Ameliorative Effect of Ethanolic Extract of Moringa oleifera Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico.

The ameliorative effect of ethanolic extract of M. oleifera (MOEE) leaves in combination with curcumin against seizures, cognitive impairment, and oxidative stress in the molecular docking of PTZ-induced kindled rats was performed to predict the potential phytochemical effects of MOEE and curcumin against epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250 mg/kg and 500 mg/kg, orally), curcumin (200 mg/kg and 300 mg/kg, orally), valproic acid used as a standard (100 mg/kg), and the combined effect of MOEE (250 mg/kg) and curcumin (200 mg/kg) at a low dose on Pentylenetetrazole was used for (PTZ)-induced kindling For the development of kindling, individual Wistar rats (male) were injected with pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular docking was performed by the Auto Dock 4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of human glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and M. oleifera ethanolic extracts (MOEE) showed dose-dependent effects. The combined effects of MOEE and curcumin leaves significantly improved the seizure score and decreased the number of myoclonic jerks compared with a standard dose of valproic acid. PTZ kindling induced significant oxidative stress and cognitive impairment, which was reversed by pretreatment with MOEE and curcumin. Glutathione reductase (GR) is an enzyme that plays a key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift antioxidant properties, which leads to the inhibition of ROS-induced cell death in the brain. The combination of the ethanolic extract of M. oleifera (MOEE) leaves and curcumin has shown better results than any other combination for antiepileptic effects by virtue of antioxidant effects. As per the docking study, chlorogenic acid and quercetin treated with acombination of curcumin have much more potential.

The Structural, Biological, and In-Silico Profiling of Novel Capryloyl Tetra-Glucoside and Aliphatic Ester Constituents from the Abutilon indicum Offers New Perspectives on the Treatment of Pain and Inflammation.

Abutilon indicum L. (Malvaceae), more often referred to as Peeli booti, Kanghi, and Kakhi, is a perennial shrub found in many countries of Asia. Traditionally, this plant is used as a diuretic to treat inflammation, discomfort, urethral infections, and gout. Inflammation and pain are key topics of interest for researchers throughout the globe, since they are linked to almost every illness that could affect humans or animals. The present study was conducted to isolate the phytoconstituents from the methanolic extract of Abutilon indicum collected from the Bihar state Koshi river belt in India, and to evaluate the isolated phytoconstituents' ability to reduce nociception and inflammation. Furthermore, molecular docking was performed to investigate the molecular interaction profile, with possible therapeutic targets for anti-inflammatory medicines. A. indicum methanolic extract yielded two novel phytocompounds identified as 5'-hydroxyhexyl n-hexadecanoate (AB-01) and n-octanoyl-ß-D-glucopyranosyl-(2'-1'')-ß-D-glucopyranosyl-(2''-1''')-ß-D-glucopyranosyl-(2'''-1'''')-ß-D-glucopyranoside (AB-05), together with three previously recognized phytocompounds such as ester glucoside. All isolated molecules were tested for the efficacy of analgesic and anti-inflammatory characteristics at doses of 5 and 10 mg/kg body weight. The isolated compound's molecular interaction profile with anti-inflammatory drug targets cyclooxygenase-2 and tumor necrosis factor-alpha possessed high potential energy in molecular docking. These findings may aid in developing anti-inflammatory and analgesic drugs from A. indicum.

Cirsilineol Inhibits the Proliferation of Human Prostate Cancer Cells by Inducing Reactive Oxygen Species (ROS)-Mediated Apoptosis.

Cirsilineol has been reported to exhibit anticancer effects against several human cancer cell lines. The present study was designed to evaluate the anticancer effects of cirsilineol against the human DU-145 prostate cancer cells. The results showed that cirsilineol suppressed the proliferation of DU-145 cancer cells in a dose-dependent manner with minimal cytotoxic effects against the normal cells. The IC50 of cirsilineol was found to be 7 µM and 110 µM against prostate cancer DU-145 and normal HPrEC prostate cells, respectively. Acridine orange and ethidium bromide (AO/EB) staining showed that cirsilineol induced apoptosis in DU-145 prostate cancer cells. The Annexin V/PI staining further confirmed the induction of apoptosis in DU-145 cells. The western blot analysis showed that cirsilineol suppressed the expression of Bax and upregulated the expression of Bcl-2 in prostate cancer DU-145 cells. Moreover, cirsilineol caused a dose-dependent increase in reactive oxygen species (ROS) levels in prostate cancer. Wound healing and Transwell assays showed that cirsilineol inhibits migration and invasion of DU-145 prostate cancer cells. Summing up, the results suggest that cirsilineol suppresses the proliferation of prostate cancer cells and may prove to be a beneficial lead molecule for the development of chemotherapy for prostate cancer.

Impact of Bariatric Surgery in Reducing Macrovascular Complications in Severely Obese T2DM Patients.

BACKGROUND: Evidence from real-world studies have suggested a reduced rate of macrovascular complications following bariatric surgery. We undertook this meta-analysis to investigate the impact of bariatric surgery on macrovascular disease outcomes in severely obese type 2 diabetes mellitus (T2DM) patients. METHODS: An extensive literature search was performed in PubMed from inception until March 2020. All cohort studies assessing the association between bariatric surgery and macrovascular complications in severely obese T2DM patients were included. Two independent reviewers screened the articles, extracted data, and assessed the quality using the Newcastle-Ottawa Scale. The primary outcome was to assess the impact of bariatric surgery and the risk of macrovascular complications. Statistical analysis was performed using Review Manager 5.3. RESULTS: This meta-analysis comprised of five studies including 49,211 participants (75% female), of which 14,434 underwent bariatric surgery and 34,777 underwent usual care. Participants who underwent bariatric surgery had a significantly lower risk of macrovascular complications as compared to those with non-surgical interventions (RR: 0.50 [95% CI: 0.35-0.73], p = 0.0003). In the subgroup analysis, based on the geographical regions, studies conducted in the USA showed a higher reduction (RR: 0.41 [95% CI: 0.32-0.53], p < 0.00001) in macrovascular complications as compared to other parts of the world. The risk of all-cause mortality was also significantly lower in patients with bariatric surgery (RR 0.39 [95% CI: 0.30-0.50], p < 0.00001). CONCLUSION: Bariatric surgery was associated with a 50% reduction in macrovascular complications along with 61% reduction in risk of all-cause mortality in morbidly obese T2DM patients.

Nicotinamide Therapy in Dialysis Patients: A Systematic Review of Randomized Controlled Trials.

Randomized controlled trials (RCTs) have presented variable findings concerning the reduction of phosphorous level by nicotinamide. This systematic review is aimed to explore the safety and efficacy of nicotinamide in hemodialysis patients and was conducted by adhering to the PRISMA guidelines. Studies for inclusion were identified by running the suitable keywords in PubMed, Embase, and Cochrane Central till June 13, 2018. Cochrane risk of bias tool was used to judge the quality of the included RCTs. The primary outcome was change in serum phosphorus, calcium, and calcium-phosphorus product levels. Change in other biochemical parameters including serum calcium, parathormone, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for the risk of bias estimate. A total of 12 articles were qualified for inclusion in this study. All the included RCTs showed a statistically significant reduction in mean serum phosphorous and calcium-phosphorus product levels in the treatment arm as compared to the placebo group. Among several biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant difference. Flushing and diarrhea, followed by thrombocytopenia, were the most commonly reported adverse events in the treatment group. Nicotinamide was found to be effective in reducing the phosphorous level and calcium-phosphorus product level and increasing the HDL cholesterol level in dialysis patients. The safety profile was found to be satisfactory.

Burden of diabetes mellitus and its impact on COVID-19 patients: A meta-analysis of real-world evidence.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) spreads rapidly and within no time, it has been declared a pandemic by the World Health Organization. Evidence suggests diabetes to be a risk factor for the progression and poor prognosis of COVID-19. Therefore, we aimed to understand the pooled prevalence of diabetes in patients infected with COVID-19. We also aimed to compute the risk of mortality and ICU admissions in COVID-19 patients with and without diabetes. METHODS: A comprehensive literature search was performed in PubMed to identify the articles reporting the diabetes prevalence and risk of mortality or ICU admission in COVID-19 patients. The primary outcome was to compute the pooled prevalence of diabetes in COVID-19 patients. Secondary outcomes included risk of mortality and ICU admissions in COVID-19 patients with diabetes compared to patients without diabetes. RESULTS: This meta-analysis was based on a total of 23007 patients from 43 studies. The pooled prevalence of diabetes in patients infected with COVID-19 was found to be 15% (95% CI: 12%-18%), p = <0.0001. Mortality risk was found to be significantly higher in COVID-19 patients with diabetes as compared to COVID-19 patients without diabetes with a pooled risk ratio of 1.61 (95% CI: 1.16-2.25%), p = 0.005. Likewise, risk of ICU admission rate was significantly higher in COVID-19 patients with diabetes as compared to COVID-19 patients without diabetes with a pooled risk ratio of 1.88 (1.20%-2.93%), p = 0.006. CONCLUSION: This meta-analysis found a high prevalence of diabetes and higher mortality and ICU admission risk in COVID-19 patients with diabetes.

Potential biomarkers for early detection of diabetic kidney disease.

INTRODUCTION: To assess the potential of galectin-3 and growth differentiation factor-15 (GDF-15) biomarkers for the early detection of diabetic kidney disease (DKD). METHODOLOGY: This was a cross-sectional study conducted over a period of 1.2 years. Patients were stratified based on estimated glomerular filtration rate (eGFR) and albuminuria level. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potential of biomarkers. RESULTS: A total of 90 patients included in this study. Patients were grouped as normoalbuminuria (30 patients), microalbuminuria (30 patients), and macroalbuminuria (30 patients). Galectin-3 and GDF-15 levels were significantly elevated in T2DM patients with macroalbuminuria (p = <0.05). Higher levels of galectin-3 and GDF-15 were found in patients with poor kidney function (Stage IV-V CKD). Negative correlation was observed between galectin- 3 (r = -0.472) and eGFR (p = 0.000), GDF-15 (r = -0.917) and eGFR (p <0.000). The ROC analysis yielded an area under curve (AUC) of 0.776 (95% CI: 0.677 to 0.875; p = <0.0001) for galectin-3 and an AUC of 0.963 (95% CI: 0.929 to 0.997; p = <0.0001) for GDF-15. CONCLUSION: In DKD patients the galectin-3 and GDF-15 levels were inversely related to the eGFR which was further confirmed by the ROC curve demonstrating the potential of galectin-3 and GDF-15 as a biomarker.

No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis.

BACKGROUND AND AIM: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS: Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Prevalence of peripheral neuropathy and associated pain in patients with diabetes mellitus: Evidence from a cross-sectional study.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes mellitus. It affects almost half the population with diabetes and worsens quality of life of the patient. This study was aimed to determine the prevalence of peripheral neuropathy and associated pain in patients with diabetes mellitus. METHODS: This was a cross-sectional study conducted over a period of six months. Patient's ≥ 18 years with confirmed diagnosis of diabetes mellitus were included in the study. Patients with hypothyroidism, medical illness such as cancer, liver or renal disease, cervical or lumbar spondylosis, pregnant patients with diabetes and patients receiving any treatment that might influence nerve function (e.g., cytotoxic or antiepileptic agents) were excluded from the study. DPN was diagnosed using 10 g monofilament test. The S-LANSS questionnaire was used to assess the associated painful symptoms. Association was calculated using chi-square test. A p- value of ≤0.05 was considered statistically significant. All the statistical analysis was performed using SPSS v22. RESULT: The overall prevalence of DPN was found to be 28.85% from which 88% patients were found to have painful symptoms. A significant association of DPN was observed with the duration of diabetes (p = 0.004), poor glycaemic control (p = 0.03) and other diabetic complications such as nephropathy (p = 0.002). No association of neuropathy was found with retinopathy and hypertension. Duration of diabetes (>15 years), and HbA1c (>9%) was found to be positively associated the painful DPN. CONCLUSION: The current study found a high prevalence of DPN and it was found to be significantly associated with duration of diabetes, poor glycaemic control and nephropathy.

Evaluation of the hepatoprotective, anti-inflammatory, antinociceptive and antiepileptic activities of Chrysanthemum trifurcatum.

Chrysanthemum trifurcatum is common to Mediterranean countries and widely-used in traditional medicine. Due to the scarcity of data about the pharmacological properties of C. trifurcatum, this present study was designed to determine the effects of C. trifurcatumethanolic extract (CEE) for its anti-nociceptive, anti-epileptic, anti-inflammatory, and hepatoprotective activities in mice and rat models. We demonstrate that CEE contains alkaloids, carbohydrates, and flavonoids, and in a dose-dependent (300 and 500 mg/kg) manner exhibited significant reductions in paracetamol (PCM; 500 mg/kg)-induced increased serum AST, ALT and ALP levels, similar to as seen by silymarin (25 mg/kg). Additionally, CEE (300 mg/kg) elicited inhibition in acetic acid-induced abdominal writhes, delayed latency time to paw's licking in hot plate tests, exerted an anti-convulsant effect by prolonging the onset of clonic and tonic convulsions, and reduced pentylenetetrazole (PTZ; 80 mg/kg)-induced mortality. Moreover, CEE (500 mg/kg) exhibited a prominent reduction in carrageenan-induced paw edema. These studies indicate that CEE possesses profound central and peripheral analgesic, anti-convulsant, anti-inflammatory, and hepatoprotective activities.

Warfarin use increases bleeding risk in hemodialysis patients with atrial fibrillation: A meta-analysis of cohort studies.

BACKGROUND AND AIM: Atrial fibrillation is one of the most common comorbid conditions in hemodialysis patients, and warfarin is widely prescribed anticoagulant to prevent thromboembolic complications in such patients. In the last decade, several epidemiological studies pointed out the risk of bleeding with the use of warfarin. So, this meta-analysis is aimed to assess the bleeding risk associated with the use of warfarin. METHODS: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. PubMed, Embase, Scopus, and Cochrane central databases were searched from inception to June 10, 2018. The primary outcome was to quantify the bleeding risk associated with warfarin use. The secondary outcome was to assess the bleeding risk based on different subgroups. Review Manager (RevMan) version 5.3 was used for performing statistical analysis. RESULTS: A total of 15 studies, constituting a pooled sample of 53 581 patients (37.14% female), were included. Of these, 17 469 were warfarin users. We found that warfarin use had a significant association with the bleeding risk. The pooled relative risk (RR) of bleeding was estimated to be 1.35 (95% CI: 1.18-1.53, P = < 0.00001), and the pooled RR of major bleeding (five studies) was estimated to be 1.32 (95% CI: 1.07-1.63, P = 0.009). Subgroup analysis revealed a significant association of warfarin use with the intracranial hemorrhage/hemorrhagic stroke (nine studies) (pooled RR: 1.43 [95% CI: 1.20-1.71, P = < 0.0001]). CONCLUSIONS: The results indicate that warfarin use increases the risk of bleeding in hemodialysis patients with atrial fibrillation.

Proton pump inhibitors' use and risk of hip fracture: a systematic review and meta-analysis.

In the last decade, epidemiological studies presented inconsistent findings concerning the proton pump inhibitors (PPI) use and the risk of hip fracture. So, this systematic review and meta-analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use. PubMed® and Cochrane Central databases were searched from inception to January 2018. The quality of included studies in meta-analysis was assessed using Newcastle-Ottawa scale. Primary outcome of this study was to assess the risk of hip fracture among PPI user. Secondary outcomes include subgroup analysis based on study design, study quality, duration of PPI use, calcium intake, and geographical region. Sensitivity analysis was also performed. Review Manager (RevMan) was used to perform statistical analysis. This meta-analysis was based on seventeen studies. Pooled risk ratio showed a statistically significant association between PPI use and hip fracture risk (RR 1.26 [95% CI 1.17-1.35], p < 0.00001). Subgroup analysis, based on the study design, showed a highly significant association between PPI use and risk of hip fracture (p < 0.0001). The risk of hip fracture persisted even when stratified by calcium adjustment and the duration of PPI use (p < 0.0001). This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.

