JAHP_13_s1_921-928

Introduction

Artemisia herba alba, also known as white wormwood, is a perennial plant found in Mediterranean dry steppes, characterized by its white, woolly stems and foliage (Mohammed et al., 2021). White wormwood, or Artemisia herba-alba, is well-known for a wide variety of bioactive substances that support its therapeutic qualities. Artemisia herba alba therapy was linked to higher blood levels of albumin and plasma proteins in addition to decreased liver enzyme levels. This is significant because the liver produces albumin, a crucial protein whose levels reflect both overall health and liver function (Belinskaia et al., 2024). Research on Artemisia herba alba’s potential impacts on kidney health has shown that it exhibits both potentially nephrotoxic and nephroprotective qualities in certain situations (Sekiou et al., 2021). The antioxidant qualities of A. herba alba shield the tissue of the renal from oxidative stress, minimizing damage to the kidneys in particular that results from diabetes and elevated levels of blood glucose (Darenskaya et al., 2023). Nanotechnology was used to clarify in every technology that can be used to manipulate matter at the level of molecules and make matters, devices, and structures having a dimension of (1-100 nm) at least in one direction. The drugs were delivered directly to specific parts of the body using nanoparticle engineering, increasing treatment effectiveness and reducing adverse effects. For instance, medical drugs for neurological disorders can be delivered using nanoparticles, which can cross the blood-brain barrier (Elumalai et al., 2024). Formulations based on nanotechnologies, such as solid lipid nanoparticles, polymeric nanoparticles, and nanoemulsions, improve hydrophobic drug solubility by encapsulating medications, shielding them from deterioration, and promoting improved absorption (Sultana et al., 2022). Especially for low-permeability medications, nanoparticles have enhanced drug transport into systemic circulation by efficiently penetrating biological membranes and using paracellular or transcellular pathways to bypass the epithelial barriers of the gut (Zheng et al., 2024). The research focuses on developing glucose-responsive nanoparticles that improve the release of insulin in response to blood glucose levels, potentially enhancing glycaemic management compared to traditional insulin therapy (Rege et al., 2017).

The management of glycemia could be improved by using nanotechnology to produce glucose-responsive nanoparticles that release insulin in response to an increase in blood sugar levels (Andreadi et al., 2024). Cobalt nanoparticles possess unparalleled physicochemical properties and nanoscale dimensions that enable their use toward a wide range of advanced applications, including catalysis, energy storage, imaging, medicine, microelectronics, and drug delivery systems. The fundamental magnetic characteristics enable cobalt nanoparticles to serve as a targeted transporter for drug delivery, offering an opportunity for site-specific therapeutic interventions. Moreover, their special surface properties and small size make cobalt nanoparticles effective sensors for detecting several substances, supporting their incorporation into biomedical, analytical, and monitoring technologies (Vodyashkin et al., 2022).

This study aims evaluation and effectiveness of the new synthesized cobalt nanoparticles coated with Artemisia herba alba, Artemisia herba alba nanoparticles, and the extract of Artemisia herba alba on hyperglycemia induced in laboratory male rats.

Materials and Methods

Collection and preparation of Artemisia herba alba

In Basrah, Iraq, Artemisia herba alba was gathered from the neighbourhood market. Sultana et al. (2009) state that in independent studies, 100 grammes of air-dried powdered plant material were extracted using 500 milliliters of an aqueous methanol solvent (methanol: water, 80% v/v) for eight hours under Soxhlet conditions on a water bath. The plant extract was liberated, and its solvent was concentrated using a rotary evaporator set at 45 °C. To determine the yield, the dried crude concentrated extracts of Artemisia herba alba were weighed and kept in a refrigerator at 4 °C until they were utilized.

Hydrothermal method of CoNPs biosynthesis

According to Ansari et al. (2017), 10 ml of the Artemisia herba alba extract (200 mg/ ml) concentration was added to cobalt nitrate solution (6 g) to synthesize cobalt oxide (Co3O4) nanoparticles, and then a KOH solution was added, followed by 15 min stirring, after adding the hydrazine monohydrate and oleic acid solutions, the mixture’s volume reached two-thirds of the autoclave’s total volume. It was then stirred for two hours to completely dissolve the solid reagents before being transferred into a Teflon-coated autoclave and placed in an electric oven, where it was kept at 160 oC for twenty-four hours. The autoclave has been allowed to naturally cool to ambient temperature after twenty-four hours. Ultimately, the solution’s final preparation was centrifuged, the liquid phase was decanted, and the resulting black precipitate was dried in an oven at 70 oC to separate the produced Cobalt NPs from the liquid phase (Ansari et al., 2017).

Experimental animals

Mature domestic 30 male rats in good health, weighing between 300 and 400 grams. Before the research, the animals were given a week to acclimate to the lab environment under strict clean, hygienic and standard managing conditions at temperature (20-25°C), controlled room on a 12 hour light and 12 h dark (Shehab et al., 2024). The animals were divided into five groups, each containing eight male rats, and were given the following care:

Group 1: A control group, giving normal saline 0.5ml (I.P)
Group 2: Each rat was injected with alloxan (150 mg/kg) (Nagappa et al., 2003)
Group 3: Each rat was daily treated with cobalt nanoparticles coated with A. herba alba (104.5µg\ml)
Group 4: Each rat was daily treated with Artemisia herba alba nanoparticles (146µg\ml)
Group 5: Each rat was daily treated with Artemisia herba alba extract (500 mg/kg) (Awad et al., 2012)

Collection of blood sample and organs

At the end of the trail, blood samples have been collected from the hearts of the rats for biochemical analysis (glucose and insulin). Four ml of the blood was placed in an anticoagulant-free tube and centrifuged for 15 minutes at 4000 rpm. The serum was used for glucose and insulin analysis (Hafth et al., 2025). The pancreas was isolated and weighed using an electronic balance. The organ has been fixed by using formalin 10% for the histological examinations, and it was kept in a test cup until the examination.

Results

The Co3O4-NPs solution exhibited characteristic absorption peaks in the 200–800 nm wavelength range. The absorbance values of biogenic cobalt nanoparticles (Co3O4 NPs) in (Figure 1) show several peaks between 214, 319, and 232 nm. The reduction of cobalt ions is shown by the distinct peak that was seen at 232 nm. The absorption spectrum of Artemisia herba alba extract is distinguished by prominent bands with several peaks occurring at wavelengths of 250, 261, 292, and 660 nm. The first three peaks are likely due to the presence of flavonoids, phenolic acids, and terpenoids in the leaves and seeds extract. Lastly, the peak at 660 nm is indicative of the presence of chlorophyll (Figure 2). A shift in the Ar-Co NPs absorption peak following conjugation onto cobalt oxide nanoparticles suggests that artemisia herba alba and the CoO surface are interacting. enhanced or altered absorption peak intensity, indicating that the nanocomposite was successfully formed. Thus, the successful integration of Artemisia into CoO as well as the creation of nanoparticles are confirmed by the UV-Vis spectrum. Fourier-transform infrared spectroscopy (FT-IR) has been used to identify the functional groups on the surfaces of the Co3O4-NPs as well as the functional groups of the plant metabolites present in the aqueous extractof Artemisia herba alba. The FT-IR spectra showed strong peaks at wavenumbers such as 3554, 3415, and 3284 cm−1 that were generated by O-H and N-H stretch vibrations (Figure 3). The C=C and C=O vibration modes are prominent in 1734 and 1600, while the peaks at 2924 and 2854 cm−1 are associated with the s vibration of C-H groups. The band originating from the Co-O stretching vibration showed a prominent peak at 570 cm−1, with comparable peaks at 430 cm−1. According to the FT-IR results, acids, proteins, polyphenols, alkaloids, and carboxylic acid functional groups could be found in the Co3O4-NPs (Figure 4) (Abdulkareem et al., 2025). Scanning electron microscopy (SEM) has been employed to examine the surface morphology of the biosynthesized cobalt oxide nanoparticles (CoO-NPs). The appearance of small, smooth, spherical nanoparticles, individually and clustered, and the reason for this clustering may be due to the rapid evaporation of the sample for examination. The SEM image shows several NP sizes, including 56.85 nm, 80.72 nm, and 83.63 nm (Figure 5).

The images reveal a mixture of cuboidal and spherical morphologies, though some degree of agglomeration is observed. Such agglomeration is common in the synthesis of nanoparticles and can be attributed to factors such as van der Waals forces and high surface energy between particles. The EDX spectrum displays a significant signal in the Cobalt area, confirming CoNPs production. Because of plasmon surface resonance, metallic Cobalt nanocrystals often display an optical absorption peak at 1.5 KeV (Figure 6). Data from energy dispersive X-ray (EDX) reveal highly significant Cobalt. The presence of a dense Cobalt peak verified the reduction of Co(NO3)3 to nanoparticles. According to Figure 6, the EDX spectrum result showed that the elements C, O, Cl, and Co had the highest percentage of weight (63.9%, 19.5%, 10.0%, and 6.2%, respectively), while the elements K and Mo had the lowest percentages (0.3%) and 0.1%, respectively. The presence of carbon and oxygen indicates that the surface of the nanoparticles is accompanied by organic molecules, most likely phytochemicals from the green synthesis process. These phytochemicals are thought to play a crucial part in the production and stabilisation of the Co3O4-NPs by acting as both capping and reducing agents during synthesis. The synthesis of the Co3O4 NPs has been confirmed via X-ray diffraction (XRD) analysis. The Bragg’s reflections at (100), (101), and (201), respectively, were represented by the diffraction characteristics pertaining to 2θ at 24.95◦, 30.00◦, and 37.65◦ (Figure 7).

The nanoparticles crystal size was 109 nm. Debye Scherrer’s equation was used to determine the average crystalline structure size of the biosynthesised Co3O4-NPs. In this equation, k stands for the shape constant of the geometric factor (0.9), for wavelength, for line broadening at half-maximum intensity, for Bragg angle, and D for average crystalline size of the nanoparticles. According to Figure 7, the diffraction of the (111) plane has a sharp peak at 2θ = 29.00 that corresponds to Co3O4-NPs. This suggests that the synthesised Co3O4-NPs are monoclinic and crystalline. During synthesis, photomolecules were deposited on the surfaces of the Co3O4-NPs, causing these unknown peaks to form (Figure 7).

As shown in Table 1, the glucose and HbA1c have been significantly increased at (p≤0.05) after administrated of alloxan, but insulin has been significantly decreased at (p≤0.05) compared with the control group. Treated with cobalt nanoparticles causes a significant decrease in glucose and HbA1c levels but a significant increase in insulin levels at (p≤0.05) compared with the control group. Artemisia herba alba nanoparticles cause a significant decrease in glucose and HbA1c, and a significant increase in the levels of insulin (p≤0.05) compared with the untreated group. Additionally, the table shows a significant decrease in glucose and HbA1c, and a significant increase in insulin level (p ≤ 0.05) compared with the alloxan group. Figure 8 show the levels of glucose, HbA1c, and insulin in all groups. The histological section of the pancreas from the control group reveals the normal architecture of pancreatic parenchyma, comprising normal Langerhans islets and beta cells (Figure 9A). The pancreas of the alloxan group exhibits a disrupted architecture of pancreatic parenchyma, characterized by atrophied Langerhans islets, degenerative changes in beta cells, and cystic dilation of the pancreatic parenchyma (Figure 9B). CoNPs coated with A. herba alba pancreas show regenerated architecture of pancreatic parenchyma, consisting of normal Langerhans islets, normal beta cells (Figure 9C).

Table 1: Glucose, HbA1c, and insulin values in male rats.

Parameters/ Groups

Glucose (mg/dl)

HbA1c (%)

Insulin (ng/ml)

Control (0.9% N.S)

136.16

±15.36

4.17

±0.10

1.61

±0.52

Alloxan (150mg/kg)

483.66

±15.50

5.72

±0.68

0.40

±0.19

CoNPs coated with AHA(104.5µg\ml)

118.50

±8.43

3.40

±0.18

2.32

±0.59

Artemisia herba alba NPs(146µg\ml)

132.00

±12.99

3.65

±0.40

1.42

±0.31

Artemisia herba alba (500mg/kg)

212.33

±37.90

3.83

±0.55

0.84

±0.34

LSD

4.16

0.17

0.19

Discussion

This study showed that treating diabetic animals with Artemisia herba alba aqueous extract at a dose of 500 mg/kg once daily for one month caused a significant decrease

in the levels of glucose. This result was consistent with (Afolayan and Sunmonu, 2013; Mansi and Lahham, 2008). Artemisia herba alba contains glycosides and saponins, which reduce the glucose levels (Abdel-Hassan et al., 2002). It also contains flavonoids, which lower cholesterol and triglycerides, increase the secretion of insulin, and stimulate the beta cells of the pancreas to secrete more insulin by increasing the enzyme hepatic glucokinase (Al-Ishaq et al., 2019). The blood glucose-lowering effect could be due to causes beyond the pancreas, such as stimulating its uptake by peripheral tissues (Naik et al., 1991; Obatomi et al., 1994), increasing the activity of glycogenolytic enzymes (Naik et al., 1991), or Artemisia herba alba may decrease the secretion of opposing regulatory hormones such as cortisone, growth hormone, and glucagon (Roman-Ramos et al., 1995), or reduce the absorption of glucose from the digestive tract (Akhtar, 1991; Sharma et al., 1996). The study showed that treating diabetic animals with A. herba alba aqueous extract at a dose of 500 mg/kg once a day for one month leads to a significant increase in insulin levels in the blood serum. The result was consistent with (Mansi and Lahham, 2008). This is attributed to the fact that Artemisia herba alba extract contains active substances with an insulin-like effect. This stimulates pancreatic beta cells to secrete more insulin into the bloodstream (Wadood et al., 1992), which leads to increased glycogen deposition in the liver, leading to a reduction in glucose levels or an increase in insulin receptors (Kouzi et al., 1994).

The saponins found in wormwood also stimulate the secretion of insulin from undamaged pancreatic beta cells (Afolayan and Sunmonu, 2011). The presence of flavonoids in Artemisia herba alba, which lowers cholesterol and triglycerides, increases the secretion of insulin, and stimulates the beta cells of the pancreas to secrete more insulin by increasing the enzyme hepatic glucokinase (Al-Ishaq et al., 2019) or by increasing the activity of glycogenolytic enzymes (Naik et al., 1991), Through increased cell viability, decreased apoptosis, and improved insulin signaling pathways, an ethanolic extract of AHA was shown to reduce hyperglycemia (Ansari et al., 2022). AHA’s strong antioxidant properties help reduce oxidative stress caused by diabetes. By improving the function of the mitochondrial and reducing reactive oxygen species (ROS) levels, AHA protects pancreatic cells and enhances their insulin secretion efficiency (Caturano et al., 2023) Due to the properties of the plant and the characteristics of nanotechnology that makes the drugs could be delivered directly to specific parts of the body using nanoparticle engineering, increasing the effectiveness of the treatment and reducing adverse effects (Elumalai et al., 2024), and they corset the encapsulated nanoparticles from early metabolic collapse by gut wall or liver enzymes, guaranteeing that the active medication reaches its intended location. By using other absorption pathways to circumvent initial hepatic metabolism, they also eliminate the first-pass impact (Zheng et al., 2024).

We reported that Artemisia herba alba nanoparticles show an improvement in the decrease in blood glucose levels more than when treated with the extract of Artemisia herba alba. Furthermore, we revealed for the first time that using CoNPs coated with A. herba alba to treat diabetes improves glucose, HbA1c, and insulin levels more than using Artemisia herba alba extract due to the improvement of the pancreatic beta cells. The study’s findings demonstrated that, compared to the negative control group, male rabbits with diabetes had a higher incidence of pancreatic alterations. This finding aligns with research conducted on rats (Rasheed et al., 2021). Degenerative alterations in the Endocrine glands secreting from the pancreas, including islet atrophy, islet cell rupture, vascular congestion, and the presence of inflammatory cells, were observed in the diabetic control group. Oxidative stress may link these alterations, as high blood sugar lowers antioxidant levels and increases oxygen radicals (Nugent et al., 2008). Moreover, diabetes is frequently linked to deteriorating issues that impact the macrovascular and microvascular systems (Hanssen, 1997), which can lead to congestion. These results are in line with those of Jones et al. (2010), who noted that the islets of Langerhans displayed significant necrotic alterations and elevated connective tissue congestion, resulting in a relative reduction in the islets’ size. Additionally, diabetic pancreatic tissue sections treated with 500 mg/kg of the aqueous extract showed improvement. This outcome was in line with a study (Ghazanfar et al., 2014) that demonstrated that beta cells in pancreatic tissue were repaired and protected by alcoholic wormwood extract at 500 and 250 mg/kg.

The current study provides the first report demonstrating the therapeutic potential of cobalt nanoparticles coated with Artemisia herba alba in reduced the hyperglycemia and enhancing the function of pancreatic in alloxan-induced diabetic rats. The treatments show significantly decreased in the levels of glucose and HbA1c while the insulin concentration is increase, indicating enhanced glycemic control. This study revealed markedly pancreatic regeneration in the histological analysis, with restored Langerhans islets and normal beta cells, predominately in the cobalt nanoparticle-treated group. Notably, compared with the others treatment the cobalt nanoparticles exhibited superior efficacy, suggesting their promising role as potent antidiabetic and pancreatic restorative agents in experimental diabetes.

Acknowledgment

We thank Dr. Labeeb A. Al-Zubaidi (senior of researchers, biology, Ministry of Science and Technology, and the grateful continued to physiology, Pharmacology and Chemistry Department in our college for facilities.

Novelty Statement

This study utilized cobalt oxide nanoparticles to treated diabetes mellitus. To our knowledge, it represents the first investigation to coated cobalt oxide nanoparticles with Artemisia herba alba as a drug delivery. While prior research has been explored the effect of Artemisia herba alba extract on diabetic rats. Using cobalt oxide nanoparticles coated with Artemisia herba alba is a practical and effective approach on treating diabetes.

Author’s Contribution

The work that has been provided here was a collaborative effort by all authors. Furthermore, to writing the final publication, each of the authors’ influence on the idea, design, the data collection, analysis and interpretation of the study.

Ethical approval

The study was approved by the Research Ethics Committee of the College of Veterinary Medicine, University of Basrah, according to Protocol No. 94/37/2025, dated September 1, 2024.

Generative AI and AI-assisted technology statement

The authors declare that no genrative AI was used in the creation of this manuscript.

Conflict of interest

The authors have declared no conflict of interest.

References

Abdel-Hassan IA, Abdel-Barry JA, Mohammed ST (2002). The hypoglycemia and anti hyperglycemic effect of Citrullus colocynthis fruit aqueous extract in normal and alloxan diabetic rabbits. J. Ethnopharmacol., 71: 325–330. https://doi.org/10.1016/S0378-8741(99)00215-9

Abdulkareem GK, Hasan BF, Al-Masoudi WA (2025). Effects of Nanocurcumin on physiological parameters in rat with gastric ulcer. J. Appl. Biol. Chem., 68(40): 310–316. https://doi.org/10.3839/jabc.2025.040

Afolayan AJ, Sunmonu TO (2011). Artemisia afra jacqamelio rates oxidative stress in the pancreas of streptozotocin induced diabetic Wistar rats. Biosci. Biotechnol. Biochem., 75(11). https://doi.org/10.1271/bbb.100792

Afolayan AJ, Sunmonu TO (2013). Protective role of artemisia afra aqueous extract on tissue antioxidant defense systems in streptozotocininduced diabetic rats afolayan and Sunmonu. Afr. J. Tradit. Complement. Altern. Med., 10(1): 15-20. https://doi.org/10.4314/ajtcam.v10i1.3

Akhtar MS, Iqbal J (1991). Evaluation of the hypoglycaemic effect of Achyrantes aspera in normal and alloxan- diabetic rabbits. Ethnopharmacol. J., 31: 49–57. https://doi.org/10.1016/0378-8741(91)90143-2

Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D (2019). Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules, 9(9): 430. https://doi.org/10.3390/biom9090430

Andreadi A, Lodeserto P, Todaro F, Meloni M, Romano M, Minasi A, Lauro D (2024). Nanomedicine in the treatment of diabetes. Int. J. Mol. Sci., 25(13): 7028. https://doi.org/10.3390/ijms25137028

Ansari S, Bhor R, Pai K, Sen D, Mazumder S, Ghosh K, Kolekar Y, Ramana C (2017). Cobalt nanoparticles for biomedical applications: Facile synthesis, physiochemical characterization, cytotoxicity behavior and biocompatibility. Appl. Surf. Sci., 414: 171–187. https://doi.org/10.1016/j.apsusc.2017.03.002

Ansari, P., Hannan, J.M.A., Choudhury, S.T., Islam, S.S., Talukder, A., Seidel, V., Abdel-Wahab, Y.H. (2022). Antidiabetic actions of ethanol extract of Camellia sinensis leaf ameliorates insulin secretion, inhibits the DPP-IV enzyme, improves glucose tolerance, and increases active GLP-1 (7–36) levels in high-fat-diet-fed rats. Medicines, 9(11), 56.

Awad NE, Seida AA, El-Khayat Z, Shaffie N, Abd El-Aziz AM (2012). Hypoglycemic activity of Artemisia herba-alba (Asso.) used in Egyptian traditional medicine as hypoglycemic remedy. J. Appl. Pharma. Sci., (Issue): 30-39.

Belinskaia DA, Jenkins RO, Goncharov NV (2024). Albumin is an integrative protein of blood plasma and beyond. Int. J. Mol. Sci., 25(23): 12627. https://doi.org/10.3390/ijms252312627

Caturano A, D’Angelo M, Mormone A, Russo V, Mollica MP, Salvatore T, Sasso FC (2023). Oxidative stress in type 2 diabetes: Impacts from pathogenesis to lifestyle modifications. Curr. Issues Mol. Biol., 45(8): 6651-6666. https://doi.org/10.3390/cimb45080420

Darenskaya M, Kolesnikov S, Semenova N, Kolesnikova L (2023). Diabetic nephropathy: Significance of determining oxidative stress and opportunities for antioxidant therapies. Int. J. Mol. Sci., 24(15): 12378. https://doi.org/10.3390/ijms241512378

Elumalai K, Srinivasan S, Shanmugam A (2024). Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment. Biomed. Technol., 5: 109-122. https://doi.org/10.1016/j.bmt.2023.09.001

Ghazanfar K, Ganai BA, Akbar S, Ahmad KS, Younis M, Tantry MA (2014). Antidiabetic activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats. https://doi.org/10.1155/2014/185676

Hafth HA, Alkatrani ZAS, Alahmed HAA (2025). Effects of drenching aqueous extracts of licorice root (Glycyrrhiza glabra) and Matricaria chamomile on hematological parameters of adult female rabbits (Lepus cunicolus). Lab. Diagn. Eastern Eur., 14(1): 39–46. https://doi.org/10.34883/PI.2025.14.1.018

Hanssen KF (1997). Blood glucose control and microvascular complications in diabetes. Diabetes, 46: 101–103. https://doi.org/10.1016/S1056-8727(96)00048-7

Jones HB, Nugent D, Jenkins R (2010). Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains. Int. J. Exp. Pathol., 91(3): 288-301. https://doi.org/10.1111/j.1365-2613.2010.00713.x

Kouzi SA, McMurtry RJ, Nelson SD (1994). Hepatotoxicity of germander Teucrium chamedrys and one of its constituent neoclerodane iterpenes teucrine A in the mouse. Chem. Res. Toxicol., 7: 850-856. https://doi.org/10.1021/tx00042a020

Mansi K, Lahham J (2008). Effects of artemisia sieberi besserherba-alba on heart rate and some hematological values in normal and alloxan induced diabetic rats. J. Basic Appl. Sci., 4(2): 57-62

Mohammed MJ, Anand U, Altemimi AB, Tripathi V, Guo Y, Pratap-Singh A (2021). Phenolic composition, antioxidant capacity and antibacterial activity of white wormwood (Artemisia herba-alba). Plants, 10(1): 164. https://doi.org/10.3390/plants10010164

Nagappa AN, Thakurdesai PA, Rao NV, Singh J (2003). Antidiabetic activity of Terminalia catappa Linn fruits. J. Ethnopharmacol., 88(1): 45-50. https://doi.org/10.1016/S0378-8741(03)00208-3

Naik SR, Filho JMB, Dhuley JN, Deshmukh A (1991). Probable mechanism of hypoglycaemic activity of basic acid, a natural product isolated from Bumelia sartorum. J. Ethnopharmacol., 33: 37–44. https://doi.org/10.1016/0378-8741(91)90158-A

Nugent DA, Smith DM, Jones HB (2008). A review of islet of Langerhans degeneration in rodent models of type 2 diabetes. Toxicol. Pathol., 36(4): 529-551. https://doi.org/10.1177/0192623308318209

Obatomi DK, Bikomo EO, Temple VJ (1994). Anti-diabetic properties of the African Mistletoe in streptozotocin induced diabetic rats. J. Ethnopharmacol., 43: 13–17. https://doi.org/10.1016/0378-8741(94)90111-2

Rasheed K, Thamer I, Hussine FA, Ibraheem A (2021). Physiological and histological changes in pancreatic gland associated with ageing in local rabbits in Iraq. Arch. Razi Inst., 76(4): 957.

Rege NK, Phillips NF, Weiss MA (2017). Development of glucose-responsive smart insulin systems. Curr. Opin. Endocrinol. Diabet. Obesit., 24(4): 267-278. https://doi.org/10.1097/MED.0000000000000345

Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ (1995). Anti-hypertensive effect of some edible plants. J. Ethnopharmacol., 48: 25–32. https://doi.org/10.1016/0378-8741(95)01279-M

Sekiou O, Boumendjel M, Taibi F, Tichati L, Boumendjel A, Messarah M (2021). Nephroprotective effect of Artemisia herba alba aqueous extract in alloxan-induced diabetic rats. J. Tradit. Complement. Med., 11(1): 53-61. https://doi.org/10.1016/j.jtcme.2020.01.001

Sharma SR, Dwivedi SK, Varshney VP, Swarup D (1996). Antihyperglycaemic and insulin release effects of Aegle marmelos in STZ-diabetic rats. Phytother. Res., 10: 426–428. https://doi.org/10.1002/(SICI)1099-1573(199608)10:5<426::AID-PTR861>3.3.CO;2-5

Shehab ZA, Eissa AH, Alahmed HAA (2024). Investigation of physiological and immunohistochemical changes in rat treated with 5-fluorouracil. J. Anim. Health Prod., 12(S1): 168-173. https://doi.org/10.17582/journal.jahp/2024/12.s1.168.173

Sultana B, Anwar F, Ashraf M (2009). Effect of extraction solvent/ technique on the antioxidant activity of selected medicinal plant extracts molecules, 14: 2167-2180. https://doi.org/10.3390/molecules14062167

Sultana A, Zare M, Thomas V, Kumar TS, Ramakrishna S (2022). Nano-based drug delivery systems: Conventional drug delivery routes, recent developments and future prospects. Med. Drug Discov., 15: 100134. https://doi.org/10.1016/j.medidd.2022.100134

Vodyashkin AA, Kezimana P, Prokonov FY, Vasilenko IA, Stanishevskiy YM (2022). Current methods for synthesis and potential applications of cobalt nanoparticles: A review. Crystals, 12(2): 272. https://doi.org/10.3390/cryst12020272

Wadood N, Abdulwadood S, Shah A (1992). Effect of Tinospora cordifolia on blood glucose and total lipid levels of normal and Alloxan-diabetic rabbits. Planta Med., 58: 131-136. https://doi.org/10.1055/s-2006-961414

Zheng Y, Luo S, Xu M, He Q, Xie J, Wu J, Huang Y (2024). Transepithelial transport of nanoparticles in oral drug delivery: From the perspective of surface and holistic property modulation. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2024.06.015