Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet

Abstract: AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg)..

Second T = 3/2 state in 9^9B and the isobaric multiplet mass equation

Recent high-precision mass measurements and shell model calculations~[Phys. Rev. Lett. {\bf 108}, 212501 (2012)] have challenged a longstanding explanation for the requirement of a cubic isobaric multiplet mass equation for the lowest $A = 9$ isospin quartet. The conclusions relied upon the choice of the excitation energy for the second $T = 3/2$ state in $^9$B, which had two conflicting measurements prior to this work. We remeasured the energy of the state using the $^9{\rm Be}(^3{\rm He},t)$ reaction and significantly disagree with the most recent measurement. Our result supports the contention that continuum coupling in the most proton-rich member of the quartet is not the predominant reason for the large cubic term required for $A = 9$ nuclei

Administration of S-allyl cysteine to neonatal rats modulates inflammatory biomarkers in high-fructose-fed rats in adulthood

PURPOSE : To investigate the potential prophylactic effect of S-allyl cysteine (SAC), found in garlic (Allium sativum), against the development of apro-inflammatory status induced by diet in neonatal rats later on in adulthood. METHODS : Suckling Wistar rat pups (4-day-old; male = 21 and female = 21) were randomly allocated to either of 3 groups and orally gavaged daily with the following treatments from postnatal day (PND) 6 – 20: group 1 (control) - 10 mL/kg distilled water; group 2 - 10 mL/kg of 20 % w/v fructose solution (FS) and group 3 - 10 mL/kg FS + SAC. The rat pups were weaned on PND 21, and given ad libitum access to standard rat chow and plain drinking up to PND 115. The rats were euthanized on PND 116 and plasma was collected for the determination of interleukins (IL-1β, IL-4, IL-5, IL-10), vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)] using Bio-Plex Pro magnetic beadbased assays on Bio-Plex platform. RESULTS : Oral administration of FS during suckling increased significantly (p < 0.05) plasma concentrations of IL-5, MCP-1 and VEGF in adult male rats, and plasma MCP-1 in adult female rats. Neonatal oral administration of SAC prevented FS-programmed increase in pro-inflammatory cytokines (p < 0.05) later on in adulthood. CONCLUSION : Oral administration of SAC during the neonatal period protected against FS-induced proinflammatory status and thus, could possibly be exploited as a prophylactic or intervention agent against a pro-inflammatory status induced by a high fructose diet.https://www.tjpr.org/homeam2021Physiolog

Modulatory effects of oleanolic acid on cardiac anti-oxidant status and inflammatory response in high fructose-fed neonatal Sprague-Dawley rats

This present study investigated the antioxidant and inflammatory properties of oleanolic acid (OA) on neonatal rats administered with high fructose diet (HFD). Neonatal rats (24) were assigned at random to four (4) groups namely: Group A (control) which had distilled water only; Group B was administered with OA only; Group C was administered with HFD; Group D received HFD and OA. Animals were administered orally using orogastric gavage at a dosage of 10 ml/kg for 7 days (postnatal day 7-14. The antioxidant status of the hearts such as TEAC, Ferric Reducing Anti-oxidant Power, FRAP, Trolox Equivalence Antioxidant Capacity and oxidative stress biomarkers (MDA, Malondialdehyde and GSH, Glutathione) were evaluated using standard procedures. The levels of inflammatory cytokines in the hearts were determined using magnetic bead-based assays procedure. The TEAC values were significantly decreased in HFD+OA treatment (p < 0.05) in comparison with HFD group. Glutathione concentration in the HFD group had significant increase (p < 0.05) following treatment with oleanolic acid. FRAP values and MDA level were significantly (p < 0.01) elevated post exposure to HFD and treatment with oleanolic acid insignificantly decreased MDA level when compared with HFD group. The pro-inflammatory cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-a and MCP-1) were significantly (p < 0.05) increased HFD group when compared to the control. Oleanolic acid administration significantly reduced inflammation in postexposure to HFD. Neonatal intake of oleanolic acid may help to prevent inflammation and oxidative damage in the progression of cardiovascular related diseases.https://www.tjnpr.orgam2023Physiolog

Isospin mixing and the cubic isobaric multiplet mass equation in the lowest <i>T</i>=2, <i>A</i>=32 quintet

The isobaric multiplet mass equation (IMME) is known to break down in the first T = 2, A = 32 isospin quintet. In this work we combine high-resolution experimental data with state-of-the-art shell-model calculations to investigate isospin mixing as a possible cause for this violation. The experimental data are used to validate isospin-mixing matrix elements calculated with newly developed shell-model Hamiltonians. Our analysis shows that isospin mixing with nonanalog T = 1 states contributes to the IMME breakdown, making the requirement of an anomalous cubic term inevitable for the multiplet

The Effect of Temperature on Pressurised Hot Water Extraction of Pharmacologically Important Metabolites as Analysed by UPLC-qTOF-MS and PCA

Metabolite extraction methods have been shown to be a critical consideration for pharmacometabolomics studies and, as such, optimization and development of new extraction methods are crucial. In the current study, an organic solvent-free method, namely, pressurised hot water extraction (PHWE), was used to extract pharmacologically important metabolites from dried Moringa oleifera leaves. Here, the temperature of the extraction solvent (pure water) was altered while keeping other factors constant using a homemade PHWE system. Samples extracted at different temperatures (50, 100, and 150°C) were assayed for antioxidant activities and the effect of the temperature on the extraction process was evaluated. The samples were further analysed by mass spectrometry to elucidate their metabolite compositions. Principal component analysis (PCA) evaluation of the UPLC-MS data showed distinctive differential metabolite patterns. Here, temperature changes during PHWE were shown to affect the levels of metabolites with known pharmacological activities, such as chlorogenic acids and flavonoids. Our overall findings suggest that, if not well optimised, the extraction temperature could compromise the “pharmacological potency” of the extracts. The use of MS in combination with PCA was furthermore shown to be an excellent approach to evaluate the quality and content of pharmacologically important extracts

Histone deacetylase modulators provided by Mother Nature

Protein acetylation status results from a balance between histone acetyltransferase and histone deacetylase (HDAC) activities. Alteration of this balance leads to a disruption of cellular integrity and participates in the development of numerous diseases, including cancer. Therefore, modulation of these activities appears to be a promising approach for anticancer therapy. Histone deacetylase inhibitors (HDACi) are epigenetically active drugs that induce the hyperacetylation of lysine residues within histone and non-histone proteins, thus affecting gene expression and cellular processes such as protein–protein interactions, protein stability, DNA binding and protein sub-cellular localization. Therefore, HDACi are promising anti-tumor agents as they may affect the cell cycle, inhibit proliferation, stimulate differentiation and induce apoptotic cell death. Over the last 30 years, numerous synthetic and natural products, including a broad range of dietary compounds, have been identified as HDACi. This review focuses on molecules from natural origins modulating HDAC activities and presenting promising anticancer activities