Preclinical Data Extrapolation to Clinical Reality: A Translational Approach.

In vivo investigations are much more complex than trials conducted in a test tube; the results sometimes aren't as illuminating and could raise more questions than answers. Preclinical data projection into clinical truth is a transcriptional science that remains a compelling trial in drug development. Preclinical in vivo and in vitro education is important in novel drug's non-violent or active growth. Pharmacokinetic and metabolic research is necessary to better understand the chemical and biological effects of medicines and their metabolites. Information produced by such a policy can be used to progress Phase I studies, primarily for anticancer medication. Both living and deceased in vitro models are theoretically excellent preclinical tools for calculating the pharmacological action of counterparts from the same family, such as vinca alkaloids. The animal species most closely linked to humans are chosen based on metabolic patterns. The estimation of the duration of drug action, particularly for medicines with varied metabolic clearances (e.g., benzodiazepines); The empathetic or estimate of medicine relations, i.e., those defined for cyclosporin A and macrolide antibiotics; and Sclarification of the metabolic roots of individual inconsistencies in pharmaceutical action.

Neuropathy, its Profile and Experimental Nerve Injury Neuropathic Pain Models: A Review.

Neuropathy is a terrible disorder that has a wide range of etiologies. Drug-induced neuropathy, which happens whenever a chemical agent damages the peripheral nerve system, has been linked here to the iatrogenic creation of some drugs. It is potentially permanent and causes sensory impairments and paresthesia that typically affects the hands, feet, and stockings; motor participation is uncommon. It might appear suddenly or over time, and the long-term outlook varies. The wide range of chronic pain conditions experienced by people has been one of the main obstacles to developing new, more effective medications for the treatment of neuropathic pain. Animal models can be used to examine various neuropathic pain etiologies and symptoms. Several models investigate the peripheral processes of neuropathic pain, whereas some even investigate the central mechanisms, such as drug induce models like vincristine, cisplatin, bortezomib, or thalidomide, etc., and surgical models like sciatic nerve chronic constriction injury (CCI), sciatic nerve ligation through spinal nerve ligation (SNL), sciatic nerve damage caused by a laser, SNI (spared nerve injury), etc. The more popular animal models relying on peripheral nerve ligatures are explained. In contrast to chronic sciatic nerve contraction, which results in behavioral symptoms of less reliable stressful neuropathies, (SNI) spared nerve injury generates behavioral irregularities that are more feasible over a longer period. This review summarizes the latest methods models as well as clinical ideas concerning this mechanism. Every strongest current information on neuropathy is discussed, along with several popular laboratory models for causing neuropathy.

Oxazoline/amide derivatives against M. tuberculosis: experimental, biological and computational investigations.

Tuberculosis (TB) is a treatable contagious disease that continuously kills approximately 2 million people yearly. Different oxazoline/amide derivatives were synthesized, and their anti-tuberculosis activity was performed against different strains of Mtb. This study designed the anti-Mtb compounds based on amide and oxazoline, two different structural moieties. The compounds were further synthesized and characterized by spectral techniques. Their anti-Tb activity was evaluated against strain (M. tuberculosis: H37Rv). Selectivity and binding affinity of all synthesized compounds (2a-2e, 3a-3e) against PanK in Mtb were investigated through molecular docking. Molecular dynamics simulation studies for the promising compounds 2d and 3e were performed for 100 ns. The stability of these complexes was assessed by calculating the root mean square deviation, solvent-accessible surface area, and gyration radius relative to their parent structures. Additionally, free energy of binding calculations were performed. Among all synthesized compounds, 2d and 3e had comparable antitubercular activity against standard drug, validated by their computational and biological study.

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats.

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.

Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy.

