Gross appearance of the gastric mucosa. Niruri : no damage to the gastric mucosa was observed and gastric mucosa appeared flat as compared to the ethanol control. The section of gastric mucosal layer showed normal tissue architecture and absence of gastric tissue degeneration.

Whereas the ethanol control group demonstrated mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section Fig. Histological evaluation of anti-ulcer effect of methanolic extract of P.

Upon phytochemical screening the methanolic extract of P. niruri disclosed the presence of alkaloids, phenols, steroids, triterpinoids, flavonoids and coumarins.

Many studies have reported that certain terpenoids, steroids and phenolic compounds tannins, coumarins and flavonoids have protective effects due to their antioxidant properties. Lately, a number of natural products of traditional medicines and ingredients of healthy foods have been comprehensively explored and subjected to clinical trials to establish as anti-inflammatory agents [ 33 ].

Presence of major Phytoconstituents in the methanolic extract of leaves of P. niruri makes it a potential candidate for further investigation.

The edema induced by carrageenan was expressed in two phases first phase and second phase [ 34 ]. In the first phase: a rapid rise in edema was detected instantly after sub-plantar injection of carrageenan.

In the second phase at the end of 2nd hour , a significant increase in edema was detected. The release of prostaglandins is thought to be the main reason for the swelling in second phase [ 35 ].

In this study, MEPN inhibited the carrageenan induced edema in a dose-dependent manner and had a potential anti-inflammatory effect in the second phase 2 nd -6 th hour. In the treatment groups, the development of inflammation in the second phase was less. MEPN might have demonstrated their anti-inflammatory activity by inhibiting the synthesis and release of prostaglandins, proteases, and lysosomal enzymes.

In the present study, the histopathogical examination of the hind paw tissue showed that methanolic extract of P. niruri suppressed the massive influx and accumulation of inflammatory cells in the paw tissue after carrageenan induction.

The suppressive effects were observed at all doses of the test drugs. However, the present investigation concluded that methanolic extract of P. niruri reduced the inflammatory cells infiltration, in a dose-dependent manner and at the higher dose the effect was similar to that of reference drug.

The anti-ulcer effect of the methanolic extract was evaluated using ethanol induced gastric ulcer model. Ethanol induced gastric lesions formed due to interference in gastric blood flow which contributes to the development of the hemorrhage and necrotic aspects of tissue injury.

Alcohol swiftly penetrates the gastric mucosa superficially causing cell and plasma membrane damage leading to augmented intracellular membrane permeability to sodium and water.

The mammoth buildup of calcium describes a chief step in the pathogenesis of gastric mucosal injury. The results revealed that the ethanol administration in the control group resulted in immense ulceration in comparison with the normal group. Among the test samples, the best result was obtained with P.

Edema, cellular debris and damaged mucosal epithelium were found in ulcerated stomach membranes. Protections against these histopathological changes by MEPN in pre-treated rats were observed, similar to the result of omeprazole. However, the findings observed in the current studies support and extend previous results that reported the anti-inflammatory and anti-ulcer activities of Phyllanthus niruri aerial part and leave extract, respectively.

Furthermore, the present studies also revealed a better inhibition of inflammation and gastric ulcer as compare to the previously reported. In our study the extract exhibited protection against characteristic lesions produced by ethanol administration. This antiulcer effect of methanolic extract of P.

niruri may be due to both reductions in gastric acid secretion and gastric cytoprotection. Further studies are needed for their exact mechanism of action on gastric acid secretion and gastric cytoprotection. In conclusion, MEPN exhibited anti-inflammatory and antiulcerogenic activity.

The depletion in inflammation may have occurred due to high flavonoid, triterpenoids, steroids, saponins and tannin content. However, the mechanisms behind these events are still vague. Therefore, further experiments should be undertaken to identify which of the phytoconstituents and mechanisms are involved in the actions illustrated by the results.

Fung HB, Kirschenbaum HL. Selective cyclooxygenase-2 inhibitors for the treatment of arthritis. Clin Ther. Article Google Scholar. Kinoshita M, Noto T, Tamaki H. Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats.

Biol Pharm Bull. Ariyphisi I, Toshiharu A, Sugimura F, Abe M, Matsuo Y, Honda T. Recurrence during maintenance therapy with histamine H2 receptors antagonist in cases of gastric ulcers.

Nikon Univ J Med. Google Scholar. Campos MM, Mata LV, Callxto JB. Expression of B1 kinin receptors mediating paw edema and formalin-induced nociception. Modulation by glucocorticoids. Can J Physiol Pharmacol.

Di Rosa ML, Giroud JP, Willoughby DA. Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J Pathol. Rates SMK. Plants as source of drugs. Schmeda-Hirschmann G, Yesilada E. Traditional medicine and gastroprotective crude drugs.

J Ethnopharmacol. Micali S, Sighinolfi MC, Celia A, De Stefani S, Grande M, Cicero AF, Bianchi G. Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study. J Urol. Freitas AM, Schor N, Boim MA.

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int. Boim MA, Heilberg IP, Schor N. Phyllanthus niruri as a promising alternative treatment for nephrolithiasis. Int Braz J Urol.

Patel JR, Tripathi P, Sharma V, Chauhan NS, Dixit VK. Phyllanthus amarus : ethnomedicinal uses, phytochemistry and pharmacology: a review. Porto CRC, Soares LAL, Souza TP, Petrovick PR, Lyra IL, Araújo RF Jr, Aurigena SMZL, Ferreira AA, Guerra GCB.

Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract. Rev Bras Farmacogn. Santos AR. Analgesic effects of callus culture extracts from selected species of Phyllanthus in mice. J Pharm Pharmacol.

