scholarly journals Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582098794
Author(s):  
Imran Mukhtar ◽  
Haseeb Anwar ◽  
Osman Asghar Mirza ◽  
Qasim Ali ◽  
Muhammad Umar Ijaz ◽  
...  
Keyword(s):  
Oral Administration ◽  
Gut Microbiome ◽  
Drug Target ◽  
Membrane Transporters ◽  
Intestinal Microbiome ◽  
Albino Rats ◽  
Body Organ ◽  
Total Absorbance ◽  
Research World

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

scholarly journals In vitro Antioxidant and In vivo Hepatocurative and Nephrocurative Activities of Aqueous Leaf Extract of Newbouldia laevis in Albino Rats

2021 ◽  
pp. 114-125
Author(s):  
Mohammed A. Sulaiman ◽  
Mahmoud S. Jada ◽  
Augustine Elizabeth ◽  
Abubakar Umar Modibbo
Keyword(s):  
Oral Administration ◽  
Leaf Extract ◽  
Kidney Diseases ◽  
Albino Rats ◽  
Protein Levels ◽  
Ameliorative Effect ◽  
Liver And Kidney ◽  
Aqueous Leaf Extract

The in vitro antioxidant activity and in vivo hepatocurative and nephrocurative potential of Newbouldia laevis aqueous leaf extract (NLALE) was evaluated. The study used 30 male, albino rats (Rattus norvegicus) weighing 180 ± 20 g, of which 25 were intoxicated by oral administration of a single dose of diclofenac (100 mg/kg b. wt.). Animals were treated by oral administration of silymarin (200 mg/kg b. wt.), furosemide (1.5 mg/kg b. wt.) and NLALE (200 mg/kg and 400 mg/kg b. wt.) for seven consecutive days before animals were sacrificed on the 8th day and serum/plasma was analyzed for biochemical markers of hepatotoxicity and nephrotoxicity. Phytochemical screening of NLALE revealed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids and tannins. The extract scavenged DPPH radical, reduced Fe3+ and inhibited TBARs in comparable manner to ascorbic acid in vitro. NLALE also attenuated diclofenac-induced liver and kidney intoxication as indicated by the significantly (p<0.05) reduced levels of serum biomarkers of hepatotoxicity: ALT, AST, bilirubin, but increased total protein levels and nephrotoxicity: urea, creatinine, Na+ and K+. The observed effects are dose dependent as the 400 mg/kg b. wt. appeared to be more potent than the 200 mg/kg b. wt. dose. It may be concluded from this study that Newbouldia laevis leaf has ameliorative effect against diclofenac-induced hepatotoxicity and nephrotoxicity probably through antioxidative mechanism and the curative claim and the folkloric use of the plant in the treatment of liver and kidney diseases have been scientifically validated

scholarly journals The Competitive Absorption by the Gut Microbiome Suggests the First-Order Absorption Kinetics of Caffeine

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110331
Author(s):  
Imran Mukhtar ◽  
Arslan Iftikhar ◽  
Muhammad Imran ◽  
Muhammad Umar Ijaz ◽  
Shahzad Irfan ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Drug Targets ◽  
Structural Similarity ◽  
Drug Uptake ◽  
Intestinal Microbiome ◽  
Absorption Kinetics ◽  
Albino Rat ◽  
First Order ◽  
Protein Transporters

In the literature archive, the intestinal microbiome is now considered as a discrete organ system. Despite living symbiotically with the human body, the gut microbiome is represented as potential drug targets because of its ability to modify the pharmacokinetics of orally administered drugs. Structural biology analysis indicates the existence of homology between transport proteins of microbial cells and membranes of enterocytes. It is speculated that structural similarity in the protein transporters may provoke an unwanted phenomenon of drug uptake by the gut microbiome present in the small intestine of the host. Considering this hypothesis, we analyzed the absorbance of orally administered caffeine by the gut microbiota in in vivo albino rat model through the RP-HPLC-UV approach. Microbiome absorbed the caffeine maximally at 2 hours and minimally at 5 hours post-drug administration following first-order absorption kinetics in a nonlinear way. Drug absorbance of microbial pellet and percent dose recovery was found significantly higher ( P ≤ .05) at 2 hours post-administration as compared to all other groups. As speculated, our findings advocated the phenomenon that the gut microbiome influences the absorption of caffeine molecules. Members of the gut microbiome exhibited grouped behavior following first-order absorption kinetics in a nonlinear pattern.

