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J Herbmed Pharmacol. 2022;11(4): 562-574.
doi: 10.34172/jhp.2022.65

Scopus ID: 85143236727
  Abstract View: 1159
  PDF Download: 665

Original Article

Insulin supplemented with phenolic fraction concentrates displays anxiolytic and antidepressant-like properties with reductions of oxidative brain damage in chronically stressed diabetic rats

Samir BIKRI 1* ORCID logo, Abdeljalil Talhaoui 1 ORCID logo, Nada Fath 2 ORCID logo, Asmae Hsaini 1 ORCID logo, Hajar Benmhammed 3 ORCID logo, Ahmed Omar Touhami Ahami 1 ORCID logo, Youssef Aboussaleh 1 ORCID logo

1 Laboratory of biology and health, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco
2 Comparative Anatomy Unit, Department of Biological and Pharmacological Veterinary Sciences, Hassan II Agronomy and Veterinary Medicine Institute, Rabat-Institute
3 Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Science, The State University of New York, New York, USA
*Corresponding Author: Email: samir.bikri@uit.ac.ma

Abstract

Introduction: The current study aimed to investigate if insulin supplemented with phenolic fraction concentrates (PFC) improves chronic hyperglycemia-related behavioral changes by mitigating oxidative stress in diabetic rats exposed to chronic mild stress (CMS). Methods: Experimental type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). After diabetes confirmation, rats were treated with insulin supplemented with PFC and exposed to two unpredictable mild stressors per day for 12 weeks. Body weight changes, fasting blood glucose (FBG), and corticosterone levels were evaluated. The behavioral tests were performed to evaluate anhedonia, anxiety, and depressive-like behaviors. Twenty-four hours after behavioral tests, all rats were anesthetized, and the blood was collected for the analysis of lipid, hepatic, and renal parameters. Finally, the brain areas (striatum, hippocampus, and prefrontal cortex), pancreas, and adrenal glands were dissected for the analysis of oxidative stress markers. Results: The results of this study revealed that treatment with insulin supplemented with PFC for 12 weeks significantly enhanced antioxidant defenses (catalase [CAT] and superoxide dismutase [SOD]) and reduced oxidative stress damage (nitric oxide and malondialdehyde [MDA]), especially in brain regions (prefrontal cortex, hippocampus, and striatum) in stressed diabetic rats (P < 0.001). This combination also ameliorated the corticosterone level (P < 0.001) as well as glucose homeostasis (P < 0.001) and lipid parameters (P < 0.001), which are markedly altered in T1D associated with stress. Conclusion: The associated treatment possesses important anxiolytic and antidepressant-like effects in this rat model, which might be mainly mediated by its capacity to protect brain cells against reactive oxygen species (ROS) triggered by T1DM and/or chronic stress.

Implication for health policy/practice/research/medical education: Insulin supplemented with phenolic fraction concentrates (PFC) has a significant effect on controlling the corticosterone level as well as glucose homeostasis and lipid parameters, which are markedly altered in type 1 diabetes associated with stress. Likewise, this work shows the promising anxiolytic and antidepressant-like effects of insulin supplemented with PFC, which can be mainly mediated by its capacity to protect brain cells against reactive oxygen species (ROS) triggered by diabetes and/or chronic stress.
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Submitted: 14 Jun 2022
Revision: 12 Jul 2022
Accepted: 13 Jul 2022
ePublished: 21 Sep 2022
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