Antiulcer activity of Muntingia calabura leaves involves the modulation of endogenous nitric oxide and nonprotein sulfhydryl compounds

Context: Muntingia calabura L. (Muntingiaceae) is a native plant species of the American continent and is widely cultivated in warm areas in Asia, including Malaysia. The plant is traditionally used to relieve pain from gastric ulcers. Objective: This study was designed to determine the antiulcer activity of a methanol extract of M. calabura leaves (MEMC) and the possible mechanisms of action involved. Materials and methods: An acute toxicity study was conducted using a single oral dose of 2000 mg/kg MEMC. The antiulcer activity of MEMC was evaluated in absolute ethanol- and indomethacin-induced gastric ulcer rat models. MEMC was administered orally (dose range 25–500 mg/kg) to rats fasted for 24 h. The animals were pretreated with NG-nitro-l-arginine methyl esters (l-NAME) or N-ethylmaleimide (NEM) prior to MEMC treatment to assess the possible involvement of endogenous nitric oxide (NO) and nonprotein sulfhydryl (NP-SH) compounds in the gastroprotective effect of MEMC. Results: As the administered dose did not cause toxicity in the rats, the oral median lethal dose (LD50) of MEMC was >2000 mg/kg in rats. MEMC exerted significant (p < 0.001) gastroprotective activity in the ethanol- and indomethacin-induced ulcer models dose-dependently. Histological evaluation supported the observed antiulcer activity of MEMC. l-NAME and NEM pretreatment significantly (p < 0.05) reversed and abolished the gastroprotective effect of MEMC, respectively. Discussion and conclusion: The results obtained indicate that MEMC has significant antiulcer activity that might involve the participation of endogenous NO and NP-SH compounds. These findings provide new pharmacological information regarding the potential use of M. calabura

Mechanisms of gastroprotection of methanol extract of Melastoma malabathricum leaves

Background: Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the gastroprotective mechanisms of methanol extract of M. malabathricum leaves (MEMM) in rats. Methods: The extract's mechanisms of gastroprotection (50, 250, 500 mg/kg) were studied using the pylorus-ligation in rat model wherein volume, pH, free and total acidity of gastric juice, and gastric wall mucus content were determined. The involvement of endogenous nitric oxide (NO) and sulfhydryl (SH) compounds in the gastroprotective effect of MEMM were also measured. MEMM was subjected to the antioxidant, anti-inflammatory and phytochemical analysis and HPLC profiling. Results: MEMM contained various phyto-constituents with quercitrin being identified as part of them. MEMM and quercitrin: i) significantly (p < 0.05) reduced the volume and acidity of gastric juice while increasing the pH and gastric wall mucus content.; ii) significantly (p < 0.05) increased the level of SOD, GTP and GTR while significantly (p < 0.05) reduced the level of CAT, MPO and TBARS activities.; iii) exerted gastroprotective activity when assessed using the ethanol-induced gastric ulcer assay, which was reversed by NG-nitro-l-arginine methyl esters (L-NAME; an inhibitor of NO synthase) and N-ethylmaleimide (NEM; a sulfhydryl (SH) blocker). MEMM inhibited the lipoxygenase (LOX) and xanthine oxidase (XO) activities with the highest affinity for the former while quercitrin showed high affinity for XO activity. Conclusions: MEMM exhibited a gastroprotective activity due partly to the presence of quercitrin, its antioxidant and anti-inflammatory activities, and via the modulation of NO and SH groups

Mode of action for gastroprotective activity of Muntingia calabura L. leaves in rats

