Study on the Complex Prescription Compatibility Law of the Cold and Hot Nature of Mahuang Decoction(麻黄汤) and Its Categorized Formulae Based on the Cold-Hot Pad Differentiating Assay

Objective：To explore the complex prescription compatibility law of the cold and hot nature of Mahuang Decoction（麻黄汤,MHD） and Maxing Shigan Decoction（麻杏石甘汤,MXSGD）,both categorized formulas but with different hot/cold natures.Methods：Oxygen consumption of mice was determined among three groups：MHD,MXSGD and the control;a cold-hot pad differentiating assay was used to observe the variability of temperature tropism among the groups of mice which was treated with MHD,MXSGD,and their compositions. Meanwhile,the total anti-oxidant capability（T-AOC） activity were detected.Results：After administration of MHD, the mice showed increased oxygen consumption（P0.01）.Compared with MHD group,the remaining rate of MXSGD mice on the hot pad was found to be significantly increased with the cold-hot pad differentiating assay （P0.05）.There was no significant difference（P0.05） among the remaining rates of MXSGD,MXSGD with high dose Gypsum Fibrosum（MXHGF） group,and MXSGD with low dose Gypsum Fibrosum（MXLGF） group mice.Compared with the MHD group,T-AOC activity of the mice in the Consensus Compositons group was significantly decreased（P=0.0494）.Compared with the MXSGD group,T-AOC activity of Gypsum Fibrosum （GF） group was increased significantly（P=0.0013）.Conclusions：The differences in cold and hot nature could be represented objectively between MHD with a hot nature and MXSGD with a cold nature.The reason may be the Gypsum Fibrosum which decreased the efficacy of the consensus compositions.However,increasing or decreasing the dose of Gypsum Fibrosum will not change the cold and hot nature of MXSGD.

Different Effects of Mahuang Decoction and Maxing Shigan Decoction on Animal Temperature Tropism and Correlation to Differences of Cold and Hot Nature of Chinese Materia Medica

Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica (CMM) through the different effects of Mahuang decoction (MHD) and Maxing Shigan decoction (MSD) on animal temperature tropism. Methods The equipment with cold/hot pads was used to investigate the variety of the temperature tropism between two groups of mice treated by MHD and MSD, respectively. Meanwhile, the activities of adenosine triphosphatase (ATPase), superoxide dismutase, succinate dehydrogenase, and malondialdehyde were measured. Results After treated by MHD, the macroscopic behavioral index of remaining rate on warm pad (40 ℃ ) of mice decreased significantly (P < 0.05), suggesting the enhancement of cold tropism, meanwhile, the internal indices of ATPase activity and oxygen consuming volume increased significantly (P < 0.05), suggesting the enhancement of energy metabolism. On the other hand, the above-mentioned indices in MSD group changed on the inverse way. Conclusion The relative drug nature of MHD and MSD revealed in this study is consistent with the theoretical prognostication or definition. It indicates that the internal cold and hot nature of CMM could be reflected in ethological way on the changes of animal temperature tropism which might be internally regulated by body energy metabolism.

Mechanism of improving skin barrier function in a mouse model of atopic dermatitis using Mahuang Lianqiao Chixiaodou decoction and its disassembled formula

Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis(AD).Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group,model group, whole formula group(WF), exterior-releasing formula group(ERF), interior-clearing formula group(ICF), and positive control group(PC). A mouse model of AD was established using the semiantigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and p H, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin,and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction.Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly.Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Intervention of the Mahuang Lianqiao Chixiaodou decoction on immune imbalance in atopic dermatitis-like model mice

