Sien-Hung Yang

Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component.

BACKGROUND Indigo naturalis has shown efficacy in treating psoriasis in our previous clinical studies. OBJECTIVES To investigate the potential effect of indigo naturalis on regulating keratinocyte proliferation and differentiation. METHODS Skin samples from six patients were analyzed for proliferating cell nuclear antigen (PCNA) and involucrin expression by immunohistochemical staining. In addition, indigo naturalis extracts from 10 to 500 microg/ml were added to cultured keratinocytes and cell viability determined. Real-time RT-PCR, Western blotting analysis and indirect immunofluorescent labeling were used to investigate the messenger (m)RNA and protein expressions of PCNA and involucrin. Finally, high-performance liquid chromatography (HPLC) was used to identify major components of indigo naturalis and their in vitro effects compared. RESULTS Immunohistochemical results demonstrated decreased PCNA and increased involucrin in psoriatic lesions after indigo naturalis treatment. Cultured keratinocytes decreased after indigo naturalis treatment, while G(0)/G(1) arrest was observed to dose-dependently increase. Staining revealed decreased PCNA-stained nuclei and increased cytosolic involucrin in treated keratinocytes. Decreased PCNA and increased involucrin at both the mRNA and protein levels were confirmed. Both major components, indirubin and indigo, could cause G(0)/G(1) phase arrest; however, only indirubin modulated the expressions of PCNA and involucrin similar to indigo naturalis. CONCLUSIONS Together, these findings indicate that the anti-psoriatic effects of indigo naturalis are mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes, with indirubin as the major active component.

Prescription patterns of Chinese herbal products for menopausal syndrome: analysis of a nationwide prescription database.

UNLABELLED ETHNO-PHARMACOLOGICAL RELEVANCE: Chinese herbal products (CHP) are commonly used for menopausal syndrome in traditional Chinese medicine (TCM). AIM OF THE STUDY Because menopausal syndrome is a common issue among women worldwide, this study analyzed the prescription patterns and frequencies of CHP in relieving menopausal syndrome in Taiwan. MATERIALS AND METHODS Prescriptions of CHP for menopausal syndrome were obtained from the nationwide prescription database (National Health Insurance Research Database) of Taiwan. Every prescription with a leading diagnosis of menopausal syndrome made in the year 2002 for women out-patients aged 45-55 years was analyzed. Descriptive statistics and data mining method (association rule mining) were applied to the pattern of co-prescription. RESULTS A total of 54456 prescriptions were made for 15486 subjects in clinical visits. Salvia miltiorrhiza and Dan-zhi-xiao-yao-san were the most commonly prescribed single herb (SH) and herbal formula (HF), respectively. For combinations of two CHP, Salvia miltiorrhiza with Dan-zhi-xiao-yao-san, Zhi-bai-di-huang-wan with Dan-zhi-xiao-yao-san, and Ligustrum lucidum with Eclipta prostrata were the most frequently co-prescribed CHP couplets as SH-HF, HF-HF, and SH-SH, respectively. The most commonly used combination of three CHP was Eclipta prostrata with Ligustrum lucidum and Dan-zhi-xiao-yao-san. The core formula for menopausal syndrome was Dan-zhi-xiao-yao-san. CONCLUSIONS Combinations of CHP are widely used for menopausal syndrome. Data mining analysis demonstrates the core formula and the commonly combined CHP in prescriptions. Further studies are needed to evaluate their efficacy for menopausal syndrome.

