Efficacy of TurmiZn, a Metallic Complex of Curcuminoids-Tetrahydrocurcumin and Zinc on Bioavailability, Antioxidant, and Cytokine Modulation Capability.

Complexes of curcumin with metals have shown much-improved stability, solubility, antioxidant capability, and efficacy when compared to curcumin. The present research investigates the relative bioavailability, antioxidant, and ability to inhibit inflammatory cytokine production of a curcuminoid metal chelation complex of tetrahydrocurcumin-zinc-curcuminoid termed TurmiZn. In vitro uptake assay using pig intestinal epithelial cells showed that TurmiZn has an ~3-fold increase (p ≤ 0.01) in uptake compared to curcumin and a ~2-fold increase (p ≤ 0.01) over tetrahydrocurcumin (THC). In a chicken model, an oral 1-g dose of TurmiZn showed a ~2.5-fold increase of a specific metabolite peak compared to curcumin (p = 0.004) and a ~3-fold increase compared to THC (p = 0.001). Oral doses (5 g/Kg) of TurmiZn in rats also showed the presence of curcumin and THC metabolites in plasma, indicating bioavailability across cell membranes in animals. Determination of the antioxidant activity by a 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay indicated that TurmiZn was about 13x better (p ≤ 0.0001) than curcumin and about 4X better (p ≤ 0.0001) than THC, in reducing free radicals. In vitro experiments further showed significant (p ≤ 0.01) reductions of lipopolysaccharide (LPS)-induced proinflammatory cytokines such as interleukin (IL) IL-6, IL-8, IL-15, IL-18, and tumor necrosis factor (TNF)-alpha, while showing a significant (p ≤ 0.01) increase of granulocyte-macrophage colony-stimulating factor (GM-CSF) in dog kidney cells. In vivo cytokine modulations were also observed when TurmiZn was fed for 6 weeks to newborn chickens. TurmiZn reduced IL-1 and IL-6, but significantly reduced (p ≤ 0.01) IL-10 levels while there was a concurrent significant (p = 0.02) increase in interferon gamma compared to controls. Overall, these results indicate that TurmiZn has better bioavailability and antioxidant capability than curcumin or THC and has the ability to significantly modulate cytokine levels. Thus, TurmiZn could be an excellent candidate for a novel ingredient that can be incorporated into food and supplements to help overall health during the aging process.

Prevalence of anemia in pre-school tribal children with reference to parasitic infections and nutritional impact.

Objectives: Anemia is a global health problem and has very high prevalence in developing as well as developed countries, particularly in children and women. The present study evaluates hematological predictors, nutrition deficiency, parasitic infections and their association with the prevalence of anemia. This analysis will help to identify the anemic status of tribal preschool children. Methods: This was a cross-sectional study conducted in 300 children (age: 6 months to 5 years) in Santrampur village, Gujarat. Blood was collected and used to determine complete blood count (CBC); we also performed ELISA (enzyme-linked immunoassay) for the estimation of ferritin, transferrin, sTfR (soluble transferrin receptor), vitamin B12 and vitamin B9 (folate). Stool samples were also collected and assessed by ELISA for Entamoeba histolytica, Giardia lamblia and Cryptosporidium parvum. Microscopy was used to screen samples for malaria. Results: Of the 300 children analyzed, 87.7% were anemic, 239 children were mildly anemic, 20 were moderately anemic and 4 were severely anemic. Mean Hb level was 9.49 ± 1.47 g/dL; males and females had an Hb level of 9.39 ± 1.59 g/dL and 9.58 ± 1.34 g/dL, respectively. Twenty-six children had sickle cell anemia and five had thalassemia. Over 50% of the children had vitamin B12 and B9 deficiency and 16% had abnormalities in CRP (C-reactive protein) levels. Parasitic infection by C. parvum was positively associated the anemia followed by the prevalence of G. lamblia and E. histolytica. Conclusion: An increased awareness of parents in the improvement of sanitary facilities and nutritional counselling with regards to iron-rich food consumption is recommended to if we are to prevent anemia among pre-school children. To reduce parasitic infestation, effective periodic deworming measures are also recommended.

