The prospect of Xihuang pill in the treatment of cancers.

Background: Xihuang pill, a Traditional Chinese Medicine (TCM) prescription and a representative of Huoxuehuayu therapy (one of the TCM therapies to promote blood circulation and remove blood stasis), has been widely used in breast cancer treatments. Although some evidence suggests the efficacy and safety of the Xihuang pill in treating certain cancer, the overall efficacy of the Xihuang pill in other cancer treatment is uncertain. Objective: This study aimed to summarize the current clinical literature and provided evidence support for addressing the research question of whether the Xihuang pill is safe and effective in the treatment of various cancers as Huoxuehuayu therapy, and possibly identify the clinical dosage range and therapeutic effect of Xihuang pills. Method: Seven Chinese and English databases such as PubMed, CNKI, and Google Scholar were searched to collect the publications on Xihuang pill and cancer. Then the researchers extracted data from the articles that met the inclusion criteria and used SAS statistical program version 9.4 (by SAS Institute, Cary, North Carolina, USA) for statistical statistics. Results: Our search identified 78 studies, including 69 RCTs (randomized control trials), 6 NRCCs (non-randomized concurrent control trials), and 3 BAS (before-after study), evaluating 3151 patients in total. The daily doses of Xihuang pills/capsule were between 2 g and 60 g, and duration between 2 weeks and 5 years, mostly used in the middle or late stage of cancer. The therapeutic effect of the Xihuang pill was mainly reflected in improving Complete Response (CR, a term from The Response Evaluation Criteria In Solid Tumors) or Partial Response (PR, a term from The Response Evaluation Criteria In Solid Tumors), reducing adverse reactions, promoting quality of life (QoL), regulating immunity, alleviating pain, prolonging survival, reducing metastasis and recurrence, reducing inflammation, regulating estrogen levels, decreasing hypercoagulative status, and reducing tumor markers. Conclusion: Xihuang pill representing Huoxuehuayu therapy has a good prospect in the treatment of cancer.

Effectiveness and Safety of the Traditional Chinese Medicine Treatment (HuoxueHuayu Therapy) for Malignant Tumors: A Systematic Review and Meta-Analysis.

Background: A malignant tumor is one of the refractory diseases that threaten human life and health. HuoxueHuayu therapy (one of the Traditional Chinese Medicine therapies to promote blood circulation and remove blood stasis) is widely used as an antitumor supplementary method. However, its efficacy and safety are still controversial. Therefore, the objective of this study was to provide evidence-based evidence for HuoxueHuayu therapy in the treatment of malignant tumors and confirm its safety and effectiveness. Methods: A systematic search in 8 electronic databases targeted randomized clinical studies evaluating HuoxueHuayu therapy for response evaluation, tumor progression rate, quality of life (QoL), peripheral hemogram, performance status, immunologic function, tumor marker, and blood coagulation function in cancer patients, published from the establishment of the database to December 31, 2020. Risk ratio (RR) was used for counting data, mean difference (MD) or standardized mean difference (SMD) was used for measurement data, and 95% confidence interval (CI) was used as efficacy analysis statistics. Results: Our search identified 69 studies, evaluating 4402 patients in total. Randomized controlled trials (RCTs) evaluated gastric (n = 14), lung (n = 18), pancreatic (n = 2), colorectal (n = 10), liver (n = 14), breast (n = 2), ovarian (n = 2), gallbladder (n = 1), esophagus (n = 1), and combined (n = 14) cancers and hematological malignancies (n = 2). The duration of HuoxueHuayu therapy ranged from 3 to 48 weeks. Methodological bias was low in 64 studies and high in 5 studies. HuoxueHuayu therapy was associated with significant improvement in response evaluation (Response Evaluation Criteria in Solid Tumor (RECIST): RR: 1.44, 95% CI: 1.27 to 1.63, I2 = 0%, n = 33 studies; World Health Organization Criteria in Solid Tumors (WHOCIST): RR: 1.40, 95% CI: 1.23 to 1.59, I2 = 0%, n = 26 studies), recurrence rate (RR: 0.85, 95% CI: 0.72 to 0.99, I2 = 0%, n = 2 studies), quality of life, performance status (MD: 5.60, 95% CI: 5.04 to 6.15, p < 0.001), immunologic function (CD3: SMD: 1.23, 95% CI: 0.79 to 1.66, p < 0.001; CD4: SMD: 1.25, 95% CI: 0.77 to 1.74, p < 0.001; CD4/CD8: SMD: 1.05, 95% CI: 0.69 to 1.42, p < 0.001; natural killer cell (NK): SMD: 0.74, 95% CI: 0.32 to 1.15, p < 0.001), tumor marker, and blood coagulation function (D-dimer (D-D); fibrinogen (FIB)). In addition, HuoxueHuayu therapy could reduce toxicity caused by chemotherapy and radiotherapy without risks of liver and kidney injury or bleeding, although the effect on tumor metastasis was uncertain. Conclusions: The present update of our systematic review and meta-analyses provided essential evidence for the beneficial effect of HuoxueHuayu therapy to show promise in cancer treatment, improving quality of life, addressing cancer-related symptoms, and reducing toxicity in a secure way.

Chidamide combined with ibrutinib improved the prognosis of primary bone marrow diffuse large B cell lymphoma.

