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African Journal of Traditional,... 2014The stem-bark extract of Carpolobia lutea (Polygalaceae), used in ethno-medicine as anti-diarrhea was pharmacologically evaluated. This was the first report of...
BACKGROUND
The stem-bark extract of Carpolobia lutea (Polygalaceae), used in ethno-medicine as anti-diarrhea was pharmacologically evaluated. This was the first report of assessment of the ethanolic stem extract (ESE), of C. lutea as anti-diarrhoeal agent in rats. The anti-diarrhoeal effects, acute toxicity and ionic profile are investigated and reported.
MATERIALS AND METHODS
The acute toxicity was established using Lock's method. The anti-diarrhoeal effects were demonstrated using castor oil-induced diarrheal and fluid accumulation and its effect on normal intestinal transit. The mechanism elucidated using yohimbine, isosorbide dinitrate, and diphenoxylate. The elemental and ionic profile of ESE was established using inductively coupled argon-plasma emission spectrometer and potentiometric titration respectively. The finger print of ESE was revealed by Jasco (Tokyo, Japan), HPLC and active compounds by phytochemical screening using standard procedure.
RESULTS
The LD50 obtained is 866.025 mg/kg (i.p). The doses of 43.3, 86.6, and 173.2 mg/kg of ESE showed inhibition of castor oil-induced diarrheal (p<0.05 -0.001). The most abundant cations in the extract are potassium and phosphorus (1.00 ±0.01 and 0.80 ± 0.030 mg/g respectively); while the most abundant anions are phosphate and sulphate (33.50±7.09 and 7.19±3.29 mg/g respectively). The HPLC fingerprint of ESE revealed UV spectra of biomolecules. Phytochemical screening revealed presence of saponins, polyphenols and glycosides.
CONCLUSION
These investigations indicate presence of bioactive and elemental substances which could play major role in diarrheal management. This investigation justifies the use of stem-bark of C. lutea in illicit gin (akpatashi), among the Effiks in Nigeria as antidiarrheal.
Topics: Animals; Antidiarrheals; Diarrhea; Female; Humans; Male; Mice; Nigeria; Plant Bark; Plant Extracts; Plant Stems; Polygalaceae; Rats
PubMed: 25435605
DOI: No ID Found -
PloS One 2016Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment...
OBJECTIVES
Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms.
STUDY DESIGN
A prospective experimental animal study.
METHODS
The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR).
RESULTS
The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level.
CONCLUSION
The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.
Topics: Animals; Constipation; Disease Models, Animal; Female; Gastrointestinal Motility; Glucosides; Interstitial Cells of Cajal; Neurotransmitter Agents; Nitric Oxide; Nitric Oxide Synthase; Paeonia; Prospective Studies; Proto-Oncogene Proteins c-kit; Rats; Rats, Wistar; Stem Cell Factor; Substance P; Vasoactive Intestinal Peptide
PubMed: 27478893
DOI: 10.1371/journal.pone.0160398 -
Bioinformatics and Biology Insights 2019Diarrhoeal disease kills about 1.5 million human beings per year across the continents. The enterotoxigenic (ETEC) pathotype has been noted as a major cause of...
Diarrhoeal disease kills about 1.5 million human beings per year across the continents. The enterotoxigenic (ETEC) pathotype has been noted as a major cause of diarrheal disease in human and livestock. The aim of this study is to identify broad-spectrum molecular targets in bacteria and broad-spectrum lead compounds (functional inhibitors) with high efficacy and no significant adverse implication on human systems, in relevance to diarrhea therapy through computational approaches which include phylogenetics, target prediction, molecular docking, and molecular flexibility dynamic simulations. Three molecular target genes, , and , which code for uridine diphosphate--acetylglucosamine-1-carboxyvinyltransferase, 1-deoxy-D-xylulose-5-phosphate reductoisomerase, and deoxyribonucleic acid polymerase III alpha subunit, respectively, were found to be highly conserved in 7 diarrhea-causing microbes. In addition, 21 potential compounds identified showed varied degree of affinity to these enzymes. At free energy cutoff of -8.0 kcal/mol, the highest effective molecular target was DNA polymerase III alpha subunit (PDB ID: 4JOM) followed by UDP--acetylglucosamine-1-carboxyvinyltransferase (PDB ID: 5UJS), and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PDB ID: 1ONN), while the highest effective lead compound was -coeleneterazine followed by amphotericin B, MMV010576, MMV687800, MMV028694, azithromycin, and diphenoxylate. The flexibility dynamics of DNA polymerase III alpha subunit unraveled the atomic fluctuation which potentially implicated Asp593 as unstable active site amino acid residue. In conclusion, bacteria gene or its protein is a highly promising molecular target for the next generation of antibacterial drugs of the class of -coeleneterazine.
PubMed: 31695343
DOI: 10.1177/1177932219884297 -
Archives of Disease in Childhood Mar 197945 children were admitted to hospital after ingesting varying quantities of diphenoxylate (Lomotil). One died and 44 recovered without any sequelae. Four patients were...