New 4'-substituted benzoyl-ß-D glycoside from the fruit pulp of Terminalia belerica with antiplatelet and antioxidant potency.

BACKGROUND: The fruit Terminalia belerica is a rich source of vitamins, acids, and nutraceuticals which have free radical scavenging activity. Thus, the ethanolic extract of fruit and its isolated compound (Tb-01) were intended to estimate antiplatelet and antioxidant activities. METHODS: The ethanolic extract was submitted to Si-gel CC and the compound was isolated. The compound Tb-01 was characterized as benzoyl-ß-D-(4'→10″ geranilanoxy)-pyranosides on the basis of spectral data [ultra violet (UV), infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and Mass Spectroscopy] and chemical analyses. The ethanolic extract and Tb-01 at different concentrations were in vitro screened for antiplatelet and antioxidant activity. The antiplatelet activity was carried out by using platelet rich plasma prepared by centrifugation of rabbit whole blood (containing 0.9% sodium citrate as anticoagulant) and antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl, reducing power, and nitric oxide anion scavenging activity models. RESULTS: The compound Tb-01 was an amorphous brownish powder, yield 0.64% (w/w), melting point 105-110 °C, Retardation factor/Retention Value (R f value) at 0.42 in methanol:chloroform (20:80) solvent system, UV absorption maxima at 243 nm, and molecular peak [M + H]+ at 394.15 m/z. It was observed that the ethanolic extract and Tb-01 at different concentrations showed significant antiplatelet and antioxidant activity. The antioxidant activity, like scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals, nitric oxide radical, and reductive power were found to be concentration-dependent and increased when increasing amounts of sample were used. CONCLUSION: Mass spectra and 1H NMR confirmed the isolated compound structure which was supported by 13C NMR and IR spectra. Tb-01could be promising for future applications in the treatment of blood clots, pulmonary embolism, and other related diseases.

Anti-endotoxin effects of terpenoids fraction from Hygrophila auriculata in lipopolysaccharide-induced septic shock in rats.

CONTEXT: Hygrophila auriculata (K. Schum) Heine (Acanthaceae) has been traditionally used for the treatment of various ailments such as inflammation, rheumatism, jaundice and malaria. OBJECTIVE: The present study aims to separate terpenoid fraction (TF) from alcohol (70%) extract of the whole plant of Hygrophila auriculata and assess its anti-inflammatory activity. MATERIALS AND METHODS: HPTLC analysis of TF was performed for the estimation of lupeol. Edema was induced in Wistar albino rats by subplanter injection of 0.1 ml of 1% (w/v) carrageenan into the right hind paw after 1 h of TF administration (100 and 200 mg/kg oral). Septic shock was induced by intraperitoneal administration of LPS (100 µg/kg) in rats and interleukins (IL-1ß and IL-6), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), lipid peroxidation (LPO), and nitric oxide (NO) were measured in serum. AutoDock 4.2 was used for molecular docking. RESULTS: Administration of TF significantly (p < 0.005) restored the serum levels of cytokines, LPO (7.77 ± 0.034 versus 4.59 ± 0.059 nmole of TBARS), NO (9.72 ± 0.18 versus 4.15 ± 0.23 µmol nitrite/mg of wet tissue), and SOD (4.89 ± 0.036 versus 7.83 ± 0.033 Unit/mg protein) compared with the LPS-challenged rats. Analysis of in silico results revealed that TNF-α is the most appropriate target in eliciting anti-inflammatory activity. CONCLUSION: The present findings suggest that TF of Hygrophila auriculata possesses great promise as an anti-inflammatory agent which may be due to its antioxidant effect. Molecular docking results could be exploited for lead optimization and development of suitable treatment of inflammatory disorders.

Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait.

