San-Zhong-Kui-Jian-Tang Exerts Antitumor Effects Associated With Decreased Cell Proliferation and Metastasis by Targeting ERK and the Epithelial-Mesenchymal Transition Pathway in Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive cancer whose 5-year survival rate remains poor. San-Zhong-Kui-Jian-Tang (SZKJT), a Chinese herbal formula, has long been used in clinical practice as adjuvant therapy in cancers. However, its therapeutic effects and molecular mechanisms in OSCC remain unclear. METHODS: We investigated the potential therapeutic effects and molecular mechanism of SZKJT in OSCC in tumor cell lines and in tumor xenograft mice and evaluated combined SZKJT and cisplatin treatment efficacy. In vitro-cultured OSCC cells were administered SZKJT at different doses or SZKJT plus cisplatin, and cell proliferation, colony formation assays, and cell cycle analysis were used to assess the effects on cancer cell proliferation and apoptosis. We also analyzed the effects of SZKJT on oral cancer cell line migration, the regulation of mitogen-activated protein kinase (MAPK) signaling, and epithelial-mesenchymal transition (EMT)-associated genes. The antitumor effects of SZKJT plus cisplatin were also tested in vivo using a tumor-bearing NOD/SCID mice model. RESULTS: The results showed that SZKJT effectively inhibited OSCC cell proliferation, induced cell cycle S phase arrest, and induced cell apoptosis. SZKJT also inhibited cell migration by modulating the MAPK signaling and epithelial-mesenchymal transition (EMT) pathway. Further exploration suggested that SZKJT affects OSCC by modulating ERK pathway; downregulating vimentin, fibronectin, and Oct-4; and upregulating E-cadherin. In vivo, SZKJT significantly inhibited tumor growth, and SZKJT and cisplatin exerted synergistic antitumor effects in model animals. CONCLUSIONS: SZKJT exerts antitumor effects in OSCC cells. Additionally, SZKJT and cisplatin exhibit synergy in OSCC treatment. These findings support the clinical usage of Chinese herbal formulas as adjuvant therapy with chemotherapy in cancer treatment.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear. The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions. Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd . was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort. The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.

The survival outcome of nasopharyngeal cancer patients with traditional Chinese medicine external use: A hospital-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: External-use traditional Chinese medicine (TCM) agents are widely used to relieve the adverse effects of radiation therapy in nasopharyngeal cancer patients. AIM OF THE STUDY: Our study aimed to evaluate the influence of external-use TCM agents to relieve radiotherapy-related adverse effects on the efficacy of radiation therapy and the prognosis of nasopharyngeal cancer patients. MATERIALS AND METHODS: By using the Chang Gung Research Database (CGRD), we analyzed 1823 newly diagnosed nasopharyngeal cancer patients with radiotherapy-related adverse effects between 2001/01 and 2015/12. We used Kaplan-Meier analysis and a Cox regression model to estimate the differences in effects on survival outcomes between two groups, TCM external users and non-TCM external users. RESULTS: We found that TCM external users had significantly better 3-year and 5-year overall survival rates (log-rank test, p = 0.0377 and p = 0.034, respectively) than non-TCM external users. The 3-year and 5-year disease-free survival rates were not statistically significantly different between the groups. We also found a trend of improved 3-year and 5-year overall survival rates in TCM external users with advanced-stage disease, without statistical significance (log-rank test, p = 0.10 and p = 0.089, respectively). The subgroup analysis revealed lower risks of mortality in TCM external users among the nonhypertension, nonhyperlipidemia, nonischemic heart disease, noncirrhosis, and nonchronic kidney disease groups. CONCLUSIONS: Our study showed that TCM agents external use could significantly improve 3-year and 5-year overall survival rates in nasopharyngeal cancer patients with radiotherapy-related adverse effects.

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

The Relationships between Leptin, Genotype, and Chinese Medicine Body Constitution for Obesity.

METHODS: The adults with body mass index (BMI) more than 27 kg/m2 were enrolled in the study. General personal information, physical condition, TCMBC, biochemical, and SNPs were collected for eligible subjects. The body constitution questionnaire (BCQ) was used to evaluate the relationships between TCMBC tendency, biochemical values, and obesity-related SNPs. RESULTS: Obesity patients tended to have a yin deficiency constitution (YinDC) (n = 33, 66.0%); however, TCMBC in combination is not uncommon (30 subjects with more than two TCMBC in combination). For biochemical profiles, leptin was higher among patients with yang deficiency constitution (YangDC) (YangDC versus non-YangDC: 29.7 ± 24.8 versus 15.9 ± 9.9, P=0.020) and YinDC (YinDC versus non-YinDC: 28.8 ± 23.5 versus 14.4 ± 9.6, P=0.020). The leptin level was highest among YangDC subjects. Higher leptin was found among subjects with three-combined TCMBC than balanced TCMBC subjects who were not inclined to any of three TCMBC. For obesity-related SNPs, the adrenergic receptor beta-3 (ADRB3) gene tended to be high expression among YangDC (YangDC versus non-YangDC: 89.7% versus 71.4%, P=0.091) and uncoupling protein 1 (UCP1) tended to be high expression among phlegm-stasis constitution (PSC) (PSC versus non-PSC: 37.9% versus 9.5%, P=0.052). CONCLUSIONS: The relationships between TCMBC, leptin, and SNPs present alternative viewpoints about TCMBC and could be used as a guide to treat obese patients.

Associations Between Using Chinese Herbal Medicine and Long-Term Outcome Among Pre-dialysis Diabetic Nephropathy Patients: A Retrospective Population-Based Cohort Study.

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear. Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan's National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis. Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value <0.001), and the risk of mortality was 0.42 (95% CI: 0.36-0.49; p-value <0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55-0.63; p-value <0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.), Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf., Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs. Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials.

Identifying the Chinese Herbal Medicine Network and Core Formula for Allergic Rhinitis on a Real-World Database.

MATERIALS AND METHODS: Patients with a primary diagnosis of AR (ICD-9-CM code: 477.9) in 2010 were included, and the National Health Insurance Research Database in Taiwan was used as the data source. Association rule mining and social network analysis were used to establish and explore the CHM network. Possible molecular pathways of the CHM network were summarized and compared with commonly used western medicine (WM) by conducting overrepresentation analysis in the Reactome pathway database. The potential proteins acted by CHMs were obtained from the CHM ingredient-protein databases, including STITCH, TCMSP, TCMID, and TCM@Taiwan. RESULTS: There were 89,148 AR subjects found in 2010, and a total of 33,507 patients ever used CHM. On an average, 5.6 types of CHMs were utilized per prescription. Xin-Yi-Qing-Fei-Tang was used most frequently (25.5% of 222,279 prescriptions), while Xiao-Qing-Long-Tang with Xin-Yi-San was the most commonly prescribed CHM-CHM combination. Up to six distinctive clusters could be found among the CHM network, and core CHMs could be found for AR, such as Xiao-Qing-Long-Tang and Xin-Yi-Qing-Fei-Tang. A total of 140 molecular pathways were covered by the CHM network (2,432 ingredients from 31 kinds of CHMs), while 39 WMs covered 55 pathways. Among pathways responding to the immune system, WM mainly acted on cytokine signaling-related pathways, while CHM mostly acted on neutrophil/macrophage-related innate pathways and dendritic cell-related adaptive immunity pathways. CONCLUSION: Our study demonstrated and analyzed the CHM network for AR. Core CHM for AR and possible molecular pathways were presented as well, and this information is crucial for researchers to select candidates for CHM-related studies.

Traditional Chinese medicine use is associated with lower end-stage renal disease and mortality rates among patients with diabetic nephropathy: a population-based cohort study.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. METHODS: A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan-Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. RESULTS: Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9-15.0] and 16.6% for nonusers (95% CI: 16.0-17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1-34.6) and 49.2% for nonusers (95% CI: 48.5-49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78-0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47-0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6-59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4-30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. CONCLUSIONS: The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed.

A Randomized Clinical Efficacy Trial of Red Yeast Rice (Monascus pilosus) Against Hyperlipidemia.

Red yeast rice (RYR) has been used as an alternative treatment for hyperlipidemia. According to the previous studies, other compounds, besides monacolin K in RYR, may also reduce the serum lipid level. This study aims at examining the efficacy of monacolin K-rich and Gamma-Aminobutyric Acid (GABA)-rich RYR (Monascus pilosus) with regards to treating hyperlipidemia in a randomized control, double-blind clinical trial. In the research, we assigned 50 eligible subjects to monacolin K-rich RYR, GABA-rich RYR and placebo groups ( n=16 , 17, 17, respectively). The concentrations of TC, LDL-C, HDL, TG and blood biochemical data were evaluated at different phases: before applying (visit 1), after 1-month (visit 2), 2-month (visit 3), 3-month (visit 4) of providing the intervention and 1-month after ending the test food (visit 5) among three groups. During the 3-month intervention, the serum TC and LDL-C levels decreased significantly in the monacolin K group compared to the baseline and the other two groups. The Serum TG level declined steadily but was not statistically significant. Meanwhile, no marked differences in the serum HDL level were revealed among the three groups. Most safety assessment data had minor variation except two subjects (in monacolin K and GABA group separately) reported elevated liver enzymes. Monacolin K-rich RYR can reduce cholesterol as expected, while the GABA-rich RYR performed non-significant reduction on serum triglyceride. The research results demonstrate that using different concentrations and ratios between monacolin K and GABA could be beneficial for antihyperlipidemia.

An Investigation of the Prescription Patterns of Chinese Herbal Products for Chronic Glomerulonephritis Patients: A Hospital-Based Cross-Sectional Study.

Chronic kidney disease (CKD) has a high incidence and prevalence worldwide, and chronic glomerulonephritis (CGN) is one of the main causes of CKD. Therefore, it is important to diagnose and treat CGN early. The purpose of this study is to analyze the prescription patterns and frequencies of Chinese herbal products (CHPs) for CGN by using a hospital-based database from the Chang Gung Memorial Hospital (CGMH), a large, tertiary hospital system in Taiwan, and to evaluate the safety and possible efficacy of CHPs by blood test. The International Classification of Disease Ninth Revision (ICD-9) code 582 was used to identify patients with CGN. From 2004 to 2015, a total of 54726 CHP prescriptions for CGN were provided. Association rule mining was used to analyze the prevalent of CHP combination patterns in treating CGN. Jia-Wei-Xiao-Yao-San (JWXYS) and Gorgon (Euryale feroxSalisb.) were the most frequently prescribed herbal formula (HF) and single herb (SH), respectively. The most frequently prescribed combination of CHPs was that of JWXYS with Bu-Yang-Huan-Wu-Tang (BYHWT) in CGMH. In statistical, the level of eGFR in Stage 3a and 3b group was increasing after treatment in 6 and 12 months and might not cause the renal function to worsen within 12-month treatments. To the best of our knowledge, this is the first pharmacoepidemiological study to review CHP treatments for CGN. However, additional studies and clinical trials are needed to provide data on the safety and efficacy of these CHPs.

Identifying Chinese Herbal Medicine Network for Endometriosis: Implications from a Population-Based Database in Taiwan.

BACKGROUND: Endometriosis is a common but bothersome gynecological disease, and Chinese herbal medicine (CHM) is used for treating endometriosis. The aim of this study is to explore CHM network and core treatments for endometriosis by analyzing nationwide CHM prescription database. METHODS: From 1998 to 2013, the CHM prescriptions made primarily for endometriosis among women diagnosed with endometriosis (ICD-9-CM code: 671) by gynecologists during their reproductive age were collected. CHM network analysis was then carried out by using association rule mining and social network analysis. RESULTS: A total of 12,986 CHM prescriptions made for endometriosis were analyzed. There were 556 kinds of CHM ever used, and, in average, each prescription was composed of 6.2 CHMs. Gui-Zhi-Fu-Ling-Wan (GZFLW) was used most frequently, followed by Cyperus rotundus (28.1% and 18.8% of all prescriptions, resp.). Additionally, the combination of Cyperus rotundus with GZFLW (8.0%) was the most frequently used combination of two CHMs. CHM network showed that GZFLW was the core CHM for endometriosis and graphically demonstrated the extensive coverage of TCM syndromes and pathogenesis of endometriosis. CONCLUSIONS: CHM network provides graphical demonstration and summary of commonly used CHMs for endometriosis, and further studies are warranted based on these findings.

Efficacy of Traditional Chinese Medicine in Xerostomia and Quality of Life during Radiotherapy for Head and Neck Cancer: A Prospective Pilot Study.

Xerostomia is one of the most common acute and late complications of radiotherapy for head and neck cancer, and it affects quality of life. We conducted a prospective study to evaluate the efficacy of traditional Chinese medicine (TCM) in toxicities and quality of life during radiotherapy. Head and neck cancer patients who were scheduled for radiotherapy were checked for inclusion/exclusion criteria before enrollment. Patients in the study group (inpatients) were hospitalized in a Chinese medicine ward and received concomitant TCM intervention during radiotherapy, while those in the control group (outpatients) received only conventional cancer treatments at the Western outpatient department. The primary end point was amelioration of postradiotherapy side effects. The secondary end points were quality of life during the cancer therapy and occurrence of adverse events following the TCM treatments. Thirty inpatients and 50 outpatients completed the study. Compared to the control group, those in the TCM group had decreased severity of xerostomia. There was no treatment-related impairment of renal or hepatic function among TCM group. Although better outcomes of social contact, dyspnea, physical and emotional function, and financial problems were found in the TCM group, we need further confirmation about the impact of hospitalization itself on these results.

Immune-modulatory effects of bu-zhong-yi-qi-tang in ovalbumin-induced murine model of allergic asthma.

BACKGROUND: Bu-zhong-yi-qi-tang (BZYQT), an herbal formula of traditional Chinese medicine, has been an effective regimen of allergic diseases for nearly 800 years. Our previous report has demonstrated its anti-inflammatory effects in patients with perennial allergic rhinitis, and the aim of this study is to investigate the anti-asthmatic effect of BZYQT. METHODS: Female BALB/cByJNarl mice were sensitized with normal saline (control group) or OVA. Mice sensitized by OVA were fed with distilled water (OVA group), oral 0.5 g/Kg (low-dose group) or 1 g/Kg (high-dose group) of BZYQT solution once daily on days 36-40 besides their routine diet. Airway hyper-responsiveness (AHR), eosinophil infiltration, levels of cytokines and total immunoglobulin E (IgE) in broncho-alveolar lavage fluid (BALF) were determined. The lungs and tracheas were removed, and histopathologic examination was subsequently performed. RESULTS: AHR was significantly reduced in both low- and high-dose BZYQT groups compared with the OVA group after inhalation of the highest dose of methacholine (50 mg/ml). The levels of eotaxin, Th2-related cytokines (IL-4, IL-5, IL-13), IgE, and eosinophil infiltration in BALF were significantly decreased in both BZYQT groups compared with the OVA group. Histopathologic examination revealed that eosinophil infiltration of the lung and trachea tissues was remarkably attenuated in both BZYQT groups. CONCLUSIONS: Oral administration of BZYQT solution may exert anti-asthmatic effect by relieving AHR in OVA-sensitized mice, which is compatible with our clinical experience. Although detailed mechanism is to be determined, we surmise that it may be correlated with the immune-modulatory effects of inhibiting Th2 responses on the basis of our limited results.

Identifying chinese herbal medicine network for eczema: implications from a nationwide prescription database.

Eczema is a highly prevalent dermatological disease that can severely affect the patient's quality of life. Chinese herbal medicine (CHM) is commonly used in combination for eczema due to the complicated pathogenesis. This study aimed to identify a CHM network for the treatment of eczema by using a nationwide database. During 2011, 381,282 CHM prescriptions made for eczema (ICD-9-CM 692.x) were obtained from the National Health Insurance Research Database (NHIRD) in Taiwan and analyzed by using association rule mining and social network analysis. Among 661 available CHMs, 44 important combinations were identified. Among the CHM networks, seven clusters with the predominant traditional Chinese medicine (TCM) pattern were recognized. The largest CHM cluster was used to treat the wind-dampness-heat pattern, and Xiao-Feng-San (24.1% of all prescriptions) was the core of this cluster with anti-inflammation, antioxidation, and antiallergic effects. Lonicera japonica (11.0% of all prescriptions) with Forsythia suspense (17.0% of all prescriptions) was the most commonly used CHM combination and was also the core treatment for treating the heat pattern, in which an antimicrobial effect is found. CHM network analysis is helpful for TCM doctors or researchers to choose candidates for clinical practice or further studies.

Use of traditional Chinese medicine reduces exposure to corticosteroid among atopic dermatitis children: a 1-year follow-up cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis is a prevalent dermatologic disease in children. Corticosteroid is an important treatment but side effects caused by long-term and excessive use heavily concern patients. Traditional Chinese medicine (TCM) is potentially an alternative treatment and might cause less adverse effects. This nationwide retrospective cohort study aimed to examine the hypothesis that TCM use is associated with lower exposure to corticosteroid. MATERIALS AND METHODS: Children under 12 years of age with ICD-9 codes 691.8 and 692.x were identified as atopic dermatitis patients from 2007/1/1 to 2007/12/31. Corticosteroid use was compared between TCM users and non-users for one-year follow-up by using a general estimation equation model with propensity-score matching. RESULTS: A total of 9012 TCM users were identified and the use of corticosteroid after treatment was compared with matched TCM non-users. Use of TCM significantly reduced exposure to corticosteroids after 1-year follow-up. Among TCM users, the exposure to any corticosteroids was lower (42.1% reduction in TCM users versus 34.5% increase in TCM non-users, relative risk: 0.36; p-Value<0.001), the duration was shorter (relative risk for using corticosteroid more than 14 days: 0.37; p-Value<0.001), and the rate of frequent visits with steroid prescription was also lower. CHM was the most commonly used TCM modality (98.5% of all visits) and Xiao-Feng-San was the most commonly used CHM (33% of all prescriptions) with extensive coverage for pathogenesis of atopic dermatitis. CONCLUSIONS: Lower use rate of corticosteroid can be found after TCM treatment, which can be considered as an integrative therapy for atopic dermatitis. Further studies are warranted on the basis of this study.

In vitro and in vivo effects of xanthorrhizol on human breast cancer MCF-7 cells treated with tamoxifen.

This study investigated the herb-drug interaction of xanthorrhizol and tamoxifen in human breast cancer cells. Using MCF-7 cell line as an in vitro model, the herb-drug interaction between xanthorrhizol and tamoxifen was measured by MTT assay, luciferase reporter assay, and cell cycle analysis. The effects of xanthorrhizol on growth/autophagy related signaling were determined by immunostaining, western blotting, and real time RT-PCR. Additionally, the in vivo effect of xanthorrhizol and tamoxifen on athymic nude mice implanted with MCF-7 cells was evaluated. When MCF-7 cells were co-treated with tamoxifen and xanthorrhizol, there were no significant changes in terms of cell number, luciferase activity, percentage S-phase cells and LC3-II expression. However, using the MCF-7 implanted nude mice model, it was possible to detect significantly increased tumor volumes, a larger tumor size, and increased protein expression of P38 and P27(Kip1) in the xanthorrhizol + tamoxifen group compared to the tamoxifen-alone group. It can be concluded that while there is no significant herb-drug interaction between xanthorrhizol and tamoxifen in vitro, there is such an interaction in tumor-bearing mice, which provides important information that affects breast cancer treatment translational research.

Screening to Identify Commonly Used Chinese Herbs That Affect ERBB2 and ESR1 Gene Expression Using the Human Breast Cancer MCF-7 Cell Line.

Aim. Our aim the was to screen the commonly used Chinese herbs in order to detect changes in ERBB2 and ESR1 gene expression using MCF-7 cells. Methods. Using the MCF-7 human breast cancer cell line, cell cytotoxicity and proliferation were evaluated by MTT and trypan blue exclusion assays, respectively. A luciferase reporter assay was established by transient transfecting MCF-7 cells with plasmids containing either the ERBB2 or the ESR1 promoter region linked to the luciferase gene. Chinese herbal extracts were used to treat the cells at 24 h after transfection, followed by measurement of their luciferase activity. The screening results were verified by Western blotting to measure HER2 and ER α protein expression. Results. At concentrations that induced little cytotoxicity, thirteen single herbal extracts and five compound recipes were found to increase either ERBB2 or ESR1 luciferase activity. By Western blotting, Si-Wu-Tang, Kuan-Shin-Yin, and Suan-Tsao-Ren-Tang were found to increase either HER2 or ER α protein expression. In addition, Ligusticum chuanxiong was shown to have a great effect on ERBB2 gene expression and synergistically with estrogen to stimulate MCF-7 cell growth. Conclusion. Our results provide important information that should affect clinical treatment strategies among breast cancer patients who are receiving hormonal or targeted therapies.

Identifying Chinese herbal medicine for premenstrual syndrome: implications from a nationwide database.

BACKGROUND: Premenstrual syndrome (PMS) occurs in women during their reproductive age with a quite negative impact on their daily lives. Women with PMS experience a wide range of physical or psychological symptoms and seek treatment for them. Chinese herb medicine (CHM) is commonly used for PMS and the goal of this study is to investigate the prescription patterns of CHM for PMS by using a nationwide database. METHODS: Prescriptions of CHM were obtained from two million beneficiaries randomly sampled from the National Health Insurance Research Database, a nationwide database in Taiwan. The ICD-9 code 625.4 was used to identify patients with PMS. Association rule mining and social network analysis were used to explore both the combinations and the core treatments for PMS. RESULTS: During 1998-2011, a total of 14,312 CHM prescriptions for PMS were provided. Jia-Wei-Xiao-Yao-San (JWXYS) was the CHM which had the highest prevalence (37.5% of all prescriptions) and also the core of prescription network for PMS. For combination of two CHM, JWXYS with Cyperus rotundus L. was prescribed most frequently, 7.7% of all prescriptions, followed by JWXYS with Leonurus heterophyllus Sweet, 5.9%, and Cyperus rotundus L. with Leonurus heterophyllus Sweet, 5.6%. CONCLUSIONS: JWXYS-centered CHM combinations were most commonly prescribed for PMS. To the best of our knowledge, this is the first pharmaco-epidemiological study to review CHM treatments for PMS. However, the efficacy and safety of these commonly used CHM were still lacking. The results of this study provide valuable references for further clinical trials and bench studies.

Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based Study.

Traditional Chinese medicine (TCM), which is the most common type of complementary and alternative medicine (CAM) used in Taiwan, is increasingly used to treat patients with breast cancer. However, large-scale studies on the patterns of TCM prescriptions for breast cancer are still lacking. The aim of this study was to determine the core treatment of TCM prescriptions used for breast cancer recorded in the Taiwan National Health Insurance Research Database. TCM visits made for breast cancer in 2008 were identified using ICD-9 codes. The prescriptions obtained at these TCM visits were evaluated using association rule mining to evaluate the combinations of Chinese herbal medicine (CHM) used to treat breast cancer patients. A total of 37,176 prescriptions were made for 4,436 outpatients with breast cancer. Association rule mining and network analysis identified Hedyotis diffusa plus Scutellaria barbata as the most common duplex medicinal (10.9%) used for the core treatment of breast cancer. Jia-Wei-Xiao-Yao-San (19.6%) and Hedyotis diffusa (41.9%) were the most commonly prescribed herbal formula (HF) and single herb (SH), respectively. Only 35% of the commonly used CHM had been studied for efficacy. More clinical trials are needed to evaluate the efficacy and safety of these CHM used to treat breast cancer.