Primary bone marrow diffuse large B cell lymphoma (DLBCL) is an independent pathologic type with a poor prognosis when treated with standard chemoimmunotherapy. Generally, rituximab-based high-dose chemotherapy regimens such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) can be administered to young patients, followed by autologous stem cell transplantation. For elderly patients, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen is well tolerated, but it is an insufficient induction therapy for this group. Herein, we reported an elderly patient diagnosed with primary bone marrow DLBCL, germinal center B-cell-like subtype. Considering tolerance, the R-CHOP regimen was administered. However, his disease progressed after two treatment cycles. Then, the rituximab, gemcitabine, dexamethasone, cisplatin, lenalidomide regimen was administered, but the patient still experienced disease progression. Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton's tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission. We found that the response of primary bone marrow DLBCL to chemotherapy was poorer than that of de novo DLBCL. High-dose chemotherapy regimens such as DA-EPOCH should be administered to young patients in combination with rituximab. For elderly patients, new targeted drugs such as HDAC and BTK inhibitors appear to produce favorable outcomes.

Analysis of the water-soluble polysaccharides from Camellia japonica pollen and their inhibitory effects on galectin-3 function.

Pollen has been defined as dietary supplement used to supplement the diet in many countries, but the primary structure and activity of Camellia japonica pollen polysaccharide remain unclear. In this study, the water-soluble polysaccharide extracted from Camellia japonica pollen (WCPP) was fractionated into one neutral fraction (WCPP-N) and two acidic fractions (WCPP-A1 and WCPP-A2) by DEAE-cellulose column, and WCPP-A2 was further fractionated into two homogeneous sub-fractions (WCPP-A2a and WCPP-A2b) by Sepharose CL-6B column. Monosaccharide composition results showed that WCPP-N might mainly contain starch-like glucan as well as some arabinogalactan, while WCPP-A1, WCPP-A2 and its sub-fractions might mainly composed of rhamnogalacturonan I (RG-I) pectic polysaccharide domain backbone with some different types of side chains, including arabinan, galactan, and/or arabinogalactan. The primary structure analysis of WCPP-A2a by NMR spectra analysis suggested that WCPP-A2a was an RG-I-like pectic polysaccharide, branched at the O-4 of Rha residues in the backbone, with α-(1 â†’ 3,5)-L-arabinan as well as type-II arabinogalactan side chain to which were attached. The results of galectin-3-mediated hemagglutination assay indicated that WCPP-A2a exhibited the strongest inhibitory effect on galectin-3 with MIC value around 0.27 µg/mL. These results suggested the potential use of Camellia japonica pollen polysaccharide as a galectin3 inhibitor in functional foods.

System Prediction and Validation of TCM for Chronic Myeloid Leukemia Treatment from the Perspective of Low-Toxicity Chemotherapy: A Stilbene α-Viniferin Has a Proapoptotic Effect on K562 Cells via the Mitochondrial Pathway.

OBJECTIVE: In traditional Chinese medicine (TCM), chronic myeloid leukemia (CML) has been attributed to "poisoned bone marrow," which is viewed as a loss of Qi or blood, a deficiency in Yin or Yang that causes a complex imbalance between cell growth and death. Malignant myeloid progenitor cells display excessive growth that is difficult to control without toxicity. More than 60 herbs in TCM have shown efficacy against CML. However, the key molecules and mechanisms involved in the holistic-level characterization, as well as the effective target associations, are still unknown. METHODS: The present study employed a computational approach with filtering potential compounds via admetSAR, systems biology-based functional data prediction, and biochemical and molecular biological validation. RESULTS: We generated 118 bioactive compounds from 11 herbs within four dialectical therapy groups that are most commonly used to treat CML and predicted 141 potential targets. The stilbene resveratrol and its derivatives were found to be highly related to these targets. Among them, α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. In vitro, experimental data showed a nonnecrotic growth limitation of K562 cells caused by α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. µg·mL-1 at 24 h. Finally, we validated the chemotherapeutic effect of α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. CONCLUSIONS: Our work sheds light on the mechanism of the efficacy of the stilbene α-viniferin in TCM for the prevention of CML. This work also predicts and validates targets in the mitochondrial signaling pathway, providing a novel strategy for CML treatment.α-viniferin was predicted to target Bcl-2, caspase-3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies.

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis.

This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the "ingredient-target-pathway" mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury.

Oxidative stress is an important mechanism in acute lung injury (ALI) induced by paraquat (PQ), one of the most widely used herbicides in developing countries. In clinical prophylaxis and treatment, licorice is a widely used herbal medicine in China due to its strong alexipharmic characteristics. However, the corresponding biochemical mechanism of antioxidation and detoxification enzymes induced by licorice's ingredients is still not fully demonstrated. In this study, the detoxification effect of licorice was evaluated in vivo and in vitro. The detoxification and antioxidation effect of its active ingredients involved in the treatment was screened systematically according to Absorption, Distribution, Metabolism, and Excretion (ADME): predictions and evidence-based literature mining methods in silico approach. Data shows that licorice alleviate pulmonary edema and fibrosis, decrease Malondialdehyde (MDA) contents and increase Superoxide Dismutase (SOD) activity in PQ-induced ALI mice, protect the morphologic appearance of lung tissues, induce cytochrome 3A4 (CYA3A4) and Nuclear factor erythroid 2-related factor 2 (Nrf2) expression to active detoxification pathways, reduce the accumulation of PQ in vivo, protect or improve the liver and renal function of mice, and increase the survival rate. The 104 genes of PPI network contained all targets of licorice ingredients and PQ, which displayed the two redox regulatory enzymatic group modules cytochrome P450 (CYP450) and Nrf2 via a score-related graphic theoretic clustering algorithm in silico. According to ADME properties, glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A were employed due to their oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.1, and being highly associated with CYP450 and Nrf2 pathways, as potential activators to halt PQ-induced cells death in vitro. Both 3A4 inhibitor and silenced Nrf2 gene decreased the alexipharmic effects of those ingredients significantly. All these disclosed the detoxification and antioxidation effects of licorice on acute lung injury induced by PQ, and glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A upregulated CYP450 and Nrf2 pathways underlying the alexipharmic mechanisms of licorice.