Evaluation of anti-nociceptive,anti-inflammatory and antipyretic potential of Mikania cordata (Burm. f.) Robinson in experimental animal model

Mikania cordata is widely used for the treatment of cuts, wounds, and dengue fever in Bangladesh. In the present study, essential oil (12.5, 25 and 50?mg/kg) and two extracts, viz., chloroform and ethyl acetate extracts (200, 400, 800?mg/kg b.w.) were tested for peripheral and central anti-nociceptive activity by acetic acid-induced writhing and hot plate method, respectively. Carrageenan-induced rat paw edema assay and yeast-induced hyperthermia assay were also carried out to evaluate anti-inflammatory and antipyretic properties of oil and extracts, respectively at aforesaid doses. The essential oil (50?mg/kg), chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) showed potent peripheral anti-nociceptive activity having 47.33%, 29.33% and 16.65% of writhing inhibition, respectively, comparable with standard diclofenac (52.0%). Essential oil (50?mg/kg), chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) presented promising central anti-nociceptive activity as well having 95.86%, 79.18% and 42.37% elongation of reaction time, respectively, at 90?min after administration of essential oil, ethyl acetate extract and 60?min after administration of chloroform extract. In anti-inflammatory activity screening, the essential oil (50?mg/kg) produced the highest 72.80% edema inhibition at 4?h after administration of carrageenan which was comparable with that of standard phenylbutazoe (87.87%). On the other hand, chloroform extract (800?mg/kg) and ethyl acetate extract (800?mg/kg) showed up to 34.31% and 15.27% of edema inhibition, respectively, at 4?h after administration of carrageenan. In antipyretic assay, the essential oil and chloroform extract displayed a strong antipyretic effect in yeast-induced rats, whereas the ethyl acetate extract had no antipyretic activity. The present study revealed anti-nociceptive, anti-inflammatory and antipyretic potential of M. cordata which could be the therapeutic option against fever, inflammations as well as painful conditions and confirmed the traditional use of M. cordata.     

Evaluation of traditional medicinal plant,Cissus setosa Roxb. (Vitaceae) for antiulcer property

Cissus setosa is an indigenous medicinal herb commonly used for the treatment of gastro ulcers. In the current investigation the aerial methanolic extract of C. setosa was investigated for their antiulcer activity using pylorus ligation and ethanol in experimental rats. The extract was administered at the doses of 200 and 400 mg/kg b.w. orally for 3 days. However, higher dose of the extract subsequently reduced gastric ulcer induced aberrations by pylorus ligation (70.05%) and ethanol (78.16%) as judged by their altered biochemical parameters such as free acidity, total acidity, total carbohydrate, total protein and pepsin activity. Furthermore, macroscopic examination of rat’s stomach also showed that the pretreatment with methanolic extract notably lowered the pylorus ligation and ethanol induced ulcers. As perceived in the present study, evidently, our findings basically supports the potency of the methanol extracts of C. setosa to treat gastrointestinal related disorders, thus lends pharmacological credence to the suggested folklore use.     

A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins

Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA) with human and bovine serum albumins (HSA & BSA) were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (K_b) ~10⁵ M^-1 and free energy (ΔG) ~ -7.5 kcal.mol^-1. It also binds at site II of BSA but with lesser binding affinity (K_b) ~10⁵ M^-1 and ΔG ~ -6.5 kcal.mol^-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra.     

Effects of ganglion blocking agents on post-train facilitation in the rabbit superior cervical ganglion

The effect of ganglion blocking agents, hexamethonium and tubocurarine, on post-train facilitation and ganglionic transmission was studied and compared in isolated superior cervical ganglion of the rabbit, using electrophysiological technique--the conditioning-testing methodology. The preganglionic nerve trunk was stimulated, with either a single unconditioned stimulus (UR)-or a train of conditioning stimuli at 10 or 30 Hz, followed by a post-train test stimulus (PTR). The transmitted postganglionic, compound action potential (PCAP) was recorded following single and trains of stimuli, in the presence and absence of ganglion blocking drugs, hexamethonium (1-100 microM) and tubocurarine (1-100 microM). Hexamethonium and tubocurarine produced concentration-dependent reduction in the amplitude of the transmitted PCAP, increased post-train facilitation values and proportionately reduced those of the subliminal fringe (SF). The mean IC50 values (concentration to produce 50% block of PCAP) of hexamethonium and tubocurarine-induced blockade of the single unconditioned response were 15 +/- 1 microM and 26 +/- 2 microM (n = 6, P less than 0.01) respectively. A dose-ratio (tubocurarine)/hexamethonium) of 1.7 was obtained.     

