Research Article Etlingera elatior Flower Aqueous Extract Protects against Oxidative Stress-Induced Nephropathy in a Rat Model of Type 2 Diabetes Liza Noordin , 1 Wan Amir Nizam Wan Ahmad , 2 Nor Asiah Muhamad Nor , 3 Nor Hidayah Abu Bakar , 4 and Azizah Ugusman 5 1 Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Penang 16150, Malaysia 2 Biomedicine Programme, School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Penang 16150, Malaysia 3 Faculty of Health Science, Universiti Sultan Zainal Abidin, Gong Badak Campus, Kuala Terengganu 21300, Malaysia 4 Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Kuala Terengganu 20400, Malaysia 5 Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia Correspondence should be addressed to Liza Noordin; lizakck@usm.my and Wan Amir Nizam Wan Ahmad; wanamir@usm.my Received 11 January 2022; Revised 23 March 2022; Accepted 5 April 2022; Published 23 April 2022 Academic Editor: Min Li Copyright © 2022 Liza Noordin et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetes mellitus (DM) is a known systemic disease with increasing global prevalence and multi-organ complications including diabetic nephropathy (DN). e trend of using medicinal plants in the management of DM is increasing exponentially. Etlingera elatior is a medicinal plant that contains chemicals and antioxidants that delay the oxidation process. However, available data focusing on its use on DN are inconsistent and scarce. is study aims to investigate the antidiabetic and nephroprotective effects of E. elatior flower aqueous extract (EEAE) in a type 2 DM rat (T2DR) model. e T2DR model was developed using a combination of a high-fat diet (HFD) and a low dose of streptozotocin (STZ) at 35 mg/kg. irty-two Sprague Dawley male rats were randomly divided into four groups (n 8): (1) control (normal rat), (2) T2DR (untreated-type 2 diabetic rat), (3) Met (250 mg/kg metformin-treated T2DR), and (4) EEAE (1000 mg/kg EEAE-treated T2DR). All treatments were administered orally for 6 weeks. EEAE significantly reduced fasting blood glucose (FBG), microalbuminuria, serum creatinine, and serum blood urea nitrogen. EEAE also reduced malondialdehyde (MDA) and enhanced the levels of antioxidant markers—superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC). e inflammatory marker (interleukin (IL)- 6) and fibrosis markers (transforming growth factor-beta (TGF-β), and connective tissue growth factor (CTGF)) were significantly decreased in the EEAE-treated group. e T2DR group developed DN, which was characterized by segmental sclerosis of the glomeruli associated with focal tubular atrophy and interstitial fibrosis. Interestingly, the histology of kidney tissue in the EEAE group was preserved. is effect was similar to that of the control drug metformin. In summary, the antidiabetic and neph- roprotective effects might be related to the antioxidant properties and anti-inflammatory effects of the EEAE. e antidiabetic activity could be due to the presence of the active compound cyanidin-3-O-glycosides, which is an anthocyanin antioxidant, that is present in the EEAE. E. elatior has the potential to be developed as a natural source of antioxidants that can be used for the prevention or even the treatment of DM. ese findings could lead to future research into the therapeutic use of E. elatior in alleviating the progression of DM and thus preventing nephropathy. Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2022, Article ID 2814196, 12 pages https://doi.org/10.1155/2022/2814196