Medicinal plants possess sedative and anxiolytic effect with emphasis on their mechanisms of action

Insomnia and anxiety are worldwide medical problems. Plant extracts possessed sedative and anxiolytic effect via different mechanisms included interactions with Na+ channels, γ-aminobutyric acid type A receptors, N-methyl-D-aspartate receptors and chatecholamines. In the current review, Web Science, PubMed, Scopus and Science Direct, were searched to investigate the plants with sedative and anxiolytic effects

Ebola: Destroys Na+/K+ Ion Exchange to Accelerate Electrolyte Imbalance by Scorpion Venom-like System

Ebola sickness is a hemorrhagic fever caused by the Ebola virus that has an extremely high fatality rate. Electrolyte imbalance is a typical sign in Ebola patients who have already contracted the virus. The use of bioinformatics calculation tools to research Ebola's electrolyte imbalance mechanism is critical for halting the development of the epidemic and saving lives. The computational method of conserved domain search was employed to investigate the protein function of EBOV in this work. This study demonstrates that L, N, S, VP24, and VP35 have LCN type CS-α/β domains. It is a peptide neurotoxin found in scorpions, sea anemone, and snake venom. It can activate Na+ channels and gradually deactivate them, and deactivate voltage- and Ca+2-activated K+ channels. S LCN type CS-α/β is a neurotoxin with a lengthy chain that can activate Na+ channels. VP24, VP35, and N LCN type CS-α/β are short-chain toxins that inhibit voltage-dependent or Ca+2-activated K+ channels and partially inactivate sodium channels. L contains both long- and short-chain LCN type CS-α/β toxins that can activate Na+ channels and inhibit K+ channels. These LCN type CS-α/β can activate Na+ channels and Na+/K+ pumps while simultaneously inactivating K+ channels. It may result in many Na+ entering the cell and a large amount of K+ accumulating within the cell. Simultaneously, the Na+/Ca+ exchange pump outputs Na+ and inputs Ca+2 in “the reverse” mode. The results in an electrolytic environment outside the cell with hyponatremia, hypocalcemia and hypokalemia.

The neuropeptide RhoprCCHamide2 inhibits serotonin-stimulated transcellular Na+ transport across the anterior midgut of the vector of Chagas disease Rhodnius prolixus

Rhodnius prolixus is a blood-feeding insect vector of Tripanosoma cruzi, a protozoan parasite that causes Chagas' disease. During each blood meal the animals ingest large volumes of blood, that may be up to 12 times the unfed body mass. These blood meals impose a significant osmotic stress for the animals due to the hyposmotic condition of the ingested blood compared to the insect's haemolymph. Thus, the insect undergoes a massive postprandial diuresis that allows for the excretion of the plasma fraction of the blood in less than two hours. Diuresis is performed by the excretory system, consisting of the Malpighian tubules and gut, under the control of diuretic and antidiuretic factors. We investigated the ion transport machinery triggered by stimulation with the diuretic factor serotonin in the anterior midgut (i.e. crop) and the effect of the diuretic modulator RhoprCCHamide2. Ussing chamber assays revealed that serotonin-stimulated increase in transepithelial short circuit current (Isc) was more sensitive to the blockage with amiloride than EIPA, suggesting the involvement of Na+ channels. Incubation in Na+-free, but not Cl−-free saline, blocked the effect of serotonin on Isc. Moreover, treatment with NKCC and NCC blockers had no effect on fluid secretion but was blocked by amiloride. Blockage of Na+/K+-ATPase with ouabain inhibit Isc but the H+-ATPase inhibitor bafilomycin had no effect. The neuropeptide RhoprCCHamide2 diminished serotonin-stimulated Isc across the crop. The results suggest that Na+ undergoes active transport via an apical amiloride-sensitive Na+ channels and a basolateral ouabain-sensitive Na+/K+-ATPase while Cl− is transported through passive paracellular pathway.

Changes in Ion Selectivity Following the Asymmetrical Addition of Charge to the Selectivity Filter of Bacterial Sodium Channels

Voltage-gated sodium channels (NaVs) play fundamental roles in eukaryotes, but their exceptional size hinders their structural resolution. Bacterial NaVs are simplified homologues of their eukaryotic counterparts, but their use as models of eukaryotic Na+ channels is limited by their homotetrameric structure at odds with the asymmetric Selectivity Filter (SF) of eukaryotic NaVs. This work aims at mimicking the SF of eukaryotic NaVs by engineering radial asymmetry into the SF of bacterial channels. This goal was pursued with two approaches: the co-expression of different monomers of the NaChBac bacterial channel to induce the random assembly of heterotetramers, and the concatenation of four bacterial monomers to form a concatemer that can be targeted by site-specific mutagenesis. Patch-clamp measurements and Molecular Dynamics simulations showed that an additional gating charge in the SF leads to a significant increase in Na+ and a modest increase in the Ca2+ conductance in the NavMs concatemer in agreement with the behavior of the population of random heterotetramers with the highest proportion of channels with charge −5e. We thus showed that charge, despite being important, is not the only determinant of conduction and selectivity, and we created new tools extending the use of bacterial channels as models of eukaryotic counterparts.