Syringic Acid Ameliorates Cardiac, Hepatic, Renal and Neuronal Damage Induced by Chronic Hyperglycaemia in Wistar Rats: A Behavioural, Biochemical and Histological Analysis.

This study investigated the effects of syringic acid (SA) on renal, cardiac, hepatic, and neuronal diabetic complications in streptozotocin-induced neonatal (nSTZ) diabetic rats. STZ (110 mg/kg i.p) was injected into Wistar rat neonates as a split dose (second and third postnatal day). Diabetes mellitus was diagnosed in adults by measuring fasting blood glucose levels, urine volume, and food and water intake. The treatment of SA (25 mg/kg, 50 mg/kg p.o) was given from the 8th to 18th postnatal week. To assess the development of diabetic complications and the effect of therapy, biochemical indicators in serum and behavioural parameters were recorded at specific intervals during the study period. SA (25 mg/kg, 50 mg/kg p.o) treatment reduced hyperglycaemia, polydipsia, polyphagia, polyuria, relative organ weight, cardiac hypertrophic indices, inflammatory markers, cell injury markers, glycated haemoglobin, histopathological score, and oxidative stress, and increased Na/K ATPase activity. These findings suggest that SA might significantly alleviate diabetic complications and/or renal, neuronal, cardiac, and hepatic damage in nSTZ diabetic rats.

Safety Assessment of Vanillic Acid: Subacute Oral Toxicity Studies in Wistar Rats.

OBJECTIVES: Vanillic acid (VA) is a flavoring agent, a phenolic acid, and an intermediary by-product formed during transformation of ferulic acid to vanillin. It has been investigated for diverse pharmacological actions and used in Chinese medicine for decades. However, there is no information in the literature about its mechanism of toxicity or safety with long-term use. The present study will not only supply information on its pharmacological profile but also encourage evidence-based pharmacotherapeutic use. Hence, we performed a subacute toxicity study. MATERIALS AND METHODS: According to the Organisation for Economic Co-operation and Development Test Guideline 407 (2008), 3 groups of rats were formed consisting of 12 rats (6 male and 6 female) in each group. For the subacute toxicity, the dose was chosen after a limit test was conducted. VA (1000 mg/kg/day) was orally administered for 2 weeks to the treatment group, whereas the control group received an equivalent volume of the vehicle. To assess reversibility, VA (1000 mg/kg/day, p.o.) was administered to the satellite group for 2 weeks and animals were observed for an additional 2 weeks after treatment. The adverse signs, variation in body weight, and mortality were evaluated throughout the study period. On days 15 and 29, blood was collected to evaluate essential biochemical and hematological parameters. The animals were subsequently weighed and sacrificed. The weights of internal organs were recorded; gross necroscopy and histopathological studies were performed. RESULTS: The hematological parameters of the satellite group increased and the serum sodium level decreased after the treatment. Satellite groups showed no other major change in biochemical parameters when compared to the control group. In addition, relative organ weights, gross necropsy examinations and histopathological structure of the internal organs showed no major alterations. CONCLUSION: VA showed no adverse effect on the process of leukopoiesis, erythropoiesis or on internal organs, as verified by hematological and biochemical evaluations, gross necropsy, and histopathological studies. The decrease in serum sodium is not considered as a major toxic effect.

Safety evaluation of syringic acid: subacute oral toxicity studies in Wistar rats.

Syringic acid (SA) is a phenolic acid and have been investigated for diverse pharmacological activities, but the safety and/or mechanism of toxicity is still lacking in the literature. Subacute toxicity studies will add value to its pharmacological profile and support its exploration as a future medicine. According to OECD TG 407 (OECD, 2008), rats were divided into 3 groups (n = 12). The dose of SA was decided by limit test. Treatment and satellite groups received SA (1000 mg/kg/day, p.o for 14 days), whereas an equal volume of vehicle was given to control groups. In order to access reversibility, satellite groups were kept for another 14 days post-treatment. The toxic signs, mortality and body weight changes were recorded. On day 15 and 29 the rats were anesthetized to collect blood for estimation of hematological and biochemical parameters and then sacrificed to collect internal body organ for weighing and histopathological studies. SA has no major adverse effect on the body weight, food intake, erythropoiesis, leucopoiesis and on internal body organs which was confirmed by evaluating various biochemical and hematological parameters, relative body organ weight and histopathological studies. Therefore, SA could be considered safe over limited period of time and this study may help researchers in establishing the doses for the longer-term subchronic studies. Further, subchronic and chronic toxicity studies are required to evaluate safety on long term use.

