Bioactive compounds from the leaves of Maytenus ilicifolia Mart. ex Reissek: Inhibition of LDL oxidation, glycation, lipid peroxidation, target enzymes, and microbial growth.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds-terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. AIMS OF THE STUDY: We aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. MATERIALS AND METHODS: Organic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. RESULTS: HPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 µg/mL and 7.95 µg/mL) compared to acarbose (0.144 µg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. CONCLUSION: This study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.

Annona crassiflora Mart. Fruit Peel Polyphenols Preserve Cardiac Antioxidant Defense and Reduce Oxidative Damage in Hyperlipidemic Mice.

Dyslipidemia and oxidative stress are directly related to the pathogenesis of cardiovascular diseases. Annona crassiflora Mart. (ACM) has been traditionally used in folk medicine to alleviate inflammation and pain. This plant is rich in polyphenols, which exhibit high antioxidant capacity. The present study aimed to elucidate the antioxidant properties of ACM in the heart of hyperlipidemic mice. The animals were orally administered either a crude ethanol extract (CEAc) or a polyphenols-rich fraction (PFAc) obtained from ACM fruit peel. There were correlations between blood and fecal biochemical data with cardiac oxidative stress biomarkers. Here, the pre-treatment with CEAc for 12 d led to an increase in glutathione content (GSH) and a reduction in the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase. Moreover, PFAc was found to enhance the total antioxidant capacity as well as GSH, SOD and CAT activities, which were reduced by Triton WR-1339-induced hyperlipidemia. Moreover, the administration of PFAc before the treatment resulted in a decrease in protein carbonylation and lipid peroxidation levels, as well as a reduction in the activities of glutathione reductase and glucose-6-phosphate dehydrogenase. ACM fruit peel showed improvement in the glutathione system, mainly its polyphenols-rich fraction, indicating a potential cardioprotective antioxidant usage of this plant extract.

Antioxidant compounds from Annona crassiflora fruit peel reduce lipid levels and oxidative damage and maintain the glutathione defense in hepatic tissue of Triton WR-1339-induced hyperlipidemic mice.

Dyslipidemia is a risk factor for the pathogenesis of several diseases, such as obesity, hypertension, atherosclerosis and cardiovascular diseases. In addition to interfering with serum concentrations of cholesterol and triglycerides, hyperlipidemia is involved in oxidative stress increase and reduction of the endogenous antioxidant defenses. The fruit peel of Annona crassiflora crude extract (CEAc) and its polyphenols-rich fraction (PFAc) were investigated against hypertriglyceridemia, hypercholesterolemia and hepatic oxidative stress in Triton WR-1339-induced hyperlipidemic mice. Lipid parameters in serum, feces and liver, as well as hepatic oxidative status, and enzymatic and non-enzymatic antioxidant defense systems were analyzed. Pre-treatment with CEAc for 12 days decreased hepatic triglycerides and total cholesterol, and similar to PFAc, increased the high-density lipoprotein level. There were reductions in lipid peroxidation and protein carbonylation, as well as restoration of the glutathione defense system and total thiol content in the liver of the hyperlipidemic mice treated with PFAc. The fruit peel of A. crassiflora, a promising natural source of bioactive molecules, showed a potential lipid-lowering action and hepatoprotective activities triggered by reduction of oxidative damage and maintenance of the enzymatic and non-enzymatic antioxidant systems impaired by the hyperlipidemic state.

Palmitate treated-astrocyte conditioned medium contains increased glutathione and interferes in hypothalamic synaptic network in vitro.

Excessive fat consumption increases the level of fatty acids (FAs) in the blood, which reach the hypothalamus and damage the circuit related to energy balance. In the present study, we used palmitate in a primary culture of purified astrocytes to mimic the fat-rich environment found in obesity. Our results showed increased glial fibrillary acidic protein (GFAP) reactivity in hypothalamic astrocytes compared to cortical astrocytes. In addition, palmitate-treated astrocytes showed no significant changes in cytokine expression and an upregulation of glutathione in the culture medium that may serve as an intrinsic neuroprotective property against excess FA. Additionally, purified hypothalamic neurons were incubated with palmitate-treated astrocyte-conditioned medium (MPAL). MPAL treated-neurons exhibited a reduction in excitatory synapses and enhanced neuritogenesis. Our results suggest that hypothalamic astrocytes react to palmitate differently than cortical astrocytes and influence the behavior of the neural network related to energy balance. Our work brings a better understanding of the interactions among hypothalamic neurons in a high FA environment, similarly to obesity induced by a high-fat diet.