Synergistic antidiabetic effects of GC-MS profiled Prunus persica kernel extract and chromium picolinate in alloxan-induced diabetic rats

Abstract

Diabetes mellitus continues to be a significant worldwide health burden, necessitating safe and efficient treatment alternatives. In alloxan-induced diabetic rats, this study examined the combined antidiabetic effectiveness of chromium picolinate and Prunus persica kernel extract. Gas chromatography/mass spectrometry was used to phytochemically characterize a polyphenolic-rich extract (60% acetone). Alloxan monohydrate (140 mg/kg b.w.) was administered intraperitoneally to develop diabetes in rats. The animals were split into groups for normal control, diabetic control, chromium picolinate, Prunus kernel extract, three combination therapy groups, and conventional medication. The treatments were administered orally on a 21-day basis. Insulin levels in serum were also measured following dissection, and body weight and fasting blood glucose (FBG) were monitored prior to and after treatment. Pancreatic tissue was taken in order to determine the preservation and regeneration of B-cells through a histological analysis. Compared to individual therapy, the combined therapy had a significant benefit of reducing the level of FBG (p < .01), increasing serum insulin significantly, and rescuing the morphology of the pancreatic B-cells. These findings confirm the P. persica kernel extracts and chromium picolinate as supplementation therapies in diabetes management because they suggest that the two compounds act synergistically to enhance pancreatic protection and control glucose levels.

Keywords

chromium picolinate synergistic effect alloxan diabetes mellitus

Introduction

Diabetes is a complex metabolic condition that is associated with either or both the release of insulin and action, leading to hyperglycemia. The International Diabetes Federation (IDF) confirmed that more than 425 million individuals worldwide had diabetes in 2017. By 2045, 629 million individuals worldwide—a 48% increase—are expected to develop diabetes. In 2017, diabetes and its consequences cost the world's healthcare system USD 727 billion.¹ According to IDF data from 2022, there are over 33 million cases of diabetes in Pakistan, accounting for 26.7% of people.²

Because they are typically less toxic and more affordable than synthetic medications, medicinal plants have drawn interest as potential substitutes for pharmaceuticals due to their high cost and adverse effects. It provides a promising path for creating novel, secure, and economical treatment solutions.³ To date, more than 400 traditional herbal remedies have been suggested as treatments for diabetes. The majority of plants’ ability to restore pancreatic tissue function through increased insulin production, inhibiting intestinal glucose absorption, or stimulating metabolites in the insulin-dependent processes is frequently credited with their anti-hyperglycemic properties.⁴

Before 1100 BC, the Rosaceae family's stone fruit, Prunus persica, originated in China.⁵ Prunus persica, or peaches, are indigenous to China, where traditional Chinese medicine has long linked them to a variety of therapeutic benefits. According to Nowicka et al.,⁶ peaches are rich in phenolic compounds that have strong antibacterial, antidiabetic, antioxidant, and antiobesity qualities, including lowering adiposity and improving lipid metabolism.⁷

About 5% to 60% of its weight is made up of peach seeds, which have strong anti-inflammatory, antioxidant, and enzyme-inhibiting qualities that are important for controlling Alzheimer's disease and diabetes. Peach kernels are very beneficial against obesity and type 2 diabetes. The kernels’ bioactive compounds, especially polyphenols, exhibit a positive link with their inhibitory effect on diabetes-related enzyme activity.⁸ According to Elshamy et al.,⁹ it contains flavonoids with good analgesic, antipyretic, antinociceptive, and anti-inflammatory properties.¹⁰ When amygdalin from peach kernels comes into touch with beta-glucosidase during digestion, it can be poisonous and break down into hydrogen cyanide, exhibiting cytotoxic activity.¹¹

According to OECD criteria, the Prunus kernel extract (PKE) is safe because it showed no signs of acute oral toxicity and had an LD50 > 400 mg/kg BW.¹¹

There are three valence states for chromium, a glossy metallic element that is mostly used to make glass and alloys: II, III, and VI. Because trivalent chromium (Cr³⁺) is less hazardous than its hexavalent equivalent, it has been the focus of much research among its variants.¹² When compared to dietary forms of chromium, the picolinate receptor's binding to chromium improves its bioavailability and absorption.¹³

The recommended daily intake of 50 mg of Cr is not met by most diets. In individuals with Type 2 diabetes, Cr supplementation can improve blood glucose, insulin, cholesterol, and HbA1C in a dose-dependent manner.¹⁴ CrPic improves the resistance to insulin in T2DM patients, increases GLUT4 expression, controls fat and carbohydrate metabolism, and has insulin-sensitive and antihyperglycemic effects by modifying pathways like phosphorylation of Akt and PI3 kinase activity by increasing phosphorylated AKT activity and decreasing TRB3 activity.

Thus, this study aims to investigate the synergistic restorative potential of P. persica kernel extract when administered together with chromium in alloxan-induced diabetic mice. Compared to administering either drug alone, we predict that this combination therapy will dramatically improve hyperglycemia and associated biochemical problems. The methods employed to test this hypothesis, the biochemical data that were obtained, and the implications of our results for new combination therapy for diabetes mellitus will all be covered in this study.

Materials and methods

Chemicals and reagents

This investigation employed only analytical-grade chemicals and reagents. Sigma-Aldrich (St Louis, MO, USA) supplied acetone and alloxan monohydrate through a local importer in Lahore, Pakistan. Chromium picolinate (Natural Factors; 250 µg elemental chromium per unit) and metformin hydrochloride (Don Valley Pharma (Pvt.) Ltd, Pakistan) were utilized. A commercially available ELISA kit (Randox Laboratories Ltd, UK) was used to measure serum insulin levels in accordance with the manufacturer's instructions.

Plant material and extract preparation

Prunus persica seeds were gathered from the Lahore local market. The Department of Botany at Government College University, Lahore, Pakistan, recognized and verified the taxonomic characteristics of P. persica kernels after the seeds were cracked open. The verified plant material was stored in the college herbarium under the voucher number GC. Herb. Bot. 4077.

The kernels were separated, air-dried, and ground into a fine powder. A total of 200 g of powder was extracted with 2000 mL of 60% aqueous acetone (1:10, w/v) at 25 °C for 3–4 h under continuous agitation. Aqueous acetone was selected for its high efficiency in extracting polyphenolic compounds. The mixture was filtered (Whatman No. 1), and the filtrate was concentrated under reduced pressure at 45 °C and stored at 4 °C until use. The extraction yielded 12.4 g of dried extract, corresponding to a 6.2% (w/w) yield.

Selection of chromium source

As chromium picolinate was utilized as a chromium supply, trivalent chromium was utilized as an additional medicinal supplement.¹⁵

Phytochemical analysis by gas chromatography/mass spectrometry

A gas chromatography/mass spectrometry (GC-MS) system equipped with an HP-5MS capillary column (30 m × 0.25 mm i.d., 0.25 µm film thickness) was used to analyze the P. persica kernel extract. To increase volatility, the extract was derivatized with BSTFA containing 1% TMCS at 70 °C for 30 min. The oven program began at 60 °C with a 2-min hold, increased to 280 °C at a rate of 10 °C per minute, and was then maintained for 10 min. The carrier gas was helium (1.0 mL/min). One microliter of the sample was injected in split mode (1:50) with the injector temperature set at 250 °C. Mass spectra were obtained at m/z 40–600 in EI mode (70 eV). Using ≥90% match grade and retention index confirmation, compounds were found by comparing spectral information with the NIST and Wiley libraries.

Experimental animals

On November 13, 2024, the experiment was carried out with ethical approval from the Institutional Animal Ethical Committee and permission from the Office of Research Innovation and Commercialization at UVAS, Lahore (No. DR/510). For the study, 24 male Albino rats in good health who weighed between 150 and 200 grams and were between 10 and 12 weeks old were selected. Throughout the experiment, the rats were given a standard pellet diet and kept hydrated. The animals were kept in polypropylene cages at The Animal Research Facility, Institute of Biochemistry and Biotechnology at UVAS in Lahore, Pakistan, under conventional laboratory settings (temperature 22 ± 2 °C, relative humidity 55 ± 5%, and 12-h light/dark cycle).

Diabetes induction

Rats were starved for sixteen hours in order to induce diabetes. After then, an intraperitoneal dose of alloxan monohydrate (140 mg/kg) dissolved in normal saline was given. Rats with fasting blood glucose (FBG) values more than 180 mg/dl were chosen for additional research when blood glucose levels were measured 72 h after an injection using a glucometer (ACCU-CHEK Instant).¹⁶

Experimental groups

Diabetic rats were split up into eight groups, given below

G1. Normal Control—used to establish baseline parameters for comparison

G2. Diabetic Control—Alloxan-induced diabetic rats

G3. Chromium picolinate—Diabetic rats administered with 20 µg/kg Chromium picolinate (CrPic)

G4. Kernel Extract—Diabetic rats administered with 150 mg/kg PKE

G5. Combination Therapy—Diabetic rats administered with 10 µg/kg CrPic and 50 mg/kg PKE

G6. Combination Therapy—Diabetic rats administered with 15 µg/kg CrPic and 100 mg/kg PKE

G7. Combination Therapy—Diabetic rats administered with 20 µg/kg CrPic and 150 mg/kg PKE

G8. Positive control—Diabetic rats administered with 500 mg/kg Metformin

Treatments were provided according to the guidelines for each group, and doses were given depending on body weight. The animals received each of these doses orally through gavage.

Monitoring parameter

To track changes in the rats’ body weight, an electronic balance was used to weigh them on the first and end days of the experiment.

Hypoglycemic activity

Hypoglycemic activity was assessed by measuring FBG levels on days 1, 7, 14, and 21 as shown in Table 1. A glucometer (ACCU-CHEK Instant) was employed to assess the blood glucose levels after 0.2 ml of blood was extracted from the rats’ tails following their overnight fast.

Biochemical testing

On the 21st day, the rats were put to sleep, and at the conclusion of the day, blood was carefully drawn from the heart vein. Centrifugation of the blood at 3500 rpm (10 minutes) was then used to remove the serum. The level of insulin in the serum was then measured using a commercial ELISA kit.

Histopathological analysis

A histopathological analysis of the pancreas organ was performed to assess the changes that occurred in the pancreatic cell following treatment. They were initially anesthetized using chloroform and the peritoneum carefully removed using the rats. The pancreas was then excised and kept in 10% formalin to proceed further.¹⁷ After this, tissue samples were slowly dipped in alcohol solutions of different concentrations in order to dry them. After dehydration, the xylene cleaning agents were used twice on it followed by embedding in paraffin wax. Microtome was used to slice the tissue to 4–5 µm thick slices, and stained with eosin and hematoxylin. Subsequently, a slide was viewed under a computer and camera connected microscope.

Statistical analysis

All the results were analyzed statistically in one-way analysis of variance (ANOVA) by the use of SPSS (Statistical Package of the Social Sciences) program to define the presence of significant differences.¹⁸

Results

Phytochemical identification

The active ingredients in P. persica kernel were identified using the GC/MS. The acetone extract of the plant was taken to an analysis of GC/MS to identify its phytochemical composition as shown in Figure 1. The analysis proved the presence of flavonoids, phenols, triterpenoids, saponins, polyphenols, and others as shown in Table 2. The kernels of P. persica are poisonous, large, polar, nonvolatile, and amygdalin. It decomposes fast to produce mandelic acid and benzaldehyde. Even when amygdalin is subjected to derivatization, it cannot be detected by GC-MS. The existence of it is deduced with the help of benzaldehyde and mandelic acid.

Body weight

To evaluate changes brought about by the treatments, body weight was measured for every group of rat at the beginning and end of the 21-day study as shown in Figure 2. Table 3 shows the initial and end weights. To assess the effect of the supplied chemicals, percentage changes were computed.

Table 2.

Gas chromatography/mass spectrometry (GC-MS) profiling of bioactive compounds in Prunus persica kernel extract.

Compound	Class	Derivatized form	Approx. RT (min)	Retention index (HP-5MS, C8–C40 n-alkanes)	Key bioactivities
Benzaldehyde	Aldehyde	None	5.092	960	Anti-inflammatory, Antioxidant
Mandelic acid	Hydroxy acid	di-TMS	11.04	1462	Weak antioxidant
Gallic acid	Phenolic acid	tetra-TMS	15.289	2125	Strong antioxidant
p-Coumaric acid	Phenolic acid	di-TMS	8.954	1688	Antioxidant, Anti-inflammatory
Caffeic acid	Phenolic acid*	tri-TMS	18.637	1912	Antioxidant, Anti-inflammatory, Antidiabetic
Chlorogenic acid	Phenolic ester	penta-TMS	18.166	2635	Antidiabetic, Anti-inflammatory, Antioxidant
Catechins	Flavan-3-ol	Hexa-TMS	17.969	2315	Antidiabetic, Anti-inflammatory, Antioxidant, Anticancer
Ferulic acid	Phenolic acid	tri-TMS	19.91	1798	Antioxidant
Hexadecanoic acid	Saturated FA	TMS ester	13.591	1968	–
(9Z)-Octadec-9-enoic acid	MUFA	TMS ester	17.137	2162	Anti-inflammatory, Antidiabetic
(9Z,12Z)-Octadeca-9,12-dienoic acid	PUFA	TMS ester	19.314	2128	Anti-inflammatory, Antidiabetic

Table 3.

Effect of extract of Prunus persica kernel and chromium picolinate, on body weight (g) in alloxan-induced diabetic rats (n = 3).

Sr. no.	Groups	Before treatment	After treatment	% increase or decrease in body weight
1	Normal	210 ± 5.79	228 ± 3.94	8.57%
2	Diabetic Control	198.3 ± 11.8	174.3 ± 17.1	−12.10%
3	CrPic (20 µg/kg)	251.1 ± 21.94	265.1 ± 13.49	5.58%
4	PKE (150 mg/kg)	214.8 ± 9.4	244.8 ± 17.7	13.79%
5	10 µg/kg CrPic + 50 mg/kg PKE	200.3 ± 14.51	217.3 ± 21.1	8.49%
6	15 µg/kg CrPic + 100 mg/kg PKE	180 ± 7.84	220.3 ± 12.4	22.39%*
7	20 µg/kg CrPic + 150 mg/kg PKE	195.2 ± 4.17	255.2 ± 11.14	30.74%**
8	Metformin 500 mg/kg	185.25 ± 3.15	228.25 ± 8.15	23.21%

*Significant results as control group.

**Highly significant similar results as control group.

Table 1.

Mean values of blood glucose level (mg/dl) by treatment of PKE and chromium picolinate extracts of in alloxan-induced diabetic rats.

Groups	1st day	7th day	14th day	21st day
Normal	101 ± 5.79	100.8 ± 4.03	95.7 ± 6.88	92.73 ± 2.3
Diabetic Control	281.8 ± 31.8	299.9 ± 18.82	343 ± 21.7	371.8 ± 9.79
CrPic (20 µg/kg)	241.55 ± 5.94	228.32 ± 3.54	201.8 ± 7.39	162.12 ± 11.88
PKE (150 mg/kg)	301 ± 19.4	236.76 ± 6.09	182.5 ± 5.51	132.26 ± 4.99
10 µg/kg CrPic + 50 mg/kg PKE	308.8 ± 9.51	274.4 ± 4.5	212.14 ± 6.93	168.19 ± 8.84
15 µg/kg CrPic + 100 mg/kg PKE	290 ± 12.84	199.27 ± 7.22	151.83 ± 6.26	109.5 ± 4.75*
20 µg/kg CrPic + 150 mg/kg PKE	312.2 ± 16.17	221.02 ± 9.67	149.27 ± 7.01	95.6 ± 4.52**
Metformin 500 mg/kg	298.25 ± 14.17	194.25 ± 11.17	139 ± 6.0	101.25 ± 3.17

*Significant results as control group.

**Highly significant similar results as control group.

Hypoglycemic activity

The blood glucose levels were measured on the 1st, 7th, 14th, and 21st days of the study after the rats were given Alloxan 140 mg/kg of body weight to induce diabetes. For these measurements, the standard deviations and mean values were computed. Following the administration of extracts at varying dosages, the results showed a decrease in blood glucose levels as shown in Figure 3. This decline was noted when compared to the common medication, metformin.

A repeated measures ANOVA was performed to evaluate the hypoglycemic activity over time. Mauchly's test indicated that the assumption of sphericity was violated (p < .05). Therefore, the Greenhouse–Geisser correction was applied to adjust the degrees of freedom. Post hoc pairwise comparisons were subsequently conducted using Bonferroni adjustment to determine differences between treatment groups at various time points.

Coadministration of 15 µg/kg chromium picolinate and 100 mg/kg PKE and 20 µg/kg chromium picolinate + 150 mg/kg PKE produced findings that were strikingly similar to those of the metformin-treated positive control group. When 20 µg/kg of chromium picolinate and 150 mg/kg of PKE were administered together, the blood sugar dropped dramatically from 312 mg/dl to 95 mg/dl. Similarly, blood sugar levels dropped from 290 mg/dl to 109.5 mg/dl when 15 µg/kg chromium picolinate and 100 mg/kg PKE were administered together as shown in Figure 4.

Serum insulin

Serum insulin levels were measured at the conclusion of the experiment to see how the therapies influenced the generation of insulin. Table 4 shows that the serum insulin level in diabetic rats was significantly lower than in the control group. Because diabetes pathophysiology is characterized by the loss of pancreatic β-cells, diabetic rats showed significantly reduced insulin levels.

Table 4.

Serum insulin level in different experimental groups.

Sr. no.	Groups	Serum insulin (µU/mL)
1	Normal	7.1 ± 0.20
2	Diabetic Control	1.49 ± 0.11
3	CrPic (20 µg/kg)	4.44 ± 0.26
4	PKE (150 mg/kg)	5.6 ± 0.08
5	10 µg/kg CrPic + 50 mg/kg PKE	4.2 ± 0.11
6	15 µg/kg CrPic + 100 mg/kg PKE	6.14 ± 0.17
7	20 µg/kg CrPic + 150 mg/kg PKE	6.88 ± 0.09
8	Metformin 500 mg/kg	6.56 ± 0.03

Significant results as control group.

The serum insulin levels (µU/mL) and standard deviations for each experimental group at the conclusion of the study period are shown in the table. Insulin secretion improved to differing degrees when peach kernel extract, chromium, and their combination were administered; the combined treatment group had the largest increase in blood insulin levels, albeit still below the control group. Serum insulin levels increased significantly in rats treated with P. persica kernel extract alone (5.6 ± 0.08), however, the combination therapy groups 6 and 7 outperformed all other treatment groups in terms of insulin levels. These results imply that chromium and P. persica kernel extract work in concert to increase insulin production and improve insulin sensitivity in diabetic rats.

Histopathology of pancreas

In control rats, pancreatic islets displayed normal architecture, with well-defined β-cells and intact exocrine tissue (Figure 5A). Essential information about tissue alterations brought on by diseases such as diabetes and inflammation can be obtained by histopathological investigation. In order to examine the effects of peach kernel extract and chromium picolinate on the integrity of islet cells and the general structure of the pancreas, the histological changes in the pancreas of rats with diabetes caused by alloxan were evaluated.

Varied therapy groups exhibit varied levels of injury and healing, according to the histological analysis of pancreatic tissue. Significant islet shrinkage and β-cell death were observed in the diabetes group. While 150 mg/kg kernel extract (Figure 5D) demonstrated partial preservation of islet structure, treatment with chromium picolinate (Figure 5C) produced moderate islet changes. Islet size and beta cell integrity improved with combined treatments, such as 15 µg/kg chromium picolinate and 100 mg/kg kernel extract (Figure 5F). With nearly normal pancreatic histology, the maximum recovery was seen with 20 µg/kg chromium picolinate + 150 mg/kg kernel extract (G). Additionally, metformin therapy (H) dramatically decreased β-cell atrophy and retained islet structure. Semiquantitative histopathological scoring (Table 5) supports the qualitative observations from photomicrographs.

Table 5.

Semiquantitative histopathological scoring of pancreatic tissue in control, diabetic, and treated rats (hematoxylin and eosin [H&E], 10 × 10).

Group	Islet integrity	β-cell density	Pancreatic architecture	Notes
Control	Normal	Normal	Intact	–
Diabetic	Severe degeneration	Reduced	Distorted	–
Kernel extract 150 mg/kg	Partial preservation	Moderate	Mildly altered	–
CrPic 20 µg/kg	Moderate preservation	Moderate	Some alterations	–
CrPic + Kernel (20 + 150)	Nearly normal	High	Intact	Best recovery
Metformin 500 mg/kg	Nearly normal	High	Intact	Standard reference

Discussion

The various therapy groups exhibit different levels of injury and healing, according to the histological analysis of pancreatic tissue. Significant islet shrinkage and β-cell death were observed in the diabetes group. While 150 mg/kg kernel extract (Figure 5D) demonstrated partial preservation of islet structure, treatment with chromium picolinate (Figure 5C) produced moderate islet changes. Islet size and beta cell integrity improved with combined treatments, such as 15 µg/kg chromium picolinate and 100 mg/kg kernel extract (Figure 5F). With nearly normal pancreatic histology, the maximum recovery was seen with 20 µg/kg chromium picolinate + 150 mg/kg kernel extract (G). Additionally, metformin therapy (H) dramatically decreased β-cell atrophy and retained islet structure.

The amount of phenolic chemicals, flavonoids, and essential fatty acids in P. persica kernel extract has been shown in recent studies to have considerable medicinal benefits. These bioactive substances are thought to have antidiabetic, anti-inflammatory, and antioxidant properties. In line with earlier findings that peach kernel extracts improved glucose homeostasis in diabetic animal models due to their strong antioxidative and anti-inflammatory effects, the current study found that administering P. persica kernel extract caused a noticeable drop in blood glucose levels.¹⁹ Moreover, when P. persica kernel extract and chromium were used together, greater decrease in the levels of blood glucose was observed compared to those of either therapy. This implies that the synergistic effect of the complementary mechanisms of action of these two agents could be synergistic.

Chromium, particularly trivalent chromium (Cr +3), has been shown to enhance glucose uptake and to enhance insulin sensitivity. Chromium supplement has been demonstrated to enhance insulin sensitivity and lower blood sugar especially in insulin-resistant individuals.²⁰ Blood glucose levels reduced significantly in rats that were administered chromium in this study, and this correlation is in line with existing literature on the potential of chromium as an antidiabetic. However, the combination of 150 mg/kg P. persica kernel extract and 20 µg/kg chromium yielded the most interesting results and therefore performed better than single treatments. This implies that the two agents can have various but complementary mechanisms in order to have a larger therapeutic impact.

The mechanism of action of the effects observed in this study is a complex one. Peach kernel essential oil contains polyphenolic chemicals that have high antioxidant properties. The antioxidants play a crucial role in minimizing the oxidative stress, which exacerbates insulin resistance, suppresses the activity of 0-cells, and extends the diabetes pathophysiology. It is proven that the pancreatic 8-cells are not under the effects of oxidative damage due to the strong ROS scavenging property of the phenolic compounds of peach kernels.²¹

The combination of CrPic (20 µg/kg) and PKE (150 mg/kg) was most effective in reducing blood glucose to levels comparable to metformin. Rats treated with only CrPic or PKE presented significant glucose reduction. From these results, one can observe that both PKE and CrPic have a synergistic interaction in the regulation of blood glucose. Mechanisms that could explain this effect are an enhancement of insulin sensitivity and antioxidant properties, as previously reported for CrPic and PKE. This finding is consistent with previous studies showing that the antioxidant effect of PKE may contribute to the reduction of oxidative stress associated with diabetes, while CrPic has been shown to enhance insulin activity. The statistical significance of the reductions in the treated groups, especially the combination therapy, supported the therapeutic potential of CrPic and PKE as potent antidiabetic agents. These drugs should, therefore, be further clinically studied, representing a promising alternative in the management of diabetes with efficacy comparable to Metformin, with a possibility of fewer side effects.²²

Histological examination of pancreatic tissue further confirmed the damaging effects of hyperglycemia on pancreatic function, as evident from significant pathological changes such as β-cell degeneration and a decrease in islet cell density in diabetic rats. In contrast, an improved structure of the pancreatic islets with reduced interstitial fibrosis and more intact β-cells was observed following the administration of chromium picolinate and P. persica kernel extract in rats. This is in agreement with recent studies that natural plant extracts, such as those from peach kernels, prevent pancreatic damage in diabetic rats. Moreover, with the changes in the islet cell structure and function, the combined therapy appeared to confer more profound protection, substantiating the hypothesis of a synergistic effect.

Assessing the impact of the combined treatment on insulin sensitivity was among the primary objectives of this study. Lower blood glucose levels and higher insulin secretion supported the fact that insulin sensitivity in the combination treatment group had improved remarkably. This corresponds with other studies identifying that both chromium and P. persica kernel extract possess insulin-sensitizing properties. The P. persica kernel extract enhances blood glucose control by increasing glucose uptake in muscle and adipose tissue, while chromium enhances the function of insulin receptors through its effect on insulin signaling.

Conclusion

These findings thus suggest that P. persica kernel extract combined with chromium offers a potentially effective therapeutic approach to the treatment of alloxan-induced diabetes. This combined regimen may eventually provide a multimodal approach to diabetes therapy through the amelioration of metabolic disturbances underlying the disease and conferring protection against its complications, based on the observed synergy in the regulation of glucose, enhancement of insulin sensitivity, and pancreatic protection. These results also underscore how important it is to combine chromium with natural products, such as P. persica kernel extract, in the development of safe and effective diabetes treatments. However, these findings should be interpreted with caution due to the limited sample size, relatively short study duration, and the absence of detailed molecular mechanistic investigations, warranting further large-scale and mechanistic studies to validate these results.

Footnotes

Data availability statement

Data will be available on request.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

This animal study was conducted in accordance with the guidelines set forth by the Institutional Animal Ethics Committee (IAEC) of the University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan. Ethical approval for the experimental protocol was obtained under approval number 58976. Furthermore, the study was carried out in compliance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines, ensuring the humane care and use of animals in all experimental procedures.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Statement of human and animal rights

This study was approved by the Ethical Review Committee of UVAS, adhering to institutional and international guidelines for animal care and use.

Statement of informed consent

No human subjects were involved; ethical approval was obtained for animal experimentation following ethical research standards.

ORCID iD

Tahir Mehmood

References

Uslu

. Evaluating the effects of Prunus laurocerasus seed, fruit and leaf extracts on hyperglycaemia, insulin sensitivity and anti-oxidative activities in experimental diabetes in rat. Thai J Vet Med 2021; 51: 667–673.

Azeem

Khan

Liaquat

. The increasing rate of diabetes in Pakistan: a silent killer. Ann Med Surg 2022; 79: 103901.

Aranzana

Decroocq

Dirlewanger

, et al. Prunus genetics and applications after de novo genome sequencing: achievements and prospects. Hortic Res 2019; 6: 58.

Bahrami

Izadi

Miraghaee

, et al. Antidiabetic potential of the isolated fractions from the plants of Rosaceae family in streptozotocin-induced diabetic rats. Res Pharm Sci 2021; 16: 505–515.

Bento

Goncalves

Silva

, et al. Peach (Prunus persica): phytochemicals and health benefits. Food Rev Int 2022; 38: 1703–1734.

Nowicka

Wojdyło

Laskowski

. Inhibitory potential against digestive enzymes linked to obesity and type 2 diabetes and content of bioactive compounds in 20 cultivars of the peach fruit grown in Poland. Plant Foods Hum Nutr 2018; 73: 314–320.

Song

Kim

Y-S

Kim

, et al. Anti-obesity effects of the flower of Prunus persica in high-fat diet-induced obese mice. Nutrients 2019; 11: 2176.

Kumari

Kumar

Puri

, et al. Peach (Prunus persica (L.) Batsch) seeds and kernels as potential plant-based functional food ingredients: a review of bioactive compounds and health-promoting activities. Food Biosci 2023; 54: 102914.

Elshamy

Abdallah

HMI

El Gendy

AE-NG

, et al. Evaluation of anti-inflammatory, antinociceptive, and antipyretic activities of Prunus persica var. nucipersica (nectarine) kernel. Planta Med 2019; 85: 1016–1023.

10.

Cassiem

de Kock

. The anti-proliferative effect of apricot and peach kernel extracts on human colon cancer cells in vitro. BMC Complement Med Ther 2019; 19: 1–12.

11.

Esraa Fadl

MHH

El-Mehiry

El-Sayed

, et al. Effect of antioxidants and cytotoxic activities of apricot (Prunus Armeniaca L.) and peach (Prunus Persica L.). Kernels Extracts on Experimental Rats. Res J Spec Educ 2023; 2023: 387–411.

12.

Ghosh

Bhattacharya

Mukherjee

, et al. Role of chromium supplementation in Indians with type 2 diabetes mellitus. J Nutr Biochem 2002; 13: 690–697.

13.

Yeghiazaryan

Schild

Golubnitschaja

. Chromium-picolinate therapy in diabetes care: individual outcomes require new guidelines and navigation by predictive diagnostics. Infect Disord Drug Targets 2012; 12: 332–339.

14.

Dubey

Thakur

Chattopadhyay

. Role of minerals and trace elements in diabetes and insulin resistance. Nutrients 2020; 12: 1864.

15.

Georgaki

M-N

Tsokkou

Keramas

, et al. Chromium supplementation and type 2 diabetes mellitus: an extensive systematic review. Environ Geochem Health 2024; 46: 515.

16.

Opara

Iwuji

Onyebuagu

, et al. Antihyperglycaemic activities of plant-extracted succinic acid and hexamethylcyclotrisiloxane in diabetic albino rats. Eur J Med Sci 2024; 11: 427–433.

17.

Khalaf

Aljader

Sarhat

, et al. Antidiabetic effect of aqueous extract of Medicago Sativa with enhanced histopathology of pancreas in alloxan induced diabetic rats. Pak J Med Health Sci 2021; 15: 492–496.

18.

Saadane

Lessieur

, et al. Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. PLoS One 2020; 15: e0238727.

19.

Moharram

Alburyhi

Al-Maqtari

, et al. Evaluating the antidiabetic activity of Aloe niebuhriana latex in alloxan-induced diabetic rats and the development of a novel effervescent granule-based delivery system. Sci World J 2025; 2025: 5648662.

20.

Morsi

. Anti-Hyperglycemic and antioxidant effect of peach (Prunus Persica L.). Seed Extract. Middle East J Appl Sci 2022; 12: 499–514.

21.

Vajdi

Safaei

Moeinolsadat

, et al. Effects of chromium supplementation on body composition in patients with type 2 diabetes: a dose-response systematic review and meta-analysis of randomized controlled trials. J Trace Elem Med Biol 2024; 81: 127338.

22.

Shi

Xue

, et al. Essential oil extracted from peach (Prunus persica) kernel and its physicochemical and antioxidant properties. Food Sci Technol 2011; 44: 2032–2039.