Investigations of Limeum Indicum Plant for Diabetes Mellitus and Alzheimer's Disease Dual Therapy: Phytochemical, GC-MS Chemical Profiling, Enzyme Inhibition, Molecular Docking and In-Vivo Studies.

Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method. The inhibitory potential of the extracts/fractions against α-, ß-glucosidase acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoaminine oxidases (MAO-A & B) was evaluated. Results revealed that acetonitrile fraction has highest inhibitory potential against α-glucosidase (IC50=68.47±0.05 µg/mL), methanol extract against ß-glucosidase (IC50=91.12±0.07 µg/mL), ethyl acetate fraction against AChE (IC50=59.0±0.02 µg/mL), ethanol extract against BChE (28.41±0.01 µg/mL), n-hexane fraction against MAO-A (IC50=150.5±0.31 µg/mL) and methanol extract for MAO-B (IC50=75.95±0.13 µg/mL). The docking analysis of extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. During the in-vivo investigation, ethanol extract produced hypoglycemic effect (134.52±2.79 and 119.38±1.40 mg/dl) after 21 days treatment at dose level of 250 and 500 mg/Kg. Histopathological findings further supported the in-vivo studies.

Photobiomodulation in Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Photobiomodulation (PBM) is a therapeutic modality that has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its proposed mechanisms for therapeutic effect when delivered to the injured brain include antiapoptotic and anti-inflammatory effects. This systematic review summarizes the available evidence for the value of PBM in improving outcomes in acute TBI and presents a meta-analysis of the pre-clinical evidence for neurological severity score (NSS) and lesion size in animal models of TBI. A systematic review of the literature was performed, with searches and data extraction performed independently in duplicate by two authors. Eighteen published articles were identified for inclusion: seventeen pre-clinical studies of in vivo animal models and one clinical study in human patients. The available human study supports safety and feasibility of PBM in acute moderate TBI. For pre-clinical studies, meta-analysis for NSS and lesion size were found to favor intervention versus control. Subgroup analysis based on PBM parameter variables for these outcomes was performed. Favorable parameters were identified as: wavelengths in the region of 665 nm and 810 nm; time to first administration of PBM ≤4 h; total number of daily treatments ≤3. No differences were identified between pulsed and continuous wave modes or energy delivery. Mechanistic substudies within included in vivo studies are presented and were found to support hypotheses of antiapoptotic, anti-inflammatory, and pro-proliferative effects, and a modulation of cellular metabolism. This systematic review provides substantial meta-analysis evidence of the benefits of PBM on functional and histological outcomes of TBI in in vivo mammalian models. Study design and PBM parameters should be closely considered for future human clinical studies.

The dietary supplementation of zinc oxide and selenium nanoparticles enhance the immune response in freshwater fish Oreochromis mossambicus against aquatic pathogen Aeromonas hydrophila.

BACKGROUND: Green nanoparticles are subjected as an immunostimulant against bacterial pathogens. METHODS: Murraya koenigii berry extract-based synthesized zinc oxide nanoparticles (Mb-ZnO NPs) and selenium nanoparticles (Mb-Se NPs) were relatively analyzed for immunostimulation in serum and mucus fish Oreochromis mossambicus against Aeromonas hydrophila infections. Initial minimum inhibitory concentration (MIC) was determined for both Mb-ZnO NPs and Mb-Se NPs followed by specific growth rate (SGR), antioxidant level (Superoxide dismutase activity (SOD), Catalase activity (CA), and Glutathione peroxidase activity (GPx)), and immune parameters Myeloperoxidase activity (MPO), Respiratory burst activity (RBA), Lysozyme activity (LYZ), Alkaline phosphatase activity (ALP), Serum antiprotease activity and Natural complement activity (NAC). RESULTS: The potential bacterial inhibition property of Mb-ZnO NPs and Mb-Se NPs exhibited the most negligible concentration of 25 and 15 µg mL-1, respectively, against A. hydrophila. In addition, Mb-ZnO NPs and Mb-Se NPs exhibited 70-80 % and 90-95 % diminished biofilm activity at 50 µg mL-1 that was viewed under an inverted research microscope and confocal laser scanning microscopy (CLSM). Protein leakage and nucleic acid leakage assay quantified oozed out protein and nucleic acid from A. hydrophila that confirms Mb-Se NPs exhibited vigorous antibacterial activity than Mb-ZnO NPs at tested concentrations. Oreochromis mossambicus fed with Mb-ZnO NPs and Mb-Se NPs supplemented diet at different concentrations (0.5 mg/kg, 1 mg/kg and 2 mg/kg) improved SGR along with a rise in the immune response of those fishes against A. hydrophila infection. Serum and mucus of fish fed with Mb-Se NPs supplemented diet exhibited a significant rise in antioxidant level SOD, CA and GPx at a dosage of 2 mg/kg. Likewise, lipid peroxidation assay detected significantly diminished oxidative stress in the serum and mucus of fish fed with Mb-Se NPs supplemented diet (2 mg/kg). Enhanced immune parameters in serum and mucus of fish fed with Mb-Se NPs supplemented diet determined by MPO, RBA, LYZ, ALP, Serum antiprotease activity and NAC. CONCLUSION: Thus O. mossambicus fed with Mb-Se NPs supplemented diet was less prone to become infected by aquatic pathogen A. hydrophila established by challenge study. On the whole, Mb-Se NPs supplemented diet ensured the rise in antioxidant response that boosts the immune responses and reduces the chance of getting infected against A. hydrophila infections.

Photocatalytic, antiproliferative and antimicrobial properties of copper nanoparticles synthesized using Manilkara zapota leaf extract: A photodynamic approach.

Copper nanoparticles were synthesized using Manilkara zapota leaf extract. The synthesis of the nanoparticle was primarily visualized when the colour of the reaction mixture turned into reddish-brown. Biosynthesized nanoparticles were characterized by UV-vis, FT-IR, XRD, SEM and EDX. The UV spectra showed maximum absorption at 584 nm. FT-IR studies showed stretching frequency at 592.76 cm-1, which is the fingerprint region for Cu-O bond. The crystallinity of the synthesized copper nanoparticles (Mz-Cu NPs) was revealed through XRD analysis. The synthesized Mz-Cu NPs were spherical with an average size of 18.9-42.5 nm and it was shown by SEM analysis. EDX analysis displayed that the nano sample contains 58 % of copper. The antimicrobial property of the synthesized nanoparticles was evaluated against fungal plant pathogens Rhizoctonia solani (MTCC 12232), Sclerotium oryzae (MTCC 12230) and bacterial species, namely Bacillus subtilis (ATCC 23857), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Vibrio harveyi (ATCC 35084), Vibrio parahaemolyticus (ATCC 33845). In in-vitro haemolytic assay, the particle showed 5.73, 3.34, 0.5 % hemolysis at 100, 50, 25 µg/mL concentration respectively. In the antiproliferative assay, the IC50 values of MCF7 and Vero cells were found to be 53.89 and 883.69 µg/µl. The particle degraded Methyl violet, Malachite green and Coomassie brilliant blue by 92.2, 94.9 and 78.8 %, within 50, 40 and 60 min, respectively, through its photocatalytic activity.

Zinc-deficiency acrodermatitis in a patient with chronic alcoholism and gastric bypass: a case report.

Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.

Usher proteins in inner ear structure and function.

Usher syndrome (USH) is a neurosensory disorder affecting both hearing and vision in humans. Linkage studies of families of USH patients, studies in animals, and characterization of purified proteins have provided insight into the molecular mechanisms of hearing. To date, 11 USH proteins have been identified, and evidence suggests that all of them are crucial for the function of the mechanosensory cells of the inner ear, the hair cells. Most USH proteins are localized to the stereocilia of the hair cells, where mechano-electrical transduction (MET) of sound-induced vibrations occurs. Therefore, elucidation of the functions of USH proteins in the stereocilia is a prerequisite to understanding the exact mechanisms of MET.

Polypharmacy (herbal and synthetic drug combination): a novel approach in the treatment of type-2 diabetes and its complications in rats.

The aim of present study was to evaluate the effect of aqueous leaf extract of Annona squamosa with Glipizide in a high fat diet and streptozocin-induced type-2 diabetes. Nine groups (n = 6) of male Sprague-Dawley rats were used for the study, with. Basal blood glucose, urine volume, and body weights were measured and the rate were kept on a high fat diet. After 15 days, streptozocin in sub-diabetic dose (35 mg/kg) was administered to the animals to induce diabetes. With 1 week of consistent hyperglycemia, treatment was initiated. Aqueous extract of Annona squamosa was administered orally at 350 mg/kg body weight alone and in combination with reduced and reducing dose combinations of Glipizide. Blood glucose, body weight, urine volume were measured every 10th day. The elevated blood-glucose level in diabetic rats was controlled better with combination therapy compared with the synthetic drug alone or the herbal stand-alone drug. All the results were statistically significant (P < 0.001). A combination of Annona squamosa along with Glipizide may be helpful in dose reduction of Glipizide up to 50%, reducing the risk of the onset of insulin therapy.

Sedative, antiepileptic and antipsychotic effects of Viscum album L. (Loranthaceae) in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum album L. is claimed in traditional medical practice, to be useful in the treatment of epilepsy and insomnia in Himachal Pradesh, India. MATERIALS AND METHODS: The effect of Viscum album L. on epilepsy, psychosis and sedative activity was evaluated in mice and rats using standard procedure. RESULTS: The aqueous leaf extract of Viscum album L. prolonged the pentobarbital induced sleeping time and reduced the locomotor activity in actophotometer. This suggests that reduced locomotor activity facilitate GABAergic transmission. In addition the extract reduced MES, INH and PTZ-induced convulsions which suggest that there may be possibility of blocking Na(+) channels, opening of Cl(-) channels or enhancing the GABAergic system. The extract decreased the apomorphine-induced stereotyped behavior and potentiates the HAL-induced cataleptic score which suggests the extract possess antidopaminergic activity. CONCLUSION: The results obtained in present study suggested that title plant exhibited sedative, antiepileptic and antipsychotic activity in mice and rats.

Pharmacological inhibition of caspase-2 protects axotomised retinal ganglion cells from apoptosis in adult rats.

Severing the axons of retinal ganglion cells (RGC) by crushing the optic nerve (ONC) causes the majority of RGC to degenerate and die, primarily by apoptosis. We showed recently that after ONC in adult rats, caspase-2 activation occurred specifically in RGC while no localisation of caspase-3 was observed in ganglion cells but in cells of the inner nuclear layer. We further showed that inhibition of caspase-2 using a single injection of stably modified siRNA to caspase-2 protected almost all RGC from death at 7 days, offering significant protection for up to 1 month after ONC. In the present study, we confirmed that cleaved caspase-2 was localised and activated in RGC (and occasional neurons in the inner nuclear layer), while TUNEL⁺ RGC were also observed after ONC. We then investigated if suppression of caspase-2 using serial intravitreal injections of the pharmacological inhibitor z-VDVAD-fmk (z-VDVAD) protected RGC from death for 15 days after ONC. Treatment of eyes with z-VDVAD suppressed cleaved caspase-2 activation by >85% at 3-4 days after ONC. Increasing concentrations of z-VDVAD protected greater numbers of RGC from death at 15 days after ONC, up to a maximum of 60% using 4000 ng/ml of z-VDVAD, compared to PBS treated controls. The 15-day treatment with 4000 ng/ml of z-VDVAD after ONC suppressed levels of cleaved caspase-2 but no significant changes in levels of cleaved caspase-3, -6, -7 or -8 were detected. Although suppression of caspase-2 protected 60% of RGC from death, RGC axon regeneration was not promoted. These results suggest that caspase-2 specifically mediates death of RGC after ONC and that suppression of caspase-2 may be a useful therapeutic strategy to enhance RGC survival not only after axotomy but also in diseases where RGC death occurs such as glaucoma and optic neuritis.

Biological nitrogen and phosphorus removal and changes in microbial community structure in a membrane bioreactor: effect of different carbon sources.

Bacterial community structures in four sequencing anoxic/anaerobic-aerobic membrane bioreactors (SAMs) that were fed with synthetic medium composed of different organic compounds in substrate as carbon source; acetate-dominant (acetate/propionate = 4/1), propionate-dominant (acetate/propionate = 1/4), glucose-dominant (glucose/acetate = 4/1) and methanol-dominant (methanol/acetate/propionate = 6/3/1) were analyzed by respiratory quinone profile and fluorescent in situ hybridization (FISH) techniques. The SAMs were operated at controlled pH range 7-8.5 and at constant temperature 25 degrees C. Total nitrogen (TN), total phosphorus (TP) and COD removal performances were also evaluated and compared. In addition, trans-membrane pressure was monitored to observe the impact of substrate composition on membrane fouling. The dominance of the mole fraction of ubiquinone (UQ-8) in the SAMs indicated dominance of the beta-subclass of Proteobacteria; however, its population comparatively decreased when the substrate was glucose dominant or methanol dominant. A relatively higher and stable enhanced biological phosphorus removal performance was observed when methanol-dominant substrate was used concurrently with an increase in the gamma-subclass of Proteobacteria. The population of the alpha-subclass of Proteobacteria slightly increased along with a decrease in phosphate removal activity when the substrate was glucose-dominant. Results from FISH analysis also supported the findings of the quinone profile. The trans-membrane pressure variation in the SAMs indicated that fouling was relatively rapid when propionate-dominant or methanol-dominant substrate was used and most stable when glucose-dominant substrate was used. A combination of methanol and acetate would be a better choice as an external carbon source when nutrients removals, as well as fouling, are considered in the membrane bioreactor- (MBR-) coupled biological nutrients removing (BNR) process.

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.