Protective effect of co-administration of caffeine and piracetam on scopolamine-induced amnesia in Wistar rats.

Alzheimer's disease is a cerebrovascular disorder characterized by progressive loss of the mental capabilities. The novel therapeutic agent piracetam is a cyclic derivative of γ-aminobutyric acid and one of the oldest recognized synthetic nootropics. Piracetam improves cognitive function without stimulation or sedation. Caffeine is a central nervous system stimulant with nootropic activity. Caffeine promotes the performance of tasks that involve working memory to a limited extent, and it also retards cognitive decline in healthy individuals. The present study aimed to determine the protective effect of co-administering piracetam and caffeine on scopolamine-induced amnesia in rats. Pre-treatment with caffeine and piracetam decreased scopolamine-induced cognitive damage and amnesia. The preventive response was demonstrated by an improved learning tendency. The mechanism responsible for these effects requires further investigation. The co-administration of caffeine and piracetam has potential as a novel therapeutic strategy for combating amnesia.

Evaluation of Antiarthritic Effect of Culinary-Medicinal Oyster Mushroom Pleurotus ostreatus cv. Florida (Agaricomycetes) on Complete Freund's Adjuvant Induced Arthritis in Rats.

The present study evaluates the antiarthritic effect of hydroethanolic extract of Pleurotus ostreatus cv. Florida, which was tested against adjuvant induced arthritis in rat models. Arthritis was induced by administration of complete Freund's adjuvant into the subplantar surface of left paw of rats. The extract was given orally at doses 200 mg/ kg and 400 mg/kg and piroxicam was administered intraperitonially (4 mg/kg). In vitro testing on parameters including antiproteinestrase, albumin denaturation and heat induce hemolysis was also carried out. There was significant decrease (p < 0.001) in proteinase activity and membrane stabilization in vivo studies on cv. Florida extract treated rats showed a significant (p < 0.001) decrease in paw volume, joint diameter, and spontaneous change in body weight recorded for 21 days. The treatment also resulted in an increase in rats' gripping activity compared with arthritic control rats. X-ray examinations showed a decrease in joint swelling. Histopathological examination of the extract treated group showed a significant decrease in joint space. There was also an increase in antibody levels. The antioxidant parameters showed a significant (p < 0.001) increase in superoxide dismutase and catalase enzymatic activities. Thus P. ostreatus cv. Florida extract demonstrates a potent antioxidant activity in a rat model. It is concluded that the P. ostreatus cv. Florida extract contains medicinally important constituents that show antiarthritic activity in rats.

Hematopoietic Effect of Amaranthus cruentus Extract on Phenylhydrazine-Induced Toxicity in Rats.

Amaranthus cruentus (Amaranthaceae) is one of the popularly grown leafy vegetables in the Indian subcontinent. Leaves of the plant are rich in polyphenols, tannins, flavonoids, steroids, terpenoids, saponins, and betalains. The plant also contains rich amounts of protein, calcium, iron, vitamins A, E, and C, and folic acid. The present work was undertaken to evaluate the antianemic effect of Amaranthus cruentus. Ethanol extract of Amaranthus cruentus was prepared. Acute oral toxicity of the extract was determined by Organization for Economic Cooperation and Development (OECD) Guideline 423. Doses of 200 and 400 mg/kg were used in the present study. Phenylhydrazine (60 mg/kg, intraperitoneal injection for three consecutive days) was used to induce anemia in rats. After anemia induction, animals were treated with standard preparation and extract. Amaranthus cruentus extract significantly aided in restoring the levels of red blood cells, white blood cells (WBCs), and hemoglobin. There was also an increase in hematocrit. Thus, it can be concluded that Amaranthus cruentus is a rich source of phytochemicals that are responsible for demonstrating hematopoietic effects. Isolation and structure elucidation of constituents, responsible for antianemic activity, is necessary to affirm the aforementioned effect.

Lactobionic acid coupled liposomes: an innovative strategy for targeting hepatocellular carcinoma.

