Phenolic extracts from various Algerian plants as strong inhibitors of porcine liver carboxylesterase

Carboxylesterases (CE), expressed at high levels in human liver and intestine, are thought to detoxify xenobiotics. The goal of this study was to study the effect of phenolic compounds from several plants from the Algerian Atlas used traditionally in Arab folk medicine on the enzymatic activity of porcine liver carboxylesterase. The plants have shown a potent inhibition of carboxylesterase (CE) enzymatic activity in a concentration-dependent manner. Results indicate that the Phenolic extracts from these plants lead to the inactivation of the CE pI = 5.1 with K_i values in micromolar range (1.4–38 μM). These results encourage further biological investigation and identification the inhibitors responsible for this activity.     

Lack of effect of ghrelin treatment on melatonin production in rat pineal and Harderian glands

The effects of ghrelin, a peptide hormone secreted from the stomach, on melatonin remain unknown. The aim of the study was to investigate possible ghrelin-melatonin interactions by studying the effect of ghrelin treatment on melatonin production in rat pineal and Harderian glands. Young (9 weeks) and old (20 months) male Wistar rats, maintained under a light:dark cycle regimen of 12:12, were assigned randomly to either a single subcutaneous (s.c.) injection of saline or ghrelin (1 microg/rat or 15 microg/rat) 1 h before sacrifice in the middle of the dark phase, or repeated s.c. saline or ghrelin injections (15 microg/rat), 3, 2 and 1 h before sacrificed in the middle of the dark phase. Neither ghrelin doses (1 microg/rat or 15 microg/rat) nor type of treatment (acute or repeated) influenced melatonin levels or the melatonin synthesizing enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase activities, either in pineal gland or in Harderian glands. At the concentrations used, ghrelin does not influence melatonin production in rat pineal and Harderian glands, and therefore is not involved in the regulation of melatonin secretion, at least under our experimental conditions.     

Phenolic extracts from various Algerian plants as strong inhibitors of porcine liver carboxylesterase

Carboxylesterases (CE), expressed at high levels in human liver and intestine, are thought to detoxify xenobiotics. The goal of this study was to study the effect of phenolic compounds from several plants from the Algerian Atlas used traditionally in Arab folk medicine on the enzymatic activity of porcine liver carboxylesterase. The plants have shown a potent inhibition of carboxylesterase (CE) enzymatic activity in a concentration-dependent manner. Results indicate that the Phenolic extracts from these plants lead to the inactivation of the CE pI = 5.1 with K(i) values in micromolar range (1.4-38 microM). These results encourage further biological investigation and identification the inhibitors responsible for this activity.     

Effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide in rat atria: an in vitro study

Scorpion envenomation is considered public health problem in Northern African countries. The mechanisms of cardiac dysfunction following scorpion envenomation are not fully understood. This study examined the effect and mechanisms underlying scorpion toxin action from Androctonus australis garzonii on atrial natriuretic peptide (ANP) release from rat atrium using in vitro organ perifusion. Male Sprague Dawley rats were used in this study. Three experiments were conducted. In experiment 1, atrial tissues were exposed either to Krebs-bicarbonate buffer medium (control) or to scorpion toxin (10(-8) M to 10(-6) M). In experiment 2, animals were chemically sympathectomized with a single intraperitoneal injection of 6-hydroxydopamine (6-OHDOPA) at a dose of 40 microg/g 24 h before sacrifice. Vehicle-treated rats served as control. Atrial tissues were collected and perifused in the presence of 10(-6) M scorpion toxin. In experiment 3, atrial tissues were exposed to 10(-6) M scorpion toxin either in the absence or presence of 10(-6) M propranolol (a beta-adrenoceptor blocker), or 10(-6) M tetrodotoxin (a sodium channel blocker). ANP levels released in the perifusion medium were determined by radioimmunoassay. The scorpion toxin at 10(-6) M induced a significant (p<0.01) increase (106%) in ANP levels. This effect was decreased (20%) by 6-OHDOPA. Propranolol and tetrodotoxin significantly (p<0.01) inhibited 55% and 60%, respectively, the toxin-induced ANP release. The data show that the North African scorpion toxin from Androctonus australis garzonii increases the ANP release in rat atrium through stimulation of sympathetic cardiac nerves and sodium channels activation.     

Inhibition of porcine liver carboxylesterase by a new flavone glucoside isolated from Deverra scoparia

An endemic North African Saharan plant from of the Apiaceae family, Deverra scoparia, used locally for medicinal preparations, showed a strong inhibitory effect on porcine liver carboxylesterase. The active compound from the aerial part of the plant was purified by semi-preparative HPLC and photodiode array detection, and structurally determined by (1)H, (13)C NMR and mass spectroscopy methods. This compound was identified as flavone-3,4',7-trihydroxy-3'-methoxy-7-glucoside and it was found to be a powerful competitive inhibitor of porcine liver carboxylesterase with a inhibition constant value of 16 microM. Based on the structural features of the inhibitor and the enzyme active site region, it seems that the flavonoside binds to the surface of the enzyme. The low K(i) value suggests some physiological significance of such inhibitory activity, especially concerning the bio-transformation of xenobiotics.     

Malignant melanoma with areas of rhabdomyosarcomatous differentiation arising in a giant congenital nevus with RAF1 gene fusion

A girl, born with a posterior lumbosacral giant congenital nevus, developed a central nodule that expanded over a period of 14 months into a 10‐cm pedunculated mass. Histological analysis of the mass revealed melanoma of myxoid, small round‐cell type with areas of rhabdomyosarcomatous transformation confirmed by immunohistochemistry. RNA sequencing identified an in‐frame SASS6(e14)‐RAF1(e8) fusion in both components and the nevus. A RAF1 FISH break‐apart test found a balanced rearrangement pattern in the nevus and an unbalanced pattern in the malignant areas. Wild‐type status of NRAS and BRAF was confirmed by NGS techniques. The array‐CGH profile displayed copy number alterations commonly found in rhabdomyosarcomas. Despite intensive treatment, widespread metastatic evolution of the melanomatous component was observed.