Objective:To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis(AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction(MLCD) on skin damage and inflammation factors in an AD-like mouse model.Methods:Ninety-six male BALB/c mice were divided into normal,model,positive control(mometasone furoate),and traditional Chinese medicine treatment(MLCD) groups by a random number table.2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group.The treatment or intervention was administered for seven consecutive days on days 4,18,32,and 39.The mRNA relative expressions of interleukin-4(IL-4),IL-10,interferon-γ(IFN-γ),thymic stromal lymphopoietin(TSLP),and the TSLP receptor(TSLPR) were measured using quantitative real-time polymerase chain reaction,and the serum immunoglobulin E,IL-4,IL-10,and IFN-γ levels were detected using enzyme-linked immunosorbent assay.Results:Compared with the normal group,the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11,25,and 39.Compared with the model group,the epidermal thickness of the positive control group was significantly alleviated on day 39(P <.001),and that of the MLCD group was significantly improved on days 25 and 39(P <.001).Compared with the four observation time points,MLCD had the best treatment effect on day 39 of the experiment and significantly improved the skin damage performance and relieved pathological lesions.On day 39,compared with the model group,MLCD downregulated the skin mRNA relative expressions of IL-4(P=.009),TSLP(P=.030),and TSLPR(P <.001),and reduced the mouse serum levels of IL-4(P=.003).For other serum indicators,no significant difference was observed between the model and MLCD groups.Conclusion:MLCD improved AD-like mice skin damage by regulating the Th1/Th2 immune imbalance.

Efficacy and safety of Mahuang Fuzi Xixin Decoction on sick sinus syndrome： Ameta – analysis

Objective： To evaluate the efficacy and safety of Mahuang Fuzi Xixin Decoction on sick sinus syndrome andprovide evidence for clinical practice. Methods： Randomized controlled trials of all the languages of MahuangFuzi Xixin Decoction on sick sinus syndrome were collected by computer search and manual retrieval. Theretrieval time was from January 2000 to January 2017. According to the inclusion and exclusion criteria, 2reviewers independently selected and extracted data, then evaluated the quality, cross-checked the information andevaluated the quality of menthodology. Through discussion or third reviewer to help solve the divergence, RevMan5.3 software was used to perform meta analysis. Results： A total of 7 documents （n = 612） were finally enrolled,with 358 in Mahuang Fuzi Xixin Decoction group （treatment group） and 254 in control group. Meta analysisshowed that the treatment （86.9%） was more effective than the control （70.1%）, the difference was statisticallysignificant （RR = 1.25, 95% CI：（1.15-1.37）, P 〈 0.001）; the treatment （17.0%） was safer than the control （49.8%）,the difference was statistically significant （RR=0.23,95% CI：（0.06-0.93）, P =0.04）. Conclusion： The existingclinical studies suggest that Mahuang Fuzi Xixin Decoction on sick sinus syndrome is effective and safe; due to thelimited quality of the enrolled documents, the above conclusions need more high-quality randomized controlledtrials to be verified.

Mahuang Xixin Fuzi decoction protects against ovalbumin-induced allergic rhinitis by inhibiting type 2 innate lymphoid cells in mice

Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1/Th2 immunity.Type 2 innate lymphoid cells(ILC2s)are closely associated with GATA3.However,it remains unknown whether ILC2s could be one mechanism through which MXFD acts.We sought to elucidate the efficacy and mechanism of action of this decoction in AR treatment.Methods:Forty C57BL/6J female mice were equally divided into control,model,loratadine-and MXFDtreated groups in random.AR was induced by ovalbumin(OVA),and then treatment with loratadine or MXFD was administered.AR scores were evaluated and compared before and after treatment.Pathological changes in the nasal mucosa and lung were observed using hematoxylin-eosin staining of tissue samples.Activation of ILC2 in nasal mucosa was assessed by immunofluorescence and quantitative polymerase chain reaction analysis.ILC2 cell count in lungs was measured by flow cytometry and levels of interleukin-(IL)4,IL-5 and IL-13 in serum were detected by ELISA.Results:The decoction alleviated the symptoms of AR in mice,improved vascular congestion and expansion,glandular hyperplasia and inflammatory cell infiltration in mouse nasal mucosa and slowly improved the interstitial pneumonia and lesions.Meanwhile,MXFD reduced the number and percentage of ILC2s in the nasal mucosa and lungs,downregulated the expression of GATA3 mRNA and RORa mRNA,and reduced the related inflammatory cytokine levels,including IL-4,IL-5 and IL-13.Conclusion:These data suggest that inhibition of ILC2s by MXFD may be an important means by which to treat AR.