Gastric ulcer is one of the most common gastrointestinal disorders. As current antiulcer treatments are associated with wide range of side effects, there is a need to discover an effective and safer new antiulcer agent. Muntingia calabura L. (family Muntingiaceae), known as Jamaican cherry or kerukup siam has been employed traditionally to treat various ailments including gastrointestinal disorders. The traditional use of M. calabura and its potential antioxidant properties lead to the present research with the hope of finding an effective gastroprotective agent. The present study aimed to investigate the antiulcer activity of M. calabura methanolic leaves extract (MEMC) and its fractions using rat models, determine the underlying mechanism(s) of action and identify the phytochemical constituents present in the plant. Acute toxicity study was conducted using a single oral dose of 2000 mg/kg MEMC. The antiulcer activity of MEMC was evaluated in ethanol- and indomethacin-induced gastric ulcer rat models. The rats were administered 8% Tween 80, 100 mg/kg ranitidine, and MEMC (doses 25-500 mg/kg) orally for seven days, followed by ulcer induction using absolute ethanol (5 mL/kg) or indomethacin (100 mg/kg). The rats were euthanized; macroscopic and histological observations of the stomach were done. Fractionation of MEMC yielded petroleum ether (PEF), ethyl acetate (EAF) and aqueous (AQF) fractions. Their antiulcer property was investigated using ethanol-induced gastric ulceration as described above. MEMC and its fractions were subjected to antioxidant and anti-inflammatory studies including superoxide and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, oxygen radical absorbance capacity (ORAC), total phenolic content (TPC), inhibition of nitric oxide (NO), lipoxygenase (LOX) and xanthine oxidase (XO) activity. Evaluation of gastric content and quantification of mucus were carried out in pylorus-ligated model. Possible involvement of endogenous NO and sulfhydryl (SH) compounds was determined in animals pre-treated with NGnitro- L-arginine methyl esters (L-NAME) or N-ethylmaleimide (NEM) prior to MEMC or EAF treatment. Superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the stomach tissue homogenate treated with EAF was determined. Phytochemical screening and High Performance Liquid Chromatography (HPLC) analysis was conducted on MEMC, PEF and EAF. EAF was further subjected to Ultra-high-Performance Liquid Chromatography-Electrospray Ionization (UHPLC-ESI) analysis. The LD50 of MEMC was >2000 mg/kg. MEMC exerted significant (p<0.001) gastroprotection in both the ulcer models. PEF and EAF significantly (p<0.001) attenuated the ethanol-induced gastric lesions. MEMC and its fractions showed high antioxidant and anti-inflammatory activities. MEMC and EAF significantly (p<0.01) reduced volume of gastric content and increased the mucus production. Pre-treatment with L-NAME or NEM reversed the gastroprotection of MEMC and EAF. EAF markedly ameliorated the SOD, GSH, CAT, PGE2 and NO level while reducing MDA level. HPLC profiling showed the presence of quercetin and gallic acid in MEMC, PEF and EAF. UHPLC-ESI confirmed the presence of these compounds in EAF. In conclusion, MEMC and EAF exert significant antiulcer activity. The underlying gastroprotective mechanisms of MEMC and EAF could be associated with the antioxidant, anti-inflammatory, antisecretory, participation of mucus, antiperoxidative, modulation of NO and SH compounds and presence of flavonoids and phenols

Antiulcer activity of Muntingia calabura leaves involves the modulation of endogenous nitric oxide and nonprotein sulfhydryl compounds

Context: Muntingia calabura L. (Muntingiaceae) is a native plant species of the American continent and is widely cultivated in warm areas in Asia, including Malaysia. The plant is traditionally used to relieve pain from gastric ulcers. Objective: This study was designed to determine the antiulcer activity of a methanol extract of M. calabura leaves (MEMC) and the possible mechanisms of action involved. Materials and methods: An acute toxicity study was conducted using a single oral dose of 2000 mg/kg MEMC. The antiulcer activity of MEMC was evaluated in absolute ethanol- and indomethacin-induced gastric ulcer rat models. MEMC was administered orally (dose range 25-500 mg/kg) to rats fasted for 24 h. The animals were pretreated with NG-nitro-L-arginine methyl esters (L-NAME) or N-ethylmaleimide (NEM) prior to MEMC treatment to assess the possible involvement of endogenous nitric oxide (NO) and nonprotein sulfhydryl (NP-SH) compounds in the gastroprotective effect of MEMC. Results: As the administered dose did not cause toxicity in the rats, the oral median lethal dose (LD50) of MEMC was >2000 mg/kg in rats. MEMC exerted significant (p < 0.001) gastroprotective activity in the ethanol- and indomethacin-induced ulcer models dose-dependently. Histological evaluation supported the observed antiulcer activity of MEMC. L-NAME and NEM pretreatment significantly (p < 0.05) reversed and abolished the gastroprotective effect of MEMC, respectively. Discussion and conclusion: The results obtained indicate that MEMC has significant antiulcer activity that might involve the participation of endogenous NO and NP-SH compounds. These findings provide new pharmacological information regarding the potential use of M. calabura

Mechanism(s) of action involved in the gastroprotective activity of Muntingia calabura