Fate of 131I-Phenylstearic Acid and 131I-Oleic Acid after Intravenous and Oral Administration

1968 ◽  
Vol 07 (02) ◽  
pp. 173-183
Author(s):  
L. J. Anghileri
Keyword(s):  
Oleic Acid ◽  
Oral Administration ◽  
Comparative Study ◽  
Intestinal Tract ◽  
Albino Rats ◽  
Fat Absorption ◽  
Intestinal Fat Absorption ◽  
Intravenous And Oral Administration

SummaryA comparative study of the fates of 131I-phenylstearic and 131I-oleic acids, administered orally and intravenously to albino rats, has been made. Because of its higher stability against in vivo deiodination and its good absorption in the intestinal tract, the 131I-phenylstearic acid has been adjudged superior to the 131I-oleic acid for studies of intestinal fat absorption.

scholarly journals Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 667 ◽  
Author(s):  
Wei Tian ◽  
Liang Yang ◽  
Di Wu ◽  
Zixin Deng ◽  
Kui Hong
Keyword(s):  
Breast Cancer ◽  
Oral Administration ◽  
Gut Microbiome ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Reproductive Organs ◽  
Marine Fungus ◽  
Log P ◽  
D Values

Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid chromatography technique coupled with tandem mass spectrometry (LC–MS/MS) method in mice, and the effect of MHO7 on mice gut microbiota at different time points was revealed by 16S rRNA sequencing. Log P/D values ranged 0.93–2.48, and the compound in SGF and SIF is stable under the concentration of 5 mM·L−1. The maximum tolerance dose (MTD) of oral administration in mice was 2400 mg·kg−1. The main pharmacokinetics parameters were as following: Cmax of 1.38 μg·mL−1, Tmax of 8 h, a half-life (t1/2) of 6.97 h, an apparent volume of mean residual time (MRT) of 8.76 h, and an area under the curve (AUC) of 10.50 h·μg·mL−1. MHO7 displayed a wide tissue distribution in mice, with most of the compound in liver (3.01 ± 1.53 μg·g−1) at 1 h, then in fat (5.20 ± 3.47 μg·g−1) at 4 h, and followed by reproductive organs with the concentrations of 23.90 ± 11.33 μg·g−1,13.69 ± 10.29 μg·g−1, 1.46 ± 1.23 μg·g−1, and 0.36 ± 0.46 μg·g−1 at 8, 12, 20 and 30 h, respectively. The most influenced genera of gut microbiome belonged to phylum Firmicutes (21 of 28), among which 18 genera originated from the order Clostridiales, class Clostridia, and families of Ruminococcaceae (11 of 18) and Lachnospiraceae (4 of 18). These results provide that MHO7 is suitable for oral administration in the treatment of breast cancer with the target organs of reproductive organs and regulation on Ruminococcaceae and Lachnospiraceae.

A Comparative Pharmacokinetic Profile of Trahydropalmatine After Oral Administration of its Monomer, Rhizoma Corydalis Alkaloid Extracts and Tong-Bi-Si-Wei-Fang to Rats

2019 ◽  
Vol 15 (4) ◽  
pp. 338-345
Author(s):  
Lijun Ni ◽  
Lu Ding ◽  
Liguo Zhang ◽  
Shaorong Luan
Keyword(s):  
Oral Administration ◽  
Panax Notoginseng ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Bone Diseases ◽  
Glycyrrhiza Uralensis ◽  
Pharmacokinetic Property ◽  
Time Curve ◽  
Concentration Time

Background: Tong-Bi-Si-Wei-Fang (TBSWF) is a candidate formula of Traditional Chinese Medicine (TCM) for treating rheumatoid bone diseases, which is composed of rhizoma corydalis alkaloids, saponins of glycyrrhiza uralensis and panax notoginseng, flavonoids of rhizoma drynariae and glycyrrhiza uralensis. </P><P> Objective: Trahydropalmatine (THP), the main active ingredient of rhizoma corydalis alkaloids, was selected to study in vivo pharmacokinetics and druggability of TBSWF. Methods: The plasma concentration-time (C-T) profiles of THP and the pharmacokinetic property parameters after oral administration of THP monomer, extract of corydalis alkaloids (ECA) and TBSWF to rats, respectively were compared by a fully-validated HPLC method. Results: Compared to the THP monomer, the THP in TBSWF is absorbed faster, resides in the plasma longer and has a similar apparent volume of distribution Vz/F (10~20 L/kg). Compared to THP monomer and THP in TBSWF, the area under the concentration-time curve AUC 0-t of THP in ECA decreases two-third; Vz/F of THP in ECA (85.02 L/kg) is significantly higher than that of THP in TBSWF(p <0.05). Unlike THP monomer and THP in ECA, double peaks are observed in the C-T profile of THP after oral administration of TBSWF. THP in TBSWF exhibits slow release to a certain degree. Conclusion: The interactions among the ingredients of TBSWF promote the adsorption and prolong the residence time of THP in vivo, and provide an explanation for the advantages of TBSWF from the point of pharmacokinetics.

Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin

2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi
Keyword(s):  
Blood Glucose ◽  
Drug Release ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Albino Rats ◽  
Sustained Delivery ◽  
In Vivo Evaluation ◽  
Hemolytic Toxicity

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections

Nano Letters ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 1124-1131
Author(s):  
Le Wang ◽  
Junchuan Yang ◽  
Sixiang Li ◽  
Qizhen Li ◽  
Shaoqin Liu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Oral Administration ◽  
In Vivo Synthesis

scholarly journals Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti
Keyword(s):  
Body Weight ◽  
Serum Levels ◽  
Northeast India ◽  
Scientific Data ◽  
Antidiabetic Activity ◽  
Histological Evaluation ◽  
Albino Rats ◽  
Antiulcer Activity ◽  
Dose Dependent

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.

Sign in / Sign up

Export Citation Format

Share Document