BACKGROUND: The current perspective for the search of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor has been shifted towards a natural agent also having antioxidant property. Thus, this study was intended to isolate and identify the bioactive compounds from methanolic extract of Ficus virens bark (FVBM) and to evaluate their antioxidant, HMG-CoA reductase inhibitory and hypolipidemic activity. METHODS: Bioactivity guided fractionation and isolation of bioactive compound from FVBM extract has been done to isolate and characterize the potent HMG-CoA reductase (HMGR) inhibitor with antioxidant activity by using repeated extensive column chromatography followed by spectroscopic methods, including Infrared (IR), 1H & 13C nuclear magnetic resonance (NMR) and Mass spectrum analysis. The in vitro HMGR inhibition and enzyme kinetic assay was determined using HMG-CoA as substrate. In addition, antioxidant activity of the new isolated compound, was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and FRAP value. In-silico molecular informatics of HMGR enzyme type inhibition and pharmacokinetics data of the new compound was further evaluated through molecular docking and ADME-T studies. Further, in-vivo hypolipidemic property of FVBM extract and newly isolated compound was also analyzed in triton-WR 1339 induced rats. RESULTS: Thereby, we report the discovery of n-Octadecanyl-O-α-D-glucopyranosyl(6'→1″)-O-α-D-glucopyranoside (F18) as a novel HMG-CoA reductase inhibitor with strong antioxidant property. This inhibitor exhibited not only higher free radical scavenging activity but also marked HMG-CoA reductase inhibitory activity with an IC50 value of 84±2.8 ng/ml. This inhibitory activity concurred with kinetic study that showed inhibition constant (K i) of 84 ng/ml via an uncompetitive mode of inhibition. The inhibition was also corroborated by molecular docking analysis and in silico pharmacokinetics data. The in vivo study revealed that administration of FVBM extract (at higher dose, 100 mg/rat) and the inhibitor (1 mg/rat) to Triton WR-1339-induced hyperlipidemic rats significantly ameliorated the altered levels of plasma lipids and lipoproteins including hepatic HMG-CoA reductase activity; this effect was comparable to the effect of standard drug atorvastatin. CONCLUSIONS: The in vitro, in silico and in vivo results clearly demonstrated the antioxidant potential and therapeutic efficacy of the inhibitor as an alternate drug against hyperlipidemia.

Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS).

The oral delivery of hydrophobic drug presents a major challenge because of the low aqueous solubility of such compounds. Self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS), which are isotropic mixtures of oils, surfactants, solvents and co-solvents/surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds. The efficiency of oral absorption of said drug from such type of formulation depends on many formulation-related parameters, such as surfactant concentration, oil/surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self-emulsification ability. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. With the growing interest in this field, there is an increasing need for guidelines in excipient selection to obtain effective delivery system with improved bioavailability. The aim of this review is to present the recent approaches in selecting the most appropriate lipid system(s); methods for its characterization and role of various excipients for improved delivery of dosage form.

Current approaches toward production of secondary plant metabolites.

Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals.

Patient counseling about herbal-drug interactions.

Many people have the mistaken notion that, being natural, all herbs and foods are safe; this is not so. Very often, herbs and food may interact with medications you normally take, result in serious reactions. During the latter part of this century the practice of herbalism has become mainstream throughout the world. This is due remove to the recognition of the value of traditional medical systems in the world. Herbal medicines are mixtures of more than one active ingredient. The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb-drug interactions is theoretically higher than drug-drug interactions because synthetic drugs usually contain single chemical entity. Case reports and clinical studies have highlighted the existence of a number of clinically important interactions, although cause-and-effect relationships have not always been established. Herbs and drugs may interact either pharmacokinetically or pharmacodynamically. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine; result in a significant reduction of drug presystemic metabolism. An additional mechanism is the inhibition of Pglycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, result in a further increase in the fraction of drug absorbed. Some herbal products (e.g. St. John's wort) have been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of conventional drugs including cyclosporine, indinavir, irinotecan, nevirapine, oral contraceptives and digoxin. The data available so far, concerning this interaction and its clinical implications are reviewed in this article. It is likely that more information regarding such interaction would crop up in the future, awareness of which is necessary for achieving optimal drug therapy.