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Journal of Ethnopharmacology Dec 2023Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders.
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.
Topics: Animals; Rabbits; Antidiarrheals; Parasympatholytics; Bronchodilator Agents; Rosa; Isoproterenol; Molecular Docking Simulation; Calcium; Prospective Studies; Tandem Mass Spectrometry; Plant Extracts; Diarrhea; Verapamil; Jejunum; Gastrointestinal Agents; Calcium Channels; Asthma
PubMed: 37315649
DOI: 10.1016/j.jep.2023.116696 -
Current Pharmaceutical Design 2022Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10%...
Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics; designing less addictive opioids is an active area of pharmaceutical research that may lead to significant improvements in chronic pain management. Recently, the International Agency for Research on Cancer (IARC) has classified opium consumption as carcinogenic to humans (Group 1) based on sufficient evidence of carcinogenicity in human studies. However, all human studies analyzed by the IARC Working Group included participants who consumed opium that was mixed, adulterated, and/or contaminated with known and probable human carcinogens (e.g., tarry residues of combusted opium, arsenic, lead, and chromium). The working group considered that these carcinogens were part of the complex mixture that opium is, rather than co-exposure or confounders. No evidence of carcinogenicity was available for pure opium in human, animal, or mechanistic studies. To avoid confusion and concern among health professionals and patients using medicinal opium preparations and in scientists involved in the design and development of new opium derivatives, opium should be classified in Group 3 (not classifiable as to its carcinogenicity to humans). The term 'street opium' could be used to refer to opium that probably contains human carcinogens not present in pure opium and should remain in Group 1 (carcinogenic to humans).
Topics: Analgesics, Opioid; Animals; Carcinogens; Humans; Morphine; Neoplasms; Opium; Papaver
PubMed: 35674306
DOI: 10.2174/1381612828666220607104805 -
The regulatory effects of fucoidan and laminarin on functional dyspepsia mice induced by loperamide.Food & Function Jul 2023Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many...
Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many physiological properties; however, their relative abilities in regulating gastrointestinal motility have not been illustrated yet. In this study, we aimed to investigate the regulatory effect of fucoidan and laminarin on functional dyspepsia mice induced by loperamide. Mice with gastrointestinal dysmotility were treated with fucoidan (100 and 200 mg per kg bw) and laminarin (50 and 100 mg per kg bw). As a result, fucoidan and laminarin reversed the dysfunction mainly through regulating gastrointestinal hormones (motilin and ghrelin), the cholinergic pathway, the total bile acid level, c-kit protein expression, and gastric smooth muscle contraction-related gene expression (ANO1 and RYR3). Moreover, fucoidan and laminarin intervention modulated the gut microbiota profile including the altered richness of Muribaculaceae, Lachnospiraceae, and . The results indicated that fucoidan and laminarin may restore the rhythm of the migrating motor complex and regulate gut microecology. In conclusion, we provided evidence to support that fucoidan and laminarin might have potential abilities to regulate gastrointestinal motility.
Topics: Mice; Animals; Dyspepsia; Loperamide; Polysaccharides
PubMed: 37377021
DOI: 10.1039/d3fo00936j -
Nutrients Mar 2022Carob is one of the major food trees for peoples of the Mediterranean basin, but it has also been traditionally used for medicinal purposes. Carob contains many... (Review)
Review
Carob is one of the major food trees for peoples of the Mediterranean basin, but it has also been traditionally used for medicinal purposes. Carob contains many nutrients and active natural products, and D-Pinitol is clearly one of the most important of these. D-Pinitol has been reported in dozens of scientific publications and its very diverse medicinal properties are still being studied. Presently, more than thirty medicinal activities of D-Pinitol have been reported. Among these, many publications have reported the strong activities of D-Pinitol as a natural antidiabetic and insulin regulator, but also as an active anti-Alzheimer, anticancer, antioxidant, and anti-inflammatory, and is also immune- and hepato-protective. In this review, we will present a brief introduction of the nutritional and medicinal importance of Carob, both traditionally and as found by modern research. In the introduction, we will present Carob's major active natural products. The structures of inositols will be presented with a brief literature summary of their medicinal activities, with special attention to those inositols in Carob, as well as D-Pinitol's chemical structure and its medicinal and other properties. D-Pinitol antidiabetic and insulin regulation activities will be extensively presented, including its proposed mechanism of action. Finally, a discussion followed by the conclusions and future vision will summarize this article.
Topics: Biological Products; Fabaceae; Galactans; Hypoglycemic Agents; Inositol; Insulin; Mannans; Plant Gums
PubMed: 35406064
DOI: 10.3390/nu14071453 -
Frontiers in Pharmacology 2023L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several species were...
L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several species were traditionally used to manage wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of and leaves as well as to assess their anti-diarrheal activity. Polyphenolic content of and AME were investigated using UHPLC/MS. The antidiarrheal potential of the obtained extracts was evaluated by conducting a castor oil-induced diarrhea model. Twenty-five and twenty-six polyphenolic compounds were tentatively identified in and AME, respectively. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species AME of (250, 500, and 1000 mg/kg) exhibited a significant prolongation in the onset of diarrhea by 17.7 %, 42.6%, and 79.7% respectively while AME of at the same doses significantly prolonged the onset of diarrhea by 38.6%, 77.3%, and 2.4 folds respectively as compared to the control. Moreover, the percentage of diarrheal inhibition of was 23.8%, 28.57%, and 42,86% respectively, and for 33.34%, 47.3%, and 57.14% respectively as compared to the control group. Both extracts significantly decreased the volume of intestinal fluid by 27%, 39.78%, and 50.1% for respectively; and by 38.71%, 51.19%, and 60% for respectively as compared to the control group. In addition, AME of exhibited a peristaltic index of 53.48, 47.18, and 42.28 with significant inhibition of gastrointestinal transit by 18.98%, 28.53%, and 35.95 % respectively; while AME of exhibited a peristaltic index of 47.71, 37, and 26.41 with significant inhibition of gastrointestinal transit by 27.72%, 43.89%, and 59.99% respectively as compared with the control group. Notably, showed a better antidiarrheal effect in comparison with and, the highest effect was observed for at 1000 mg/kg as it was nonsignificant from the loperamide standard group in all measured parameters.
