In silico identification of natural products from Traditional Chinese Medicine for cancer immunotherapy.

Advances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.

Advances in Molecular Mechanisms for Traditional Chinese Medicine Actions in Regulating Tumor Immune Responses.

Traditional Chinese medicine (TCM) has been developed for thousands of years with its various biological activities. The interest in TCM in tumor prevention and treatment is rising with its synergistic effect on tumor cells and tumor immunosuppressive microenvironment (TIM). Characteristic of TCM fits well within the whole system and multi-target cancer treatment. Herein we discuss the underlying mechanisms of TCM actions in TIM via regulating immunosuppressive cells, including restoring the antigen presentation function of dendritic cells, enhancing NK cells-mediated killing activity, restraining the functions of myeloid cell-derived suppressor cells, and inhibiting cancer-associated fibroblasts. TCM also regulates tumor progression through enhancing immune response, preventing immune escape and inducing cell death of tumor cells, which triggers immune response in nearby cells. In addition, we discuss TCM in clinical applications and the advantages and disadvantages of TCM in cancer prevention and treatment, as well as current therapeutic challenges and strategies. It might be helpful for understanding the therapeutic potential of TCM for cancer in clinic.

TCMIO: A Comprehensive Database of Traditional Chinese Medicine on Immuno-Oncology.

Advances in immuno-oncology (IO) are making immunotherapy a powerful tool for cancer treatment. With the discovery of an increasing number of IO targets, many herbs or ingredients from traditional Chinese medicine (TCM) have shown immunomodulatory function and antitumor effects via targeting the immune system. However, knowledge of underlying mechanisms is limited due to the complexity of TCM, which has multiple ingredients acting on multiple targets. To address this issue, we present TCMIO, a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology, which can be used to explore the molecular mechanisms of TCM in modulating the cancer immune microenvironment. Over 120,000 small molecules against 400 IO targets were extracted from public databases and the literature. These ligands were further mapped to the chemical ingredients of TCM to identify herbs that interact with the IO targets. Furthermore, we applied a network inference-based approach to identify the potential IO targets of natural products in TCM. All of these data, along with cheminformatics and bioinformatics tools, were integrated into the publicly accessible database. Chemical structure mining tools are provided to explore the chemical ingredients and ligands against IO targets. Herb-ingredient-target networks can be generated online, and pathway enrichment analysis for TCM or prescription is available. This database is functional for chemical ingredient structure mining and network analysis for TCM. We believe that this database provides a comprehensive resource for further research on the exploration of the mechanisms of TCM in cancer immunity and TCM-inspired identification of novel drug leads for cancer immunotherapy. TCMIO can be publicly accessed at http://tcmio.xielab.net.

Curcumin ameliorates health-related quality of life in patients with liver cirrhosis: A randomized, double-blind placebo-controlled trial.

OBJECTIVES: Current study aimed to find the effects of curcumin on quality of life (QoL) in liver cirrhotic patients. DESIGN: In this randomized double-masked placebo-controlled trial, 70 cases with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1000 mg/day curcumin (n = 35) or placebo (n = 35) for 12 weeks. The health-related QoL (HRQoL) was assessed by CLDQ, LDSI 2.0, and SF-36. RESULTS: Fifty-eight patients (28 in curcumin and 30 in placebo groups) finished the research. Compared with baseline, overall scores as well as most of CLDQ domains (e.g. Fatigue, Emotional Function, Worry, Abdominal Symptoms, and Systemic Symptoms) and the Physical and Mental health (Total) scores and most of SF-36 domains (e.g. Physical Functioning, Bodily Pain, Vitality, Social Functioning, and Mental Health) increased considerably (P < 0.05) after curcumin administration. Furthermore, curcumin reduced most of LDSI 2.0 domains (e.g. Itch, Joint pain, Pain in the right upper abdomen, Sleeping during the day, Decreased appetite, Depression, Fear of complication, Jaundice, Hindrance in Financial Affairs, Change in use of time, Decreased sexual interest, and Decreased sexual activity) significantly (P < 0.05). Significant differences were noticed between two groups in CLDQ domains and overall scores, LDSI 2.0 domains and overall scores, SF-36 Physical and Mental health (total) scores and all its domains scores (P < 0.05), adjusting for baseline values and disease duration. CONCLUSIONS: Curcumin improved QoL in liver cirrhotic patients according to CLDQ, LDSI 2.0, and SF-36 domains. Additional studies are warranted to consider curcumin as a safe, accessible, and low-cost complementary therapeutic option in cirrhosis.