Bile acids (BAs) are a major component of bile salt, which plays a vital role in the metabolism of lipids in humans. Ninety-five percent of bile acids are recycled by the enterohepatic circulation (EHC), and therefore EHC is essential for bile acid homeostasis. There are four transporters that mediate the transmembrane transport of bile acids, each of which plays an important role in the enterohepatic circulation. Gene defects in bile acid transporters can lead to disorders of the enterohepatic circulation, ultimately leading to clinical phenotypes such as metabolic diseases and even death. Bile transporter expression is altered in patients with various metabolic disease states, suggesting that disruption of bile acid transporters may be a pivotal pathological mechanism for the development of metabolism diseases. Thus, many drugs targeting bile acid transporters are being developed. We provide a concise overview of the progress of bile acid transporters research, discuss the relationship between different bile acid transporters and disease development, and summarize the current progress in drug development targeting bile acid transporters.

Acute lung injury (ALI) is a kind of lung disease mainly caused by excessive inflammatory reaction. At present, there is a lack of effective therapeutic drugs in clinic. The aim of this study was to investigate the improvement effect of Panax notoginseng saponins (PNS) on ALI and its potential mechanism. The model of wild-type C57BL/6J mice was established by intratracheal instillation of 50 μL 25 mg·mL^-1 lipopolysaccharide (LPS). 24 h later, 200 and 400 mg·kg^-1 PNS was given intragastric, respectively. 24 h after administration, the improvement effect of PNS on ALI mice was evaluated by lung function, wet-to-dry weight ratio (W/D), total protein, interleukin 6 (IL6) and tumor necrosis factor α (TNFα) concentration of bronchoalveolar lavage fluid (BALF), expression levels of IL6 and TNFα in lung tissues, pathological changes of lung tissues and expression of inflammatory cells in BALF. The protein expression levels of NF-κB and its upstream kinases in Raw264.7 cells and ALI mice lung tissues were further detected to evaluate the potential mechanism of PNS improving ALI mice. The experimental scheme was approved by the Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine. It was found that 400 mg·kg^-1 PNS could significantly improve the lung function of ALI mice, reduce the contents of W/D, BALF total protein, IL6 and TNFα, neutrophils expression in BALF and the infiltration of inflammatory cells in lung tissue. In Raw264.7 cells and ALI mice lung tissue, PNS significantly reduced the expression of NF-κB, reduced the protein expression and phosphorylation of NF-κB, promoted the expression of IκBα, and inhibited the inflammatory response. This study showed that PNS can improve ALI by inhibiting the activity of NF-κB, inhibiting the release of inflammatory factors and inflammatory cells infiltration, alleviating lung inflammation.

Fifteen compounds were isolated from fruits of Cornus officinalis by various chromatographic techniques such as Toyopearl HW-40C, Sephadex LH-20, silica gel, and the semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as neolignan A (1), caffeic acid (2), trans-p-hydroxy cinnamic acid (3), esculetin (4), scopoletin (5), benzyl-7-O-β-D-glucopyranoside (6), tachioside (7), 6-O-(4-hydroxybenzoyl) arbutin (8), 2-(3′, 4′-dihydroxyphenyl)-1, 3-benzodioxole-5-carboxaldehyde (9), (-)-pinoresinol-4-O-β-D-glucopyranoside (10), (7S, 8R)-dihydrodehydrodiconiferyl alcohol-9-O-β-D-glucopyranoside (11), (7S, 8R)-dihydrodehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (12), (+)-lyoniresinol (13), (+)-isolariciresinol-9-O-β-D-glucopyranoside (14), and isolariciresinol-9′-O-β-D-glucopyranoside (15). Compound 1 was a new compound and named as neolignan A, and compounds 6-9 and 14 were isolated from Cornus officinalis for the first time. Compounds 2, 3 and 15 efficiently alleviated the PC12 cells injury induced by Aβ_25-35, suggesting their potential anti-Alzheimer's disease activity.

Aging can cause degenerative changes in the function of multiple tissues and organs in the body. Gastrointestinal diseases and intestinal dysfunction are very common in the elderly people. The purpose of this study is to explore the effect of the total extract of Astragalus membranaceus (Fisch.) Bge. on intestinal function and gut microbiota homeostasis in natural aging mice, which will provide clues for further mechanism study. The natural aging mice model is established and animal experiments follow the regulations of the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The overall health of the mice was evaluated by the "frailty index" scoring method. The intestinal absorption and transport function were measured by detecting intestinal glucose absorption capacity, transport time, lipase and amylase activities of aging mice. Intestinal inflammation was assessed by detecting inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the intestines of aging mice were tested by hematoxylin-eosin (H & E) staining and alizarin blue (AB) staining. The qRT-PCR method was used to explore the gene transcription level related with the proliferation and differentiation of intestinal stem cells. Microbiota analysis based on 16S rDNA were used to evaluate the composition of gut microbiota. The results showed that Astragalus had a tendency to reduce the "frailty index" of aging mice, but did not show a significant difference. In some indicators of aging phenotype, Astragalus has the most significant effect on hair loss and physical fitness. In terms of intestinal function, Astragalus could increase intestinal glucose absorption capacity, shorten intestinal transportation time and promote lipase secretion in aging mice. The levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-‍α) in the aging intestinal tissue were reduced after Astragalus administration. Astragalus also ameliorated the pathological degeneration of the intestinal tissue of aging mice by increasing the length of small intestinal villi, the thickness of colonic mucosa and goblet cell number. In addition, Astragalus elevated the expression of genes associated with the proliferation and differentiation in jejunum and modulated gut microbiota, especially restoring the abundance of Lachnospiraceae. Taken together, the above research results demonstrate the total extract of Astragalus as a key factor improving the intestinal function and gut microbiota homeostasis of aging mice.

