DIOSPYROS MESPILIFORMIS HOCHST. EX A. DC. (EBENACEAE) YAPRAKLARININ FİTOKİMYASAL PROFİLLENDİRMESİ, ANTİOKSİDAN, ANTİDİYABETİK VE ADMET ÇALIŞMASI

Year 2024, Volume: 48 Issue: 2, 412 - 435, 20.05.2024

Muhammad Mubarak Dahıru , Neksumi Musa

https://doi.org/10.33483/jfpau.1354293

Cited By: 3

Abstract

Amaç: Bu çalışmada Diospyros mespiliformis (DM) ham etanol ekstraktı (CR), etil asetat (EEF) ve sulu fraksiyonları (AQF) üzerinde fitokimyasal profilleme, antioksidan, antidiyabetik ve ADMET çalışmasının yapılması amaçlandı.
Gereç ve Yöntem: Fitokimyasallar GC-MS ile tanımlandı. Antioksidan aktivite in vitro ve silico olarak belirlenirken, antidiyabetik ve ADMET in silico olarak belirlendi.
Sonuç ve Tartışma: EEF ve AQF'de sırasıyla tam olarak 54 ve 44 bileşik tanımlandı. 300 µg/ml'de CR (73.59 ± 0.011 µg/ml), EEF (41.28 ± 0.003 µg/ml AAE) ve AQF (31.28 ± 0.005 µg/ml AAE)’den önemli ölçüde (p<0.05) daha yüksek askorbik asit eşdeğeri (AAE) toplam antioksidan kapasitesi (TAC) gösterdi. 100 µg/ml’de AQF'nin (106.84 ± 3.46 µg/ml) toplam indirgeme gücü (TRP), CR'den (93.23 ± 5.63 µg/ml AAE) ve EEF'den (92.35 ± 6.96 µg/ml AAE) önemli ölçüde (p <0.05) daha yüksekti. 1 mg/ml EEF, ferrik tiyosiyanat yönteminde önemli ölçüde (p<0.05) daha yüksek bir inhibisyon yüzdesi (%48.38 ±4.61) ve tiyobarbitürik asit yönteminde daha düşük bir malonaldehid konsantrasyonu (0.75 nmol/ml ±0.01) gösterdi. AQF, 100 µg/ml'de CR (%33.33 ± 2.16) ve EEF'den (%63.64 ± 2.66) önemli ölçüde (p < 0.05) daha yüksek (%82.72 ± 1.88) peroksit temizleme aktivitesi gösterdi. Bileşik VII, ksantin oksidaz ile sırasıyla -8.8 kcal/mol ve 0.35 µM ve NADH oksidaz ile sırasıyla -8.0 kcal/mol ve 1.35 µM ile en düşük bağlanma afinitesini (BA) ve inhibisyon sabitini (Ki) sergiledi. X, CytP450 21A2 ile etkileşime giren en düşük BA (-8.5 kcal/mol) ve Ki'yi (0.58 uM) sergiledi. Bileşik III, PTP1B ile en düşük BA (-7.5 kcal/mol) ve Ki'yi (3.14 µM) sergilerken; bileşik X, PPARy ile sırasıyla -8.5 kcal/mol ve 0.58 µM BA ve Ki değerlerine sahipti. ADMET sonucu, bazı bileşiklerin antioksidan ve antidiyabetik ilaçlar için güçlü adaylar olabileceğini gösterdi. Tüm ekstraktlar önemli antioksidan aktiviteye sahiptir ve tanımlanan bileşiklerin bazıları yeni antioksidanlar ve antidiyabetik ilaçlar için aday olabilir.

Keywords

ADMET, antidiyabetik, antioksidan, moleküler yerleştirme, moleküler dinamik

PHYTOCHEMICAL PROFILING, ANTIOXIDANT, ANTIDIABETIC, AND ADMET STUDY OF DIOSPYROS MESPILIFORMIS HOCHST. EX A. DC. (EBENACEAE) LEAF

Abstract

Objective: This study aimed to carry out phytochemical profiling, antioxidant, antidiabetic, and ADMET study on the crude ethanol extract (CR) of Diospyros mespiliformis (DM) and its ethyl acetate (EEF) and aqueous fractions (AQF).
Material and Method: The phytochemicals were identified by GC-MS. The antioxidant activity was determined in vitro and silico while the antidiabetic and ADMET were in silico.
Result and Discussion: Exactly 54 and 44 compounds were respectively identified in the EEF and AQF. At 300 µg/ml, the CR demonstrated a significantly (p < 0.05) higher ascorbic acid equivalent (AAE) total antioxidant capacity (TAC) (73.59 ± 0.011 µg/ml) than the EEF (41.28 ± 0.003 µg/ml AAE) and AQF (31.28 ± 0.005 µg/ml AAE). The total reducing power (TRP) of the AQF (106.84 ± 3.46 µg/ml) was significantly (p <0.05) higher than the CR (93.23 ± 5.63 µg/ml AAE) and EEF (92.35 ± 6.96 µg/ml AAE) at 100 µg/ml. A significantly (p < 0.05) higher percentage inhibition (48.38% ± 4.61) was demonstrated by the EEF at 1 mg/ml in the ferric thiocyanate and a lower malonaldehyde concentration (0.75 ± 0.01 nmol/ml) in the thiobarbituric acid methods. The AQF demonstrated a significantly (p < 0.05) higher (82.72% ± 1.88) peroxide scavenging activity at 100 µg/ml than the CR (33.33% ± 2.16) and EEF (63.64% ± 2.66). Compound VII exhibited the lowest binding affinity (BA) and inhibition constant (Ki) of -8.8 kcal/mol and 0.35 µM, respectively with xanthine oxidase and -8.0 kcal/mol and 1.35 µM, respectively with NADH oxidase. X exhibited the lowest BA (-8.5 kcal/mol) and Ki (0.58 µM) interacting with CytP450 21A2. Compound III exhibited the lowest BA (-7.5 kcal/mol) and Ki (3.14 µM) with PTP1B while compound X had BA and Ki values of -8.5 kcal/mol and 0.58 µM, respectively with PPARγ. The result of ADMET showed some of the compounds might be strong candidates for antioxidant and antidiabetic drugs. All the extracts possess significant antioxidant activity and some of the identified compounds might be candidates for novel antioxidants and antidiabetic drugs.

Keywords

ADMET, antidiabetic, antioxidant, molecular docking, molecular dynamics

Supporting Institution

Tertiary Education Trust Fund of Nigeria

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