• Correlation
• Diagnostic value
• Interleukin-17
• Primary liver cancer
• Serum level
• Vascular endothelial growth factor

• clinical applications
• compounds
• pharmacology
• processing
• rhubarb

• competing endogenous RNA
• hepatocellular carcinoma
• progress
• therapy
• traditional Chinese medicine

• China Postdoctoral Science Foundation
• Science and Technology Department of Sichuan Province
• Natural Science Foundation of Sichuan Province

Background: Prepared rhubarb was obtained by steaming raw rhubarb with wine. Different from raw rhubarb with a purgative effect, prepared rhubarb shows effects of promoting blood circulation and removing blood stasis. However, the mechanisms of its action through regulating endogenous metabolites remain unclear.

Purpose: The purpose of this study was to explore active chemical components in prepared rhubarb for its activity on noxious heat blood stasis syndrome (NHBS) by comprehensive metabolomics profiling.

Study design: Plant extracts usually show their activities in a synergistic way; therefore, integrated omics was developed as a rational way for a better understanding of their biological effects and potential active compounds.

Methods: The activities of prepared rhubarb were evaluated by biochemical and metabolomic analysis; meanwhile, serum chemical profiles were sought using UHPLC-Q-TOF-MS. Gray correlation analysis (GCA) was used for calculating the underlying correlations between them.

Results: The metabolomics profiles of rat plasma from model and control groups were significantly different, with 31 endogenous metabolites changed by NHBS. Then, after the administration of prepared rhubarb, 18 of them were regulated. Multiple metabolic pathways were disturbed after NHBS modeling and restored by prepared rhubarb, among which had a greater impact on sphingolipid metabolism. A total of 28 compounds from prepared rhubarb absorbed into the plasma were identified, including nine prototypes and 19 metabolites. Statistical results suggested that rhein and its metabolites accounted for half of the top 10 active compounds in prepared rhubarb for its biomedical activities.

Conclusion: This study presented evidence for the therapeutic effects and active chemicals of prepared rhubarb on NHBS in the way of metabolomics.

Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma (p < 0.05). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4⁺/CD8⁺ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.

• Chinese medicine compounds
• antitumor immunity
• cancer
• immune cell
• microenvironment