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.

Benzazepine is a kind of fused ring structure, which is composed of nitrogen-containing seven-membered ring and benzene ring. The introduction of benzazepine scaffolds into compounds can not only adjust the physicochemical properties, maintain or enhance the biological activities of the compounds, but also improve the pharmacokinetic properties, increase the brain permeability, and reduce the toxicity of hERG of the compounds, which is one of the privileged scaffolds for rational design and structural optimization of drug molecules. Benzazepine scaffolds can be constructed by different synthetic methods such as Dickmann condensation reaction, Mitsunobu reaction, Pictet-Spengler reaction, CMD reaction, multicomponent reactions (MCRs), metal catalysis reactions and asymmetric catalysis etc., which play an important role in enriching the structure diversity of drug molecules.

2-Oxoglutarate/Fe(II)-dependent dioxygenases (2-ODD) play an important role in plant primary and secondary metabolism. Based on the high-throughput sequencing platform Illumina NovaSeq 6000, the transcriptome of Salvia apiana Jepson was sequenced, and the obtained reads were de novo assembled. A total of 38 534 unigenes were obtained from the transcriptome. The assembled unigenes were annotated and 29 982 unigenes were given functional annotations. The 2-ODD genes were identified from the assembled S. apiana transcriptome database by bioinformatics methods, and the genes were analyzed, including the homology of the sequences, physicochemical characteristics, signal peptides, transmembrane domains, subcellular localization, secondary structure and tertiary structure, etc. The evolutionary relationships and the expression patterns of the identified 2-ODD genes were also analyzed. 39 full-length 2-ODD genes were identified from the transcriptome of S. apiana. The average length of these 2-ODD encoding proteins was 320 amino acids, the molecular weight was about 36.00 kDa, and most of them were hydrophilic proteins. Phylogenetic analysis divided these 2-ODD genes into several subfamilies. Gene expression analysis indicated that the 2-ODD genes were expressed in different parts of S. apiana, and the expression level of most genes was much higher in roots than that in leaves. This study can lay a foundation for further study of 2-ODD genes in S. apiana.

In this study, the ameliorative effects of Flos Abelmoschus manihot on mice with chronic inflammatory bowel disease (IBD) were investigated and its effects on the structure of the intestinal flora as well as the lipid profile in feces of IBD mice were analyzed. All animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese medicine. A mouse model with chronic IBD induced by dextran sulfate sodium (DSS) was used to evaluate changes in body weight, disease activity index (DAI), colonic histopathological damage as well as gene expression levels of inflammatory factors in the colon. Fecal samples from mice in each group were collected and subjected to Illumina high-throughput sequencing to detect the abundance of intestinal flora; samples were analyzed by UHPLC-Q-Exactive^® HF Quadrupole-Orbitrap^® of untargeted lipidomics, which detects lipid content in feces. Administration of Flos Abelmoschus manihot could significantly restore the body weight and ameliorate colonic histopathological damage in IBD mice. Sequencing of the gut microbiota revealed that the species diversity and richness of the gut microbiota in IBD mice were decreased, with a significant increase in the abundance of Verrucomicrobia and a significant decrease in the abundance of Bacteroidetes; Flos Abelmoschus manihot significantly increased the richness and diversity of intestinal microbiota in IBD mice, increased the number of taxa species at each level, and restored the abundance of bacteria in the phylum Bacteroidetes. Analysis of fecal lipid profiles identified the most significant changes in sphingolipid and glycerophospholipid metabolic pathways in IBD mice, with Flos Abelmoschus manihot inhibiting ceramide and sphingomyelin synthesis in sphingolipid metabolism. In summary, Flos Abelmoschus manihot can effectively improve the disease condition of mice with chronic IBD, and it has the effect of regulating intestinal flora homeostasis and lipid metabolism, but the related mechanism between the two still needs to be deeply explored.

A fungal strain WXF1904, was isolated from a starfish sample corrected in the South China Sea. According to its internal transcribed spacer (ITS) analysis, the strain was identified as a member of the genus Aspergillus and designated as Aspergillus sp. WXF1904. One new isocoumarin containing halogennamed 6-chloro-5, 7-dihydroxy-3, 8-dimethylisocoumarin (1), along with six known compounds pilobolusate (2), p-hydroxybenzaldehyde (3), methyl orsellinate (4), catechol (5), vanillic acid (6), and wasabidienone E (7), were isolated from the cultures of Aspergillus sp. WXF1904 by silica gel column chromatography, ODS gel column chromatography, and high performance liquid chromatography (HPLC). Their structures were elucidated by high resolution mass spectrometry (HR-MS), nuclear magnetic resonance (NMR) as well as literature comparison. The new compound 5-chloro-6, 7-dihydroxy-3, 8-dimethylisocoumarin and compound 2 showed weak acetylcholinesterase inhibitory activity.

By means of several chromatographic techniques, such as silica gel, Sephadex LH-20 and semi-preparative high performance liquid chromatography (HPLC), two caryolane-type sesquiterpenoids were isolated from the petroleum ether soluble fraction of the aerial parts of Pogostemon cablin (Blanco) Benth., and their structures were identified as caryolanol A (1) and 1α-ethoxy-9α-hydroxy-senecrassane (2) by various spectroscopic methods, including NMR and HR-ESI-MS. Compounds 1 and 2 were a pair of C₅ epimers, and compound 1 was a new compound. In addition, the anti-influenza virus activity of compounds 1 and 2 was evaluated.