Hypolipidemic effect of aqueous leaf extract of carmona microphylla G Don

Purpose: To investigate the hypolipidemic effects of the aqueous leaf extract of Carmona microphylla (Lam.) G. Don. (CAE) in vitro and in vivo.Methods: The lipid-lowering effect of CAE was investigated in oleic acid (OA)-induced steatosis in HepG2 liver cells, as well as in high-fat diet (HFD)- and triton WR-1339 (TRI)-induced hyperlipidemic mice. The levels of intracellular, serum and/or hepatic total cholesterol (TC); triglyceride (TG); low density lipoprotein-cholesterol (LDL-c); high density lipoprotein-cholesterol (HDL-c); hepatic superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by oil-red O staining and appropriate kits.Results: Treatment with CAE inhibited lipid accumulation in HepG2 cells and reduced the elevated levels of serum TC, TG and LDL-c as well as hepatic TC and TG in hyperlipidemic mice induced by HFD. CAE administration also significantly decreased arteriosclerosis index (AI) and LDL-c/HDL-c ratio, but improved oxidative status as revealed by increased hepatic SOD activity and decreased MDA level. The lipid ameliorating and antioxidative effects of CAE (600 mg/kg) were comparable to those of the standard lipid-lowering drug, sivastatin (5 mg/kg).Conclusion: These results suggest that C. microphylla aqueous extract (CAE) protects against hyperlipidemia induced by HFD in mice and may find therapeutic application in hyperlipidemic patients.Keywords: Carmona microphylla, Hyperlipidemia, Atherosclerosis, Oxidative stress, Sivastatin, Lipidlowerin

Analysis of Akkermansia muciniphila in Mulberry Galacto-Oligosaccharide Medium via Comparative Transcriptomics

Akkermansia muciniphila is a common member of the human gut microbiota and belongs to the phylum Verrucomicrobia. Decreased levels of A. muciniphila are associated with many diseases, so it is thought to be a beneficial resident of the intestinal mucosal layer. In this study, we found that different prebiotics promoted the proliferation of A. muciniphila, and mulberry galacto-oligosaccharide (MGO) had the greatest effect. We cultured A. muciniphila in a brian heart infusion (BHI) medium containing 5% galactooligosaccharides (GOS), mulberry polysaccharide solution (MPS), and MGO, and transcriptomic analyses were performed. The results revealed that, after 6 days of cultivation, the numbers of upregulated functional genes (based on Gene Ontology) were approximately 0.7 and 19% higher with MPS and MGO, respectively, than with GOS. Analysis using the Kyoto Encyclopedia of Genes and Genomes showed that, when A. muciniphila was cultured with MGO, genes that were upregulated were enriched in the carbohydrate metabolism, the metabolism of cofactors and vitamins, the energy metabolism, the amino acid metabolism, and the lipid metabolism. Upregulated genes included galM and pfkA in the galactose metabolism, and pgi, pfk, fbaA, tpiA, gapA, pgk, gpml, eno, pyk, and lpd in the glycolysis/gluconeogenesis pathway. Real-time quantitative PCR results were consistent with the RNA-Seq data. This work provides valuable knowledge which can be available for the functional application of A. muciniphila and MGO

Drug monomers from Salvia miltiorrhiza Bge. promoting tight junction protein expression for therapeutic effects on lung cancer

Abstract Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC

Diverse Galactooligosaccharides Differentially Reduce LPS-Induced Inflammation in Macrophages

The effects of natural and synthetic galactooligosaccharides (GOS) on inflammation were explored by investigating the structure-activity relationship between the degree of GOS polymerization and in vitro anti-inflammatory activity, together with the potential underlying mechanism of their anti-inflammatory effects. The results demonstrated that GOS had strong anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, including the inhibition of nitric oxide production and the reduced expression of pro-inflammatory mediators (interleukin-1β, interleukin-6, and tumor necrosis factor α), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and proteins related to the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway. GOS4, which has the highest degree of polymerization, exerted the strongest anti-inflammatory activity among the GOS examined. More importantly, our findings confirmed the anti-inflammatory effects of GOS on RAW264.7 macrophages via the TLR4/NF-κB pathway. Our experimental results could provide further support for the exploration of GOS in human nutrition and health

Sulfur Vacancy-Rich Carbonaceous Co₉S₈‑ZnS Nanotubes for the Oxygen Evolution Reaction

Metal sulfide electrocatalysts with high activity toward the oxygen evolution reaction (OER) are crucial for renewable energy technologies. However, it remains challenging to rationally design and synthesize metal sulfides integrated with high conductivity and rich porosity to achieve a superior activity. Herein, we report a brand-new, carbonaceous Co9S8-ZnS nanotube (Co9S8-ZnS/NTC) electrocatalyst synthesized via a two-step procedure including zinc-trimesic acid (ZnBTC) fiber nanocrystallization and its assembling with ZIF-67 before solid-state transformation (including sulfuration, gas-phase ion exchange, and carbonization). It is found that rich sulfur vacancies (point defect) and a hollow cavity (3-dimensional defect) are integrated into the resulting carbonaceous Co9S8-ZnS nanotube, originated from the non-equilibrium interdiffusion, which could facilitate electron transfer and OH– transport during the oxygen evolution. As expected, the designed Co9S8-ZnS/NTC delivers a low overpotential of 290 mV, a Tafel slope of 69 mV–1, an electrical resistance of 44 Ω for OER at 10 mA cm–2 in alkaline media, and a high electrochemically active surface area and turnover frequency of 12.2 mF cm–2 and 0.70 O2 s–1, respectively, at 1.50 V, superior to single-component electrocatalysts of Co9S8 and ZnS anchored on N-doped carbon. Density functional theory calculation demonstrates that the sulfur vacancy in Co9S8-ZnS/NTC delivers the decreased theoretical overpotential (1.29 V) and the enhanced activity of its neighboring Co sites, which was also beneficial to OER kinetics. Sulfur vacancy reparation results in a much lower electrocatalytic activity (overpotential, 465 mV) for Co9S8-ZnS/NTC, indicative of its critical role in OER. The concept demonstrated in this study paves the avenue to design other high-performance non-noble electrocatalysts for OER