Infusion from Miconia albicans (Melastomataceae) leaves exhibits anti-inflammatory and anti-hyperalgesic activities without toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Miconia albicans have been extensively used as a traditional medicine to treat inflammation, infection, arthritis, joint pain, and analgesia, which can be purchased easily. Nevertheless, the scientific evidence of chemical profile identification and toxicity investigation is meager. AIM OF THE STUDY: This study aimed to determine the chemical profile of Miconia albicans aqueous extract (MAAE), to investigate its anti-inflammatory and hyperalgesic effects, and toxicity (acute and repeated-dose oral) in vivo studies. MATERIALS AND METHODS: MAAE was obtained by infusion method and its chemical constituents were analyzed and annotated by LC-DAD-MS. The in vivo tests were performed with male and female Swiss mice. Toxicity studies were examined by acute (2000 mg/kg) and repeated-dose oral assays (51.2; 256; 1280 mg/kg); anti-inflammatory evaluation was performed by paw edema and leukocyte migration, and anti-hyperalgesic properties were analyzed by abdominal writhing induced by acetic acid and formalin. The animals were treated by oral means with 51.2, 256, and 1280 mg/kg of MAAE. RESULTS: Twenty-four compounds were annotated from MAAE by LC-DAD-MS, such as ellagitannins, ellagic acid derivatives, flavan-3-ol, and O-glycosylated compounds, including flavonols, triterpenes, and megastigmanes. MAAE induced no significant toxicological effects in the acute and repeated-dose oral assays at lower doses and no histological changes were observed. Hematological and biochemical showed no significant alterations. The oral administration of MAAE 256 mg/kg inhibited the edematogenic effect and reduced the leukocyte migration. In addition, MAAE decreased the abdominal writhings induced by acetic acid and the paw-licking time by formalin assay. CONCLUSION: MAAE showed a significant reduction in inflammatory levels and leukocyte migration, revealing anti-hyperalgesic properties. Additionally, MAAE revealed no acute and repeated-doses toxicities.

Protease inhibitor from Libidibia ferrea seeds attenuates inflammatory and nociceptive responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz is a Brazilian native tree locally known as jucá and pau-ferro, and it has been used in folk medicine for relieving, asthma, bronchitis, sore throat, rheumatism, enterocolitis and fever. The anti-inflammatory properties of L. ferrea were confirmed for its stem, fruit, leaves, bark and seeds extracts, however little is known about the natural compounds that may be associated with that response. AIM OF THIS STUDY: In a normal physiological condition, many enzymes play an important role in catalyzing biological functions. Among them, proteases are of great interest. Although they take part of many biological systems, as the inflammatory process, when deregulated, proteases may cause system malfunctions, such as under- or overproduction of cytokines, or immune cells activation. Thus, protease inhibitors prevent these immune responses by regulating proteases. The objective of this study was to evaluate the anti-inflammatory and anti-nociceptive response of a protease inhibitor purified from L. ferrea seeds (LfTI). MATERIALS AND METHODS: In vitro (5, 50 and 250 µg/mL of LfTI) and in vivo (0.6, 3 e 15 mg/kg of LfTI) assays were performed. Male Swiss mice weighing 18-25 g were used for cell harvesting and for the in vivo assays. The anti-inflammatory activity was analyzed in vitro by macrophage cytotoxicity, hydrogen peroxide (H2O2) production, and cell adhesion assays; and in vivo by leukocyte recruitment, nitric oxide (NO) production, vascular permeability, paw edema and mast cell degranulation assays. The anti-nociceptive activity was evaluated through abdominal writhing test induced by acetic acid and formalin sensitization. RESULTS: Our results showed that, in vitro, LfTI is not cytotoxic. Also, LfTI (50 µg/mL) inhibited macrophage H2O2 production (48.2%), and adhesion (48.4%). LfTI (0.6, 3 e 15 mg/kg) decreased polymorphonuclear cell recruitment dose-dependently, and it inhibited NO production (53%), vascular permeability (40.7%) and paw edema at 3 mg/kg at different time, but it did not inhibit mast cell degranulation. Besides, LfTI did not inhibit either the number of writhing or the licking time in the formalin test in the second phase (inflammatory). However, LfTI (3 mg/kg) inhibited licking time at the first phase (neurogenic) in the formalin sensitization (46.1%). CONCLUSIONS: Our results show that LfTI has anti-inflammatory and antinociceptive (neurogenic pain) effects, and these effects might be associated with the inhibition of inflammatory proteases and/or protease-activated receptors activation hindering.

