Aqueous Fraction from Cucumis sativus Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt.

BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. METHODS: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. RESULTS: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1ß and TGF-ß, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. CONCLUSIONS: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.

Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment, and the available therapies aim to modify the course of the disease. It has been demonstrated that extracts of Tagetes lucida have immunomodulatory and neuroprotective effects. This work induced motor damage and neuroinflammation in male BALB/c mice by oral administration of cuprizone (CPZ) (40 mg/kg) for five weeks. In addition, the extracts and coumarins of Tagetes lucida (25 mg/kg) were used to control these damage variables; during the experiment, animals were subject to behavioral tests, and at the end of 5 weeks, mice from each group were used to measure the integrity of biological barriers (brain, kidneys, and spleen) through the extravasation test with blue Evans dye. In another group of animals, the ELISA method measured the brain concentrations of IL-1ß, IL-4, IL-10, and TNF-α. The results presented here allow us to conclude that the extracts and coumarins IC, HN, PE, DF, and SC of Tagetes lucida exert a neuroprotective effect by controlling the motor damage and neuroinflammation by increasing the expression of IL-4 and IL-10 and decreasing IL-1ß and TNF-α; notably, these treatments also protect organs from vascular permeability increase, mainly the BBB, in mice with CPZ-induced experimental encephalomyelitis (VEH * p < 0.05). However, more studies must be carried out to elucidate the molecular mechanisms of the pharmacological effects of this Mexican medicinal plant.

Characterization of a murine model of endothelial dysfunction induced by chronic intraperitoneal administration of angiotensin II.

Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1ß, IL17A, IL4, TGFß, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.

Data of the effects of acetone fraction from Sechium edule (Jacq.) S.w. edible roots in the kidney of endothelial dysfunction induced mice.

Endothelial dysfunction induced by Angiotensin II (AG II) plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage including the kidney (Schmitt and Dirsch, 2009) [1]. New drugs that can control several of these pathologies are required. Sechium edule has been reported to possess antioxidant, anti-inflammatory and antihypertensive activity (Ibarra-Alvarado et al., 2010) [2]. This paper contains data complementary to those published in Journal of Ethnopharmacology (Moreno et al., 2018) [3], evaluating the effect in kidney of hypertensive mice of the acetone fraction from S. edule to control de pro-oxidative state, reduction of the inflammatory adhesion molecule (ICAM) and recruitment of inflammatory cells.

Acetone fraction from Sechium edule (Jacq.) S.w. edible roots exhibits anti-endothelial dysfunction activity.

ETHNOPHARMACOLOGICAL RELEVANCE: A recent ethnomedical survey on medicinal plants grown in Mexico revealed that Sechium edule (Jacq.) Sw. (Cucurbitaceae) is one of the most valued plant species to treat cardiovascular diseases, including hypertension. Fruits, young leaves, buds, stems, and tuberous roots of the plant are edible. Considering that endothelial dysfunction induced by Angiotensin II plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage, and that S. edule has been reported to possess antioxidant, anti-inflammatory and antihypertensive activity, its capability to control endothelial dysfunction was also assessed. AIM OF THE STUDY: To assess in vivo the anti-endothelial dysfunction activity of the acetone fraction (rSe-ACE) of the hydroalcoholic extract from S. edule roots. MATERIALS AND METHODS: Endothelial dysfunction was induced in female C57BL/6 J mice by a daily intraperitoneal injection of angiotensin II for 10 weeks. Either rSe-ACE or losartan (as a control) were co-administered with angiotensin II for the same period. Blood pressure was measured at weeks 0, 5, and 10. Kidney extracts were prepared to determine IL1ß, IL4, IL6, IL10, IL17, IFNγ, TNFα, and TGFß levels by ELISA, along with the prooxidative status as assessed by the activity of antioxidant enzymes. The expression of ICAM-1 was evaluated by immunohistochemistry in kidney histological sections. Kidney and hepatic damage, as well as vascular tissue remodeling, were studied. RESULTS: The rSe-ACE fraction administered at a dose of 10 mg/kg was able to control hypertension, as well as the prooxidative and proinflammatory status in kidney as efficiently as losartan, returning mice to normotensive levels. Additionally, the fraction was more efficient than losartan to prevent liver and kidney damage. Phytochemical characterization identified cinnamic acid as a major compound, and linoleic, palmitic, and myristic acids as the most abundant non-polar components in the mixture, previously reported to aid in the control of hypertension, inflammation, and oxidative stress, three important components of endothelial dysfunction. IN CONCLUSION: this study demonstrated that rSe-ACE has anti-endothelial dysfunction activity in an experimental model and highlights the role of cinnamic acid and fatty acids in the observed effects.