Comparative evaluation of cardioprotective activity of Gala and Fuji apple juice against isoprenaline-induced cardiotoxicity in rats.

OBJECTIVES: Comparative evaluation of cardioprotective activity of Gala and Fuji apple juice against isoprenaline induced cardiotoxicity in rats. METHODS: Rats (125-150 g) were orally administered Gala (GA) and Fuji (FA) apple juice (3 mL/day, per oral) for 13 days. Myocardial injury was inducted on 14th and 15th day by the administration of Isoprenaline (85 mg/kg/day, subcutaneous). RESULTS: In treated group i.e. GA and FA, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), Troponin-I level and malondialdehyde (MDA) content was reduced while glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) level was significantly increased. Marked reduction in cholesterol, triglyceride, phospholipids, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was observed while high-density lipoprotein (HDL) level increased significantly. In tissue and serum total serum protein (TSP) level, Albumin, Globulin and A/G ratio increased very significantly in the treated group while the level of white blood corpuscles (WBC), haemoglobin (Hb), erythrocyte sedimentation rate (ESR), total fibrinogen (TF), bleeding time (BT), c-reactive protein (C-rP), red blood corpuscles (RBC), clotting time (CT) and prothrombin time (PT) showed a significant rise in the level. The level of Sialic acid, hexose, fucose and hexosamine was highly significantly increased, there was an increase in the level of K+ and glycogen while a significant reduction in electrolyte and glucose level was observed when all these parameters were compared to Isoprenaline (ISO) group. The above findings were supported by histopathological examination of hearts. Cardioprotective activity was compared with standard drug, metoprolol. On comparative analysis of both juices, GA juices have found more effective when compared to FA juice. CONCLUSIONS: The study was concluded that Gala and Fuji apple possessed significant prophylactic and protective effects against Isoprenaline-induced cardiotoxicity in rats through maintaining inhibiting lipid peroxidation, endogenous antioxidant enzyme activities and cytokine levels.

Diligent profiling of preclinical safety of the silk protein sericin.

BACKGROUND: Sericin is a widely used protein in the pharmaceutical industry derived from the silkworm, Bombyx mori, and used for the treatment of various diseases and pathological conditions. It is the main ingredient of the Unani preparation khameera abresham. The study was conducted to evaluate the preclinical toxicity of the silk protein sericin in mice. METHODS: In the acute toxicity study, sericin was administered once orally to different groups of animals at doses of 500, 1000, and 2000 mg/kg. Animals were observed for 14 days. In the sub-acute toxicity study, sericin was administered in mice for 4 weeks in the toxic group at doses of 500, 1000, and 2000 mg/kg, while in the recovery group it was administered for 4 weeks at doses of 500 and 2000 mg/kg followed by 2 weeks of distilled water administration. RESULTS: In the acute toxicity study, the observed parameters showed no significant difference, and no mortality was reported. In the sub-acute toxicity study, there were no toxicological effects in any of the estimated parameters, while histopathological analysis showed inflammation in vital organs at the dose of 2000 mg/kg. CONCLUSIONS: Results of our acute toxicity study suggest that sericin is safe at all administered doses, while the sub-acute study suggests that the NOAEL (no-observed-adverse-effect level) of sericin is below 2000 mg/kg, at which it can be considered safe.

A conglomeration of preclinical models related to myocardial infarction

Cardiovascular diseases are the main source of death and morbidity in developed and developing nations. Animal models are required to propel our understanding of the pathogenesis, increase our knowledge, disease progress, and mechanism behind cardiovascular disorder, providing new approaches focused to improve the diagnostic and the treatment of these pathological conditions and additionally to test various therapeutic ways to deal with tissue regeneration and re-establish heart working following damage. A perfect model framework ought to be reasonable, effectively controlled, reproducible, and physiologically illustrative of human disease, show cardinal signs and pathology that resembles after the human ailment and ethically stable. The decision of selection of animal model should be considered precisely since it influences exploratory results and whether results of the research can be sensibly matched with the human. In this way, no specific technique splendidly reproduces the human disease, and relying upon the model, extra cost burden, resources, infrastructure and the necessity for technical hands, should also be kept under consideration. Here we have discussed and compiled various methods of inducing myocardial infarction in animals, basically by surgery, chemicals and through genetic modification, this may benefit the researchers in getting a complied data regarding various methods through which they can induce myocardial infarction in animals.