INTRODUCTION: Liver cancer or hepatocellular carcinoma (HCC) is a major cause of death worldwide. Targeted delivery of drug to the carcinoma cell can be achieved by conjugation of ligand on the carrier system. METHODS AND MATERIALS: In this study, oxaliplatin-loaded hepatoma-targeted liposome were designed and prepared using galactosylated distearoylphosphatidylethanolamine. The liposomes were prepared by cast film method and coupled with lactobionic acid (LA-LP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a coupling agent. The coupling was confirmed by infrared spectroscopy. They were further characterized for various parameters such as vesicle shape and surface morphology, size, entrapment efficiency and in vitro release pattern. RESULTS AND DISCUSSION: The vesicle size of the uncoupled liposome (256 nm) was found to be less than LA-LP (310 nm). The uptake of LA-LP and uncoupled liposomes by BEL7402 HCC cell lines was visualized using fluorescence microscopy that revealed the dependence of liposomal recognition and higher uptake of the LA-LP. Organ distribution studies provided evidence that coupling of lactobionic acid on liposomal surface significantly enhanced the tumor uptake of drug, which is reflected by recovery of higher percentage of drug from tumor as compared to uncoupled liposomes or free drug. CONCLUSION: These studies suggest them as effective vectors for HCC targeting.

Immunoprophylactic potential of wheat grass extract on benzene-induced leukemia: An in vivo study on murine model.

OBJECTIVES: Wheat grass (Triticum aestivum) is a gift of nature given to mankind. A number of scientific research on wheatgrass establishes its anticancer and antioxidant potential. Current work was focused to determine antileukemic effect of wheat grass. MATERIALS AND METHODS: The commercial wheatgrass powder was extracted with 95% of methanol. Methanol extract of wheat grass was studied for acute oral toxicity as per revised Organization for Economic Cooperation and Development Guidelines number 423. Leukemia was successfully induced in Wister rats by intravenous injection of benzene. The blood was collected and analyzed for hematological parameters. Phagocytotic activity of the extract was determined. RESULTS: Phytochemical screening revealed the presence of flavonoids, phenolics, carbohydrates, and amino acids. From acute toxicity studies, it was found that the methanol extract of wheatgrass was safe up to a dose level of 2000 mg/kg of body weight. Outcomes of hematological parameters in various experimental groups of murine model demonstrated antileukemic effect of extract. Methanol extract of wheatgrass aroused the process of phagocytosis of killed Candida albicans and also demonstrated a significant chemotactic activity at all tested concentrations. CONCLUSION: In the current work, methanol extract of wheat grass demonstrated antileukemic potential that might be due to the presence of flavonoids and polyphenolics in it. Further isolation, structural characterization of active constituents is necessary to extrapolate the mechanism of action.

Protective effect of rutin on impairment of cognitive functions of due to antiepileptic drugs on zebrafish model.

AIM: The severity of adverse reactions due to antiepileptics is observed during initiation and early treatment in which impairment of cognitive effects are common. Since long time, herbal medicine is a natural remedy to treat neural symptoms. Phytochemicals have been proven to be potent neuro-protective agents. Rutin, a bioflavonoid is established to be nootropic in many studies. In this study, we aimed to determine the protective effect of rutin in zebrafish against the side effects produced by AEDs. MATERIALS AND METHODS: Seizures were induced in zebrafish by phenylenetetrazole. Rutin pretreatment (50 mg/kg, single injection, i.p.) was done before commencement of the study. Behavioral studies were performed as: latency to move high in the tank, locomotion effects, color effect, shoal cohesion, light/dark test on Zebrafish. RESULTS: Treatment with rutin reverted the locomotor behavior to normal. Treatment with AEDs caused fishes to move in all regions while, in case of treatment with rutin, the response reverted to normal. Treatment with AEDs altered swimming behavior of zebrafish, however, rutin showed a positive effect over this behavior. Treatment with AEDs resulted in restricted movement of zebrafish to the dark zone. Treatment with rutin caused increased latency of zebrafish to move in the light compartment. Similarly, time spent in the light compartment by zebrafish treated with rutin was significantly (P < 0.01) higher as compared to zebrafish treated with AEDs. CONCLUSION: The results suggest a protective role of rutin on cognition impaired by AEDs.

