Experimental and in silico evaluation of Carthamus tinctorius L. oil emulgel: a promising treatment for bacterial skin infections.

Purpose: The current study aimed to develop a topical herbal emulgel containing Carthamus tinctorius L. (CT) oil extract, which has been scientifically proven for its antibacterial and antioxidant activities for the ailment of bacterial skin infections. Method: The CT emulgel was formulated by response surface methodology (RSM) and was evaluated by various parameters like extrudability, spreadability, pH, viscosity, and antibacterial and antioxidant activities. Molecular docking was also performed using AutoDock. Results: Among all formulated CT emulgels, F9 and F8 were optimized. Optimized formulations had shown good spreadability and extrudability characteristics. Sample F8 had % inhibition of 42.131 ± 0.335, 56.720 ± 0.222, and 72.440 ± 0.335 at different concentrations. Sample F9 had % inhibition of 26.312 ± 0.280, 32.461 ± 0.328, and 42.762 ± 0.398 at concentrations of 250 µg/ml, 500 µg/ml, and 1,000 µg/ml, respectively, which shows that both samples F8 and F9 have significant antioxidant potential. Optimized CT emulgels F8 and F9 had significant antibacterial activity against Staphylococcus aureus and Escherichia coli at p-value = 0.00, the Emulgel-F8 shows zone of inhibition of 24 mm for E-coli and 19 mm for S-aureus. Emulgel-F9 shows zone of inhibition of 22 mm for E-coli and 15 mm for S-aureus while pure CT- Oil extract shows zone of inhibition of 25 mm for E-coli and 20 mm for S-aureus and ciprofloxacin used as standard shows 36mm zone of inhibition against both E-coli and S-aureus. The comparative investigation through molecular docking binding affinities and interactions of ligands with various target proteins provides insights into the molecular processes behind ligand binding and may have significance for drug discovery and design for the current study. Conclusion: The current study suggests that C. tinctorius L.-based emulgel has good antioxidant and antibacterial activities against E. coli for the treatment of bacterial skin infections.

Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders. AIM OF THE STUDY: This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana. MATERIALS AND METHODS: The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments. RESULTS: The phytochemical analysis indicates the presence of rutin (742.91 µg/g), kaempferol (726.32 µg/g), and quercitrin (688.20 µg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 µM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 µM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg. CONCLUSION: Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.

Mechanistic insights of Cucumis melo L. seeds for gastrointestinal muscle spasms through calcium signaling pathway-related gene regulation networks in WGCNA and in vitro, in vivo studies.

BACKGROUND: In addition to the nutritional benefits of Cucumis melo L., herbalists in Pakistan and India employ seeds to treat various ailments. This study aimed to determine the regulatory role of C. melo seeds in calcium-mediated smooth muscle contraction. METHODS: We identified and quantified the phytochemicals of C. melo with LC ESI-MS/MS and HPLC, then conducted in vitro and in vivo tests to confirm the involvement in smooth muscle relaxation. Then, diarrhea-predominant irritable bowel syndrome gene datasets from NCBI GEO were acquired, DEGs and WGCNA followed by functional enrichment analysis. Next, molecular docking of key genes was performed. RESULTS: The quantification of C. melo seeds revealed concentrations of rutin, kaempferol, and quercetin were 702.38 µg/g, 686.29 µg/g, and 658.41 µg/g, respectively. In vitro experiments revealed that C. melo seeds had a dose-dependent relaxant effect for potassium chloride (80 mM)-induced spastic contraction and exhibited calcium antagonistic response in calcium dose-response curves. In in vivo studies, Cm.EtOH exhibited antidiarrheal, antiperistaltic, and antisecretory effects. The functional enrichment of WGCNA and DEGs IBS-associated pathogenic genes, including those involved in calcium-mediated signaling, MAPK cascade, and inflammatory responses. MAPK1 and PIK3CG were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. CONCLUSIONS: The bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth contraction.

Possible Mechanisms Underlying the Antispasmodic, Bronchodilator, and Antidiarrheal Activities of Polarity-Based Extracts of Cucumis sativus L. Seeds in In Silico, In Vitro, and In Vivo Studies.

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI-MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K+ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects.

Pharmacological exploration of traditional plants for the treatment of neurodegenerative disorders.

Alzheimer's disease (AD) is clinically characterized as memory deficits, altered behavior and impaired cognitive functions. The most important risk factor for AD is aging and mounting. Evidences suggested in different studies that traditionally used plants in Asia, China, and Europe significantly affect aging and AD involved neurodegeneration pathways. Research into ethnobotanicals for impaired memory and cognition has been burgeoned in last decades. The inclusion and exclusion criteria for the plant selection were based on reputed herbs recommended for treatment of neurological disorders and their scientific validation to cure neurodegenerative disorders. A range of traditional plants imparts effects via acetylcholinesterase activity, ß-amyloid peptide formation in plaques, neurotrophic factors and through antioxidant activity. On one side preclinical investigations identified promising drug candidates for AD, on the other side, clinical evidences are still pending. Presently, according to WHO, around more than 80% world population relay on natural remedies to cure their health related issues. Plants contain rich source of primary and secondary metabolites for improving health problems. Pharmaceutical industry is facing intriguing challenges like elevated cost and unendurable risk management due to the high burden of neurodegenerative disorders. A significant shift of drug discovery is being witnessed from synthetic moieties to herbal formulation.

"Pulling the plug"--management of meconium plug syndrome in neonates.

BACKGROUND: The significance of meconium plug syndrome (MPS) is unclear but has been associated with Hirschsprung's disease and magnesium tocolysis. We reviewed our experience to attempt to identify any potential association with these conditions and to review our outcomes. METHODS: Using the International Classification of Diseases, Ninth revision, code for meconium obstruction, patient charts were identified during the 1998-2008 period. A total of 61 cases of MPS were found, after excluding 7 of meconium ileus. Data regarding the hospital course and outcomes were collected and analyzed. RESULTS: Approximately 30% of patients had spontaneous resolution of the meconium plug without any treatment. Of those patients requiring treatment, contrast barium enema was used, with 97% success. Only 2 patients required surgical intervention owing to worsening distension and subsequent peritonitis. When we stratified the patients according to gestational age of >36 and <36 wk, contrast barium enemas were performed 2.2 ± 1.8 versus 8.6 ± 7.8 d after birth (P = 0.003), respectively, and the lower gestational age patients had a longer length of stay. Contrast barium enema was still successful in 94% of patients with a gestational age of <36 wk. Magnesium tocolysis was noted in 16% of the cases, and Hirschsprung's disease was only found in 3.2% of patients. CONCLUSIONS: Patients with MPS have excellent outcomes, independent of gestational age. Contrast barium enema remains the initial diagnostic and treatment of choice for patients with MPS. Also, although previous reports have shown a link between magnesium tocolysis and Hirschsprung's disease with MPS, our experience suggests otherwise.