Preparative separation of iridoid glucosides and crocins from Gardeniae Fructus using sequential macroporous resin column chromatography and evaluation of their anti-inflammatory and antioxidant activities.

Iridoid glycosides (geniposide (GP), genipin-1-gentiobioside (GB), etc.) and crocins (crocin Ⅰ (CR1), crocin Ⅱ(CR2), etc.) are two main bioactive components in Gardeniae Fructus (GF), which is a famous traditional Chinese medicine. Iridoid glycosides exhibit many activities and are used to manufacture gardenia blue pigment for the food industry. Crocins are rare natural water-soluble carotenoids that are often used as food colorants. A sequential macroporous resin column chromatography technology composed of HC-500B and HC-900B resins was developed to selectively separate iridoid glucosides and crocins from GF. The adsorption of GP on HC-900B resin was an exothermic process. The adsorption of CR1 on HC-500B resin was an endothermic process. The two kinds of components were completely separated by a sequential resin column. GB and GP were mainly found in product 1 (P1) with purities of 11.38% and 46.83%, respectively, while CR1 and CR2 were mainly found in product 2 (P2) with purities of 12.32% and 1.40%, respectively. The recovery yields of all the compounds were more than 80%. The above results showed that sequential resin column chromatography technology achieved high selectivity and recovery yields. GF extract, P1 and P2 could significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that iridoid glycosides and crocins provide a greater contribution to the anti-inflammatory activity of GF. At the same time, compared to the GF extract and P1, P2 exhibited stronger scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, indicating that crocins may provide a significant contribution to the antioxidant activity of GF.

Quercetin Ameliorates Diabetic Kidney Injury by Inhibiting Ferroptosis via Activating Nrf2/HO-1 Signaling Pathway.

Diabetic nephropathy (DN) is thought to be the major cause of end-stage renal disease. Due to its complicated pathogenesis and the low efficacy of DN treatment, a deep understanding of new etiological factors may be useful. Ferroptosis, a nonapoptotic form of cell death, is characterized by the accumulation of iron-dependent lipid peroxides to lethal levels. Ferroptosis-triggered renal tubular injury is reported to participate in the development of DN, and blocking ferroptosis might be an effective strategy to prevent the development of DN. Quercetin (QCT), a natural flavonoid that is present in a variety of fruits and vegetables, has been reported to ameliorate DN. However, its underlying nephroprotective mechanism is unclear. Herein, we explored the antiferroptosic effect of QCT and verified its nephroprotective effect using DN mice and high glucose (HG)-incubated renal tubular epithelial cell models. We found HG-induced abnormal activation of ferroptosis of renal tubular epithelial cells, and QCT treatment inhibited ferroptosis by downregulating the expression of transferrin receptor 1 (TFR-1) and upregulating the expression of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH-1), and the cystine/glutamate reverse antiporter solute carrier family 7 member (SLC7A11) in DN mice and HG-incubated HK-2 cells. Subsequently, both in vitro and in vivo results confirmed that QCT activated the NFE2-related factor 2 (Nrf2)/Heme oxygenase-1(HO-1) signaling pathway by increasing the levels of Nrf2 and HO-1. Therefore, this study supports that QCT inhibits the ferroptosis of renal tubular epithelial cells by regulating the Nrf2/HO-1 signaling pathway, providing a novel insight into the protective mechanism of QCT in DN treatment.

Comparative analysis of chloroplast genomes of five Robinia species: Genome comparative and evolution analysis.

The black locust (Robinia pseudoacacia) is widely distributed, and has strong drought resistance and salt tolerance. These characteristics make it the best type of tree for landscaping and resource conservation in China. In this study, the chloroplast genomes of five black locusts were identified de novo and the evolutionary relationship among these black locusts and their taxonomic statuses in leguminous plants were determined. The chloroplast structures of the five black locusts were typical and had four parts, including two single copy regions (large and small single copy sections) and a pair of inverted repeats (IRs). Genome sizes were between 155,364 bp and 155,655 bp; the genome of R. pseudoacacia var. decaisneana was the smallest, while that of R. pseudoacacia var. tortuosa was the largest. The genomes contained 124-130 protein-coding genes; R. pseudoacacia var. tortuosa had the fewest, while R. hispida and R. pseudoacacia var. decaisneana had the most. In this study, eight to ten genes from chloroplast genomes contained introns. Nine genes from the chloroplast genomes of R. pseudoacacia and R. pseudoacacia f. unifolia contained introns that had lost the trnL-CAA gene via evolution, while eight chloroplast genes of R. pseudoacacia var. tortuosa contained introns that had lost the trnL-CAA and psaA genes. Among them, the rpoC1 gene had the longest introns at 2828 bp, and rps12+ had the smallest introns at only 533 bp. There were various amplification phenomena in the IR region among the five black locusts. Most of the protein-coding genes of the five black locusts had a high degree of codon preference. To determine the phylogenetic positions of the five black locusts, we conducted a systematic evolutionary analysis using common protein-coding genes in chloroplast sequences from 34 species of leguminous plants and 12 other species. The results showed that the relationship between Robinia and Acacia ligulata was the most distant among those of the leguminous plants, and the relationship between Robinia and Lotus japonicus was the closest. The chloroplast protein-coding genes in different black locusts were relatively conservative by evolutionary selection pressure analysis standards. These results are important for our understanding of their photosynthetic mechanisms and evolution, and the transgenic engineering of their chloroplasts.

Biomacromolecule/lipid hybrid nanoparticles for controlled delivery of sorafenib in targeting hepatocellular carcinoma therapy.

AIM: Hybrids composed of various materials are highly versatile for drug delivery in tumor therapy including hepatocellular carcinoma. Herein, a sorafenib (SF)-loaded biomacromolecule hyaluronic acid (HA)/lipid hybrid nanoparticles (HA/SF-cLNS) were developed for targeting drug delivery. MATERIALS & METHODS: In vitro assays determined HA/SF-cLNS release behavior, enzymatic degradation, uptake and cytotoxicity. H22-bearing liver cancer xenograft murine models were used to evaluate the biodistribution and therapeutic efficacy in vivo. RESULTS: HA/SF-cLNS could be disassembled and drug was released in response to hyaluronidase. In vivo imaging results demonstrated HA/cLNS could enhance drug accumulation at tumor site. Meanwhile, HA/SF-cLNS exhibited improved antitumor efficacy in vitro and in vivo. CONCLUSION: HA/SF-cLNS demonstrated the potential to enhance antitumor efficacy of SF.