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

Protective effect of rutin on cognitive impairment caused by phenytoin.

OBJECTIVE: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. MATERIALS AND METHODS: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. STATISTICAL ANALYSIS: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. RESULTS: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. CONCLUSION: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy.

Formulation and characterization of floating microballoons of nizatidine for effective treatment of gastric ulcers in murine model.

BACKGROUND: The purpose of the present study was to formulate and characterize Nizatidine-encapsulated microballoons for enhancing bioavailability and increasing the residence time of drug in the gastrointestinal tract. METHODS: Microballoons were prepared using emulsion solvent diffusion method using Eudragit S-100 and HPMC as the polymer. The formulation process was optimized for polymer ratio, drug: polymer ratio, emulsifier concentration, stirring speed, stirring time. Optimized formulation was subjected to scanning electron microscopy, drug entrapment, buoyancy studies, in-vitro drug release and in-vivo floating efficiency (X-ray) study. In-vivo antiulcer activity was assessed by ethanol-induced ulcer in murine model. RESULTS: The microballoons were smooth and spherical in shape and were porous in nature due to hollow core. A sustained release of drug was observed for 12 h. Examination of the sequential X-ray images taken during the study clearly indicated that the optimized formulation remained buoyant and uniformly distributed in the gastric contents for a period of 12 h. In ethanol-induced ulcer model, drug-loaded Microballoon-treated group showed significant (p < 0.01) ulcer protection index as compared to free drug-treated group. CONCLUSION: Nizatidine-loaded floating microballoons may serve as a useful drug delivery system for prolonging the gastric residence time and effective treatment of gastric ulcers.

Mesalazine-probiotics beads for acetic acid experimental colitis: formulation and characterization of a promising new therapeutic strategy for ulcerative colitis.

BACKGROUND: Acetic acid ulcerative colitis (UC) is an experimental condition created due to intra-rectal administration of acetic acid which causes inflammation and ulceration in the lining of colon and rectum. In such condition, the colon cannot absorb liquid from the stools, resulting in larger volume of watery stools. Mesalazine is mainly used for the treatment of UC but suffers from the drawback of having poor bioavailability. UC is also characterized by alteration in colonic microflora. The present work was focused on delivering mesalazine along with probiotic, which would facilitate to refurbish customary growth of microflora. Mesalazine and probiotic were encapsulated in pectin beads with an aim to protect the drug from gastric environment and target to colonic region. METHODS: Pectin beads were prepared, formulation process was optimized for polymer concentration, drug concentration, cross-linking agent concentration. Formulation was characterized for surface morphology, in vitro drug release studies, determination of viable cell count, in vivo ulcer protective studies and stability studies. RESULTS: Average particle diameter of beads was ∼1.44-1.72 mm. Drug entrapment efficiency was found to be optimal (78-79%). A sustained release of drug was observed for 5 h; nearly 60% of drug was released at the end of 10 h. Microbiological studies of probiotic showed best cell viability. In acetic acid induced UC model, Mesalazine-probiotic beads-treated group showed significant (p < 0.01) ulcer protection index with respect to free drug-treated group. CONCLUSION: In conclusion, mesalazine-probiotic loaded beads may serve as a useful colon specific drug delivery system for treatment of colitis.

Delivery of Amphotericin B for Effective Treatment of Candida Albicans Induced Dermal Mycosis in Rats via Emulgel System: Formulation and Evaluation.