Background: Morus alba Linn, referred to as white mulberry, is a potential traditional medicine for diabetes and neuroprotection. Aim: Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy. Material and methods: The stem Bark of M. alba was peeled and subjected to extraction. A phytoconstituent was then isolated by column chromatography and characterized using Mass spectroscopy, FTIR, and NMR. The isolated phytoconstituent was used to formulate a nanoemulsion. Nanoemulsion was also characterized for viscosity, surface tension, refractive index, pH, and particle size. Selected nanoemulsion formulations were then tested for acute oral toxicity and diabetic neuropathy, including behavioral, hematological, histopathological, and biomarker examinations. Results: The spectral analysis affirmed that the isolated compound was found to be chrysin. A nanoemulsion formulation was made using the chrysin and was characterized and found to be stable during the stability testing and fulfilled all other testing parameters. Then acute oral toxicity study of the formulations was found to be safe. Formulations were found to possess significant results against diabetic neuropathy in rats. Biomarkers were analyzed for their mechanistic involvement in reducing neuropathy in rats, and it was found that the oxidative pathway was considerably restored, suggesting that chrysin causes these effects via this pathway. Conclusions: Results suggests that isolated phytoconstituent (chrysin) from the bark of Morus alba derived nanoemulsion has protective and beneficial effects by diminishing the oxidative damage against alloxan-induced diabetic neuropathy in rats.

A critical review on the role of nanotheranostics mediated approaches for targeting ß amyloid in Alzheimer's.

Alzheimer's is one of the most common neurodegenerative illnesses that affect brain cellular function. In this disease, the neurons in the brain are considered to be decaying steadily but consistently by the accumulation of amyloid mass, particularly the ß-amyloids, amyloid proteins, and Tau proteins. The most responsible amyloid-proteins are amyloid-40 and amyloid-42, which have a high probability of accumulating in excess over the brain cell, interfering with normal brain cell function and triggering brain cell death. The advancement of pharmaceutical sciences leads to the development of Nanotheranostics technology, which may be used to diagnose and treat Alzheimer's. They are the colloidal nanoparticles functionalised with the therapeutic moiety as well as a diagnostic moiety. This article discusses the prognosis of Alzheimer's, various nanotheranostics approaches (nanoparticles, quantum dots, aptamers, dendrimers, etc), and their recent advancement in managing Alzheimer's. Also, various in-vitro and in-vivo diagnostic methodologies were discussed with respect to nanotheranostics.

Describing the pathophysiology of Alzheimer's with respect to amyloid ß in the prognosis of the diseasePresenting the various nanotheranostics techniques for the detection and treatment of Alzheimer's diseaseNanoparticles, Aptamers, and Dendrimers used as diagnostic and treatment entitiesIn-vivo (MRI, OI) and In-vitro (STM, TRPS) diagnostic approaches for detecting Alzheimer's disease.

Harnessing the potential of probiotics in the treatment of alcoholic liver disorders.

In the current scenario, prolonged consumption of alcohol across the globe is upsurging an appreciable number of patients with the risk of alcohol-associated liver diseases. According to the recent report, the gut-liver axis is crucial in the progression of alcohol-induced liver diseases, including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Despite several factors associated with alcoholic liver diseases, the complexity of the gut microflora and its great interaction with the liver have become a fascinating area for researchers due to the high exposure of the liver to free radicals, bacterial endotoxins, lipopolysaccharides, inflammatory markers, etc. Undoubtedly, alcohol-induced gut microbiota imbalance stimulates dysbiosis, disrupts the intestinal barrier function, and trigger immune as well as inflammatory responses which further aggravate hepatic injury. Since currently available drugs to mitigate liver disorders have significant side effects, hence, probiotics have been widely researched to alleviate alcohol-associated liver diseases and to improve liver health. A broad range of probiotic bacteria like Lactobacillus, Bifidobacteria, Escherichia coli, Sacchromyces, and Lactococcus are used to reduce or halt the progression of alcohol-associated liver diseases. Several underlying mechanisms, including alteration of the gut microbiome, modulation of intestinal barrier function and immune response, reduction in the level of endotoxins, and bacterial translocation, have been implicated through which probiotics can effectively suppress the occurrence of alcohol-induced liver disorders. This review addresses the therapeutic applications of probiotics in the treatment of alcohol-associated liver diseases. Novel insights into the mechanisms by which probiotics prevent alcohol-associated liver diseases have also been elaborated.

Mechanistic approach towards diabetic neuropathy screening techniques and future challenges: A review.

Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.

Isolation of Thymol from Trachyspermum ammi Fruits for Treatment of Diabetes and Diabetic Neuropathy in STZ-Induced Rats.

Terpenoids and phenols from Trachyspermum ammi (T. ammi) have reported some pharmacological actions. The objective of the work was to isolate the active constituent, its identification by spectroscopic techniques, and evaluation of the antidiabetic and neuroprotective activity from T. ammi on STZ Wistar rats. The dried fruits of T ammi were kept in a hydrodistillation apparatus to collect essential oil. The isolated fraction went through TLC, UV, FTIR, HPLC, HRMS, C13, and 1H NMR for characterization. Two dosage concentrations from the isolated compound were prepared as 10 and 20 mg/kg for treatment groups. The groups were tested for thermal and mechanical hyperalgesia, writhing, grip strength, spontaneous locomotor test, neuromuscular coordination tests, and histopathological and lipid profile analysis. Diabetes was induced by streptozotocin (45 mg/kg i.p.) and 12 weeks of treatment-induced diabetic neuropathy in Wistar rats. Biomarkers were evaluated to understand the neuropathic protection of thymol on STZ-treated Wistar rats. The biomarker studies (SOD, NO, LPO, Na+K+ATPase, and TNF-α) further confirmed thymol's diabetic neuropathy protective action. This study suggests that isolated compound thymol was antidiabetic and neuroprotective as it has shown controlled glucose levels defensive nerve damage in STZ Wistar rats. P < 0.05 level of significance was observed in the levels of endogenous biomarkers, fasting blood glucose levels, actophotometer response, and response latency in treated groups compared to the diabetic group, whereas P < 0.001 level of significance during lipid profile levels, thermal algesia, and neuromuscular comparison tests was noted in treated groups compared to the diabetic group.

Evaluation of the Antidepressant-like Effect of Total Sterols Fraction and Stigmasterol Isolated from Leaves of Aegle marmelos and Possible Mechanism( s) of Action Involved.

BACKGROUND: Aegle marmelos Corr. (Rutaceae) commonly known as 'Indian Bael' has been used as a brain tonic traditionally. However, despite this traditional use, not enough scientific report is present that can confirm the use of this plant in neurological disorders. Thus, the total sterols fraction and stigmasterol from the leaves of Aegle marmelos were investigated for antidepressant-like effect along with their possible mechanism(s) of action by primarily performing acute toxicity study of total sterols. METHODS: An acute toxicological study was carried out at a single oral dose of 2000 mg/kg. Sign of toxicity was observed by estimating biochemical and performing histopathological analysis. For the antidepressant-like effect, different doses of total sterols (50-200 mg/kg, p.o. for seven days) and stigmasterol (5- 20 mg/kg, i.p. acute) were administered in mice using TST and FST models. To evaluate the mechanism of action, mice were pretreated with GABA, 5-HT, DA, adrenergic antagonists, and glutamate agonists. Furthermore, a neurochemical study was performed following TST and molecular docking study was also performed to determine the binding affinity of stigmasterol. RESULTS: Total sterols fraction presents no sign of toxicity up to the oral dose of 2000 mg/kg. Oral treatment of total sterols and acute intraperitoneal treatment of stigmasterol (except 5 mg/kg) reduced the immobility time significantly. Pretreatment with pCPA (5-HT synthesis inhibitor) and NMDA (an agonist of the glutamate site) effectively reversed the immobility time of total sterols and stigmasterol (except pCPA) in TST. However, bicuculline (competitive GABA antagonist), haloperidol (D2 dopaminergic antagonist) and prazosin (α1 adrenergic antagonist) could not reverse the immobility time. Meanwhile, total sterols also effectively altered the hippocampus 5-HT and Glu levels. Also, the result of the molecular docking study depicted that stigmasterol has an affinity to the NMDA receptor. CONCLUSIONS: The present study suggests that the total sterols fraction did not produce any acute toxicity in rats. Also, we reported that total sterols, stigmasterol and sub-effective stigmasterol coadministration with fluoxetine significantly reduced the time of immobility in TST and FST confirmed the antidepressant-like effect of total sterols fraction and stigmasterol. Moreover, further findings suggest that the antidepressant-like effect of total sterols might be mediated by the serotonergic and glutamatergic systems. Whereas only the glutamatergic system was involved in the antidepressant activity of stigmasterol.

