Yuyun Yueniwati, Mokhamad Fahmi Rizki Syaban, Dedy Budi Kurniawan, Afrizal Alif Azam, Desak Made Alvenia, Yushidayah Nur Savira, Rislan Faiz Muhammad, Basyar Adnani, Aldita Husna Violita, Safira Dita Arviana, Aminah Hasibuan, Eviana Norahmawati, Yasmin Fatmasari, Arinal Mufidah, Kania Aviandi Savitri, Unzila Rafsi Zulfikri, Diana Yuswanti Putri, Sri Utami
Stroke is a medical condition characterized by a sudden, localized neurological impairment caused by damage to the central nervous system due to either a blockage or bleeding in the blood vessels. This process leads to increased oxidation, which can exacerbate brain damage. Flavonoids are compounds that are widely found in nature and are consid‑ ered to have numerous health benefits. 7,8‑dihydroxyflavone (7,8‑DHF) is a flavonoid that has tropomyosin receptor kinase B agonist activity. However, the other beneficial activities of 7,8‑DHF remain to be explored, particularly in neuron‑related diseases. The present study aimed to explore 7,8‑DHF as an antioxidant agent using in vivo and in silico analyses. An in vivo experiment was conducted using Rattus novergicus, in which ischemia‑reperfusion brain injury was induced. A total of 30 rats were divided into the sham‑operated, control and treatment groups. The treatment groups were administered doses of 10, 20 and 50 mg/kg body weight of 7,8‑DHF orally, once daily for a duration of 14 days following the induction of ischemia‑reperfusion brain injury. Subsequently, blood and brain tissues were collected for the examination of nuclear factor E2‑related factor 2 (Nrf2) expression, glutathione perox‑ idase‑1 (GPX‑1) expression and the malondialdehyde (MDA) level. Molecular docking analysis and dynamic simulations of 7,8‑DHF and Kelch like ECH‑associated protein 1 (Keap1) protein interactions were performed using AutoDock Vina and AMBER. The visualization of the interaction was performed using ChimeraX and Discovery Studio. The drug‑like proper‑ ties of 7,8‑DHF were predicted using the SwissADME web server, and the bioactivity of the compounds was evaluated using the PASS online server. The results revealed that 7,8‑DHF exhibits antioxidant activity through the inhibition of Keap1, thereby increasing Nrf2 and GPX‑1 expression and decreasing the levels of MDA. In silico analysis revealed that 7,8‑DHF can bind Keap1 protein, thereby disrupting the interaction between Nrf2 and Keap1. Molecular dynamics also demonstrated that 7,8‑DHF has good stability compared to the control. On the whole, as demonstrated in the present study 7,8‑DHF has promising biological activity as an antioxidant agent in the rat model of ischemia‑reperfusion brain injury. Further studies on the effects of 7,8‑DHF are required to clarify its potential as a novel therapeutic agent for cerebral infarction. © 2024 Yueniwati et al.
Department of Radiology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar Hospital Malang, Malang, 65111, Indonesia; Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Pathological Anatomy, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar Hospital Malang, Malang, 65111, Indonesia; Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
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