PubMed: 36874027
DOI: 10.3389/fphar.2023.1120146 -
Biochemical Pharmacology Dec 2023Bladder cancer is one of the most common carcinomas in the human urinary system worldwide. Loperamide, known as an antidiarrheal drug, exerts anti-tumor activities...
Bladder cancer is one of the most common carcinomas in the human urinary system worldwide. Loperamide, known as an antidiarrheal drug, exerts anti-tumor activities against various cancers. However, the effect of loperamide on bladder cancer cells remains unclear. Our study aimed to investigate the effect of loperamide on bladder cancer and explore the underlying mechanisms. We found that loperamide suppressed the proliferation of 5637 and T24 cells in a dose-dependent manner. Loperamide treatment showed both pro-apoptotic and pro-autophagic effects on bladder cancer cells. Moreover, it was revealed that loperamide induced reactive oxygen species (ROS) accumulation, leading to the activation of c-Jun N-terminal kinase (JNK) signaling pathway. Notably, ROS scavenger N-acetyl-L-cysteine (NAC) and JNK inhibitor SP600125 effectively attenuated the induction of autophagy and apoptosis triggered by loperamide. Finally, blocking autophagy with CQ could significantly enhance the anti-cancer effect of loperamide both in vitro and in vivo. Overall, these findings demonstrated that loperamide induced autophagy and apoptosis through the ROS-mediated JNK pathway in bladder cancer cells. Our results suggest that the strategy of combining loperamide with autophagy inhibitor CQ may provide a therapeutic option for the treatment of bladder cancer.
Topics: Humans; MAP Kinase Signaling System; Loperamide; Reactive Oxygen Species; Cell Line, Tumor; Apoptosis; Urinary Bladder Neoplasms; Autophagy; JNK Mitogen-Activated Protein Kinases
PubMed: 37863323
DOI: 10.1016/j.bcp.2023.115870 -
Drug Development Research Nov 2019Salvia tiliifolia is used in folk medicine as a relaxant agent and for the treatment of diarrhea and neurodegenerative diseases. Tilifodiolide (TFD) is a diterpene...
Salvia tiliifolia is used in folk medicine as a relaxant agent and for the treatment of diarrhea and neurodegenerative diseases. Tilifodiolide (TFD) is a diterpene obtained from this plant. The purpose of this work was to evaluate the antidiarrheal, vasorelaxant, and neuropharmacological actions of TFD. These effects were selected based on the folk medicinal use of S. tiliifolia. The antidiarrheal activity of 1-50 mg/kg p.o. TFD was assessed with the castor oil related tests. The vasorelaxant effect of TFD (0.9-298 μM) was performed with smooth muscle tissues from rats, and its mechanism of action was evaluated using different inhibitors. The sedative, anxiolytic, and antidepressant effects of 1-100 mg/kg TFD were assessed. The possible mechanisms of action of the anxiolytic and antidepressant effects of TFD were evaluated using inhibitors. TFD exhibited antidiarrheal (ED = 10.62 mg/kg) and vasorelaxant (EC = 48 ± 3.51 μM) effects. The coadministration of TFD with N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), reverted the vasorelaxant action showed by TFD alone. TFD exerted anxiolytic actions (ED = 20 mg/kg) in the cylinder exploratory test, whereas TFD (50 mg/kg) showed antidepressant actions in the tail suspension test by 44%. The pretreatment with 2 mg/kg flumazenil partially reverted the anxiolytic actions of TFD, whereas the pretreatment with 1 mg/kg yohimbine abolished the antidepressant effects of TFD. In summary, TFD exerted antidiarrheal activity by decreasing the intestinal fluid accumulation and vasorelaxant effects mediated by nitric oxide and cyclic guanosine monophosphate. TFD showed anxiolytic and antidepressant effects by the partial involvement of gamma-Aminobutyric acid (GABA) receptors and the possible participation of α2-adrenoreceptors, respectively.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antidiarrheals; Behavior, Animal; Diterpenes; Dose-Response Relationship, Drug; Drug Interactions; Flumazenil; Hypnotics and Sedatives; Male; Mice; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Oxadiazoles; Quinoxalines; Vasodilator Agents; Yohimbine
PubMed: 31343767
DOI: 10.1002/ddr.21578 -
Open Biology May 2023L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of... (Review)
Review
L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information on including its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates.
Topics: Opium; Alkaloids; Benzylisoquinolines; Papaver; Codeine; Neoplasms; Morphine Derivatives
PubMed: 37132222
DOI: 10.1098/rsob.220355 -
Journal of the American College of... Oct 2023
Topics: Humans; Loperamide; Arrhythmias, Cardiac; Drug Overdose
PubMed: 37852701
DOI: 10.1016/j.jacc.2023.07.033 -
JAMA Jan 2021
Topics: Appendectomy; Appendicitis; France; History, 19th Century; Humans; Opium; United States
PubMed: 33496764
DOI: 10.1001/jama.2020.17750