Diabetes mellitus is a worldwide illness that causes significant morbidity, mortality and long-term sequelae such as peripheral nerve damage, retinopathy, nephropathy and cardiovascular disorders (Ghaheri et al., 2018). Chronic hyperglycemia, along with compromised metabolic functions related to protein, lipid and carbohydrate metabolism that results from either an absolute or relative lack of insulin action or secretion, is characteristic of Type 2 Diabetes Mellitus (Bal et al., 2011). Additionally, there are multiple risk factors for developing type 2 diabetes, including obesity, genetics, physical inactivity and unhealthy diet. As of 2015, the International Diabetes Federation suggests that 415 million people aged 20-79 years worldwide have a diagnosis of diabetes mellitus. Furthermore, diabetes mellitus has been shown to be a global public health burden; by 2040, it is predicted that there will be 200 million diabetic individuals worldwide (Khaneshi et al., 2013; Ahmed et al., 2025). Strong substances found in medicinal plants can be utilized to treat illnesses or as fundamental ingredients to make synthetic medications (Dkhil et al., 2016). Berberis vulgaris is utilized traditionally as a beneficial medical herb because it contains a unique therapeutic chemical called berberine, a powerful alkaloid with antidiabetic, anti-inclement and antimicrobial characteristics confirmed by current science (Hemmati et al., 2016). According to (Minaiyan et al., 2011) has revealed that Berberis vulgaris is a herb rich in isoquinoline alkaloid, which has lipid-modulating qualities in addition to its beneficial actions, such as broad antibacterial and glucose-lowering qualities that show both in vitro and clinical. Berberine and other compounds have been shown to have significant worldwide benefits, making medicinal herbs an enormous biological source that can be utilized in cutting-edge contemporary medications (Rafati et al., 2025; Al-Mashhadani  et al., 2026). Over the past 30 years, 50% of approved drugs are either directly or indirectly derived from natural ingredients, with plants predominating in this group According to (Rahimi-Madiseh et al., 2017). Due to their accessibility and cultural acceptance, medicinal herbs may be an excellent alternative for human healthcare, particularly in areas of the world where standard medical procedures are either unavailable or too expensive (Ahmad et al., 2019).

Induction of diabetes using streptozotocin (STZ)
 
All forty male Wistar rats were given 2 weeks worth of 10% fructose in drinking water prior to receiving one (1) 40 mg/kg body weight STZ injection into the peritoneum to induce diabetes. The glucose levels were determined at 72 hours post STZ injection (diabetes confirmed if glucose ³250 mg/dL with the Acu-Check glucometer).
 
Grouping and treatment of experimental animals
 
Four groups of rats were created.
G1: Regular control rats.
G2: BVE rats at dose oraly 200 mg/kg according to (Sonei et al., 2020).
G3: Control rats with diabetes by intra-abdominal injection 40 mg/kg bwt according to (Al-Attar  et al., 2019).
G4: 250 mg/kg of BE plus diabetic rats.
       
The rats were given a single daily dose of plant extracts (200 mg/kg of BVE) after 21 days of diabetes maintenance. Group 1 was the control group, receiving simply food and water. Normal rats in Group 2 were given 250 mg/kg of BVE. Group 4 consisted of diabetes groups that received 250 mg/kg of BVE, while Group 3 was the untreated diabetic (diabetic control) group. For 21 days, the treatments were given as single daily doses of 1 milliliter of the extract.
 
Blood and tissue sampling
 
After sodium pentobarbital euthanasia each rat received an intraperitoneal injection of ≥100 mg/kg anesthetic. After collection serum was frozen at -20°C until analyzed biochemically. Liver samples were collected after rinsed with cold saline and placed in 10% neutral buffer formalin until analyzed histologically.
 
Serum liver enzymes
 
The DxC800 system was used to measure serum ALP using an AMP buffer (2-Amino-2-Methyl-1-Propanol) in order to examine the rate of change in absorbance. The DxC800 kinetic rate method was used to assess serum ALT and AST, looking at the rate of change in absorbance as directly related to the ALT activity (Hasan et al., 2024).
 
Histological investigation
 
Each rat’s liver was fixed in a neutral buffer with 10% a formalin in order to prepare it for paraffin wax sectioning. Hematoxylin and eosin were used to stain a portion of the liver. must undergo a histopathological examination in accordance with (Hameed et al., 2025).
 
Immunohistochemical detection
 
Conferring to (Hasan et al., 2023), Apoptotic ki67 in the liver was detected using the Avidin-Biotin-Complex method.

Ethical approval
 
Ethical approval for working on laboratory animals was obtained under the approval obtained from Biotechnology Research Center/ Al-Nahrain University.
 
Statistical analysis
 
As described previously, the data was expressed as mean±standard deviation (SD) (n=3). Statistical analysis of data was performed with a 1-way analysis of variance (ANOVA) to assess statistical significance, followed by Duncan’s multiple comparisons method between the treated and control groups, within each treatment group.

Effect of BVE on Liver functions
 
Our results (Table 1) show that animals treated with STZ exhibited elevated levels of both ALT and AST. However, when these same animals were treated with BVE extract, a significant improvement in both ALT and AST was observed.


 
Liver histopathology
 
Our results (Fig 1) show that animals treated with STZ suffered liver tissue damage and that a slight improvement was observed when STZ-treated animals were treated with BVE extract.


 
ki67 immunohistochemical changes in liver
 
Our results (Fig 2) show that STZ-treated animals experienced damage to the ki67 protein in liver tissue. However, when STZ-treated animals were treated with BVE extract, a slight improvement in the ki67 protein in liver tissue was observed.


       
An herbal supplement called common barberry (Berberis vulgaris) extract is usually made from the bark of the roots or stems. It is well-known for its strong active ingredients, most notably berberine, which is used medicinally to control blood sugar, enhance metabolism, reduce inflammation and support digestive and heart health according to Dkhil et al., (2016; Ghiath et al., (2025). It is regarded as one of the most effective natural supplements for treating insulin resistance and controlling blood sugar levels. Its applications include blood sugar and metabolism modulation. Its effects are comparable to those of metformin in certain trials according to Fatehi et al., (2005). Additionally, it encourages regular bowel movements and eases digestive discomfort by lowering inflammation and improving digestive health according to (Kiasalari et al., 2011). In addition, it is proven to reduce LDL (bad) and triglyceride levels, thereby reducing overall cholesterol levels; and it has anti-inflammatory, antioxidant, antimicrobial and antibacterial properties (Javad-Mousavi et al., 2016; Rasheed et al., 2025). The present study demonstrated that barberry extract improved liver function markers in STZ treated diabetic rat models (Table 1). Consistent with previous findings (Imenshahidi et al., 2016), treatment with BVE improved hepatic architecture as assessed by histological analysis (Fig 1) and increased Ki67 expression (Fig 2) in STZ treated diabetic rat models. The findings of this study are consistent with those of another study that demonstrated the benefits of using BVE as an adjunct to therapy for a variety of diseases (Rahimi-Madiseh  et al., 2017).
       
A kind of type 1 diabetes called as “streptozotocin-induced diabetes” is caused by intraperitoneal streptozotocin injections, which kill pancreatic beta cells and reduce insulin output (Amer et al., 2004). A cytotoxic chemical substance called streptozotocin (STZ) is mostly utilized in research to create animal models of diabetes by killing pancreatic beta cells. Additionally, some forms of pancreatic islet cancers are treated with it as a chemotherapy (Khaki et al., 2010). Beta cell toxicity is one of the main causes of the death of the pancreatic beta cells that produce insulin, which results in a reduction in insulin release and the onset of type 1 diabetes (Furman, 2015). In scientific research, it is also employed in high or repeated dosages to cause hyperglycemia (Navarro Casado et al., 2010). Additionally, it damages cells’ DNA, which results in cell death, especially in pancreatic cancer cells (Abeeleh et al., 2009). From the results in Table 1, we observe that rats treated with the diabetic STZ exhibited elevated liver enzymes due to damage to pancreatic beta cells. These findings agree with those of Nelli et al., (2013), who demonstrated in his research that STZ causes damage to liver enzymes.Our results also demonstrate that STZ in the third group causes damage to liver tissue (Fig 1) and also damages KI67 expression (Fig 2). These results are consistent with those of (Suresh et al., 2012).

Our study concludes that the BVE significantly improves liver enzymes, liver tissue and Ki67 expression in the liver tissue of diabetic male rats. We suggest conducting further experiments on the BVE and on various diseases.

Thanks to the authors for their financial support of the article.
 
Funding
 
None.
 

 The authors declare that there is no conflict of interest between the authors.