COMPARATIVE ANALYSIS OF ANTI-INFLAMMATORY ACTIVITY OF AQUEOUS AND METHANOLIC EXTRACTS OF C. CASSIA AND C. ZEYLANICUM IN RAW264.7, SW1353 AND PRIMARY CHONDROCYTES

Objectives: The objective of this research was to compare the anti-inflammatory activity of aqueous and methanolic extracts of C. cassia (CC) and C. zeylanicum (CZ) in mouse macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines as well as in human primary chondrocytes, to correlate their efficacy in management of osteoarthritis (OA) related pathophysiology.Methods: RAW264.7, SW1353 and human primary chondrocytes were pre-treated with aqueous extracts of C. cassia (CCW) and C. zeylanicum (CZW) and methanolic extracts of C. cassia (CCM) and C. zeylanicum (CZM) at various concentrations (0.1-100 µg/ml) for 1 h, followed by stimulation with LPS and IL-1β, respectively. The effect of CCM, CCW, CZM and CZW on the production of nitric oxide (NO) was evaluated by Griess reaction. Evaluation of prostaglandin E2 (PGE2) and leukotriene (LTB4) proteins was performed by EIA-Monoclonal based kits. The effect of these extracts on matrix metalloproteinase (MMPs-2, 9 and 13) levels was analyzed by SensoLyte® fluorimetric MMP assay kit.Results: The methanolic extracts (CCM, CZM) of both the varieties of cinnamon were found to be more effective than the aqueous extracts in terms of PGE2, LTB4 and MMP inhibition.We found that in RAW 264.7, CCM and CZM decreased NO and PGE2 production by45.40%±8.6; 65.63%±5.7 and 79.88%±1.2; 95.91%±0.3, respectively. Similarly, in SW1353 and chondrocytes, CCM decreased PGE2 production by 68.8%±6.4;36.1%±9.5, respectively whereas CZM reduced PGE2 production by 70.2%±2.3; 52.3%±5.4, respectively. Moreover, in SW1353 and chondrocytes CCM decreased LTB4 production by 85.47%±3.03; 99.6%±0.2, respectively whereas CZM reduced LTB4 production by 67.5%±5.6; 75.6%±1.2, respectively. In chondrocytes both CCM and CZM significantly reduced the levels of MMP-2(55.7%±5.2; 73.1%±7.1), MMP-9 (57.5%±4.7; 74.5%±5.2) and MMP-13 (90.1%±2.6; 71.2%±12.5), respectively. However, on comparing the two species of cinnamon, C. zeylanicumwas found to be more effective than C. cassia andthus could be considered for its potential therapeutic application in the management of inflammatory conditions associated with OA.Conclusion: The present study would help in choosing better of the two species of cinnamon for their possible therapeutic application in the management of inflammatory condition associated with OA.Â

Short Conduction Delays Cause Inhibition Rather than Excitation to Favor Synchrony in Hybrid Neuronal Networks of the Entorhinal Cortex

How stable synchrony in neuronal networks is sustained in the presence of conduction delays is an open question. The Dynamic Clamp was used to measure phase resetting curves (PRCs) for entorhinal cortical cells, and then to construct networks of two such neurons. PRCs were in general Type I (all advances or all delays) or weakly type II with a small region at early phases with the opposite type of resetting. We used previously developed theoretical methods based on PRCs under the assumption of pulsatile coupling to predict the delays that synchronize these hybrid circuits. For excitatory coupling, synchrony was predicted and observed only with no delay and for delays greater than half a network period that cause each neuron to receive an input late in its firing cycle and almost immediately fire an action potential. Synchronization for these long delays was surprisingly tight and robust to the noise and heterogeneity inherent in a biological system. In contrast to excitatory coupling, inhibitory coupling led to antiphase for no delay, very short delays and delays close to a network period, but to near-synchrony for a wide range of relatively short delays. PRC-based methods show that conduction delays can stabilize synchrony in several ways, including neutralizing a discontinuity introduced by strong inhibition, favoring synchrony in the case of noisy bistability, and avoiding an initial destabilizing region of a weakly type II PRC. PRCs can identify optimal conduction delays favoring synchronization at a given frequency, and also predict robustness to noise and heterogeneity

The COGs (context, object, and goals) in multisensory processing

Our understanding of how perception operates in real-world environments has been substantially advanced by studying both multisensory processes and “top-down” control processes influencing sensory processing via activity from higher-order brain areas, such as attention, memory, and expectations. As the two topics have been traditionally studied separately, the mechanisms orchestrating real-world multisensory processing remain unclear. Past work has revealed that the observer’s goals gate the influence of many multisensory processes on brain and behavioural responses, whereas some other multisensory processes might occur independently of these goals. Consequently, other forms of top-down control beyond goal dependence are necessary to explain the full range of multisensory effects currently reported at the brain and the cognitive level. These forms of control include sensitivity to stimulus context as well as the detection of matches (or lack thereof) between a multisensory stimulus and categorical attributes of naturalistic objects (e.g. tools, animals). In this review we discuss and integrate the existing findings that demonstrate the importance of such goal-, object- and context-based top-down control over multisensory processing. We then put forward a few principles emerging from this literature review with respect to the mechanisms underlying multisensory processing and discuss their possible broader implications

Hepatoprotective activity of Indian Phyllanthus

Context: Phyllanthus (Euphorbiaceae) species are traditionally well-known for their medicinal properties including hepatoprotective activity. Objective: The study assessed the hepatoprotective and antioxidant activities of 11 Phyllanthus species, P. amarus Schumach., P. urinaria L., P. debilis Klein ex Willd, P. tenellus Roxb., P. virgatus G. Forst., P. maderaspatensis L., P. reticulatus Poir., P. polyphyllus Willd., P. emblica L., P. indofischerii Bennet. and P. acidus (L.) Skeels. Materials and methods: The dried leaves and stems of each plant species were extracted in methanol and successively in water. The extracts were screened for hepatoprotective activity at a concentration of 50 μg/mL against tert-butyl hydroperoxide (t-BH) induced toxicity in HepG2 cells. Seven extracts from five species that showed hepatoprotective activity were assessed for their 50% effective concentration (EC50) values and their antioxidant activity using a DPPH assay. Phyllanthin and hypophyllanthin contents were also determined in these Phyllanthus species. Results: The methanol extracts of P. polyphyllus, P. emblica and P. indofischeri showed high levels of hepatoprotective activity with EC50 values of 12, 19 and 28 μg/mL and IC50 of 3.77, 3.38 and 5.8 μg/mL for DPPH scavenging activity respectively against an IC50 of 3.69 μg/mL for ascorbic acid. None of these activities could be attributed to phyllanthin and hypophyllanthin. Discussion and conclusion: The hepatoprotective and antioxidant activities of P. indofischeri are demonstrated for the first time in literature. The study also confirms the hepatoprotective and antioxidant activities of leaves of P. emblica and P. polyphyllus. The molecule(s) responsible for the activities is being investigated

Temporal Causal Inference With Stochastic Audiovisual Sequences

Data and stimulus sequences described in the paper.NIH EY082