Avaliação da possível ação anti-hipertensiva e cardioprotetora dos extratos de Coriandrum sativum e Ocimum basilicum em ratos espontaneamente hipertensos (SHR)
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Data
2023-10-30
Autores
Biquiza, Alexandre Simão [UNIFESP]
Orientadores
Bergamaschi, Cássia Marta de Toledo [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: a hipertensão arterial (HA) se caracteriza pela manutenção da pressão arterial acima de 140/90 mmHg, respetivamente para pressões arteriais sistólica (PAS) e diastólica (PAD). A HA afeta mais de 30% da população adulta em todo mundo e de-safios importantes no seu controle a tornam o principal fator de risco cardiovascular. Coriandrum sativum (CS) e Ocimum basilicum (OBL) são plantas ricas em compostos antioxidantes comumente utilizadas como condimento alimentar e na medicina tradici-onal de vários países. A capacidade antioxidante destas plantas representa um poten-cial anti-hipertensivo e cardioprotetor por poder melhorar a sensibilidade barorreflexa que está prejudicada em indivíduos hipertensos. Objetivo: investigar possíveis ações anti-hipertensiva e cardioprotetora dos extratos de CS e OBL em ratos espontanea-mente hipertensos (SHR). Material e métodos: partes aéreas secas de CS e OBL fo-ram trituradas e maceradas no metanol 80% por 7 dias. Todo teor alcoólico foi removido no evaporador rotativo e o resíduo aquoso foi liofilizado para posterior diluição em água destilada. Os extratos foram sujeitos a dosagem de compostos fenólicos e análise da capacidade antioxidante pelos métodos ABTS e DPPH. De acordo com o protocolo aprovado (CEUA/Unifesp n° 3797030122), animais SHR de 11 a 16 semanas (290 – 350g) foram distribuídos em grupos e tratados com 3 doses de cada extrato por gava-gem durante 15 dias: SHR CS 100 (n=12), SHR CS 300 (n=6) e SHR CS 400 (n=6); SHR OBL 100 (n=12), SHR OBL 300 (n=6) e SHR OBL 400 (n=6). Cada um dos grupos foi comparado com seu controle (SHR) tratado com água destilada. Após o tratamento os animais foram cateterizados sub anestesia, e 24 h depois, a PAM, PAD, PAS e FC foram registradas e avaliou-se a sensibilidade barorreflexa por infusão de drogas va-soativas. Os animais foram expostos ao teste de reatividade cardiovascular ao estresse (cage switch stress, CSS) e bloqueio ganglionar com hexametônio. O Sangue arterial, rim e coração foram coletados após eutanásia e junto com a urina (antes e após trata-mento), procedeu-se avalições bioquímicas, histológicas e moleculares. Teste t-student e two-way ANOVA foram usados para verificar diferença entre os grupos, estabelecida quando p<0.05. Os resultados são apresentados em média ± desvio e padrão (DP) ou erro padrão da média (EP). Resultados: a capacidade antioxidante em µM TE/g do CS foi de 17,32 ± 1,13 (ABTS) e 6,42 ± 1,07 (DPPH), resultante de compostos antioxidan-tes totais de 3,25 ± 0,29 g/g. O extrato de OBL apresentou 168,62 ± 43,84 (ABTS), 30,55 ± 2,79 (DPPH) e 32,67 ± 1,42 g/g de fenólicos totais. Partindo de valores basais simila-res, no final do tratamento, SHR CS 300 e SHR CS 400 apresentaram valores signifi-cativamente reduzidos de parâmetros cardiovasculares face aos SHR: PAM 125 ± 8 mmHg vs. 139 ± 6 mmHg e FC 340 ± 15 bpm vs 357 ± 8 bpm. Quanto a sensibilidade ba-rorreflexa, foi observada melhor resposta bradicárdica no SHR CS 300 ( 1.53 ± 0.91 bpm/mmHg vs -0.88 ± 0.54 bpm/mmHg), SHR OBL 300 ( 1.83 ± 0.71 bpm/mmHg vs -0.98 ± 0.64 bpm/mmHg) e SHR OBL 400 ( 2.13 ± 0.91 bpm/mmHg vs -1.48 ± 0.84 bpm/mmHg). O SHR CS 300 apresentou menor reatividade cardiovascular ao estresse nos minutos 20, 27 e 28 do teste CSS. Valores de proteinúria foram significativamente reduzidos no SHR CS 300 (22 ± 8 mg/24h vs 38 ± 7 mg/24h) e SHR CS 400 (24 ± 6 mg/24h vs 42 ± 5 mg/24h). Conclusão: o CS foi capaz de reduzir a PA e FC, melhorar sensibilidade barorreflexa e reduzir a proteinúria no SHR. O OBL melhora a sensibili-dade barorreflexa independente da redução da PA e FC. Ambos extratos conferem redução do risco cardiovascular. Estudos adicionais são necessários para aprofundar os mecanismos de ação.
Introduction: Arterial hypertension (AH) is characterized by the maintenance of blood pressure above of 140/90 mmHg, respectively for systolic blood pressure (SBP) and di-astolic blood pressure (DBP). AH affects more than 30% of the adult population worldwide and important challenges in controlling it make it the main cardiovascular risk factor. Co-riandrum sativum (CS) and Ocimum basilicum (OBL) are rich in antioxidant compounds commonly used as food flavoring and in traditional medicine in my countries. The antiox-idant capacity of these plants represents an antihypertensive and cardioprotective poten-tial to improve baroreflex sensitivity, which is impaired in hypertensive individuals. Objec-tive: to investigate possible antihypertensive and cardioprotective actions of CS and OBL extracts in spontaneously hypertensive rats (SHR). Material and methods: dried aerial parts of CS and OBL were crushed and macerated in 80% methanol for 7 days. All alco-holic content was removed in the rotary evaporator and the aqueous residue was lyophi-lized for subsequent dilution in distilled water. Extract´s phenolic compounds were meas-ure and its antioxidant capacity analysis using the ABTS and DPPH methods were pro-ceeded. According to the approved protocol (CEUA/UNIFESP n° 3797030122), SHR aged 11 to 16 weeks (290 – 350g) were distributed into groups and treated with 3 doses of each extract by gavage for 15 days: SHR CS 100 (n =12), SHR CS 300 (n=6) and SHR CS 400 (n=6); SHR OBL 100 (n=12), SHR OBL 300 (n=6) and SHR OBL 400 (n=6). Each group was compared with its control (SHR) treated with distilled water. At the end of treat-ment, the animals were catheterized under anesthetic, and 24 h later, cardiovascular pa-rameters were recorded and baroreflex sensitivity was evaluated by infusion of vasoactive drugs. The animals were exposed to the cardiovascular stress reactivity test (cage switch stress, CSS) and ganglionic blockade with hexamethonium. After euthanasia, arterial blood, kidney, heart and urine (before and after treatment) were collected for biochemical, histological and molecular analysis. Student's t-test and two-way ANOVA were used to verify differences between groups, established when p<0.05. Results are presented as mean ± SD or SEM. Results: the antioxidant capacity in μM TE/g of CS was 17.32 ± 1.13 (ABTS) and 6.42 ± 1.07 (DPPH), resulting in total phenolic compounds of 3.25 ± 0.29 g/g. The OBL extract presented 168.62 ± 43.84 (ABTS), 30.55 ± 2.79 (DPPH) and 32.67 ± 1.42 g/g of total phenolic compounds. Beginning from similar baseline values, at the end of treatment, SHR CS 300 and SHR CS 400 showed significantly reduced values of car-diovascular parameters compared to SHR: MAP 125 ± 8 mmHg vs. 139 ± 6 mmHg and HR 340 ± 15 bpm vs 357 ± 8 bpm. Regarding baroreflex sensitivity, ameliorating of brad-ycardic response was observed in the SHR CS 300 (1.53 ± 0.91 bpm/mmHg vs -0.88 ± 0.54 bpm/mmHg), SHR OBL 300 (1.83 ± 0.71 bpm/mmHg vs -0.98 ± 0.64 bpm/mmHg) and SHR OBL 400 (2.13 ± 0.91 bpm/mmHg vs -1.48 ± 0.84 bpm/mmHg). The SHR CS 300 showed lower cardiovascular reactivity to stress in the 20th, 27th and 28th minutes of the CSS test. Proteinuria values were significantly reduced in SHR CS 300 (22 ± 8 mg/24h vs 38 ± 7 mg/24h) and SHR CS 400 (24 ± 6 mg/24h vs 42 ± 5 mg/24h). Conclusion: CS was able to reduce BP and HR, improve baroreflex sensitivity and reduce protheinuria in SHR. OBL improved baroreflex sensitivity independent of BP and HR reduction. Both extracts reduce cardiovascular risk. Additional studies are needed to delve deeper into the mechanisms of action.
Introduction: Arterial hypertension (AH) is characterized by the maintenance of blood pressure above of 140/90 mmHg, respectively for systolic blood pressure (SBP) and di-astolic blood pressure (DBP). AH affects more than 30% of the adult population worldwide and important challenges in controlling it make it the main cardiovascular risk factor. Co-riandrum sativum (CS) and Ocimum basilicum (OBL) are rich in antioxidant compounds commonly used as food flavoring and in traditional medicine in my countries. The antiox-idant capacity of these plants represents an antihypertensive and cardioprotective poten-tial to improve baroreflex sensitivity, which is impaired in hypertensive individuals. Objec-tive: to investigate possible antihypertensive and cardioprotective actions of CS and OBL extracts in spontaneously hypertensive rats (SHR). Material and methods: dried aerial parts of CS and OBL were crushed and macerated in 80% methanol for 7 days. All alco-holic content was removed in the rotary evaporator and the aqueous residue was lyophi-lized for subsequent dilution in distilled water. Extract´s phenolic compounds were meas-ure and its antioxidant capacity analysis using the ABTS and DPPH methods were pro-ceeded. According to the approved protocol (CEUA/UNIFESP n° 3797030122), SHR aged 11 to 16 weeks (290 – 350g) were distributed into groups and treated with 3 doses of each extract by gavage for 15 days: SHR CS 100 (n =12), SHR CS 300 (n=6) and SHR CS 400 (n=6); SHR OBL 100 (n=12), SHR OBL 300 (n=6) and SHR OBL 400 (n=6). Each group was compared with its control (SHR) treated with distilled water. At the end of treat-ment, the animals were catheterized under anesthetic, and 24 h later, cardiovascular pa-rameters were recorded and baroreflex sensitivity was evaluated by infusion of vasoactive drugs. The animals were exposed to the cardiovascular stress reactivity test (cage switch stress, CSS) and ganglionic blockade with hexamethonium. After euthanasia, arterial blood, kidney, heart and urine (before and after treatment) were collected for biochemical, histological and molecular analysis. Student's t-test and two-way ANOVA were used to verify differences between groups, established when p<0.05. Results are presented as mean ± SD or SEM. Results: the antioxidant capacity in μM TE/g of CS was 17.32 ± 1.13 (ABTS) and 6.42 ± 1.07 (DPPH), resulting in total phenolic compounds of 3.25 ± 0.29 g/g. The OBL extract presented 168.62 ± 43.84 (ABTS), 30.55 ± 2.79 (DPPH) and 32.67 ± 1.42 g/g of total phenolic compounds. Beginning from similar baseline values, at the end of treatment, SHR CS 300 and SHR CS 400 showed significantly reduced values of car-diovascular parameters compared to SHR: MAP 125 ± 8 mmHg vs. 139 ± 6 mmHg and HR 340 ± 15 bpm vs 357 ± 8 bpm. Regarding baroreflex sensitivity, ameliorating of brad-ycardic response was observed in the SHR CS 300 (1.53 ± 0.91 bpm/mmHg vs -0.88 ± 0.54 bpm/mmHg), SHR OBL 300 (1.83 ± 0.71 bpm/mmHg vs -0.98 ± 0.64 bpm/mmHg) and SHR OBL 400 (2.13 ± 0.91 bpm/mmHg vs -1.48 ± 0.84 bpm/mmHg). The SHR CS 300 showed lower cardiovascular reactivity to stress in the 20th, 27th and 28th minutes of the CSS test. Proteinuria values were significantly reduced in SHR CS 300 (22 ± 8 mg/24h vs 38 ± 7 mg/24h) and SHR CS 400 (24 ± 6 mg/24h vs 42 ± 5 mg/24h). Conclusion: CS was able to reduce BP and HR, improve baroreflex sensitivity and reduce protheinuria in SHR. OBL improved baroreflex sensitivity independent of BP and HR reduction. Both extracts reduce cardiovascular risk. Additional studies are needed to delve deeper into the mechanisms of action.
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Citação
BIQUIZA, Alexandre Simão. Avaliação da possível ação anti-hipertensiva e cardioprotetora dos extratos de Coriandrum sativum e Ocimum basilicum em ratos esponta-neamente hipertensos (SHR). 2023. 76 f. Dissertação (Mestrado em farmacologia) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2023.