Streptozotocin-Induced Diabetes Mellitus in Neonatal Rats: An Insight into its Applications to Induce Diabetic Complications.

BACKGROUND: Diabetic complications are the major contributor in the mortality of diabetic patients despite controlling blood glucose level. In the journey of new drug discovery, animal models have to play a major role. A large number of chemical-induced and genetically modified animal models have been investigated to induce diabetic complications but none of them was found to be mimicking the pathophysiology of the human. Therefore, the search and identification of the appropriate animal model become essential. OBJECTIVE: In the present review, we have made an attempt to understand the pathophysiology of diabetic complication in the neonatal streptozotocin-diabetic rat model and tried to identify the targets for therapeutic agents. The review will help the researchers to explore the animal model to induce diabetic complications, to identify targets and further to find lead molecules for treatment or prevention of diabetic complications. METHODS: We have compiled the available research work from 1974 by using prominent databases, organized the available information and analyzed the data to improve the understanding of the pathophysiology of streptozotocin-induced diabetic complications in neonates of rats. RESULTS: The neonatal streptozotocin-diabetic rat model is frequently used and well-established animal model for type 2 diabetes mellitus. We have found that this model has been used to study the pathogenesis of various micro and macrovascular diabetic complications and also investigated for its effects on the liver, thymus gland, and brain. The underlying pathophysiology for complications had a resemblance to the human. CONCLUSION: The neonatal streptozotocin-diabetic rat model may demonstrate symptomatic diabetic complications due to persistent hyperglycemia at the age of approximately 18-24 weeks. Critical interpretations of available research work showed that the researcher can explore split dose STZ (90- 100mg/kg b.w) model to induce Type 2 DM in neonates of rats at 2nd or 3rd postnatal day.

Evaluation of genotoxic and modulatory effects of Nyctanthes arbor-tristis calyx extract and the isolated crocin in Ames' assay.

Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal systems of several Asian countries. In the present study, potential genotoxicity and modulatory effects of ethanolic extract of NAT flower calyx (NAT FCE) and crocin, a carotenoid principle were evaluated employing standard Salmonella assay. Experiments evaluating the genotoxic potential of NAT FCE and crocin, with and without the S9-activation in TA 98, TA 100 and TA 102 showed a lack of increase in revertant mutants. Evaluation of modulatory effects of NAT FCE and crocin, without the S9, showed significant decrease in the number of 4-nitro-o-phenylenediamine-, sodium azide- and ethyl methanesulfonate-induced revertants. However, with S9, NAT FCE and crocin moderately increased the 2-aminoanthracene-induced revertants in TA 98; they moderately decreased revertants in TA 100 and TA 102. Both NAT FCE and crocin have been shown to be non-genotoxic and to be able to modulate responses of standard mutagens.

Ellagic acid: Insights into its neuroprotective and cognitive enhancement effects in sporadic Alzheimer's disease.

Sporadic Alzheimer's disease (SAD), an age-associated dementia, is described as neuronal loss and marked cognitive impairment. Ellagic acid (EA) is a phenolic phytoconstituent obtained from grains and fruits, having evident antioxidant effects and known to modulate several endogenous molecular signals in humans in a beneficial way. The current study evaluated the safety profile of EA in the SH-SY5Y human neuroblastoma cell line, performing anti-oxidative effect by DPPH assay, and evaluating anti-AchE (acetylcholinesterase) effect against AchE enzyme from Electrophorus electricus. The observations were further confirmed by in vivo therapeutic effects in streptozotocin (STZ)-induced SAD rats in the context of altered biochemical and behavioral features. Treatment with EA (50 mg/kg, p.o.) for 30 days revealed reduction in STZ (3 mg/kg i.c.v.) prompted SAD and associated biochemical abnormalities in experimental rats which included diminished oxidative stress profile, pro-inflammatory markers i.e. GFAP and CRP; AchE level, and amyloid-ß plaque level. Moreover, an elevated level of synaptophysin indicated improved synaptic connectivity, and intact neural architecture showed neuroprotection in the EA group. Furthermore, the behavioral investigation by maze paradigms revealed reduced locomotor behavior, irregular spontaneous alternation, declination in memory score and increased memory errors in SAD rats. EA treatment normalized these SAD-associated abnormal behavioral representations in rats. Hence our findings suggest neuroprotective effects of EA and improvement in cognitive behavior in SAD rats.

