• Genistein
• flavonoids
• nanoformulations.
• natural compound
• ovarian cancer
• pharmaceutical efficacy

• Humans
• Genistein/pharmacology
• Genistein/administration & dosage
• Genistein/chemistry
• Genistein/therapeutic use
• Female
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/pathology
• Animals
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemistry
• Nanoparticles/chemistry

Over the past several decades, type 2 diabetes mellitus (T2DM) has been considered a global public health concern. Currently, various therapeutic modalities are available for T2DM management, including dietary modifications, moderate exercise, and use of hypoglycemic agents and lipid-lowering medications. Although the curative effect of most drugs on T2DM is significant, they also exert some adverse side effects. Biologically active substances found in natural medicines are important for T2DM treatment. Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM. This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on islet β cell function, adipose tissue inflammation, and insulin resistance. Additionally, this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.

• Type 2 diabetes
• Natural product
• β cell
• Adipose tissue inflammation
• Insulin resistance

• diabetes
• genistein
• glucose
• insulin
• review

Diabetes mellitus is a severe health problem in Mexico, and its prevalence is increasing exponentially every year. Recently, DPP-4 (dipeptidyl peptidase-4) inhibitors have become attractive oral anti-hyperglycemic agents to reduce the pathology of diabetes. Gliptin’s family, such as sitagliptin, vildagliptin, and alogliptin, are in clinical use to treat diabetes mellitus but possess side effects. Therefore, there is a specific need to look for new therapeutic scaffolds (biomolecules). Garlic bulb is widely used as a traditional remedy for the treatment of diabetes. The garlic extracts are scientifically proven to control glucose levels in patients with diabetes, despite the unknown mechanism of action. The aim of the study is to investigate the antidiabetic effects of ultrasonication assisted garlic bulb extract. To achieve this, in-vitro assays such as DPP-4 inhibitory and antioxidant activities were investigated. Further, functional group analysis using FTIR and identification of phytochemicals using mass spectrometry analysis was performed. The results showed that 70.9 µg/mL of garlic bulb extract inhibited 50% DPP-4 activity. On top of that, the garlic extract exhibited a 20% scavenging activity, equivalent to 10 µg/mL of ascorbic acid. Molecular docking simulations on identified phytochemicals using mass spectrometry revealed their potential binding at the DPP-4 druggable region, and therefore the possible DPP-4 inhibition mechanism. These results suggest that prepared garlic extract contains phytochemicals that inhibit DPP-4 and have antioxidant activity. Also, the prepared extract induces skeletal muscle cell proliferation that demonstrates the antidiabetic effect and its possible mechanism of action.

• diabetes mellitus
• dipeptidyl peptidase-4 inhibition
• garlic extract
• serine protease inhibition
• ultrasonic-assisted extraction

• Animals
• Antioxidants/therapeutic use
• Cell Culture Techniques
• Cell Proliferation/drug effects
• Diabetes Mellitus, Type 2/drug therapy
• Dipeptidyl Peptidase 4/chemistry
• Dipeptidyl Peptidase 4/metabolism
• Dipeptidyl Peptidase 4/therapeutic use
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Garlic/metabolism
• Hypoglycemic Agents/pharmacology
• Mexico
• Molecular Docking Simulation
• Muscle, Skeletal/drug effects
• Phytochemicals/therapeutic use
• Plant Extracts/pharmacology
• Rats

Purpose: We aimed to prepare two oral drug delivery systems consisting of polyoxyl 15 hydroxystearate (HS15) with pluronicF127 (F127) and HS15 with pluronicL61 (L61) to overcome the challenges of genistein’s poor oral bioavailability. This provides a good strategy for enhancing the potential value of genistein.

Methods: We designed two binary mixed micelle systems employing the organic solvent evaporation method using surfactants (HS15, L61, and F127). Formulations (GEN-F and GEN-L) were characterized by transmission electron microscopy. Drug content analysis, including entrapment efficiency (EE%), drug loading (DL%), and the cumulative amount of genistein released from the micelles, was performed using HPLC. The permeability of optimum formulation was measured in Caco-2 cell monolayers, and the oral bioavailability was evaluated in SD rats.

Results: The solutions of GEN-F and GEN-L were observed to be transparent and colorless. GEN-F had a lower EE% of 80.79±0.55% and a DL% of 1.69±0.24% compared to GEN-L, which had an EE% 83.40±1.36% and a DL% 2.26±0.18%. TEM results showed that the morphology of GEN-F and GEN-L was homogeneous and resembled a spherical shape. The dilution and storage conditions had no significant effect on particle size and EE%. Genistein demonstrated a sustained release behavior when encapsulated in micelles. Pharmacokinetics study showed that the relative oral bioavailability of GEN-F and GEN-L increased by 2.23 and 3.46 fold while also enhancing the permeability of genistein across a Caco-2 cell monolayer compared to that of raw genistein.

Conclusion: GEN-F and GEN-L as a drug delivery system provide an effective strategy for enhancing and further realizing the potential value of GEN.

• genistein
• micelles
• oral bioavailability
• pluronicF127
• pluronicL61
• polyoxyl 15 hydroxystearate

• Diabetic nephropathy
• JNK signaling pathway
• asiatic acid
• desmin
• nephrin
• podocytes

Chemotherapy has been assuring more important roles in the treatment of carcinoma. Developing new types of drugs with less adverse effects and low drug resistance has become an important researching focus. The present study aimed to investigate the anticancer effects of 5-hydroxy-4′-nitro-7-propionyloxy-genistein (HNPG) and to elucidate its underlying molecular mechanism.

The inhibitory effects of cell viability of HNPG were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flat plate clone formation method, and Transwell assay. The distribution of cell cycle was analyzed using flow cytometry (FCM) method. The morphological alteration, root-mean-squared roughness (Rq), average roughness (Ra), Young’s modulus, and adhesive force were measured by atomic force microscope (AFM) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to explore the possible molecular mechanism.

We found that HNPG had dramatic activity against Ji Endometrial cells (JEC) in vitro, inhibited the proliferation and colony formation, attenuated invasion and migration ability, and arrested cell cycle in G1 phase, all in a dose-dependent manner. Simultaneously, cell bodies shrunk, pseudopod structures retracted, Rq and Ra were reduced, and Young’s modulus and adhesive force increased, accompanied by downregulation of β-catenin, C-Myc, Cyclin D1, matrix metalloprotease 2 (MMP-2), matrix metalloprotease 7 (MMP-7), and matrix metalloprotease 9 (MMP-9).

HNPG dramatically inhibited invasion and metastasis of JEC cells in vitro. Its molecular mechanism might be related to inactivation of the wnt/β-catenin signal pathway, accumulated cells in G1/S phase, inhibited cell proliferation, improved adhesive force between cells, and reduced cell plasticity and elasticity.