Mahmood AA, Khaled AAA, Fouad HA, Yaghma M. Gastroprotective effect of Phyllanthus niruri leaf extract against ethanol-induced gastric mucosal injury in rats. Afr J Pharm Pharmacol. Raphael KR, Sabu MC. Antidiabetic activity of Phyllanthus niruri.

Amala Res Bull. Latha U, Rajesh MG. Hepatoprotective effect of an Ayurvedic medicine. Indian Drugs. Shimizu M. Studies on aldose reductase inhibitors from natural products. Active components of a Paraguayan crude drug Para-parai mi, Phyllanthus niruri. Chem Pharm Bull.

Thyagarajan SP, Subramanian S. Effect of Phyllanthus niruri on chronic carriers of hepatitis B virus. Article CAS PubMed Google Scholar.

Neraliya S, Gaur R. Juvenoid activity in plant extracts against filarial mosquito Culex quinquefasciatus. J Med Aromat Plant Sci. Grewal RC. Medicinal Plants. New Delhi: Campus Book International; Nimmi I, Jahan IA, Hossain MH, Uddin MB, Rana MS, Haq MM.

A comparative study on antioxidant properties of two Phyllanthus species growing in Bangladesh, Dhaka University. J Pharm Sci. Formagio AS, Kassuya CA, Neto FF, Volobuff CR, Iriguchi EK, Do C Vieira M, Foglio MA. The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St.

BMC Complement Altern Med. Alsabri SG, Rmeli NB, Zetrini AA, Mohamed SB, Meshri MI, Aburas KM, Bensaber SM, Mrema IA, Mosbah AA, Allahresh KA, Hermann A. Phytochemical, anti-oxidant, anti-microbial, anti-inflammatory and anti-ulcer properties of Helianthemum lippii.

J Pharmacogn Phytochem. Kokate CK, Purohit AP, Gokhale SB. Nirali Prakashan, Pune. Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs.

Proc Soc Exp Biol Med. Crunkhorn P, Meacock SCR. Mediators of the inflammation induced in the rat paw by carrageenin. Br J Pharmacol. Zhuikova SE, Badmaeva KE, Bakaeva ZV, Samonina GE. Antiulcer effects of the tripeptide PGP and its possible metabolites PG, GP, glycine, and proline in different models of ulcer induction in rats.

Izv Akad Nauk Ser Biol. The influence of hydroxyproline-and proline-containing glyproline on ethanol-induced gastric lesions in rats. Mosc Univ Biol Sci Bull. Ganguly AK, Bhatnagar OP. Effect of bilateral adrenalectomy on production of restraint ulcers in the stomach of albino rats.

Bors W, Michel C. Chemistry of the antioxidant effect of polyphenols. Ann N Y Acad Sci. DeFeudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy.

Brucine was purchased from Sigma CO, Merck. Normal saline, absolute ethanol, and chloroform were acquired from Sigma-Aldrich St.

Louis, MO, United States. Omeprazole and metronidazole were purchased from Barrett Hodgson and Sanofi Aventis, Pakistan. Abcam, United Kingdom, provided secondary antibodies. Elabscience, China, provided the rat NFB ELISA kit catalog no. E-EL-R , rat TNF-α ELISA kit catalog no.

E-EL-ROO19 , and rat PGE2 ELISA kit catalog no. All of the chemicals used in this experiment were of analytical quality.

Sprague—Dawley rats weighing — g of either gender, purchased from the Riphah Institute of Pharmaceutical Sciences RIPS in Islamabad, were subjected to conduct this research work.

The rats were kept in standard cages with a constant temperature of 22°C. All of the animals were fed a regular meal and had unlimited access to water. The experiments were performed by following the guidelines and principles of the Institute of Laboratory Animal Resources, Commission on Life Sciences University, National Research Council The study was approved by the Research and Ethics Committee of RIPS Ref.

The three-dimensional structure of a typical medication was obtained using a Biovia Discovery Studio Visualizer DSV. The standard drug omeprazole was used. In gastric ulcer pathophysiology, human protein targets 3D structure involved were selected and acquired from an online protein data bank, Research Collaboratory for Structural Bioinformatics RCSB PDB.

The ligand and water molecules were removed from DSV, H-atoms polar were inserted, and the file was saved in PDB format. For molecular docking, the AutoDock tool By the disc diffusion method, the antibacterial activity of the selected natural compound against H.

pylori was evaluated. From the gastric biopsy of a patient with gastric ulcer, three strains of H. pylori were received under consent at the care endoscopy clinics and laboratories Rawalpindi, Pakistan. Biopsies to be analyzed were placed in a modified Campy-Thio medium.

Plates were kept at 37°C in a microaerophilic environment. Identification of isolates was carried out by morphology and using a urease test kit. Isolates were kept at 80°C in sterile McCartney bottles containing 0. Frozen clinical isolates were injected onto Mueller—Hinton agar plates for subsequent inoculation.

Brucine with various concentrations of 0. Following an incubation period of 3 to 5 days at 37°C, the zone of inhibition for each disk was measured. All tests were carried out in triplicate, and the antibacterial activity was calculated as the average inhibitory diameter mm.

Metronidazole was used as a positive control Foroumadi et al. All rats were sacrificed by cervical dislocation after 1 h of ethanol administration. The stomachs of the participants were separated and cleaned with normal saline before the lesion index was computed by measuring each lesion in millimeters along its greater curvature.

For each stomach, the sum of the length mm of all lesions was used as the ulcer index UI. The homogenate of stomach tissue was centrifuged for 10—15 min at 3, rpm. As a result of the supernatant, spectrophotometrically at nm, the inorganic phosphate release was determined.

One ATPase activity unit has been described as one µ mole of inorganic phosphorus released by ATP hydrolysis through ATPase at 1 mg per hour of tissue protein.

The antioxidant activity of brucine was analyzed in the isolated tissues of the pretreated animals and compared with disease and positive control group tissues. The stomach tissues were homogenized and centrifuged at 1, rpm for 30 min to collect the supernatant.

The obtained supernatant was estimated for glutathione GSH , catalase, glutathione-S-transferase GST , and lipid peroxidation LPO.

The oxidation of GSH and DTNP produced a yellow end product, which was used to determine their levels. Using a GSH microplate reader, the absorbance of 2-nitrothiobenzoic acid was determined at nm. The synthesis of the CDNB conjugate was used to determine the GST level, and the absorbance at nm was measured.

In the presence of catalase, the degradation of H 2 O 2 was measured. A microplate reader was used to measure absorbance at nm. The end product of LPO, malondialdehyde, was used to determine the level of LPO MDA. On coated slides, in percent pure xylene, tissue sections were deparaffinized and then rehydrated in 70 percent ethyl alcohol.

The slides were immersed in hematoxylin for 10 min after being cleaned with distilled water. The slides were immersed in eosin solution for 5—10 min. After the required length of time had passed, the slides were cleaned in water and air—dried.

In graded ethyl alcohol, the dried slides were dehydrated 70 percent, 95 percent, and percent. The slides were cleaned with xylene and mounted with glass coverslips. The slides were photographed using an Olympus light microscope and analyzed by ImageJ, a computer-based application, with particular attention paid to the gastric cell size and shape, inflamed infiltrating cells, and vacuolation.

The TIF images were arranged at the same threshold intensity for all groups and examined in GraphPad Prism. The immunohistochemical examination was carried out, as previously described by Gim et al. The slides were deparaffinized, then treated for antigen retrieval enzymatic technique , and washed with PBS.

For 10 min, 3 percent hydrogen peroxide was used to block the endogenous peroxidase in methanol H 2 O 2. The slides were incubated for a period of time in a solution containing 0. After being blocked, the slides were treated overnight with murine anti-TNF-α, p-NFkB, and anti-COX-2 antibodies dilution , Santa Cruz Biotechnology.

Slides were handled for incubation with the biotinylated secondary antibody dilution , depending on the source of the primary antibody, and the serum was used the next morning after cleaning with 0. The ABC Elite kit was used to incubate slides in a humidified room for 1 h after secondary antibody application Santa Cruz Biotechnology.

The slides were cleaned in 0. A light microscope was used to capture immunohistochemical TIF pictures. By modifying the backdrop of photos according to the threshold intensity and analyzing p-NFκB, COX-2, and TNF-α positive cells at the same threshold intensity for all groups, ImageJ software was utilized to quantitatively detect hyperactivated p-NFκB, COX-2, and TNF-α.

The relative integrated density of the samples compared to saline is used to compute the intensity Ansari et al. Using the Silent Crusher M Heidolph apparatus, the tissues were homogenized at 15, RPM; after centrifugation, the supernatant was collected for 1 h at 1, g. TNF-α, PGE2, and p-NFκB concentrations were measured using an ELISA microplate reader.

Ansari et al. Gastric tissues were homogenized after being lysed in a buffer. A bicinchoninic acid BCA protein test kit was used to assess the protein content. On a 12 percent sodium dodecyl sulfate-polyacrylamide gel, 30 g of protein homogenate was electrophoretically separated and transferred to a polyvinylidene fluoride membrane.

After being cleansed three times with Tris-buffered saline with 0. To see the immunoreactive bands, an enhanced Western blotting substrate kit was used. Densitometry was used to assess the measurement of protein expression by ImageJ software.

Irshad et al. The TRIzol technique was used to extract total ribonucleic acid RNA from gastric tissues, as directed by the manufacturer.

Using a reverse transcriptase enzyme mix and a PCR thermocycler, the first strand of cDNA was generated from 1 to 2 g of total RNA.

The data are presented as a mean with a standard error of the mean SEM. In this study, brucine binds to a variety of protein receptors with varying affinities. Supplementary Figures S1—S8 illustrate the 2D depiction of brucine interactions with common medications. Brucine had an E-value of Brucine has an E-value of —2.

Table 1. TABLE 1. The minimum inhibitory concentration MIC and zone of inhibition of three different strains of H.

pylori against brucine were measured. Different concentrations of brucine were used against strain A that are 0. The same concentration of brucine was used for strain B , and the inhibition values are 1. For strain C , same concentrations of brucine were used, and the inhibitory values are 1.

TABLE 2. Antibacterial effect of brucine against three clinical strains of H. pylori using the disk diffusion method. The stomach mucosa of rats was observed under a microscope Figure 2. TABLE 3. Protective effect of brucine and omeprazole against ethanol-induced gastric ulcer in rats.

FIGURE 2. FIGURE 3. ethanol group. In ethanol-induced ulcer stomach tissues, GST, GSH, and catalase levels were decreased, but LPO levels were increased.

FIGURE 4. Effect of brucine and omeprazole against glutathione sulfotransferases GST , reduced glutathione GSH , catalase, and lipid peroxidase LPO in ethanol-induced ulcer rat gastric tissues. FIGURE 5.

Histopathological slides represent effect of brucine and omeprazole in ethanol- induced ulcer rats gastric tissues. Crean, G. and Bates, C: The effects of prolonged administration of large doses of cimetidine on the gastric mucosa of rats; in Wastell and Lance Eds Cimetidine. The Westminster Hospital Symposium, p.

Dawes, P. and Atherton, ST. Delaney, J. and Ravey, M. Delitala, G. and Besser, G. British Journal of Clinical Pharmacology 7: — Doll, R. and Shawdon, H. Gut 9: 42—45 Dronfield, M. and Langman, M. Dubb, J. and Alexander, F. Clinical Pharmacology and Therapeutics 76—83 Edmonds, C.

