Preliminary Phytochemical Screening, In Vitro Antidiabetic, Antioxidant Activities, and Toxicity of Leaf Extracts of Psychotria malayana Jack

Psychotria malayana Jack belongs to the Rubiacea and is widespread in Southeast Asian countries. It is traditionally used to treat diabetes. Despite its potential medicinal use, scientific proof of this pharmacological action and the toxic effect of this plant are still lacking. Hence, this study aimed to investigate the in vitro antidiabetic and antioxidant activities, toxicity, and preliminary phytochemical screening of P. malayana leaf extracts by gas chromatography-mass spectrometry (GC-MS) after derivatization. The antidiabetic activities of different extracts of this plant were investigated through alpha-glucosidase inhibitory (AGI) and 2-NBDG glucose uptake using 3T3-L1 cell line assays, while the antioxidant activity was evaluated using DPPH and FRAP assays. Its toxicological effect was investigated using the zebrafish embryo/larvae (Danio rerio) model. The mortality, hatchability, tail-detachment, yolk size, eye size, beat per minute (BPM), and body length were taken into account to observe the teratogenicity in all zebrafish embryos exposed to methanol extract. The LC50 was determined using probit analysis. The methanol extract showed the AGI activity (IC50 = 2.71 ± 0.11 μg/mL), insulin-sensitizing activity (at a concentration of 5 µg/mL), and potent antioxidant activities (IC50 = 10.85 μg/mL and 72.53 mg AAE/g for DPPH and FRAP activity, respectively). Similarly, the water extract exhibited AGI activity (IC50 = 6.75 μg/mL), insulin-sensitizing activity at the concentration of 10 μg/mL, and antioxidant activities (IC50 = 27.12 and 33.71 μg/mL for DPPH and FRAP activity, respectively). The methanol and water extracts exhibited the LC50 value higher than their therapeutic concentration, i.e., 37.50 and 252.45 µg/mL, respectively. These results indicate that both water and methanol extracts are safe and potentially an antidiabetic agent, but the former is preferable since its therapeutic index (LC50/therapeutic concentration) is much higher than for methanol extracts. Analysis using GC-MS on derivatized methanol and water extracts of P. malayana leaves detected partial information on some constituents including palmitic acid, 1,3,5-benzenetriol, 1-monopalmitin, beta-tocopherol, 24-epicampesterol, alpha-tocopherol, and stigmast-5-ene, that could be a potential target to further investigate the antidiabetic properties of the plant. Nevertheless, isolation and identification of the bioactive compounds are required to confirm their antidiabetic activity and toxicity.

Cyclin-Dependent Kinase 5 Inhibitor Butyrolactone I Elicits a Partial Agonist Activity of Peroxisome Proliferator-Activated Receptor γ

Adiponectin is an adipocyte-derived cytokine having an insulin-sensitizing activity. During the phenotypic screening of secondary metabolites derived from the marine fungus Aspergillus terreus, a poly cyclin-dependent kinase (CDK) inhibitor butyrolactone I affecting CDK1 and CDK5 was discovered as a potent adiponectin production-enhancing compound in the adipogenesis model of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). CDK5 inhibitors exhibit insulin-sensitizing activities by suppressing the phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ). However, the adiponectin production-enhancing activities of butyrolactone I have not been correlated with the potency of CDK5 inhibitor activities. In a target identification study, butyrolactone I was found to directly bind to PPARγ. In the crystal structure of the human PPARγ, the ligand-binding domain (LBD) in complex with butyrolactone I interacted with the amino acid residues located in the hydrophobic binding pockets of the PPARγ LBD, which is a typical binding mode of the PPARγ partial agonists. Therefore, the adiponectin production-enhancing effect of butyrolactone I was mediated by its polypharmacological dual modulator activities as both a CDK5 inhibitor and a PPARγ partial agonist.