α-Hydroxylation and oxidation of lignoceric acid in brain: The role of heat-stable and heat-labile factors

Our previous investigations disclosed that the heat-stable and heat-labile factors obtained from brain cytosol are required for -hydroxylation and oxidation of lignoceric acid by rat brain particulate fraction. The heat-stable factor was recently found to contain glucose-6-phosphate, N-acetylaspartate, glutamate, aspartate, glutamine, inorganic phosphate and low levels of adenosine nucleotide as active components. A combination of these compounds was as effective as the crude heat-stable factor for enzymic activity. Using these compounds, we reinvestigated the requirement for the heat-labile factor. With crude heat-stable factor there was an absolute requirement for the heat-labile factor; however, with various combinations of the individual components of the heat-stable factor, some degree of activity was obtained without the heat-labile factor. When aspartate or one of its derivatives, N-acetylaspartate or oxaloacetate, was used in place of the heat-stable factor, the activity was relatively low but highly stimulated by the addition of heat-labile factor. On the other hand, higher activity was obtained when glutamate or one of its derivatives, glutamine or -ketoglutarate, was used without heat-labile factor. The addition of heat-labile factor to this system did not stimulate the activity. When studying the aspartate family, we discovered that the requirement for the heat-labile factor varied in a descending order: N-acetylaspartate > aspartate > oxaloacetate. Lignoceric acid oxidation was further characterized with rat brain particulate fraction, NADPH, Mg²⁺, glutamate, inorganic phosphate, and AMP without heat-stable and heat-labile factors. It was found that the requirement for NADPH was also partially eliminated with glutamate but not aspartate. The effects of various inhibitors, such as inhibitors of the electron transfer system, oxidative phosphorylation, the enzymes involved in citric acid cycle, and glycolysis, suggest that the heat-stable factor is involved in producing ATP or other high energy compounds to be used for the activation of lignoceric acid. ATP added to the system in place of heat-stable factor resulted in less than one-half of the lignoceric acid oxidation.     

Apocynin ameliorates NADPH oxidase 4 (NOX4) induced oxidative damage in the hypoxic human retinal Müller cells and diabetic rat retina

Molecular and Cellular Biochemistry - NADPH oxidase (NOX) is a main producers of reactive oxygen species (ROS) that may contribute to the early pathogenesis of diabetic retinopathy (DR). ROS has...     

Surfactant-mediated amyloidogenesis behavior of stem bromelain; a biophysical insight

Neurodegenerative disorders are mainly associated with amyloid fibril formation of different proteins. Stem bromelain (SB), a cysteine protease, is known to exist as a molten globule state at pH 10.0. It passes through the identical surrounding (pH 10.0) in the gut epithelium of intestine upon oral administration. Protein–surfactant complexes are widely employed as drug carriers, so the nature of surfactant toward protein is of great interest. The present work describes the effect of cationic surfactants (CTAB & DTAB) and their hydrophobic behavior toward amyloidogenesis behavior of SB at pH 10.0. Multiple approaches including light scattering, far UV-CD, turbidity measurements, and dye binding assay (ThT, Congo red and ANS) were performed to measure the aggregation propensity of SB. Further, we monitored the hydrodynamic radii of aggregates formed using dynamic light scattering technique. Structure of fibrils was also visualized through fluorescence microscopy as well as TEM. At pH 10.0, low concentration of CTAB (0–200 μM) induced amyloid formation in SB as evident from a prominent increase in turbidity and light scattering, gain in β-sheet content, and enhanced ThT fluorescence intensity. However, further increase in CTAB concentration suppressed the fibrillation phenomenon. In contrast, DTAB did not induce fibril formation at any concentration used (0–500 μM) due to lower hydrophobicity. Net negative charge developed on protein at high pH (10.0) might have facilitated amyloid formation at low concentration of cationic surfactant (CTAB) due to electrostatic and hydrophobic interactions.     

The Ribosome Biogenesis Protein Nol9 Is Essential for Definitive Hematopoiesis and Pancreas Morphogenesis in Zebrafish

Ribosome biogenesis is a ubiquitous and essential process in cells. Defects in ribosome biogenesis and function result in a group of human disorders, collectively known as ribosomopathies. In this study, we describe a zebrafish mutant with a loss-of-function mutation in nol9, a gene that encodes a non-ribosomal protein involved in rRNA processing. nol9 ^{sa1022/sa1022} mutants have a defect in 28S rRNA processing. The nol9 ^{sa1022/sa1022} larvae display hypoplastic pancreas, liver and intestine and have decreased numbers of hematopoietic stem and progenitor cells (HSPCs), as well as definitive erythrocytes and lymphocytes. In addition, ultrastructural analysis revealed signs of pathological processes occurring in endothelial cells of the caudal vein, emphasizing the complexity of the phenotype observed in nol9 ^{sa1022/sa1022} larvae. We further show that both the pancreatic and hematopoietic deficiencies in nol9 ^{sa1022/sa1022} embryos were due to impaired cell proliferation of respective progenitor cells. Interestingly, genetic loss of Tp53 rescued the HSPCs but not the pancreatic defects. In contrast, activation of mRNA translation via the mTOR pathway by L-Leucine treatment did not revert the erythroid or pancreatic defects. Together, we present the nol9 ^{sa1022/sa1022} mutant, a novel zebrafish ribosomopathy model, which recapitulates key human disease characteristics. The use of this genetically tractable model will enhance our understanding of the tissue-specific mechanisms following impaired ribosome biogenesis in the context of an intact vertebrate.