analgesic use, hospital stay, and complication and success rates were compared. Mean total operative time with stent placement in LP group was 244.2 min (188-300 min) compared to 122 min (100-140 min) in open group. Compared to open pyeloplasty the post operative diclofenac requirement was significantly less in LP group (mean107.14 mg) and open group required mean of (682.35 mg) The duration of analgesic requirement was also significantly less in LP group. The post operative hospital stay in LP was mean 8.29 days (7-11) and was significantly less than open group (mean 3.14 Days (2-7 days). Open pyeloplasty has been the gold standard for UPJO repair and achieves success rates exceeding 90%. Laparoscopic pyeloplasty provides a minimally invasive alternative to repair UPJO and has developed world wide as the first minimally option to match success rate of open pyeloplasty. Its potential advantages including less post op pain, shorter hospital stay an improved cosmesis has been proved in some comparative series. The only disadvantage seems to be longer operative time. LP has a minimal level of morbidity and short hospital stay compared to open approach Although Laparoscopic pyeloplasty has the disadvantages of longer operative time and requires significant skill of intracorporeal knotting but it is here to stay and represents an emerging standard of care.

Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives.

A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC(50) values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity.