A Controlled Trial of Sheng-Yu-Tang for Post-Hematopoietic Stem Cell Transplantation Leukemia Patients: A Proposed Protocol and Insights From a Preliminary Pilot Study.
ABSTRACT: INTRODUCTION:Hematopoietic stem cell transplantation has become a well-established treatment for hematologic disorders including acute leukemia. However, long-term survival rates following this procedure are still extremely low, due to posttransplantation relapse, infections, and graft-versus-host disease. We propose that adjunctive Chinese herbal medicine may benefit posttransplantation patients. In preparation for a randomized clinical trial, we conducted a pilot trial. Methods and Analysis: Between September 2015 and June 2017, 18 patients were consecutively enrolled at China Medical University Hospital and followed for up to 1 year. Fresh blood samples were obtained on a monthly basis, and immune reconstitution was analyzed. In addition to the standard-care treatment administered by their oncologist, a number of patients also received a Chinese herbal formula (Sheng-Yu-Tang) for up to 6 months. Results were used to improve on study protocol and estimate required sample size for a future randomized trial. Ethics and Dissemination: Study protocol was approved by the institutional review board of China Medical University Hospital (DMR-105-005), and all participants provided informed consent.
Project description:Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.
Project description:As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than thirty years to treat postpartum diseases, especially anaemia. However, the underlying therapeutic mechanisms of XSHG for anaemia were still unclear.
Project description:To investigate whether Du-Huo-Ji-Sheng-Tang (DHJST) attenuate inflammation of RA related to lymphatic drainage function in vivo, we treated eight 3-month-old TNF-Tg mice with DHJST (12?g/kg) or the same volume of physiological saline once every day for 12 weeks, and 3-month-old WT littermates were used as negative control. After twelve weeks, we performed NIR-ICG imaging and found that DHJST increased the ICG clearance at the footpad and the pulse of efferent lymphatic vessel between popliteal lymph node and footpad. Histology staining at ankle joints showed that DHJST decreases synovial inflammation, bone erosion, cartilage erosion, and TRAP+ osteoclast area in TNF-Tg mice. Immunohistochemical staining by using anti-Lyve-1 and anti-podoplanin antibody showed that DHJST stimulated lymphangiogenesis in ankle joints of TNF-Tg mice. And zebrafish study suggested that DHJST promoted the formation of lymphatic thoracic duct. In conclusion, DHJST inhibits inflammation severity and promotes lymphangiogenesis and lymphatic drainage function of TNF-Tg mice.
Project description:Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of <i>Cxcr4</i>, <i>Oprd1</i>, and <i>Htr2a</i>, while upregulated <i>Adrb2</i>, <i>Drd</i>, <i>Drd4</i>, and <i>Hrh1</i>. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand-receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.
Project description:As a well-known traditional Chinese medicine (TCM) prescription, Xin-Sheng-Hua Granule (XSHG) has been applied in China for more than 30 years to treat postpartum diseases, especially anemia. However, underlying therapeutic mechanisms of XSHG for anemia were still unclear. In this study, plasma metabolomics profiling with UHPLC-QTOF/MS and multivariate data method was firstly analyzed to discover the potential regulation mechanisms of XSHG on anemia rats induced by bleeding from the orbit. Afterward, the compound-target-pathway network of XSHG was constructed by the use of network pharmacology, thus anemia-relevant signaling pathways were dissected. Finally, the crucial targets in the shared pathways of metabolomics and network pharmacology were experimentally validated by ELISA and Western Blot analysis. The results showed that XSHG could exert excellent effects on anemia probably through regulating coenzyme A biosynthesis, sphingolipids metabolism and HIF-1? pathways, which was reflected by the increased levels of EPOR, F2, COASY, as well as the reduced protein expression of HIF-1?, SPHK1, and S1PR1. Our work successfully explained the polypharmcological mechanisms underlying the efficiency of XSHG on treating anemia, and meanwhile, it probed into the potential treatment strategies for anemia from TCM prescription.
Project description:Zeng Sheng Ping (ZSP) is a traditional herbal remedy used to prevent progression and growth of neoplastic lesions. It has been shown to inhibit Notch2 expression in a murine lung cancer model, leading us to investigate its therapeutic potential in Notch-dependent brain tumors.3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), apoptosis, and quantitative real-time polymerase chain reaction (RT-PCR) analyses were performed in glioma and medulloblastoma cell lines, and morphological analyses in DAOY flank xenografts.ZSP inhibited brain tumor growth in vitro, in part, by apoptotic induction. Down-regulation of the Notch2 receptor, the pathway target Hairy/Enhancer of Split homolog 1 (Hes1), and of the stem cell markers Nestin and CD133 was also observed. Reductions in tumor mass and increases in the necrotic fraction of DAOY xenografts, in mice treated with oral ZSP were also observed, but these were not significant.ZSP can block brain tumor growth and the expression of Notch pathway members and stem cell markers in vitro.
Project description:Roots of Angelica sinensis (Danggui) have been used in promoting blood circulation as herbal medicine for over 2000 years in China. Another species of Angelica roots called A. gigas is being used in Korea. To reveal the efficiency of different Angelica roots, the chemical and biological properties of Angelica roots from different cultivated regions were compared. Roots of A. sinensis contained higher levels of ferulic acid, Z-ligustilide, and senkyunolide A, while high amounts of butylphthalide and Z-butylenephthalide were found in A. gigas roots. The extracts deriving from A. gigas roots showed better effects in osteogenic and estrogenic properties than that of A. sinensis from China. However, this difference was markedly reduced when the Angelica roots were being prepared in a Chinese herbal decoction together with Astragali Radix as Danggui Buxue Tang. In contrast, the herbal decoction prepared from A. sinensis roots showed better responses in cell cultures. In addition, the extracts of A. gigas roots showed strong cell toxicity both as single herb and as Danggui Buxue Tang. This result revealed the distinct properties of Angelica roots from China and Korea suggesting the specific usage of herb in preparing a unique herbal decoction.
Project description:<h4>Purpose</h4>Tong Sheng tablets (TSTs) have long been used for treating cerebral ischemic reperfusion injury (CIRI) in clinic, but the underlying mechanism remains unknown. Therefore, in this study, TSTs were evaluated systematically using chemical analysis, network pharmacology and classical pharmacology.<h4>Methods</h4>The first part was TSTs quality control including TSTs fingerprint establishment and chemicals identification. In the second part, network pharmacology analysis and bioinformatics were combined to construct a compound-target-disease network, which can screen out key targets or pathways, revealing complex molecule mechanism of TSTs. The last part was experiment verification. Classical pharmacology of TSTs was investigated <i>in vivo</i> to verify the results of network pharmacology.<h4>Results</h4>(1) Fingerprints of TSTs were established, and 11 characteristic peaks were identified using HPLC. (2) Network pharmacology and bioinformatics suggested that the protection of TSTs in treating CIRI might be related to regulation of oxidative stress, inflammation and apoptosis, and some key molecules such as Nrf2, IL-1?, TNF, Bcl-2 and Cyt-C involved in the pathways. (3) TSTs significantly improved neurologic behavior scores, decreased the areas of ischemic necrosis and neuronal necrosis, and increased Nissl body counts. Besides, TSTs significantly decreased pro-inflammatory cytokine (IL-1?, TNF-?) and pro-oxidative product levels (LPO, MDA) and increased anti-oxidative product levels (NO, SOD). TSTs downregulated the protein expressions of Nrf2 and HO-1. Meanwhile, TSTs reduced apoptotic cell counts, downregulated the protein expressions of Cyt-C and Bax, and upregulated the protein expression of Bcl-2. In terms of autophagy, TSTs enhanced LC-3B protein expression.<h4>Conclusion</h4>The present results illustrated that TSTs effectively alleviated CIRI, and the underlying mechanism might be associated with multiple molecular pathways. Herein, we established a primary pattern for studying Chinese herbal compounds and provided basic guidance for future investigation.
Project description:<h4>Background</h4>The eosinophil cationic protein (ECP) is cytotoxic to bacteria, viruses, parasites and mammalian cells. Cells are damaged via processes of pore formation, permeability alteration and membrane leaking. Some clinical studies indicate that ECP gathers in the bronchial tract of asthma sufferers, damages bronchial and airway epithelial cells, and leads to in breathing tract inflammation; therefore, prevention of the cytotoxicity caused by ECP may serve as an approach to treat airway inflammation. To achieve the purpose, reduction of the ECP-cell interactions is rational. In this work, the Chinese herbal combinative network was generated to predict and identify the functional herbs from the pools of prescriptions. It was useful to select the node herbs and to demonstrate the relative binding ability between ECP and Beas-2B cells with or withour herb treatments.<h4>Results</h4>Eighty three Chinese herbs and prescriptions were tested and five effective herbs and six prescription candidates were selected. On the basis of effective single-herbal drugs and prescriptions, a combinative network was generated. We found that a single herb, Gan-cao, served as a node connecting five prescriptions. In addition, Sheng-di-huang, Dang-guei and Mu-tong also appeared in five, four and three kinds of prescriptions, respectively. The extracts of these three herbs indeed effectively inhibited the interactions between ECP and Beas-2B cells. According to the Chinese herbal combinative network, eight of the effective herbal extracts showed inhibitory effects for ECP internalizing into Beas-2B cells. The major components of Gang-cao and Sheng-di-huang, glycyrrhizic acid and verbascose, respectively, reduced the binding affinity between ECP and cells effectively.<h4>Conclusions</h4>Since these Chinese herbs reduced the binding affinity between ECP and cells and inhibited subsequent ECP entrance into cells, they were potential for mitigating the airway inflammation symptoms. Additionally, we mentioned a new concept to study the Chinese herbs using combinative network in the field of systems biology. The functional single herbs could be identified from the set of prescriptions.
Project description:INTRODUCTION:Cancer-related fatigue is a frequent symptom in patients with cancer and one of the most distressing symptoms in patients with breast cancer. Sipjeondaebo-tang (Juzen-taiho-to in Japanese or Shi-Quan-Da-Bu-Tang in Chinese) is a widely used herbal medicine for the treatment of fatigue in Korea, China and Japan. The purpose of the present study is to evaluate the feasibility of Sipjeondaebo-tang for cancer-related fatigue. METHODS AND ANALYSIS:The present study is a randomised, double-blind, placebo-controlled, cross-over study. Forty-eight patients with breast cancer who are indicated for doxorubicin and cyclophosphamide will be recruited. The participants will receive 3?g of Sipjeondaebo-tang or a placebo three times a day for 56?days. The primary outcome measurement is the change in the Brief Fatigue Inventory scores. The secondary outcome measurements include the changes in the Visual Analogue Scale (VAS) of fatigue, and quality of life measured by the European Organization for Research and Treatment of Cancer-QLQ-C30 and QLQ-BR23. VAS of fatigue will be measured on every visit, and other outcomes will be measured on visits 2, 4, 6 and 7. The total study period is 14?weeks. ETHICS AND DISSEMINATION:This study has been approved by the Institutional Review Board of the Catholic Kwandong University International St Mary's Hospital (reference IS16MNSI0011). The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER:NCT02858856; Pre-results.