Caveolins; An Assailant or An Ally of Various Cellular Disorders.

Caveolae have impressive morphological highlights of the cytomembrane of mammalian cells which involve in wide diversity of cellular functions involving signaling pathways and cholesterol hastening. Caveolin proteins possess a 'scaffolding' domain which for caveolin-1 and caveolin-3 appear to act a dominant role in signal regulation through caveolae. Caveolin-1 is treated to be protein in the cytomembrane entrapped with caveolae in endothelial cells and vascular smooth muscle cells which diminish nitric oxide (NO) by fill up the calcium/calmodulin (Ca2+/CaM) confining point of endothelial nitric oxide synthase (eNOS), decrease NO generation produce endothelial dysfunction and atherosclerotic injury development. It is a cholesterol-binding layer protein associated with cell cholesterol transport and also shows cardioprotective action through ischemic preconditioning (IPC) in diabetic and postmenopausal rat heart. Additionally it is ensnared in the procedures of tumorigenesis, prostate disease, and inflammation. The present study in the paper is to explore the structural functionalities of caveolins and their contributory role in CVS disorders and various other diseases.

Herbal Remedies: A Boon for Diabetic Neuropathy.

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

Cure of human diabetic neuropathy by HPLC validated bark extract of Onosma echioides L. root.

HPLC validated hexane bark extract of Onosma echioides L. root (OE) was evaluated for cure of human diabetic neuropathy in human neuroblastoma cell line. HPLC analysis was performed. Human neuroblastoma cells were grouped into control, normal glucose, high glucose (HG) and HG plus different concentrations of OE extract (10, 25 and 50 µg/mL). MTT, DCFH-DA staining and nuclear condensation assays were performed on neuroblastoma cells to evaluate antiproliferative activity, ROS activity level and apoptotic effect of OE. HPLC analysis revealed the existence of maximum yield of shikonin in n-hexane extract of OE. Exposure with different concentrations of OE effectively decreased ROS level and apoptosis of cells and as a result improved the viability of cells in a dose dependent manner in response to HG-induced oxidative stress. Thus, OE possesses the property to cure human diabetic neuropathy and further can be clinically tested for its use in diabetic neuropathy.

Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats.

Background Development of drug-induced hepatic damage (DIHD) during chemotherapy is the most common reason for interruption in chemotherapy. This study evaluated the hepatoprotective activity of the ethanolic extract of Tamarindus indica stem bark (EETI) against the induced DIHD in Sprague Dawley rats. Methods The rats were divided into five groups (n=5). Group I, group III, group IV, and group V rats received 1 mL 1% carboxymethyl cellulose, EETI 100 mg/kg body weight (b.wt), EETI 200 mg/kg b.wt, and silymarin 100 mg/kg b.wt, respectively, orally once every day for 28 days. After 1 h-group II, group III, group IV, and group V rats were administered with isoniazid (INH) and rifampicin (RIF) 50 mg/kg b.wt each orally once every day for 28 days. Then, 24 h after the last dosing, blood was withdrawn from the rats and analyzed for liver specific enzymes and biochemical markers. They were examined for histopathology. Results Co-administration of INH and RIF in group II significantly increased alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, serum bilirubin, and cholesterol levels while reduced the total protein and albumin levels compared to that of group I. EETI in group III and group IV rats significantly restored the liver specific enzymes and biochemical markers altered due to co-administration of INH and RIF to normal in a dose-dependent manner. EETI 200 mg/kg b.wt showed better protection to liver than EETI 100 mg/kg b.wt and was comparable to silymarin 100 mg/kg b.wt. It was well supported with histopathology of liver tissues. Conclusions EETI possesses hepatoprotective activity against DIHD in rats. It may have a substantial impact on developing clinical strategies to treat patients with hepatic damage.

An Insight on Silk Protein Sericin: From Processing to Biomedical Application.

