The Effect of an Aqueous Extract of Teucrium polium on Glutathione Homeostasis In Vitro: A Possible Mechanism of Its Hepatoprotectant Action

Background. Teucrium polium is used in Arab traditional medicine to treat liver diseases. Glutathione is an important intracellular antioxidant, and intrahepatic glutathione levels are depleted in liver diseases. Hypothesis and Aim. This investigation tested the hypothesis that aqueous extracts of T. polium maintains intracellular glutathione levels by augmenting glutathione peroxidase and glutathione reductase activity in cultured hepatocytes. Methods. The effects of increasing concentrations (0.01–1 mg/mL) of aqueous extract of T. polium were assessed in cultured HepG2 cells following 24 hours incubation on (1) cellular integrity using (a) the Trypan blue exclusion assay, (b) the [di-methylthiazol-2yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay, and (c) the lactate dehydrogenase (LDH) assay; (2) glutathione redox state; and (3) glutathione peroxidase and glutathione reductase activities using a repeated measures experimental design. Results. At concentrations of 0.375 mg/mL and 0.5 mg/mL, the extract increased the intracellular levels of total and reduced glutathione and had no effect on the intracellular amounts of oxidized glutathione. The extract had no effect on glutathione peroxidase and glutathione reductase activities. Conclusion. These data indicate that the mechanism of the hepatoprotective action of aqueous extracts of T. polium may be, in part, due to augmenting intracellular glutathione levels

MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells

The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR- 124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non- neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells

The role of the Notch signalling pathway in regulating the balance between neuronal and nonneuronal cells in sympathetic ganglia and the adrenal gland

Sympathetic neurons and endocrine chromaffin cells of the adrenal medulla are catecholaminergic cells that derive from the neural crest. According to the classic model, they develop from a common sympathoadrenal (SA) progenitor that has the ability to differentiate into both sympathetic neurons and chromaffin cells depending on signals provided by their final environment. Our previous data revealed that a single premigratory neural crest cell can give rise to both sympathetic neurons and chromaffin cells, indicating that the fate decision between these cell types occurs after delamination. A more recent study demonstrated that at least half of chromaffin cells arise from a later contribution by Schwann cell precursors. Since Notch signalling is known to be implicated in the regulation of cell fate decisions, we investigated the early role of Notch signalling in regulating the development of neuronal and non-neuronal SA cells within sympathetic ganglia and the adrenal gland. To this end, we implemented both gain and loss of function approaches. Electroporation of premigratory neural crest cells with plasmids encoding Notch inhibitors revealed an elevation in the number of SA cells expressing the catecholaminergic enzyme tyrosine-hydroxylase, with a concomitant reduction in the number of cells expressing the glial marker P0 in both sympathetic ganglia and adrenal gland. As expected, gain of Notch function had the opposite effect. Numbers of neuronal and non-neuronal SA cells were affected differently by Notch inhibition depending on the time of its onset. Together our data show that Notch signalling can regulate the ratio of glial cells, neuronal SA cells and nonneuronal SA cells in both sympathetic ganglia and the adrenal gland

The role of the Notch signalling pathway in regulating the balance between neuronal and nonneuronal cells in sympathetic ganglia and the adrenal gland.

Sympathetic neurons and endocrine chromaffin cells of the adrenal medulla are catecholaminergic cells that derive from the neural crest. According to the classic model, they develop from a common sympathoadrenal (SA) progenitor that has the ability to differentiate into both sympathetic neurons and chromaffin cells depending on signals provided by their final environment. Our previous data revealed that a single premigratory neural crest cell can give rise to both sympathetic neurons and chromaffin cells, indicating that the fate decision between these cell types occurs after delamination. A more recent study demonstrated that at least half of chromaffin cells arise from a later contribution by Schwann cell precursors. Since Notch signalling is known to be implicated in the regulation of cell fate decisions, we investigated the early role of Notch signalling in regulating the development of neuronal and non-neuronal SA cells within sympathetic ganglia and the adrenal gland. To this end, we implemented both gain and loss of function approaches. Electroporation of premigratory neural crest cells with plasmids encoding Notch inhibitors revealed an elevation in the number of SA cells expressing the catecholaminergic enzyme tyrosine-hydroxylase, with a concomitant reduction in the number of cells expressing the glial marker P0 in both sympathetic ganglia and adrenal gland. As expected, gain of Notch function had the opposite effect. Numbers of neuronal and non-neuronal SA cells were affected differently by Notch inhibition depending on the time of its onset. Together our data show that Notch signalling can regulate the ratio of glial cells, neuronal SA cells and nonneuronal SA cells in both sympathetic ganglia and the adrenal gland

Research Article The Effect of an Aqueous Extract of Teucrium polium on Glutathione Homeostasis In Vitro: A Possible Mechanism of Its Hepatoprotectant Action

Copyright © 2010 Stella Shtukmaster et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Teucrium polium is used in Arab traditional medicine to treat liver diseases. Glutathione is an important intracellular antioxidant, and intrahepatic glutathione levels are depleted in liver diseases. Hypothesis and Aim. This investigation tested the hypothesis that aqueous extracts of T. polium maintains intracellular glutathione levels by augmenting glutathione peroxidase and glutathione reductase activity in cultured hepatocytes. Methods. The effects of increasing concentrations (0.01–1 mg/mL) of aqueous extract of T. polium were assessed in cultured HepG2 cells following 24 hours incubation on (1) cellular integrity using (a) the Trypan blue exclusion assay, (b) the [di-methylthiazol-2yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay, and (c) the lactate dehydrogenase (LDH) assay; (2) glutathione redox state; and (3) glutathione peroxidase and glutathione reductase activities using a repeated measures experimental design. Results. At concentrations of 0.375 mg/mL and 0.5 mg/mL, the extract increased the intracellular levels of total and reduced glutathione and had no effect on the intracellular amounts of oxidized glutathione. The extract had no effect on glutathione peroxidase and glutathione reductase activities. Conclusion. These data indicate that the mechanism of the hepatoprotective action of aqueous extracts of T. polium may be, in part, due to augmenting intracellular glutathione levels. 1