Ocimum gratissimum and Ocimum basilicum are plants ethnopharmacologically used to treat diabetes mellitus, a life-threatening disease that affects millions of people worldwide. In order to further understand their antidiabetic potential, which has been previously demonstrated in animal models, we aimed to investigate the acute and chronic effects of major phenolic substances from both plants on insulin secretion and gene expression in pancreatic islets isolated from NMRI mice. Insulin secretion was measured after acute (1 h) and long-term (72 h) incubation of islets with one of four cinnamic acid derivatives (caftaric, caffeic, chicoric, and rosmarinic acids) or a C-glucosylated flavonoid (vicenin-2). All substances acutely enhanced glucose-stimulated insulin secretion (GSIS) from islets at concentrations from 10 to 10 M. They also increased GSIS after chronic incubation (10 M). None of them increased insulin secretion in the presence of low glucose concentration. Furthermore, these substances markedly changed the gene expression profile of key insulin regulatory genes INS1, INS2, PDX1, INSR, IRS1, and proliferative genes as well as glucose transporter 2 (GLUT2), in treated islets. Thus, they may play an important role in diabetes treatment. This is the first report on the insulin-secretory activity of caftaric acid, rosmarinic acid, and vicenin-2.

Ovarian cancer is a lethal gynaecologic malignancy with poor diagnosis and prognosis. The long non‐coding RNA plasmacytoma variant translocation1 (PVT1) and argonaute 1 (AGO1) are associated with carcinogenesis and chemoresistance; however, the relationship between PVT1 and AGO1 and the downstream mechanisms in ovarian cancer remains poorly known. PVT1 and AGO1 expression was assessed through RT‐qPCR and Western blotting in both human tissues and cell lines. The viability and proliferation of ovarian cancer cells were determined by CCK‐8 assay and TUNEL assay in vitro and immunohistochemistry in vivo. Cell invasion and migration were investigated through transwell and wound‐healing assays. The roles and mechanisms of AGO1 on cell functions were further probed via gain‐ and loss‐of‐function analysis. We reveal that PVT1 expression was significantly increased in ovarian cancer tissues which is associated with advanced FIGO stage, lymph‐node metastasis, poor survival rate, and high expression of AGO1. PVT1 or AGO1 knockdown significantly reduced the cell viability and increased the cell apoptosis and inhibited ovarian tumour growth and proliferation. Furthermore, we discovered that PVT1 up‐regulated the expression of AGO1 and thus regulated the transforming growth factor‐β (TGF‐β) pathway to promote ovarian cancer progression through sponging miR‐148a‐3p. Additionally, the activation of ERK1/2, smad2 and smad4 is observed to be related to the PVT1/miR‐148a‐3p/AGO1/TGF‐β pathway‐induced cascades. Taken together, the present study reveals that PVT1/miR‐148a/AGO1 axis plays an important role in the progression of ovarian cancer and emphasize the potential as a target of value for ovarian cancer therapy.

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Aims Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action. Materials and Methods Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10−9‐10−5 mol/L SVG at 16.7 mmol/L glucose and (b) 10−7 mol/L SVG at 3.3‐16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10−7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10−7 mol/L SVG. Results SVG dose‐dependently increased insulin secretion from mouse islets with 10−7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10−7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10−7 mol/L) had a long‐acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene‐transcript levels of B2m and Gcgr were markedly altered. Conclusion This is the first report to demonstrate that SVG stimulates insulin secretion in a dose‐ and glucose‐dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.

Isosteviol (ISV), a diterpene molecule, is an isomer of the backbone structure of a group of substances with proven antidiabetic capabilities. The aim of this study was to investigate if ISV elicits dynamic insulin release from pancreatic islets and concomitantly is able to ameliorate gluco-, lipo-, and aminoacidotoxicity in clonal β-cell line (INS-1E) in relation to cell viability and insulin secretion. Isolated mice islets placed into perifusion chambers were perifused with 3.3 mM and 16.7 mM glucose with/without 10−7 M ISV. INS-1E cells were incubated for 72 h with either 30 mM glucose, 1 mM palmitate or 10 mM leucine with or without 10−7 M ISV. Cell viability was evaluated with a Cytotoxic Fluoro-test and insulin secretion was measured in Krebs-Ringer Buffer at 3.3 mM and 16.7 mM glucose. In the presence of 3.3 mM glucose, 10−7 M ISV did not change basal insulin secretion from perifused islets. However, at a high glucose level of 16.7 mM, 10−7 M ISV elicited a 2.5-fold increase (−ISV: 109.92 ± 18.64 ng/mL vs. +ISV: 280.15 ± 34.97 ng/mL; p < 0.01). After 72 h gluco-, lipo-, or aminoacidotoxicity in INS-1E cells, ISV treatment did not significantly affect cell viability (glucotoxicity, −ISV: 19.23 ± 0.83%, +ISV: 18.41 ± 0.90%; lipotoxicity, −ISV: 70.46 ± 3.15%, +ISV: 65.38 ± 2.81%; aminoacidotoxicity: −ISV: 8.12 ± 0.63%; +ISV: 7.75 ± 0.38%, all nonsignificant). ISV did not improve impaired insulin secretion (glucotoxicity, −ISV: 52.22 ± 2.90 ng/mL, +ISV: 47.24 ± 3.61 ng/mL; lipotoxicity, −ISV: 19.94 ± 4.10 ng/mL, +ISV: 22.12 ± 3.94 ng/mL; aminoacidotoxicity: −ISV: 32.13 ± 1.00 ng/mL; +ISV: 30.61 ± 1.54 ng/mL, all nonsignificant). In conclusion, ISV acutely stimulates insulin secretion at high but not at low glucose concentrations. However, ISV did not counteract cell viability or cell dysfunction during gluco-, lipo-, or aminoacidotoxicity in INS-1E cells.