###### Abstract  
Background: Diabetes mellitus (DM) has become a disease prevalent worldwide. Honey, which comprises predominantly bioactive constituents, has anti-inflammatory, antioxidant, and immunomododulating properties. Aim: Recent developments and benefits of natural products in treating various diseases have caught the attention of researchers. This study aims to investigate the antidiabetic effect of bee honey extract on induced diabetic Swiss mice. Materials and Methods: Fifty Swiss male mice were randomly assigned to five groups of 10 mice each. Group I served as the negative control; in group II, the mice received 2 mg/kg/b.wt of honey extract only; and groups III, IV, and V received cyclosporine (CsA) (20 mg/kg/day, s.c.) daily for 10 days prior to receiving streptozotocin (STZ) inoculated at multiple low doses (MLDSTZ) (30 mg/kg/day, i.p.) for five consecutive days. Group IV was administered with insulin initiated at a dose of 0.5 U/kg/b.wt as a standard treatment (positive control). Group V was administered 2 mg/kg/b.wt of honey extract, while group III received no treatment. Results: The results showed a significant hypoglycemic effect, increased body weight, increased liver glycogen levels, and the amelioration of antioxidant activities in groups IV and V compared with the diabetic group III. Moreover, serum matrix metalloproteinase (MMP-9) concentrations were significantly reduced in the mice treated with the insulin and honey extract in groups IV and V and the tissue inhibitor metalloproteinase-1 (TIMP-1) levels were significantly higher than the serum levels in group III. Furthermore, the histopathological examination of groups IV and V revealed regenerative changes with the restoration of normal islet cell architecture, as compared to the diabetic mice in group III. Compared to group I, group II showed no changes and exhibited non-significant data. Conclusion: Honey extract plays an effective role in improving all biomarkers in treated group V. Furthermore, MMP-9 and TIMP-1 are considered prognostic markers in the progression, severity, diagnosis, and treatment of type 1 DM. This may play an important role for the treatment of individuals in the future. bee honey extract; type 1 diabetes mellitus; MMP-9; TIMP-1; antioxidants +
Footnote †: journal: Medical  
medications, DM remains a major factor in both morbidity and mortality worldwide [5]. There is treatment available, but there is no known cure for DM. Some diabetic patients have turned to complementary and alternative therapies, such as acupuncture, chiropractic care, natural products, and herbal remedies [6]. Additionally, individuals with diabetes are more likely to experience recurrent coronary episodes, die from myocardial infarction, and develop heart insufficiency. This poor prognosis could be brought on by the abnormal production and activity of metalloproteinases (MMPs) [7]. Furthermore, it is unclear how diabetic angiopathy is related to MMPs and their inhibitors (specifically, tissue inhibitor matrix metalloproteinases (TIMP)). Hyperglycemia may increase MMP activity and production in major arteries, either directly or indirectly (for example, through oxidative stress or advanced glycation products) [8]. Due to the increased glycation-related activity of TIMP-2, the primary MMP-2 inhibitor, diabetic nephropathy may be brought on by MMPs' decreased proteolytic activity [9]. The matrix of atherosclerotic plaques may deteriorate because of an imbalance between MMPs and TIMPs, thereby raising the danger of plaque rupture. MMPs may also play a role in the developing acute thrombotic artery blockages and subsequent cardiovascular events, because they increase blood coagulability [10]. Moreover, it is unclear how MMPs contribute to the emergence of problems in DM. Evidence suggests that the venous monocytes of DM patients produce MMPs in higher quantities, but there is no evidence of enhanced MMP activity in the diabetic vasculature or skin fibroblasts [11].