Chitosan Nanoparticles of Gamma-Oryzanol: Formulation, Optimization, and In vivo Evaluation of Anti-hyperlipidemic Activity.

The elevated blood levels of cholesterol and low-density lipoproteins result in hyperlipidemia. The available expensive prophylactic treatments are kindred with severe side effects. Therefore, we fabricated the polymeric nanoparticles of gamma-oryzanol to achieving the improved efficacy of drug. The nanoparticles were prepared by ionic gelation method and optimized using 23 full factorial design taking drug/polymer ratio (X1), polymer/cross linking agent ratio (X2), and stirring speed (X3) as independent variables. The average particle size, percentage entrapment efficiency, and in vitro drug release at 2, 12, and 24 h were selected as response parameters. The factorial batches were statistically analyzed and optimized. The optimized nanoparticles were characterized with respect to particle size (141 nm) and zeta potential (+ 6.45 mV). Results obtained with the prepared and characterized formulation showed 83% mucoadhesion towards the intestinal mucosa. The in vitro findings were complemented well by in vivo anti-hyperlipidemic activity of developed formulation carried out in Swiss albino mouse model. The in vivo studies showed improved atherogenic index, malondialdehyde, and superoxide dismutase levels in poloxamer-407-induced hyperlipidemic animals when treated with oryzanol and gamma-oryzanol nanoformulation. Based on our findings, we believe that chitosan-mediated delivery of gamma-oryzanol nanoparticles might prove better in terms of anti-hyperlipidemic therapeutics.

Reduction of liver tumerogenic effect of N-nitrosodiethylamine by treatment with ɣ-oryzanol in Balb/C mice.

In recent years, naturally occurring phytochemicals with antioxidant capacity have generated surmount interest in their therapeutic usage against a wide range of pathological and toxicological conditions. The present study was designed to evaluate potential of ɣ-oryzanol (OZ), a bio-active natural antioxidant against hepatocellular carcinoma effect of the carcinogen N-nitrosodiethylamine in Balb/c mice. OZ inhibited the proliferation of Hep-3B cell line in concentration dependent manner. Administration of OZ to N-nitrosodiethylamine induced Balb/c mice for 16 and 32 weeks showed reduction in levels of liver injury markers, restored the levels of liver tumor markers, suppressed the hepatic nodular incidence and multiplicity, and favorably modulated the liver antioxidant status in a time dependent manner. Histologically, no obvious signs of neoplasia in the liver tissues were observed in OZ supplemented rats with N-nitrosodiethylamine induced liver tumerogenesis. OZ was found to be effective for reduction of N-nitrosodiethylamine induced hepatocellular carcinoma.

Euphorbia neriifolia L.: Review on botany, ethnomedicinal uses, phytochemistry and biological activities.

The present review is intended to provide information on botany, ethnomedicinal uses, phytochemistry and biological activities of various parts of Euphorbia neriifolia (E. neriifolia). E. neriifolia has several ethnomedicinal uses. The latex of E. neriifolia is used as laxative, purgative, rubefacient, carminative and expectorant as well as in treatment of whooping cough, gonorrhoea, leprosy, asthma, dyspepsia, jaundice, enlargement of the spleen, tumours, stone in the bladder, abdominal troubles and leucoderma. Leaves are brittle, heating, carminative, and good for improving the appetite and treatment of tumours, pains, inflammations, abdominal swellings and bronchial infections. Roots are used as symptomatic treatment of snake bite, scorpion sting and antispasmodic. Various plant parts or whole E. neriifolia extract and its isolates have been reported scientifically using various in-vivo and in-vitro experimental methods for anaesthetic, analgesic, anti-anxiety, anti-convulsant, anti-psychotic, anti-arthritis, anti-carcinogenic, antidiabetic, anti-diarrhoeal, anti-inflammatory, anti-thrombotic, antimicrobial, antioxidant, antiulcer, cytotoxic, death-receptor expression enhancing, dermal irritation, diuretic, haemolytic, immunomodulatory, radioprotective, scorpion venom and wound healing properties. It is reported to have chemical constituents like, neriifolin-S, neriifolin, neriifoliene, euphol, neriifolione, cycloartenol, nerifoliol, lectin, euphonerins A-G, 3-O-acetyl-8-O-tigloylingol, taraxerol, antiquorin, etc. Identified chemical constituents are still required to be explored for their advanced isolation techniques and biological activities.