Silks are naturally occurring polymers that have been used clinically as sutures for hundreds of years. It's so for obtained from insects or worms, silk consists of a filament core protein, termed fibroin, and a glue-like coating made up of sericin proteins. An important component of silk has an extended history of being discarded as a waste in the course of silk processing. The cost of sericin for tissue engineering is underestimated and its capability in using as regenerative remedy has simply began to be explored. Its variable amino acid composition and various functional groups confer upon it attractive bioactive proteins, which are particularly interesting for biomedical programs. Because of its antioxidant properties, moisturizing ability, and mitogenic effect on mammalian cells, sericin is beneficial in cell regeneration and tissue engineering. Research shows that keratinocytes and fibroblasts have brought about the improvement of sericin-primarily based biomaterials for skin tissue repair, in particular as wound dressings. Moreover, sericin may be used for bone tissue engineering due to its ability to set off nucleation of bone-like hydroxyapatite. Stable silk sericin biomaterials, as films, sponges, and hydrogels, are obtained by means of cross-linking, ethanol precipitation, or mixing with different polymers. Now a day, sericin may also be used for delivery of drugs due to its chemical reactivity and pH-responsiveness which facilitate the fabrication of nano and microparticles, hydrogels, and conjugated molecules, enhancing the bioactivity of drugs. In this review, we outlined the current headways from extraction of sericin till its physical properties and biomedical applications.

Gold Nanoparticles Conjugated Levofloxacin: For Improved Antibacterial Activity Over Levofloxacin Alone.

BACKGROUND: Levofloxacin is a potent antibiotic with severe side effects due to its high doses. Bacterial resistance may be due to frequent use of antibiotics. Biogenic gold nanoparticles conjugated levofloxacin (Au-HSA-LvN-NPs) were developed by Human Serum Albumin (HSA) and nitrate reductasemediated pathways. METHODS: Au-HSA-LvN-NPs (size = 27.2 ± 1 nm) were readily generated with high emulsion stability zeta potential (-13.3 mV). The developed nanoparticles were also characterized by UVvisible spectroscopy, Transmission Electron Microscopy and Dynamic Light Scattering techniques. RESULTS: The optimized nanoparticles were found efficient against both Gram-positive bacteria and Gramnegative bacteria specifically S. aureus (MIC-0.373 µg/ml), E. coli (MIC-0.149 µg/ml) and P. aeruginosa (MIC-0.346 µg/ml) respectively. CONCLUSION: The efficiency of bioconjugated levofloxacin got improved by 1.94 times, 2.89 times and 1.46 times against S. aureus, E. coli and P. aeruginosa respectively, in comparison to pure levofloxacin.

Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats.

Many traditional systems of medicines employ herbal drugs for the hepatoprotection. Aim of the study was designed to evaluate the hepatoprotective potential of 'ethanolic extract of Aquilaria agallocha ( Chen Xiang) leaves' (AAE) against paracetamol (PCM) induced hepatotoxicity in SD rats. Group I animals were treated with 1% CMC for 8 days. Group II, III, IV and V animals were first treated with '1% CMC' 1 ml/kg/day, AAE 200 mg/kg/day, AAE 400 mg/kg/day and silymarin 100 mg/kg/day respectively for 7 days and then, orally administered with PCM 3 g/kg b. wt. on 8th day in a single dose. 24 h after the last dosing by PCM, the blood was obtained through the retro-orbital plexus under light anesthesia and the animals were sacrificed. Hepatoprotective potential was assessed by various biochemical parameters such as ALT, AST, ALP, LDH, bilirubin, cholesterol, TP and ALB. Group IV rats showed significant (p < 0.01) decrease in ALT, AST, ALP, LDH, cholesterol, bilirubin, liver wt. and relative liver wt. levels while significant (p < 0.01) increase in final b. wt., TP and ALB levels as compared to group II rats. Hepatoprotective potential of AAE 400 mg/kg/day was comparable to that of standard drug silymarin 100 mg/kg/day. Results of the study were well supported by the histopathological observations. This study confirms that AAE possesses hepatoprotective potential comparable to that of standard drug silymarin as it exhibited comparable protective potential against PCM induced hepatotoxicity in SD rats.

Bromelain capped gold nanoparticles as the novel drug delivery carriers to aggrandize effect of the antibiotic levofloxacin.

To develop bromelain capped gold nanoparticles (BRN capped Au-NPs) as the effective drug delivery carriers of the antibiotic levofloxacin (LvN) and evaluate antibacterial potential of its bioconjugated form compared to pure LvN. BRN capped Au-NPs were synthesized by in vitro method and bioconjugated to LvN using 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide as activator to form Au-BRN-LvN-NPs. These were characterized for mean particle size by dynamic light scattering analysis, zeta potential by Zetasizer nanosystem analysis and transmission electron microscopy (TEM) on carbon coated TEM copper grids by TEM respectively. Drug loading efficiency of LvN was calculated using UV-visible spectroscopy by standard curve of pure LvN. Antibacterial efficacy of Au-BRN-LvN-NPs and pure LvN was determined by evaluating minimum inhibitory concentration (MIC) against Staphylococcus aureus and Eschereschia coli. Two peaks were observed in Au-BRN-LvN-NPs spectrum one at 307 nm and other at 526 nm while one peak in BRN capped Au-NPs at 522 nm during UV spectroscopy suggesting red shift. The drug loading efficiency of LvN was found to be 84.8 ± 2.41 %. The diameter of Au-BRN-LvN-NPs and BRN capped Au-NPs were found to be (58.65 ± 2 nm, 38.11 ± 2 nm), zeta potential (-9.01 mV, -13.8 mV) and surface morphology (~13.2 nm, 11.4 nm) respectively. The MICs against S. aureus and E. coli were found to be (0.128 µg/mL, 1.10 µg/mL) for Au-BRN-LvN-NPs and (0.547 µg/mL, 1.96 µg/mL) for pure LvN. The results suggested that BRN capped Au-NPs can be used as effective drug delivery carriers of the antibiotic LvN. The Au-BRN-LvN-NPs exhibited enhanced antibacterial activity compared to pure LvN alone. (Graphical abstract see Figure 1(Fig. 1)).

Protection of hepatotoxicity using Spondias pinnata by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers in Wistar rats.

BACKGROUND: Traditional systems of medicine use herbal drugs for hepatoprotection. Thus, the study was designed to evaluate the hepatoprotective and antioxidant effects of Spondias pinnata bark extracts against ethanol-induced liver injury in Wistar rats. METHODS: Group I animals were treated with 1 mL/kg 0.3% carboxymethyl cellulose and Group II with 12 mL/kg 50% ethanol for 8 consecutive days. Groups III-VII animals were first treated with 400 mg/kg petroleum ether extract, chloroform extract, acetone extract (AE), ethanol extract (EE), and 100 mg/kg silymarin, and then 12 mL/kg 50% ethanol orally after 2 hours pretreatment each day for 8 consecutive days. Six hours after the last dose, blood was withdrawn. The hepatoprotective activity was assessed by several biochemical and antioxidant parameters. It was accomplished by the histopathology and DNA fragmentation study of liver tissues. RESULTS: Treatment with S. pinnata extracts, mainly AE and EE significantly (p < 0.05-0.01) and dose-dependently prevented the ethanol-induced increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, bilirubin, and malondialdehyde, and decrease in reduced glutathione, catalase, superoxide dismutase, and albumin. They also attenuated the ethanol-induced DNA damage. Hepatoprotective potential of the extract was less than that of standard drug silymarin. Results of the study were well supported by the histopathological observations. CONCLUSION: S. pinnata extracts AE and EE possess a potent hepatoprotective effect against ethanol-induced liver injury in Wistar rats, and protect them from hepatotoxicity by prevention of ethanol-induced oxidative stress, DNA-damage and altered biochemical markers.

Improved efficiency and stability of secnidazole - An ideal delivery system.

Secnidazole (α,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol) is a highly effective drug against a variety of G(+)/G(-) bacteria but with significant side effects because it is being used in very high concentration. In this study, gold nanoparticles (GNPS) were selected as a vehicle to deliver secnidazole drug at the specific site with more accuracy which made the drug highly effective at substantially low concentrations. The as-synthesized GNPs were capped with Human Serum Albumin (HSA) and subsequently bioconjugated with secnidazole because HSA provides the stability and improves the solubility of the bioconjugated drug, secnidazole. The quantification of covalently bioconjugated secnidazole with HSA encapsulated on enzymatically synthesized GNPs was done with RP-HPLC having SPD-20 A UV/VIS detector by using the C-18 column. The bioconjugation of GNPs with secnidazole was confirmed by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The bioconjugated GNPs were characterized by UV-VIS spectroscopy, TEM, Scanning Electron Microscopy (SEM) and DLS. Zeta potential confirmed the stability and uniform distribution of particles in the emulsion of GNPs. The separation of bioconjugated GNPs, unused GNPs and unused drug was done by gel filtration chromatography. The minimal inhibitory concentration of secnidazole-conjugated gold nanoparticles (Au-HSA-Snd) against Klebsiella pneumonia (NCIM No. 2957) and Bacillus cereus (NCIM No. 2156) got improved by 12.2 times and 14.11 times, respectively, in comparison to pure secnidazole. Precisely, the MIC of Au-HSA-Snd against K. pneumonia (NCIM No. 2957) and B. cereus (NCIM No. 2156) were found to be 0.35 and 0.43 µg/ml, respectively whereas MIC of the pure secnidazole drug against the same bacteria were found to be 4.3 and 6.07 µg/ml, respectively.

