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Full Research Article

Effects of Nigella Sativa Oil extract: Histopathological Changes and Blood Glucose Level in Diabetic Male Rats

S
Sura Maan Salim1,*
0000-0003-2361-6812
1Pharmacognosy department, College of Pharmacy, University of Mosul, Iraq.

ABSTRACT

Background: Nigella sativa has been traditionally used for treatment of different diseases and their complication including diabetes. The purpose of this study was to examine the consequences of diabetic mellitus on the tissue of pancreas and kidney and the curative and protective impacts of nigella sativa oil compared to metformin.

Methods: A total of 30 male Wistar rats were subclassified into 5 groups, control group on normal diet and no intervention, diabetic group administered 70 mg/kg STZ as a single IP injection, metformin group administered70 mg/kg STZ as a single IP injection and 150 mg/kg/day metformin. Nigella sativa 2 ml group administered70 mg/kg STZ as a single IP injection and Nigella sativa 2 mL/kg/rat daily. Nigella sativa 4 ml group administered 70 mg/kg STZ as a single IP injection and Nigella sativa 2 mL/kg/rat daily. The treatment continued for 40 days. Blood collected for glucose measurement every 10 days and animal sacrificed at the end of the study, pancreas and kidneys harvested for histological study.

Result: The serum glucose levels in STZ group significantly increased reaching up to 600 mg/dl over different time points compared to less than 100 mg/dl in control group. The glucose levels were significantly (p<0.05) reduced in STZ+Met, Nigella sativa 2 ml group and Nigella sativa 4 ml group compared to STZ group. The histological sections have shown comparable improvement of kidney and pancreas sections. Although the amount and rate of damage reduction differ between treatments, the results showed that both doses considerably lowered blood glucose levels over time. However, the most significant glucose-lowering effect was established by metformin, which is align with its well-established pharmacological profile.

INTRODUCTION

Diabetes mellitus is one of the major causes of morbidity in affluent nations and is likely to cause serious metabolic problems with the greatest rate of global growth (Alhur et al., 2025). Particularly in underdeveloped nations with limited resources, medicinal plants are crucial in the treatment of diabetes mellitus (Sadiq et al., 2021). The benefits of medicinal plants with hypoglycemic effects in the treatment of diabetes mellitus have been validated by various investigations and researches (Tawfeeq et al., 2025), These plants’ actions may rectify biochemical parameters imbalances and slow the onset of diabetes consequences (Erkılıç and Bayraktar, 2025; Jamir et al., 2024; Sahu et al., 2025). Furthermore, several of the novel bioactive medications that have been extracted from medicinal plants in recent years have demonstrated antidiabetic effect that is more efficient than oral hypoglycemic medications used in clinical therapy (Chahrour et al., 2025; Dahy et al., 2026). Due to the adverse consequences associated with the use of insulin and oral hypoglycemic medications, there is currently a greater need for natural substances with antidiabetic activity (Alqahtani et al., 2022; Assi et al., 2016; Willcox et al., 2021).
       
It is known that around 400 plants have the ability to reduce blood sugar. Additionally, certain plants have lowering effects on blood sugar (AL-Ishaq  et al., 2019; Singab and Youssef, 2014). On the other hand, little is known about herbs that have hypoglycemic impacts. Insulin and oral hypoglycemic medications such biguanides and sulfonylureas are used to treat the pathophysiology of diabetic mellitus (Rashwan et al., 2023). Unfortunately, none of the oral manufactured hypoglycemic medications have been effective in preserving glucose levels, aside from a number of adverse effects (Khajuria et al., 2018; Stein et al., 2013). In order to treat hyperglycemia and rectify dyslipidemia, which would lower the risk of cardiovascular problems from diabetes, novel, comparatively non-toxic therapeutic treatments are required (Ahmad et al., 2024; Furman, 2021).
       
Seed of blessing (Habatul-barakah in Arabic nations), black seed and black cumin are some of the common names for the herbal plant Nigella sativa (Family Ranunculaceae) (Miah et al., 2023; Mollazadeh et al., 2017). For many years, the seeds have been utilized regionally in the Middle East, Far East and Asia as a condiment or food flavoring and as a potent herbal remedy for many ailments (Dabeer et al., 2022). Folklore uses the seed or its oil to treat a variety of illnesses (Bhat, 2011; Dabeer et al., 2022). It serves as a condiment, lactagogue, vermifuge and diuretic (Bhat, 2011). Fever, the flu, inflammation, asthma, headaches, warts, scorpion stings and snake bites are all commonly treated with it (Rashidmayvan et al., 2019). Numerous studies have shown that Nigella sativa seeds or their oil have a wide range of pharmacological effects, including antimicrobial, antioxidant, analgesic, anti-diabetic, anticancer, anti-inflammatory and antihypertensive (Mahomoodally et al., 2022; Maideen, 2025; Qahwaji and Serafi, 2023). In rats, nigella sativa oil (NSO) exhibited strong anti-inflammatory and analgesic effects, as well as immunosuppressive and cytotoxic effects both in vitro and in vivo. In rats, the petroleum ether extract had insulin-sensitizing and lipid-lowering effects (Sangi et al., 2020). The effects of NSO on blood glucose and histological parameters in STZ-induced diabetic rats are little understood and few studies have been done. Thus, the purpose of this study is to determine whether giving NSO to STZ-induced diabetic rats after eight weeks may improve blood glucose and protect histological tissues.

MATERIALS AND METHODS

Materials
 
Nigella sativa seeds were purchased from local markets in Mosul, Iraq. The oil was produced by cold pressing Nigella sativa seeds using a squeezing machine. Ten days after extraction, the oil was filtered to get rid of solid residues and before being used, it was kept in a container away from heat and sunlight. Streptozotocin (STZ) was obtained from Sigma Chemical Co. (St. Louis, MO, USA) and metformin tablets from Merck Sante’ S.A.S. (Lyon, France).
 
Animals
 
Male Wistar rats weighing (190-220 g) were obtained from the Animal Experimental Unit in faculty of veterinary medicine, University of Mosul. The rats were kept in cages in a well-ventilated room and a controlled temperature (25°C±2°C) with nearly 12 hours light and 12 hours dark cycle, 50%±10% humidity. The rats consumed normal commercial food and drinking water as desired, without restriction.
 
Methods and experimental design
 
Streptozotocin was diluted in saline, 70 mg/kg and injected by a single intraperitoneal injection to induce diabetes mellitus. The Rats were allocated into five groups each group comprise six rats: Group 1 (control), basal diet rats. Group 2: the diabetic rats (STZ). Group 3, the diabatic rats were administrated metformin 150 mg/kg/day. Group 4, the diabetic rats were administrated with NSO 2 mL/kg/rat daily. Group 5, the diabetic rats were administered NSO  via gavage 4mL/kg/rat daily for 40 days (Khaldi et al., 2018; Pop et al., 2020).
 
Histopathological analysis
 
A midline, longitudinal incision was made in the sedated rats, extending from the manubrium sterni to the lower belly. To reveal the abdominal viscera, the skin, fascia and muscles were removed. Following exposure, the kidneys and pancreas were removed and placed in a vial with a 10% formaldehyde solution for histological study.
 
Blood collection
 
The rats were fasted for eight hours on days 0, 10, 20, 30 and 40 prior to blood collection; water was not limited. Using a heparinized capillary tube, blood samples were drawn from the rats’ orbital venous plexus and placed into non-heparinized tubes. Before the glucose level was measured using an automatic analyzer (Architect c8000 Clinical Chemistry System, USA). Centrifuge was used at 3000 rpm for 20 minutes to separate clear serum samples and kept at -20°C for further investigations.
 
Statistical analysis
 
Statistical analysis was performed using SPSS version 26. Data were expressed as mean±SD. One-way ANOVA followed by comparison of each treated group with control were used to analyze differences between groups, p<0.05 was considered statistically significant. Each treatment group (Metformin, 2 mL NSO, 4 mL NSO) is compared directly with the Control group using Welch’s t-test.
 

RESULTS AND DISCUSSION

All body organs are known to be harmed or damaged by diabetes mellitus, the pancreas and kidneys are vulnerable to these side effects. Diabetes mellitus has become a worldwide problem as the number of patients raises daily. Finding a medication with little or no adverse effects is crucial and challenging for most researchers (Manikandan et al., 2018). In the current study, the impacts of the anti-hyperglycemic effect of Nigella sativa oil, was compared to the drug metformin, which is commonly prescribed to treat diabetes mellitus (Rashwan et al., 2023). The purpose of this study was to examine the preventive effects of nigella sativa oil on the histological damages of the kidney and pancreas caused by diabetes. According to this study, diabetes mellitus damaged the kidney and pancreas even in a brief period of time. Nigella sativa oil was used at two doses (2 mL/kg and 4 mL/kg) in comparison to metformin. Although the amount and rate of damage reduction differ between treatments, the results showed that both doses considerably lowered blood glucose levels over time (Wang et al., 2015; Wang et al., 2015). However, the most significant glucose-lowering effect was established by metformin, which is align with its well-established pharmacological profile (Foretz et al., 2019).
       
The results presented in Table 1 demonstrated the effects of Metformin, 2 mL/kg NSO and 4 mL/kg NSO on blood glucose levels over 40 days, compared with the Control group. Mean±SD values demonstrate the glucose profile for each group across the different time points and significance stars indicate the statistical difference between treatment groups and control. The results of the histopathological sections mainly focused on two features of the tissue, infiltration of the cell and interstitial changes occurring in the pancreas and kidney, over a period of time after induction of diabetic in experimental rats.

Table 1: Blood glucose levels of the studied groups over different time periods.


       
The starting point of all study groups began at day zero with comparable glucose measurements. On day 10, the significant decrease was noted of treatment groups with comparison to control, meanwhile, metformin records a noticeable decline in glucose level. By day 20, the drop was very significant and the reduction continued into Days 30 and 40. These findings indicates the ability of metformin to suppress hepatic gluconeogenesis, promote peripheral insulin sensitivity and enhance glucose digestion. Previous researches documents similar results as metformin are the ideal glucose lowering agent for diabetic individuals (Rena et al., 2017).
       
However, a significant reduction in glucose levels were recorded by both doses of NSO, though the lowering effect was more gradual compared to Metformin. Starting on Day 10, group 4 (2 mL/kg) had gradual but steady declines, then by Days 30 and 40 the reduction was very significant. An obvious dose-response relationship was recorded as the higher dose of NSO (4 mL/kg) had a greater antihyperglycemic impact than the lower dose (2 mL/kg). Higher concentrations of bioactive compounds such as thymoquinone and other ingredients that have anti-inflammatory, antioxidant and insulin-sensitizing properties could be the cause of this improved efficacy. These results are comparable with growing evidence that Nigella sativa improve insulin signaling, protects pancreatic β-cells and modifies glucose metabolism to improve glycemic control (Faisal Lutfi  et al., 2021; Maideen, 2021).
       
In the current study, nigella sativa oil lowers blood glucose significantly in both doses (2 ml and 4 ml/kg) on day 10 (2 ml) day 20, 30 and 40 (2 ml and 4 ml) in comparison to day 0, thus, demonstrating nigella sativa oil possess antidiabetic impact (Table 1). The metformin (150 mg/kg body weight) also reduce blood glucose significantly on day 10, 20,30 and day 40 in comparison to day 0. Thus, the therapeutic effect of nigella sativa oil was close to that of metformin. As the blood glucose lowering effect of Nigella sativa oil (2 ml and 4 ml) was comparable with metformin group on day 10, day 20, 30 and day 40. As a result, these outcomes demonstrate that blood glucose reducing effect of Nigella sativa oil (2 ml and 4 ml) is comparable with metformin but with less efficiency (150 mg/kg body weight) (Rashwan et al., 2023).
       
Our study’s findings indicate that diabetes mellitus significantly harms the tissue of the kidneys and pancreas (Fig 1 and Fig 2). Despite the short period of this study, certain detrimental consequences were obvious in the histological results. Acute inflammation was noticed; interstitial congestion and infiltration alterations were observed as well. These results were consistent with previous researches. Due to the anti-hyperglycemic effect of Nigella sativa oil, it was able to decrease the severity of tissue damage caused by diabetes mellitus. These results of Nigella sativa oil were found to be similar to those of metformin, which is also comparable with previous findings. Histopathology of these studies also revealed a significant reduction in capillary density, which is consistent with the current study (Assi et al., 2016; Foretz et al., 2019; Maideen, 2021).

Fig 1: A representative image for the histological section of pancreas of the rats of the studied groups.



Fig 2: A representative image for the histological section of kidney of the rats of the studied groups.


       
The histological sections from group 4 show that the pancreas tissue is partially protected from STZ complications and maintains the islet form, compared to the diabetic group, that show there is β-cell necrosis, vacuolation, bleeding and islet shrinkage (Fig 1). On the other hand, the pancreatic tissue of group 5 shows greater structural preservation and the islet architecture has been almost fully recovered. This indicates that 4 mL/kg of NSO preserve vacuolar destruction, blood vessels protection and reduce pancreatic inflammation. In addition, round, pale and normal β-cells, indicates the ability of NSO4 mL to lower STZ cytotoxity and insulin granules preservation. These findings are consistent with recent study conducted by (Rashid  et al., 2022).
       
The histological sections of kidney group 4, dose 2 mL/kg shows considerable but little renal protection, compared to group 5, dose 4 mL/kg has better improvements (Fig 2). The 4 mL dose offers: better tubular protection that was observed in STZ diabetic results, increased vascular stability and decreased capillary fragility and bleeding. Restoring glomerular filtration structures stops basement membrane thickening and glomerulosclerosis. With only minor residual damage, both doses maintained tubular and glomerular architecture. These results are consistent with current research outlining NSO’s renoprotective, antioxidant and anti-inflammatory activities (Alicic et al., 2017; AlSuhaymi, 2024). And, aligns with previous research showing that higher dosages of NSO improve renal tissue in diabetic rat models (Mahomoodally et al., 2022).

CONCLUSION

In conclusion, our findings show that Nigella sativa oil possess a strong antihyperglycemic effect and could be useful as a complementary natural treatment for controlling high blood sugar. In order to completely clarify NSO’s therapeutic potential and long-term safety profile, more research with bigger sample sizes, varying dosses, mechanistic analysis and histopathological study is recommended. It is challenging to predict the final outcome in such a short period. However, the findings indicate that diabetes mellitus damages numerous organs, including the pancreas and kidney, even in a brief period of time. Nigella sativa oil and the common medication Metformin both improve glucose levels and tissue damage. Throughout the study, metformin was most effective treatment compared to both doses of NSO. However, NSO could be a good complementary intervention for long-term glycaemic control, especially for people looking for natural remedies.

ACKNOWLEDGEMENT

The author is grateful for the University of Mosul for provided facility to accomplish this work.
 
Funding sources
 
The author received no financial support for the research, authorship, nor publication of this article.

CONFLICT OF INTEREST

The author does not have any conflict of interest

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    Full Research Article

    Effects of Nigella Sativa Oil extract: Histopathological Changes and Blood Glucose Level in Diabetic Male Rats

    S
    Sura Maan Salim1,*
    0000-0003-2361-6812
    1Pharmacognosy department, College of Pharmacy, University of Mosul, Iraq.

    ABSTRACT

    Background: Nigella sativa has been traditionally used for treatment of different diseases and their complication including diabetes. The purpose of this study was to examine the consequences of diabetic mellitus on the tissue of pancreas and kidney and the curative and protective impacts of nigella sativa oil compared to metformin.

    Methods: A total of 30 male Wistar rats were subclassified into 5 groups, control group on normal diet and no intervention, diabetic group administered 70 mg/kg STZ as a single IP injection, metformin group administered70 mg/kg STZ as a single IP injection and 150 mg/kg/day metformin. Nigella sativa 2 ml group administered70 mg/kg STZ as a single IP injection and Nigella sativa 2 mL/kg/rat daily. Nigella sativa 4 ml group administered 70 mg/kg STZ as a single IP injection and Nigella sativa 2 mL/kg/rat daily. The treatment continued for 40 days. Blood collected for glucose measurement every 10 days and animal sacrificed at the end of the study, pancreas and kidneys harvested for histological study.

    Result: The serum glucose levels in STZ group significantly increased reaching up to 600 mg/dl over different time points compared to less than 100 mg/dl in control group. The glucose levels were significantly (p<0.05) reduced in STZ+Met, Nigella sativa 2 ml group and Nigella sativa 4 ml group compared to STZ group. The histological sections have shown comparable improvement of kidney and pancreas sections. Although the amount and rate of damage reduction differ between treatments, the results showed that both doses considerably lowered blood glucose levels over time. However, the most significant glucose-lowering effect was established by metformin, which is align with its well-established pharmacological profile.

    INTRODUCTION

    Diabetes mellitus is one of the major causes of morbidity in affluent nations and is likely to cause serious metabolic problems with the greatest rate of global growth (Alhur et al., 2025). Particularly in underdeveloped nations with limited resources, medicinal plants are crucial in the treatment of diabetes mellitus (Sadiq et al., 2021). The benefits of medicinal plants with hypoglycemic effects in the treatment of diabetes mellitus have been validated by various investigations and researches (Tawfeeq et al., 2025), These plants’ actions may rectify biochemical parameters imbalances and slow the onset of diabetes consequences (Erkılıç and Bayraktar, 2025; Jamir et al., 2024; Sahu et al., 2025). Furthermore, several of the novel bioactive medications that have been extracted from medicinal plants in recent years have demonstrated antidiabetic effect that is more efficient than oral hypoglycemic medications used in clinical therapy (Chahrour et al., 2025; Dahy et al., 2026). Due to the adverse consequences associated with the use of insulin and oral hypoglycemic medications, there is currently a greater need for natural substances with antidiabetic activity (Alqahtani et al., 2022; Assi et al., 2016; Willcox et al., 2021).
           
    It is known that around 400 plants have the ability to reduce blood sugar. Additionally, certain plants have lowering effects on blood sugar (AL-Ishaq  et al., 2019; Singab and Youssef, 2014). On the other hand, little is known about herbs that have hypoglycemic impacts. Insulin and oral hypoglycemic medications such biguanides and sulfonylureas are used to treat the pathophysiology of diabetic mellitus (Rashwan et al., 2023). Unfortunately, none of the oral manufactured hypoglycemic medications have been effective in preserving glucose levels, aside from a number of adverse effects (Khajuria et al., 2018; Stein et al., 2013). In order to treat hyperglycemia and rectify dyslipidemia, which would lower the risk of cardiovascular problems from diabetes, novel, comparatively non-toxic therapeutic treatments are required (Ahmad et al., 2024; Furman, 2021).
           
    Seed of blessing (Habatul-barakah in Arabic nations), black seed and black cumin are some of the common names for the herbal plant Nigella sativa (Family Ranunculaceae) (Miah et al., 2023; Mollazadeh et al., 2017). For many years, the seeds have been utilized regionally in the Middle East, Far East and Asia as a condiment or food flavoring and as a potent herbal remedy for many ailments (Dabeer et al., 2022). Folklore uses the seed or its oil to treat a variety of illnesses (Bhat, 2011; Dabeer et al., 2022). It serves as a condiment, lactagogue, vermifuge and diuretic (Bhat, 2011). Fever, the flu, inflammation, asthma, headaches, warts, scorpion stings and snake bites are all commonly treated with it (Rashidmayvan et al., 2019). Numerous studies have shown that Nigella sativa seeds or their oil have a wide range of pharmacological effects, including antimicrobial, antioxidant, analgesic, anti-diabetic, anticancer, anti-inflammatory and antihypertensive (Mahomoodally et al., 2022; Maideen, 2025; Qahwaji and Serafi, 2023). In rats, nigella sativa oil (NSO) exhibited strong anti-inflammatory and analgesic effects, as well as immunosuppressive and cytotoxic effects both in vitro and in vivo. In rats, the petroleum ether extract had insulin-sensitizing and lipid-lowering effects (Sangi et al., 2020). The effects of NSO on blood glucose and histological parameters in STZ-induced diabetic rats are little understood and few studies have been done. Thus, the purpose of this study is to determine whether giving NSO to STZ-induced diabetic rats after eight weeks may improve blood glucose and protect histological tissues.

    MATERIALS AND METHODS

    Materials
     
    Nigella sativa seeds were purchased from local markets in Mosul, Iraq. The oil was produced by cold pressing Nigella sativa seeds using a squeezing machine. Ten days after extraction, the oil was filtered to get rid of solid residues and before being used, it was kept in a container away from heat and sunlight. Streptozotocin (STZ) was obtained from Sigma Chemical Co. (St. Louis, MO, USA) and metformin tablets from Merck Sante’ S.A.S. (Lyon, France).
     
    Animals
     
    Male Wistar rats weighing (190-220 g) were obtained from the Animal Experimental Unit in faculty of veterinary medicine, University of Mosul. The rats were kept in cages in a well-ventilated room and a controlled temperature (25°C±2°C) with nearly 12 hours light and 12 hours dark cycle, 50%±10% humidity. The rats consumed normal commercial food and drinking water as desired, without restriction.
     
