Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently.

BACKGROUND: Inflammation is an important factor contributing to obesity-induced metabolic disorders. Different investigations confirm that local inflammation in adipose issues is the primary reason for such disorder, resulting in low-grade systemic inflammation. Anti-inflammatory, antioxidant, and epigenetic modification are among the varied properties of Quercetin (QCT) as a natural flavonoid. OBJECTIVE: The precise molecular mechanism followed by QCT to alleviate inflammation has been unclear. This study explores whether the anti-inflammatory effects of QCT in 3T3-L1 differentiated adipocytes may rely on SIRT-1. METHODS: The authors isolated 3T3-L1 pre-adipocyte cells and exposed them to varying concentrations of QCT, lipopolysaccharide (LPS), and a selective inhibitor of silent mating type information regulation 2 homolog 1 (SIRT-1) called EX-527. After determining the optimal dosages of QCT, LPS, and EX-527, they assessed the mRNA expression levels of IL-18, IL-1, IL-6, TNF-α, SIRT-1, and adiponectin using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The study showed considerable cytotoxic effects of LPS (200 ng/mL) + QCT (100 µM) + EX-527 (10 µM) on 3T3-L1 differentiated adipocytes after 48 h of incubation. QCT significantly upregulated the expression levels of adiponectin and SIRT-1 (p < 0.0001). However, introducing SIRT-1 inhibitor (p < 0.0001) reversed the impact of QCT on adiponectin expression. Additionally, QCT reduced SIRT-1-dependent pro-inflammatory cytokines in 3T3-L1 differentiated adipocytes (p < 0.0001). CONCLUSION: This study revealed that QCT treatment reduced crucial pro-inflammatory cytokines levels and increased adiponectin levels following LPS treatment. This finding implies that SIRT-1 may be a crucial factor for the anti-inflammatory activity of QCT.

Chalcogen Noncovalent Interactions between Diazines and Sulfur Oxides in Supramolecular Circular Chains.

The noncovalent chalcogen interaction between SO2/SO3 and diazines was studied through a dispersion-corrected DFT Kohn-Sham molecular orbital together with quantitative energy decomposition analyses. For this, supramolecular circular chains of up to 12 molecules were built with the aim of checking the capability of diazine molecules to detect SO2/SO3 compounds within the atmosphere. Trends in the interaction energies with the increasing number of molecules are mainly determined by the Pauli steric repulsion involved in these σ-hole/π-hole interactions. But more importantly, despite the assumed electrostatic nature of the involved interactions, the covalent component also plays a determinant role in its strength in the involved chalcogen bonds. Noticeably, π-hole interactions are supported by the charge transfer from diazines to SO2/SO3 molecules. Interaction energies in these supramolecular complexes are not only determined by the S···N bond lengths but attractive electrostatic and orbital interactions also determine the trends. These results should allow us to establish the fundamental characteristics of chalcogen bonding based on its strength and nature, which is of relevance for the capture of sulfur oxides.

Adjusting UV-Vis Spectrum of Alizarin by Insertion of Auxochromes.

First synthesized in 1868, alizarin became one of the first synthetic dyes and was widely used as a red dye in the textile industry, making it more affordable and readily available than the traditional red dyes derived from natural sources. Despite extensive both experimental and computational analyses on the electronic effects of substituents on the shape of the visible spectrum of alizarin and alizarin Red S, no previous systematic work has been undertaken with the aim to fine tune the dominant absorption region defining its color by introducing other electron-withdrawing or electron-donor groups. For such, we have performed a comprehensive study of electronic effects of substituents in position C3 of alizarin by means of a time dependent DFT approach. These auxochromes attached to the chromophore are proven to alter both the wavelength and intensity of absorption. It is shown that the introduction of an electron-donor group in alizarin causes the transition bands to be significantly red-shifted whereas electron-withdrawing groups cause a minor blue-shifting.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition.

BACKGROUND: Diabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. METHODS: 54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-ß) in wound tissues, alongside histological assessment of cellular changes. RESULTS: NR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. CONCLUSION: This study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Protective and curative effects of unconjugated bilirubin on gene expression of LOX-1 and iNOS in the heart of rats receiving high-fat diet and low dose streptozotocin: a histomorphometric approach.

BACKGROUND: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. METHODS: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. RESULTS: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. CONCLUSION: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels.