Antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of pentacyclic triterpenes isolated from Ziziphus oxyphylla Edgew.

Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla. Ceanothic acid and zizybrenalic acid showed significant DPPH and H2O2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl4)-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl4-induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.

Protective effect of the solvent extracts of Portulacca oleracea against acidified ethanol induced gastric ulcer in rabbits.

Portulacca oleracea L. has been used for treatment of different ailments. The aim of this study was to investigate the effectiveness and possible mechanism of action involved in the anti gastric ulcerogenic effect of Portulacca oleracea. Methanolic extract & subsequent fractions (100, 200 and 400 mg/kg) of Portulacca oleracea (P. oleracea) were administered orally to experimental rabbits one hour before oral administration of HCl/ethanol (40:60). Anti gastric ulcerogenic potential of P. oleracea was evaluated by assessment of gastric pH, pepsin, free acidity, ulcer index, mucus content and total acidity. For the investigation of possible mechanism of action malondialdehyde (MDA), histamine, and H + K + ATPase content were determined in the stomach homogenate. Histopathological study of stomach tissue was carried out by H&E dye. Ethyl acetate fraction (EAF) of P. oleracea was the most potent fraction among all fractions that exhibited efficient protection against acidified ethanol mediated gastric-ulcer. The ethyl acetate fraction (EAF) significantly increased the pH of gastric juice, while pepsin and histamine was observed to decrease significantly in comparison to acidified ethanol group (***p ≤ 0.001). The EAF showed moderately H + K + ATPase inhibitory activity. Moreover, it was also observed that EAF decreased the malondialdehyde (MDA) level in the stomach tissue homogenate showing antioxidant effect. Histopathological studies showed that among the tested fractions, EAF significantly prevented acidified ethanol induced gastric mucosal damage. These results showed that mechanism of anti gastric ulcerogenic potential of P. oleracea could be associated with the reduction in histamine level, H + K + ATPase inhibition and reduced MDA level.

Occurrence of adverse events in patient receiving community-based therapy for multidrug-resistant tuberculosis in Pakistan.

INTRODUCTION: Pakistan ranks 4th among 22 multidrug resistant tuberculosis (MDR-TB) high burden countries. The increasing rate of MDR-TB in Pakistan underscores the importance of effective treatment programs of drug-resistant TB. Clinical management of MDR-TB requires prolonged multidrug regimens that often cause adverse events (AEs). MATERIALS AND METHODS: This retrospective case series study include all patients who were enrolled for MDR-TB treatment during January 2014 till April 2015 at Programmatic Management of Drug Resistant TB (PMDT) unit at tertiary care hospital, Lady Reading Hospital (LRH) Peshawar Pakistan. In this study we sought to ascertain the occurrence of treatment related adverse events and factors associated with these events. Here we also examined the frequency of and reasons for changing drug regimens. We further sought to determine whether the occurrence of adverse events negatively impacts the treatment outcome and management of adverse effects without requiring the discontinuation of MDR-TB therapy. RESULT: At the time of analysis final outcomes of all 200 enrolled patients exist. Among these 52.5% were females and (81.5%) were aged ≤ 44 years. Among study cases 155 (77.2%) experienced at least one adverse event during treatment. The most commonly reported events were psychiatric issues (70%) whereas the less common was skin rashes (7.5%). A change in drug dose due to adverse events occurred in 16.5% cases, while 13.5% cases had at least one drug discontinued temporarily. Younger age and lung cavities at baseline were positive association with occurrence of adverse events. Association was also found between adverse events and treatment outcomes (OR 0.480, 0.236-0.978, p= 0.041). CONCLUSIONS: Adverse events were prevalent among MDR-TB patients treated at PMDT-LRH Peshawar. All patients who were younger aged and cavitory lungs should be closely monitored for occurrence of adverse events.

Nephrotoxic effects of Valeriana wallichii.

Aminoglycosides are the commonly used antibiotics against Gram negative bacteria. Their clinical applications are limited due to nephrotoxic side effects. Therefore, the current study was undertaken in an attempt to increase the use of these drugs without causing nephrotoxicity by exploring the nephroprotective effects of a medicinal plant with high flavonoid contents and strong antioxidant properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract derived from V. wallichii was employed for a period of three weeks. The results obtained revealed that co-therapy of extract with gentamicin protected some changes in renal functions; however, failed to provide a complete protection as assessed by biochemical, physiological and histological parameters. It can be concluded from the current findings that V. wallichii failed to deliver protective effects against gentamicin induced renal damage in spite of strong flavonoid contents and antioxidant properties.

Hepatoprotective effect of the solvent extracts of Viola canescens Wall. ex. Roxb. against CCl4 induced toxicity through antioxidant and membrane stabilizing activity.

BACKGROUND: Viola canescens Wall. ex. Roxb. exhibits analgesic, antimalarial and antispasmodic activities. It is used folklorically for the treatment of liver diseases, hypertension, malaria and cancer. The current study investigates phytochemical constituents, antioxidant and hepatoprotective activity of solvent extracts of whole plant of Viola canescens. METHODS: Phytochemicals, acute toxicity study and antioxidant activity of Viola canescens methanolic extract (VCME), ethyl acetate fraction (EAF), and partially purified EAF (90% EAF and combination of 80% EAF + 20% methanol fraction (EAF + Me) was carried out. Hepatoprotective activity of VCME, EAF (200 and 400 mg/kg body weight) and partially purified EAF (50 mg/kg body weight) was investigated in carbon tetrachloride (CCl4) intoxicated BALB/c mice for 7 days. Membrane stabilization effect was determined by hypotonic solution induced hemolysis while DNA ladder assay was carried out by polyacrylamide gel electrophoresis. RESULTS: Phytochemical screening of VCME showed the presence of alkaloids, phenols, flavonoids, saponins, carbohydrates, tannins and triterpenes. VCME, EAF (at 200 and 400 mg/kg body weight) and partially purified EAF (90% EAF and EAF + Me) at 50 mg/kg body weight significantly reduced the level of ALT, ALP, total bilirubin and restored the level of serum protein in comparison to CCl4 treated group. A significant reduction in malondialdehyde (MDA) and elevation in catalase (CAT) and superoxide dismutase (SOD) level was observed in extract treated animals as compared to CCl4 (p < 0.05). The IC50 values in membrane stabilization potential for VCME, EAF and sodium salicylate were 3.7 ± 0.11, 3.4 ± 0.15 and 3.2 ± 0.09 mg/ml, respectively. Similarly, CCl4 induced degradation of DNA was counteracted by VCME and EAF. The liver biopsy of mice treated with the solvent extracts showed remarkable restoration of normal histological archeitecture. CONCLUSIONS: Viola canescens showed significant hepatoprotective potential due to its antioxidant and membrane stabilization effect.

Nephroprotective property of Cinnamomum zeylanicum and its antibacterial activity in combination with gantamicin.

Cinnamomum zeylanicum has strong antioxidant properties and has been presented to have nephroprotective effects. Present work was aimed to study the nephroprotective property of the plant extract through urinary enzymes excretion, to confirm its protective effects and to observe the antibacterial activities of gentamicin in combination with the plant extract. 200mg/kg/day of the plant extracts were administered alone and as co-therapy with gentamicin. Urinary lactate dehydrogenase (LDH) and Urinary alkaline phospatase (ALP) excretions were observed through reagents kits with the help of Power-Lab 300. Antibacterial activities were assessed for gentamicin alone and in combination with the extract. Present study showed that the plant extract have excess quantity of flavonoids, which may responsible for attenuating the excessive excretion of urinary LDH. However, Urinary ALP excretion was found remained same throughout the study period in all experimental groups; might be detected in acute damage. Further, the plant also proved to have no decreasing impact on the antibacterial activities of gentamicin.

Nephro-protective potential of Morus alba, a prospective experimental study on animal models.

CONTEXT: Morus alba L. (Moraceae) is traditionally used for the treatment of urinary incontinency due its strong diuretic properties. OBJECTIVE: The present study explores the renal protective effects of M. alba, due to its free radical scavenging properties, in order to provide experimental evidence for its established use. MATERIALS AND METHODS: Ethanolic extract (200 mg/kg/d) derived from M. alba fruit was employed in rabbits as a co-therapy (GM-al) with gentamicin (80 mg/kg/d) for a period of 3 weeks. Biochemical kidney functioning parameters, urinary isozymes, and histopathological examination were performed. RESULTS: The results showed that ethanol extract of Morus alba L. prevented alterations in serum creatinine (4.02 ± 0.14, p < 0.0001), blood urea nitrogen (54.18 ± 2.60, p < 0.0001), and serum uric acid levels (2.34 ± 0.12, p < 0.001). However, a decrease in creatinine clearance and urinary volume was observed in experimental groups. Histopathological examination and urinary enzymes excretion also suggested the protective role of the extract. DISCUSSION AND CONCLUSIONS: The co-administration of M. alba with gentamicin prevented renal functioning alterations expected with the use of gentamicin alone. Therefore, it can be concluded that M. alba to protect from kidney damage, which may be because of its free radical scavenging and diuretic properties.

Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: a preliminary anti- Alzheimer's study.

BACKGROUND: Cholinesterase inhibition is a vital target for the development of novel and mechanism based inhibitors, owing to their role in the breakdown of acetylcholine (ACh) neurotransmitter to treat various neurological disorders including Alzheimer's disease (AD). Similarly, free radicals are implicated in the progression of various diseases like neurodegenerative disorders. Due to lipid solubility and potential to easily cross blood brain barrier, this study was designed to investigate the anticholinesterase and antioxidant potentials of the standardized essential oils from the leaves and flowers of Polygonum hydropiper. METHODS: Essential oils from the leaves (Ph.LO) and flowers (Ph.FO) of P. hdropiper were isolated using Clevenger apparatus. Oil samples were analyzed by GC-MS to identify major components and to attribute the antioxidant and anticholinesterase activity to specific components. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials of the samples were determined following Ellman's assay. Antioxidant assays were performed using 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. RESULTS: In the GC-MS analysis 141 and 122 compounds were indentified in Ph.LO and Ph.FO respectively. Caryophylene oxide (41.42 %) was the major component in Ph.FO while decahydronaphthalene (38.29 %) was prominent in Ph.LO. In AChE inhibition, Ph.LO and Ph.FO exhibited 87.00** and 79.66***% inhibitions at 1000 µg/ml with IC50 of 120 and 220 µg/ml respectively. The IC50 value for galanthamine was 15 µg/ml. In BChE inhibitory assay, Ph.LO and Ph.FO caused 82.66*** (IC50 130 µg/ml) and 77.50***% (IC50 225 µg/ml) inhibitions respectively at 1000 µg/ml concentration. In DPPH free radical scavenging assay, Ph.LO and Ph.FO exhibited IC50 of 20 and 200 µg/ml respectively. The calculated IC50s were 180 & 60 µg/ml for Ph.LO, and 45 & 50 µg/ml for Ph.FO in scavenging of ABTS and H2O2 free radicals respectively. CONCLUSIONS: In the current study, essential oils from leaves and flowers of P. hydropiper exhibited dose dependent anticholinesterase and antioxidant activities. Leaves essential oil were more effective and can be subjected to further in-vitro and in-vivo anti-Alzheimer's studies.

Comparative studies of binding potential of Prunus armeniaca and Prunus domestica gums in tablets formulations.

The current study was undertaken to compare the binding potential of Prunus armeniaca L. and Prunus domestica L. gums in tablets' formulations. Tablet batches (F-1 to F-9) were prepared Diclofenac sodium as model drug using 5%, 7.5% and 10% of each Prunus armeniaca L., Prunus domestica L. gums as binder. PVP K30 was used as a standard binder. Magnesium stearate was used as lubricant. Flow properties of granules (like bulk density, tapped density, Carr's index, Hausner's ratio, angle of repose) as well as the physical parameters of compressed tablets including hardness, friability, thickness and disintegration time were determined. Flow parameters of granules of all the batches were found good. Physical parameters (drug content, weight variation, thickness, hardness, friability, disintegration time) of formulated tablets were found within limit when tested. The dissolution studies showed that tablets formulations containing each Prunus domestica showed better binding capacity compared to Prunus armeniaca gum. The binding potential increased as the concentration of gums increased. The FTIR spectroscopic investigation showed that the formulations containing plant gum are compatible with the drug and other excipients used.

Nephroprotective potentials of Citrus aurantium: a prospective pharmacological study on experimental models.

Citrus aurantium is traditionally used in various kidney problems like burning of urine, urinary hesitancy and renal colic. The main objective of the present work was to evaluate the protective role of Citrus aurantium against gentamicin induced renal damage, due to its free radical scavenging properties to present experimental facts for their traditional use. 200 mg/kg/day of ethanolic extract of the plant employed in combination with the toxic doses of gentamicin for twenty-one days. The group GC-au (animals treated with co-administration of Citrus aurantium and gentamicin) protected renal damage expected with gentamicin, assessed by known functional and morphological parameters, significantly different from group G (animals treated with gentamicin). All the renal functioning parameters including; Blood urea nitrogen, Serum creatinine, Serum uric acid, Creatinine clearance, Serum electrolytes, Body weight, Urinary volume, Enzyme excretions, Urinary protein excretions and histological examination was performed for each and every group animals. The plant extract proved to have nephroprotective potentials may because of its known flavonoid contents and antioxidant properties.

Citrullus colocynthis failed to combat against renal derangements, in spite of its strong antioxidant properties.

Gentamicin is a potent antibiotic, effective against Gram negative bacteria. The most common adverse effect of gentamicin is nephrotoxicity. Present study was aimed to explore the protective potentials of Citrullus colocynthis against gentamicin induced nephrotoxicity due to its strong antioxidant properties. Toxic doses of gentamicin (80 mg/kg/day, i.m.) were administered alone and as co-therapy with the extract of C. colocynthis (25 mg/kg/day, p.o.). Physiological, biochemical and histological examinations were performed to compare the experimental and toxic groups (n = 6) with control group animals. Co-therapy of C. colocynthis with gentamicin protected changes in the body weight, blood urea nitrogen, creatinine clearance, proteins and lactate dehydrogenase excretions. However, a significant rise in serum creatinine and serum uric acid with fall in serum calcium and serum potassium was observed, which were significantly different from control group animals. Necrotic and ruptured tubules were also found abundantly. This study revealed that co-theapy of C. colocynthis with gentamicin for twenty one days, failed to protect renal injury associated by gentamicin in spite of its strong antioxidant properties.

Radical Scavenging, Anti-Inflammatory, and Hepatoprotective Activities of Pentacyclic Triterpene isolated from Rosa webbiana.

INTRODUCTION: Rosa webbiana (RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated. OBJECTIVE: The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities. METHODS: Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated via xylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used. RESULTS: A triterpene compound (3α, 21ß-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2 scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 µg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4. CONCLUSION: The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

In-vivo inhibition of latanoprost induced iridal hyperpigmentation in rabbits- An investigational study.

Objectives: To evaluate the inhibitory effects of different concentrations of α-methyl-DL-tyrosine on latanoprost-induced iridal hyperpigmentation in rabbits. Methods: We investigated 4 groups of rabbits. Both eyes of the pink, red, and blue groups were treated with latanoprost followed by 0.5%, 1%, and 2% α-methyl-DL-tyrosine (inhibitor) in the right eyes respectively and the green group received only inhibitor. We prospectively investigated the irides, estimated quantitatively total melanin contents, and studied any histopathological changes that occurred. Results: The observers favored hyperpigmentation in the left eyes while in the right eyes they noted a decrease in pigmentation as compared to the baseline. An increase in pigmentation was noted by 93.33% of observers in the left eye of the blue group. A significant difference in the mean melanin contents was noted in the blue group (Right eye = 09.560 µg/g (±0.750), Left eye = 3.730 µg/g (±1.062). There was no evidence of stromal malignant changes, Hemorrhage, mitosis, inflammation, and atypical melanocytes in all specimens. A moderate degree of pigmentation in the left eye of the red group was noted. Mild stromal-free melanin pigment was present in all samples of pink, red and blue groups. Conclusions: The α-methyl-DL-tyrosine significantly inhibited latanoprost-induced iridal pigmentation without causing any histopathological changes at a 2% dose.

Formulation Design, Characterization and In-Vivo Assessment of Cefixime Loaded Binary Solid Lipid Nanoparticles to Enhance Oral Bioavailability.

Cefixime; widely employed cephalosporin antibiotic is unfortunately coupled to poor water solubility with resultant low oral bioavailability issues. To solve this problem micro-emulsion technique was used to fabricate binary SLNs using blend of solid and liquid lipids, surfactant as well as co-surfactant. The optimized nano suspension was characterized followed by modification to solidified dosage form. During characterization, optimized nano-suspension (CFX-4) produced particle size 189±2.1 nm with PDI 0.310±0.02 as well as -33.9±2 mV zeta potential. Scanning electron microscopy (SEM) presented nearly identical and spherical shaped particles. Differential scanning calorimetry and X-ray powder diffraction analysis ascertained decrease in drug's crystallinity. In-vitro release of drug pursued zero-order characteristics and demonstrated non-fickian pattern of diffusion. The freeze dried nano suspension (CFX-4) was transformed to capsule dosage form to perform comparison based In-Vivo studies. In-Vivo evaluation corresponded to 2.20-fold and 2.11-fold enhancement in relative bioavailability of CFX nano-formulation (CFX-4) as well as the prepared capsules respectively in contrast to the commercialized product (Cefiget®). In general; the obtained results substantiated superior oral bioavailability along with sustained pattern of drug release for CFX loaded binary nano particles. Thus, binary SLNs could be employed as a resourceful drug carrier for oral CFX delivery.

Predictors of Mortality in COVID-19-Positive Patients On and Off CPAP: A Review From a Tertiary Care Setting in the NHS.

Introduction Since the first description of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that causes the infection/disease coronavirus disease 2019 (COVID-19) has evolved into a pandemic, and as of today, millions have been affected. Objectives Our aim was to identify the predictors of mortality in COVID-19-positive patients on or off continuous positive airway pressure (CPAP). Methodology This was an observational study. Data were collected from February 2020 to April 2020 with patients admitted to the COVID-19 ward at The James Cook University Hospital, Middlesbrough, England. The inclusion criteria were COVID-19-positive patients confirmed through PCR tests on or off CPAP. Patients who had negative RT-PCR for COVID-19 and those who were intubated were excluded. Results A total of 56 patients diagnosed with COVID-19 (through RT-PCR) were included in the final analysis, among which 27 were on CPAP, while 29 did not require CPAP (NCPAP). The overall mean age of the patients was 66 ± 14 (range: 26-94) years. The mean age of CPAP and NCPAP patients was 63 ± 15 (range: 26-85) years and 68 ± 13 (range: 40-94) years, respectively. The ethnicity of 54 (96.4%) patients was White-Caucasian, while 2 (3.6%) were British-Asian. In the study sample, 16 (28.6%) patients expired, of which 11 (40.7%) were on CPAP, while 5 (16.7%) did not require CPAP during the disease course. Correlation analysis showed that overall higher age, Medical Research Council Dyspnoea (MRCD) score, performance status (PS), and consolidation affecting more than one quadrant of the lungs were significantly correlated with increased mortality. Among patients receiving CPAP, higher age, MRCD score, and PS were significant predictors of mortality. Among the NCPAP group, advancing age, respiratory rate, MRCD score, PS, increased creatinine levels, and consolidation affecting more than one quadrant of the lungs were the predictors of mortality. Conclusion Even with a small sample size, we can see that there are definitive predictors that are directly proportional to increased mortality in COVID-19 patients on CPAP, such as higher age, performance status, MRCD score, and increased lung involvement of consolidation in more than one quadrant, which can help us rationalize management.

Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review.

Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. To our knowledge, this is the second case report which shows lisinopril-induced liver injury though a cholestatic mechanism. The patient was a 59-year-old woman with type 2 diabetes, a high body mass index and hypertension, who presented with a 5-week history of jaundice and itching. She had been started on lisinopril for diabetic nephropathy 8 weeks before admission. Other causes for cholestasis had been excluded through non-invasive immunology and virology screening, an ultrasound of the liver, magnetic resonance cholangiopancreatography and a liver biopsy. The biopsy was consistent with drug-induced liver injury. Lisinopril was stopped 2 weeks before admission. The patient's hospital stay was complicated by contrast nephropathy and influenza A which were both treated appropriately. Unfortunately, the liver cholestasis did not completely resolve following withdrawal of lisinopril and the patient died after 4 months. A literature search yielded only six other reported cases of lisinopril-induced liver injury. Five cases described hepatocellular damage and one showed cholestatic injury. LEARNING POINTS: Angiotensin converting enzyme inhibitors (ACE-I) rarely have serious or life-threatening side effects.Lisinopril-induced liver injury can present as hepatocellular or cholestatic injury.Severe hepatotoxicity secondary to lisinopril can be life threatening irrespective of the liver injury pattern.

Spectrofluorimetric determination of vitamin B(1) using horseradish peroxidase as catalyst in the presence of hydrogen peroxide.

In this work a new spectrofluorimetric method for the determination of vitamin B(1), based on the catalytic activity of horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2), has been developed. Non-fluorescent vitamin B(1) was easily converted through catalytic oxidation in alkaline medium into a fluorescent compound, even without exposure to light. The linear range for vitamin B(1) observed was 0.026-16.83 microg/mL (RSD = 1.75%). The correlation coefficient for the calibration curve and limit of detection were found to be 0.9964 and 0.015 microg/mL, respectively. The developed method is practical, simple, sensitive and relatively free from interference by coexisting substances and has been successfully applied for the determination of vitamin B(1) in pharmaceutical preparations.

Evaluation of Paeonia emodi for its cardioprotective potentials: An investigative study towards possible mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia emodi Wall. ex Royle (peony) is an important member of family Paeoniaceae. Different parts of the plant have been folklorically used for treatment of different diseases. Infusion of dried flowers is used to treat diarrhea, the seeds are emetic and cathartic while the rhizome has been indicated for the treatment of hysteria, abdominal spasm, nervine tonic and headache. Besides these, peony has also been used in different respiratory and cardiovascular diseases (CVDs) like hypertension, palpitations, congestive heart failure and atherosclerosis. Being a folkloric remedy for the treatment of CVDs, Paeonia emodi (P. emodi) requires to be explored scientifically for MI management. AIM: The current research work was designed to explore the possible cardioprotective mechanism of P. emodi in Isoproterenol hydrochloride (ISO) induced MI in mice. MATERIALS AND METHODS: Experimental animals randomly divided in different groups, received methanolic extract of P. emodi (Pe.ME) and its subsequent fractions for 15 days followed by ISO (100 mg/kg s.c) at 24 h interval for two days. The cardioprotective potential of the test samples were investigated by determining the serum levels of Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Lactate Dehydrogenase (LDH) and Creatine Phosphokinase (CPK). The ethyl acetate fraction (Pe.EA) was found potent among all the tested samples of P. emodi. Based on its high potency, Pe.EA was subjected to GC-MS analysis and further relevant experiments including anti-hyperlipidemic, antioxidant, lipid peroxidation, membrane stabilization, thrombolytic, DNA ladder assay and histopathological study. RESULTS: Pe.EA exhibited significant cardioprotective activity through reduction in levels of serum biomarkers responsible for MI. It significantly reduced serum levels of ALT (p < 0.001), AST (p < 0.001), CPK (p < 0.05) and LDH (p < 0.001) at a dose of 300 mg/kg as compared to ISO treated group. The GC-MS analysis confirmed the presence of potential compounds (esculetin, methyl eugenol, isovanillic acid) which might play a role in cardioprotection. Further screening confirmed that the effect of Pe.EA is mediated through multiple targets/mechanisms, which include anti-hyperlipidemia, antioxidant, lipid peroxidation inhibition, membrane stabilization, thrombolytic and DNA protective effects. Histopathological studies revealed the palliative effect for the damage caused in myocardial tissues. CONCLUSION: Findings of current study provide evidence that P. emodi is a potential candidate for the treatment and management of MI.

Evaluation of Paeonia emodi and its gold nanoparticles for cardioprotective and antihyperlipidemic potentials.

Paeonia emodi Wall. ex Royle is an important member of family Paeoniaceae and folklorically used for constipation, hysteria, respiratory diseases, epilepsy and cardiac diseases like hypertension, palpitations, congestive heart failure and atherosclerosis. In the present study, ethyl acetate fraction of P. emodi (Pe.EA) was subjected to column chromatography to obtain sub- fractions. These sub-fractions were screened for their cardioprotective activity in isoproterenol hydrochloride (ISO) induced myocardial infarction (MI) in mice. The most active fraction Pe. EA 40 was used for its gold nanoparticles synthesis (Pe.EA 40-AuNPs). Pe.EA 40 and Pe.EA 40-AuNPs were investigated for their cardioprotective, antihyperlipidemic, DNA fragmentation assay and histopathological study. Pe.EA 40 (80 mg/kg body weight) significantly reduced the serum levels of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH), Creatine Phosphokinase (CPK) to 66.07 ±â€¯1.54, 77.08 ±â€¯1.79, 84.86 ±â€¯1.34 and 265.34 ±â€¯4.34 IU/L respectively as compared to ISO treated group. Pe.EA 40-AuNPs (40 mg/kg) reduced the levels of ALT, AST, CPK and LDH to 60.74 ±â€¯2.79, 75.47 ±â€¯1.67, 80.48 ±â€¯2.64 and 247.54. ±â€¯5.57 IU/L respectively. A significant reduction was observed in lipid profile, protection in DNA damage and restoration of histopathological changes as compared to ISO treated group. Based on the results, it can be suggested that preparation of Pe.EA 40-AuNPs enhances the therapeutic potential of plant extract for the treatment of atherosclerosis and MI.

Fabrication of Niclosamide loaded solid lipid nanoparticles: in vitro characterization and comparative in vivo evaluation.

Niclosamide (NCS) is an oral anthelminthic drug having low solubility and hence low bioavailability. Current investigation shows an approach to fabricate solid lipid nanoparticles (SLNs) of NCS and evaluated for pharmaceutical, in vitro and in vivo characterization. NFM-3 showed particle size 204.2 ± 2.2 nm, polydispersity index 0.328 ± 0.02 and zeta potential -33.16 ± 2 mV. Entrapment efficiency and drug loading capacity were 84.4 ± 0.02% and 5.27 ± 0.03%, respectively. Scanning electron microscopy image indicated that particles were nanoranged. DSC and P-XRD results showed change in physicochemical properties of NCS. FT-IR spectra confirmed compatibility between NCS and excipients. The drug release profile showed sustained release (93.21%) of NCS in 12 h. Different kinetic models showed zero-order kinetics and Case-II transport mechanism. Study showed maximum stability at refrigerated temperature. In vivo pharmacokinetic study showed 2.15-fold increase in NCS peak plasma concentration as solid lipid nanoparticle formulation (NFM-3) compared to commercial product while relative bioavailability was 11.08. Results including in vitro and in vivo release studies of NCS confirmed that SLNs system is suitable to improve oral delivery of NCS with increased aqueous solubility, permeability and finally bioavailability.