AbstractEthnopharmacological relevanceMuntingia calabura L. (Muntingiaceae) is locally known as kerukup siam. Its leaves, flowers, barks and roots have been used traditionally in East Asia and South America to treat various diseases including ulcer-related diseases. The present study aimed to investigate the mechanism(s) of gastroprotective effect of methanol extract of Muntingia calabura leaves (MEMC) using the pylorus ligation induced gastric ulceration in rats.Materials and methodsFive groups of rats (n=6) were administered orally once daily for 7days with 8% Tween 80 (negative control), 100mg/kg ranitidine (positive control), or MEMC (100, 250 or 500mg/kg), followed by the ulcer induction via ligation of the pyloric part of the rat’s stomach. This was followed by the macroscopic analysis of the stomach, evaluation of gastric content parameters, and quantification of mucus content. The antioxidant (measured using the superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assays), anti-inflammatory (evaluated using the in vitro lipoxygenase and xanthine oxidase assays), phytoconstituents and HPLC analysis of MEMC were also carried out.ResultsThe MEMC significantly (p<0.05) reduced gastric lesion in this model. Furthermore, the extract also significantly (p<0.01) reduced the volume of gastric content whereas the total acidity was significantly (p<0.05) reduced in the doses of 100 and 500mg/kg MEMC. Moreover, the mucus content increased significantly (p<0.01) in MEMC-treated rats. The extract also showed high antioxidant and anti-inflammatory activities in all assays tested, and demonstrated the presence of high tannins and saponins followed by flavonoids.ConclusionThe MEMC exerted gastroprotective effect via several mechanisms including the anti-secretory, antioxidant and anti-inflammatory activities. These activities could be attributed to the presence of tannins, saponins and flavonoids (e.g. rutin, quercitrin, fisetin and dihydroquercetin)

Metabolomics combined with chemometric analysis to identify α-glucosidase inhibitors in Phaleria macrocarpa fruit extracts and its molecular docking simulation

Phaleria macrocarpa is a medicinal plant widely available in Malaysia. The plant parts have been traditionally used as an antidiabetic remedy. This study aimed to identify the putative inhibitors of the α-glucosidase enzyme from P. macrocarpa using a gas chromatography-mass spectrometry (GC–MS)-based metabolomics approach and further subjected them to in silico molecular docking analysis to elucidate the possible mechanism of action. This study assessed the inhibitory potential of P. macrocarpa fruit extracts (aqueous, 20 %, 40 %, 60 %, 80 %, and 100 % ethanol) against the α-glucosidase enzyme using GC–MS and chemometric analysis. Orthogonal partial least squares (OPLS) combined with GC–MS analysis were applied to correlate the inhibition of enzyme activity to the metabolites profile of P. macrocarpa. All the potential inhibitors identified were further docked to the yeast (Saccharomyces cerevisiae) protein crystal structure (PDB3A4A). The generated score scatter plot of OPLS showed a recognizable separation of all the extracts into six different clusters. GC–MS, incorporated with multivariate data analysis techniques, was used to identify significant chemical markers. Methyl α-D-glucopyranoside, squalene, palmitic acid, myo-inositol and isoquinoline metabolites were identified as putative inhibitors against α-glucosidase activity from P. macrocarpa. In conclusion, the GC–MS-based metabolomics approach identified potential chemical markers of P. macrocarpa that could be utilized in the development of herbal based medicine. © 2024 SAA

Antiulcer potential of Sapium indicum aqueous extract: towards the development of halal pharmaceutical ingredient with gastroprotective property

With the growing number of population suffering of gastro-related diseases such as ulcer and gastritis, the need to find novel Halal pharmaceutical ingredients with gastroprotective activity is also increasing significantly, especially among the Muslim population. The conventional antiulcer drugs are overshadowed with unwanted side effects. Plant kingdom is regarded as one of the valuable source to fulfil such need. One of the plants that currently caught our attention is Sapium indicum. Therefore, based on the traditional use of S. indicum to relieve pain and to heal wound, as well as the scientifically reported antimicrobial, antinociceptive and antioxidant properties, this study was intended to evaluate the antiulcer potential of S. indicum aqueous extract (SIAE) using established ethanol- and indomethacin-induced ulcer models, followed by pylorus ligation model for antiulcer mechanisms. The SIAE was prepared at doses of 25, 125 and 250 mg/kg, together with distilled water (negative control) and ranitidine 100 mg/kg (positive control). In ethanol- and indomethacine-induced ulcer models, all doses of SIAE showed reduction in ulcer area formation with 250 mg/kg exhibited the best activity with approximately 85.8% and 82% protection respectively when compared to the control group. This is supported by histological findings which showed reduction in epithelial and glandular disruption, congestion, oedema and haemorrhage score with the absence of necrosis and erosion when compared to negative control. The pylorus ligation study also confirmed the SIAE ability to retard ulcer formation by reducing the free and total acidity of gastric secretion in the rats, and enhancement of the gastric mucosal defence action by increased mucus secretion amount. In conclusion, the study suggested that SIAE illustrated good gastroprotective property, which will become a strong basis to develop Halal S. indicum-based pharmaceutical ingredients with gastroprotective property