Investigation on Chinese herbal medicine for primary dysmenorrhea: Implication from a nationwide prescription database in Taiwan

OBJECTIVE Primary dysmenorrhea is a common gynecological condition, for which Chinese herbal medicine (CHM) has been widely used in addition to western medicine. The aim of this study is to explore CHM commonly used to treat dysmenorrhea in young Chinese women. DESIGN Observational retrospective study. SETTING The National Health Insurance Research Database in Taiwan. POPULATION Women aged from 13 to 25 years with single diagnosis of primary dysmenorrhea. METHODS CHM prescriptions made for primary dysmenorrhea women during 1998-2008 were extracted to build up CHM prescription database. Association rule mining was used to explore the prevalent CHM combination patterns in treating primary dysmenorrhea. MAIN OUTCOME MEASURES Prevalence and mechanisms of CHM combinations. RESULTS Totally 57,315 prescriptions were analyzed and, on average, 5.3 CHM was used in one prescription. Dang-Gui-Shao-Yao-San (DGSYS) was the most commonly used herbal formula (27.2%), followed by Jia-Wei-Xiao-Yao-San (JWXYS) (20.7%) and Wen-Jing-Tang (WJT) (20.5%). Corydalis yanhusuo and Cyperus rotundus were the most commonly used single herb, found in 33.1% and 29.2% of all prescriptions. Additionally, C. yanhusuo with C. rotundus is the most commonly used two CHM in combination, accounting for 14.24% of all prescriptions, followed by DGSYS with C. yanhusuo (10.47%). Multi-target effects on primary dysmenorrhea, such as analgesia, mood modifying and hormone adjustment, were found among commonly prescribed CHM in this study. CONCLUSIONS This study discovered the potential importance of C. yanhusuo, C. rotundus and DGSYS in treating primary dysmenorrhea. Further clinical trials or bench studies are warranted based on the results.

Inhibitory effect of indigo naturalis on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells.

The use of indigo naturalis to treat psoriasis has proved effective in our previous clinical studies. The present study was designed to examine the anti-inflammatory effect of indigo naturalis in primary cultured human umbilical vein endothelial cells (HUVECs). Pretreatment of cells with indigo naturalis extract attenuated TNF-α-induced increase in Jurkat T cell adhesion to HUVECs as well as decreased the protein and messenger (m)RNA expression levels of vascular cell adhesion molecule-1 (VCAM-1) on HUVECs. Indigo naturalis extract also inhibited the protein expression of activator protein-1 (AP-1)/c-Jun, a critical transcription factor for the activation of VCAM-1 gene expression. Since the reduction of lymphocyte adhesion to vascular cells by indigo naturalis extract could subsequently reduce the inflammatory reactions caused by lymphocyte infiltration in the epidermal layer and help to improve psoriasis, this study provides a potential mechanism for the anti-inflammatory therapeutic effect of indigo naturalis extract in psoriasis.

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.

Identifying Core Herbal Treatments for Children with Asthma: Implication from a Chinese Herbal Medicine Database in Taiwan

Asthma is one of the most common allergic respiratory diseases around the world and places great burden on medical payment. Chinese herbal medicine (CHM) is commonly used for Taiwanese children to control diseases. The aim of this study is to analyze the CHM prescriptions for asthmatic children by using a nationwide clinical database. The National Health Insurance Research Database (NHIRD) was used to perform this study. Medical records from 1997 to 2009 with diagnosis with asthma made for children aged 6 to 18 were included into the analysis. Association rule mining and social network analysis were used to analyze the prevalence of single CHM and its combinations. Ma-Xing-Gan-Shi-Tang (MXGST) was the most commonly used herbal formula (HF) (20.2% of all prescriptions), followed by Xiao-Qing-Long-Tang (13.1%) and Xing-Su-San (12.8%). Zhe Bei Mu is the most frequently used single herb (SH) (14.6%), followed by Xing Ren (10.7%). MXGST was commonly used with Zhe Bei Mu (3.5%) and other single herbs capable of dispelling phlegm. Besides, MXGST was the core formula to relieve asthma. Further studies about efficacy and drug safety are needed for the CHM commonly used for asthma based on the result of this study.

Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs

Objective Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs. Methods We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption. Results The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin. Conclusion We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.