Elder, J. and Gillespie, I. Lancet 1: — a. Lancet 2: b. Engel, T. and Luck, J. Field, R. and Meyer, G. New England Journal of Medicine Fink, M. and Irwin, P. Scandinavian Journal of Gastroenterology 15 Suppl.

Flind, A. Fraser, P. and Hill, M. International Journal of Epidemiology 9: 3—11 Garty, M. and Hurwitz, A. Geismar, P. and Myren, J. Scandinavian Journal of Gastroenterology 8: — Gilbert, J.

Greenblatt, D. and Shader, R. and Koch-Weser, J. Grimson, T. Gudmand-Høyer, E. and Wulff, H. PubMed Google Scholar. Gugler, R. and Somogyi, A. Hawker, P. and Keighley, M. Hayes, M. Henry, D. British Medical Journal Hiatt, R. and Risser, C: Systemically administered anticholinergic drugs and intraocular pressure.

Archives of Ophthalmology — Horwich, L. and Galloway, R. Clinical and radiological evaluation. Hurwitz, A. Clinical Pharmacokinetics 2: — Jefferys, D. and Vale, J. Johnson, N. and Clarke, S. Kaehny, W. and Alfrey, A. Khoury, W.

and Johnson, M. Gastroenterology Kimelblatt, B. and Schentag, J. Klotz, U. and Reimann, I. Langman, M. MTP Press, Lancaster Leslie, G. and Walker, T. Ligumsky, M. and Rachmilewitz, D. Annals of Internal Medicine — Loiseau, P. and Leroux, M.

Journal of Neurological Sciences — Lorber, S. Trial of Carbenoxolone Biogastrone® in gastric ulcer, in Beck Ed North American Symposium on Carbenoxolone, p.

Lotz, M. and Bartter, F. McDaniel, J. and Stein, J. McElnay, J. C; Harron, D. and Collier, P. McGregor, C. and Forrester, J.

Mignon, M. and Bonfils, S. British Journal of Clinical Pharmacology — Morrison, P. and Parsons, C: Concurrent administration of cimetidine and enteric coated prednisolone: Effect on plasma levels of prednisolone. British Journal of Clinical Pharmacology 87—89 Nicholls, P.

and Henry, K. Nistico, G. and Naecari, F. Patwardhan, R. and Speeg, K. Pelkonen, O. and Puurunen, J. Biochemical Pharmacology — Porter, G. and Sacra, P. Pharmacology — Puurunen, J. and Pelkonen, O. European Journal of Clinical Pharmacology — Reed, P. and Walters, C.

and Baron, J. Rendic, S. and Ruf, H. Xenobiotica 9: — Rivera-Calimlim, L. and Bianchine, J. European Journal of Clinical Investigation 1: — Rogers, H.

A deep violet colour at the junction of two layers indicated the presence of carbohydrates. The methanol extract 50 mg was diluted with distilled water and made up to 20 ml. The suspension was shaken in a graduated cylinder for 15 min. Appearance of persistent foam indicated the presence of saponins.

The methanol extract 6 g. For the detection of glycosides, 50 mg of methanol extract was hydrolysed with concentrated hydrochloric acid for 2 h on water bath, filtered and the hydrolysate 4 ml of filtered hydrolysate was taken in a test tube; 6 ml of chloroform was added and shaken.

In this test, the methanol extract 20 mg was taken in chloroform 2 ml and concentrated sulphuric acid was poured from side of the test tube. The colour of the ring at the junction of the two layers was noted. A violet green colour indicated the presence of cholesterol, sitosterol.

To dry methanol extract 30 mg , ethanol 2 ml was added and dropped small piece of Magnesium ribbon. The drop wise addition of conc. HCl leads to the development of colour ranging from orange to red was confirmatory for flavonoids. A bluish black colour was produced which disappears on addition of few ml of dilute sulphuric acid followed by the formation of a yellowish-brown precipitate indicated the presence of tannins.

Appearance of a pink, red or violet colour in the ammoniacal lower phase was taken as the presence of free anthraquinones. A small amount of methanol extract was placed in test tube and covered the test tube with a filter paper moistened with dilute sodium hydroxide solution.

The covered test tube was placed on water bath for several minutes. Removed the paper and exposed it to ultraviolet UV light, the paper showed green fluorescence. Female Swiss albino rats weighing g were used in the experiment. Animals were housed in polypropylene cages in groups of six per cage and were kept in a room maintained at 25 ± 2 °C with a 12 h light-dark cycle, and were allowed to acclimatize for one week before the experiment commenced.

They were given free access to standard laboratory animal feed and water ad libitum. The procedures were conducted with efforts to minimize preventable harm to the rats.

Animal care and research protocols were centered on values and guidelines sanctioned by the Guide for the Care and Use of Laboratory Animals NIH publication No: , revised in The prior approval for conducting the experiments on rats was obtained from the Departmental Ethics Committee of Dhaka University.

The methanolic extract of P. niruri MEPN was evaluated for anti-inflammatory activity as recommended by Winter et al. There were six groups containing six rats each. The normal healthy group received distilled water only.

All the test samples were administered orally 0. However, the control group received no carrageenan injection. The swelling of the paws were measured by slide calipers in one hour intervals. The observations were tabulated.

The percentage of inhibition of paw edema was calculated at the end of the 6th hour. The experimental animals were divided into the following groups and received the subsequent treatments accordingly:.

The animals were barred from access to any nutrients for a day and were only allowed access to drinking water for two hours before the experiment commenced.

During the fasting period, the rats were placed individually in separate cages to prevent coprophagy. These rats were sacrificed 90 min after induction and their stomachs were immediately excised. Each stomach was opened along the larger curvature, washed with distilled water. The gastric mucosa was examined for ulcers by magnifying lens and scoring of ulcer was made as follows [ 29 ].

Mean ulcer score for each animal was expressed as ulcer index. The percentage of ulcer protection was determined as follows The experimental animals were divided into six groups, each consisting of six rats and received following treatment:. niruri , p. For histological examination, paw tissues were taken 6 h after edema was induced by carrageenan.

Then the tissue specimens were processed for paraffin embedding tissue sections. The samples were sectioned with a microtome, stained with hematoxyline and Eosin H and E and mounted on Canada balsam. All sections were examined under light microscope.

Photographs of the lesions were taken with an Olympus photo microscope for observation and documentation of histopathological changes such as oedema, inflammation, infiltration and erosion.

The values are represented as mean ± S. The traditional use of the species was scientifically validated through the identification of the phytochemicals responsible for their use in indigenous systems of health care. The result of qualitative chemical analysis of the methanolic extract of P.

niruri is tabulated in Table 1. Ibuprofen was used as the reference drug during the anti-inflammatory evaluation of the methanolic extract of the leaves of P. niruri in carrageenan induced acute inflammation model. exhibited significant reduction in paw thickness from 1st to the 6th hour Table 2.

After 6 h of carrageenan treatment, swelling and redness were observed in carrageenan control group, while swelling and redness were significantly reduced in the groups which were given MEPN. Effect of methanolic extract of P. niruri on carrageenan induced paw edema after 6 h.

b Carrageenan control: severe erythema and swelling were observed. niruri : moderate amount of erythema and swelling were observed. niruri : mild amount of erythema and swelling were observed.

The small arrow indicates the absence of swelling and erythema whereas the large arrow indicates severe swelling and erythema in the rats paw. The tissue architecture was preserved, showing dermal collagen and minimal number of leukocytes.

However, groups treated with methanolic extract of P. Histological evaluation of anti-inflammatory effects of methanolic extract of P. MEPN showed significant protection index of respectively in comparison to ethanol control.

Whereas omeprazole standard drug reduced ulcer by Ethanol controlled rats exhibited severe mucosal injury whereas, the rats that were treated with P. niruri leaves extract before ethanolic induction had significantly reduced areas of gastric ulceration revealing flattening of gastric mucosal folds compared to rats treated with only distilled water.

Gross appearance of the gastric mucosa. Niruri : no damage to the gastric mucosa was observed and gastric mucosa appeared flat as compared to the ethanol control.

The section of gastric mucosal layer showed normal tissue architecture and absence of gastric tissue degeneration. Whereas the ethanol control group demonstrated mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section Fig.

Histological evaluation of anti-ulcer effect of methanolic extract of P. Upon phytochemical screening the methanolic extract of P. niruri disclosed the presence of alkaloids, phenols, steroids, triterpinoids, flavonoids and coumarins.

Many studies have reported that certain terpenoids, steroids and phenolic compounds tannins, coumarins and flavonoids have protective effects due to their antioxidant properties. Lately, a number of natural products of traditional medicines and ingredients of healthy foods have been comprehensively explored and subjected to clinical trials to establish as anti-inflammatory agents [ 33 ].

Presence of major Phytoconstituents in the methanolic extract of leaves of P. niruri makes it a potential candidate for further investigation.

The edema induced by carrageenan was expressed in two phases first phase and second phase [ 34 ]. In the first phase: a rapid rise in edema was detected instantly after sub-plantar injection of carrageenan.

In the second phase at the end of 2nd hour , a significant increase in edema was detected. The release of prostaglandins is thought to be the main reason for the swelling in second phase [ 35 ]. In this study, MEPN inhibited the carrageenan induced edema in a dose-dependent manner and had a potential anti-inflammatory effect in the second phase 2 nd -6 th hour.

In the treatment groups, the development of inflammation in the second phase was less. MEPN might have demonstrated their anti-inflammatory activity by inhibiting the synthesis and release of prostaglandins, proteases, and lysosomal enzymes.

In the present study, the histopathogical examination of the hind paw tissue showed that methanolic extract of P. niruri suppressed the massive influx and accumulation of inflammatory cells in the paw tissue after carrageenan induction. The suppressive effects were observed at all doses of the test drugs.

However, the present investigation concluded that methanolic extract of P. niruri reduced the inflammatory cells infiltration, in a dose-dependent manner and at the higher dose the effect was similar to that of reference drug.

The anti-ulcer effect of the methanolic extract was evaluated using ethanol induced gastric ulcer model. Ethanol induced gastric lesions formed due to interference in gastric blood flow which contributes to the development of the hemorrhage and necrotic aspects of tissue injury.

Alcohol swiftly penetrates the gastric mucosa superficially causing cell and plasma membrane damage leading to augmented intracellular membrane permeability to sodium and water. The mammoth buildup of calcium describes a chief step in the pathogenesis of gastric mucosal injury.

The results revealed that the ethanol administration in the control group resulted in immense ulceration in comparison with the normal group. Among the test samples, the best result was obtained with P. Edema, cellular debris and damaged mucosal epithelium were found in ulcerated stomach membranes.

Protections against these histopathological changes by MEPN in pre-treated rats were observed, similar to the result of omeprazole. However, the findings observed in the current studies support and extend previous results that reported the anti-inflammatory and anti-ulcer activities of Phyllanthus niruri aerial part and leave extract, respectively.

Furthermore, the present studies also revealed a better inhibition of inflammation and gastric ulcer as compare to the previously reported. In our study the extract exhibited protection against characteristic lesions produced by ethanol administration. This antiulcer effect of methanolic extract of P.

niruri may be due to both reductions in gastric acid secretion and gastric cytoprotection. Further studies are needed for their exact mechanism of action on gastric acid secretion and gastric cytoprotection. In conclusion, MEPN exhibited anti-inflammatory and antiulcerogenic activity.

The depletion in inflammation may have occurred due to high flavonoid, triterpenoids, steroids, saponins and tannin content. However, the mechanisms behind these events are still vague. Therefore, further experiments should be undertaken to identify which of the phytoconstituents and mechanisms are involved in the actions illustrated by the results.

Fung HB, Kirschenbaum HL. Selective cyclooxygenase-2 inhibitors for the treatment of arthritis. Clin Ther. Article Google Scholar. Kinoshita M, Noto T, Tamaki H. Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats.

Biol Pharm Bull. Ariyphisi I, Toshiharu A, Sugimura F, Abe M, Matsuo Y, Honda T. Recurrence during maintenance therapy with histamine H2 receptors antagonist in cases of gastric ulcers.

Nikon Univ J Med. Google Scholar. Campos MM, Mata LV, Callxto JB. Expression of B1 kinin receptors mediating paw edema and formalin-induced nociception.

Modulation by glucocorticoids. Can J Physiol Pharmacol. Di Rosa ML, Giroud JP, Willoughby DA. Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine.

J Pathol. Rates SMK. Plants as source of drugs. Schmeda-Hirschmann G, Yesilada E. Traditional medicine and gastroprotective crude drugs. J Ethnopharmacol. Although bismuth may be absorbed from some preparations, encephalopathy has not been reported with the popular form tripotassium-dicitrato-bis-muthate.

Experimental single dose studies have shown altered disposition of many drugs when taken with antacids; clinically important interactions during long term therapy seem to be rare.

Anticholinergic drugs taken in doses which reduce gastric acid secretion produce the expected side effects of dry mouth, constipation and urinary retention. Although interference with the accommodation reflex can be troublesome, the danger of precipitating acute glaucoma has probably been overstated.

The development of selective muscarinic antagonists should provide antisecretory agents with minimal side effects. The H 2 -receptor antagonist cimetidine has been in widespread clinical use for 5 years, and serious adverse reactions seem rare. The unwanted effects most commonly seen are gynaecomastia when used alone in high doses, confusion in the elderly or those with impaired excretory mechanisms, and modest inhibition of the oxidative metabolism of other drugs.

Overall the drug has proved remarkably safe. In practice the only significant adverse effect encountered with carbenoxolone is salt retention and hypokalaemia. Although identified quite frequently, this is seldom severe enough to warrant cessation of therapy. The elderly and those with pre-existing abnormalities of salt and water handling are at greater risk, and the drug should be avoided in these patients.

This output contributes to the following UN Sustainable Development Goals SDGs. Kumar V, Jain P, Rathore K, Ahmed Z Biological evaluation of Pupalia lappacea for antidiabetic, antiadipogenic, and hypolipidemic activity both in vitro and in vivo.

Article PubMed PubMed Central Google Scholar. Pandey RK, Shukla SS, Vyas A, Jain V, Jain P, Saraf S Fingerprinting analysis and quality control methods of herbal medicines.

CRC Press, Boca Raton. Book Google Scholar. Jain P, Pandey R, Shukla SS Inflammation: Natural resources and its applications. Springer briefs. Springer, New Delhi.

Kumar V, Rathore K, Jain P, Ahmed Z Biological activity of bauhinia racemose against diabetes and interlinked disorders like obesity and hyperlipidemia. Clin Phytosci Singh P, Jain P, Pandey R, Shukla SS Phytotherapeutic review on diabetes. Spatula DD. Sharwan G, Jain P, Pandey R, Shukla SS Toxicity and safety profiles of methanolic extract of Pistacia integerrima J.

Stewart ex Brandis PI for Wistar Rats. J Pharmacopunct 19 3 — Jain P, Rao SP, Singh V, Pandey R, Shukla SS Acute and sub-acute toxicity studies of an ancient ayurvedic formulation: agnimukha churna.

Columbia J Pharm Sci — Jain P, Pandey R, Shukla SS Reproductive and developmental toxicity study of talisadya churna: an ancient polyherbal formulation. IAJPR 6 5 — CAS Google Scholar. Jain P, Pandey R, Shukla SS Acute and subacute toxicity studies of polyherbal formulation talisadya churna in experimental animal model.

MJPMS 1 1 :7— Sharwan G, Jain P, Pandey R, Shukla SS Toxicity profile of traditional herbal medicine. J Ayu Herb Med 1 3 — Zinatloo-Ajabshir Z, Zinatloo-Ajabshir S Preparation and characterization of curcumin niosomal nanoparticles via a simple and eco-friendly route.

J Nanostruct 9 4 — Ghule BV, Murugananthan G, Yeole PG Analgesic and antipyretic effects of Capparis zeylanica leaves. Fitoterapia 78 5 — Arulmozhi P, Vijayakumar S, Kumar T Microbial pathogenesis phytochemical analysis and antimicrobial activity of some medicinal plants against selected pathogenic microorganisms.

Microb Pthogenes — Arulmozhi P, Vijayakumar S, Praseetha PK, Jayanthi S Extraction methods and computational approaches for evaluation of antimicrobial compounds from Capparis zeylanica L. Anal Biochem — Tlili N, Elfalleh W, Saadaoui E, Khaldi A, Triki S, Nasri N The caper Capparis L.

Fitoterapia 82 2 — Haque ME, Haque M, Rahman MM, Rahman MM, Khondkar P, Wahed M, Mossadik MA, Gray AI, Sarker SD E-octadecenynoic acid from the roots of Capparis zeylanica. Fitoterapia 75 2 — Article PubMed CAS Google Scholar. Sini KR, Sinha BN, Rajasekaran A Protective effects of Capparis zeylanica Linn.

leaf extract on gastric lesions in experimental animals. Avicenna J Med Biotechnol 3 1 — PubMed PubMed Central Google Scholar. OECD OECD guideline for testing of chemicals: acute oral toxicity—acute toxic class method. OECD Guidel Test Chem — Satoh H, Guth PH, Grossman MI Roll of food in gastrointestinal ulceration produced by food in the rat.

Gastroenterol — Sirmagul B, Kilic FS, Batu O, Erol K The effects of verapamil on stress and histamine induced gastric lesions in rats. Meth Exp Clin Pharmacol Sheeba MS, Asha VV Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats. J Ethnopharmacol — Kalies I, Li H, Mellgard B A rat model of chronic H.

pylori infection. Studies of epithelial cell turn over and gastric ulcer healing. Scand J Gastroenterol — Ibrahim M, Khan AA, Tiwari SK, Khaja MN, Habeeb AK, Habibullah CM Antimicrobial activity of Sapindus mukorossi and Rheum emodi extracts against H. pylori : in vitro and in vivo studies. World J Gastroenterol 12 44 — Article CAS PubMed PubMed Central Google Scholar.

Tiwari SK, Khan AA, Manoj G, Ahmed S, Abid Z, Habeeb A et al A simple multiplex PCR assay for diagnosing virulent Helicobacter pylori infection in human gastric biopsy specimens from subjects with gastric carcinoma and other gastro-duodenal diseases.

J Appl Microbiol 6 — Kaur M, Singh A, Kumar B Comparative antidiarrheal and antiulcer effect of the aqueous and ethanolic stem bark extracts of Tinospora cordifolia in rats. J Adv Pharm Technol Res 5 3 — Lichtenberger LM, Wang ZM, Romero JJ, Ulloa C, Perez JC, Giraud MN Non-steroidal anti-inflammatory drugs NSAIDs associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury.

Nat Med — Halter F, Tarnawski AS, Schmassmann A, Peskar BM Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives.

Gut 49 3 — Warzecha Z, Dembinski A, Brozozowski-Ceranowicz P, Konturek SJ Histamine in stress ulcer prophylaxis in rats. J Physiol Pharmacol 52 3 — CAS PubMed Google Scholar. Narra S, Nisha KS, Nagesh HS Evaluation of antiulcer activity of hydroalcoholic fruit pulp extract of Cucumis sativus.

Int J Pharm Sci Res 6 11 — Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases.

Physiol Rev 94 2 — Uchida M, Keiko K Yogurt containing Lactobacillus gasseri OLL exerts gastroprotective action agaisnt acute gastric lesion and antral ulcers in rats. J Pharmacol Sci — Srivastava A, Mukerjee A, Ramteke P, Pandey H, Mishra DS Antiulcer potential of Cucumis melo Var.

J Pharm Res — Sharma A Antiulcer activity of methanolic extract of leaf of tylophora indica on histamine and naproxen induced gastric lesions in rats.

Pharmacologyonline — Achukwu DC, Eze AA Anti-ulcer activity of the leaf extracts of borreria ocymoides in rats. Biol Res 7 6 — Abebaw M, Mishra B, Gelayee DA Evaluation of anti-ulcer activity of the leaf extract of Osyris quadripartita Decne. Santalaceae in rats. J Exp Pharmacol — Yoshida N, Sugimoto N, Hirayama F, Nakamura Y, Ichikawa H, Naito Y, Yoshikawa T Helicobacter pylori infection potentiates aspirin induced gastric mucosal injury in Mongolian gerbils.

Gut — Tsuji S, Tsuji M, Murata H, Nishida T, Kamori M, Yasumara M, Ishli S, Sasayama Y, Kawanio S, Hayashi M Helicobacter pylori eradication to prevent gasric cancer; underlying molecular and cellular mechanisms. World J Gasteroenterol 12 11 — Download references. The authors are thankful to the institute providing laboratory facilities.

We are extending our gratitude toward Probecell: Scientific Writing Services for proofreading and editing of the manuscript.

Department of Pharmaceutical Sciences, United Institute of Pharmacy, Naini, Allahabad, , India. You can also search for this author in PubMed Google Scholar.

All authors have read and approved the manuscript. AT contributed to manuscript preparation and proofreading. SKS was involved in laboratory work and performance of experimental task. AM contributed to statistics and analysis of data. All authors read and approved the final manuscript. Correspondence to Abhishek Tripathi.

Institutional Animal Ethical Committee approved the above protocol with approval no. Plant authentication: Plant leaves were authenticated by the Department of Pharmacognosy, United Institute of Pharmacy, Allahabad, and samples were deposited in the herbarium of the institute with voucher no. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Reprints and permissions. Tripathi, A. Antiulcer activity of ethanolic leaf extract of Capparis zeylanica against chemically induced ulcers. Futur J Pharm Sci 7 , Download citation.

Received : 30 September Accepted : 06 October Published : 18 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all SpringerOpen articles Search. Download PDF. Abstract Background Peptic ulcer is the term which refers to acid peptic injury of the digestive tract, and it results in mucosal break reaching the submucosa.

Results Results exhibited that the area of ulcer was significantly reduced in both acute [naproxen-induced ulcer model 3. Conclusion It can be concluded from the study that C.

Background Peptic ulcer is one of the most prevalent diseases around the world affecting four million people each year. Methods Drugs, chemical and reagents Naproxen sodium Extraction of C.

zeylanica leaves Fresh leaves of C. Experimental animals Swiss albino mice 25—30 gm and male Wistar rats — gm were obtained from Central animal house of the United Institute of Pharmacy, Allahabad.

