Enhanced oral bioavailability of linagliptin by the influence of gallic acid and ellagic acid in male Wistar albino rats: involvement of p-glycoprotein inhibition

2019 ◽  
Vol 34 (2) ◽  
Author(s):  
Munthaj Shaik ◽  
Swaroopa Rani Vanapatla
Keyword(s):  
Serum Concentration ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Oral Bioavailability ◽  
Intestinal Transport ◽  
Diabetic Rats ◽  
Time Profile ◽  
Albino Rats ◽  
P Glycoprotein ◽  
Oral Pharmacokinetics

Abstract Background Linagliptin is an antidiabetic drug used for the treatment of type-2 diabetes. The oral bioavailability of linagliptin is low (29.5%) due to its first pass metabolism in the intestine and liver. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. Gallic acid and ellagic acid have been reported to inhibit p-glycoprotein (p-gp) and enhance the bioavailability of p-gp substrate drugs. Hence, the purpose of the study was to evaluate the effect of gallic acid and ellagic acid on intestinal transport and bioavailability of linagliptin, a p-gp substrate in diabetic rats. Methods The intestinal transport of linagliptin was assessed by conducting an in situ single-pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study in diabetic rats. Results After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of linagliptin was observed at the ileum part of the rat intestine. A significant improvement in the peak serum concentration (Cmax) and area under the serum concentration time profile (AUC), AUMC, AUCtotal and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Conclusions This study demonstrates that gallic acid and ellagic acids increase the bioavailability of oral linagliptin in rats due to the inhibition of p-gp. These animal data need to be confirmed in a clinical setting to determine whether linagliptin dosing should be adjusted when given concomitantly with these phytochemicals or gallic acid/ellagic acid-containing dietary supplements.

Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition

2016 ◽  
Vol 31 (4) ◽  
Author(s):  
Bhargavi Latha Athukuri ◽  
Prasad Neerati
Keyword(s):  
Drug Interactions ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Intestinal Transport ◽  
Herbal Drug ◽  
Male Wistar Rats ◽  
Mixed Function Oxidase System

Abstract Background: Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity Methods: The intestinal transport of metoprolol was assessed by conducting an Results: After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (C Conclusions: Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

scholarly journals Repercussion of piperine on pharmacokinetics parameters of eletriptan in albino rats: Involvement of CYP3A and P-GP inhibition

2021 ◽  
Vol 12 (3) ◽  
pp. 2115-2122
Author(s):  
Hematheerthani N ◽  
Siva Reddy CH ◽  
Prameela Rani A ◽  
Suresh Kumar P
Keyword(s):  
Plasma Concentration ◽  
Drug Metabolism ◽  
Oral Bioavailability ◽  
Volume Of Distribution ◽  
Oral Route ◽  
Severe Headache ◽  
Albino Rats ◽  
Time Points ◽  
P Glycoprotein ◽  
Cytochrome P 450

Eletriptan is at the type of triptan medication suggested for the management of episodes of severe headache with or without aura. Piperine (1-piperoylpiperidine) is a pure alkaloid as well as the basic tanginess material from the pipli and peppercorn. There are signs that piperine inhibits Cytochrome P-450 enzymes and P-glycoprotein, rather than arouses, drug metabolism generally, thus increasing the bioavailability and effect of several medications. The analysis was undertaken to assess the results of Piperine on the pharmacokinetics of Eletriptan. Samples of blood were taken at different time points for example 0 (predose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 12, 24 hours post-treatment. The plasma concentration of Eletriptan was estimated with the HPLC procedure.  In our study Cmax, Tmax, AUC0-24 , AUC0-8, AUC%, AUMC0-24, AUMC0-8, t1/2, MRT0-24, MRT0-8 and Volume of distribution were increased by approximately 51.76%, 7.55%, 72.93%, 84.42%, 42.72%, 93.56%, 128.82%, 19.97%, 11.74%, 23.96% and 3% respectively, where as clearance decreased by 42.10% when eletriptan co-administered with piperine. In summary, the results obtained herein imply that Piperine is improving the bioavailability of Eletriptan by strengthening the exposure (AUC) of their Eletriptan when concomitantly administered by the oral route. The Piperine improved the oral bioavailability of eletriptan by inhibiting CYP3A and P-GP in rats. This observation indicates the possibility that the combo of piperine along with other CYP3A and P-GP double substrates can also enhance bioavailability.

scholarly journals Repercussion of piperine on pharmacokinetics parameters of eletriptan in albino rats: Involvement of CYP3A and P-GP inhibition

2020 ◽  
Vol 11 (4) ◽  
pp. 8079-8086
Author(s):  
Hematheerthani N ◽  
Siva Reddy CH ◽  
Prameela Rani A ◽  
Suresh Kumar P
Keyword(s):  
Plasma Concentration ◽  
Drug Metabolism ◽  
Oral Bioavailability ◽  
Volume Of Distribution ◽  
Oral Route ◽  
Severe Headache ◽  
Albino Rats ◽  
Time Points ◽  
P Glycoprotein ◽  
Cytochrome P 450