Antileishmanial Activity, Toxicity and Mechanism of Action of Complexes of Sodium Usnate with Lanthanide Ions: Eu(III), Sm(III), Gd(III), Nd(III), La(III) and Tb(III).

Leishmaniases are neglected diseases with limited therapeutic options. Diffuse cutaneous leishmaniasis can occur in Brazil due to Leishmania amazonensis. This study details the antileishmanial activity and cytotoxicity of complexes of sodium usnate (SAU) with lanthanide ions ([LnL3 (H2O)x] (Ln = La(III), Nd(III), Gd(III), Tb(III), Eu(III) and Sm(III); L = SAU). All lanthanide complexes were highly active and more potent than SAU against L. amazonensis promastigotes and intracellular amastigotes (Pro: IC50 < 1.50 µM; Ama: IC50 < 7.52 µM). EuL3·3H2O and NdL3·3H2O were the most selective and effective on intracellular amastigotes, with a selectivity index of approximately 7.0. In silico predictions showed no evidence of mutagenicity, tumorigenicity or irritation for all complexes. Treatment with EuL3·3H2O triggered NO release even at the lowest concentration, indicating NO production as a mechanism of action against the parasite. Incubating promastigotes with the lanthanide complexes, particularly with SmL3·4H2O and GdL3·3H2O, led to a change in the mitochondrial membrane potential, indicating the ability of these complexes to target this essential organelle. The same complexes caused cell death through cell membrane disruption, but their relationship with early or late apoptotic processes remains unclear. Thus, the inclusion of lanthanide ions in SAU improves selectivity with a promising mechanism of action targeting the mitochondria.

Baccharis trimera Infusion Reduces Macrophages Activation and High-Fat Diet-Induced Metabolic Disorders in Mice.

The aim of this study is to evaluate the efficacy of Baccharis trimera infusion on high-fat diet-induced metabolic disorders in mice and macrophages activation. This study evaluated obesity, insulin resistance, dyslipidemia and hepatic steatosis induced by a high-fat diet in Swiss mice. Cellular parameters in macrophages, such as cell viability (MTT), the production and release of nitric oxide (NO) and hydrogen peroxide (H2O2), cell spreading, cell adhesion and phagocytosis were determined. Our results showed that treatment with B. trimera prevented the mentioned conditions, except for the production of hydrogen peroxide. B. trimera prevented the development of obesity and associated comorbidities, as well as activation of macrophages. In conclusion, B. trimera is able to prevent obesity and metabolic disorders and macrophages activation, minimizing inflammation and validating the popular use of this plant tea.

Linseed, Baru, and Coconut Oils: NMR-Based Metabolomics, Leukocyte Infiltration Potential In Vivo, and Their Oil Characterization. Are There Still Controversies?

Different fatty acid proportions produce potential inflammatory and metabolic changes in organisms. However, the evidence for how each fatty acid mediates the metabolic pathway, and its lipid stability remains controversial. To resolve this controversy, the present study investigated the metabolic effects of cold-pressed linseed (LG), coconut (CG), and baru (BG) oils in comparison to those of soybean oil (SG) in mice, in terms of their oil characterization and stability. The quality analysis showed less oxidative behavior among PUFA-rich oils (SO, BO, and LO, with induction periods lower than 2 h compared to 39.8 h for CG), besides the high contents of tocopherols and carotenoids in SG and LG. In the experimental study, CG presented higher triglyceride (257.93 ± 72.30) and VLDL-cholesterol levels (51.59 ± 14.46, p < 0.05), while LG reduced LDL levels (59.29 ± 7.56, p < 0.05) when compared to SG (183.14 ± 22.06, 36.63 ± 4.41 and 131.63 ± 29.0, respectively). For visceral fats, the adiposity index was lower for BG (7.32 ± 3.13) and CG (9.58 ± 1.02, p < 0.05) in relation to SG (12.53 ± 2.80), and for leukocyte recruitment, CG presented lower polymorphonuclear (PMN) (p < 0.0001) and mononuclear (MN) (p < 0.05) cell infiltration, demonstrating anti-inflammatory potential. In NMR-based metabolomics, although CG presented higher values for the glucose, lactate, and LDL/VLDL ratio, this group also evidenced high levels of choline, a lipotropic metabolite. Our study emphasized the controversies of saturated fatty acids, which impair serum lipids, while alfa-linolenic acid presented cardioprotective effects. However, coconut oil also has a positive immunomodulatory pathway and was found to reduce visceral bodyfat in mice. Therefore, for future applications, we suggest a combination of lauric and al-fa-linolenic acid sources, which are present in coconut and linseed oil, respectively. This combination could be less obesogenic and inflammatory and exert cardioprotective action.