Identifying core herbal treatments for urticaria using Taiwan’s nationwide prescription database

ETHNOPHARMACOLOGICAL RELEVANCE Urticaria is a common skin disease that has a high impact on a patients daily life. Chinese herbal medicine (CHM) has been frequently used for treatment of skin manifestations in addition to Western medicine. The aim of this study is to analyze a nationwide prescription database to explore the most commonly used CHM for urticaria. MATERIALS AND METHODS A nationwide CHM prescription database was used, and data from ambulatory visits of patients with a single diagnosis of urticaria (ICD-9 code: 708) were identified for the study. Association rule mining was applied to explore the core formula and popular combinations of CHM for urticaria. RESULTS A total of 33,355 ambulatory visits made by 12,498 patients were included in this study. On average, 6.18 CHMs were used per prescription. Xiao Feng San (XFS) and Cryptotympana pustulata Fabricius were the most commonly used herbal formula (HF) and single herb (SH), found in 49.44% and 24.67% of all prescriptions, respectively. XFS with Cryptotympana pustulata Fabricius were used most frequently in a two-combination CHM (9.95%). Moreover, XFS with Kochia scoparia (L.) Schrad. plus Dictamnus dasycarpus Turcz. were the most frequent three-combination CHM (3.46%). XFS was the core formula for urticaria since it was included in nearly all combinations prescribed for the treatment of urticaria. CONCLUSIONS XFS is the most important core herbal treatment used for urticaria in Taiwan, and Cryptotympana pustulata Fabricius with XFS is the most popular combination. Further well-designed clinical trials and animal model studies for urticaria are still needed to explore the efficacy and mechanism of CHM in urticaria.

The Exploration of Disease Pattern, Zheng, for Differentiation of Allergic Rhinitis in Traditional Chinese Medicine Practice

Pattern, or “zheng,” differentiation is the essential guide to treatment with traditional Chinese medicine (TCM). However, the considerable variability between TCM patterns complicates evaluations of TCM treatment effectiveness. The aim of this study was to explore and characterize the relationship between patterns and the core patterns of allergic rhinitis. We summarized 23 clinical trials of allergic rhinitis with mention of pattern differentiation; association rule mining was used to analyze TCM patterns of allergic rhinitis. A total of 205 allergic rhinitis patients seen at Chang Gung Memorial Hospital from March to June 2005 were included for comparison. Among the 23 clinical trials evaluated, lung qi deficiency and spleen qi deficiencies were the core patterns of allergic rhinitis, accounting for 29.50% and 28.98% of all patterns, respectively. A higher prevalence of lung or spleen qi deficiency (93.7%) was found in Taiwan. Additionally, patients with lung or spleen qi deficiency were younger (27.99 ± 12.94 versus 58.54 ± 12.96 years) and the severity of nasal stuffiness was higher than among patients with kidney qi deficiency (1.35 ± 0.89 versus 0.62 ± 0.65; P < 0.05). Lung and spleen qi deficiencies are the core patterns of allergic rhinitis and determining the severity of nasal stuffiness is helpful in differentiating the TCM patterns.

Effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy: An experimental pilot study

BACKGROUND This study explored the effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy. PATIENTS AND METHODS For this experimental study, 57 subjects were randomly assigned to three groups: acupressure with essential oils (n=17), acupressure only (n=24), and sham acupressure (n=16). Acupoints were Hegu (LI4), Zusanli (ST36), and Sanyingjiao (SP6). All subjects received acupressure once every morning for 5 months, with each acupoint pressed for 1 min. Fatigue, functional status, anxiety, depression, and sleep quality were measured before initial chemotherapy (T0), on Day 1 of third chemotherapy (T1), and on Day 1 of sixth chemotherapy (T2). Outcome differences between groups were analyzed at T0, T1, and T2 by general estimating equations. RESULTS After controlling for baseline outcome values, age, and adherence to acupressure, subjects who received acupressure with essential oils and acupressure had significantly less fatigue in daily living activities and sleep better quality at T1 than subjects who received sham acupressure. Subjects who received acupressure with essential oils had significantly better sleep quality at T2 than the sham acupressure group. Subjects who received acupressure with or without essential oils had greater odds of better functional status at T1 than the sham group. CONCLUSION It is plausible that acupressure with or without essential oils helps lung cancer patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level. Further study is wanted to test this hypothesis.