Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

Abstract

Atranorin (ATR) is the main compound from the lichen Cladina kalbii Ahti, which grows in the arid regions of northeastern Brazil. This study was conducted to evaluate the anti-inflammatory and toxicological properties of ATR. To evaluate anti-inflammatory properties, paw edema was induced by injecting 0.1 mL of carrageenan into the subplantar region of the right hind paw of rats, and leukocyte migration was induced by injection of 500 µL of carrageenan into the peritoneal cavity of mice. In addition, we determined ATR cytotoxicity in L929 cells by MTT assay and acute (5 g/kg-single dose) and subchronic (50 mg/kg-30 days) toxicity tests in Wistar rats. The results showed that ATR (100 mg/kg and 200 mg/kg) exhibited significant anti-inflammatory activity (paw edema and leukocyte migration). In the acute toxicity test, the animals showed hypoactivity and lethargy during the initial period (first 6 hours) and increase in total protein, total and indirect bilirubin, and alkaline phosphatase after 14 days in ATR-treated male rats. The subchronic toxicity test revealed increases in total protein, globulin, gamma-glutamyl transferase, alkaline phosphatase, and total and direct bilirubin in ATR-treated female rats. Histological analysis revealed no changes in the architecture and morphology of the organs. These results suggest that ATR has significant anti-inflammatory activity, with no significant acute and subchronic toxicity or cytotoxicity.Uniterms: Cladina kalbii/pharmacognosy. Atranorin/anti-inflamatory activity. Atranorin/toxicity. Medicinal plants.Atranorina (ATR) é o principal composto do líquen Cladina kalbii Ahti, que cresce em terras áridas do nordeste brasileiro. Este estudo foi realizado para avaliar as propriedades antiinflamatórias e toxicológicas da ATR. Para avaliar as propriedades antiinflamatórias, o edema de pata foi induzido, administrando-se 0,1 mL de carragenina na região subplantar da pata traseira direita e a migração leucocitária foi induzida pela injeção de 500 µL de carragenina no peritônio. Além disso, determinou-se a citotoxicidade da ATR, utilizando-se a linhagem celular L929, através do teste de MTT e dos testes de toxicidade aguda (5 g/kg -dose única) e subcrônica (50 mg/kg-30 dias) em ratos Wistar. Os resultados mostraram que nas doses de (100 mg/kg e 200 mg/kg) a ATR exibiu atividade antiinflamatória significativa nos ensaios de edema de pata e migração leucocitária. Nos testes de toxicidade aguda, os animais apresentaram hipoatividade e letargia no período inicial (primeiras 6 horas) e aumento das proteínas totais, bilirrubinas total e indireta e fosfatase alcalina depois de 14 dias nos machos tratados. Para o ensaio subcrônico, houve aumento das proteínas totais, gama-glutamil-transferase, fosfatase alcalina e bilirrubina total e direta nas fêmeas tratadas com ATR. Não foram encontradas alterações na arquitetura e morfologia das lâminas histológicas observadas. Esses resultados sugerem que a ATR apresenta atividade antiinflamatória significativa, sem apresentar significativa toxicida...

Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites

“…Meaning that ATR is more likely to affect the viability of piroplasm parasites rather than host cells. This finding conforms to the report by de Melo et al [8] that ATR lacked toxicity in animal studies. In contrast, Zofou et al [13] showed that ATR had mild cytotoxic action on LLC/MK2 monkey kidney epithelial cells.…”

“…Whereas oral administration of HYD and DFMO exhibited a chemotherapeutic effect lower than the 89% and 91% shown by 17-DMAG [28] and nitidine chloride [27], respectively but similar to that shown by trans-chalcone [22]. These results are compatible with those ofde Melo et al [8], who reported the anti-inflammatory activity of ATR, without any significant cytotoxicity in Wistar rats. Although DA is the most effective antibabesial drug used in the veterinary field, it has not been able to remove all parasites from the host animals.…”

“…ATR also reportedly possesses antimalarial activity toward the chloroquine-resistant W-2 and the CAM10 and SHF4 Plasmodium falciparum isolates [13,14]. Experiments on animals revealed the antioxidant as well as anti-inflammatory potentials of ATR which indicate that it might be an important therapeutic component in managing inflammatory disorders because it has a demonstrated active redox action and thus acts as either a pro-oxidant or antioxidant agent in addition to its cytoprotective efficacy on cells under oxidative stress [8,15]. ATR revealed other interesting impacts on cancer cells due to its capacity to intercalate with DNA and prevent topoisomerase II enzyme, without affecting topoisomerase I [16].…”

“…It was first isolated by Hesse in 1898 and since then its pharmacological and biological properties have been extensively examined and evaluated [6]. Notably, previous studies documented its in vitro as well as in vivo activities as an anti-inflammatory, antioxidant, analgesic, immunomodulatory, anticancer, antiprotozoal, antiviral, antifungal, and antibacterial agent against Gram-negative bacteria [7][8][9][10]. Ranković et al [11] documented the potent antibacterial activity of ATR against the most dangerous respiratory tract bacteria, Staphylococcus aureus, comparable to streptomycin.…”

Lichens as a source of chemical compounds with anti-inflammatory activity

“…The results proved the anti-inflammatory properties of atranorin. Moreover, it was stated that the depside is a safe compound, since the experiment conducted in rats showed no symptoms of sub-acute (50 mg/kg/day for 30 days) and acute (5 g/kg) toxicity [8].…”