Averrhoa carambola leaves prevent dyslipidemia and oxidative stress in a rat model of poloxamer-407-induced acute hyperlipidemia

Background: The star fruit [Averrhoa carambola L (Oxalidaceae)] is traditionally used in the treatment of many ailments in many countries. It possesses several pharmacological activities, including antioxidant and anti-inflammatory effects. However, it contains the neurotoxic caramboxin and its high content of oxalic acid limits its consumption by individuals with compromised kidney function. This study assessed the anti-hyperlipidemic and antioxidant activities of different fractions of the methanolic extract of A. carambola leaves (MEACL). Methods: The antioxidant activity was investigated using FRAP, and ABTS and DPPH radical-scavenging assays and the inhibitory activity toward pancreatic lipase (PL) and HMG-CoA reductase was assayed in vitro. Acute hyperlipidemia was induced by poloxamer-407 (P-407) in rats and different fractions of MEACL (n-hexane, chloroform, n-butanol, ethyl acetate (EA), water, and chloroform) were orally administered. Cholesterol and triglycerides were determined at 0, 12, 24, and 48 h and LDL-C, vLDL-C, HDL-C, lipid peroxidation (LPO) and antioxidants were assayed after 48 h. The expression of ABCA1, ABCG5, ABCG8, LDL-R, SREBP-1, and SREBP-2 and the activity of HMG-CoA reductase were assayed in the liver of P-407-administered rats treated with the EA fraction. Results: The in vitro data revealed potent radical-scavenging activities of MEACL fractions with the most potent effect showed by the EA fraction that also suppressed the activities of HMG-CoA reductase and PL. In P-407-induced hyperlipidemic rats, all fractions prevented dyslipidemia as shown by the decrease in total cholesterol, triglycerides, LDL-C, vLDL-C and atherogenic index. MEACL and its fractions prevented LPO and boosted GSH, superoxide dismutase, glutathione peroxidase, and catalase in P-407-administered rats. The EA fraction showed more effective anti-hyperlipidemic and antioxidant effects than other fractions and downregulated SREBP-2 while upregulated ABCA1 and LDL-R and ameliorated LPL and HMG-CoA reductase in hyperlipidemic rats. Conclusion: MEACL showed in vitro and in vivo antioxidant activity and the EA fraction significantly ameliorated dyslipidemia in a rat model of P-407-induced acute hyperlipidemia by modulating LPL, PL, HMG-CoA reductase, and cholesterolgenesis-related factors. Therefore, the leaves of A. carambola represent a safe alternative for the star fruit particularly in kidney disease patients, and the EA is the most effective anti-hyperlipidemic and antioxidant fraction

Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies

Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC values of lower than 20.5 μM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC values of 1.24 and 1.78 μM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while γ-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that α-mangostin, γ-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations

Densidade de plantio e idade de colheita de quebra-pedra [Phyllanthus amarus (Schumach. & Thonning) genótipo Unicamp-CPQBA 14] na produtividade de filantina Density of planting and age of Phillanthus amarus genotype UNICAMP/CPQBA-14 on the productivity of phyllanthin

Avaliou-se o efeito da densidade de plantio e da idade de Phyllanthus amarus CPQBA-14, sobre o teor e produtividade de filantina. O delineamento experimental foi em blocos ao acaso, em esquema fatorial 4 x 6, com cinco repetições, envolvendo 4 tratamentos de densidade de plantio (400.000 pl ha -1; 200.000 pl ha -1; 100.000 pl ha -1 e 66.667,68 pl ha -1) com 6 colheitas (30, 45, 60, 75, 90 e 105 dias após o transplante (DAT)). Os dados foram submetidos a Análise de Variâncias e Regressão (P > 0.001). Para o teor de Filantina, foram observados efeitos significativos e independentes dos tratamentos de idade da planta na colheita e densidade de plantio. O teor de filantina aumentou linearmente com a idade da planta, atingindo o máximo aos 105 DAT, com teor de 11,52 g Kg-1. O adensamento populacional estimado que proporcionou máximo teor de filantina (8,66 g kg-1) foi de 299.860 pl ha-1. A produtividade de filantina apresentou interação significativa entre densidade de plantio e idade da planta na colheita. Observou-se que ao longo do crescimento da planta, os tratamentos com 200 e 400.000 pl ha -1 apresentaram as maiores produtividades de filantina (39,3 e 37,8 kg ha-1) aos 97,12 e 95,17 DAT, respectivamente. Conclui-se que o espaçamento apropriado para o melhor arranjo espacial de cultivo é de 299.860 pl ha-1 para as produtividades de 3.974,19 Kg (massa de matéria seca foliar) x 0,00866 kg (teor de filantina) = 34,416 kg ha-1 de filantina, com colheita programada aos 97 DAT.<br>The effect of planting density and age of Phyllanthus amarus- genotype CPQBA-14, on the content and productivity of phyllanthin were evaluated. The experimental design was randomized blocks in factorial scheme 4 x 6, with five replicates, consisting of 4 treatments of planting density (400.000 pl ha-1; 200.000 pl ha-1; 100.000 pl ha-1 and 66667.68 pl ha-1) with six ages of plants (30, 45, 60, 75, 90 and 105 days after transplanting (DAT)). Data were subjected to analysis of variance and regression (P>0.005). For phyllanthin content independent and significant effects of harvest and planting density were observed. The phyllanthin contents increased with plant age, peaking at 105 DAT, with a content of 11.52 g kg-1. The estimated population density that provided the high phyllanthin contents (8.66 g kg-1) was at 299.860 pl ha-1. The productivity of phyllanthin showed significant interaction between planting density and plants ages. It was observed during the plant growth, the treatments with 200 and 400.000 pl ha -1 had the highest yield of phyllanthin (39.3 and 37.8 kg ha-1) with 95.17 and 97.12 DAT, respectively. We conclude that the proper spacing for best spatial arrangement of the cultivation is 299.860 pl ha-1 for the yield of 3974.19 kg (dry weight leaf) x 0.00866 kg (phyllanthin contents) = 34.416 kg ha-1 of phyllanthin with harvest scheduled at 97 DAT