Identification of Potential Diuretic and Laxative Drug Candidates from Avicennia officinalis L. Bark through In Vivo Mice Model Studies and In Vitro Gas Chromatography-Mass Spectrometry and Molecular Docking Analysis.

Background: Avicennia officinalis is a medicinal plant that has traditionally been used as a diuretic, anti-infective, and antiasthmatic. Our investigation was designed to explore the diuretic and laxative potentials of different fractions of this plant's bark extract as well as the identification of possible drug candidates for the activity. Methods: Collected bark was extracted in ethanol and fractionated in different polar and nonpolar solvents, i.e., water, chloroform, ethyl acetate, and n-hexane. Phytoconstituents were identified following the published protocols and gas chromatography-mass spectrometry (GC-MS). In the diuretic test, Na+ and K+ ions were measured using a flame photometer whereas the Cl- ion content was measured by titrimetric method against AgNO3. In the laxative test, feces amount and consistency were also measured. Molecular docking analysis was conducted using the "Vina Wizard" program in PyRx-Python Prescription 0.8. Results: Phytochemical analysis indicated that alkaloids, tannins, flavonoids, saponins, glycosides, and terpenoids were detected in the most bioactive crude extracts, whereas alkaloids, terpenoids, saponins, and gums were found in bioactive n-hexane fraction and steroids, glycosides, and terpenoids were found positive in chloroform fraction. Almost all the fractions demonstrated a dose-dependent increment of stool production with a soft consistency; however, the chloroform fraction was found to be the most active (p < 0.001). The crude extract and n-hexane fractions significantly increased (p < 0.01) the urinary output at the dose of 200 and 400 mg/kg. The concentrations of Na+, K+, and Cl- in collected urine were found to be more compared with the control group. The GC-MS analysis identified seven compounds in bioactive n-hexane fraction (phenolic and ester-type mainly) whereas seven other compounds (acidic and ester-type mainly) were identified in chloroform fraction. In molecular docking, two drug candidates of this extract (2,4-bis(2-phenylpropan-2-yl)phenol and 2-[4-[2-(dimethylamino)-2-oxo-1,1-diphenylethyl]phenyl]-2-phenylacetic acid) showed excellent binding affinity with the receptor compared with furosemide. Conclusion: A. officinalis bark might be a potential source of bioactive compounds for treating hypertension, edema, and constipation.

Screening of Natural Bioactive Metabolites and Investigation of Antioxidant, Antimicrobial, Antihyperglycemic, Neuropharmacological, and Cytotoxicity Potentials of Litsea polyantha Juss. Ethanolic Root Extract.

This study was designed to identify some bioactive phytochemicals from ethanolic extract of roots of Litsea polyantha and to evaluate some of its pharmacological activities. Phytochemical tests indicated the presence of reducing sugar, combined reducing sugar, tannins, flavonoids, alkaloids, terpenoids, and phenol. In the antioxidant assay using 2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging method, the IC50 value was found to be 82.31 µg/mL. Total content of phenolic compounds, flavonoid, and tannin was found to be 152.69 mg GAE/gm, 85.60 mg QE/gm, and 77.22 mg GAE/gm of dry extract, respectively. In disc diffusion antibacterial assay, the extract exhibited highest zone of inhibition up to 12.25 mm against Escherichia coli at the concentration of 500 µg/disc. For brine shrimp lethality bioassay, the extract exhibited LC50 56.082 µg/mL. In in vivo antihyperglycemic activity test by oral glucose tolerance test using Swiss Albino mice at the oral dose of 250 and 500 mg/kg, the extract showed statistically significant antihyperglycemic effect. Finally, in vivo, the extract exhibited the dose dependent CNS depressant effects by reducing the locomotors of Swiss Albino mice which was confirmed through three different neuropharmacological activity tests such as open field, hole cross, and hole board test.

Design, synthesis and evaluation of N-aryl-glyoxamide derivatives as structurally novel bacterial quorum sensing inhibitors.

Bacteria cooperatively regulate the expression of many phenotypes through a mechanism called quorum sensing (QS). Many Gram-negative bacteria use an N-acyl homoserine lactone (AHL)-mediated QS system to control biofilm formation and virulence factor production. In recent years, quorum sensing inhibitors (QSIs) have become attractive tools to overcome antimicrobial resistance exhibited by various pathogenic bacteria. In the present study, we report the design and synthesis of novel N-arylisatin-based glyoxamide derivatives via the ring-opening reaction of N-aryl isatins with cyclic and acylic amines, and amino acid esters. The QSI activity of the synthesized compounds was determined in the LasR-expressing Pseudomonas aeruginosa MH602 and LuxR-expressing Escherichia coli MT102 reporter strains. Compounds 31 and 32 exhibited the greatest QSI activity in P. aeruginosa MH602, with 48.7% and 42.7% reduction in QS activity at 250 µM, respectively, while compounds 31 and 34 showed 73.6% and 43.7% QSI activity in E. coli MT102. In addition, the ability of these compounds to inhibit the production of pyocyanin in P. aeruginosa (PA14) was also determined, with compound 28 showing 47% inhibition at 250 µM. Furthermore, computational docking studies were performed on the LasR receptor protein of P. aeruginosa, which showed that formation of a hydrogen bonding network played a major role in influencing the QS inhibitory activity. We envisage that these novel non-AHL glyoxamide derivatives could become a new tool for the study of QS and potentially for the treatment of bacterial infections.

Indole-based novel small molecules for the modulation of bacterial signalling pathways.

Gram-negative bacteria such as Pseudomonas aeruginosa use N-acylated L-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation and antibiotic resistance. Some bacteria use indole moieties for intercellular signaling and as regulators of various bacterial phenotypes important for evading the innate host immune response and antimicrobial resistance. A range of natural and synthetic indole derivatives have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, various indole-based AHL mimics were designed and synthesized via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N,N'-dicyclohexylcarbodiimide (DCC) mediated coupling reactions of a variety of substituted or unsubstituted aminoindoles with different alkanoic acids. All synthesized compounds were tested for QS inhibition using a P. aeruginosa QS reporter strain by measuring the amount of green fluorescent protein (GFP) production. Docking studies were performed to examine their potential to bind and therefore inhibit the target QS receptor protein. The most potent compounds 11a, 11d and 16a showed 44 to 65% inhibition of QS activity at 250 µM concentration, and represent promising drug leads for the further development of anti-QS antimicrobial compounds.

Antinociceptive and antioxidant activity of Zanthoxylum budrunga wall (Rutaceae) seeds.

Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 µg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity.

Antinociceptive, anti-inflammatory and antidiarrheal activities of ethanolic calyx extract of Hibiscus sabdariffa Linn. (Malvaceae) in mice.

OBJECTIVE: To evaluate the antinociceptive, anti-inflammatory and antidiarrheal activities of the ethanolic calyx extract of Hibiscus sabdariffa Linn. in mice. METHODS: In the present study, the dried calyxes of H. sabdariffa were subjected to extraction with 95% ethanol and the extract was used to investigate the possible activities. Antinociceptive activity of the extract was evaluated by using the acetic acid-induced writhing test. The anti-inflammatory effect of the extract was tested by using the xylene-induced ear edema model mice. Castor oil-induced diarrheal model mice were used to evaluate the antidiarrheal activity of the extract. RESULTS: In acetic acid-induced writhing test, the extract produced inhibited writhing in mice significantly compared with the blank control (P<0.01). The extract showed significant inhibition of ear edema formation in xylene-induced ear edema model mice in a dose-related manner compared with the blank control (P<0.01). The extract demonstrated a significant antidiarrheal activity against castor oil-induced diarrheal in mice in which it decreased the frequency of defecation and increased the mean latent period at the doses of 250 and 500 mg/kg body weight (P<0.01). CONCLUSION: The above mentioned findings indicate that the calyx extract of H. sabdariffa possesses significant antinociceptive, anti-inflammatory and antidiarrheal activities that support its uses in traditional medicine.