Immunomodulatory effects of modified Liu-Wei-Di-Huang-Wan Traditional Chinese medicine on allergic asthmatic mice.

BACKGROUND: Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma. METHODS: This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice. RESULTS: At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL-4, IL-5, and IL-13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung. CONCLUSION: It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology.

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology / 中国天然药物

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Paeonifiorin sulfonate as a characteristic marker for specifically inspecting Chinese patent medicine Liu-Wei-Di-Huang-Wan contained sulfur-fumigated Moutan Cortex.

Sulfur fumigation can induce chemical transformation of bioactive components, consequently the alteration of bioactivities or even toxicities of medicinal herbs. Inspecting Chinese patent medicines (CPM) contained sulfur-fumigated constituent herbs is crucial for ensuring the safety and efficacy of CPM. Paeonifiorin sulfonate is a sulfur-fumigation induced compound of Moutan Cortex (MC), one of the main constituent herbs of a commonly used CPM Liu-Wei-Di-Huang-Wan (LWDHW). Herein, we investigated the approach of paeonifiorin sulfonate as a characteristic marker for specifically inspecting LWDHW potentially contained sulfur-fumigated MC (SFMC). First, mimic LWDHW samples contained SFMC (SFMC-LWDHW) and non-fumigated MC (NFMC-LWDHW) were prepared respectively. Second, an LC-MS method was developed and validated to qualitatively and quantitatively determine paeonifiorin sulfonate in the mimic LWDHW samples. Third, the established method was applied to analyze the commercial LWDHW samples. The results showed that paeoniflorin sulfonate could only be detectable in SFMC-LWDHW, but not in NFMC-LWDHW samples. The CPM matrix could enhance the response of paeoniflorin sulfonate in mass spectrometry analysis. In addition, the LOQ, linearity, precision, accuracy and stability were also demonstrated to be acceptable for quantifying paeoniflorin sulfonate in LWDHW. Commercial samples analysis indicated that paeoniflorin sulfonate were detectable in 9 of 10 commercial LWDHW samples, with the content varied between 105.53µg/g and 438.61µg/g. All the results suggested that paeoniflorin sulfonate could be used as a characteristic and reliable chemical marker for specifically inspecting commercial LWDHW contained SFMC. This study also provides a new strategy for the quality control of other CPMs potentially produced from sulfur-fumigated constituent herbs.

Effects ofLiuwei-Dihuang Pills combined with Ginkgo Biloba Leaves Extract Tablets on complications of type 2 diabetes mellitus / 国际中医中药杂志

Objective To investigate the effects ofLiuwei-Dihuang Pills combined with Ginkgo Biloba Leaves Extract Tablets on diabetic complications in patients with type 2 diabetes mellitus (T2DM). Methods Seventy-eight patients with T2DM were randomized into a TCM treatment group and a conventional treatment group by random number table method, 39 in each group. The patients in the conventional treatment group were regularly using antihyperglycemic drugs or insulin. On the basis of conventional treatment group, the patients in the TCM treatment group were additionally treated withLiuwei-Dihuang Pills and Ginkgo Biloba Leaves Extract Tablets. Intima-media thickness (IMT) of internal carotid artery, vibration perception threshold (VPT) and diabetic retinopathy in both groups were detected before the treatment, 12 and 36 months after the treatment.Results The VPT in the left foot 12 months after the treatment in the TCM treatment group were significantly lower than that in the conventional treatment group (13.98 ±4.38 Vvs. 18.70 ±2.43 V;t=2.764, P=0.008). IMT of internal carotid artery (left: 0.81 ± 0.16 mmvs.0.70 ± 0.10 mm,t=3.120,P=0.003; right: 0.81 ± 0.17 mmvs. 0.73 ± 0.12 mm,t=2.286,P=0.026), VPT (left foot: 14.82 ± 6.45 Vvs. 20.63 ± 9.75 V,t=2.714, P=0.009; right foot: 16.73 ± 7.10 Vvs. 20.73 ± 10.35 V,t=2.001,P=0.048) and incidence of diabetic retinopathy (35.9%vs. 53.8%;χ2=5.804,P=0.016) 36 months after the treatment in the TCM treatment group were significantly lower than those in the conventional treatment group.ConclusionsLiuwei-Dihuang Pills combined with Ginkgo Biloba Leaves Extract Tablets can effectively reduce the progression of diabetic complications in patients with T2DM.

Integrating traditional Chinese medicine healthcare into diabetes care by reducing the risk of developing kidney failure among type 2 diabetic patients: a population-based case control study.

ETHNOPHARMACOLOGICAL RELEVANCE: Our previous study indicated that the traditional Chinese medicine (TCM) formula Liu-Wei-Di-Huang-Wan, which consists of six type of herbs, namely Rehmannia glutinosa (Gaertn.) DC., root, dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica subsp. orientale (Sam.) Sam., tuber, dried; Paeonia × suffruticosa Andrews, bark, dried; Poria cocos (Fr.) Wolf., sclerotium, dried, is the most frequently prescribed herbal formula used to treat type 2 diabetes patients. The aim of the study was to evaluate the integration of TCM into diabetes care in terms of how it reduces the risk of developing kidney failure. MATERIALS AND METHODS: The Taiwan׳s National Health Insurance Research Database (NHIRD) provided detailed information of health care services for each patient and covers 98% of all Taiwan residents as of 2007. Case and control subjects were selected from the NHIRD. Two multivariable logistic regression models were constructed in order to explore two types of exposure assessments including prescription of TCMs (model 1) and prescription of different estimated dosages of Liu-Wei-Di-Huang-Wan (model 2). RESULTS: Using logistic regression model 1, having used TCMs was independently associated with a decreased risk of kidney failure by multivariable analysis (OR=0.69, 95% CI: 0.61-0.77). Using logistic regression model 2, there was no difference between non-Liu-Wei-Di-Huang-Wan TCM users and Liu-Wei-Di-Huang-Wan TCM users in terms of the risk of developing kidney failure. Furthermore, there was also no linear dose-response trend when we used exposure to prescribed Liu-Wei-Di-Huang-Wan as a continuous variable (for non-Liu-Wei-Di-Huang-Wan TCM users, OR=0.68, 95% CI: 0.60-0.77; for TCM users consuming 1-30 g of Liu-Wei-Di-Huang-Wan, OR=0.69, 95% CI: 0.54-0.87; for >30 g of Liu-Wei-Di-Huang-Wan, OR=0.84, 95% CI: 0.49-1.44). CONCLUSIONS: Integrating TCM healthcare into diabetes care was found to be associated with a decreased risk of developing kidney failure. Having recognized the use of TCM, exploring any potential interactions and adverse effects, and integrating both technologies into a holistic treatment system may be beneficial to the relief of diabetic nephropathy on patients with type 2 diabetes.

Evaluation of symptom, clinical chemistry and metabolomics profiles during Rehmannia six formula (R6) treatment: an integrated and personalized data analysis approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannia Six Formula (R6, Chinese name is Liu Wei Di Huang Wan) is one of the most important classic Chinese medicine formula used to treat metabolic disorders related to aging. It was first reported in the Chinese medicine book titled 'Xiao Er Yao Zheng Zhi Jue by Qian Yi' (Chinese Song dynasty: 1035-1117). In modern times it is therefore often used to treat diabetes, pre-diabetes, fatigue and people with metabolic syndrome. The aim of this study is to measure changes in symptoms, clinical parameters and serum metabolite profiles during R6 treatment of human subjects with features of metabolic syndrome. MATERIALS AND METHODS: Symptoms, clinical parameters and serum metabolites were measured before and after 4 and 8 weeks of R6 treatment. Nonlinear Principal Component Analysis was applied for the first time to conduct an integrated analysis of the three data sets. Correlation structures were compared before treatment and after 4 and 8 weeks of treatment. Additionally, a State Space Grid approach was used to study personalized changes in symptom profiles. RESULTS: The symptoms 'hectic fever' and 'spontaneous sweating' were found to be most relieved during R6 treatment. Most of the symptoms were less correlated with other variables after 8 weeks of R6 treatment. LDL-C, total cholesterol, systolic blood pressure and waist size were found to decrease during R6 treatment. Additionally, 10 of the 15 measured phosphatidylcholines were found to decrease. Personalized symptom profiles as described by Chinese medical terms show that most Yin deficiencies are addressed first by R6 treatment. However, in subjects with reduced or less Yin deficiency but which do have a substantial Qi deficiency a reduction of Qi deficiency is subsequently observed. CONCLUSIONS: R6 treatment was shown to improve the lipid profile indicating a reduction of cardiovascular risk. Additionally, the changes observed in correlation structure indicate a different angle of looking at treatment effects. Less strong correlations between symptoms and metabolites suggest a healthier situation after R6 treatment. A State Space Grid analysis showed that the effect of R6 was different for the Yin deficiency subjects and the Qi deficiency subjects. The observed decrease of Yin deficiency related symptoms is in agreement with the use of R6 in Chinese medicine to nourish Yin. Observing individual differences in treatment effects is therefore an essential step in the development of personalized medicine.

Immunopharmacological Studies on LWDHW and RGL / 中国免疫学杂志

The effect of Liu Wei Di Huang Wan(LWDHW)and Rehmannia glutinosa Libosch(RGL)on the immune function of normal and immune-suppressed mice were observed.The results showed that the two medicinal herbs given orally can correct the suppres-sive effect of cyclophosphamide on spleen and thymus weight,serum specific antibodylevel and lymphocyte transformation.They can also improve the phagocytic activity ofperitoneal macrophages and enhance peripheral blood ANAE~+ lymphocyte ratio of mi-ce.Under the same conditions,no obvious effect of LWDHW and RGL on the normalmice was found except that RGL can increase the antibody level of normal mice.Theresults implicate that LWDHW and RGL may have some immunomodulatary effect.