Eletriptan is at the type of triptan medication suggested for the management of episodes of severe headache with or without aura. Piperine (1-piperoylpiperidine) is a pure alkaloid as well as the basic tanginess material from the pipli and peppercorn. There are signs that piperine inhibits Cytochrome P-450 enzymes and P-glycoprotein, rather than arouses, drug metabolism generally, thus increasing the bioavailability and effect of several medications. The analysis was undertaken to assess the results of Piperine on the pharmacokinetics of Eletriptan. Samples of blood were taken at different time points for example 0 (predose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 12, 24 hours post-treatment. The plasma concentration of Eletriptan was estimated with the HPLC procedure.  In our study Cmax, Tmax, AUC0-24 , AUC0-8, AUC%, AUMC0-24, AUMC0-8, t1/2, MRT0-24, MRT0-8 and Volume of distribution were increased by approximately 51.76%, 7.55%, 72.93%, 84.42%, 42.72%, 93.56%, 128.82%, 19.97%, 11.74%, 23.96% and 3% respectively, where as clearance decreased by 42.10% when eletriptan co-administered with piperine. In summary, the results obtained herein imply that Piperine is improving the bioavailability of Eletriptan by strengthening the exposure (AUC) of their Eletriptan when concomitantly administered by the oral route. The Piperine improved the oral bioavailability of eletriptan by inhibiting CYP3A and P-GP in rats. This observation indicates the possibility that the combo of piperine along with other CYP3A and P-GP double substrates can also enhance bioavailability.

scholarly journals Influence of Toad Parotid Gland Secretion from Indian Toad (Bufo melanostictus) in Diabetic Rats: An Experimental Evidence of P-Glycoprotein Inhibition

2020 ◽  
pp. 125-135
Author(s):  
Naveen Kumar Madugula ◽  
Prasad Neerati
Keyword(s):  
Parotid Gland ◽  
Inhibitory Activity ◽  
Oral Bioavailability ◽  
Multiple Dose ◽  
Diabetic Rats ◽  
Rat Jejunum ◽  
Bufo Melanostictus ◽  
Toxic Dose ◽  
P Glycoprotein ◽  
New Compounds

The study was conducted to improve the oral bioavailability of glyburide (GLY) with Indian Toad Parotid Gland Secretions (TPGS). P-glycoprotein is an efflux transporter cellular protein and effluxes xenobiotics and drugs to the outside of cells lead to decreased concentration of drugs at the target site. P-gp inhibitors essentially increase the levels and there is a need for new P-gp inhibitors to develop for the improvement of the oral bioavailability of P-gp substrate drugs because the existing inhibitors have serious side effects. This study was aimed to describe the P-gp inhibitory action from TPGS, Bufo melanostictus, in diabetic rats by using glyburide as p-gp substrate. Acute toxicity studies showed 300 mg/kg as toxic dose and 50 mg/kg was selected as study dose according to OECD 423. LC-HRMS study conducted to identify the new compounds. Apparent permeability (Papp) was estimated by non-everted sac method (In Vitro) with rat jejunum and ileum to confirm the P-gp inhibitory activity of TPGS by using fexofenadine (FEX) as P-gp substrate. In in-vivo protocol rats grouped into 4 groups (n=6), the first one is normal, second diabetic, third GLY 30 mg/kg, and fourth group GLY+ TPGS, 50 mg/kg for the single and multiple-dose treatment study. The spectrometric analysis revealed the new compounds, and TPGS Papp (X10-6 cm/s) in rat jejunum and ileum was significantly increased from 2.0±0.1 to 6.4±0.3 and 1.2±0.3 to 3.0±0.3 respectively. Blood glucose concentration in rats more than 250 mg/dl were considered as diabetic and in single, multiple-dose interaction studies (SDI, MDI) the concentrations decreased from 140.0±2.0 and 122.0±2.2 µg/dl respectively. The pharmacokinetic parameters like Cmax, Cl and in SDI, MDI and significant increase of C max and AUC t and decrease of Cl was observed. The above results conclude that TPGS had the potential P-gp inhibitory activity and improved the oral bioavailability of GLY significantly. Subsequent experimentation is warranted to chemically characterize the compounds from TPGS as potential new P-gp inhibitors.

Phytochemical Investigation and Antimutagenic Potential of Ethanolic Extracts of Emblica officinalis, Terminalia chebula and Terminalia bellirica

2020 ◽  
Vol 10 (4) ◽  
pp. 488-494 ◽  
Author(s):  
Venugopal Singamaneni ◽  
Sudheer Kumar Dokuparthi ◽  
Nilanjana Banerjee ◽  
Ashish Kumar ◽  
Tulika Chakrabarti
Keyword(s):  
Ethyl Acetate ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Antimutagenic Activity ◽  
Dependent Manner ◽  
Terminalia Chebula ◽  
Emblica Officinalis ◽  
Dried Fruits ◽  
Terminalia Bellerica ◽  
The Family

Background: Emblica officinalis Gaertn. which belongs to the family Euphorbiaceae, Terminalia chebula Retz. and Terminalia bellerica Roxb. belong to the family Combretaceae. These are well known medicinal plants with phytochemical reservoir of great medicinal values and possess a vast ethnomedical history. Objective: The aim of the present study is to isolation of major compounds and to evaluate antimutagenic potential of the ethanol extracts of these plants. Methods: The dried fruits of E. officinalis, T. bellirica and T. chebula were powdered and extracted with 95% ethanol. The ethyl acetate portions were chromatographed over silica gel to isolate major compounds. Antimutagenic activity was determined by Ames test using TA98 and TA100 strains of Salmonella typhimurium. Results: Two major known compounds, gallic acid and ellagic acid were isolated from the dried fruits of Emblica officinalis, Terminalia chebula and T. bellirica. All the three extracts counteracted the mutagenicity induced by different genotoxic compounds in a dose dependent manner. Conclusion: This study showed that ethyl acetate portion of three extracts contain two major compounds, gallic acid and ellagic acid which might be responsible for potent antimutagenic activity of these extracts.

Evaluation of Anti-diabetic and Anti-hyperlipidemic Activity of Isolated Bioactive Compounds of Leaves of Annona reticulata Linn.

2020 ◽  
Vol 10 ◽  
Author(s):  
Kalyani Pathak ◽  
Aparoop Das ◽  
Anshul Shakya ◽  
Riya Saikia ◽  
Himangshu Sarma
Keyword(s):  
Spectral Analysis ◽  
Gallic Acid ◽  
Liver Enzymes ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Traditional Use ◽  
Per Oral ◽  
Diabetes And Obesity ◽  
Annona Reticulata

Background: The leaves of Annona reticulata Linn. have been traditionally used by the tribes of Assam as a source of medicine to mitigate a range of health ailments including diabetes and obesity. Objectives: The current study aimed to evaluate the anti-diabetic and anti-hyperlipidemic potential of bioactive fractions isolated from the methanolic extract of Annona reticulata Linn. leaves using Nicotinamide + Streptozotocin (60 mg/kg, i.p.) induced diabetic rats. Methods: The partially purified bioactive fractions, namely F1, F2, F3 and F4 were administered to diabetic rats with the dose of 200 mg/kg, per oral (p.o.) and the effect of the fractions on serum glucose were studied up to 21 days. The potent fractions were further subjected for spectral analysis for identification of the isolated active compounds. Results: The in-vivo anti-diabetic activity of the isolated fractions F2 and F3 were found significant controlling blood glucose level, alike glibenclamide. Interestingly, F2 and F3 treated animals were found significant in restoring the lipid and liver enzymes profile in streptozotocin challenge rats. Further, spectral analysis revealed that F2 and F3 were comprises Quercetin and Gallic acid, respectively. Conclusion: Outcome of finding demonstrate the anti-diabetic and anti-hyperlipidemic potential of the isolates/fractions of A. reticulata, which were found enriched in polyphenolics including Quercetin and Gallic acid; and provides logistic behind the traditional use of the A. reticulata against Diabetes and obesity.

Hepato-renal protective effects of gallic acid and p-coumaric acid in nicotinamide/streptozotocin-induced diabetic rats

2016 ◽  
Vol 5 (06) ◽  
pp. 4641 ◽  
Author(s):  
Adel Abdel Moneim* ◽  
Sanaa M. Abd El-Twab ◽  
Mohamed B. Ashour ◽  
Ahmed I. Yousef
Keyword(s):  
Body Weight ◽  
Gallic Acid ◽  
Protein Profile ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Hypoglycemic Agents ◽  
Protective Effects ◽  
Coumaric Acid ◽  
Experimental Type

The goal of diabetes treatment is primarily to save life and alleviate symptoms and secondary to prevent long-term diabetic complications resulting from hyperglycemia. Thus, our present investigation was designed to evaluate the hepato-renal protective effects of gallic acid and p-coumaric acid in nicotinamide/streptozotocin (NA/STZ)-induced diabetic rats. Experimental type 2 diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (65 mg/kg b.wt.), after 15 min of i.p. injection of NA (120 mg/kg b.wt.). Gallic acid and p-coumaric acid were orally administered to diabetic rats at a dose of 20, 40 mg/kg b.wt./day, respectively, for 6 weeks. Body weight, serum glucose, protein profile, liver function enzymes and kidney function indicators was assayed. Treatment with either gallic acid or p-coumaric acid significantly ameliorated the elevated levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and uric acid. Both compounds were also found to restore total protein, albumin, and globulin as well as body weight of diabetic rats to near normal values. It can conclude that both gallic acid and p-coumaric acid have potent hypoglycemic and hepato-renal protective effects in diabetic rats. Therefore, our results suggest promising hypoglycemic agents that can attenuate the progression of diabetic hepatopathy and nephropathy.

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