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

Purpose. γ-Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods. Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF-α and IL-6. Structural damage in eye was examined by histopathological studies. Results. In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF-α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions. Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Effect of potassium channel openers in acute and chronic models of glaucoma.

PURPOSE: Glaucoma is characterized by increased intraocular pressure (IOP). The effect of nicorandil and pinacidil on IOP in experimentally induced acute and chronic models of glaucoma and the mechanism of action involved were studied. METHODS: New Zealand white rabbits were used for the study. After the measurement of IOP, nicorandil (1%), pinacidil (1%), and pilocarpine as standard (1%) were instilled topically into the left eye. The other eye served as control. Dextrose (5%) was used to induce acute glaucoma. IOP changes were recorded every 15 minutes until the pressure became normal. Freshly prepared α-chymotrypsin solution was introduced in the posterior chamber to induce chronic glaucoma. Rabbits with ocular hypertension were selected for the study. Similar drug solutions were used to study the effect on IOP. Glibenclamide, pilocarpine, and indomethacin (1%) were used to study the mechanism of action of both drugs. The IOPs were measured just prior to drug instillation and at suitable time intervals using a tonometer. RESULTS: Pretreatment with topical nicorandil and pinacidil significantly lowered the rise in IOP in the acute model. Nicorandil and pinacidil initially caused rise in IOP for 15-30 minutes in chronic glaucoma. This was followed by reduction in IOP. Pretreatment with indomethacin and pilocarpine did not modify the effect of nicorandil and pinacidil on IOP. Pretreatment with glibenclamide blocked IOP from the lowering effect of nicorandil and pinacidil. CONCLUSION: The oculohypotensive effect shown by these drugs appears to be attributable to enhancement of the aqueous humor outflow. This effect is perhaps mediated through potassium channels.

Anti-obesity activity of chloroform-methanol extract of Premna integrifolia in mice fed with cafeteria diet.

AIM OF THE STUDY: Aim of the present study was to evaluate the anti-obesity activity of chloroform:methanol extract of P. integrifolia (CMPI) in mice fed with cafeteria diet. MATERIALS AND METHODS: Female Swiss Albino mice were divided into six groups, which received normal and cafeteria diet, standard drug simvastatin (10 mg/kg) and CMPI (50, 100 and 200 mg/kg) daily for 40 days. Parameters such as body weight, body mass index (BMI), Lee index of obesity (LIO), food consumption, locomotor behavior, serum glucose, triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index, organ weight and organ fat pad weight were studied for evaluating the anti-obesity activity of P. integrifolia. High performance liquid chromatography (HPLC) fingerprint profile of chloroform-methanol extract was also studied using quercetin as the reference standard. RESULTS: There was a significant increase in body weight, BMI, LIO, food consumption, organ weight (liver and small intestine), organ fat pad weight (mesenteric and peri-renal fat pad) and in the levels of serum glucose, triglyceride, total cholesterol, LDL and VLDL with a significant decrease in locomotor behavior (ambulation, rearing, grooming) and HDL level in cafeteria diet group. Animals treated with CMPI showed dose dependent activity. P. integrifolia (200 mg/kg) supplementation attenuated all the above alterations, which indicates the anti-obesity activity. HPLC fingerprint profile of CMPI showed two peaks in the solvent system of 50 mm potassium diphosphate (pH-3 with ortho phosphoric acid): Methanol (30:70 v/v) at 360 nm. CONCLUSION: Present findings suggest that, CMPI possessed anti-obesity activity that substantiated its ethno-medicinal use in the treatment of obesity.

