Metabolomics represents an emerging and powerful discipline concerned with the comprehensive analysis of small molecules and provides a powerful approach to discover biomarkers in biological systems. Recent development of biomarkers for diagnosis and therapeutic monitoring of liver-stagnation and spleen-deficiency syndrome (LSS)-type disease remains challenging. This study was undertaken to discover novel potential biomarkers for the non-invasive early diagnosis of human LSS. Urine samples which are potentially a rich source of metabolites were collected from patients with LSS, together with healthy control samples. Metabolite profiling was performed by ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry (UPLC-Q-TOF-HDMS) in conjunction with multivariate data analysis and ingenuity pathway analysis that were used to select the metabolites to be used for the non-invasive diagnosis of LSS. Twelve urinary differential metabolites contributing to the complete separation of LSS patients from matched healthy controls were identified involving several key metabolic pathways such as pentose and glucuronate interconversions, ascorbate, aldarate, cysteine, methionine, tyrosine, tryptophan, amino sugar and nucleotide sugar metabolism. More importantly, of the 12 differential metabolites, 4 metabolite markers, prolylhydroxyproline, L-homocystine, 2-octenoylcarnitine and α-N-phenylacetyl-L-glutamine, were effective for the diagnosis of human LSS, with an achieved sensitivity of 93.0%. These results demonstrate that robust metabolomics has the potential as a non-invasive strategy and promising screening tool to evaluate the potential of these metabolites in the early diagnosis of LSS patients and provides new insight into pathophysiological mechanisms.

Ephedrae Herba (Ephedra), known as “MaHuang” in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Rhein is a natural active ingredient in traditional Chinese medicine that has attracted much attention due to its wide range of pharmacological activities. However, its clinical application is limited by low water solubility, poor oral absorption, and potential toxicity to the liver and kidneys. Recently, advanced extraction and synthesis techniques have made it possible to develop derivatives of rhein, which have better pharmacological properties and lower toxicity. This article comprehensively summarizes the biological activity and action mechanism of rhein. Notably, we found that TGF-β1 is the target of rhein improving tissue fibrosis, while NF-κB is the main target of its anti-inflammatory effect. Additionally, we reviewed the current research status of the pharmacokinetics, toxicology, structural optimization, and potential drug applications of rhein and found that the coupling and combination therapy of rhein and other active ingredients exhibit a synergistic effect, significantly enhancing therapeutic efficacy. Finally, we emphasize the necessity of further studying rhein’s pharmacological mechanisms, toxicology, and development of analogs, aiming to lay the foundation for its widespread clinical application as a natural product and elucidate its prospects in modern medicine.

As an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM.