Antidiabetic lead compounds and targets for drug development

Tupas, Genevieve D.; Otero, Maria Catherine B.; Ebhohimen, Israel Ehizuelen; Egbuna, Chukwuebuka; Aslam, Maria

doi:10.1016/b978-0-12-817890-4.00008-1

Cited by 13 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibitor of these enzymes delays the digestion and absorption of dietary carbohydrates from the epithelium of the small intestine, and, thus, decreases the demand for insulin. Differently, STG acts to reduce the incretin effect in the small intestine by blocking the DPP-4 enzyme [13].…”

Section: Antidiabetic Activitymentioning

confidence: 99%

“…The present therapeutic drugs used in the management of T2DM are sulfonylureas, biguanides, SGLT2 inhibitors, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists, thiazolidinediones, amylin analogs, and insulin [13]. However, continuous use of some FDA-approved oral drugs is accompanied by side effects; for instance, acarbose (ACB) leads to abdominal or stomach pain, flatulence, diarrhea, bloating, and cramping [14].…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes increase glucose absorption and, as a result, increase the glucose level in the bloodstream [15]. Another potential therapeutic approach that lowers blood glucose concentration in T2DM is blocking the action of DPP-4, an enzyme that degrades the hormone incretin, which is secreted into the blood after a meal to stimulate insulin secretion from pancreatic β-cells and to regulate glucose production by the liver [13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antidiabetic, Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro

et al. 2022

View full text Add to dashboard Cite

The objective of this work was to investigate the antidiabetic, antiglycation, and antioxidant potentials of ethanolic extract of seeds of Brazilian Passiflora edulis fruits (PESE), a major by-product of the juice industry, and piceatannol (PIC), one of the main phytochemicals of PESE. PESE, PIC, and acarbose (ACB) exhibited IC50 for alpha-amylase, 32.1 ± 2.7, 85.4 ± 0.7, and 0.4 ± 0.1 µg/mL, respectively, and IC50 for alpha-glucosidase, 76.2 ± 1.9, 20.4 ± 7.6, and 252 ± 4.5 µg/mL, respectively. The IC50 of PESE, PIC, and sitagliptin (STG) for dipeptidyl-peptidase-4 (DPP-4) was 71.1 ± 2.6, 1137 ± 120, and 0.005 ± 0.001 µg/mL, respectively. PESE and PIC inhibited the formation of advanced glycation end-products (AGE) with IC50 of 366 ± 1.9 and 360 ± 9.1 µg/mL for the initial stage and 51.5 ± 1.4 and 67.4 ± 4.6 µg/mL for the intermediate stage of glycation, respectively. Additionally, PESE and PIC inhibited the formation of β-amyloid fibrils in vitro up to 100%. IC50 values for 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) scavenging activity of PESE and PIC were 20.4 ± 2.1, and 6.3 ± 1.3 µg/mL, respectively. IC50 values for scavenging hypochlorous acid (HOCl) were similar in PESE, PIC, and quercetin (QCT) with values of 1.7 ± 0.3, 1.2 ± 0.5, and 1.9 ± 0.3 µg/mL, respectively. PESE had no cytotoxicity to the human normal bronchial epithelial (BEAS-2B), and alpha mouse liver (AML-12) cells up to 100 and 50 µg/mL, respectively. However, 10 µg/mL of the extract was cytotoxic to non-malignant breast epithelial cells (MCF-10A). PESE and PIC were found to be capable of protecting cultured human cells from the oxidative stress caused by the carcinogen NNKOAc at 100 µM. The in vitro evidence of the inhibition of alpha-amylase, alpha-glucosidase, and DPP-4 enzymes as well as antioxidant and antiglycation activities, warrants further investigation of the antidiabetic potential of P. edulis seeds and PIC.

show abstract

Section: Antidiabetic Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antidiabetic, Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Biguanides are a class of herbal drugs [100] classified as non-sulfonylureas that act directly against insulin resistance [101]. In addition to one of the drugs in the class of statins, biguanide drugs can be used to treat intrabony defects.…”

Section: Biguanidesmentioning

confidence: 99%

From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release

Egle

Šalma

Dubņika

2021

IJMS

View full text Add to dashboard Cite

The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally.

show abstract

“…Globally, there are 537 million people living with diabetes in 2021, of which around 90% of the cases accounted for type 2 diabetes [1,2]. To date, existing drugs cannot completely cure type 2 diabetes, but they can manage glucose levels and prevent complications associated with the different organs [3,4]. There is a strong interest in the discovery and development of more effective drugs for the treatment of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

Valicherla

Katekar²,

Dadge³

et al. 2022

Molecules

View full text Add to dashboard Cite

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood–plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.

show abstract

Antidiabetic lead compounds and targets for drug development

Cited by 13 publications

References 57 publications

Antidiabetic, Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro

Antidiabetic, Antiglycation, and Antioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro

From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

Contact Info

Product

Resources

About