Self micro-emulsifying drug delivery system of tacrolimus: Formulation, in vitro evaluation and stability studies.

BACKGROUND: Tacrolimus has poor solubility in water ranging from 4 to 12 µg/mL. The oral bio availabilities of tacrolimus is poor and exhibits high intra and inter-subject variability (4-89%, average 25%) in the liver and the kidney transplant recipients and in patients with renal impairment. AIM: The present study deals with the development and characterization of self-micro-emulsifying drug delivery system to improve the oral bioavailability of poorly soluble drug tacrolimus. MATERIALS AND METHODS: Solubility of the tacrolimus was estimated in various oils, surfactants, and co-surfactants. Various in vitro tests such as percentage transmittance, emulsification time, cloud point, precipitation, and thermodynamic stabilities were used to find out optimized formulations. Optimized liquid self micro-emulsifying (SMEDDS) were characterized by particle size analysis and converted in solid by using the Florite RE as an adsorbent, which is further characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and particle size analysis. RESULTS: The optimized liquid SMEDDS formulation contained 10% Lauroglycol FCC as an oil, 60% Cremophor RH, and 30% PEG (polyethylene glycol) 400 as a surfactant and co-surfactant respectively. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API (active pharmaceutical ingredient) powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found 113 nm and 209 nm respectively. The solid state characterization of solid-SMEDDS by SEM, DSC, FTIR, and XRD revealed the absence of crystalline tacrolimus in the solid-SMEDDS. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.84 and 2.25 year respectively. CONCLUSIONS: The results indicate that liquid SMEDDS and solid SMEDDS of tacrolimus, owing to nano-sized, have potential to enhance the absorption of the drug.

Reversal of experimentally induced seizure activity in mice by glibenclamide.

BACKGROUND: ATP sensitive potassium channels are widely distributed in central nervous system (CNS) and these channels could be the target in CNS disorders by their modulators. PURPOSE: The present study was designed to investigate the anticonvulsant potential of glibenclamide on MES induced seizure and pentylenetetrazole induced seizure in mice. METHODS: Seizures were induced in 7 months albino mice with a single 12 mA intensity of 50 Hz stimulus for 0.2 s using electroconvulsiometer. Tonic flexion, tonic extension, clonic convulsion and mortality protection were recorded, 60 minutes after the oral administration of the vehicle (3% Tween 80), Standard (diazepam 3 mg/kg i.p.) and glibenclamide (5 mg/kg). In second model, seizures were induced with a single convulsive dose (80 mg/kg i.p) of pentylentetrazole (PTZ). Seizures were assessed in terms of onset of seizure, number of jerks, onset of tonic convulsion and clonic convulsions and mortality protection. The study was performed at antidiabetic dose of glibenclamide 5 mg/kg per oral. RESULTS: Glibenclamide (5 mg/kg p.o.) showed significant (p<0.05) protective activity in MES induced seizures and attenuated pentylenetetrazole-induced seizure activity in mice. The anticonvulsant action of glibenclamide was noticeable in this study. However, further studies are required to elucidate its full anticonvulsant potential. CONCLUSIONS: Glibenclamide is able to exert protective effects in MES induced seizures and attenuates pentylenetetrazole induced seizure activity in mice.

A review on phyto-pharmacological potentials of Euphorbia thymifolia L.

Euphorbia thymifolia L. (Euphorbiaceae) is a small branched, hispidly pubescent, prostate annual herb, commonly known as laghududhika or choti-dudhi. The leaves, seeds and fresh juice of whole plant are used in worm infections, as stimulant, astringent. It is also used in bowel complaints and in many more diseases therapeutically. The present work is an extensive review of published literature concerning phytochemical and pharmacological potential of E. thymifolia. Data was searched and designed using various review modalities manually and using electronic search engines with reference to all aspects of E. thymifolia and was arranged chronologically. Complete information of the plant has been collected from the various books and journals since the last 32 years, internet databases, etc., were searched. Compiled data reflects the safety and therapeutic efficacy of the plant. This will be helpful for researchers to focus on the priority areas of research yet to be explored and in scientific use of the plant for its wide variety of traditional therapeutic claims and also as to find out new chemical entities responsible for its claimed traditional activities.

Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy

Several studies have implicated the involvement of poor glycemic control and oxidative/nitrosative stress in the development of diabetic neuropathic pain, an important microvascular complication affecting more than 50% of diabetic patients. However, lack of understanding of the underlying etiology, development of tolerance, inadequate relief and possible toxicity associated with classical analgesics warrant the investigation of the novel agents. Therefore, the present study was carried out to investigate the effect of oryzanol (OZ), a commercially-important potent antioxidant component isolated from from crude rice bran oil (cRBO), in streptozotocin (STZ)-induced diabetic neuropathy in rats. After eight weeks, diabetic rats developed neuropathy which was evident from decreased tail-flick latency (thermal hyperalgesia) and increased nociceptive behavior during the formalin test. This was accompanied by decreased motor coordination based on the evaluation of neuromuscular strength. Na+ K+ ATPase, a biochemical marker associated with the development of diabetic neuropathy, was significantly inhibited in the sciatic nerve of diabetic animals. The activities of antioxidant enzymes and lipid peroxidation levels were significantly elevated in diabetic rats, indicating the involvement of oxidative stress in diabetic neuropathy. Chronic treatment with oryzanol (OZ) (50 and 100 mg/kg) per oral (p.o.) and standard drug glibenclamide (Gl) (10 mg/kg, p.o.) significantly attenuated the behavioral as well as biochemical changes associated with diabetic neuropathy. The findings provide experimental evidence to the protective effects of OZ on hyperglycemia-induced thermal hyperalgesia and oxidative stress which might be responsible for diabetes induced nerve damage.

Anti-hyperlipidemic activity of oryzanol, isolated from crude rice bran oil, on Triton WR-1339-induced acute hyperlipidemia in rats

Experimental studies carried out for evaluating the anti-hyperlipidemic properties of rice bran components have given interesting but often contrasting results. Therefore, the current study was initiated to investigate the anti-hyperlipidemic activity of oryzanol (OZ), a commercially-important bioactive phytochemical, isolated from crude rice bran oil (cRBO). OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Subsequently, OZ (50 and 100 mg/kg, p.o.) was evaluated for anti-hyperlipidemic activity in Triton WR-1339-induced acute hyperlipidemic albino rats by estimating serum triacylglyceride (TG), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) levels with atorvastatin as the reference standard. The degree of protection was also assessed by measuring the levels of various hepatic anti-oxidant enzymes. OZ evoked a significant decrease in the levels of serum cholesterol, triacylglycerides, LDL, VLDL and a significant increase in the level of serum HDL and hepatic anti-oxidant enzymes. It also showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios. These findings indicate that OZ possesses the potential to lower plasma lipid concentrations and might be of therapeutic benefit in hyperlipidemia and atherosclerosis.

Investigation of the immunomodulatory potential of oryzanol isolated from crude rice bran oil in experimental animal models.

Nutrition and nutritional status can influence the development, maintenance and optimal functioning of the immune system. Oryzanol (OZ), a commercially important bioactive phytochemical component of rice bran oil, has generated global interest on account of its several beneficial physiological effects on human health. The aim of the present investigation was to examine the effect of OZ, isolated from crude rice bran oil (cRBO), on the regulation of the immune response in experimental animal models. The isolated OZ was identified with respect to the standard by melting point determination, thin-layer chromatography (TLC), UV-visible spectrophotometry and high-performance liquid chromatography (HPLC). Cellular immunity in rats was assessed by carbon clearance assay, delayed-type hypersensitivity (DTH) response and cyclophosphamide-induced myelosuppression, whereas humoral immunity was analysed by haemagglutinating antibody (HA) titre assay. Oryzanol (25, 50 and 100 mg/kg, p.o.) evoked a significant increase in antibody titre values in the haemagglutination test and potentiated the delayed type hypersensitivity reaction induced by sheep red blood cells. It also significantly ameliorated myelosuppression in cyclophosphamide treated rats and showed an increase in phagocytic index in the carbon clearance assay. The findings from the study indicate that OZ possesses sufficient potential for augmenting immune activity by cellular and humoral mediated mechanisms.