ANTI-INFLAMMATORY EFFECT OF Anadenanthera colubrina var. cebil (Griseb.) Altschul IN EXPERIMENTAL ELASTASE-INDUCED PULMONARY EMPHYSEMA IN RATS.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have shown promise in the search for new treatments of pulmonary emphysema. Anadenanthera colubrina, a species native to the Caatinga biome in northeastern Brazil, is widely recognized and traditionally employed in the treatment of pulmonary diseases. Many studies corroborate popular knowledge about the medicinal applications of A. colubrina, which has demonstrated a remarkable variety of pharmacological properties, however, its anti-inflammatory and antioxidant properties are highlighted. AIM OF THE STUDY: The objective of this study was to investigate the anti-inflammatory potential of the crude hydroethanolic extract of A. colubrina var. cebil (Griseb.) Altschul on pulmonary emphysema in rats as well as to determine its potential genotoxic and cytotoxic effects using the micronucleus assay. MATERIALS AND METHODS: The stem bark of the plant was collected in Pimenteiras-PI and sample was extracted by maceration using 70% ethanol. A portion of the extract underwent phytochemical analyses using TLC and HPLC. In this study, 8-week-old, male Wistar rats weighing approximately ± 200 g was utilized following approval by local ethics committee for animal experimentation (No. 718/2022). Pulmonary emphysema was induced through orotracheal instillation of elastase, and treatment with A. colubrina extract or dexamethasone (positive control) concomitantly during induction. Twenty-eight days after the initiation of the protocol, plasma was used for cytokine measurement. Bronchoalveolar lavage (BAL) was used for leukocyte count. After euthanasia, lung samples were processed for histological analysis and quantification of oxidative stress markers. The micronucleus test was performed by evaluating the number of polychromatic erythrocytes (PCE) with micronuclei (MNPCE) to verify potential genotoxic effects of A. colubrina. A differential count of PCE and normochromatic erythrocytes (NCE) was performed to verify the potential cytotoxicity of the extract. Parametric data were subjected to normality analysis and subsequently to analysis of variance and Tukey or Dunnett post-test, non-parametric data were treated using the Kruskal-Wallis test with Dunn's post-test for unpaired samples. P value <0.05 were considered significant. RESULTS: The A. colubrina extract did not show a significant increase in the number of MNPCE (p>0.05), demonstrating low genotoxicity. No changes were observed in the PCE/NCE ratio of treated animals, compared with the vehicle, suggesting low cytotoxic potential of the extract. A significant reduction (p<0.05) in neutrophilic inflammation was observed in the lungs of rats treated with the extract, evidenced by presence of these cells in both the tissue and BAL. The extract also demonstrated pulmonary antioxidant activity, with a significant decrease (p<0.05) in myeloperoxidase, malondialdehyde, and nitrite levels. TNFα, IL-1ß, and IL-6 levels, as well as alveolar damage, were significantly reduced in animals treated with A. colubrina extract. Phytochemical analyses identified the presence of phenolic compounds and hydrolysable tannins in the A. colubrina extract. CONCLUSIONS: The findings of this study highlights the safety of the hydroethanolic extract of Anadenanthera colubrina, and demonstrates its potential as a therapeutic approach in the treatment of emphysema. The observed properties of this medicinal plant provide an optimistic outlook in the development of therapies for the treatment of pulmonary emphysema.

The Isopropyl Gallate Counteracts Cyclophosphamide-Induced Hemorrhagic Cystitis in Mice.

Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1ß (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.

Correction to: α-Phellandrene attenuates tissular damage, oxidative stress, and TNF-α levels on acute model ifosfamide-induced hemorrhagic cystitis in mice.

The published online version contains figure in poor quality.

Ethyl ferulate/ß-cyclodextrin inclusion complex inhibits edema formation.

