The aim of this study was to evaluate the efficacy and safety of a Chinese herbal formula modified Mai-Men-Dong-Tang (mMMDT) for treatment of persistent, mild-to-moderate asthma. A total of 100 asthmatic patients were enrolled and assigned to three treatment groups in this double-blind, randomized, placebo-controlled clinical trial. Over a period of 4 months, patients in groups A and B received 80 and 40 mg/kg/day of mMMDT, while those in group C received a placebo. Efficacy variables included changes in forced expiratory volume in 1 s (FEV1), symptom score, serum total immunoglobulin E (IgE), and dust mite-specific IgE. Safety assessments included complete blood count, and liver and kidney function. Relative to baseline, significantly greater increases in FEV1 were demonstrated for both A and B groups in comparison with the placebo-treated analog (both p <0.05). Further, similar improvements in symptom score were observed for both mMMDT treatment groups. The serum total IgE for group A showed a decreasing tendency after treatment but no statistical difference was noted. Furthermore, no drug-related adverse effects were reported. Blood test, and liver and kidney function were within normal range during the study, with no marked changes demonstrated over time. In conclusion, the Chinese herbal formula mMMDT provided improvements in lung function and relieved asthma symptoms in our sample of patients. Given its efficacy and safety, we consider mMMDT a credible treatment regimen for persistent, mild-to-moderate asthma.

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IGF-IIR activation regulates cardiac remodeling leading to apoptosis. Here, we identified the novel IGF-IIRα (150 KDa), a truncated IGF-IIR transcript enhances cardiac apoptosis under highsalt uptake in transgenic rat model. Echocardiographic analysis revealed decline in ejection fraction and fractional shortening percentage in IGF-IIRα (TG) rats. We found that IGF-IIRα TG rats developed severe apoptosis and fibrosis as identified through TUNEL assay and Masson's trichrome staining. Importantly, the heart functioning, apoptosis, and fibrosis were significantly affected under high-salt conditions in IGF-IIRα (TG) rats. Significant upregulation of apoptosis was evident from decreased Bcl-2, p-AKT, and p-PI3K expressions with concomitant increase in Bad, cytochrome C, cleaved caspase 3 levels. We found that, IGF-IIRα highly induced tissue fibrosis through collagen accumulation (col I, col III) and up regulated various fibrotic markers such as tPA, uPA, TGF-β, and vimentin expressions. The observed upregulation of fibrosis were significantly regulated under high-salt conditions and their over regulation under IGF-IIRα over expressions shows the key role of IGF-IIRα in promoting high-salt induced fibrosis. During IGF-IIRα over expression induced cardiotoxicity, under high salt condition, and it destroys the interaction between CHIP and HSF1, which promotes the degradation of HSF1 and results in upregulation of IGF-IIR/IGF-IIRα expressions. Altogether, the study unveils novel IGF-IIRα in the regulation of cardiac apoptosis and fibrosis under high-salt diet.

Aberrations in cyclic adenosine monophosphate (cAMP) signaling cascade has been linked to the allergic responses that associate with the risks of stroke or cardiovascular diseases. Phosphodiesterase 4D (PDE4D) has been shown to be highly involved in cAMP regulation and is hence implied to be a potential drug target in stroke prevention. To identify potential PDE4D inhibitors from traditional Chinese medicine (TCM), we employed machine learning modeling techniques to screen a comprehensive TCM database. The multiple linear regression (MLR) and support vector machine (SVM) models constructed have correlation coefficients of 0.8234 and 0.7854 respectively. Three candidates from the ginger family were identified based on the prediction models. Molecular dynamics simulation further validated the binding stabilities of each candidate in comparison to the control inhibitor L-454560. The intermolecular distances suggested that the candidates could hinder PDE4D from binding to cAMP. Furthermore, the HypoGen validation suggested that top2, top3, and the control L-454560 mapped with the predicted pharmacophores. The results suggested that the 3 compounds identified from the ginger family were capable in inhibiting cAMP binding and hydrolysis by PDE4D. We further identified and characterized the ligand binding properties that are associated with the inhibition of PDE4D.