seed of Coix lacryma-jobi L. var. meyuan (Romen.) Stapf
Coixol is a natural product extracted from Coix Lachryma-Jobi var. ma-yuen.IC50 value:Target:In vitro: Confluent NCI-H292 cells were pretreated with oleic acid, linoleic acid, glyceryl trilinoleate, beta-stigmasterol or coixol for 30 min and then stimulated with PMA (phorbol 12-myristate 13-acetate), EGF (epidermal growth factor) or TNF-α (tumor necrosis factor-α) for 24 h. Coixol inhibited the expression of MUC5AC mucin gene and production of MUC5AC mucin protein, induced by EGF or TNF-α from NCI-H292 cells; Coixol decreased PMA-induced MUC5AC mucin secretion from NCI-H292 cells . βTC-6 cells were incubated in 2 mM and 20 mM glucose in thepresence of coixol (200 μM) for 60 min at 37°C in Krebs-RingerBicarbonate buffer. Decreased insulin staining was observed by coixol at 20 mM glucose (bottom) suggest that coixol stimulated insulin secretion at high glucose concentration .In vivo:
DMSO : ≥ 30 mg/mL (181.65 mM);
292.97°C (rough estimate)
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Recently, we reported the role of coixol (6-methoxy-2(3H)-benzoxazolone), an alkaloid from Scoparia dulcis, in glucose-dependent insulin secretion; however, its insulin secretory mechanism(s) remained unknown. Here, we explored the insulinotropic mechanism(s) of coixol in vitro and in vivo. Mice islets were batch incubated, perifused with coixol in the presence of agonists/antagonists, and insulin secretion was measured by ELISA. Intracellular cAMP levels were measured using enzyme immunoassay. K+- and Ca2+-currents were recorded in MIN6 cells using whole-cell patch-clamp technique. The in vivo glucose tolerance and the insulinogenic index were evaluated in diabetic rats treated with coixol at 25 and 50 mg/kg, respectively. Coixol, unlike sulfonylurea, enhanced insulin secretion in batch incubated and perifused islets at high glucose, with no effect at basal glucose concentrations. Coixol showed no pronounced effect on the inward rectifying K+- and Ca2+-currents in whole-cell patch recordings. Moreover, coixol-induced insulin secretion was further amplified in the depolarized islets. Coixol showed an additive effect with forskolin (10 μM)-induced cAMP level, and in insulin secretion; however, no additive effect was observed with isobutylmethylxanthine (IBMX, 100 μM)-induced cAMP level, nor in insulin secretion. The PKA inhibitor H-89 (50 μM), and Epac2 inhibitor MAY0132 (50 μM) significantly inhibited the coixol-induced insulin secretion (P < 0.01). Furthermore, insulin secretory kinetics revealed that coixol potentiates insulin secretion in both early and late phases of insulin secretion. In diabetic animals, coixol showed significant improvement in glucose tolerance and on fasting blood glucose levels. These data suggest that coixol amplifies glucose-stimulated insulin secretion by cAMP-mediated signaling pathways.
Copyright © 2019 Elsevier B.V. All rights reserved.
Coixol; Epac2; Insulin secretion; Intracellular cAMP; Mice islets; Protein kinase A
Coixol amplifies glucose-stimulated insulin secretion via cAMP mediated signaling pathway.
Hameed A1, Hafizur RM2, Khan MI3, Jawed A3, Wang H4, Zhao M4, Matsunaga K4, Izumi T4, Siddiqui S3, Khan F3, Adhikari A5, Sharma KR6.
2019 Sep 5
By changing soil properties, plants can modify their growth environment. Although the soil microbiota is known to play a key role in the resulting plant-soil feedbacks, the proximal mechanisms underlying this phenomenon remain unknown. We found that benzoxazinoids, a class of defensive secondary metabolites that are released by roots of cereals such as wheat and maize, alter root-associated fungal and bacterial communities, decrease plant growth, increase jasmonate signaling and plant defenses, and suppress herbivore performance in the next plant generation. Complementation experiments demonstrate that the benzoxazinoid breakdown product 6-methoxy-benzoxazolin-2-one (MBOA), which accumulates in the soil during the conditioning phase, is both sufficient and necessary to trigger the observed phenotypic changes. Sterilization, fungal and bacterial profiling and complementation experiments reveal that MBOA acts indirectly by altering root-associated microbiota. Our results reveal a mechanism by which plants determine the composition of rhizosphere microbiota, plant performance and plant-herbivore interactions of the next generation.
Root exudate metabolites drive plant-soil feedbacks on growth and defense by shaping the rhizosphere microbiota.
Hu L1, Robert CAM1, Cadot S2, Zhang X1, Ye M1, Li B1, Manzo D1, Chervet N3, Steinger T3, van der Heijden MGA2,4,5, Schlaeppi K6,7, Erb M8.
2018 Jul 16
Plant secondary metabolite 6-methoxybenzoxazolinone (6-MBOA) has been suggested to stimulate animal reproduction. 6-MBOA is detected in Leymus chinensis, a main diet of Brandt’s vole (Lasiopodomys brandtii). We have previously reported a stimulatory effect of 6-MBOA on reproduction of male Brandt’s voles under a short-day photoperiod. The goal of this study was to investigate the effect of 6-MBOA on reproductive physiology of male Brandt’s voles under a long-day photoperiod and examine if 6-MBOA under this photoperiodic regime altered the reproductive status of male Brandt’s voles differently than the short-day photoperiod. Under the long-day photoperiod, a high dose of 6-MBOA decreased KiSS-1 mRNA in the arcuate nucleus (ARC), and we also saw a decrease in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T). Steroidogenic acute regulatory protein (StAR) and cytochrome P45011a1 (CYP11a1) in the testes, and relative testis weight also decreased with 6-MBOA administration. Compared to the short-day photoperiod, animals under the long-day photoperiod exhibited increased body weight as well as all other reproductive parameters. Our results showed that 6-MBOA inhibited the reproduction of male Brandt’s vole under a long-day photoperiod, a stark contrast from its stimulatory effects under a short-day photoperiod. The paradoxical effects of 6-MBOA suggest it may act as a partial agonist of melatonin. These results provide insight into the complex interactions between environmental factors such as photoperiod and diet in the control of Brandt’s vole reproduction.
Copyright © 2017 Elsevier Inc. All rights reserved.
6-MBOA; Brandt’s vole; KiSS-1/GPR54 system; Photoperiod; Reproductive activity
Effect of photoperiod and 6-methoxybenzoxazolinone (6-MBOA) on the reproduction of male Brandt's voles (Lasiopodomys brandtii).
Dai X1, Shi J2, Han M2, Wang AQ2, Wei WH1, Yang SM3.
2017 May 15;