Ethyl ferulate, a phenylpropanoid derived from rice hulls has aroused interest because of its antioxidant, anti-inflammatory and neuroprotective properties. However, it has low solubility in water which compromises the absorption in the gastrointestinal tract, decreases the bioavailability and compromises the reproducibility of the effects in vivo. To increase the solubility of ethyl ferulate, inclusion complexes were obtained by physical mixing, malaxing, lyophilization and spray drying and characterized using thermal analysis, XRD and FTIR. The complexes obtained were evaluated for ethyl ferulate content, stability, dissolution profile and evaluation of anti-inflammatory activity in vivo through carrageenan-induced paw edema model in rats. The inclusion complexes obtained resulted in increased solubility and stability compared to the isolated ethyl ferulate. In addition, the complexes obtained by malaxage, lyophilization and spray drying showed greater inhibition of the edema formation induced by carrageenan compared to ethyl ferulate 100 mg/kg v.o. The inclusion of ethyl ferulate in B-cyclodextrin resulted in the formation of stable inclusion complexes with potent antidematogenic activity possibly attributed to the increased solubility, dissolution profile of the active.

The partial root-zone saline irrigation system and antioxidant responses in tomato plants.

Salinity is a limiting factor that can affect plant growth and cause significant losses in agricultural productivity. This study provides an insight about the viability of partial root-zone irrigation (PRI) system with saline water supported by a biochemical approach involving antioxidant responses. Six different irrigation methods using low and high salt concentrations (S1-0.5 and S2-5.0 dS m-1) were applied, with or without PRSI, so that one side of the root-zone was submitted to saline water while the other side was low salinity water irrigated. The results revealed different responses according to the treatments and the PRSI system applied. For the treatments T1, T2 and T3, the PRSI was not applied, while T4, T5 and T6 treatments were applied with PRSI system. Lipid peroxidation, proline content, and activities of SOD, CAT, APX, GR and GSH in tomato plants subjected to PRSI system were analyzed. Plant growth was not affected by the salt concentrations; however, plants submitted to high salt concentrations showed high MDA content and Na+ accumulation when compared to the control plants. Plants submitted to treatments T4, T5 and T6 with PRSI system exhibited lower MDA compared to the control plants (T1). Proline content and activities of SOD, CAT, APX, GR and GSH content were maintained in all treatments and tissues analyzed, with only exception for APX in fruits and GSH content, in roots. The overall results showed that PRSI system could be an applicable technique for saline water supply on irrigation since plants did not show to be vulnerable to salt stress, supported by a biochemical approach involving antioxidant responses.

α-Terpineol Induces Gastric Retention of Liquids by Inhibiting Vagal Parasympathetic Pathways in Rats.

α-Terpineol is a monoterpene with smooth muscle relaxant properties. In this study, its effects on the gastric emptying rate of awake rats were evaluated with emphasis on the mode by which it induces gastrointestinal actions. Administered by gavage, α-terpineol (50 mg/kg) delayed gastric emptying of a liquid test meal at 10 min postprandial. Hexamethonium or guanethidine did not interfere with the retarding effect induced by α-terpineol, but atropine and L-NG-nitroarginine methyl ester abolished it. In vagotomized rats, α-terpineol did not delay gastric emptying. In isolated strips of gastric fundus, concentration-effect curves in response to carbamylcholine were higher in magnitude after treatment with the monoterpene. α-Terpineol (1 to 2000 µM) relaxed sustained contractions induced by carbamylcholine or a high K+ concentration in a concentration-dependent manner. This relaxing effect was not affected by the presence of L-NG-nitroarginine methyl ester, 1 H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one, tetraethylammonium, or atropine. Smooth muscle contractions induced by electrical field stimulation were inhibited by α-terpineol. In conclusion, α-terpineol induced gastric retention in awake rats through mechanisms that depended on intact vagal innervation to the stomach, which involved cholinergic/nitrergic signalling. Such a retarding effect induced by α-terpineol appears not to result from a direct action of the monoterpene on gastric smooth muscle cells.