Cryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation‐induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut‐lung axis angle, specifically focusing on the bile acid (BA)‐gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs‐targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation‐induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation‐induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF.

Ophiopogonis Radix, also known as “Maidong” (MD) in China, is frequently sulfur-fumigated (SF) in the pretreatment process of MD to improve the appearance and facilitate preservation. However, the process leads to changes in chemical composition, so it is essential to develop an approach to identify the chemical characteristics between nonfumigated and sulfur-fumigated products. This paper provided a practical method based on UPLC-QTOF-MS combined Global Natural Products Social Molecular Networking (GNPS) with multivariate statistical analysis for the characterization and discrimination of MD with different levels of sulfur fumigation, high concentration sulfur fumigation (HS), low concentration sulfur fumigation (LS) and without sulfur fumigation (WS). First, a number of 98 compounds were identified in those MD samples. Additionally, the results of Principal component analysis (PCA) and Orthogonal partial least-squares-discriminant analysis (OPLS-DA) demonstrated that there were significant chemical differences in the chemical composition of MD with different degrees of SF. Finally, fourteen and sixteen chemical markers were identified upon the comparison between HS and WS, LS and WS, respectively. Overall, these results can be able to discriminate MD with different levels of SF as well as establish a solid foundation for further quality control and pharmacological research.

Euphorbiasteroid, a lathyrane-type diterpene from Euphorbiae semen (the seeds of Euphorbia lathyris L.), has been shown to have a variety of pharmacological effects such as anti-tumor and anti-obesity. This study aims to investigate the metabolic profiles of euphorbiasteroid in rats and rat liver microsomes (RLMs) and Cunninghamella elegans bio-110930 by integrating ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS), UNIFI software, and NMR techniques. A total of 31 metabolites were identified in rats. Twelve metabolites (M1–M5, M8, M12–M13, M16, M24–M25, and M29) were matched to the metabolites obtained by RLMs incubation and the microbial transformation of C. elegans bio-110930 and their structures were exactly determined through analysis of NMR spectroscopic data. In addition, the metabolic pathways of euphorbiasteroid were then clarified, mainly including hydroxylation, hydrolysis, oxygenation, sulfonation, and glycosylation. Finally, three metabolites, M3 (20-hydroxyl euphorbiasteroid), M24 (epoxylathyrol) and M25 (15-deacetyl euphorbiasteroid), showed significant cytotoxicity against four human cell lines with IC50 values from 3.60 μM to 40.74 μM. This is the first systematic investigation into the in vivo metabolic pathways of euphorbiasteroid and the cytotoxicity of its metabolites, which will be beneficial for better predicting the metabolism profile of euphorbiasteroid in humans and understanding its possible toxic material basis.

Cistanche tubulosa (CT), a well‐known traditional Chinese medicine, has always been processed with rice wine for the treatment of kidney‐yang deficiency syndrome (KYDS) since time immemorial. To explore the effect of processing on the efficacy and metabolites of CT in vivo, a comprehensive method using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was established for the analysis of the altered endogenous metabolites in response to the intervention of the raw and processed CT in KYDS model and the metabolites of the absorbed compounds in rats after gastric perfusion. It was shown that CT could improve KYDS, and the effect of the processed product was more significant. A total of 47 differential metabolites were identified in urine. Pathway analysis proved that purine metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were the main pathways. Furthermore, 53 prototypes and 48 metabolites have been detected in rats. This was the first systematic research focus on the metabolites of raw and processed CT in vivo, which could provide a scientific basis for explaining the increasing efficiency of the processed CT. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other TCM prescriptions.

Leukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.