Toxicological Profile and Anti-Inflammatory Effect of Mucoadhesive Gel from Residues of Agave sisalana and Punica granatum.

Inflammation is a natural protective reaction of the body against endogenous and exogenous damage, such as tissue injuries, trauma, and infections. Thus, when the response is adequate, inflammation becomes a defense mechanism to repair damaged tissue, whereas when the response is inadequate and persistent, the increase in inflammatory cells, cytosines, and chymosins impair tissue regeneration and promote a response harmful to the organism. One example is chronic tissue inflammation, in which a simple lesion can progress to ulcers and even necrosis. In this situation, the anti-inflammatory medications available in therapy are not always effective. For this reason, the search for new treatments, developed from medicinal plants, has increased. In this direction, the plants Agave sisalana (sisal) and Punica granatum (pomegranate) are rich in saponins, which are secondary metabolites known for their therapeutic properties, including anti-inflammatory effects. Although Brazil is the world's leading sisal producer, approximately 95% of the leaves are discarded after fiber extraction. Similarly, pomegranate peel waste is abundant in Brazil. To address the need for safe and effective anti-inflammatory treatments, this study aimed to create a topical mucoadhesive gel containing a combination of sisal (RS) and pomegranate residue (PR) extracts. In vitro experiments examined isolated and combined extracts, as well as the resulting formulation, focusing on (1) a phytochemical analysis (total saponin content); (2) cytotoxicity (MTT assay); and (3) a pharmacological assessment of anti-inflammatory activity (phagocytosis, macrophage spreading, and membrane stability). The results revealed saponin concentrations in grams per 100 g of dry extract as follows: SR-29.91 ± 0.33, PR-15.83 ± 0.93, association (A)-22.99 ± 0.01, base gel (G1)-0.00 ± 0.00, and association gel (G2)-0.52 ± 0.05. In MTT tests for isolated extracts, cytotoxicity values (µg/mL) were 3757.00 for SR and 2064.91 for PR. Conversely, A and G2 exhibited no cytotoxicity, with increased cell viability over time. All three anti-inflammatory tests confirmed the presence of this activity in SR, PR, and A. Notably, G2 demonstrated an anti-inflammatory effect comparable to dexamethasone. In conclusion, the gel containing SR and PR (i.e., A) holds promise as a novel herbal anti-inflammatory treatment. Its development could yield economic, social, and environmental benefits by utilizing discarded materials in Brazil.

Toxicity and Anti-Inflammatory Effects of Agave sisalana Extract Derived from Agroindustrial Residue.

BACKGROUND: In several countries, the leaf juice of Agave sisalana (also known as sisal) is widely used topically, especially as an antiseptic, and orally for the treatment of different pathologies. However, in Brazil, which is the largest producer of Agave sisalana, its residue, which represents the majority of its weight, has been thrown away. For this reason, the determination of the pharmacological and toxicological potentials of sisal residue and its possible therapeutic use is seen as a way to contribute to the sustainable development and social promotion of the largest producer of sisal in Brazil, the interior of Bahia State, which is among the poorest areas in the country. Given the scarcity of available scientific studies on the pharmacological and toxicological properties of sisal residue juice, this study aimed to promote the acid hydrolysis of this juice to potentiate the anti-inflammatory effect already described in the literature. Furthermore, it aimed to evaluate the toxicological profile of the hydrolyzed extract (EAH) and to determine its acute toxicity, as well as its side effects on the reproductive aspects of rats. METHOD: The anti-inflammatory effect of EAH was evaluated in vitro using the induction of hemolysis by hypotonic solution and in vivo in rats using the carrageenan-induced paw edema test and the xylene-induced ear edema test. The acute toxicity, resulting from a single-dose administration, was investigated for some manifestation of toxic symptoms related to motor control and consciousness in rats. At a concentration of 100 mg/kg, by repeated doses, the reproductive toxicity effects of EAH in rats were assessed. RESULTS: In vitro anti-inflammatory activity was positive using the human red blood cell membrane stabilization method. In both in vivo tests used to assess the anti-inflammatory activity, EAH (at three doses) significantly inhibited edema when compared to the control group. At a dose of 50 mg/kg, EAH exhibited a greater effect than indomethacin, a nonsteroidal anti-inflammatory drug with known activity. In vivo toxicological studies have shown that EAH does not present toxic effects when administered orally in a single dose, up to 1000 mg/kg. Finally, EAH promoted a gonadotoxic effect and increased the embryonic mortality rate after implantation. CONCLUSIONS: It is suggested that the anti-edematogenic effect of the acid hydrolysis extract from sisal juice is due to the high concentration of steroidal sapogenins. Therefore, this extract can be considered a potential new anti-inflammatory or even an important sapogenin source for the development of steroidal glucocorticoids. However, further studies are needed to elucidate the chemical composition of sisal juice. Regarding toxicology studies, EAH did not show cytotoxic and clastogenic potentials, but it presented a powerful reproductive toxic effect in rats.

Role of tyrosol on Candida albicans, Candida glabrata and Streptococcus mutans biofilms developed on different surfaces.

PURPOSE: To assess the effect of tyrosol on the production of hydrolytic enzymes (by Candida biofilm cells) and acid (by Streptococcus mutans biofilms), as well as to quantify single and mixed biofilms of these species formed on acrylic resin (AR) and hydroxyapatite (HA). METHODS: Candida and S. mutans biofilms were formed on AR and HA in the presence of tyrosol during 48 hours. Next, acid proteinase, phospholipase and hemolytic activities of Candida biofilm cells were determined, while acid production by S. mutans biofilms was assessed by pH determination. The effect of tyrosol on mature biofilms (96 hours) was evaluated through quantification of total biomass, metabolic activity, number of colony-forming units and composition of biofilms' extracellular matrix. Data were analyzed by one- and two-way ANOVA, followed by Tukey's and Holm-Sidak's tests (α = 0.05). RESULTS: Treatments with tyrosol were not able to significantly reduce hydrolytic enzymes and acid production by Candida and S. mutans. Tyrosol only significantly reduced the metabolic activity of single biofilms of Candida species. CLINICAL SIGNIFICANCE: Tyrosol on its own had a limited efficacy against single and mixed-species oral biofilms. Its use as an alternative antimicrobial for topical therapies still demands more investigation.

Farmacología en la tercera edad: medicamentos de uso continuo y peligros de la interacción medicamentosa / Pharmacology in the elderly: continuous use medicines and drug-drug interaction risks

Introducción: Se observó un considerable crecimientodel contingente poblacional de ancianos. Ellos son losmayores usuarios de medicamentos. Los cambios fisiológicosrelacionados con el envejecimiento pueden alterarla propiedad farmacocinética y la farmacodinamia.El cuadro de declinación cognitiva, las limitaciones físicasy las enfermedades crónicas asociadas afectan la habilidadde usar adecuadamente los medicamentos.Objetivo: Indicar las principales clases farmacológicasadministradas a pacientes geriátricos y los riesgos de lainteracción medicamentosa en base a una revisión de literatura.Conclusión: La mayor parte de los ancianoshacen uso continuo de por lo menos tres fármacos, losmás prescritos son aquellos destinados a problemas cardiovascularesy trastornos psíquicos(AU)

Introduction: It was observed a considerable growth of elderlypeople. They are who use more medicines. The physiologicalchanges associated with the age advancing can makepharmacokinetic and pharmacodynamic alterations. Thecognitive decline, physical limitations and associate chronicpathology affect the medications appropriately use ability.Aims: Based in a literature review, appoint the main pharmacologicalgroups prescribed to the elderly and the drugdruginteraction risks. Conclusion: The most of elderly usecontinually at least 3 medicines, the most prescribed are tocardiovascular and psychic diseases treatment(AU)