45 children were admitted to hospital after ingesting varying quantities of diphenoxylate (Lomotil). One died and 44 recovered without any sequelae. Four patients were comatose, 32 were drowsy, and 9 suffered respiratory depression. No correlation was found between ingested dose and the severity of symptoms. Because of its action in rendering the gut atonic, removal of diphenoxylate by gastric lavage is mandatory, even in patients admitted at least 24 hours after drug ingestion. Naloxone is the narcotic antagonist of choice, and should be used in all cases where suspected diphenoxylate poisoning leads to respiratory depression or coma. The use of Lomotil as an antidiarrhoeal agent in children is difficult to justify.
Topics: Child; Child, Preschool; Diphenoxylate; Dose-Response Relationship, Drug; Female; Gastric Lavage; Humans; Infant; Isonipecotic Acids; Male; Naloxone; Respiratory Insufficiency
PubMed: 434909
DOI: 10.1136/adc.54.3.222 -
The Manufacturing Process of Kiwifruit Fruit Powder with High Dietary Fiber and Its Laxative Effect.Molecules (Basel, Switzerland) Oct 2019Kiwifruit is rich in vitamins, minerals, dietary fiber and other functional components, and it has long been used as a functional food to treat intestinal ailments such...
Kiwifruit is rich in vitamins, minerals, dietary fiber and other functional components, and it has long been used as a functional food to treat intestinal ailments such as constipation. The current research made full use of the kiwifruit, the juice was prepared by microencapsulation, and the dietary fiber in kiwifruit pomace was modified by enzymatic hydrolysis and grinding, then, the two were mixed to obtain an ultra-micro kiwifruit powder (UKP). In addition, the laxative effect of the UKP was verified by a diphenoxylate induced constipated mice model. The results demonstrated that compared with the raw samples, the retention rate of vitamin C, lutein and catechin in UKP were 83.3%, 81.9% and 88.3%, respectively, thus effectively avoiding the loss of functional components during the processing of kiwifruit. Moreover, α-amylase, protease and the ball milling process effectively reduced the size of dietary fiber in kiwifruit pomace, and its water-holding capacity (WHC), oil-holding capacity (OHC) and swelling capacity (SWC) were enhanced by 1.26, 1.65 and 1.10 times, respectively. Furthermore, to analyze the laxative effect of the UKP, a constipation mice model was established by diphenoxylate treatment (5 mg·kg, i.g.) for the last week, with or without UKP supplementation (2.4 g·kg B.W. per day) for 4 weeks. The results demonstrated that UKP significantly increased feces condition (fecal output and dejecta moisture content, gut transit (the intestinal propulsion rates) and substance P (SP) levels in portal vein plasma, and it decreased the whole gut transit time and mucinogen granules secreted by goblet cell in constipated mice.
Topics: Actinidia; Animals; Constipation; Dietary Fiber; Fruit; Laxatives; Male; Mice; Plant Extracts
PubMed: 31652679
DOI: 10.3390/molecules24213813 -
Annals of Translational Medicine Mar 2022Functional constipation (FC) is a common gastrointestinal (GI) disorder characterized by symptoms of constipation without a clear physiologic or anatomic cause. Gut...
BACKGROUND
Functional constipation (FC) is a common gastrointestinal (GI) disorder characterized by symptoms of constipation without a clear physiologic or anatomic cause. Gut microbiome dysbiosis has been postulated to be a factor in the development of FC, and treatment with probiotic regimens, including strains of , has demonstrated efficacy in managing symptoms. To further understand the role of in GI health, we conducted an animal study and a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of a specific sub-strain, Lp3a, on FC.
METHODS
For the animal study, male Kunming mice were treated with doses of Lp3a ranging from 0.67 to 2.00 g/kg or an equivalent amount of placebo for 15 days prior to the induction of constipation via 20 mL/kg of 25% diphenoxylate solution. GI motility parameters including intestinal motion and stool amount were then assessed. In the human study, 120 patients with FC were randomized to treatment [ Lp3a; 2×1.0×10 (colony forming units; CFU) ×7 days] or control groups (n=60 each). The primary endpoint was survey information on FC signs/symptoms. Participants and observers were blinded to group allocation. A subset of 20 Lp3a treated patients underwent pre- and post-treatment 16 s ribosomal ribonucleic acid (rRNA) gene sequencing. Whole genome sequencing (WGS) of Lp3a was also performed.
RESULTS
Lp3a-treated mice showed significantly improved intestinal motion, reduced time to first defecation, and increased stool amounts. Similarly, patients in the treatment group (n=59) reported significant improvements in FC signs/symptoms compared to controls (n=58; all P<0.05). Although 16 s rRNA sequencing revealed no significant variations between pre- and post-treatment samples, WGS of Lp3a itself revealed several biological pathways that may underlie the relief of FC symptoms in animals and humans, including methane and fatty acid metabolism and bile acid biosynthesis.
CONCLUSIONS
We found that the use of the novel probiotic sub-strain, Lp3a, led to clinically significant improvements in FC in both mice and humans, and identified the potential biological mechanisms underlying this activity.
PubMed: 35434041
DOI: 10.21037/atm-22-458 -
Drug, Healthcare and Patient Safety 2019The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the...
