Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as ß-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 µg/mL; STIG and ß-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

Novel steroid derivatives: synthesis, antileishmanial activity, mechanism of action, and in silico physicochemical and pharmacokinetics studies.

The search for new drugs for the treatment of leishmaniasis is an important strategy for improving the current therapeutic arsenal for the disease. There are several limitations to the available drugs including high toxicity, low efficacy, prolonged parenteral administration, and high costs. Steroids are a diverse group of compounds with various applications in pharmacology. However, the antileishmanial activity of this class of molecules has not yet been explored. Therefore, in the present study, we investigated the antileishmanial activity and cytotoxicity of novel steroids against murine macrophages with a focus on the derivatives of cholesterol (CD), cholic acid (CA), and deoxycholic acid (DA). Furthermore, the mechanism of action of the best compound was assessed, and in silico studies to evaluate the physicochemical and pharmacokinetic properties were also conducted. Among the sixteen derivatives, schiffbase2, CD2 and deoxycholic acid derivatives (DOCADs) were effective against promastigotes of Leishmania species. Despite their low toxicity to macrophages, the majority of DOCADs were active against intracellular amastigotes of L. amazonensis, and DOCAD5 exhibited the best biological effect against these parasitic stages (IC50 = 15.34 µM). Neither the CA derivatives (CAD) nor DA alone inhibited the intracellular parasites. Thus, the absence of hydroxyl in the C-7 position of the steroid nucleus, as well as the modification of the acid group in DOCADs were considered important for antileishmanial activity. The treatment of L. amazonensis promastigote forms with DOCAD5 induced biochemical changes such as depolarization of the mitochondrial membrane potential, increased ROS production and cell cycle arrest. No alterations in parasite plasma membrane integrity were observed. In silico physicochemical and pharmacokinetic studies suggest that DOCAD5 could be a good candidate for an oral drug. The data demonstrate the potential antileishmanial effect of certain steroid derivatives and encourage new in vivo studies.