In vitro screening for ß-hydroxy-ß-methylglutaryl-CoA reductase inhibitory and antioxidant activity of sequentially extracted fractions of Ficus palmata Forsk.

Hypercholesterolemia-induced oxidative stress has been strongly implicated in the pathogenesis of atherosclerosis, which is one of the major causes of mortality worldwide. The current work, for the first time, accounts the antioxidant, genoprotective, antilipoperoxidative, and HMG-CoA reductase (EC 1.1.1.34) inhibitory properties of traditional medicinal plant, Ficus palmata Forsk. Our result showed that among sequentially extracted fractions of Ficus palmata Forsk, FPBA (F. palmata bark aqueous extract) and FPLM (F. palmata leaves methanolic extract) extracts have higher phenolic content and also exhibited significantly more radical scavenging (DPPH and Superoxide) and antioxidant (FRAP) capacity. Moreover, FPBA extract also exhibited significantly higher inhibition of lipid peroxidation assay. Additionally, results showed almost complete and partial protection of oxidatively damaged DNA by these plant extracts when compared to mannitol. Furthermore, our results showed that FPBA extract (IC50 = 9.1 ± 0.61 µg/mL) exhibited noteworthy inhibition of HMG-CoA reductase activity as compared to other extracts, which might suggest its role as cardioprotective agent. In conclusion, results showed that FPBA extract not only possess significant antioxidant and genoprotective property but also is able to attenuate the enzymatic activity of HMG-CoA reductase, which might suggest its role in combating various oxidative stress-related diseases, including atherosclerosis.

Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.

Acetylcholinesterase (AChE) is a primary target for Alzheimer's therapy while recently sodium glucose cotransporter 2 (SGLT2) has gained importance as a potential target for Type 2 Diabetes Mellitus (T2DM) therapy. The present study emphasizes the molecular interactions between a new Food and Drug Administration (FDA) approved antidiabetic drug 'Invokana' (chemically known as Canagliflozin) with AChE and SGLT2 to establish a link between the treatment of T2DM and Alzheimer's Disease (AD). Docking study was performed using 'Autodock4.2'. Both hydrophobic and π-π interactions play an important role in the correct positioning of Canagliflozin within SGLT2 and catalytic site (CAS) of AChE to permit docking. Free energy of binding (ΔG) for 'Canagliflozin-SGLT2' interaction and 'Canagliflozin - CAS domain of AChE' interaction were found to be -10.03 kcal/mol and -9.40 kcal/mol, respectively. During 'Canagliflozin-SGLT2' interaction, Canagliflozin was found to interact with the most important amino acid residue Q457 of SGLT2. This residue is known for its interaction with glucose during reabsorption in kidney. However, 'Canagliflozin-CAS domain of AChE' interaction revealed that out of the three amino acids constituting the catalytic triad (S203, H447 and E334), two amino acid residues (S203 and H447) interact with Canagliflozin. Hence, Invokana (Canagliflozin) might act as a potent dual inhibitor of AChE and SGLT2. However, scope still remains in the determination of the three-dimensional structure of SGLT2-Canagliflozin and AChE-Canagliflozin complexes by X-ray crystallography to validate the described data. Since the development of diabetes is associated with AD, the design of new AChE inhibitors based on antidiabetic drug scaffolds would be particularly beneficial. Moreover, the present computational study reveals that Invokana (Canagliflozin) is expected to form the basis of a future dual therapy against diabetes associated neurological disorders.