Banca de DEFESA: ANDERSON WILBUR LOPES ANDRADE

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ANDERSON WILBUR LOPES ANDRADE
DATE: 26/02/2021
TIME: 14:00
LOCAL: Videoconferencia
TITLE:

AVALIAÇÃO DO POTENCIAL DE EXTRATOS RICOS EM FLAVONOIDES DE Kalanchoe laciniata (L.) DC E Bryophyllum pinnatum (LAM.) OKEN NO TRATAMENTO DE DOENÇA INFLAMATÓRIA INTESTINAL: UM ESTUDO FIOQUÍMICO, DE SEGURANÇA E EFICÁCIA EM MODELOS in vivo

KEY WORDS:

Crassulaceae; Flavonoids; Acute toxicity; Subchronic Toxicity; 2,4-dinitrobenzene sulfonic acid; Dextran sulfate sodium; Immunomodulation;

PAGES: 265
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease are
characterized by chronic inflammation in the intestine. Currently, there are several therapeutic
strategies to treating IBD. However, some treatments of choice are associated with serious
adverse effects, which justifies the search for new adjuvant treatments. In this sense, the interest
in plants rich in phenolic compounds with immunomodulatory and antioxidant properties stands
out, such as Kalanchoe laciniata and Bryophyllum pinnatum, belonging to the Crassulaceae
family. These plants are popularly used in Brazil to treat gastritis, ulcer, inflammation in
general, among others. Thus, our hypothesis was evaluate if K. laciniata (HEKL) and B.
pinnatum (HEBP) hydroethanolic leaf extracts 50 % demonstrate signs of cytotoxicity (RAW
264.7 cells) and acute (14 days) and subchronic (28 days) toxicity in vivo models and intestinal
anti-inflammatory effect in two colitis models: induction by 2.4-dinitrobenzene sulfonic acid
(DNBS) in rats (preventive protocol) and by dextran sulfate sodium (DSS) in mice (curative
protocol). Initially, the total content of phenols and flavonoids in the extracts was performed.
HEKL and HEBP demonstrated, respectively, contents of 75.1±6.32 and 96.7±7.34 mg (gallic
acid/g of the extract) and total flavonoids equal to 37,4±4.82 and 64.3±4.16 mg (quercetin/g of
the extract). Ultra-fast liquid chromatography methods to evaluate the major constituents of the
two extracts was developed and validated. However, only the method for HEBP has been
validated according to the Brazilian legislation and its major flavonoids quercetin 3-O-α-Larabinopyranosyl-(1→2)-α-L-rhamnopyranoside, kaempferol 3-O-α-L-arabinopyranosyl-
(1→2)-α-L-rhamnopyranoside and quercetin-3-O-rhamnopyranoside had, respectively,
contents of 35.56±0.09, 4.66±0.08 and 4.56±0.03 mg per g of extract. The HEKL and HEBP
did not show signs of cytotoxicity and in the toxicological assay, the tested extracts did not
significantly alter (p <0.05) the control parameters (behavioral, locomotor, hematological,
biochemical, among others) and did not cause death in the animals (median lethal dose
estimated above 2000 mg/kg). Regarding the anti-colitic effect in the DNBS and DSS models,
it was observed that the extracts have chemopreventive and anti-inflammatory effects by
reducing the disease activity index score (p < 0.05) and macroscopic and microscopic. The
extracts promoted negative regulation (p < 0.05) of the Toll-type receptor and the expression
of the nuclear factor kappa B p65 gene, causing a suppression (p < 0.05) of the proinflammatory mediators (necrosis factor tumoral alpha and interleukins (IL) 1β, IL-6, IL-17)
and oxidants (nitric oxide), chemokines (monocyte chemoattractant protein-1 and macrophage
inflammatory protein-2), type I intercellular adhesion molecules. This immunomodulatory and
antioxidant properties were proposed as one of the mechanisms of action of the extracts. The
improvement in intestinal inflammation was also associated with a decrease in oxidative stress
and leukocyte infiltration exerted by the extracts. In addition, HEKL and HEBP contributed to
maintaining the integrity of the intestinal epithelial barrier by restoring the expression of
proteins (p < 0.05) associated with mucosal protection (mucin (MUC) 2 and MUC-3, occludin,
zonula occludens type 1, trefoil factor, villin). Based on the finding that the extracts did not
present toxic effects in the tested doses, and the beneficial effects in the DNBS and DSS models,
it can be inferred that HEKL and HEBP are safe and that they have an anti-inflammatory effect
compared to the models applied that can be hypothesized by antioxidant and
immunomodulatory properties of its flavonoids. These findings make the extracts as a
promising candidate for assessing the efficacy and clinical safety of adjuvant therapy for IBD.

BANKING MEMBERS:
Externo à Instituição - CLEVERSON LUIZ DOS SANTOS VIGO
Externo à Instituição - RENAN OLIVEIRA SILVA DAMASCENO - UFPE
Externa ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externo ao Programa - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Presidente - 1490222 - SILVANA MARIA ZUCOLOTTO LANGASSNER