Qi Wang

With the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), the development of new drugs targeting this condition is particularly urgent. Sabinineoside B, a new compound of phenanthrene alkaloid glycoside isolated from the traditional Chinese herb Sabia parviflora. Through establishing a high-fat diet mouse model and integrating metabolomics, proteomics, and phosphoproteomics analyses, this study elucidated the efficacy and mechanism of Sabinineoside B in treating MASLD, while preliminarily evaluating its pharmacokinetics and safety. Molecular docking, molecular dynamics simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), pull-down, dual-luciferase reporter gene assays and siRNA techniques were employed to validate the binding interaction between Sabinineoside B and key targets. We found that the Sabinineoside B protein significantly reduces lipid deposition and liver damage in mice on a high-fat diet. Integrated multi-omics analysis and Western blot experiments revealed that Sabinineoside B regulates lipid metabolism and exerts lipid-lowering effects by modulating the PPAR α signaling pathway. Knocking down PPAR α attenuates the regulatory effect of Sabinineoside B on the lipid-lowering pathway, indicating that the molecular mechanism of Sabinineoside B’s lipid-lowering activity may be achieved by targeting PPAR α. The alternative text for this image may have been generated using AI.

In this study, we examined the metabolites from different parts of Acanthopanax senticosus and their role in alleviating damage caused by oxidative stress. We used UHPLC-QTOF-MS to analyze the chemical components in the root, seed, and leaf extracts of A. senticosus. Two multivariate statistical analysis methodsnamely, principal component analysis and partial least square discriminant analysiswere used to distinguish the samples obtained from different parts of the plant. Using univariate statistics, 130 different metabolites were screened out. Among these, the relative content of flavonoids and terpenoids was found to be highest in the leaves, the lignin and phenolic acid content was highest in the roots, and the amino acid and phenolic acid levels were highest in seeds. An MTT assay was used to test the anti-H₂O₂ oxidative damage to PC12 cells in different parts of the sample. Lastly, using Pearsons correlation analysis, various metabolites from different parts of A. senticosus were correlated with their antioxidant effects from the corresponding parts. Fifty-two related different metabolites were found, of which 20 metabolites that were positively correlated to oxidative stress were present at a relatively higher level in the roots, whereas 32 metabolites that were negatively correlated were present at relatively higher levels in the seeds and leaves. The results of this study reveal the distribution characteristics and the antioxidant activity of different metabolites of A. senticosus and provide a reference for the rational development of its medicinal parts.

Gouty arthritis is characterized by the deposition of monosodium urate (MSU) within synovial joints and tissues due to increased urate concentrations. Here, we elucidated the role of the natural compound cichoric acid (CA) on the MSU crystal-stimulated inflammatory response. The THP-1-derived macrophages (THP-Ms) were pretreated with CA and then stimulated with MSU suspensions. The protein levels of p65 and IκBα, the activation of the NF-κB signaling pathway by measuring the expression of its downstream inflammatory cytokines, and the activity of NLRP3 inflammasome were measured by western blotting and ELISA. CA treatment markedly inhibited the degradation of IκBα and the activation of NF-κB signaling pathway and reduced the levels of its downstream inflammatory genes such as IL-1β, TNF-α, COX-2, and PGE2 in the MSU-stimulated THP-M cells. Therefore, we infer that CA effectively alleviated MSU-induced inflammation by suppressing the degradation of IκBα, thereby reducing the activation of the NF-κB signaling pathway and the NLRP3 inflammasome. These results suggest that CA could be a novel therapeutic strategy in averting acute episodes of gout.

Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl₄-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl₄-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.

The phenolic profiles of 12 cruciferous vegetables (pakchoi, choysum, Chinese cabbage, kailan, Brussels sprout, cabbage, cauliflower, broccoli, rocket salad, red cherry radish, daikon radish, and watercress) were studied with UHPLC-MS/MS. Antioxidant activity and total phenolic content (TPC) were also evaluated. A total of 74 phenolic compounds were identified, including 16 hydroxycinnamic acids and derivatives, and 58 flavonoids and derivatives. The main flavonoids identified were glycosylated quercetin, kaempferol and isorhamnetin, and the main hydroxycinnamic acids were ferulic, sinapic, caffeic and p-coumaric acids. Principal component analysis (PCA) revealed that the distribution of phenolic compounds in different genera of cruciferous vegetables was in accordance with their conventional taxonomy. The DPPH, ORAC and TPC values ranged from 1.11 to 9.54 µmoles Trolox equivalent/g FW, 5.34 to 32.92 µmoles Trolox equivalent/g FW, and 0.16 to 1.93 mg gallic acid equivalent/g FW respectively. Spearman’s correlation showed significant (p < 0.05) positive correlations between TPC, flavonoids and antioxidant activity.