Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J).

BACKGROUND: The fruit of Rosa moschata has traditionally been used for the treatment of abdominal spasm and diarrhoea. Therefore, the aim of this study was to investigate mechanism(s) responsible for its medicinal use in gut spasm and diarrhea. METHODS: Hydro-methanolic extract of Rosa moschata (Rm.Cr) was studied in isolated rabbit's jejunal preparations for possible antispasmodic activity. Based upon in vitro relaxant activity in isolated gut preparations, in vivo antidiarrheal activity was carried out in mice to confirm its antidiarrheal effect. Acute toxicity study was performed to determine safe dose range before in vivo experiments. RESULTS: In isolated rabbits' jejunal preparations, Rm.Cr inhibited the spontaneous and high K+-induced contractions with respective EC50 values of 0.66 (0.44-0.97; n = 5) and 2.28 mg/mL (1.43-3.62; n = 5), like that of verapamil. This suggests the presence of calcium channel blocking (CCB) activity as a possible mode of action. The Ca++ channel blocking activity was further confirmed when pre-treatment of isolated jejunums with Rm.Cr (1-5 mg/mL) caused a rightward shift in the Ca++ concentration-response curves (CRCs), similar to verapamil. Rm.Cr was safe up to 2000 mg/kg for in vivo acute toxicity. Rm.Cr provided 55% and 80% protection from diarrhoea in respective doses of 100 mg/kg and 1000 mg/kg. These data indicates that the crude extract of Rosa moschata possesses Ca++ antagonist-like constituent(s), which explains its inhibitory effect on gut motility; a mechanism that underlies its antidiarrheal and antispasmodic activities. CONCLUSION: The study shows that the crude extract of fruits of Rosa moschata possesses antispasmodic effects mediated possibly through voltage gated Ca++ channel blockade, which provides sound pharmacological base to its medicinal use in gut spasms and diarrhoea, though additional mechanism(s) cannot be ruled out.

A computational study of suppression of sharp wave ripple complexes by controlling calcium and gap junctions in pyramidal cells.

The hippocampus plays a key role in memory formation and learning. According to the concept of active systems memory consolidation, transiently stored memory traces are transferred from the hippocampus into the neocortex for permanent storage. This phenomenon relies on hippocampal network oscillations, particularly sharp wave ripples [SPW-Rs). In this process prior saved data in the hippocampus may be reactivated. Recent investigations reveal that several neurotransmitters and neuromodulators including norepinephrine, acetylcholine, serotonin, etc., suppress SPW-Rs activity in rodents' hippocampal slices. This suppression of SPW-Rs may depend on various presynaptic and postsynaptic parameters including decrease in calcium influx, hyperpolarization/depolarization and alteration in gap junctions' function in pyramidal cells. In this study, we demonstrate the impact of calcium influx and gap junctions on pyramidal cells for the modulation of SPW-Rs in a computational model of CA1.We used,SPW-Rs model with some modifications. SPW-Rs are simulated with gradual reduction of calcium and with decreasing conductance through gap junctions in PCs. Both, with calcium reduction as well as with conductance reduction through gap junctions, SPW-Rs are suppressed. Both effects add up synergistically in combination.

Full-Length Genome and Partial Viral Genes Phylogenetic and Geographical Analysis of Dengue Serotype 3 Isolates.

Dengue fever is among the most common vector-borne diseases. Dengue virus (DENV), responsible for dengue fever as well as dengue hemorrhagic fever, belongs to the genus flavivirus and family Flaviviridae. Flaviviruses infect various vertebrate species and arthropods and are also responsible for diseases in birds, wild animals, and primates. DENV consists of a single-stranded, positive-sense RNA genome ~11 kb in size. Complete genome and partial gene sequences of geographically distinct DENV-3 strains were retrieved from the GenBank database. The evolutionary divergence of the 33 whole-genome and individual gene sequences of the nucleotides and amino acids of DENV-3 strains were generated with the maximum likelihood (ML) and Bayesian phylogenetic study (BEAST) methods using the MEGA 7 software. The genome size varied from 10,484 to 10,724 nucleotides among the strains with distinct geographical backgrounds belonging to Central America, South-Central Asia, and Eastern Asia. A phylogenetic analysis of the nucleotide and amino acid sequences of these DENV-3 isolates revealed extensive differences in the topologies due to PrM/M, NS1, NS2B, and NS3 genes. These results suggest substantial variation in the evolutionary pathways of the studied genes and genomes.

Assessment of clinical variables as predictive markers in the development and progression of colorectal cancer.

Colorectal cancer (CRC) is graded as one of the most common cancer. It accounts for the second leading cause of cancer deaths worldwide. The present study intends to investigate the role and importance of different biochemical variables in the development of colorectal cancer.In this cross-sectional study we recruited ninety-one patients diagnosed with colorectal cancer and fifty-three age-sex matched controls from June 2017 to June 2018. Different variables i.e. SOD, GSH, CAT, MDA, TGF, VEGF, TNF, ILs, MMPs, etc., were estimated with the help of their respective methods. Our findings suggest a significant increase in the levels of different inflammatory and stress-related markers. The NFκB, TGF-ß, VEGFß, 8OHdG, IsoP-2α were significantly found to be increased in patients with colon cancer (0.945 ± 0.067 µg/ml, 18.59 ± 1.53 pg/ml, 99.35 ± 4.29 pg/ml, 21.26 ± 1.29 pg/ml, 102.25 ± 4.25 pg/ml) as compared to controls (0.124 ± 0.024 µg/ml, 8.26 ± 0.88 pg/ml, 49.58 ± 2.62 pg/ml, 0.93 ± 0.29 pg/ml, 19.65 ± 3.19 pg/ml). Notably, the levels of different antioxidants were shown to be significantly lower in patients of colon cancer. The present study concluded that excessive oxidative stress and lipid peroxidation result in a decrease in the antioxidative capacity of cells which may influence diverse signaling cascades including NF-KB, which results in DNA modification and gene transcription that ultimately involved in the progression of colon cancer.

Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.