RESUMO
The current mixed-method study uses Food Frequency Questionnaires and 24-hour dietary recalls (n = 41) to assess the food/nutrient intake; and qualitative interviews to identify local perceptions of food among 41 early postpartum women in Belgaum, India. The results show that total energy, protein, and most micronutrient intake were significantly lower than the Recommended Dietary Allowance of India (p < .05 individually); ninety percent of mothers restricted the consumption of some specific fruits, vegetables, and other foods during postpartum due to their perceptions of foods, folk medicines, and health beliefs. Culturally sensitive programs relevant to postpartum diet practices for women should be implemented.
Assuntos
Dieta , Ingestão de Energia , Feminino , Humanos , Estações do Ano , Índia , Período Pós-Parto , VerdurasRESUMO
BACKGROUND: Bombesin Receptor Subtype-3 (BRS-3, Bombesin-like receptor, BB3) is an orphan G-protein coupled receptor (GPCR). Recent studies have shown that BRS-3 played a vital role in glucose regulation, insulin secretion, and energy homeostasis. Therefore, discovering more novel exogenous ligands with diverse structures for BRS-3 will be of great importance for target validation and drug development. PURPOSE: In this study, we aim to discover new agonists of BRS-3 from our natural compound libraries, providing a new probe to study the function of BRS-3. STUDY DESIGN: Multiple cell-based assays and in vivo experiments were performed to identify the new ligand. METHODS: BRS-3 overexpression cells were coupled with FLIPR assay, homogeneous time-resolved fluorescence (HTRF) IP-ONE assay, dynamic mass redistribution (DMR) assay, ß-arrestin2 recruitment assay, and western blot to determine receptor activation and downstream signaling events. To further validate the target of BRS-3, a series of in vitro and in vivo experiences were conducted, including glucose uptake, glucose transporter type 4 (GLUT4) transportation in C2C12, and oral glucose tolerance test (OGTT) in mice. RESULTS: We discovered and identified oridonin as a novel small molecule agonist of BRS-3, with a moderate affinity (EC50 of 2.236 × 10-7 M in calcium mobilization assay), specificity, and subtype selectivity. Further in vitro and in vivo tests demonstrated that oridonin exerted beneficial effects in glucose homeostasis through activating BRS-3. CONCLUSIONS: Oridonin, as the discovered new ligand of BRS-3, provides a valuable tool compound to investigate BRS-3's function, especially for target validation in type 2 diabetes and obesity. Oridonin is promising as a lead compound in the treatment of metabolic disorders. Compared to the known agonists of BRS-3, we can take advantage of the multiple reported pharmacological activities of ODN as a natural product and assess whether these pharmacological activities are regulated by BRS-3. This may facilitate the discovery of novel functions of BRS-3.
Assuntos
Diabetes Mellitus Tipo 2 , Receptores da Bombesina , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diterpenos do Tipo Caurano , Glucose/metabolismo , Ligantes , Camundongos , Receptores da Bombesina/agonistas , Receptores da Bombesina/metabolismoRESUMO
Fifteen unreported compounds in Anemarrhena asphodeloides, iriflophene (3), hostaplantagineoside C (7), tuberoside G (8), spicatoside B (9), platycodin D (14), platycoside A (15), platycodin D2 (16), polygalacin D2 (17), platycodin D3 (18), isovitexin (20), vitexin (21), 3,4-dihydroxyallylbenzene-3-O-α-l-rhamnopyranosyl(1â6)-ß-d-glucopyranoside (22), iryptophan (24), adenosine (25), α-d-Glucose monoallyl ether (26), together with eleven known compounds (1, 2, 4â»6, 10â»13, 19 and 23), were isolated from the rhizomes of Anemarrhena asphodeloides. The chemical structures of these compounds were characterized using HRMS and NMR. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit LPS-induced NO production in N9 microglial cells. Timosaponin BIII (TBIII) and trans-hinokiresinol (t-HL) exhibited significant inhibitory effects on the NO production in a dose-dependent manner with IC50 values of 11.91 and 39.08 µM, respectively. Immunoblotting demonstrated that TBIII and t-HL suppressed NO production by inhibiting the expressions of iNOS in LPS-stimulated N9 microglial cells. Further results revealed that pretreatment of N9 microglial cells with TBIII and t-HL attenuated the LPS-induced expression tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at mRNAs and protein levels. Moreover, the activation of nuclear factor-κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were inhibited by TBIII and t-HL, respectively. Our findings indicate that the therapeutic implication of TBIII and t-HL for neurogenerative disease associated with neuroinflammation.