Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways.

We aimed to determine the chemical profile and unveil Anadenanthera colubrina (Vell.) Brenan standardized extract effects on inflammatory cytokines expression and key proteins from immunoregulating signaling pathways on LPS-induced THP-1 monocyte. Using the RT-PCR and Luminex Assays, we planned to show the gene expression and the levels of IL-8, IL-1ß, and IL-10 inflammatory cytokines. Key proteins of NF-κB and MAPK transduction signaling pathways (NF-κB, p-38, p-NF-κB, and p-p38) were detected by Simple Western. Using HPLC-ESI-MSn (High-Performance Liquid-Chromatography) and HPLC-HRESIMS, we showed the profile of the extract that includes an opus of flavonoids, including the catechins, quercetin, kaempferol, and the proanthocyanidins. Cell viability was unaffected up to 250 µg/mL of the extract (LD50 = 978.7 µg/mL). Thereafter, the extract's impact on the cytokine became clear. Upon LPS stimuli, in the presence of the extract, gene expression of IL-1ß and IL-10 were downregulated and the cytokines expression of IL-1ß and IL-10 were down an upregulated respectively. The extract is involved in TLR-4-related NF-κB/MAPK pathways; it ignited phosphorylation of p38 and NF-κB, orchestrating a reduced signal intensity. Therefore, Anadenanthera colubrina's showed low cytotoxicity and profound influence as a protector against the inflammation, modulating IL-1ß and IL-10 inflammatory cytokines gene expression and secretion by regulating intracellular NF-κB and p38-MAPK signaling pathways.

Anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic activities of Plinia cauliflora (Mart.) Kausel (Brazilian grape) epicarp.

ETHNOPHARMACOLOGICAL RELEVANCE: Plinia cauliflora (Mart.) Kausel, known in Brazil as jabuticaba or jaboticaba has been used by Brazilian native populations for medicinal purposes, including those related to inflammatory conditions, such as asthma, diarrhea, disorders in female genitourinary tract, and tonsillitis. Inflammation has emerged as a main factor for the oxidative stress, hyperglycemia, and dyslipidemia present in chronic noncommunicable diseases (NCDs). Such disturbances have been a leading cause of death worldwide for decades, despite significant efforts in developing new therapies. Therefore, strengthening the relevance of ethnobotanic approaches, as P. cauliflora has the potential to become a natural, native, and traditional product to prevent and treat inflammation-associated diseases more effectively for more people. AIM OF THE STUDY: Evaluate anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic properties of hydroethanolic extract of P. cauliflora epicarps (PcE). MATERIALS AND METHODS: Phytochemical compound from the PcE were identified through HPLC-DAD-ESI-MSn analysis. Antioxidant activity was determined by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The anti-inflammatory potential was investigated by carrageenan-induced paw edema and peritonitis in mice. Analgesic effect was assessed, in mice, though hot plate test and acetic acid-induced abdominal writhing. Antidiabetic and hypolipidemic potential were evaluated using alloxan-induced diabetic mice. RESULTS: Tannins, phenolic acids, and their derivatives were the predominant phytochemicals found. Overall, PcE showed different properties related to the treatment of clinical conditions associated with chronic diseases as a potent antioxidant activity, demonstrating a radical scavenging action similar to gallic acid. PcE oral administration also significantly reduced inflammation induced by paw edema and partially blocked leukocyte migration. Moreover, PcE produced peripheral and central analgesic effects, as evaluated in the writhing model and hot plate tests. Treatment with PcE significantly improved glucose levels and lipid markers in diabetic mice. CONCLUSIONS: P. cauliflora fruits are rich sources of secondary metabolites, mainly tannins and phenolic acids with high biological potential, which can effectively contribute to the approach of preventing and controlling chronic NCDs.

Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.

Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for Leishmania major and L. (Viannia) braziliensis. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against L. major and 21 lignans against L. braziliensis, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species Justicia aequilabris (Nees) Lindau. All of the identified compounds were able to inhibit the growth of L. braziliensis promastigotes, with the most active compound, (159) epipinoresinol-4-O-ß-d-glucopyranoside, presenting an IC50 value of 5.39 µM and IC50 value of 36.51 µM for L. major. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis.