Antiulcer Effect of Genus Symphytum L. and Portulaca oleracea L. as Investigated on Experimental Animals

Peptic ulcer disease (PUD) occurs when open sores, or ulcers, form in the stomach or first part of the small intestine caused by bacterial infection (H. pylori) and/or nonsteroidal anti-inflammatory drug (NSAID) use. This study was conducted to evaluate the antiulcer effect of some plants including genus Symphytum L., and Portulaca oleracea L. on aspirin-induced acute gastric ulcer in rats. Sixteen male albino rats (200–210 g b.wt. each) were divided into 4 groups, 4 rats each, one of them left as the control −ve group while the other 3 groups orally administered with aspirin at a dose of 200 mg/kg b.wt., for gastric ulcer induction, one of them left as control +ve and the rest 2 groups were orally administered with genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt., each. for seven consecutive days. Body weight gain (BWG), the length of gastric ulcer, the volume of gastric juice, the total acidity of gastric juice, and blood sample were assessed. The results showed that orally administered with genus Symphytum L. and Portulaca oleracea L. significantly reduced the length of gastric ulcer, gastric juice volume, and total acidity of gastric juice, in addition to decreasing total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), RBC, WBC, HGB, and PLT. No significant changes were observed in the pH of gastric juice among treated groups. Moreover, in comparison to Portulaca oleracea L., genus Symphytum L. showed preferable results. Accordingly, genus Symphytum L. and Portulaca oleracea L. could be used as plants as curative agents against gastric ulcer in experimental rats.


Introduction
Peptic ulcer disease occurs when open sores, or ulcers, form in the stomach or frst part of the small intestine.Many cases of peptic ulcer disease arise due to bacterial erosion of the protective lining of the digestive system.In addition, habitual consumption of pain relievers increases the risk of peptic ulcer development.Peptic ulcer disease is a condition in which painful sores or ulcers develop in the lining of the stomach or the frst part of the small intestine (the duodenum).Normally, a thick layer of mucus protects the stomach lining from the efect of its digestive juices.But many things can reduce this protective layer, allowing stomach acid to damage the tissue.Tere are a lot of medicinal plants that could be used for preventing and treating the complications of peptic ulcer [1].
It is believed that NSAIDs and aspirin may cause harm to the mucosa of the stomach and duodenum by inhibiting the synthesis of mucosal prostaglandin.Tis is considered a signifcant mechanism of gastrointestinal mucosal injury [1].Selective cyclooxygenase (COX)-2 inhibitors produce less gastric damage than conventional nonsteroidal antiinfammatory drugs (NSAIDs), suggesting that NSAIDs cause damage by inhibiting COX-1 leading to limiting mucus and bicarbonate secretion, slowing mucosal blood fow, impaired the blood platelet aggregation, and altered the structure of microvascular [2,3].
Genus Symphytum L. (Symphytum ofcinale) is a plant that can be found commonly throughout Europe and parts of Asia and has also naturalized in North America where it has spread quickly.Native Americans have also recognized its healing properties and have used it in their treatments.Moreover, genus Symphytum L. has been used in veterinary medicine [4].However, genus Symphytum L. formulations have been applied topically to treat episiotomy discomfort, cracked, sore nipples, fractured bones, lung congestion, tendon damage, gastrointestinal ulcerations, wound healing, and/or joint infammation [5,6].Allantoin as an active ingredient of genus Symphytum L. has been connected to genus Symphytum L.'s capacity to heal wounds.Also, it is used for skin protection; therefore, it has been included as an ingredient of several cosmetic products and antiulcer drugs.Previously, it was stated that the level of allantoin in genus Symphytum L. leaves was around 1 mg/g [5].
Portulaca oleracea L., a member of the Portulacaceae family, is an annual herb that thrives in warm climates.It is commonly known as khurfa in Arabic and common purslane in English, and it can be found in various tropical and subtropical regions worldwide, including many parts of the United States.Tis plant is often consumed as a vegetable and utilized for medicinal purposes.Troughout history, purslane has been used to treat a variety of ailments, including skin diseases, fever, dysentery, diarrhoea, bleeding piles, and kidney, liver, and spleen diseases [7].Due to its diverse phytoconstituents, purslane has shown to possess many pharmacological properties, such as hepatoprotective, neuroprotective, anti-infammatory, antimicrobial, antidiabetic, antioxidant, anticancer, antihypertensive, and antiulcerogenic actions [8].Accordingly, this study was conducted to evaluate the antiulcer efect of some promising medicine plants including genus Symphytum L. and Portulaca oleracea L. on aspirin-induced acute gastric ulcers in rats.

Aspirin and Medical
Herbs.Aspirin (aspegic acid) was purchased from Arabian Chemical Co.(Jeddah, KSA), and the medicinal herb Portulaca oleracea L. was purchased from the local market in Holy Makkah, genus Symphytum L. from Amazon by online purchasing.

Rats.
Sixteen Sprague-Dawley male albino rats with an average weight of 200 ± 10 g were obtained from the Department of Medical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Holy Makkah, Saudi Arabia.

Plant Extraction.
Te frst plant, genus Symphytum L., dried leaves, was extracted by the infusion process in water at 70 °C water for 15 minutes within a glass container before being fltered through paper [9].Te second plant, Portulaca oleracea L., was extracted by dissolving in ethanol for 24 hours, then the precipitate active ingredient was separated by a rotary evaporator [10].

Preparing
Rats for the Experiment.Te experimental rats were housed in a clean and sterile polyvinyl cage in a room maintained at 22-24 C and 12 h light/dark cycle.Te animals were kept on water ad libitum and basal diet for seven days for acclimatization before the beginning of the experiment.Tey were administered orally with extracts from the plants genus Symphytum L. and Portulaca oleracea L. for 7 consecutive days.

Peptic Ulcer Induction.
Peptic ulceration was induced by orally administrated with 200 mg/kg b.wt in the animals according to the procedure described by Agrawal et al. [12].Te administration of treatment to animals began 1 day following ulcer induction.

Experimental Design. Rats were divided randomly into four groups as follows:
Group 1: fed on basal diet only as a control negative (C −ve) group for 7 consecutive days Group 2: fed on basal diet only and oral injection with aspirin at a dose of 200 mg/kg b.wt as a control positive (C +ve) group for 7 consecutive days Group 3: fed on basal diet with oral injection with aspirin at a dose of 200 mg/kg b.wt.and genus Symphytum L. at a dose of 100 mg/kg b.wt.for 7 consecutive days, according to the dose carried out by (Da Silva et al.) [13] Group 4: fed on basal diet and oral injection with aspirin at a dose of 200 mg/kg b.wt.with Portulaca Oleracea L. at a dose of 100 mg/kg b.wt.for 7 consecutive days, according to the dose carried out by Kumara et al. [14] All the animals were fasted for 12 hours before being sacrifced on the next day.

Measurement of the Volume of Gastric Juice.
At the end of the experimental period, all rats were fasted for 12 hours, during which they were deprived of food but had ad libitum access to tap water.Te rats were anesthetized with diethyl ether, followed by a laparotomy.Subsequently, the stomach was excised.Te stomachs of each rat were weighed, wrapped around the pyloric and cardiac sphincter apertures, and injected with 3 ml of distilled water to collect gastric juice.Te stomachs were then centrifuged at measure and convert the amount of gastric juice into millilitres (mL).

Measurement of the Length of Gastric Ulcer.
Te stomachs of every rat were longitudinally opened, cleaned in saline, and then examined under a dissecting microscope.Following the procedure outlined by Akhtar and Ahmad [15], the length of the stomach ulcer was measured for each group and expressed as mean + SE.

Determination of the Total Acidity and pH of Gastric
Juice.By titrating 1 ml of gastric juice in 10 ml of distilled water with 0.01N NaOH and two drops of phenolphthalein as an indicator, total acidity was ascertained.Percentages were used to express the data.A pH meter was used to measure the pH level.
2.3.9.Blood Sampling.Animals from each group were sacrifced at the end of the experiment, and the blood was collected in a clean, dry centrifuge tube.Te blood was then centrifuged to separate the serum by centrifuging at 4000 RPM for 10 minutes at room temperature, followed by keeping the serum in a plastic vial (well stoppered) until analysis.

Ethical Approval.
Te University of Umm Al-Qura approved and evaluated this study before any data were collected (number:HAPO-02-K-012-2030-11-1877).Ensure that all areas of animal experimentation are done in line with the highest ethical standards.

Statistical
Analysis.Statistical analysis will be by oneway analysis of variance (ANOVA) to test diferences in means of variables between groups, and p < 0.05 will be considered statistically signifcant.All data will be analysed by using the IBM Statistical Package for Social Sciences (SPSS) for Windows, version 28.0 (Armonk, N.Y.: IBM Corp).

Efects of Plant Extracts on Body Weight Gain in Rats
Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt., each on body weight gain in rats inficted with gastric ulcer in rats inficted with gastric ulcer is listed in Table 1.
It could be observed for control positive rats that body weight gain was 10.00 ± 0.89 g/7 consecutive days, compared to 27.50 ± 0.09 g/7 consecutive days for control negative (p < 0.05).Tese results denote that there was a signifcant decrease in body weight gain in rats inficted with gastric ulcers compared to normal rats.All rats were orally administered with genus Symphytum L. and Portulaca Oleracea L. at a dose of 100 mg/kg b.wt.Rats orally administered with genus Symphytum L. showed a signifcant increase in BWG as compared to control positive which were 10.00 ± 0.89, 16.60 ± 0.52, and 10.90 ± 0.29 g/7 day, while rats orally administered with Portulaca Oleracea L. did not refect improvement in BWG which was 10.90 ± 0.29 g/7 days compared to all groups.

Efects of Plant Extracts on the Length of Gastric Ulcer in
Rats Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca Oleracea L. at a dose of 100 mg/kg.b.wt., each on the length of gastric ulcer in rats inficted with gastric ulcer are listed in Table 2.
It could be observed that the length of gastric ulcer in group No.2 (control +ve group) was 2.03 ± 0.09 mm., compared to group No. 1 (control −ve group) which was (0.00).Tis refects a signifcant increase in gastric ulcer length in the group No.2 (control +ve group) as compared to the group no. 1 (control −ve group).All rats orally administered with genus Symphytum L. showed signifcant decrease in gastric ulcer length as compared to group no. 2 (control +ve group) which were 0.91 ± 0.02 mm.As for group no.4 (Portulaca oleracea L.), 1.21 ± 0.05 mm showed a signifcant decrease in gastric ulcer length as compared to group no.1 (control −ve group).Moreover, in comparison to other groups, group no. 3 (genus Symphytum L.) had the best results.

Efects of Plant Extracts on the Volume of Gastric Juice in
Rats Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt. each on the volume of gastric juice in rats induced by gastric ulcer is listed in Table 3.
It could be observed for group no. 2 (control +ve group) that the volume of gastric juice was 2.30 ± 0.08 mL compared to 1.33 ± 0.03 mL for group no. 1 (control −ve group) (p < 0.05).Tese results were signifcant.All rats orally administered with genus Symphytum L. and Portulaca Oleracea L., at a dose of 100 mg/kg b.wt., each showed a signifcant decrease in volume of gastric juice with values of 1.50 ± 0.04, 1.70 ± 0.07, and 2.30 ± 0.08 2.30 ± 0.08 mL, respectively.For group no. 3 (genus Symphytum L.) showed a signifcant decrease in the volume of gastric juice when compared with group no. 4 (Portulaca oleracea L.) with values of 1.50 ± 0.04 and1.70 ± 0.07 mL, respectively.In addition, group no. 3 (genus Symphytum L.) was the best group in comparison to the other group.

Efects of Plant Extracts on pH of Gastric Juice in Rats
Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt. each on the pH of gastric juice in rats induced by gastric ulcer is listed in Table 4.
As listed in Table 4, the result of this study found a signifcant change in pH of gastric juice for rats in group no. 2 (control +ve group], which orally administered a dose of 200 mg/kg b.wt. of aspirin compared with group no. 1 (control −ve group) (5.60 ± 0.09 ab and 4.70 ± 0.04 d, respectively).All rats orally administered with genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt., each showed insignifcant changes in the pH of gastric juice when compared to group no. 2 (control +ve group).

Efects of Plant Extracts on the Total Acidity of Gastric Juice in Rats
Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/ kg b.wt. each on the total acidity of gastric juice in rats induced by gastric ulcer are listed in Table 5.
Te results indicate a signifcant increase in total acidity in gastric juice in rats in the control +ve group compared to the (control −ve group]), with values of 1.00 × 10 −1 ± 0.005.As compared to the (control +ve group), all groups of ulcerated rats treated with genus Symphytum L. and Portulaca oleracea L. showed a signifcant decrease in the percentage of total acidity.However, in group 3, the genus Symphytum L. dose showed the highest reduction in the percentage of total acidity in rats compared to (control +ve group), 3.50 × 10 −2 ± 0.003 and 1.00 × 10 −1 ± 0.005, respectively.Furthermore, the dose of Portulaca oleracea L. showed the lowest reduction in total acidity of gastric juice   4 Journal of Nutrition and Metabolism compared with (control +ve group) of 5.00 × 10 −2 ± 0.002 and 1.00 × 10 −1 ± 0.005, respectively.

Efects of Plant Extracts on TG and TC of Gastric Juice in
Rats Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg.b.wt. each on TG and TC in rats induced by gastric ulcer are listed in Table 6.
As cleared from Table 6 for group no. 2 (control +ve group), the results for TG and TC were 98.92 ± 2.62 and 130.30 ± 3.02 mg/dl for 7 consecutive days, Compared to 80.24 ± 1.03, 78.24 ± 1.19 1 mg/dl group no. 1 (control −ve group) for 7 consecutive days (p < 0.05).All rats orally administrated with genus Symphytum L. at a dose of 100 mg/kg b.wt.with a value of TG and TC was 80.24 ± 1.03 c and 78.24 ± 1.19 c mg/dl, respectively, showed a signifcant result when compared with group no. 2 (control +ve group).For orally administered with Portulaca oleracea L. at a dose of 100 mg/kg b.wt., values of (TG and TC) 95.15 ± 0.09 b and 103.31 ± 2.37 mg/dl b, respectively, showed a signifcant result when compared with group no. 2 (control +ve group).For group no. 3 (genus Symphytum L.), values of (TG and TC) 80.24 ± 1.03 c and 78.24 ± 1.19 c mg/dl, respectively, showed signifcant results when compared with group no. 4 (Portulaca oleracea L.) with values of (TG and TC) 95.15 ± 0.09 b and 103.31 ± 2.37 b mg/dl, respectively.We observed group no. 3 (genus Symphytum L.) had a better signifcant efect on TG and TC more than group no. 4 (Portulaca oleracea L.).

Efects of Plant Extracts on AST, ALT, and ALP of Gastric
Juice in Rats Inficted with Gastric Ulcer.Te efects of genus Symphytum L. and Portulaca oleracea L at a dose of 100 mg/ kg b.wt each on AST, ALT, and ALP in rats induced by gastric ulcer are listed in Table 7.
It could be observed for group no. 2 (control +ve group) that AST, ALT, and ALP were 130.13 ± 3.07, 116.40 ± 2.30, and 292.90 ± 5.16 U/L for 7 consecutive days, compared to 45.92 ± 2.01, 41.25 ± 1.17, and 146.40 ± 4.07 U/L for 7 consecutive days for group no. 1 (control −ve group) (p < 0.05).Tese results denote that there was a signifcant increase in AST, ALT, and ALP in rats inficted with gastric ulcers compared to normal rats.All rats were orally administered with genus Symphytum L. and Portulaca oleracea L. at a dose of 100 mg/kg b.wt.showed a signifcant decrease in AST, ALT, and ALP as compared to control-positive rats.Rats orally administered with genus Symphytum L. refected the highest signifcant decrease in AST, ALT, and ALP compared to Portulaca oleracea L.

Efects of Plant Extracts on RBC, WBC, HGB, and PLT of Gastric Juice in Rats
Inficted with Gastric Ulcer.Te efects of genus Symphytum L., and Portulaca oleracea L. at a dose of 100 mg/kg b.wt. each on RBC, WBC, HGB, and PLT in rats induced by gastric ulcer are listed in Table 8.
It could be observed in group no. 2 (control +ve group), and the blood test results for RBCs, WBCs, HGB, and PLTs were signifcantly diferent from those of group no. 1 (control −ve group) (p < 0.05).All rats orally administered with genus Symphytum L. at a dose of 100 mg/kg b.wt., and the blood test results for RBCs, WBCs, HGB, and PLTs showed a signifcant result when compared to group no. 2 (control +ve group).For rats orally administered with Portulaca oleracea L. at a dose of 100 mg/kg b.wt., the blood test results for RBCs, WBCs, and PLTs showed a signifcant result, except for HGB which showed an insignifcant result when compared to group no. 2 (control +ve group).Moreover, for group no. 3 (genus Symphytum L.), the blood test results for WBCs, HGB, and PLTs showed signifcant

Discussion
Tis study investigated the efects of genus Symphytum L. and Portulaca oleracea L. on gastric ulcer and lipid profle in rats.Te results showed that both genus Symphytum L., and Portulaca oleracea L. extract signifcantly reduced the gastric ulcer index and ulcer length and increased gastric mucus production and gastric mucosal thickness.In addition, both extract signifcantly reduced serum total cholesterol, triglyceride, and LDL cholesterol levels.
Our fndings in Table 1 are consistent with Ezejindu et al. [21] who reported a signifcant increase in body weight in rat-administered genus Symphytum L. at a low dose (0.4 ml/ 28 days) compared to the control group.
However, our fndings in contrast to some of the previous fndings [22], mentioning the results of the group treated with Portulaca oleracea L., were shown a signifcantly lower rate of weight loss (AA2) by inhibiting the oxidative stress response through the MDA, NO, and SOD activities, reducing the mRNA expressions of proinfammatory cytokines (TNF-α, IL-1β, and IL-6) and the protein expressions of TNF-α and NF-kB p65, which led to increasing the colon length, decreasing body weight loss, and the disease activity index score compared to the positive control, which may be attributed to antioxidant properties of Portulaca oleracea's components, including gallotannins, omega-3 fatty acids, ascorbic acid, tocopherols, kaempferol, quercetin, and apigenin [23].
Florentino et al. [24] agree with our results in Table 2 indicating that the extract of the genus Symphytum L. has an anti-infammatory efect, with allantoin functioning as the active ingredient, which is an alternative to drugs, especially for stomach diseases, including stomach ulcers.Moreover, Zhou et al. [23] mentioned that Portulaca oleracea L. has an anti-infammatory efect by inhibition of tumor necrosis factor (TNF-) α-induced production of intracellular reactive oxygen species (ROS) and overexpression of intercellular adhesion molecule (ICAM-)1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner.Tis extract also suppresses the translocation of nuclear factor κB (NF-κB) p65 to the nucleus, TNF-α-induced NF-κB binding, and the degradation of inhibitor molecule (IκB)α.Furthermore, an inhibition in the adhesion of HL-60 cells to TNF-α-induced HUVECs and TNF-α-induced mRNA expression of interleukin (IL).
Experimental studies have shown that ulcer models are highly sensitive because they generate an increase in aggressive factors and a decrease in defensive parameters [13].Portulaca oleracea L. is a herb that has been used traditionally to treat a variety of diseases, including ulcers, due to its phytochemical composition, which includes saponins, omega-3 fatty acids, favonoids, phenolic acids, and antimicrobial properties [7].
Genus Symphytum L. contains allantoin, a compound with antiulcer and antisecretory properties.As shown in Tables 3 and 5, our data suggest that allantoin can reduce gastric acid secretion systemically, which is in line with the fndings of Falcão et al.Our data are also consistent with the authors in [21], who reported that allantoin suppressed gastric acid secretion in a pylorus ligature model, demonstrating its clinical antisecretory properties.It is likely that the increase in PGE2 levels is due to allantoin's antisecretory and cytoprotective efects.In addition, allantoin reduces vascular permeability and MPO activity, which are key   Journal of Nutrition and Metabolism parameters of gastrointestinal acid secretion.According to other study, there is another component in genus Symphytum L. which contribute to the antisecretory properties, which is rosmarinic acid that can lead to a signifcantly diminished gastric secretion volume [25].Te reduction in gastric juice may be due to a decreasing thyroid hormone level, which has reduced the number of parietal cells that are secreting stomach juices.It is also possible that thyroid hormone efects can be infuenced by the size or metabolic function of parietal cells [26].Since NSAID-induced COX-1 inhibition in the gastrointestinal tract reduces prostaglandin secretion [27], allantoin has been previously reported to increase the activity of the COX production pathway.Terefore, increased COX-1 and COX-2 synthesis may lead to increased PGE2 secretion in gastric tissues [28].Furthermore, allantoin retains PGE2 content as it causes the rat gastric corpus to produce more prostaglandin-like substances, which indicate higher outputs of PGF2 and 6-keto-PG.Prostaglandins can protect the gastric mucosa by suppressing acid secretion, stimulating mucus and bicarbonate secretion, and altering mucosal blood fow [29].
Several components may potentially contribute to the antiulcer activity of genus Symphytum L., particularly in relation to the elevation of PGE levels.According to certain studies, the presence of ascorbic acid in genus Symphytum L. can lead to a notable increase in the production of PGE2 and PGF2 in dormant cells [30].In addition, other studies suggested that prior exposure to varying concentrations of tannin can result in a marked reduction in the ulcer index, possibly due to an enhanced synthesis of prostaglandins [31].
As listed in Table 4, our fndings disagree with other studies that claim ethanolic extracts of Portulaca oleracea L. that demonstrated an elevation of the pH of gastric juice in rats with pylorus ligation [22].Gastric acid and pH are crucial factors in ulceration [32].In a diferent study, pepsin and acid discharges were signifcantly reduced, indicating that the pH of gastric juice had increased [14].Another study concluded that when rats received oral injections of allantoin, the pH has increased [13].Our data surmised that the discrepancy between our study and others may be related to the length of time the rats with ulcers were treated.
Te correlation between aspirin-induced peptic ulcers and lipid profles unveils a complex relationship involving infammation and elevated levels of LDL cholesterol, which can disrupt the integrity of the gastric mucosa and increase oxidative stress [33].A study highlighted the antihyperlipidemic efects of Portulaca oleracea L., resulting in a signifcant reduction in total lipid and total cholesterol levels, in line with our own fndings presented in Table 6.In addition, Portulaca oleracea L. exhibited potential in normalizing levels of total lipids, triglycerides (TG), and total cholesterol (TC) through the presence of two active components, apigenin and kaempferol, demonstrating potent scavenging abilities against free radicals, such as reactive oxygen species (ROS), thereby promoting the healing of the gastric mucosa [8].Furthermore, mechanisms such as enhancing lipase enzyme activity or increasing TG excretion in stool were identifed to signifcantly reduce TG levels [34,35].Another study indicated that phenolics' ability to decrease total cholesterol (TC) can be attributed to the rapid degradation of LDL-c through its hepatic receptors before eventual excretion as bile acids [36,37].Tese combined efects indirectly contributed to the normalization of lipid profles, ultimately enhancing the healing of the gastric mucosa.Some biomolecules in genus Symphytum L., renowned for their hypoglycemic properties, are likely due to the presence of polysaccharides.Polysaccharides contain hydroxyl groups (-OH) capable of donating hydrogen atoms to neutralize free radicals, infuencing lipid metabolism and promoting healing of the gastric mucosa [38].However, further investigation into the underlying mechanisms is warranted.
Te fndings in Table 7 demonstrate that administering Symphytum ofcinale at 100 mg/kg body weight signifcantly decreased AST, ALT, and ALP levels in rats with gastric ulcers.Tis contrasts with the study by Ezejindu et al. [39], who reported increased liver enzyme levels at higher doses of Symphytum ofcinale.Te discrepancies may be due to diferences in dosage, extract preparation, and experimental conditions.While Ezejindu et al. suggest potential hepatotoxicity at higher doses, our results indicate potential hepatoprotective efects at a lower dose, particularly in the context of gastric ulcers.Tis underscores the need for further research to understand the varying efects of Symphytum ofcinale.In addition, our result agreed with that of Liu et al. [40].Shi et al. [41], who found ethanol extract from Portulaca oleracea L., could attenuate acetaminopheninduced liver injury and carbon tetrachloride-induced liver injury in mice.
In Table 8, the CBC test results of rats treated with genus Symphytum L. and Portulaca oleracea L. at 100 mg/kg body weight were improved, especially in group 3 (genus Symphytum L.).Tis may be attributed to the anti-infammatory properties of these plants.Furthermore, allantoin, one of the components in genus Symphytum L., has gastroprotective properties due to its anti-infammatory properties [13].According to other study, there is another component in genus Symphytum L. that contributes to the antiinfammatory properties, which are choline and rosmarinic acid.Choline demonstrates its anti-infammatory efect by activating alpha-7 nicotinic receptors and reducing cytokine production in macrophages.In the other hand, the rosmarinic acid prevents the synthesis of infammatory mediators [42,43].In addition, several studies revealed that Portulaca oleracea L. had a variety of pharmacological actions, including anti-infammatory properties [22].Moreover, the protection and healing of both normal and damaged gastric mucosa are heavily dependent on blood fow.Tis is because blood fow supplies the mucosa with essential elements such as oxygen and HCO3 while also extracting harmful substances like H+ and toxic agents that leak from the lumen into the mucosa; thereby, ofering efective protection, the hyperemic response enhances the delivery of HCO3-to the mucosal layer by fortifying the injured mucosa against inward difusion of H+ and corrosive substances such as ethanol, ofering adaptive protection, also gastric ulcers cause damage to blood vessels, but during the healing process, blood fow gradually returns to its normal rate.Te healing of a gastric ulcer can be infuenced by either stimulated or inhibited angiogenesis in the granulation tissue [44].
Te current study suggests that genus Symphytum L. may have potential as a phytomedicine for treating peptic ulcers.However, further research is needed to evaluate the safety and efcacy of varying doses of genus Symphytum L. in human subjects before drawing defnitive conclusions.Until comprehensive research has been conducted in human beings, a cautious approach is recommended when considering the use of genus Symphytum L. Standardized procedures for preparing herbal remedies are critical in ensuring consistent quality and purity.Additional research should be conducted using an expanded sample size and lengthier treatment durations to validate the fndings of this study.Other research needs to study histological pathophysiology to evaluate plants' efects of genus Symphytum L. and Portulaca oleracea L. on aspirin-induced acute gastric ulcer in rats.
Despite the positive results shown by this study on the efects of genus Symphytum L. and Portulaca oleracea L. on gastric ulcers in rats, it is important to consider potential biases, such as experimental design variations including the specifc dosage and method of administering aspirin to induce gastric ulcers for seven days, as well as the critical infuence of sample size on the reliability and generalizability of the fndings.Identifying and mitigating these biases is crucial for accurately assessing the efcacy of these plants and translating these results into potential human therapies.

Conclusions
In conclusion, the present study provides compelling evidence of the therapeutic properties of allantoin, kaempferol, and apigenin, particularly against agents that damage the gastric mucosa, such as nonsteroidal anti-infammatory drugs (NSAIDs) including aspirin.Te favorable impact of allantoin is linked with its antisecretory and cytoprotective pathways, possibly by increasing the levels of PGE2.Tese fndings advance our understanding of the pharmacological mechanisms of these compounds and their potential therapeutic applications in managing gastric disorders.Accordingly, genus Symphytum L. and Portulaca oleracea L. could be used as medicinal plants as curative agents against gastric ulcer in experimental rats.
Financial support posed a signifcant challenge in this study as well as the quantity of rats, carrying out complicated scientifc procedures such as isolating active compounds from plants and performing rigorous analyses and dissections on rats.

Table 1 :
Efects of genus Symphytum L. and Portulaca oleracea L. on body weight gain in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.

Table 2 :
Efects of genus Symphytum L. and Portulaca oleracea L. on the length of gastric ulcer in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.

Table 3 :
Efects of plant extracts on the volume of gastric juice in rats inficted with gastric ulcer.
Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.* LSD: low signifcant diference.

Table 4 :
Efects of genus Symphytum L. Portulaca oleracea L. on pH of gastric juice in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.

Table 5 :
Efects of genus Symphytum L. and Portulaca oleracea L. on the total acidity of gastric juice in rats inficted with gastric ulcer.
results when compared with group no. 4 (Portulaca oleracea L.),except for red blood cells (RBCs), showed an insignifcant result.In addition, group no. 3 (genus Symphytum L.) was the best group in comparison to the other group.

Table 6 :
Efects of genus Symphytum L. and Portulaca oleracea L. on TG and TC in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.

Table 7 :
Efects of genus Symphytum L. and Portulaca oleracea L. on AST, ALT, and ALP in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.

Table 8 :
Efects of genus Symphytum L. and Portulaca oleracea L. on RBC, WBC, HGB, and PLT in rats inficted with gastric ulcer.Values denote arithmetic means ± standard error of the means.Means with diferent letters (a, b, c, and d) in the same column difer signifcantly at p ≤ 0.05 using the one-way ANOVA test, while those with similar letters are nonsignifcant.