BACKGROUND
The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the FDA through the MedWatch program. A significant number of adverse events reported in the FAERS database have been for opioid use. The objective of this study was to determine the frequency counts and associated deaths of opioid drug names in the FAERS database.
METHODS
Drug data were obtained from the DRUG and OUTCOME files in the database. Drugs identified included: morphine, fentanyl, oxycodone, hydrocodone, tramadol, hydromorphone, methadone, codeine, oxymorphone, meperidine, propoxyphene, diphenoxylate, and heroin. Frequency counts and concomitant deaths of opioid drug names were determined via the MySQL database management system.
RESULTS
Fifteen different opioid drugs identified in the FAERS database were associated with ADEs, including death, and 3 drugs (oxycodone, hydrocodone, fentanyl) accounted for more than half of the reports. The highest frequency count value was 158,181 for oxycodone, which represents approximately 20.2% of the frequency counts for the opioids. The lowest frequency count value was 2,161 for dextromethorphan, which represents approximately 0.3% of the total. The opioid with the highest proportion of deaths to drug count was heroin (71.8%), followed by dextromethorphan (55.6%), methadone (37.2%), morphine (26.8%), and propoxyphene (23.7%).
CONCLUSION
The FAERS database represents an important source for detection and reporting of adverse drug events (ADEs), in particular the opioids and related drugs. It remains a challenge to estimate the true incidence of ADEs for this class of drugs in the general population.
PubMed: 31695510
DOI: 10.2147/DHPS.S214771 -
Bioorganic & Medicinal Chemistry Letters Dec 2012Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential...
Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC(50) values.
Topics: Diphenoxylate; Humans; Kinetics; Kv1.3 Potassium Channel; Potassium Channel Blockers; Protein Binding; Structure-Activity Relationship
PubMed: 23084278
DOI: 10.1016/j.bmcl.2012.09.080 -
Addiction & Health Jan 2018To self-medicate substance dependence, many substance users consume herbal medicines delivered in herbal medicine shops which are prepared through non-standard methods...
BACKGROUND
To self-medicate substance dependence, many substance users consume herbal medicines delivered in herbal medicine shops which are prepared through non-standard methods using a variety of different materials. Hence, the present study was carried out aiming to investigate and analyze the content of such herbal medicines.
METHODS
Four herbal medicine shops were selected from each of the 22 zones of Tehran City, Iran, and a total of 95 samples were purchased. A package containing 6 types of medication that was advertised by a satellite TV channel, was also purchased. Using high-performance liquid chromatography (HPLC) method, the samples were analyzed in the laboratory to detect different types of materials.
FINDINGS
Among the samples, 23 and 72 samples were uncovered compressed pills (Dragon pills) and capsules filled with colored powders (handmade self-medicating substance dependence capsules), respectively. The package advertised in the satellite TV was prepared in 6 various forms. The most common substances present in all the samples were as follows: diphenoxylate, tramadol, opioids, acetaminophen, and codeine with values of 90%, 86%, 78%, 69%, and 68%, respectively. On average, 5 of the above mentioned substances were present in each sample; moreover, 63% of the samples contained 5 or more substances. In addition, 42 (41%) of the samples contained all the 5 main substances including opioids, codeine, tramadol, diphenoxylate, and acetaminophen.
CONCLUSION
The findings of this study showed that handmade capsules and pills used for self-medicating substance dependence and also medicines advertised in the satellite TV channels contain different amounts of opioids, amphetamine, benzodiazepines, tramadol, codeine, and other substances that cause problems for substance users who are going to abandon substance abuse.
PubMed: 30627381
DOI: 10.22122/ahj.v10i1.508 -
Scientific Reports Jul 2016The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high...
The purpose of this study was to investigate the prevalences of and association between nonmedical prescription opioid use (NMPOU) and sleep quality among Chinese high school students. A cross-sectional study was conducted in Chongqing high school students in 2012, and questionnaires from 18,686 students were completed and eligible for this study. Demographic and NMPOU information was collected using a self-administered questionnaire. The Chinese Pittsburgh Sleep Quality index (CPSQI) was used to assess the occurrence of poor sleep. Among the total sample, 18.0% were classified as poor sleepers (27.4% of the subjects with past-month NMPOU), and the prevalences of lifetime, past-year and past-month NMPOU were 14.6, 4.6 and 2.8% across the entire sample, respectively. The most commonly used medicine was licorice tablets with morphine (9.1, 2.5 and 1.5% for lifetime, past-year and past-month, respectively), followed by cough syrup with codeine, Percocet, diphenoxylate and tramadol. After adjustment for potential confounders, the association between past-month NMPOU and poor sleep remained significant (AOR = 1.47, 95% CI 1.17 to 1.85). Programs aimed at decreasing NMPOU should also pay attention to sleep quality among adolescents.
Topics: Adolescent; Analgesics, Opioid; Child; China; Cross-Sectional Studies; Drug Misuse; Female; Humans; Male; Odds Ratio; Prevalence; Risk Factors; Sleep Wake Disorders; Students; Young Adult
PubMed: 27467181
DOI: 10.1038/srep30411