BACKGROUND: Amphotericin B (AmB) is among the gold standard antifungal agents used for the treatment of the wide range of fungal infections. However, the drug has various side- effects. Transdermal approach for the delivery of drug is one of the accepted and convenient modes of drug delivery. AIM: The current work was designed to formulate and to evaluate the AmB emulgel system. MATERIALS AND METHODS: In the preparation of AmB emulgel, Carbopol 930 was used as a gel in this study. The formulation was evaluated for viscosity, spreadability, drug content, drug release and in vitro and in vivo antifungal testing. RESULTS: AmB emulgel was found to penetrate skin effectively and without any irritation. Further, in vivo studies revealed effective therapeutic potential against Candida albicans induced dermal mycosis. CONCLUSIONS: The current work, for the first time, revealed effective delivery of AmB across the skin.

Harnessing the potential of bacterial ghost for the effective delivery of drugs and biotherapeutics.

It seems to be a necessary need to develop an effective drug carrier system for targeted delivery of pharmaceuticals. Bacterial ghosts are emerging drug delivery platform that are capable of delivery of proteins, antigens, nucleic acids, and pharmaceuticals. Bacterial ghosts are generally produced by lysis of gram-negative bacteria. Pharmaceutically, these ghosts could be utilized to deliver proteins peptides, vaccines, drugs effectively. However, this technology is at initial stage and systematic studies are required to implement such system over humans.

An experimetal evaluation of nephroprotective potential of Butea monosperma extract in albino rats.

OBJECTIVE: The current work was aimed to evaluate the nephroprotective potential of Butea monosperma. MATERIALS AND METHODS: Butea monosperma was collected from local forest of Jabalpur and extracted with ethanol. Healthy adult male Wistar albino rats between 5 and 6 months of age and weighing about 150-200 g were used for the study. Acute toxicity studies were performed to determine dose of extract. Nephrotoxicity was induced by gentamicin. Animals were divided in four groups in which first group served as positive control, second group as gentamicin treated toxic control; animals of group three and four were treated with Butea monosperma extract. Extract was administered to animals via oral route. Serum creatinine, serum urea, and blood urea nitrogen were estimated. Body weight was also determined. Histopathological studies were performed to access gross anatomical changes in animals. RESULTS: The extract of Butea monosperma was found to be rich in flavonoids, polyphenolics, and alkaloids. Urine creatinine, serum urea, and blood urea nitrogen were found to be significantly (P < 0.001) increased in rats treated with only gentamicin; whereas, treatment with the ethanolic extract of leaf of Butea monosperma reversed the effect of gentamicin indicating nephroprotective activity. CONCLUSION: The present study revealed that ethanolic extract of Butea monosperma is a good source of phytochemicals. The phytoconstituents flavonoids, phenolics, and alkaloids present in the extracts may be responsible for antioxidant activity. By the virtue of antioxidant activity, Butea monosperma demonstrated nephroprotective activity.

Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens.

AIM OF STUDY: The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. MATERIALS AND METHODS: Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 µg/ml and 500 µg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. RESULTS: Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (FNx01 P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. CONCLUSION: Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract.

Protective effect of curculigo orchioides extract on cyclophosphamide-induced neurotoxicity in murine model.

Free radicals are one of the frequent products of normal cellular metabolism. Disparity of metabolism and excessive generation of free radicals predisposes to disorders like Parkinson's disease, Alzheimer's disease, and aging phenomenon. Curculigo orchioides Gaertn. is known for "adaptogen" and "aphrodisiac" activity and has been proved for antiasthmatic, estrogenic, antiosteoporotic activity along with protection from cisplatin-induced cell damage. C. orchioides was powdered and subjected to soxhlet extraction using methanol. Phytochemical studies and estimation of polyphenols and flavonoids was performed. Acute toxicity studies were performed by Organization for Economic Cooperation and Development OECD guidelines. Animals were treated with cyclophosphamide to induce neurotoxicity. Curculigo orchioides was powdered and subjected to soxhlet extraction using methanol. Catalase, superoxide dismutase, glutathione peroxidase, and lipid peroxidation were estimated by reported methods. C. orchioides (400 mg/kg) significantly promoted restoration of catalase (P < 0.005), superoxide dismutase (P < 0.005), and glutathion (P < 0.05) levels. Similarly, a very significant decrease (P < 0.005) in the levels of malondialdehyde was observed. In all cases as mentioned previously, C. orchioides at dose 200 mg/kg promoted significant (P < 0.05) restoration of enzyme levels. C. orchioides (Kali Musli) is rich source of phytochemicals like flavonoids and polyphenols. Flavonoids and polyphenols are reputed to demonstrate neuroprotective effect. These phytochemicals in the present study might be responsible to demonstrate neuroprotective effect.

Preparation and biological evaluation of paclitaxel loaded biodegradable PCL/PEG nanoparticles for the treatment of human neuroendocrine pancreatic tumor in mice.

The main aim of this study was to develop and evaluate nanoparticulate system of paclitaxel loaded polymeric biodegradable Poly (ε-caprolactone) nanoparticles for targeting to neuroendocrine pancreatic tumors in mice. Nanoparticles were prepared by simple emulsion technique having surface modification with pluronic F-68. All formulations were evaluated for particle shape and size, zeta potential, encapsulation efficiency and in vitro drug release. Radiolabelling of nanoparticles with (99m)Tc was done for scintigraphy and biodistribution studies. Cytotoxicity studies were performed on BON-1 cell line using MTT cell proliferation assay. The in vivo tumor inhibition study was performed after i.v. administration of paclitaxel nanoparticles. Our results showed that optimized nanoformulation was found to have size range from 100 ± 0.03 nm to 250 ± 0.06 nm with smooth spherical shape. Negative zeta potential value confirmed the surface modification and stability of nanoformulations. The amount of drug released after 24h from the formulation was found to be 73.3% ± 2.7%. More pronounced cytotoxicity was found with nanoparticulate formulation as compared with paclitaxel. The PCL-Ptx nanoparticles reduced tumor volume significantly in comparison with paclitaxel. Higher concentration of Ptx-NPs were found in tumor which was also revealed by high quality scintigraphic image of BON-1 tumor bearing mouse model. In conclusion, polymeric nanoparticulate formulation of paclitaxel was very much efficient for chemotherapy of human pancreatic neuroendocrine tumor in mice.

Synthesis and evaluation of biodegradable PCL/PEG nanoparticles for neuroendocrine tumor targeted delivery of somatostatin analog.

PURPOSE: Neuroendocrine tumors often present a diagnostic and therapeutic challenge. We have aimed to synthesize and develop biodegradable nanoparticles of somatostatin analogue, octreotide for targeted therapy of human neuroendocrine pancreatic tumor. METHODS: Direct solid phase peptide synthesis of octreotide was done. Octreotide loaded PCL/PEG nanoparticles were prepared by solvent evaporation method and characterized for transmission electron microscopy, differential scanning calorimetery (DSC), Zeta potential measurement studies. The nanoparticles were evaluated in vitro for release studies and peptide content. For biological evaluations, receptor binding & cytotoxicity studies were done on BON-1 neuroendocrine tumor cell line. Biodistribution of radiolabeled peptide and nanoparticles, tumor regression studies were performed on tumor-bearing mouse models. RESULTS: We have synthesized and purified octreotide with the purity of 99.96% in our laboratory. PEG/PCL nanoparticles with an average diameter of 130-195 nm having peptide loading efficiency of 66-84% with a negative surface charge were obtained with the formulation procedure. Octreotide nanoparticles have a negative action on the proliferation of BON-1 cells. In vivo biodistribution studies exhibited major accumulation of octreotide nanoparticles in tumor as compared to plain octreotide. Octreotide nanoparticles inhibited tumor growth more efficiently than free octreotide. CONCLUSIONS: Thus, it was concluded that the PCL/PEG nanoformulation of octreotide showed high tumor uptake due to the enhanced permeation and retention (EPR) effect and then peptide ligand imparts targetability to the sst2 receptor and there by showing increase tumor growth inhibition. Selective entry of nanoparticles to the tumor also give the reduce side effects both in vivo and in vitro.