ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1600484
The effect of different combinations of flaxseed, melatonin, gum acacia and betaine on diabetic rats with adenine-induced chronic kidney disease
Provisionally accepted
- 1Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
- 2Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman
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Diabetes mellitus (DM) and chronic kidney disease (CKD) are associated with significant morbidity and mortality. Their progression is driven by inflammation, oxidative stress and apoptosis. This study examined the effects of nine different combinations of gum acacia (GA), melatonin, betaine and flaxseedused in pairs or trios -on adenine-induced CKD in streptozotocin (STZ)-induced diabetic rats. Rats treated with adenine and STZ exhibited significant hyperglycemia and CKD manifestations such as elevated plasma levels of cystatin C, indoxyl sulfate, as well as increased urinary levels of Nacetyl-β-D-glucosaminidase (NAG), NAG/creatinine ratio and reduced creatinine clearance. Additionally, there was a significant decrease in renalase activity and urine osmolality, alongside a significant increase in IL-1β and IL-6 and TNF-α and a decrease in IL-10 levels. Oxidative stress biomarkers including superoxide dismutase, glutathione reductase, total antioxidant capacity and catalase activities were also significantly impaired. These findings were supported by histopathological changes consistent with CKD. Treatment with the combinations of two or three agents alleviated most of these changes to varying degrees. Notably, the GA-melatonin-betaine combination demonstrated the most significant improvement across all parameters along with preservation of the kidney tissue structure. These improvements may partially be explained by the enhanced glycemic control achieved by this combination, in addition to possible synergistic molecular, pharmacokinetic, and pharmacodynamic interactions. These findings support the potential of this combination to attenuate the progression of CKD in the setting of diabetes. However, further mechanistic studies, pharmacokinetic profiling and long-term toxicity data are warranted to validate its efficacy and safety for clinical use.
Keywords: diabetes, Chronic Kidney Disease, Gum acacia, Melatonin, Betaine, Flaxseed
Received: 26 Mar 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 AL ZA'ABI, Al Suleimani, Ali, Ali and Al Maskari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Raya Al Maskari, Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
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