    Methods and experimental design
     
    Streptozotocin was diluted in saline, 70 mg/kg and injected by a single intraperitoneal injection to induce diabetes mellitus. The Rats were allocated into five groups each group comprise six rats: Group 1 (control), basal diet rats. Group 2: the diabetic rats (STZ). Group 3, the diabatic rats were administrated metformin 150 mg/kg/day. Group 4, the diabetic rats were administrated with NSO 2 mL/kg/rat daily. Group 5, the diabetic rats were administered NSO  via gavage 4mL/kg/rat daily for 40 days (Khaldi et al., 2018; Pop et al., 2020).
     
    Histopathological analysis
     
    A midline, longitudinal incision was made in the sedated rats, extending from the manubrium sterni to the lower belly. To reveal the abdominal viscera, the skin, fascia and muscles were removed. Following exposure, the kidneys and pancreas were removed and placed in a vial with a 10% formaldehyde solution for histological study.
     
    Blood collection
     
    The rats were fasted for eight hours on days 0, 10, 20, 30 and 40 prior to blood collection; water was not limited. Using a heparinized capillary tube, blood samples were drawn from the rats’ orbital venous plexus and placed into non-heparinized tubes. Before the glucose level was measured using an automatic analyzer (Architect c8000 Clinical Chemistry System, USA). Centrifuge was used at 3000 rpm for 20 minutes to separate clear serum samples and kept at -20°C for further investigations.
     
    Statistical analysis
     
    Statistical analysis was performed using SPSS version 26. Data were expressed as mean±SD. One-way ANOVA followed by comparison of each treated group with control were used to analyze differences between groups, p<0.05 was considered statistically significant. Each treatment group (Metformin, 2 mL NSO, 4 mL NSO) is compared directly with the Control group using Welch’s t-test.
     

    RESULTS AND DISCUSSION

    All body organs are known to be harmed or damaged by diabetes mellitus, the pancreas and kidneys are vulnerable to these side effects. Diabetes mellitus has become a worldwide problem as the number of patients raises daily. Finding a medication with little or no adverse effects is crucial and challenging for most researchers (Manikandan et al., 2018). In the current study, the impacts of the anti-hyperglycemic effect of Nigella sativa oil, was compared to the drug metformin, which is commonly prescribed to treat diabetes mellitus (Rashwan et al., 2023). The purpose of this study was to examine the preventive effects of nigella sativa oil on the histological damages of the kidney and pancreas caused by diabetes. According to this study, diabetes mellitus damaged the kidney and pancreas even in a brief period of time. Nigella sativa oil was used at two doses (2 mL/kg and 4 mL/kg) in comparison to metformin. Although the amount and rate of damage reduction differ between treatments, the results showed that both doses considerably lowered blood glucose levels over time (Wang et al., 2015; Wang et al., 2015). However, the most significant glucose-lowering effect was established by metformin, which is align with its well-established pharmacological profile (Foretz et al., 2019).
           
    The results presented in Table 1 demonstrated the effects of Metformin, 2 mL/kg NSO and 4 mL/kg NSO on blood glucose levels over 40 days, compared with the Control group. Mean±SD values demonstrate the glucose profile for each group across the different time points and significance stars indicate the statistical difference between treatment groups and control. The results of the histopathological sections mainly focused on two features of the tissue, infiltration of the cell and interstitial changes occurring in the pancreas and kidney, over a period of time after induction of diabetic in experimental rats.

    Table 1: Blood glucose levels of the studied groups over different time periods.


           
    The starting point of all study groups began at day zero with comparable glucose measurements. On day 10, the significant decrease was noted of treatment groups with comparison to control, meanwhile, metformin records a noticeable decline in glucose level. By day 20, the drop was very significant and the reduction continued into Days 30 and 40. These findings indicates the ability of metformin to suppress hepatic gluconeogenesis, promote peripheral insulin sensitivity and enhance glucose digestion. Previous researches documents similar results as metformin are the ideal glucose lowering agent for diabetic individuals (Rena et al., 2017).
           
    However, a significant reduction in glucose levels were recorded by both doses of NSO, though the lowering effect was more gradual compared to Metformin. Starting on Day 10, group 4 (2 mL/kg) had gradual but steady declines, then by Days 30 and 40 the reduction was very significant. An obvious dose-response relationship was recorded as the higher dose of NSO (4 mL/kg) had a greater antihyperglycemic impact than the lower dose (2 mL/kg). Higher concentrations of bioactive compounds such as thymoquinone and other ingredients that have anti-inflammatory, antioxidant and insulin-sensitizing properties could be the cause of this improved efficacy. These results are comparable with growing evidence that Nigella sativa improve insulin signaling, protects pancreatic β-cells and modifies glucose metabolism to improve glycemic control (Faisal Lutfi  et al., 2021; Maideen, 2021).
           
    In the current study, nigella sativa oil lowers blood glucose significantly in both doses (2 ml and 4 ml/kg) on day 10 (2 ml) day 20, 30 and 40 (2 ml and 4 ml) in comparison to day 0, thus, demonstrating nigella sativa oil possess antidiabetic impact (Table 1). The metformin (150 mg/kg body weight) also reduce blood glucose significantly on day 10, 20,30 and day 40 in comparison to day 0. Thus, the therapeutic effect of nigella sativa oil was close to that of metformin. As the blood glucose lowering effect of Nigella sativa oil (2 ml and 4 ml) was comparable with metformin group on day 10, day 20, 30 and day 40. As a result, these outcomes demonstrate that blood glucose reducing effect of Nigella sativa oil (2 ml and 4 ml) is comparable with metformin but with less efficiency (150 mg/kg body weight) (Rashwan et al., 2023).
           
    Our study’s findings indicate that diabetes mellitus significantly harms the tissue of the kidneys and pancreas (Fig 1 and Fig 2). Despite the short period of this study, certain detrimental consequences were obvious in the histological results. Acute inflammation was noticed; interstitial congestion and infiltration alterations were observed as well. These results were consistent with previous researches. Due to the anti-hyperglycemic effect of Nigella sativa oil, it was able to decrease the severity of tissue damage caused by diabetes mellitus. These results of Nigella sativa oil were found to be similar to those of metformin, which is also comparable with previous findings. Histopathology of these studies also revealed a significant reduction in capillary density, which is consistent with the current study (Assi et al., 2016; Foretz et al., 2019; Maideen, 2021).

    Fig 1: A representative image for the histological section of pancreas of the rats of the studied groups.



    Fig 2: A representative image for the histological section of kidney of the rats of the studied groups.


           
    The histological sections from group 4 show that the pancreas tissue is partially protected from STZ complications and maintains the islet form, compared to the diabetic group, that show there is β-cell necrosis, vacuolation, bleeding and islet shrinkage (Fig 1). On the other hand, the pancreatic tissue of group 5 shows greater structural preservation and the islet architecture has been almost fully recovered. This indicates that 4 mL/kg of NSO preserve vacuolar destruction, blood vessels protection and reduce pancreatic inflammation. In addition, round, pale and normal β-cells, indicates the ability of NSO4 mL to lower STZ cytotoxity and insulin granules preservation. These findings are consistent with recent study conducted by (Rashid  et al., 2022).
           
    The histological sections of kidney group 4, dose 2 mL/kg shows considerable but little renal protection, compared to group 5, dose 4 mL/kg has better improvements (Fig 2). The 4 mL dose offers: better tubular protection that was observed in STZ diabetic results, increased vascular stability and decreased capillary fragility and bleeding. Restoring glomerular filtration structures stops basement membrane thickening and glomerulosclerosis. With only minor residual damage, both doses maintained tubular and glomerular architecture. These results are consistent with current research outlining NSO’s renoprotective, antioxidant and anti-inflammatory activities (Alicic et al., 2017; AlSuhaymi, 2024). And, aligns with previous research showing that higher dosages of NSO improve renal tissue in diabetic rat models (Mahomoodally et al., 2022).

    CONCLUSION

    In conclusion, our findings show that Nigella sativa oil possess a strong antihyperglycemic effect and could be useful as a complementary natural treatment for controlling high blood sugar. In order to completely clarify NSO’s therapeutic potential and long-term safety profile, more research with bigger sample sizes, varying dosses, mechanistic analysis and histopathological study is recommended. It is challenging to predict the final outcome in such a short period. However, the findings indicate that diabetes mellitus damages numerous organs, including the pancreas and kidney, even in a brief period of time. Nigella sativa oil and the common medication Metformin both improve glucose levels and tissue damage. Throughout the study, metformin was most effective treatment compared to both doses of NSO. However, NSO could be a good complementary intervention for long-term glycaemic control, especially for people looking for natural remedies.

    ACKNOWLEDGEMENT

    The author is grateful for the University of Mosul for provided facility to accomplish this work.
     
    Funding sources
     
    The author received no financial support for the research, authorship, nor publication of this article.

    CONFLICT OF INTEREST

    The author does not have any conflict of interest

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