In silico evaluation and in vitro growth inhibition of Plasmodium falciparum by natural amides and synthetic analogs.

Malaria, caused by protozoa of the genus Plasmodium, is a disease that infects hundreds of millions of people annually, causing an enormous social burden in many developing countries. Since current antimalarial drugs are starting to face resistance by the parasite, the development of new therapeutic options has been prompted. The enzyme Plasmodium falciparum enoyl-ACP reductase (PfENR) has a determinant role in the fatty acid biosynthesis of this parasite and is absent in humans, making it an ideal target for new antimalarial drugs. In this sense, the present study aimed at evaluating the in silico binding affinity of natural and synthetic amides through molecular docking, in addition to their in vitro activity against P. falciparum by means of the SYBR Green Fluorescence Assay. The in vitro results revealed that the natural amide piplartine (1a) presented partial antiplasmodial activity (20.54 µM), whereas its synthetic derivatives (1m-IC50 104.45 µM), (1b, 1g, 1k, and 14f) and the natural amide piperine (18a) were shown to be inactive (IC50 > 200 µM). The in silico physicochemical analyses demonstrated that compounds 1m and 14f violated the Lipinski's rule of five. The in silico analyses showed that 14f presented the best binding affinity (- 13.047 kcal/mol) to PfENR and was also superior to the reference inhibitor triclosan (- 7.806 kcal/mol). In conclusion, we found that the structural modifications in 1a caused a significant decrease in antiplasmodial activity. Therefore, new modifications are encouraged in order to improve the activity observed.

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Extruded sorghum (Sorghum bicolor L.) reduces metabolic risk of hepatic steatosis in obese rats consuming a high fat diet.

The study investigated the effect of extruded sorghum flour (ESF) in a high fat diet (HFD) on biometric measurements and hepatic lipogenesis. Male Wistar rats were fed a normal diet (AIN-93M), HFD, HFD plus ESF replacing 50% cellulose and 100% corn starch (HFDS50), or HFD plus ESF replacing 100% cellulose and 100% corn starch (HFDS100) for eight weeks. ESF reduced the body mass index and liver weight of obese rats. Additionally, ESF reduced hepatic lipogenesis by increasing adiponectin 2 receptor gene expression and gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα), while reducing the gene expression of sterol regulatory element-binding transcription factor 1. Molecular docking analysis revealed the affinity of ESF compounds (luteolinidin, apigeninidin, 5-methoxy-luteolinidin, and 7-methoxy-apigeninidin) with the PPAR-α receptor. Histological analysis confirmed the decreased grade of hepatic steatosis in obese rats. These data indicate the potential of ESF to reduce metabolic risk of hepatic steatosis associated with lipogenesis and obesity.

Bacupari peel extracts (Garcinia brasiliensis) reduces the biometry, lipogenesis and hepatic steatosis in obese rats.

The aim was to evaluate the effect of the ethanol extract of bacupari peel (EEB) on biometric measurements, hepatic lipogenesis and progression of non-alcoholic fatty liver disease (NAFLD) in obese Wistar rats. Chemical analysis of the bacupari peel extract identified 7-epiclusianone as the major constituent (140.02 mg/g) followed by morelloflavone (35.86 mg/g). Animals treated with high fat diet plus EEB (BHFD) reduced body mass index (BMI), liver weight and hepatosomatic index in relation to the obese control. The food intake was similar between hyperlipid group (HFD) groups with or without EEB. However, the normal control group (AIN-93 M) presented higher food intake and lower final weight compared to the obese control (HFD). The PPAR-α, CPT-1a and the ADIPOR2 genes expressions, and the concentration of the PPAR-α and the adiponectin protein level increased in the BHFD group in relation to the obese control. The EEB promoted reduction of the SREBP-1c gene expression and the percentage of hepatic fat and the degree of steatosis in relation to HFD. It was concluded that EEB showed a protective effect on NAFLD, as it promoted a reduction in BMI, induced lipid oxidation, reduced lipogenesis and hepatic steatosis. Moreover, our results suggest an interaction that can lead to an agonist activity of the EEB to the PPAR-α receptor.