Evaluation of mechanism(s) of action underlying the antioxidant and antiulcer activity of Sesamum indicum leaves extract in experimental rats.

OBJECTIVE: The current study aimed to estimate phytochemical screening, in vitro antioxidant activity, and gastroprotective activity of Sesamum indicum Linn ethanolic extract. MATERIALS AND METHODS: The current study was held out by ulceration induced by pylorus ligation and indomethacin-induced ulcer screening models in Wister albino rats. The screening of antiulcer activity of ethanolic extract of S. indicum leaves (EESIL) at the different amounts (100, 200, and 400 mg/kg; per orally for 7 days) was compared with omeprazole as a usual antiulcer drug. Additional parameters such as gastric content, pH, total acidity, pepsin activity ulcer score, free acidity, ulcer index (UI), % inhibition of ulcers, mean mucin, pepsin content, and total protein content were observed. RESULTS: In the pylorus ligation model, the pepsin activity free acidity, pepsin content, UI, total acidity, ulcer score, total protein content, and percentage ulcer inhibition were considerably decreased (P < 0.05 and P < 0.01), and mean mucin and gastric content pH extensively elevated (P < 0.05 and P < 0.01) in EESIL tested groups in the comparison of the control group. Doses (100, 200, and 400 mg/kg p.o.) of EESIL showed dose-reliant gastro protective outcomes, a considerable (P < 0.05 and P < 0.01) decrease in gastric parameters as UI and ulcer score and induction in gastric pH and percentage inhibition of ulcer compared with the control group. CONCLUSION: Antioxidant, anti-Ulcer, EESIL, and EESIL show antioxidant activity at different concentration. The fallout of the study indicated that the EESIL had improved antiulcer potential due to the decrease in offensive factors and increase in defensive factors.

Anxiolytic and antidepressant-like effects of essential oil from the fruits of Piper nigrum Linn. (Black pepper) in mice: involvement of serotonergic but not GABAergic transmission system.

In this study, the anxiolytic activity of Piper nigrum essential oil (PNEO) was evaluated in the elevated plus maze (EPM) and the antidepressant-like effect was evaluated through tail suspension test (TST) in mice. Flumazenil, a competitive inhibitor of GABAA receptor in the benzodiazepine site and WAY-100635 maleate salt, a 5-HT1A receptor antagonist were used to find out the possible mechanism(s) of action of PNEO. To exclude the false-positive results due to the enhancement of the locomotor activity, the animals were submitted to open field test (OFT). We also measured monoamines levels of the mice brain after acute PNEO treatment. The data obtained from the study suggest that the anxiolytics and antidepressant-like effect of PNEO have observed in EPM and TST respectively in a dose-dependent manner after oral acute and repetitive treatment. WAY-100635, but not flumazenil was able to reverse the effect of PNEO in EPM and TST both, indicating the possible involvement of 5-HT1A receptor. The neurochemical analysis showed no alteration in monoamine levels in mice brains. Furthermore, no locomotor impairment or sign of toxicity or changes in body weight or abnormalities in the biochemical parameters, except for a significant decrease in total cholesterol level was observed after treatment with PNEO. The findings suggest that Piper nigrum EO possesses a dual anxiolytic and antidepressant-like effect through the possible involvement of serotonergic transmission.

Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as a New Lead for Treating Breast and Ovarian Cancer.

A serine/threonine-protein kinase, recognized as Glycogen Synthase Kinase-3 (GSK-3), is documented as a regulator of assorted cellular roles. GSK-3 activates by phosphorylation and thereby controls the action of many physiological, messenger, and membrane-bound structures. GSK-3α and GSK-3ß are two vastly homologous forms of GSK-3 in mammals. Recent information has recommended that GSK-3ß is a constructive controller of cancer cell proliferation and a promising key target against cancer cells. GSK-3 is overexpressed in various tumor types, including ovarian tumors. In human breast carcinoma, it has been revealed that the overexpression of GSK-3ß was linked with breast cancer patients. The inhibition of GSK-3 or inhibitors of GSK-3 is a promising therapeutic tactic to overcome breast and ovarian cancer. This article features an important aspect of inhibitors of Glycogen Synthase Kinase-3 as a new lead for treating breast and ovarian Cancer.

Acute and Sub-Acute Toxicity Studies and Pharmacodynamic Studies of Standardized Extract of Trachyspermum ammi (L.) Sprague (Fruits) Against Chemically Induced Inflammation in Rats.

INTRODUCTION: Nowadays, researchers have been attempting to use herbal products as medicines which have proven to cause lesser side effects. The fruit part of Trachyspermum ammi (L.) - Ajwain has been an integral part of the Indian medicine system with much importance in Ayurveda and Unani medicine system and is prescribed by Vaidya gurus and Hakim in raw form or as a major constituent in the powdered formulations. OBJECTIVE: This research aimed to evaluate acute and sub-acute toxicity of standardized T. ammi fruit and its anti-inflammatory property using experimental models. METHODS: The extract of herbs was spectroscopically analyzed for the estimation of the number of bioactive compounds. Then acute and sub-acute toxicity analysis of the herbal extract was performed to ensure the toxic effects, if any. Biochemical parameters like ALT, AST, ALP, etc. and histopathological analysis were determined to study the toxicity of the extract. Then, the anti-inflammatory activity of the T. ammi fruit extract employing Carrageenan and formalin-induced edema model in rats was studied. RESULTS: Ajwain seeds have a pungent smell and a characteristic odor. The powder microscopy clearly showed endosperm, unicellular warty trichomes, striated cuticle in surface view, vittae, endodermis, and vascular strand. Phytochemical tests reported the presence of carbohydrates, alkaloids, tannins, etc. and characteristic peaks in UV, Mass, NMR, FTIR and HPLC were observed for the extract. Acute and sub-acute toxicity studies did not report any toxicity, and significant anti-inflammatory action was recorded. CONCLUSION: The spectroscopic and pharmacognostic analysis has shown the strong presence of flavonoids, mineral matter, protein, phenols, saponins, carbohydrates, volatile oils, fiber, glycosides and fat. Spectroscopic study interpretations have shown the presence of compounds like thymol, para-cymene, γ-terpinene, α- and ß-pinene, carvone, limonene, saponins,, ß-phellandrene, ßfenchyl alcohol, α-thujene, ß-phellendrene, α-thujene, etc. No signs of toxicity were recorded in acute and sub-acute toxicity studies assessing the relative weight and histopathological analysis. Significant anti-inflammatory potential of T. ammi fruit extract was found and LD50 was found to be beyond 3000 mg/kg. The results of this study could be useful; in setting the quality parameters for further identification of the crude herb and preparation of the monograph.

Anti-diabetic, diabetic neuropathy protective action and mechanism of action involving oxidative pathway of chlorogenic acid isolated from Selinum vaginatum roots in rats.

Phytopharmaceuticals have always reported vital roles in the field of medicine hence the need to investigate safe and efficient drugs for treating metabolic disorders is very significant. Roots of Selinum vaginatum have therapeutic benefits and are widely used by the people of the Rohtang region for treating diabetes and its associated complications. The present study focusses on the isolation of the bioactive from the S. vaginatum roots for estimating acute toxicity studies, anti-diabetic and diabetic neuropathy protective action along with the mechanism of action in STZ induced Wistar rats. The Selinum vaginatum roots were collected from the Rohtang region, Himalayas. Chlorogenic acid was isolated and underwent identification by UV, HPLC, 1H NMR, C13 NMR, Mass, and FTIR spectroscopy methods. Chlorogenic acid was dosed at 10 and 20 mg/kg to observe the effects on experimentally induced diabetes and with time generated diabetic neuropathic complications. Biomarkers TNF-α, superoxide dismutase, nitrosative stress, lipid peroxide profile, and membrane-bound inorganic phosphate were analyzed. Histopathological evaluation of the liver and sciatic nerve was performed for all groups. Parameters like blood glucose levels, body weight, food intake, Thermal Hyperalgesia, Writhing, Cold Hyperalgesia Responses, Mechanical hyperalgesia, Grip Strength, Spontaneous Locomotor (Exploratory) Test, Neuromuscular Coordination tests, and lipid profile analysis showcased the anti-diabetic and diabetic neuropathy protective action of the drug. Inflammation, degradation, and necrosis were found to be reduced in the liver and sciatic nerve cells of treated groups. All the biomarkers used to analyze the oxidative pathway were significantly replenished indicates that chlorogenic acid produces these effects through this pathway.

Pharmacodynamic evaluation of self micro-emulsifying formulation of standardized extract of Lagerstroemia speciosa for antidiabetic activity.

BACKGROUND: Lagerstroemia speciosa (SEL) leaves are a popular folk medicine for diabetes treatment due to presence of corosolic acid. It has low water solubility resulting poor absorption after oral administration. Self micro-emulsified drug delivery system is the way by which we can improve the oral absorption of drug. OBJECTIVE: The objective of this study was to develop the self micro-emulsifying formulation of standardized extract of SEL leaves and evaluate its pharmacodynamic performance for antidiabetic activity. MATERIALS AND METHODS: The SME formulation was prepared by using sefsol-218 as oil, cremophor-EL as surfactant and transcutol-P as co-surfactant. The ratio of surfactant and co-surfactant was determined by pseudoternary phase diagram. SME formulations were characterized for dilution at different pH, self emulsification, optical clarity, globule size and thermodynamic stability. Pharmacodynamic evaluation of formulations was assessed in Wistar rats by using parameters viz. blood glucose level and serum lipid profile. RESULTS: SEL loaded SME formulation was successfully developed by using sefsol-218, cremophor-EL and transcutol-P with a droplet size 23.53 nm. Pharmacodynamic results showed a higher reduction in blood glucose by SME formulation than SEL without SMES respectively at 50 mg/kg dose while reduction produced at dose of 100 mg/kg was found significant and better on 15th day of study. The percentage reduction produced by SME formulation on serum lipid profile was also significant and was more prominent than SEL. CONCLUSION: This study confirms that the formulation elevates the pharmacodynamic performance of SEL approximately two fold.

Effect of Delonix regia (Boj. Ex Hook.) Raf. stem bark extract against experimentally induced ulcers in rats.

Delonix regia, commonly called Flame Tree or Flamboyant (locally, Gul Mohor) is a common tree traditionally used to treat various diseases like gastric problems, body pain, rheumatic pains of joints and wound healing. Here, we carried out biological profiling of Delonix regia as antiulcer agent. Antiulcer activity of the ethanol extract from stem bark was evaluated on pylorus ligation and indomethacin induced ulcer in Wistar albino rats. Ethanol extract from stem bark of D.regia was administered at the doses 100, 200 and 400 mg/kg/day, p.o. for 7 days. Ulcer index, gastric pH, volume, free acidity, total acidity, total carbohydrate (TC), protein (P), mucin content (TC/P) and gastric mucus were evaluated in pylorus ligation model, while ulcer index, malondialdehyde, GSH, PGE2, and gastric mucus were estimated in the indomethacin induced ulcer model. Ex vivo assay for the activity of H+/K+-ATPase was also done. The results showed significant inhibition on H+/K+-ATPase in a dose dependent manner and comparableto their respective positive control group of rats demonstrating that ethanol extract of stem bark of Delonix regia possesses significant antiulcer properties.

Evaluation of antisecretory, gastroprotective and in-vitro antacid capacity of Fumaria indica in rats.

Fumaria indica is used for its anthelmintic, antidyspeptic, cholagogue, diaphoretic, diuretic, laxative, stomachic, tonic properties and claimed to possess various properties for the ailments of blood, skin, gastrointestinal systems and central nervous system. The present study was undertaken to evaluate antisecretory, gastroprotective and in-vitro antacid capacity of ethanol extract from F. indica in rats. Evaluation of F. indica extract as antisecretory was carried out by pyloric ligation induced ulcer model. The gastroprotective effect was carried out by absolute ethanol induced ulcer model. Integrity of gastric mucosa was evaluated by estimation of GSH and gastric mucus level. The in-vitro antacid capacity was evaluated by titration method. Ethanol extract of F. indica at 200 mg kg(-1), orally showed inhibition of secretion in pyloric ligation model. GSH level (1.67 µg mg(-1) protein), gastricwall mucus (240.76 µg g(-1) wet glandular tissue) and percentage protection (77.59%) of ulcer were significantly (P < 0.05) increased in absolute ethanol induced ulcer model. The in-vitro antacid capacity of ethanol extract of F. indica was compared with the standard. Conclusively, it appears that F. indica possess antisecretory (inhibition of acid secretion), gastroprotective (potentiation of defensive factors) and in-vitro antacid activity.

Assessment of Antisecretory, Gastroprotective, and In-vitro Antacid Potential of Daucus carota in Experimental Rats.

OBJECTIVES: In Indo China, carrots have been reported to regulate the functions of the stomach and intestines. The objective of the present investigation was to unravel the therapeutic potential of 50% ethanol extract from Daucus carota roots (EDC) on antisecretory, gastroprotective, and in vitro antacid capacity using experimental rats. METHODS: Assessment of EDC antisecretory and in vivo antacid capacities was carried out using a pyloric ligation induced ulcer model. The gastroprotective effect was assessed with an absolute ethanol induced ulcer model. The integrity of gastric mucosa was evaluated using the estimation of glutathione and gastric mucus level and with histopathological examination of gastric mucosal cells. The in-vitro antacid capacity was evaluated using a titration method. The effect of the extract on the liver was assessed by measuring serum biochemical parameters. RESULTS: The EDC significantly (p < 0.01-0.001) reduced gastric lesions in both models. Furthermore, the EDC also significantly (p < 0.05-0.001) reduced the volume of gastric content whereas the total acidity was significantly (p < 0.05-0.001) reduced with the doses of 100 mg/kg and 200 mg/kg EDC. Moreover, the mucus content and glutathione level increased significantly (p < 0.05) in the absolute alcohol-induced ulcer. The EDC also showed in-vitro antacid capacity. Histopathological studies further confirmed the potential of EDC by inhibiting congestion, edema, hemorrhage, and necrosis in gastric mucosa. CONCLUSION: The EDC exerted antisecretory, gastroprotective, and in vitro antacid potential. These activities could be attributed due to the presence of glycosides, phenolics, tannins, alkaloids, and flavonoids.

Protective effect of Dalbergia sissoo Roxb. ex DC. (family: Fabaceae) leaves against experimentally induced diarrhoea and peristalsis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia sissoo Roxb. ex DC. (family: Fabaceae; Indian Rosewood), is used in India, especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to substantiate the claim of therapeutic success of the plant species in diarrhoea. AIM: To study the protective effect of ethanol extract from D. sissoo Roxb. ex DC. leaves (EDSL) against experimentally induced diarrhoea and peristalsis in mice. MATERIALS AND METHODS: Castor oil-induced diarrhoea and magnesium sulphate (MgSO4)-induced diarrhoea tests were used to assess the antidiarrhoeal activity of D. sissoo. Gastrointestinal tract transit of charcoal meal test and barium sulphate milk was used to assess the peristalsis activity of the extract, while the acute toxicity study and determination of total phenolics and total flavonoids were carried out using well-established protocols and methods. RESULTS: The EDSL significantly reduced faecal output in castor oil-induced and MgSO4-induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. D. sissoo significantly delayed the onset of diarrhoea induced by both castor oil and MgSO4 and comparable to loperamide, a standard antidiarrhoeal drug. Both D. sissoo and atropine sulphate significantly reduced the peristalsis activity of charcoal meal and barium sulphate milk in mice. The preliminary phytochemical analysis of EDSL revealed the presence of carbohydrates, phenolics, glycosides, and flavonoids. The median lethal dose of EDSL was greater than 2000 mg/kg (orally (p.o.)). CONCLUSION: The data obtained indicate that the EDSL has antidiarrhoeal and antiperistalsis activities and thus supports its traditional use. The data also show that the plant material given p.o. may be safe and/or non-toxic in mice.