Diabetes Mellitus Tipe 2 (T2DM) merupakan penyakit metabolik yang ditandai oleh hiperglikemia akibat resistensi insulin dan disfungsi sel ? pankreas. Enzim dipeptidyl peptidase-4 (DPP-4) menjadi salah satu target terapi penting karena berperan dalam degradasi hormon incretin yang mengatur homeostasis glukosa. Penelitian ini bertujuan mengevaluasi aktivitas antioksidan dan penghambatan DPP-4 kulit jeruk bali (Citrus maxima), mengidentifikasi senyawa bioaktifnya, serta menganalisis potensi interaksi molekulernya terhadap enzim DPP-4.
Kulit jeruk bali diekstraksi menggunakan Ultrasonic Assisted Extraction (UAE) dan difraksinasi berdasarkan kepolaran pelarut. Aktivitas antioksidan dianalisis menggunakan metode penangkapan radikal 2,2-diphenyl-1-picrylhydrazyl (DPPH) dan uji reduksi Ferric Reducing Antioxidant Power (FRAP), aktivitas antidiabetes ditentukan melalui uji penghambatan DPP-4, sedangkan profil senyawa dan interaksi molekuler dianalisis menggunakan LC-HRMS dan molecular docking.
Hasil penelitian menunjukkan bahwa aktivitas antioksidan dan antidiabetes ekstrak dan fraksi kulit jeruk bali berbeda berdasarkan tingkat kepolarannya. Fraksi etil asetat menunjukkan aktivitas antioksidan tertinggi dengan nilai IC?? DPPH sebesar 92,88 µg/mL dan nilai FRAP sebesar 299,25 µM Fe²? yang yang menunjukkan tingginya kemampuan penangkapan radikal bebas dan daya reduksinya. Uji penghambatan DPP-4 juga menunjukkan bahwa fraksi etil asetat memiliki aktivitas tertinggi dengan persen inhibisi sebesar 75,91%. Berdasarkan hasil aktivitas antioksidan dan penghambatan DPP-4 tersebut, fraksi etil asetat ditetapkan sebagai fraksi aktif dan dipilih untuk analisis lanjutan menggunakan LC-HRMS serta molecular docking. Analisis LC-HRMS terhadap fraksi aktif berhasil mengidentifikasi 427 senyawa, dengan 19 senyawa terpilih berdasarkan klasifikasi metabolit sekunder, luas area (?0,2%), dan parameter ADMET. Senyawa-senyawa tersebut didominasi oleh golongan flavonoid, fenolik, polymethoxyflavone, dan chalcone yang diketahui memiliki aktivitas antioksidan dan antidiabetes. Hasil molecular docking menunjukkan bahwa hesperidin dan neohesperidin memiliki afinitas pengikatan yang kuat terhadap enzim DPP-4 serta membentuk interaksi dengan residu kunci Ser630, His740, Glu205 dan Glu206 yang berperan dalam mekanisme penghambatan enzim DPP-4. Berdasarkan hasil tersebut, dapat disimpulkan bahwa kulit jeruk bali berpotensi dikembangkan sebagai sumber senyawa bioaktif antidiabetes melalui mekanisme penghambatan enzim DPP-4.
Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from insulin resistance and pancreatic ?-cell dysfunction. Dipeptidyl peptidase-4 (DPP-4) is an important therapeutic target due to its role in the degradation of incretin hormones involved in glucose homeostasis. This study aimed to evaluate the antioxidant and DPP-4 inhibitory activities of pomelo (Citrus maxima) peel, identify its bioactive compounds, and investigate their molecular interactions with the DPP-4 enzyme.
Pomelo peel was extracted using Ultrasonic Assisted Extraction (UAE) and subsequently fractionated based on solvent polarity. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and Ferric Reducing Antioxidant Power (FRAP) assays. Antidiabetic activity was determined through DPP-4 inhibition assay, while compound profiling and molecular interactions were analyzed using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) and molecular docking, respectively.
The results demonstrated that the antioxidant and antidiabetic activities of the extract and fractions varied according to their polarity. The ethyl acetate fraction exhibited the highest antioxidant activity, with a DPPH IC?? value of 92.88 µg/mL and a FRAP value of 299.25 µM Fe²?, indicating strong radical scavenging and reducing capacities. The DPP-4 inhibition assay also revealed that the ethyl acetate fraction showed the highest inhibitory activity, with a percentage inhibition of 75.91%. Based on these findings, the ethyl acetate fraction was designated as the active fraction and selected for further LC-HRMS and molecular docking analyses. LC-HRMS analysis of the active fraction identified 427 compounds, of which 19 compounds were selected based on secondary metabolite classification, relative peak area (?0.2%), and ADMET parameters. These compounds were predominantly classified as flavonoids, phenolics, polymethoxyflavones, and chalcones, which are known for their antioxidant and antidiabetic properties. Molecular docking results indicated that hesperidin and neohesperidin exhibited strong binding affinities toward DPP-4 and formed interactions with key residues, including Ser630, His740, Glu205, and Glu206, which are involved in the DPP-4 inhibitory mechanism. These findings suggest that pomelo peel has potential as a source of bioactive compounds with antidiabetic activity through DPP-4 inhibition.
Kata Kunci :
kulit jeruk bali, antioksidan, antidiabetes, LC-HRMS, molecular docking.
