Sócrates Golzio dos Santos

Toxicological evaluation in silico and in vivo of secondary metabolites of Cissampelos sympodialis in Mus musculus mice following inhalation

Abstract The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.

New Therapeutic Targets and Drugs for the Treatment of Asthma

Asthma is an inflammatory disease which affects millions of people worldwide. Therefore, it is necessary to search for new sources of therapies for the treatment of these patients in order to improve their quality of life. From content analysis of literature of new therapeutic targets, there are various targets and drugs reported to be promising for the treatment of asthma. Interleukins involved in inflammatory processes are often presented as candidate targets for new drugs. The action of such therapeutics would not only affect interleukins, but also their receptors. Small molecules (e.g. ligustrazine and SP600125) and large molecule antibodies (e.g. lebrikizumab, benralizumab, dupilumab) are being considered as novel agents for the pharmacotherapy of asthma. Therefore, through this research, we can see advances in the search for new targets and promising drugs to treat asthma. It is expected that these new drug candidates will eventually be approved and marketed so that asthma patients can use them to enhance their quality of life.

Anxiolytic Effect of Citrus aurantium L. in Crack Users

The objective of this study was to investigate the anxiolytic effects of the essential oil (EO) of Citrus aurantium L. in patients experiencing crack withdrawal. This was developed with internal users in therapeutic communities in Paraíba, Brazil. The test population consisted of 51 volunteers, subdivided into three groups. To elicit anxiety, the Simulated Public Speaking (SPS) method was used. Physiological measures were assessed at specific phases during the experiment using appropriate equipment. Psychological measures of anxiety were assessed using the Trait-State Anxiety Inventory (IDATE) and the Analog Smoke Scale (HAS). EO was administered by nebulization. The experiment was developed in individual sessions and consolidated to four phases. The results demonstrated that the test subjects in the groups that were given the EO maintained controlled anxiety levels during SPS, when compared to the Control Group (no treatment). Subjects who used the EO also maintained levels of “discomfort” and “cognitive impairment” during SPS. It was concluded that individuals who are experiencing internal crack cocaine withdrawal present high anxiety traits and that nebulization of the EO of Citrus aurantium L. provided an acute anxiolytic effect in crack cocaine users exposed to SPS.

Secondary Metabolites from Cissampelos, A Possible Source for New Leads with Anti-Inflammatory Activity

The genus Cissampelos comprises of 21 species which have a wide global distribution and various pharmacological activities such as analgesic and antipyretic, antiinflammatory, anti-allergic, bronchodilation, and immunomodulation among others. Several compounds, mainly alkaloids with differing biological activities have been isolated from this genus. We will highlight antipyretic activities, anti-inflammatory, antiallergic, bronchodilatory, and immunomodulatory activities. In addition, we applied ligand-based-virtual screening associated with structure-based-virtual screening of a small dataset of 63 secondary metabolites from the Cissampelos genus of an in-house data bank, in order to select compounds with potential anti-inflammatory activity. Affinities were observed for hayatine (26), isochondrondendrine (30), pelosine (52), sepeerine (59), and warifteine (63) to the inhibiting enzymes MAPK p38 alpha, PKC beta, PKC theta and PKC zeta. The cissampeloflavone compound (8) alone showed no potential inhibitory activity for PKC zeta, or affinity for the PKC alpha. The compounds can be used as starting points for further studies on structures with potential anti-inflammatory activity.

In silico and In vivo Toxicological Evaluation of Cissampelos Sympodialis Secondary Metabolites in Rattus Norvegicus

Cissampelos sympodialis is a plant in northeastern Brazil used by the populace for treating respiratory diseases. Several studies have shown that ethanol leaf extracts have immunomodulatory and anti-inflammatory activities. Infusions are widely used, popular, and an ancient technique in traditional medicine, using hot water alone as the means of extraction. This study aimed to investigate acute toxicological potential of leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg to Rattus norvegicus, combined with an in silico study of 117 alkaloids present in the Cissampelos genus; five (5) of which were determined to have high toxicity (21, 8, 93, 32 and 88), and five (5) having both low toxicity (57, 77, 28, 25 and 67) and low liver metabolism. The in vivo toxicological evaluation showed that male water consumption decreased, and the feed intake decreased in both sexes. Yet, the figures as to change in weight gain of the animals were not statistically sufficient. As for the biochemical parameters, there was an increase in urea, and decreases in uric acid and AST in males. In females, there was a decrease in albumin and globulin which consequently leads to a total protein decrease. Despite biochemical changes suggestive of kidney damage, the histological sections revealed no kidney or liver changes. The results therefore indicate that despite presenting alkaloids which may be toxic, the genus Cissampelos, or leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg present low toxicity.