Ayurvedic Medicine: A Traditional Medical System and Its Heavy Metal Poisoning.

Ayurveda is one of the oldest and most widely practiced traditional medical systems in the world. The ancient knowledge in this traditional medical system has yet to be fully explored. The interaction of rich knowledge from various traditional systems of medicine can open new pathways in the herbal drug discovery process. Apart from other hurdles in discovering plant-based medicines, the lack of knowledge of the differences and similarities between the theoretical doctrines of these systems is the greatest impediment to their convergence. Rasashastra is an Ayurvedic medicine section that deals with formulations that include minerals/metals, particularly Parad (mercury). According to the Ayurvedic Formulary of India, the most widely used heavy metals are mercury, arsenic, and lead. However, contemporary scientists are concerned about the use of heavy metals in Ayurvedic preparation. In this review article, we will discuss Ayurvedic medicine and the toxic effects of heavy metals.

PLAAT1 expression triggers fragmentation of mitochondria in an enzyme activity-dependent manner.

The phospholipase A and acyltransferase (PLAAT) family is a protein family consisting of five members (PLAAT1-5), which acts as phospholipid-metabolizing enzymes with phospholipase A1/A2 and N-acyltransferase activities. Since we previously reported that the overexpression of PLAAT3 in mammalian cells causes the specific disappearance of peroxisomes, in the present study we examined a possible effect of PLAAT1 on organelles. We prepared HEK293 cells expressing mouse PLAAT1 in a doxycycline-dependent manner and found that the overexpression of PLAAT1 resulted in the transformation of mitochondria from the original long rod shape to a round shape, as well as their fragmentation. In contrast, the overexpression of a catalytically inactive point mutant of PLAAT1 did not generate any morphological change in mitochondria, suggesting the involvement of catalytic activity. PLAAT1 expression also caused the reduction of peroxisomes, while the levels of the marker proteins for ER, Golgi apparatus and lysosomes were almost unchanged. In PLAAT1-expressing cells, the level of dynamin-related protein 1 responsible for mitochondrial fission was increased, whereas those of optic atrophy 1 and mitofusin 2, both of which are responsible for mitochondrial fusion, were reduced. These results suggest a novel role of PLAAT1 in the regulation of mitochondrial biogenesis.

PLAAT1 deficiency alleviates high-fat diet-induced hepatic lipid accumulation in mice.

The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing enzymes exhibiting phospholipase A1 /A2 and acyltransferase activities. Plaat3-deficient (Plaat3-/- ) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high-fat diet (HFD) feeding, while Plaat1-/- mice have not been analyzed. In the present study, we generated Plaat1-/- mice and investigated the effects of PLAAT1 deficiency on HFD-induced obesity, hepatic lipid accumulation, and insulin resistance. After HFD treatment, PLAAT1 deficiency caused a lower body weight gain compared to wild-type mice. Plaat1-/- mice also showed reduced liver weight with negligible hepatic lipid accumulation. In accordance with these findings, PLAAT1 deficiency improved HFD-induced hepatic dysfunction and lipid metabolism disorders. Lipidomics analysis in the liver revealed that in Plaat1-/- mice, the levels of various glycerophospholipids tended to increase, while all classes of lysophospholipids examined tended to decrease, suggesting that PLAAT1 functions as phospholipase A1 /A2 in the liver. Interestingly, the HFD treatment of wild-type mice significantly increased the mRNA level of PLAAT1 in the liver. Furthermore, the deficiency did not appear to elevate the risk of insulin resistance in contrast to PLAAT3 deficiency. These results suggested that the suppression of PLAAT1 improves HFD-induced overweight and concomitant hepatic lipid accumulation.

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia.

N-Acyl-phosphatidylethanolamines (NAPEs), a minor class of membrane glycerophospholipids, accumulate along with their bioactive metabolites, N-acylethanolamines (NAEs) during ischemia. NAPEs can be formed through N-acylation of phosphatidylethanolamine by cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) or members of the phospholipase A and acyltransferase (PLAAT) family. However, the enzyme responsible for the NAPE production in brain ischemia has not yet been clarified. Here, we investigated a possible role of cPLA2ε using cPLA2ε-deficient (Pla2g4e-/-) mice. As analyzed with brain homogenates of wild-type mice, the age dependency of Ca2+-dependent NAPE-forming activity showed a bell-shape pattern being the highest at the first week of postnatal life, and the activity was completely abolished in Pla2g4e-/- mice. However, liquid chromatography-tandem mass spectrometry revealed that the NAPE levels of normal brain were similar between wild-type and Pla2g4e-/- mice. In contrast, post-mortal accumulations of NAPEs and most species of NAEs were only observed in decapitated brains of wild-type mice. These results suggested that cPLA2ε is responsible for Ca2+-dependent formation of NAPEs in the brain as well as the accumulation of NAPEs and NAEs during ischemia, while other enzyme(s) appeared to be involved in the maintenance of basal NAPE levels.

Involvement of the γ Isoform of cPLA2 in the Biosynthesis of Bioactive N-Acylethanolamines.

Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via N-acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A2 (cPLA2) functions as an N-acyltransferase to form NAPE. Since the cPLA2 family consists of six isoforms (α, ß, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA2 isoforms were labeled with [14C]ethanolamine, the increase in the production of [14C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [14C]N-acyl-lysophosphatidylethanolamine (lysoNAPE) and [14C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA2γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-N-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA2γ is involved in the biosynthesis of NAE by its phospholipase A1/A2 and lysophospholipase activities.