Effect Of Fruit And Cork Extract Of Ficus Lacor Buch Ham On α/β -Glucosidase, α -Amylase, Lipase, Glucose Absorption And Uptake

Fruits of the plant Ficus Lacor Buch. Ham. were used traditionally for treatment of diabetes mellitus. The present study was undertaken to evaluate the antidiabetic potential of the plant using in vitro approach. Effect of Ficus Lacor Buch. Ham. was evaluated using α/β -glucosidase, α-amylase and lipase enzyme inhibition assay methods. The glucose absorption in intestine was evaluated using everted rat jejunum while glucose uptake was evaluated using isolated rat hemidiaphragm. Fruit and cork ethanolic extract was prepared by using soxhlation extraction method. In vitro assay of α-glucosidase showed that IC50 value of fruit extract was 83.03 µg/ml and cork extract 88.32 µg/ml when compared with control group acarbose. β-glucosidase enzyme was inhibited by fruit and cork extract of plant with IC50 value of fruit and cork extract 132.71 µg/ml and 171.93 µg/ml. The extracts further quantify α-amylase inhibitory activity of fruit (IC50 77.93 µg/ml) and cork (IC50 111.94 µg/ml) extract. Lipase inhibitory assay indicated the effect of plant extract on lipase enzyme was not prominent when compared to orlistat. Absorption of glucose through everted rat jejunum was reduced significantly (P ˂ 0.05) when compared with standard metformin. Effect of fruit and cork extract on rat hemidiaphragm exhibited significant (P ˂ 0.05) increase in glucose uptake when compared with standard metformin. Result suggests Ficus Lacor Buch. Ham. is effective in inhibiting carbohydrate metabolizing enzymes α/β –glucosidase and α-amylase while lipase enzyme was not affected. Fruit and cork extract of the plant was found to reduce significantly glucose absorption in everted rat jejunum. The significant increase in glucose uptake was observed in isolated rat diaphragm. The result reveals that Ficus Lacor Buch. Ham. acts by inhibiting carbohydrate metabolizing enzymes, reducing glucose absorption in intestine and increasing glucose uptake in hemidiaphragm

Intestinal Transcytosis of a Protein Cargo and Nanoparticles Mediated by a Non-Toxic Form of Pseudomonas aeruginosa Exotoxin A

The low permeability of nanoparticles (NPs) across the intestinal epithelium remains a major challenge for their application of delivering macromolecular therapeutic agents via the oral route. Previous studies have demonstrated the epithelial transcytosis capacity of a non-toxic version of Pseudomonas aeruginosa exotoxin A (ntPE). Here, we show that ntPE can be used to deliver the protein cargo green fluorescent protein (GFP) or human growth hormone (hGH), as genetic fusions, across intact rat jejunum in a model where the material is administered by direct intra-luminal injection (ILI) in vivo in a transcytosis process that required less than 15 min. Next, ntPE chemically coupled onto biodegradable alginate/chitosan condensate nanoparticles (AC NPs-ntPE) were shown to transport similarly to ntPE-GFP and ntPE-hGH across rat jejunum. Finally, AC NPs-ntPE loaded with GFP as a model cargo were demonstrated to undergo a similar transcytosis process that resulted in GFP being colocalized with CD11c+ cells in the lamina propria after 30 min. Control NP preparations, not decorated with ntPE, were not observed within polarized epithelial cells or within the cells of the lamina propria. These studies demonstrate the capacity of ntPE to facilitate the transcytosis of a covalently associated protein cargo as well as a biodegradable NP that can undergo transcytosis across the intestinal epithelium to deliver a noncovalently associated protein cargo. In sum, these studies support the potential applications of ntPE to facilitate the oral delivery of macromolecular therapeutics under conditions of covalent or non-covalent association.

Boron Modulates the Barrier Function, Antioxidant Activity, and Epithelial Cell Proliferation in Rat Jejunum

We have explored the effect of boron in drinking water on the microstructure, mechanical barrier, immune barrier, antioxidant activity, and cell proliferation in rat jejunum. The treatment resulted in a significant increase in the jejunum villi height and ratio of villus height to crypt depth compared to the control group. The results showed that the jejunum villi height and ratio of villus height to crypt depth of the rats in experimental groups IV and V significantly increased compared with the control group (P < 0.05 or P < 0.01). Furthermore, boron treatment resulted in a significant increase in the number of rat jejunum goblet cells, intraepithelial lymphocyte and proliferating cell nuclear antigen positive cells as well as the concentration of secretory immunoglobulin A along with increased activity or content of total superoxide dismutase, glutathione peroxidase, and total antioxidant capacity. However, there was a decrease in expression of these markers in rats receiving the highest dosage of boron (640 mg/L). The results show that supplementing drinking water with low doses of boron could improve the microstructure of rat jejunum, enhance mucosal immunity, mechanical barrier function, and antioxidant activity, and promote cell proliferation.

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

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.