Liver protective effect of chloroform extract of Bauhinia purpurea leaves is attributed partly to its antioxidant action and the presence of flavonoids.

CONTEXT: Bauhinia purpurea L. (Fabaceae) is used in the Ayurvedic system to treat various oxidative-related ailments (e.g., wounds, ulcers etc.). Therefore, it is believed that the plant also has the potential to alleviate oxidative-related liver damage. OBJECTIVE: This study elucidates the hepatoprotective activity of chloroform extract of B. purpurea leaves (CEBP) in paracetamol (PCM)-induced liver injury (PILI) rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 6) were pre-treated once daily (p.o.) with CEBP (50-500 mg/kg) for seven consecutive days before being administered (p.o.) a hepatotoxic agent, 3 g/kg PCM. Liver enzyme levels were determined from the collected blood, while the collected liver was used to determine the activity of endogenous antioxidant enzymes and for histopathological examination. CEBP was also subjected to radical scavenging assays and phytochemical analysis. RESULTS: CEBP significantly (p < 0.05) reversed the toxic effect of PCM by increasing the serum levels of AST and ALT, and the activity of endogenous catalase (CAT) and superoxide dismutase (SOD) while reducing the liver weight/body weight (LW/BW) ratio. Other than low TPC value and radical scavenging activity, CEBP had a high antioxidant capacity when evaluated using the oxygen radical absorbance capacity (ORAC) assay. UHPLC-ESI-MS analysis of CEBP showed the presence of flavonoids. DISCUSSION AND CONCLUSIONS: CEBP exerts its hepatoprotective activity through a non-free radical scavenging pathway that involves activation of the endogenous enzymatic antioxidant defense system. Further study is needed to identify the responsible bioactive compounds before the plant can be developed as a future alternative hepatoprotective medicament for clinical use.

In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski's drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer's animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.

Mechanism(s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura.

BACKGROUND: Muntingia calabura L. (family Muntingiaceae), commonly known as Jamaican cherry or kerukup siam in Malaysia, is used traditionally to treat various ailments. The aim of this study is to elucidate the possible underlying gastroprotective mechanisms of ethyl acetate fraction (EAF) of Muntingia calabura methanolic leaves extract (MEMC). METHODS: MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined. RESULTS: HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p < 0.01 and p < 0.05, respectively), while free and total acidity reduced in the doses of 250 and 500 mg/kg (p <0.001 and p <0.05, respectively). EAF also augmented the mucus content significantly (p < 0.001). Pre-treatment with N-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) reversed the gastroprotective activity of EAF. EAF treatment markedly ameliorated the SOD, GSH and CAT activity and PGE2 and NO level while attenuating MDA level, relative to the vehicle group. CONCLUSIONS: In conclusion, the underlying gastroprotective mechanisms of EAF could be associated with the antisecretory, participation of mucus, antiperoxidative, improvement of antioxidant status, modulation of NO and SH compounds, stimulation of PGE2 as well as presence of quercetin and gallic acid.

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 N(G)-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.

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

Abstract 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.

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

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 < 0.05) hepatoprotective activity at 250 and 500 mg/kg and significantly (p < 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.

Antioxidant and anti-inflammatory activities contribute to the prophylactic effect of semi-purified fractions obtained from the crude methanol extract of Muntingia calabura leaves against gastric ulceration in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, the leaves, flowers, barks and roots of Muntingia calabura L. (Muntingiaceae) have been employed as a treatment for various ailments including dyspepsia and to relieve pain caused by gastritis and peptic ulcer disease. The methanolic extract of Muntingia calabura leaves (MEMC) has been proven in the previous study to possess significant antiulcer activity. In this study, we attempted to determine the prophylactic effect of the fractions obtained from MEMC against ethanol-induced gastric lesion in rats and the involvement of antioxidants and anti-inflammatory mediators. MATERIALS AND METHODS: The MEMC was fractionated with petroleum ether (PEF), ethyl acetate (EAF) and distilled water (AQF). These fractions were investigated for possible antiulcer property using ethanol-induced gastric ulcer rat model. The rats were administered orally once daily with 8% Tween 80 (control), 100mg/kg ranitidine, or the fractions, in the doses of 100, 250, and 500 mg/kg, for 7 days, followed by ulcer induction using absolute ethanol. The rats were euthanized; macroscopic and histological observations of the stomach were done. The ulcer area (UA) was determined and the percentage protection afforded by the fractions was calculated. The fractions were subjected to antioxidant studies including the superoxide and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assay. Involvement of nitric oxide (NO) and inflammatory mediators such as lipoxygenase (LOX) and xanthine oxidase (XO) were evaluated. Phytochemical screening and HPLC analysis of the fractions were also conducted. RESULTS: Pre-treatment of PEF and EAF significantly (p<0.001) attenuated the gastric lesions as compared to the control group in a dose-dependent manner. On the other hand, 100 and 250 mg/kg of AQF significantly (p<0.001) prevented the ulcer formation but at the highest dose (500 mg/kg), AQF failed to significantly reduce the ulcer formation, showing a dose-independent antiulcerative effect of AQF. The histological evaluation supported the observed gastroprotective activity of PEF, EAF and AQF. All the fractions showed high superoxide and DPPH scavenging activity, meanwhile the EAF showed highest TPC followed by PEF and AQF. These fractions also significantly (p<0.05) inhibited the NO while maintaining the viability of the cells. EAF exhibited high inhibition towards both the LOX and XO enzymes, meanwhile PEF and AQF exerted high LOX inhibition but low XO inhibition. Phytochemical screening and HPLC profiling suggested the presence of flavonoid- and tannin based compounds in PEF and EAF. CONCLUSION: It can be concluded that the prophylactic effect of the fractions on gastric ulceration in rats is associated with its high antioxidant activity and its ability to effectively inhibit the inflammation mediators. Presence of several flavonoids and gallic acid explains the effectiveness of the fractions in affording protection against gastric damages.

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

ETHNOPHARMACOLOGICAL RELEVANCE: Muntingia 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 METHODS: Five groups of rats (n=6) were administered orally once daily for 7 days with 8% Tween 80 (negative control), 100 mg/kg ranitidine (positive control), or MEMC (100, 250 or 500 mg/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. RESULTS: The 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 500 mg/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. CONCLUSION: The 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).