Cordia oncocalyx and oncocalyxones: From the phytochemistry to the anticancer action and therapeutic benefits against chronic diseases.

Cordia oncocalyx Allemão is an endemic economically underexploited plant from Brazilian semi-arid region. Herein, we carried out a well-defined bibliographic review about the pharmacological activities of oncocalyxones from C. oncocalyx and mechanisms responsible for the biomedical properties. MeSH terms were used in the scientific databases for a narrative exploration. Technological development and bioproducts were also examined. Cordia oncocalyx is a deciduous tree of sexual reproduction rich in terpenoid quinones. Among them, oncocalyxone A, a 1,4-benzoquinone, the main compound from heartwood ethanol extracts, revealed anti-inflammatory and anti-edematogenic actions induced by carrageenan and dextran and antinociceptive potential in mice provoked by acetic acid and formalin. Oncocalyxone A inhibits platelet aggregation via activation of the soluble guanylate cyclase enzyme and blocks glycation processes. In addition to the antimicrobial effects against protozoa, fungi and bacteria and relaxation of smooth muscles, oncocalyxone A reduces mean blood pressure and glycemia in diabetic rats, decreases glomerular filtration parameters and tubular transport of electrolytes, and presents in vitro antimitotic and cytotoxic action upon different types of cancers, including resistant lung carcinoma lines. It has low oral acute toxicity (LD50 > 2000 mg/kg) and activates cellular apoptosis through the production of free radicals and interactions with DNA. However, no patents were found, which also emphasizes that Brazil, as the cradle of the main articles on C. oncocalyx, is wasting time and money. Moreover, slight systemic deleterious effects in mammals stimulate the use of oncocalyxone A and related compounds as lead constituents of safer drugs against chronic diseases.

Non-clinical toxicity of (+)-limonene epoxide and its physio-pharmacological properties on neurological disorders.

The compound (+)-limonene epoxide has antioxidant, anxiolytic, and antihelminthic properties. However, investigations to determine its long-term exposure were not performed. We investigated the systemic toxicological profile after chronic exposure as well as the antidepressant and antiepileptic potentialities of (+)-limonene epoxide on mice. Initially, we evaluated acute toxicity on Artemia salina nauplii and cytotoxicity on mice erythrocytes and peripheral blood mononuclear cells (PBMC). Aftterwards, mice were chronically treated for 120 days by gavage with (+)-limonene epoxide (25, 50, and 75 mg/kg/day) and this exposure was assessed by pathophysiological measurements. For antidepressant and anticonvulsivant analysis, we performed the forced swimming and tail suspension protocols and pentylenetetrazol- and picrotoxin-induced seizures, respectively. (+)-Limonene epoxide showed a LC50 value of 318.7 µg/mL on A. salina shrimps, caused lysis of red blood cells at higher concentrations only but did not show cytotoxicity on PMBC, which suggests pharmacological safety if plasma concentrations do not exceed 100 µg/mL. Macroscopic, hematological, clinical chemistry, and nutritional changes were not detected, though focal areas of hepatic necrosis, inflammatory infiltrate, and karyolysis have been detected at 75 mg/kg/day. The compound inhibited the developing of pentylenetetrazol- and picrotoxin-induced seizures, decreased deaths, and reduced immobility times, mainly at 75 mg/kg. So, it reversed reserpine effects, suggesting antidepressant effects should be linked to serotonergic and/or adrenergic transmission. It is feasible that (+)-limonene epoxide plays a benzodiazepine-like anticonvulsive action and may be also recommended as an antidote for poisonings caused by central depressants.