Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

Constituents of the anti-asthma herbal formula ASHMI(TM) synergistically inhibit IL-4 and IL-5 secretion by murine Th2 memory cells, and eotaxin by human lung fibroblasts in vitro.

OBJECTIVE: Anti-asthma herbal medicine intervention (ASHMI(TM)), a combination of three traditional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMI(TM) exhibited synergy. METHODS: Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme-linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS: Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC25) values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50 values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-1. The interaction indices at IC50 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC50 values. All interaction indices were below 1 which indicated synergy. CONCLUSION: By comparing the interaction index values, we find that constituents in ASHMI(TM) synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.

Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo.

Allergic asthma is associated with Th2-mediated inflammation. Several flavonoids were isolated from Glycyrrhiza uralensis, one of the herbs in the anti-asthma herbal medicine intervention. The aim of this investigation was to determine whether Glycyrrhiza uralensis flavonoids have inhibitory effects on memory Th2 responses in vitro and antigen-induced Th2 inflammation in vivo. The effects of three Glycyrrhiza uralensis flavonoids on effector memory Th2 cells, D10.G4.1 (D10 cells), were determined by measuring Th2 cytokine production. Isoliquiritigenin, 7, 4'-dihydroxyflavone (7, 4'-DHF) and liquiritigenin significantly suppressed IL-4 and IL-5 production in a dose-dependent manner, 7, 4'-DHF being most potent. It was also evaluated for effects on D10 cell proliferation, GATA-3 expression and IL-4 mRNA expression, which were suppressed, with no loss of cell viability. Chronic treatment with 7, 4'-DHF in a murine model of allergic asthma not only significantly reduced eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increased IFN-γ production in lung cell cultures in response to antigen stimulation.

[Clinical effect of chaipo granule combined with routine treatment on refractory asthma].

OBJECTIVE: To evaluate the therapeutic effect of Chaipo Granule (CPG) combined with routine treatment on refractory asthma. METHODS: Sixty patient with refractory asthma were assigned equally in a double-blind, randomized way to the treatment group and the control group. Routine treatment (including regular inhalation of salmeterol and fluticasone propionate 50/250 microg, and if necessary, inhalation of salbutamol + ipratropium bromide) were given to all patients. CPG (3 pouches every time, twice a day) were administered to the treatment group in addition, while to the control group, placebo with similar appearance in equal volume was given. The therapeutic course for all was 24 weeks. Asthma control test (ACT) scoring and lung function tests (FEV1 and PEF) were performed before treatment and at the end of the 4th, 12th and 24th week; daily records of asthma, dose of hormone used, withdrawal reaction and adverse reaction occurred were monitored, and serum levels of cortisol, total IgE and cytokines (IL-4, IL-5, IL-13 and IFN-gamma) were measured before treatment and at terminating the 24-week treatment. RESULTS: Symptoms and lung function were significantly improved after treatment in both groups, but the improvements were better in the treatment group than the control group at all time points, the difference between groups was statistically significant (P < 0.05). Levels of IL-5, IL-13, total IgE decreased, IFN-gamma and Cor increased in all patients after 24-week treatment, but the improvements in the treatment group was more significant, with statistical difference between groups (P < 0.05); the mean hormone withdrawal time in the treatment group was (14.6 +/- 5.1) days, with the incidence of systemic withdrawal reactions of 20%, while those in the control group was (22.1 +/- 6.8) days and 36.7% correspondingly, the difference between groups was statistically significant (P < 0.05). However, one patient in the treatment group quit the trial due to a severe seizure of asthma. No obvious treatment-related side effects appeared in the treatment group, except that 3 patients suffered from slight abdominal pain. CONCLUSIONS: CPG could improve the clinical symptoms and lung function, facilitate to Th1/Th2 balance and enhance the secretion of adrenal cortex. It is an effective and safe Chinese herbal remedy for treatment of refractory asthma.

Pharmacology and immunological actions of a herbal medicine ASHMI on allergic asthma.

Allergic asthma is a chronic and progressive inflammatory disease for which there is no satisfactory treatment. Studies reported tolerability and efficacy of an anti-asthma herbal medicine intervention (ASHMI) for asthma patients, developed from traditional Chinese medicine. To investigate the pharmacological actions of ASHMI on early- and late-phase airway responses (EAR and LAR), Ovalbumin (OVA)-sensitized mice received 6 weeks of ASHMI treatment beginning 24 h following the first intratracheal OVA challenge. EAR were determined 30 min following the fourth challenge and LAR 48 h following the last challenge. ASHMI effects on cytokine secretion, murine tracheal ring contraction and human bronchial smooth muscle cell prostaglandin (PG) production were also determined.ASHMI abolished EAR, which was associated with significantly reduced histamine, leukotriene C4, and OVA-specific IgE levels, as well as LAR, which was associated with significantly reduced bronchoalveolar lavage fluid (BALF) eosinophils, decreased airway remodeling, and lower Th2 cytokine levels in BALF and splenocyte cultures. Furthermore, ASHMI inhibited contraction of murine tracheal rings and increased production of the potent smooth muscle relaxer PGI(2). ASHMI abrogation of allergic airway responses is associated with broad effects on asthma pathological mechanisms.

Efficacy and tolerability of anti-asthma herbal medicine intervention in adult patients with moderate-severe allergic asthma.

BACKGROUND: Chinese herbal medicine has a long history of human use. A novel herbal formula, anti-asthma herbal medicine intervention (ASHMI), has been shown to be an effective therapy in a murine model of allergic asthma. OBJECTIVE: This study was undertaken to compare the efficacy, safety, and immunomodulatory effects of ASHMI treatment in patients with moderate-severe, persistent asthma with prednisone therapy. METHODS: In a double-blind trial, 91 subjects underwent randomization. Forty-five subjects received oral ASHMI capsules and prednisone placebo tablets (ASHMI group) and 46 subjects received oral prednisone tablets and ASHMI placebo capsules (prednisone group) for 4 weeks. Spirometry measurements; symptom scores; side effects; and serum cortisol, cytokine, and IgE levels were evaluated before and after treatment. RESULTS: Posttreatment lung function was significantly improved in both groups as shown by increased FEV(1) and peak expiratory flow findings (P<.001). The improvement was slightly but significantly greater in the prednisone group (P<.05). Clinical symptom scores, use of beta(2)-bronchodilators, and serum IgE levels were reduced significantly, and to a similar degree in both groups (P<.001). T(H)2 cytokine levels were significantly reduced in both treated groups (P<.001) and were lower in the prednisone-treated group (P<.05). Serum IFN-gamma and cortisol levels were significantly decreased in the prednisone group (P<.001) but significantly increased in the ASHMI group (P<.001). No severe side effects were observed in either group. CONCLUSION: Anti-asthma herbal medicine intervention appears to be a safe and effective alternative medicine for treating asthma. In contrast with prednisone, ASHMI had no adverse effect on adrenal function and had a beneficial effect on T(H)1 and T(H)2 balance.

The potential use of Chinese herbal medicines in treating allergic asthma.

OBJECTIVE: To discuss the potential use of the Chinese herbal formula MSSM-002 in treating asthma based on its effects on a murine model of allergic asthma, immunoregulatory actions on T(H)2 cells in vitro, and the means of standardization for herbal formula quality control. DATA SOURCES: Information presented at the 2002 American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting International Symposium on Complementary Alternative Medicine in San Antonio, TX. STUDY SELECTION: All presentations from the ACAAI meeting that discussed MSSM-002 were considered for this review. RESULTS: The Chinese herbal formula MSSM-002 suppressed airway hyperreactivity and eosinophilic inflammation in a murine model of allergic asthma. These effects were comparable to dexamethasone but were not accompanied by the suppression of T(H)1 responses seen with dexamethasone. In vitro studies demonstrated that MSSM-002 significantly decreased antigen-induced T(H)2 cytokine secretion by murine T(H)2 polarized splenocytes and human mucosal T(H)2 cell lines, which in contrast to dexamethasone did not cause apoptosis and was not cytotoxic but was associated with decreased GATA-3 expression. Chromatographic fingerprints of MSSM-002 and evaluation of in vivo actions showed that the quality of several batches of MSSM-002 was consistent. CONCLUSION: MSSM-002 has a therapeutic effect on allergic asthma and immunoregulatory actions on established T(H)2 cells and may prove to be of potential clinical benefit to asthma patients.