Therapeutic role of Vitis vinifera L. in Gastric Ulcer healing under Diabetic conditions: an experimental study in Rats

Km. Deeksha¹, Gyanendra Kumar Sharma², Ashutosh Solanki³, Vikash Sharma⁴*

¹Department of Pharmacology, Anand College of Pharmacy,

Sharda University Agra-282007, Uttar Pradesh, India.

²Department of Pharmaceutical Chemistry,

Sharda school of Pharmacy, Sharda University Agra-282007, Uttar Pradesh, India.

³Department of Pharmacology, College of Pharmacy, JSS University, Noida, Uttar Pradesh, 201301, India.

⁴Department of Pharmacology,

Sharda school of Pharmacy, Sharda University Agra-282007, Uttar Pradesh, India.

*Corresponding Author E-mail: vikassharma10588@gmail.com

ABSTRACT:

Background: High blood sugar levels in diabetes can prolong the healing process of stomach sores, as the body struggles to repair itself. Vitis vinifera L. Commonly known as grape, this fruit contains compounds that may help alleviate inflammation and serve as antioxidants. These qualities could assist in the healing of ulcers for individuals with diabetes. Objective: The present study aimed to evaluate the therapeutic potential of Vitis vinifera L. in promoting gastric ulcer healing in streptozotocin-induced diabetic rats. Methodology: In Wistar rats, diabetes was induced through the administration of a chemical known as streptozotocin (STZ). Once it was confirmed that the animals had elevated blood sugar levels, they were divided into three groups and treated with either a control solution, the conventional medication ranitidine, or an extract from Vitis vinifera over a period of 14 days. On the last day of treatment, stomach ulcers were induced using ethanol. Once the ulcers were created, the animals were euthanized, and assessments were made on their blood sugar levels, the extent of the ulcers, and the reduction percentage of the ulcers. Samples of stomach tissue were collected for microscopic analysis. Result: Diabetic rats treated with Vitis vinifera exhibited reduced blood sugar levels compared to those suffering from diabetic ulcers. The ulcer index showed a significant decrease, and there was an increased percentage of protection against ulcers. The study of the tissues indicated enhanced healing of the stomach lining, a decrease in the number of ulcers, and a restoration of normal stomach structure for those in the treatment group. Conclusion: Vitis vinifera L. appears to be beneficial for healing stomach ulcers in individuals with diabetes, likely due to its ability to reduce blood sugar levels and safeguard the stomach lining. These findings indicate that it could serve as a valuable aid in the management of diabetic gastropathy.

KEYWORDS: Vitis vinifera L., Gastro-protective activity, Diabetes mellitus, Histopathological examination, Ulcer in Diabetic Rats.

INTRODUCTION:

Gastric ulcers are sores that form in the stomach. These occurrences arise when there is a conflict between harmful substances, such as stomach acid and specific bacteria, and the body's protective mechanisms, including mucus and chemicals that safeguard the stomach¹. This disruption harms the stomach's protective barrier, resulting in inflammation and ulcer formation. Without proper treatment, stomach ulcers can lead to complications such as bleeding, perforations in the stomach, and challenges with food digestion². It becomes significantly more challenging for individuals living with diabetes. High blood sugar, a typical indicator of diabetes, complicates the healing of wounds and the repair of tissues. This occurs due to the accumulation of harmful substances, which heightens stress on the body's cells and impairs blood vessel function. Within the digestive system, these impacts lead to reduced circulation in smaller blood vessels, diminished defense for the internal lining, and a deceleration in the growth of skin cells³. Consequently, individuals with diabetes are at a higher risk of developing severe stomach ulcers that take a long time to heal. Additionally, diabetes can affect the nerves responsible for regulating involuntary bodily functions, altering the way food travels through the stomach and potentially harming the stomach lining. Managing stomach ulcers in individuals with diabetes can be particularly challenging. Standard therapies for ulcers, such as proton pump inhibitors (PPIs) and H2 blockers, primarily function by decreasing stomach acid production. Although these medications are effective for many individuals, their effectiveness may be limited for those with diabetes due to the unique way their bodies process and react to these drugs. Using these medicines for a long time can cause problems⁴. They may obstruct the absorption of critical nutrients, including magnesium, calcium, and vitamin B12, in your body. Stopping these medications may lead to a greater risk of infections like Clostridium difficile, as well as elevated acidity in your stomach. These constraints indicate a need for further therapies aimed at addressing the underlying issues, especially oxidative stress and inflammation. There has been an increasing fascination with natural, plant-derived treatments that offer numerous health benefits and are regarded as safe by Vitis vinifera L. is a species of grapevine commonly known for its fruit. The fruit, seeds, and leaves are rich in advantageous compounds known as polyphenols, such as resveratrol, quercetin, anthocyanins, tannins, and proanthocyanidins⁵. These plant compounds possess powerful properties to combat harm, lessen inflammation, and safeguard cells. Studies indicate that Vitis vinifera (grapevine) extracts may decrease toxic oxygen molecules, shield fats from damage, and affect the concentrations of inflammatory markers such as TNF-α, IL-6, and COX-2⁶.

Furthermore, Vitis vinifera, a variety of grape, has displayed potential in safeguarding the stomach lining. It achieves this by enhancing mucus secretion, improving blood circulation in minor vessels, and aiding the recovery of the stomach's surface cells. These impacts are particularly significant in the context of diabetic ulcers, as healing is hindered by oxidative damage and insufficient blood circulation. Preliminary studies indicate that grape-derived compounds, particularly resveratrol, could assist in regulating blood sugar levels, alleviating inflammation, and promoting tissue repair. This positions them as appealing solutions for tackling complications that arise in diabetes management. While Vitis vinifera possesses numerous beneficial properties, its specific impact on treating diabetes-related stomach ulcers remains largely unexplored. Most existing studies have concentrated on situations unrelated to diabetes or the general positive effects of antioxidants, with little attention given to their impact on digestive disorders among diabetic patients⁷. This research examines the effectiveness of Vitis vinifera L. can help treat conditions. The extract aids in the healing of stomach ulcers in diabetic rats induced by a substance known as streptozotocin. The study will examine the impact on the ulcer index, alterations in tissue, indications of oxidative stress, and levels of inflammatory markers. This research examines specific factors that suggest Vitis vinifera (grapevine) may be beneficial for stomach protection, particularly for diabetic individuals suffering from ulcers. The findings may lead to the development of safer natural therapies that offer a more comprehensive approach to managing stomach ulcers related to diabetes⁸.

MATERIAL AND METHODS:

Cultivation and Collection:

The stem bark from the Vitis vinifera L. species, belonging to the Vitaceae family, was gathered in January from a vineyard in Mainpuri, Uttar Pradesh, India. The bark was gently stripped from healthy plants, thoroughly rinsed with tap water to eliminate any dirt, and then air-dried in the shade at room temperature for 7 to 10 days to preserve its natural characteristics. Once dried, the bark was ground into a coarse powder with a machine and stored in a sealed container in a cool, dry location until it was required for extraction and testing.

Plant Authentication:

The plant (Vitis vinifera L.) was verified at the Botanical Garden in Noida, Uttar Pradesh, and approved by Dr. Priyanka Ingle, Scientist D. A plant sample was collected and sent to the department with the reference number No. /BSI/BGIR/1/TECH/2025/202 for future use.

Processing and Extraction of Plant Material:

The dried stem bark of Vitis vinifera L. was finely crushed and then extracted with a Soxhlet apparatus. Approximately 500grams of the powder was blended with a 70% ethanol and chloroform solution for a duration of 6 to 8hours, continuing until the siphon tube's liquid became clear, indicating that the extraction was complete. The liquid was filtered and subsequently heated gently to evaporate using electric water bath. The process took place at a temperature under 40°C to obtain a thick, semi-solid material. The final portion was placed in a sealed container and stored in the refrigerator at 4°C until required⁹.

Phytochemical screening of extract:

Preliminary chemical analysis of Vitis vinifera L. has been conducted. The bark extract was examined to determine the useful compounds present in it. Preliminary tests were conducted to identify the presence of substances such as flavonoids, tannins, phenols, alkaloids, and saponins¹⁰.

Animals:

Albino Wistar rats, each weighing between 150 and 200 grams, were sourced from the animal facility at Anand College of Pharmacy located in Agra. Prior to the study, the animals underwent health assessments and spent 8 to 10 days acclimating to their lab environment, which maintained standard conditions of approximately 25°C, 40 to 60% humidity, and a 12hour light/dark cycle. They were housed in plastic enclosures and provided with food and water as they desired. All procedures were conducted following the guidelines for animal care. The Animal Ethics Committee at Anand College of Pharmacy in Agra, India, granted approval for the animal study in accordance with CPCSEA guidelines. The experiment was approved prior to its commencement, as indicated by the IAEC reference number¹¹.

IAEC Approval:

The animal research was conducted after receiving permission from the Institutional Animal Ethical Committee, in accordance with CPCSEA guidelines.The research proposals received the green light from the IAEC members at Anand College of Pharmacy in Agra, U.P, India. Before initiating the animal experiments, we received the required approval, referenced by its approval number CCSEA/IAEC/ACP/44.

Acute Oral Toxicity:

The study carried out by Ahmed et al. in 2012 revealed the detrimental impacts associated with the consumption of Vitis vinifera L. (grape plant) were studied. Extracts from the bark of the stem were examined using adult male albino Wistar rats. Various quantities of the extracts were administered orally to the animals, and they were monitored closely for any indications of illness or mortality. No fatalities or significant adverse effects were observed even at doses of up to 200mg per kg of body weight, indicating the extracts are safe at these concentrations. Throughout the experiment, the treated group and the control group showed no notable differences in body weight or behavior. This supports the claim that ingesting stem bark extracts is safe⁷.

Selection of Dose:

Earlier investigations and past research indicate that administering two doses of Vitis vinifera L. has been explored. For our tests, we opted for two quantities of stem bark extract: 200mg/kg designated as the lower dosage and 400mg/kg as the higher. These quantities were selected to examine the effects of the extract at varying levels during the tests.

Induction of Diabetes:

An injection of 40mg of streptozotocin (STZ) per kilogram of body weight was administered to starving albino Wistar rats, leading to the onset of diabetes. The STZ was mixed in a cold citrate buffer solution. Blood sugar levels were monitored after a period of 72hours. The study included rats that were classified as diabetic, which had blood sugar levels exceeding 250mg/dL².

Grouping:

Group 1: Normal Control, Normal Saline (5ml/kg) administered orally.

Group 2: Diabetic control, Normal Saline (5ml/kg) administered orally.

Group 3: Diabetic+Standard control, Ranitidine (50mg/kg) administered orally.

Group 4: Test 1, Low dose of Vitis vinifera L. (200mg/kg) administered orally.

Group 5: Test 2, High dose of Vitis vinifera L. (400mg/kg) administered orally.

Ethanol induced Ulcer Model:

Gastric ulcers were induced by Absolute alcohol, a common practice employed to examine the protective effects of different treatments on the stomach and their healing properties for ulcers. Following 14 days of treatment, all test animals were deprived of food for one night (18-24hours) while still having free access to water. On the final day, administering 1mL of pure alcohol for every 200grams of body weight resulted in a stomach ulcer. One hour after giving the animals ethanol, they were gently put to sleep and then killed. The stomachs were carefully removed, opened on one side, and gently washed with a saltwater solution to get rid of food and blood clots. The inside of the stomach was checked for sores using a magnifying glass, and the seriousness of the sores was rated using a standard scoring system¹².

Ulcer Index (UI):

The ulcer index was used to measure how bad the damage to the stomach lining is by looking at and counting the visible sores. The mean ulcer score for each group was utilized for comparison purposes⁸.

Ulcer inhibition:

This illustrates the extent to which the test substance contributed to ulcer protection. This demonstrates the significant role that the test substance played in providing protection against ulcers.

Histopathological Examination:

The stomach tissues underwent preservation in a formalin solution, were divided into small pieces, and were treated with specialized stains referred to as hematoxylin and eosin. A detailed assessment was conducted to evaluate the tissue's condition, noting any signs of swelling, sores, and the healing progress⁸.

Statistical Analysis:

The data is presented as the mean along with the standard deviation (SD), with each group consisting of six animals (n = 6). To compare the data, we utilized one-way ANOVA, and then conducted a follow-up analysis with Tukey’s post hoc test. A p-value less than 0. 05 was seen as important in the results¹³.

RESULT AND DISCUSSION:

Phytochemical screening of extract: The result of phytochemical screening test are present in table 1.

Category Vitis Vinifera L.

Alkaloids Postive

Flavanoids Negative

Tanins Postive

Saponin Postive

Glycosides Postive

Terpenoids Negative

Blood Glucose level:

To ensure that diabetes had been triggered, blood sugar was assessed on the third day after the administration of streptozotocin (STZ). The study included rats that were classified as diabetic due to having blood sugar levels exceeding 250mg/dL. Additional assessments were conducted on the 7th and 14th days of the treatment. The final measurement was conducted just prior to the onset of alcohol-induced ulcers to assess blood sugar control throughout the study (Shows in table 2, Graph 1,2,3).

Graph 1: Blood Glucose Level 3^rd day

On day three, individuals with diabetes exhibit blood sugar levels close to 410 mg/dL, in stark contrast to the normal group, which has levels near 90 mg/dL. There is an initial decline in glucose levels observed in both the standard and test groups (Test 1 and Test 2), indicating that the treatment may be having an effect.

Graph 2: Blood glucose Level 7^th day

On the seventh day, a slight reduction in blood sugar levels is observed in both the diabetic participants and those undergoing standard treatment and evaluation. Test 2 demonstrates slightly greater improvement compared to Test 1, suggesting that the treatment has a moderate impact on reducing blood sugar levels.

Graph 3: Blood Glucose Level 14^th day

On the 14^th day, there is a significant decrease in blood sugar levels for both groups in Test 1 and Test 2. Test 2 reflects normal levels more closely than Test 1, indicating a strong effectiveness against diabetes that is comparable to the standard treatment.

Ulcer Index and Ulcer inhibition:

The ulcer index was much higher in the diabetic group (2. 833 ± 0.1667) than in the normal group (0. 2500 ± 0.1708) This means that diabetes makes it more likely to develop stomach ulcers (figure1). The usual medicine for ulcers lowered the ulcer score to 0. 9167 ± 0.2007, which means it prevented 67. 50% of ulcer development. In the test groups, Test 2 had a big decrease in the ulcer index (1. 000 ± 0.2582) with a 61. 84% reduction, which is important statistically (p < 0. 01) and similar to the standard. Test 1 showed a good result by lowering the ulcer index to 1. 750 ± 0.3096, which means there was a 38. 17% reduction (*p < 0. 001) (Graph 4) This suggests it has some protective effect on the stomach. (Table 3)

Table 3: Ulcer index and %inhibition on diabetic rats

Group	Ulcer Index	Ulcer Inhibition(%)
Normal Control	0.2500 ± 0.1708	-
Diabetic Control	2.833 ± 0.1667	-
Diabetic + Standard Control	0.9167 ± 0.2007**	67.50%
Test 1	1.750 ± 0.3096***	38.17%
Test 2	1.000 ± 0.2582**	61.84%

Graph 4: Ulcer index

The group with diabetes has a very high ulcer score (around 3. 0), which means they have serious stomach damage. Test 1, Test 2, and the control groups show a big decrease (p < 0. 0005), with Test 2 showing a little better ability to protect the stomach.

Histopathological examination:

A comprehensive analysis of the stomach lining was conducted to assess the effectiveness of the test compound in safeguarding diabetic rats. The samples were examined at 100X magnification using a technique known as hematoxylin and eosin (H&E) staining. The normal control cohort exhibited a properly functioning stomach with a complete inner lining, free from any abrasions or ulcers. A limited presence of inflammatory cells was observed in the subcutaneous layer, reflecting typical bodily health. Conversely, the diabetic control group exhibited obvious issues, including numerous sore areas on the tissue and moderate levels of inflammation. These alterations indicate evident harm to the body's lining and inflammation associated with diabetes. Those in the group receiving the conventional medication exhibited noticeable enhancements in the condition of their stomach lining. The images captured under the microscope revealed a large region exhibiting some surface damage along with mild, ongoing inflammation. The findings indicate a moderate degree of protection, but the inner lining did not fully heal. The participants who were administered a low dose of treatment exhibited stomach lining ulcers and displayed a moderate level of persistent inflammatory cells. Despite some level of protection, the extent of tissue damage indicated that the reduced dosage was insufficient to adequately safeguard the mucous lining. The group that received a high dose of treatment showed a lot of improvement in their tissue samples. The stomach tissue showed just a few small surface injuries and mild ongoing inflammation, which suggests that it was well protected. These results indicate that taking higher doses leads to better protection of the stomach lining in diabetic rats.

Fig. 2: Rat stomach histopathological sections (H&E, 100X) from several groups: Normal Control has intact mucosa and mild inflammation (A); multiple erosions and moderate inflammation (B); superficial erosion and mild inflammation (C); ulcerated mucosa and moderate chronic inflammation (D); and small superficial erosion and mild inflammatory infiltration (E) in Test 1 (Low Dose).

CONCLUSION AND FUTURE PERSPECTIVES:

The current study showed that in streptozotocin-induced diabetic rats, a model that closely resembles the delayed stomach repair seen in diabetic people, Vitis vinifera L. exhibits strong gastroprotective action. According to macroscopic and histological observations, the administration of Vitis vinifera extract, especially at higher dosages, resulted in a significant improvement in mucosal integrity, a decrease in ulcerated areas, and a slower infiltration of inflammatory cells. These outcomes were similar to those of the conventional antiulcer medication, suggesting that Vitis vinifera may be used as a treatment for gastric ulcers in hyperglycemic environments. Because of their cytoprotective, anti-inflammatory, and antioxidant qualities, the phytoconstituents in the extract—particularly flavonoids and polyphenols—are probably responsible for these positive effects. Even though the results are encouraging, more research is required to identify and describe the precise active ingredients causing the pharmacological effects that have been seen. The molecular mechanisms involved in mucosal defense and repair should be thoroughly investigated mechanistically. Prior to clinical translation, safety profiles and long-term toxicity investigations are also crucial. Vitis vinifera's therapeutic potential could be further increased by creating innovative pharmaceutical formulations, such as mucoadhesive or controlled-release systems. To confirm its effectiveness in humans, determine the ideal dosage, and investigate its compatibility with current treatment plans, more clinical trials will be required. As a result, Vitis vinifera shows promise as a natural remedy for diabetic gastropathy, offering safer and more effective options.

ACKNOWLEDGEMENT:

The authors wish to express their gratitude to Mr. Vikash Sharma. I appreciate your valuable guidance and assistance throughout this research. We would like to express our heartfelt gratitude to our friends for their constant support throughout our studies. The help and support they provided were essential for finishing this work. We sincerely appreciate all of the effort put in by everyone that brought this research to fruition.

CONFLICT OF INTEREST:

The author declares that there is no Conflict of interest.

LIST OF ABBREVIATION:

ANOVA: Analysis of Variance

BSI- Botanical Survey of India

CPCSEA: Committee for the Purpose of Control and Supervision of Experiments on Animals

COX-2: Cyclooxygenase-2

H&E: Hematoxylin and Eosin

IAEC: Institutional Animal Ethics Committee

IL- 6: Interleukin-6

L.: Linnaeus (used in botanical nomenclature)

mg/kg: Milligrams per Kilogram

n: Number of Animals per Group

PPI: Proton Pump Inhibitor

SD: Standard Deviation

STZ: Streptozotocin

TNF-α: Tumor Necrosis Factor-alpha

UI: Ulcer Index

HCl: Hydrochloric Acid

ROS: Reactive Oxygen Species

GI: Gastrointestinal

Fig: Figure

Graph: Graphical Representation (used in tables/figures)

REFERENCES:

1. Abdulla MA, Al-Bayaty FH, Younis LT, Abu Hassan MI. Anti-ulcer activity of Centella asiatica leaf extract against ethanol-induced gastric mucosal injury in rats. J Med Plants Res. 2010; 4(13): 1253–9.

2. Konturek PC, Brzozowski T, Burnat G, Szlachcic A, Koziel J, Kwiecien S, وآخ. Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats. J Physiol Pharmacol. 2010; 61(4): 429–36.

3. Tarnawski AS, Ahluwalia A. The critical role of growth factors in gastric ulcer healing: The cellular and molecular mechanisms and potential clinical implications. Cells. 2021; 10(8).

4. Kim HU. Diagnostic and treatment approaches for refractory peptic ulcers. Clin Endosc. 2015; 48(4): 285–90.

5. Hasona N, Hussein T. Biochemical, histopathological, and histochemical effects of Vitis vinifera L. extract on acetic acid-induced colitis. J Intercult Ethnopharmacol. 2017; 6(4): 351–6.

6. Choi J, Choi SY, Hong Y, Han YE, Oh SJ, Lee B, وآخ. The central administration of vitisin a, extracted from Vitis vinifera, improves cognitive function and related signaling pathways in a scopolamine-induced dementia model. Biomed Pharmacother. 2023; 163(March): 114812. https://doi.org/ 10.1016/j.biopha.2023.114812

7. Ahmed M, Chavan A, Lakshmikantha RY. Evaluation of Antidiabetic Activity of Vitis vinifera Stem Bark. 2012; 5(11): 5239–42.

8. Chandra P, Kaleem M, Sachan N, Pathak R, Alanazi AS, Alsaif NA. Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm J. 2023;31(11):101815. https://doi.org/10.1016/ j.jsps.2023.101815

9. Sayed DA, Fahmy SR, Soliman AM, Hussein NS. Antiulcerogenic efficacy of ethanolic extract of Vitis vinifera leaves in rats. Int J Pharm Pharm Sci. 2016; 8(9): 163–72.

10. Bibi Sadeer N, Llorent-Martínez EJ, Bene K, Fawzi Mahomoodally M, Mollica A, Ibrahime Sinan K. Chemical profiling, antioxidant, enzyme inhibitory and molecular modelling studies on the leaves and stem bark extracts of three African medicinal plants. J Pharm Biomed Anal. 2019; 174: 19–33.

11. Secretary M.

12. Al Batran R, Al-Bayaty F, Jamil Al-Obaidi MM, Abdualkader AM, Hadi HA, Ali HM, وآخ. In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats. PLoS One. 2013; 8(5): 2–12.

13. Adinortey MB, Ansah C, Galyuon I, Nyarko A. In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents . Ulcers. 2013; 2013: 1–12.

Received on 05.07.2025 Revised on 10.11.2025

Accepted on 15.01.2026 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3169-3175.

DOI: 10.52711/0974-360X.2026.00450

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Group	Blood Glucose Level
Group	3^rd Day	7^th Day	14^th Day
Normal Control	92.50 ± 0.7638	90.50 ± 2.754	93.17 ± 1.956
Diabetic Control	411.3 ± 1.145	410.5 ± 2.794	391.8 ± 1.352
Diabetic + Standard Control	272.2 ± 1.249	270.9 ± 2.716***	314.5 ± 9.845***
Test 1	288.5 ± 0.9916***	288.5 ± 3.597**	247.8 ± 1.869***
Test 2	259.2 ± 261.8***	260.6 ± 1.558***	207.2 ± 2.182***