INTRODUCTION:

Ulcer is erosion on the skin or on the mucous membrane specified by outward inflamed dead tissue. The word ulcer is derived from Latin word “ulcus” (genitive: ulceris) which stands for sore, wound or an ulcer. The erosions are most commonly seen on gastric or duodenal mucosa and are referred to as peptic ulcer. Peptic ulcers are the areas of degeneration and necrosis of gastro-intestinal mucosa which is exposed to acid and pepsin secretion.

Types:

1. Gastric ulcer: When the ulcers occur in stomach they are called gastric ulcers.

2. Duodenal ulcer: When the ulcer occurs in the duodenum it is called as duodenal ulcer.

The duodenal ulcer is the commonest of peptic ulcer with the ratio of 4:1 in duodenum and stomach respectively.

Peptic ulcer can lead to several complications such as obstruction, hemorrhage and perforation.

Prevalence:

Ulcers affect nearly 10% of world population of which 5% constitute gastric ulcer. Peptic ulcers are more common in males than in females. The prevalence is approximately 11% to 14% in men and 8% to 11% in women.

Different types of ulcers:

There are different types of ulcer differentiated based on their origin or place of occurrence in human body, of which peptic ulcer are the commonest all. Pressure ulcers, Genital ulcers, Peptic ulcers, Venous ulcers, Aphthous ulcer.

Signs and symptoms of peptic ulcer:

Abdominal discomfort and nausea, Bloating and abdominal fullness, Water brash, Hematemesis, Melena, Rarely acute peritonitis, Dark or black stools, Dry tongue, Weak or feeble pulse, Shortness of breath.

Etiology and pathogenesis:

Initially the peptic ulcers were believed to be caused by the aggressive action of hydrochloric acid and pepsin on mucosa. The enzyme gastrin stimulates the production of HCl by parietal cells and in patients with H. pylori infection the increased levels of gastrin are produced that in turn increases production of acid thus leading to erosion of gastric mucosa and subsequently ulceration. Majority of cases of peptic ulcer are due to H.pylori infection, as about 80-90% of patients with duodenal ulcer have H. pylori infection and same goes with 70-90% patients of gastric ulcer.

Herbal medicine Asanti ulcer:

In this modern era also 75–80% of the world populations still use herbal medicine mainly in developing countries, for primary health care because of better cultural acceptability, better compatibility with the human body, and lesser side effects.

Histological studies revealed that these medicinal plants did not show any acute toxicity. Preliminary photochemical screening of this medicinal plant identified the presence of important secondary metabolites like flavonoids and tannins which are the active principles of antiulcer activity.

Medicinal plants considered as gastro-protective and healing agents on ulcers in ayurvedic resources and beside that to gather evidence for their effectiveness and biological mechanisms in modern investigation. Ethno medicinal herbs, which are valuable as antiulcer agents and their use experimentally was evaluated and proved by many researchers for its antiulcer activity.

PLANTPROFILE:

Catunaregam spinosa linn. Linn:

Catunaregam spinosa linn. (Thunb.) belongs to the family Rubiaceae. The genus Catunaregum (Xeramphis Rafin.) Consist of about10 species, out of which two are in India. In Ayurveda it is known as madanaphala. Parts of plant like stem and root bark importance in treatment of diarrhea, dysentery and as well as abortifacient, anthelmintic and antipyretic. Medicinal value also considered to be sedative and hypoglycemic used in case of stomach ache as first aid remedy, roots are used in the treatment of epilepsy, eye ache and urinary infection, fruit of C. spinosa is used as fish poison, emetic and the leaves are use din Pulmonary Infections.

Botanical Description:

Small trees with small straight axillary spines. Leaves opposite on short lateral branchlets, to 4.5 x 2cm, obovate, obtuse, tomentose below, petiolate; stipule ovate, cuspidate. Flowers solitary, terminal on lateral branches, pedicellate; calyx tube 5mm long, lobes obovate, hispid; corolla tube 6mm long, broad, densely villous at the base inside; lobes 5, 12mm long, obovate, twisted, white; stamens 5, anthers sessile at the mouth of the corolla; ovary 2-6-celled; ovulesmany; style12mm long, stout; stigma fusiform, ribbed. Fruitanobovoid berry, 4x3cm, glabrous; seeds many, embeddedinpulp.

Collection of plant material:

The plant has been selected on the basis of its availability and folk use of the plant. The fruits of Catunaregam spinosa linn. Were collected from Bhopal (Madhya Pradesh) in the month of February, 2024. Drying of fresh plant parts was carried out in sun but under the shade. Dried fruits of Catunaregam spinosa linn. were preserved in plastic bags, closed tightly and powdered asper the requirements.

Extraction by Soxhlet extraction:

Fruit of Catunaregam spinosa linn. were shade dried at room temperature. The shade dried plant material (50 gram) were coarsely powdered and subjected to extraction with petroleum ether by Soxhlet extraction. The extraction was continued till the defatting of the material had taken place. Dried powdered Catunaregam spinosa linn. has been extracted with hydroalcoholic solvent (ethanol: water: 80: 20) using Soxhlet extraction process for 48 hrs, filtered and dried using vacuum evaporatorat 40ºC.

Determination of Percentage yield:

The percentage yield of an extract is a measure that quantifies the efficiency of the extraction process. It is calculated by comparing the amount of extract obtained to the initial weight of the raw material used.

Phytochemical Screening:

Medicinal plants are traditional pharmaceutical commodities and many of the current medicinal drugs are derived indirectly from plants. Phytochemical materials consist of two main bio active components (Chlorophyll, vitamins, amino acids, sugar etc.) and secondary bioactive components; (Alkaloids, Terpenoids, Phenols, Flavonoids etc.). Phytochemical examinations were carried out for all the extracts as per the standard methods.

Estimation of total flavonoids content:

Determination of total flavonoids content was based on aluminum chloride method. 10mg quercetin was dissolved in 10ml methanol, and various aliquots of 5- 25μg/ml were prepared in methanol. 10mg of dried extracts of were dissolved in 10ml methanol and filtered. 3ml (1mg/ml) of this solution was used for the estimation of flavonoid. 1ml of 2% AlCl3 solution was added to 3ml of extract or standard and allowed to stand for 15min at room temperature; absorbance was measured at 420nm.

In vivo anti ulcer activity of extract of Catunaregam spinosa Linn.

The in vivo antiulcer activity study of the extract from Catunaregam spinosa linn. aims to evaluate its potential therapeutic effects in preventing or treating ulcers, which are lesions that develop on the lining of the stomach or intestines. Catunaregam spinosalinn., a medicinal plant traditionally used in various forms of folk medicine, has been reported to possess multiple pharmacological properties. These properties suggest that the plant's extract may have protective effects against the development of ulcers.

Animals:

Wistar rats (150–200g) were group housed (n= 6) under a standard 12h light/dark cycle and controlled conditions of temperature and humidity (25±2°C, 55–65%). Rats received standard rodent chow and water adlibitum. Rats were acclimatized to laboratory conditions for 7 days before carrying out the experiments. All The experiments were carried in anoise- free room between 08.00 to 15.00 h. Separate group (n=6) of rats was used for each set of experiments. The animal studies were approved by the Institutional Animal Ethics Committee (IAEC), constituted for the purpose of control and supervision of experimental animals by Ministry of Environment and Forests, Government of India, New Delhi, India.

Experimental designs:

Inducingulcersinexperimentalanimalmodelsusingabsoluteethanolisawell-established method for studying the pathophysiology of ulcers and evaluating the protective effects of various compounds, including plant extracts. Absolute ethanol (100% ethanol) is a potent ulcerogenic agent that causes rapid and severe damage to the gastric mucosa, leading to ulcer formation. This method is widely used due to its ability to mimic the oxidative stress and direct mucosal injury associated with ulcer development in humans.

Ulcer induced by absolute ethanol

The rats were divided into four groups of six each.

Group I (toxicant control) received absolute ethanol (1 ml/animal)

Group II was treated with ranitidine (50mg/kg)

Groups III was treated with hydroalcoholic extract of Catunaregam spinosa linn.100mg/kg/p.o.

Groups IV was treated with hydroalcoholic extract of Catunaregam spinosa linn.200mg/kg/p.o.

The animals were treated with ranitidine (100mg/kg), dose of hydroalcoholic extract of Catunaregam spinosa linn.100 and 200mg/kg (once daily) for 5 days after the induction of ulcer, while the control group received only the vehicle. The rats were fasted for 24 h and they received 1ml of absolute ethanol orally. The animals were sacrificed after 1 h of ulcerogen administration, and their stomachs were excised and the gastric contents were aspirated. The contents were subjected to centrifugation at 1000rpm for 10 min and then analyzed for pH (digital Hmeter), pepsin activity, total and free acidity.

RESULTS ANDDISCUSSION:

Determination of percentage yield:

To obtain the percentage yield of extraction is very important phenomenon in phytochemical extraction to evaluate the standard extraction efficiency for a particular plant, different parts of same plant or different solvents used. The yield of extracts obtained from different samples using pet. Ether, hydro-alcohol solvents are depicted in the table

Table 1: % Yield of hydroalcoholic extract of Catunaregam spinosalinn.

S. No.	Extracts	% Yield (W/W)
1.	Pet ether	1.02%
2.	Hydroalcoholic	7.63%

The percentage yield of different extracts from Catunaregam spinosa linn. provides valuable insights into the efficiency of the extraction process and the potential concentration of bioactive compounds within each extract. As presented in Table, the hydroalcoholic extract exhibited a significantly higher yield of 7.63% compared to the petroleum ether extract, which yielded only 1.02%.

Phytochemical screening ofextract:

Small portion of the dried extracts was subjected to the phytochemical tests using standard methods to test for alkaloids, glycosides, saponins, flavonoids and phenol separately for extracts of all samples. Small amount of extract was suitably re-suspended into the distilled water to make the concentration of 1 mg per ml. The outcomes of the results are discussed in the table.

Table 2: Phytochemical screening of extract of Catunaregam spinosa linn.

S. No.	Constituents	Hydroalcoholic extract
1.	Alkaloids -Dragendroff’s test Hager’s test	+ve +ve
2.	Glycosides -Legal’stest	+ve
3.	Flavonoids - Lead acetate Alkaline test	+ve +ve
4.	Phenol - Ferric chloride test	-ve
5.	Proteins -Xanthoproteic test	+ve
6.	Carbohydrates - Fehling’s test	-ve

The phytochemical screening of the hydroalcoholic extract of Catunaregam spinosa, as outlined in Table, reveals the presence of several bioactive constituents that may contribute to the plant's medicinal properties. The screening results indicate that the extract contains alkaloids, glycosides, flavonoids, proteins, saponins, and diterpenes, while phenols, carbohydrates, and tannins were either absent or detected only in trace amounts.

Total flavonoids content estimation (TFC):

Total flavonoids content was calculated as quercetin equivalent (mg/100mg) using the equation based on the calibration curve: y = 0.027x + 0.008, R2=0.999, where X is the quercetin equivalent (QE) and Y is the absorbance.

Table 3: Preparation of Calibration curve of Quercetin

S. No.	Concentration (µg/ml)	Mean Absorbance
1.	5	0.151
2.	10	0.286
3.	15	0.432
4.	20	0.567
5.	25	0.689

Figure 1: Graph of calibration curve of Quercet

Results of antiulcer activity of extract of Catunaregam spinosa Linn. The effect of the hydroalcoholic extract of Catunaregam spinosa linn. on ethanol-induced ulceration in rats was assessed by measuring the ulcer index. Ethanol-induced gastric ulcers are a common model for studying ulcerogenesis and evaluating potential anti-ulcer agents. The results from the experiment indicate that the hydroalcoholic extract of Catunaregam spinosa linn. demonstrates significant anti-ulcerogenic activity, though the efficacy is dose- dependent.

In the control group, which received no treatment, the ulcer index was 7.00±0.25, reflecting a high level of ulceration due to the ethanol challenge. This is consistent with the well-established method for inducing ulcers using ethanol, which causes severe mucosal damage and is a reliable model for screening anti-ulcer agents.

The hydroalcoholic extract of Catunaregam spinosa linn. at 100mg/kg exhibited a notable reduction in the ulcer index to 3.40±0.15, which is statistically significant compared to the control group (p<0.05). This suggests that even at a lower dose, the extract has a protective effect against ethanol-induced gastric mucosal damage. However, it is less effective than Ranitidine, indicating that while the extract possesses anti-ulcerogenic properties, it is not as potent as the standard drug in this dosage.

At a higher dose of 200mg/kg, the hydroalcoholic extract further reduced the ulcer index to 3.05±0.10. This reduction is statistically significant and comparable to the reduction observed with Ranitidine (p<0.05). The improved efficacy at this higher dose suggests a dose-dependent response, where the protective effect of the extract becomes more pronounced with increased dosage. This aligns with the general pharmacological principle that higher doses often yield greater therapeutic effects, though the efficacy can also be influenced by other factors such as absorption, metabolism, and bioavailability.

Effect of hydroalcoholic extract of Catunaregam spinosa linn. on ulcer index by ethanol induced ulcers in rats

Effect of hydroalcoholic extract of Catunaregam spinosa linn. on gastric parameters i.e. pH by ethanol-induced ulceration in rats

The impact of the hydroalcoholic extract of Catunaregam spinosa linn. on gastric pH in an ethanol-induced ulcer model provides important insights into its potential therapeutic effects on gastric mucosal protection. In this study, the effects of the extract on gastric pH were evaluated alongside Ranitidine, a well-known anti-ulcer drug, to assess the extract's efficacy.

Effect of hydroalcoholic extract of Catunaregam spinosa linn.on gastric parameters i.e. total acidity ethanol- induced ulceration in rats

The evaluation of total acidity in gastric juice following treatment with the hydroalcoholic extract of Catunaregam spinosa linn. provides valuable insight into its potential anti-ulcerative properties. In this study, the effect of the extract on total gastric acidity, induced by ethanol, was assessed and compared to Ranitidine, a commonly used anti-ulcer agent.

SUMMARY:

The study investigated the hydroalcoholic extract of Catunaregam spinosa linn.for its potential anti-ulcerogenic effects and its influence on various gastric parameters in rats with ethanol- induced ulcers. The extraction process yielded 7.63% from hydroalcoholic solvent, significantly higher than the 1.02% yield from pet ether extraction. Phytochemical screening of the hydroalcoholic extract identified the presence of alkaloids, glycosides, flavonoids, proteins, saponins, and diterpenes, while phenols, carbohydrates, and tannins were absent.

The extract’s total flavonoids content was measured at 0.758mg/100mg, and its total alkaloid content was 0.322 mg/100mg. The antioxidant activity, assessed using the DPPH radical scavenging assay, indicated a moderate activity with an IC50 value of 81.39μg/mL, which is less potent than ascorbic acid (IC50 of 21.81μg/mL). This suggests that while the extract has some antioxidant properties, it is not as effective as the standard antioxidant.

In terms of anti-ulcerogenic effects, the hydroalcoholic extract demonstrated significant improvements across several gastric parameters. The ulcer index was notably reduced at both 100mg/kg and 200mg/kg doses, with the 200mg/kg dose showing an ulcer index of 3.5±0.10, which was comparable to the standard treatment ranitidine (2.85±0.15). Similarly, the extract improved gastric pH and reduced total and free acidity levels, with the higher dose achieving a pH of 4.45±0.13 and total acidity of 46.74±0.20mEq/L, closely aligning with ranitidine’s effects. Additionally, pepsin activity was significantly decreased at the 200mg/kg dose, reaching 2.65±0.25 per ml/h, which was comparable to ranitidine’s effect of 2.45±0.10 perml/h.

In conclusion, the hydroalcoholic extract of Catunaregam spinosa linn.exhibits significant anti- ulcerogenic properties, particularly at higher doses. The reduction in ulcer index, improvement in gastric pH, and decrease in both total and free acidity underscore its potential as a therapeutic agent for managing gastric ulcers. The presence of key phytochemicals likely contributes to these effects, although further research is required to fully understand its mechanisms and to validate its long-term safety and efficacy.

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Received on 13.10.2024 Revised on 06.11.2024

Accepted on 21.11.2024 Published on 08.03.2025

Available online from March 12, 2025

Res.J. Pharmacology and Pharmacodynamics.2025;17(1):19-24.

DOI: 10.52711/2321-5836.2025.00004

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