Pellucidin A promotes antinociceptive activity by peripheral mechanisms inhibiting COX-2 and NOS: In vivo and in silico study.

Peperomia pellucida (PP) belongs to the Peperomia genus, which has a pantropic distribution. PP is used to treat a wide range of symptoms and diseases, such as pain, inflammation, and hypertension. Intriguingly, PP extract is used by different tropical countries for its anti-inflammatory and antinociceptive effects. In fact, these outcomes have been shown in animal models, though the exact bioactive products of PP that exert such results are yet to be discovered. To determine and elucidate the mechanism of action of one of these compounds, we evaluated the antinociceptive effect of the novel dimeric ArC2 compound, Pellucidin A by using in vivo and in silico models. Animals were then subjected to chemical, biphasic and thermal models of pain. Pellucidin A induced an antinociceptive effect against chemical-induced pain in mice, demonstrated by the decrease of the number of writhes, reaching a reduction of 43% and 65% in animals treated with 1 and 5 mg/kg of Pellucidin A, respectively. In the biphasic response (central and peripheral), animals treated with Pellucidin A showed a significant reduction of the licking time exclusively during the second phase (inflammatory phase). In the hot-plate test, Pellucidin A did not have any impact on the latency time of the treated animals. Moreover, in vivo and in silico results show that Pellucidin A's mechanism of action in the inflammatory pain occurs most likely through interaction with the nitric oxide (NO) pathway. Our results demonstrate that the antinociceptive activities of Pellucidin A operate under mechanism(s) of peripheral action, involving inflammatory mediators. This work provides insightful novel evidence of the biological properties of Pellucidin A, and leads to a better understanding of its mechanism of action, pointing to potential pharmacological use.

Allantoin reduces cell death induced by cisplatin: possible implications for tumor lysis syndrome management.

Massive lysis of tumor mass in cancer patients under chemotherapy regimens generates high levels of uric acid, leading to what is known as tumor lysis syndrome (TLS). Rasburicase, a recombinant urate oxidase, converts urate to allantoin, which is readily excreted by the kidneys. Even though there is a high production of allantoin from urate in cancer patients following rasburicase treatment, there are no studies on how allantoin excess could interfere with chemotherapy. We have evaluated allantoin interference with cisplatin efficiency on the lung cancer cell line H460 in vitro. The cells were treated with cisplatin (33 µM), with or without allantoin, for 48 h, in the presence or absence of UV light, and N-acetyl-L-cysteine (NAC) for 24 h. Cell viability, cell cycle, ROS production, apoptosis and immunoblot assays were performed. We showed that allantoin reduced the apoptosis induced by cisplatin in the H460 cell line. However, the activity of carboplatin and oxaliplatin, betulinic acid, TIBA, UV and H2O2 was not affected by allantoin. NMR spectroscopy showed that allantoin reduces cisplatin activity through direct interaction with cisplatin.

Effects of Rosmarinus officinalis essential oil on germ tube formation by Candida albicans isolated from denture wearers.

INTRODUCTION: The aim of this study was to investigate the effects of Rosmarinus officinalis essential oil on germ tube formation by Candida albicans isolated from denture wearers. METHODS: Ten C. albicans isolates recovered from denture wearers were tested using 10% fetal bovine serum with or without 4% R. officinalis essential oil. RESULTS: The essential oil from R. officinalis completely inhibited germ tube formation in the investigated C. albicans isolates. CONCLUSIONS: The results demonstrate that the essential oil of R. officinalis modulates C. albicans pathogenicity through its primary virulence factor (i.e., germ tube formation was suppressed).

Chemical constituents and allelopathic and antioxidant activities of Alchorneopsis floribunda Müll. Arg. (Euphorbiaceae).

Chemical investigation of extracts from the stems and leaves of Alchorneopsis floribunda Müll. Arg., collected in the Amazon region, was performed. The main isolated compounds were triterpenes (α-amyrin, ß-amyrin, lupeol, betulin, betulinic acid, uvaol, erythrodiol and oleanolic acid) and phenolic acid derivatives from 4-hydroxybenzoic acid (gallic and protocatechuic acids and isocorilagin). In the germination assays, high inhibitory allelopathic effects of the extracts and isocorilagin were observed and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of isocorilagin was higher than those of the standards used (Trolox and butylated hydroxyanisole). This is the first chemical study of the genus Alchorneopsis (Euphorbiaceae).