Acute toxicity study Both male and female swiss albino mice 18—22 g were individually identified and allowed to acclimatize to the laboratory conditions for 7 days prior to study. Acute ulcer study Naproxen-induced ulcer model This experiment was performed according to the method of Satoh et al.

Acute study Naproxen-induced ulcers Result showed that administration of naproxen produced ulcers in all treated animals and the mean ulcer area was 5. Table 1 Effect of C. zeylanica extract on area of ulcer and ulcer index in naproxen-induced acute ulcers Full size table.

Table 2 Effect of C. zeylanica extract on area of ulcer and ulcer index in histamine-induced acute ulcers Full size table. Table 3 Effect of C.

zeylanica extract on area of ulcer and ulcer index in ethanol-induced acute ulcers Full size table. Table 4 Effect of omeprazole and C. zeylanica extract on area of ulcer in naproxen-induced therapeutic ulcers Full size table. Table 5 Effect of ranitidine and C. zeylanica extract on area of ulcer in histamine-induced acute ulcers Full size table.

Table 6 Effect of C. zeylanica extract on area of ulcer naproxen-induced H. pylori -infected therapeutic ulcers Full size table. Table 7 Effect of C. zeylanica extract on infection status in naproxen-induced H. The UV illuminated image of hrgA gene bp of H.

pylori amplified by PCR. Full size image. The UV illuminated image of 16 s RNA gene bp of H. Discussion In the present investigation, the various groups of animals were treated prophylactically with the C. Table 8 Effect of C. Conclusion The present study suggests that the C. Availability of data and materials All data and material are available upon request.

Abbreviations NTC: National Toxicology Centre IAEC: Institutional Animal Ethics Committee UI: Ulcer index RUT: Rapid urease test PCR: Polymerase chain reaction. References Jain P Secondary metabolites for antiulcer activity. Inform Med Unlocked —4 Article Google Scholar Najm WI Peptic ulcer disease.

Prim Care Clin Off Pract 38 3 — Article Google Scholar Napolitano L Refractory peptic ulcer disease. Gastroenterol Clin N Am 38 2 — Article Google Scholar Kempenich JW Acid peptic disease. Surg Clin N Am 98 5 — Article PubMed Google Scholar Lim W, Subramaniam M, Abdin E, Vaingankar J, Ann S Peptic ulcer disease and mental illnesses.

Gen Hosp Psychiatry 36 1 —67 Article PubMed Google Scholar Urs AN, Thomson M Peptic ulcer disease. Paediatr Child Health Oxf 24 11 — Article Google Scholar Awaad AS, El-meligy RM, Soliman GA Natural products in treatment of ulcerative colitis and peptic ulcer. J Saudi Chem Soc 17 1 — Article CAS Google Scholar Jain P, Satapathy T, Pandey RK Rhipicephalus microplus acari: Ixodidae : Clinical safety and potential control by topical application of cottonseed oil Gossypium sp.

Exp Parasitol Article CAS PubMed Google Scholar Jain P, Satapathy T, Pandey RK Efficacy of arecoline hydrobromide against cattle tick Rhipicephalus Boophilus microplus.

Int J Acarol 46 4 — Article Google Scholar Jain P, Satapathy T, Pandey RK First report on ticks Acari: Ixodidae controlling activity of cottonseed oil Gossypium Sp. Int J Acarol 46 4 — Article Google Scholar Jain P, Satapathy T, Pandey RK Rhipicephalus microplus : a parasite threatening cattle health and consequences of herbal acaricides for upliftment of livelihood of cattle rearing communities in Chhattisgarh.

Biocatal Agric Biotechnol Article Google Scholar Rao SP, Jain P, Rathore P, Singh VK Larvicidal and knockdown activity of Citrus limetta Risso oil against dengue virus vector.

Indian J Nat Prod Resour 7 3 — Google Scholar Kumar V, Jain P, Rathore K, Ahmed Z Biological evaluation of Pupalia lappacea for antidiabetic, antiadipogenic, and hypolipidemic activity both in vitro and in vivo.

CRC Press, Boca Raton Book Google Scholar Jain P, Pandey R, Shukla SS Inflammation: Natural resources and its applications. Springer, New Delhi Book Google Scholar Kumar V, Rathore K, Jain P, Ahmed Z Biological activity of bauhinia racemose against diabetes and interlinked disorders like obesity and hyperlipidemia.

Clin Phytosci Article CAS Google Scholar Singh P, Jain P, Pandey R, Shukla SS Phytotherapeutic review on diabetes. J Pharmacopunct 19 3 — Article Google Scholar Jain P, Rao SP, Singh V, Pandey R, Shukla SS Acute and sub-acute toxicity studies of an ancient ayurvedic formulation: agnimukha churna.

Columbia J Pharm Sci —22 Google Scholar Jain P, Pandey R, Shukla SS Reproductive and developmental toxicity study of talisadya churna: an ancient polyherbal formulation. IAJPR 6 5 — CAS Google Scholar Jain P, Pandey R, Shukla SS Acute and subacute toxicity studies of polyherbal formulation talisadya churna in experimental animal model.

MJPMS 1 1 :7—10 Google Scholar Sharwan G, Jain P, Pandey R, Shukla SS Toxicity profile of traditional herbal medicine. J Ayu Herb Med 1 3 —90 Article Google Scholar Zinatloo-Ajabshir Z, Zinatloo-Ajabshir S Preparation and characterization of curcumin niosomal nanoparticles via a simple and eco-friendly route.

J Nanostruct 9 4 — CAS Google Scholar Ghule BV, Murugananthan G, Yeole PG Analgesic and antipyretic effects of Capparis zeylanica leaves.