Polyphenolics and triterpenes presence in chloroform extract of Dicranopteris linearis leaves attenuated paracetamol-induced liver intoxication in rat

Abstract Introduction Water-soluble, but not lipid-soluble, extract of Dicranopteris linearis leaves has been proven to possess hepatoprotective activity. The present study aimed to validate the hepatoprotective and antioxidant activities, and phytoconstituents of lipid-soluble (chloroform) extract of D. linearis leaves. Methods The extract of D. linearis leaves (CEDL; 50, 250 and 500 mg/kg) was orally administered to rats for 7 consecutive days followed by the oral administration of 3 g/kg PCM to induce liver injury. Blood was collected for liver function analysis while the liver was obtained for histopathological examination and endogenous antioxidant activity determination. The extract was also subjected to antioxidant evaluation and phytochemicals determination via phytochemical screening, HPLC and UPLC-HRMS analyses. Results CEDL exerted significant (p &lt; 0.05) hepatoprotective activity at 250 and 500 mg/kg and significantly (p &lt; 0.05) reversed the PCM-induced decrease in rat’s liver endogenous antioxidant (catalase and superoxide dismutase) level. CEDL possessed a high antioxidant capacity when measured using the ORAC assay, but a low total phenolic content value and radical scavenging activity as confirmed via several radical scavenging assays, which might be attributed particularly to the presence of triterpenes. Phytochemicals screening demonstrated the presence of triterpenes and flavonoids, while UPLC-HRMS analysis showed the presence of polyphenols belonging to the hydroxybenzoic acids, hydroxycinammates and flavonoid groups. Discussion and conclusion Lipid-soluble bioactive compounds of CEDL demonstrated hepatoprotective effect against PCM intoxication partly via the modulation of the endogenous antioxidant defense system, and exerted high antioxidant capacity. Further investigation is warranted to identify the potential hepatoprotective leads from CEDL for future drug development. </jats:sec

The investigation of antioxidant and antidiabetic activities of Christia vespertilionis leaves extracts

The present study has been aimed to investigate the antioxidant and antidiabetic activities of Christia vespertilionis leaves extracts. The analysis of the extracts obtained using different solvents revealed that ethyl acetate: methanol extract as the most potential in 2, 2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging while hexane: ethyl acetate exhibited highest ferric reducing antioxidant power (FRAP) capacity and a-glucosidase inhibition. The infrared analysis displayed the presence of O-H, C-H, C=O, C=C, C-O, and N-H predominantly in the extracts reflecting some of the compounds reported previously; quercetin 3-O-glucoside, oleanolic acid methyl ester, b-sitosterol, stigmasterol, geraniol and 2’-hydroxygenistein. The latter two displayed competitive mode of inhibition in both the yeast and human protein receptors. Conclusively, C. vespertilionis leaves contain potent antioxidants and a-glucosidase inhibitors; thus, further studies can enhance its use in pharmaceutical applications

Toxicity and teratogenicity evaluation of hydroethanolic extract of momordica charantia fruit using zebrafish (DANIO RERIO) embryos model

 The use of zebrafish vertebrate model in vivo analysis of the drug toxicity and efficacy, chemical toxicity, and safety is increasing in recent researches. Momordica charantia Linn (Cucurbitaceae) has been traditionally claimed for its many protective roles. However, the development of toxicity effect may cause morphological abnormalities by using an embryo of zebrafish (Danio Rerio) is unknown. Hence, this study was designed to determine the toxicity and teratogenic effect of hydroethanolic extract of M. charantia fruit using Zebrafish (Danio Rerio) embryos. The crude extract was prepared from the fruit of M. charantia using 80% hydroethanolic solvent. The zebrafish embryos were exposed to serial dilution of crude extract. The active constituent was analyzed using gas chromatography coupled with mass spectrophotometry (GC-MS) Momordica charantia Linn (Cucurbitaceae) has been widely commercialized based on traditional usage as an antidiabetic product. The current study has shown the toxic effects of the M.  charantia fruit extract on the developing zebrafish embryos, and the median lethal concentration (LC50) was calculated to be 725.90 mg/L at 48 hpt. The observed effects are dependent on the time of exposure and concentrations of the extract. At higher concentration, the extract causes some morphological defects such as less pigmentation, dented tail, spinal curvature, oedema, reduced hatchability, and growth retardation, that indicates the presence of toxicant(s). Based on the GC-MS profiling, some of the compounds identified in the hydroethanolic extract, such as propanedioic acid and glutamine, may have caused the teratogenic effects to the embryos. Further research on the M. charantia fruit's metabolites should be carried out prior to any nutraceutical or pharmaceutical application.</jats:p