COMPARISON OF THE EFFECT OF PTEROCARPUS MARSUPIUM WITH PIOGLITAZONE IN DEXAMETHASONE-INDUCED INSULIN RESISTANCE

<p>ABSTRACT<br />Objective: This study was undertaken to evaluate the preventive effect of heartwood of P. marsupium in dexamethasone-induced hyperinsulinemia<br />and hyperglycemia and compare it with that of pioglitazone.<br />Methods: Male albino wistar rats were divided into five groups (n=6). Plain control group received gum acacia (2%) orally from d 1 to d 12. Dexa<br />control group received gum acacia (2%) orally for d 1 to d 12 and Dexa (8 mg/kg) intraperitoneal (i.p.) from d 7 to d 12, during the study period.<br />Two test groups received ethanolic extract of Pterocarpus marsupium heartwood (PME) (1 and 2 g/kg/) per oral (PO), and standard control group<br />received pioglitazone (60 mg/kg/PO) from d 1 to d 12. During the 12-d study period, the two test groups and standard control group received Dexa<br />(8 mg/kg/i.p.) from d 7 to d 12. On last day of the study, the blood samples were collected by retro-orbital sinus punctureand used for estimation of<br />serum insulin and glucose levels. Homeostatic Model Assessment (HOMA) method was employed to calculate the degree of insulin resistance(IR).<br />Results were analyzed by using one-way analysis of variance followed by Scheffe’s multiple comparison test (p&lt;0.05).<br />Results: Treatment with ethanolic extract of P. marsupium and pioglitazone significantly (p&lt;0.05) reduced the elevated insulin and glucose levels as<br />well as HOMA-IR and HOMA-IS values in dexa treated animals.<br />Conclusion: Ethanolic extract of P. marsupium heartwood effectively countered dexamethasone-induced hyperinsulinemia and hyperglycemia.<br />Insulin-sensitizing activity of P. marsupium heartwood was found to be more effective than pioglitazone.<br />Keywords: Pterocarpus marsupium, Insulin resistance, Hyperinsulinemia, Hyperglycemia.</p>

In VivoAnti-Diabetic Activity of the Ethanolic Crude Extract ofSorbus decoraC.K.Schneid. (Rosacea): A Medicinal Plant Used by Canadian James Bay Cree Nations to Treat Symptoms Related to Diabetes

A number of potential anti-diabetic plants were identified through an ethnobotanical survey of the traditional pharmacopeia of the Cree of Eeyou Istchee (CEI—Northeastern Canada) used against symptoms of diabetes and their biological activity assessed byin vitrobioassays. Among these,Sorbus decoraC.K.Schneid. (Rosacea) ranked highly and increased the transport of glucose in skeletal muscle cells in culture. The present study thus aimed at confirming the antidiabetic potential ofS. decorainin vivomodels of insulin resistance and diabetes, notably the streptozotocin Type 1 diabetic rat (STZ), the geneticKK-AyType 2 diabetic mouse and the rat rendered insulin resistant with 10% glucose water consumption for 6 weeks.Sorbus decoraethanolic crude extract (SDEE) was administered orally (200 mg kg-1) and compared to metformin (150 or 500 mg kg-1). The intragastric (i.g.) gavage of SDEE transiently decreased glycemia in STZ rats in a bi-phasic manner but the effect was cumulative over several days. InKK-Aymice, SDEE incorporated in food (0.12%) decreased glycemia by 15% within 1 week as compared to vehicle controls. In pre-diabetic insulin-resistant rats, SDEE fed daily by i.g. gavage for 2 weeks significantly decreased the slight hyperglycemia and hyperinsulinemia, without affecting sugar water intake. Using the HOMA insulin resistance parameter, the effect of SDEE was equivalent to that of metformin. In conclusion, the ethanolic crude extract ofS. decorademonstrates both anti-hyperglycemic and insulin-sensitizing activityin vivo, thereby confirming anti-diabetic potential and validating CEI traditional medicine.