Influence of thermal processing on the quality of hawthorn: Quality markers of heat-processed hawthorn.

Hawthorn and its derived products are used worldwide as foods as well as complementary medicine. During the preparation of hawthorn, heating and thermal processing are frequently reported. The thermal processing will change the medicinal purposes and modify the efficacy of hawthorn. However, details including the chemical profile shifting and quality markers of heat-processed hawthorn have not been well understood. In this study, we analyzed the hawthorn samples processed at different temperatures and different times by ultraviolet visible absorption spectrum and liquid-mass spectrometry technologies combined with multivariate statistical analysis. It was revealed for the first time that thermal processing could greatly change the ultraviolet-visible absorption spectra and chemical profiles of hawthorn even with heat treatment at 130°C for 10 min. And the ultraviolet visible absorption spectrum, especially the ratio value (RA500 nm/400 nm ), was a descriptive and qualitative indicator of heating degree for the thermal processing at the macroscopic level. Several components, such as hyperoside, chlorogenic acid, quercetin, and apigenin, decreased or increased in content during the processing, and they could be utilized as the chemical quality markers. The proposed quality markers for heat-processed hawthorn will be helpful for further optimizing the processing conditions of hawthorn.

In Vitro Drug Screening Using iPSC-Derived Cardiomyocytes of a Long QT-Syndrome Patient Carrying KCNQ1 & TRPM4 Dual Mutation: An Experimental Personalized Treatment.

Congenital long QT syndrome is a type of inherited cardiovascular disorder characterized by prolonged QT interval. Patient often suffer from syncopal episodes, electrocardiographic abnormalities and life-threatening arrhythmia. Given the complexity of the root cause of the disease, a combination of clinical diagnosis and drug screening using patient-derived cardiomyocytes represents a more effective way to identify potential cures. We identified a long QT syndrome patient carrying a heterozygous KCNQ1 c.656G>A mutation and a heterozygous TRPM4 c.479C>T mutation. Implantation of implantable cardioverter defibrillator in combination with conventional medication demonstrated limited success in ameliorating long-QT-syndrome-related symptoms. Frequent defibrillator discharge also caused deterioration of patient quality of life. Aiming to identify better therapeutic agents and treatment strategy, we established a patient-specific iPSC line carrying the dual mutations and differentiated these patient-specific iPSCs into cardiomyocytes. We discovered that both verapamil and lidocaine substantially shortened the QT interval of the long QT syndrome patient-specific cardiomyocytes. Verapamil treatment was successful in reducing defibrillator discharge frequency of the KCNQ1/TRPM4 dual mutation patient. These results suggested that verapamil and lidocaine could be alternative therapeutic agents for long QT syndrome patients that do not respond well to conventional treatments. In conclusion, our approach indicated the usefulness of the in vitro disease model based on patient-specific iPSCs in identifying pharmacological mechanisms and drug screening. The long QT patient-specific iPSC line carrying KCNQ1/TRPM4 dual mutations also represents a tool for further understanding long QT syndrome pathogenesis.

Longan (Dimocarpus longan Lour.) Aril ameliorates cognitive impairment in AD mice induced by combination of D-gal/AlCl3 and an irregular diet via RAS/MEK/ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as "forgetfulness" or "dementia", and it can be caused by spleen deficiency. Longan Aril (the aril of Dimocarpus longan Lour., LA) is a kind of Chinese medicine, and it can improve intelligence attributed to entering the spleen-meridian. This study aimed to explore the therapeutic effects of LA on AD mice with spleen deficiency, and to understand anti-AD mechanism of LA. MATERIAL AND METHODS: A mouse model of AD with spleen deficiency was established by D-gal (140 mg/kg, intraperitoneal injection) and AlCl3 (20 mg/kg, intragastrical administration) in combination with an irregular diet for 60 days, in which mice in LA group were daily given LA (0.5, 1.0 or 2.0 g/kg). The anti-AD effects of LA were evaluated by the Morris water maze, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E), Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The anti-AD mechanism of LA was studied by using metabolomics, and the expressions of RAS/MEK/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins were detected by Western blotting. RESULTS: LA improved learning and memory abilities, superoxide dismutase (SOD) level, and form and number of Nissl bodies, while reduced the levels of Aß42, phosphorylated-tau (p-tau), reactive oxygen species (ROS), malondialdehyde (MDA), monoamine oxidase-B (MAO-B), histological injury, and apoptosis rate in AD group (P < 0.05, P < 0.01 or P < 0.001). The anti-AD mechanism of LA may be related to RAS/MEK/ERK and other signaling pathways, in which the expressions of RAS/MEK/ERK signaling pathway-related proteins significantly reduced (P < 0.05 or P < 0.01). CONCLUSIONS: LA could improve the cognitive ability and reduce the pathologic impairment in AD mice, which might be partly mediated via inhibition of RAS/MEK/ERK singling pathway.

Efficient Synthesis of Structured Phospholipids Containing Short-Chain Fatty Acids over a Sulfonated Zn-SBA-15 Catalyst.

Catalytic production of structured phospholipids (SPLs) containing short-chain fatty acids (SCFAs) in an efficient heterogeneous manner is of great importance from the standpoint of food engineering. Herein, a bifunctionalized sulfonated Zn-SBA-15 catalyst was studied for SPL synthesis through interesterification of soybean lecithin with ethyl propionate or methyl butyrate. Various characterization techniques such as pyridine Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible diffuse reflectance spectroscopy were conducted to determine the physicochemical properties, so as to build the possible structure-reactivity relationship of the catalyst. In screening tests with commercial Amberlyst-15 or other SBA-15-type materials, the as-prepared sample showed promising catalytic performance probably owing to its mesoporous structure and cooperative role of Brönsted and Lewis acid sites. Notably, the sample was easily separated and recycled without obvious deactivation. In general, the investigated catalyst was regarded as one of the promising alternatives to otherwise expensive biocatalysts for SCFA-containing SPL production.

Medicine in Future and Advantages of Integrated Chinese and Western Medicine.

The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.

Renoprotective Effect of Yiqi Yangyin Huayu Tongluo Formula against Diabetic Nephropathy in Diabetic Rats.

Diabetic nephropathy is developed in 20-40% of patients with diabetes mellitus, and patients with diabetic nephropathy require dialysis and renal transplantation. Traditional Chinese medicine has been widely used in treating patients with diabetic nephropathy in China. However, the detailed mechanisms of traditional Chinese medicine remain unclear. Yiqi Yangyin Huayu Tongluo formula (ZY formula) is a traditional Chinese medicinal formula. Here, we demonstrated kidney protective effect of ZY formula on the rats with diabetic nephropathy. The therapeutic effect of ZY formula on the diabetic nephropathy was almost the same as that of Irbesartan, which proved to have excellent curative effects on diabetic nephropathy. We also demonstrated the mechanism of ZY formula effect on the diabetic nephropathy. First, we validated that the activation of ROS-JNK signaling pathway in diabetic rats could be reduced by ZY. Furthermore, collagen I expression could be downregulated by ZY formula treatment. Meanwhile, cell apoptosis in the kidney of diabetic rats could be alleviated by ZY formula.

Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/ß-Catenin Signaling Pathway in Diabetic Rats.

The study investigated the expression of Wnt/ß-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured. At the end of the 20th week, biochemical parameters and body weight were tested. The kidney tissues were observed under light microscope and transmission electron microscopy. We examined Wnt/beta-catenin signaling pathway key proteins and renal interstitial fibrosis related molecular markers expression. The results showed that HTH could reduce urinary protein excretion and relieve renal pathological damage. Wnt4, p-GSK3ß (S9), and ß-catenin expression were decreased in the signaling pathway, but GSK3ß level was not changed by HTH in diabetic rats. Furthermore, the expressions of TGF-ß1 and ILK were decreased, but the level of E-cadherin was increased in diabetic rats after treatment with HTH. This study demonstrated that HTH could inhibit the high expression of Wnt/ß-catenin pathway in kidney of diabetic rats. The effect might be one of the main ways to reduce urinary protein excretion.

Ginseng Protein Reverses Amyloid Beta Peptide and H2 O2 Cytotoxicity in Neurons, and Ameliorates Cognitive Impairment in AD Rats Induced by a Combination of D-Galactose and AlCl3.

Ginseng (Panax ginseng C.A. Meyer) is one of the most widely used herbal medicines worldwide. The present study evaluated the neuroprotective effects of ginseng protein (GP) and its possible mechanisms in a cellular and animal model of AD. The results demonstrated that GP (10-100 µg/mL) significantly improved the survival rate of neurons and reduced the cells' apoptosis and the mRNA expression of caspase-3 and Bax/Bcl-2. In addition, GP (0.1 g/kg) significantly shortened the escape latency, prolonged the crossing times and the percentage of residence time; reduced the level of Aß1-42 and p-tau, the activity of T-NOS and iNOS, and the content of MDA and NO, improved the activity of SOD, the concentration of cAMP and the protein expression of p-PKA/PKA and -CREB/CREB. The results demonstrated that GP significantly inhibited Alzheimer-like pathophysiological changes induced by Aß25-35 or H2 O2 in cells or those induced by D-gal/ Al in animals. These neuroprotective effects of GP may be associated with the cAMP/PKA/CREB pathway. Also, in combination with our previous studies, these results indicate that the anti-AD mechanism of GP was likely to activate the CREB pathway through multiple channels. Copyright © 2016 John Wiley & Sons, Ltd.

Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D-galactose/AlCl3 inducing rats model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer disease (AD) is a progressive neurodegenerative disease, with progressive memory loss, cognitive deterioration, and behavioral disorders. Ginseng (Panax ginseng C.A. Meyer) is widely used in China to treat various kinds of nervous system disorders. The study aimed to explore the therapeutic effect of ginseng protein (GP) on Alzheimer's disease and its correlation with the PI3K/Akt signaling pathway to understand the mechanism underlying the neuroprotective effect of ginseng. MATERIAL AND METHODS: The AD rat model was established by intraperitoneally injecting D-galactose [60mg/(kgd)] followed by intragastrically administering AlCl3 [40mg/(kgd)] for 90 days. From day 60, the GP groups were intragastrically administered with GP 0.05 or 0.1g/kg twice daily for 30 days. The ethology of rats was tested by Morris water maze test. The content of Aß1-42 and p-tau in the hippocampus of rats was detected by enzyme-linked immunosorbent assay. The expression of mRNAs and proteins of PI3K, Akt, phosphorylated Akt (p-Akt), Bcl-2, and Bax in the hippocampus was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blot assay. RESULTS: GP was found to significantly improve the memory ability of AD rats and prolong the times of crossing the platform and the percentage of residence time in the original platform quadrant of spatial probe test. GP also reduced the content of Aß1-42 and p-tau and improved the mRNA and protein expression of PI3K, p-Akt/Akt, and Bcl-2/Bax in the hippocampus. CONCLUSIONS: GP could improve the memory ability and reduce the content of Aß1-42 and p-tau in AD rats. The anti-AD effects of GP were in part mediated by PI3K/Akt signaling pathway activation.

[Effect of Chinese herbs for stasis removing and collaterals dredging upon angiotensin-converting enzyme 2-angiotensin-(1-7)-mas axis in the renal cortex of diabetic nephropathy rats].

OBJECTIVE: To observe the effect of Chinese herbs for stasis removing and collaterals dredging (CHSRCD) upon angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas axis in the renal cortex of diabetic nephropathy rats. METHODS: Totally 89 male Sprague-Dawley rats were randomly divided into the blank control group (C group, n=22), the high-glucose high-fat control group (H group, n=10), and the streptozotocin (STZ)-injecting group (n=57). The diabetes rat model (n=50) was induced by feeding high-glucose high-fat diet in combination with intraperitoneal injection of STZ, which were further divided into the model group (M group, n=24), the irbesartan group (I group, n=13), and the CHSRCD (Z group, n=13). Rats in I and Z groups were intragastrically fed with suspension of irbesartan and CHSRCD, once daily for 16 weeks. Equal volume of drinking water was administrated to rats in the rest groups. Blood glucose and 24 h urine protein quantitation were tested at four time points. And the mRNA expression of ACE2 and Mas at various time points was detected by Real-time PCR, immunohistochemical assay, and Western blot. Quantitative analyses of ACE2 and Mas protein expression were performed at the end of week 16. RESULTS: Compared with the C group, blood glucose increased in the H and M groups (P < 0.01). It was higher in the H group (P < 0. 01). 24 h urine protein quantitation at different time points increased in the M group, and it was higher than that in the H group (P < 0.05). Compared with the M group, 24 h urine protein quantitation decreased at the end of week 8 in the I group, and at the end of week 8 and 16 in the Z group (P < 0.05). It was lower in the Z group than in the I group at the end of week 16 (P < 0.05). Compared with the C and H groups, the expression of ACE2 mRNA in the renal cortex was lower in the M group at the end of week 16 (P < 0.01). Compared with the M group, it was higher in the Z group (P < 0. 01). There was no statistical difference in the expressions of Mas mRNA at the end of week 16 between the C group and the M group (P > 0.05). It was lower in the M group than in the H group (P < 0.05). It was higher in the Z group than in the M group (P < 0.05), and higher than in the I group (P < 0.05). The expression of ACE2 and Mas protein in the M group decreased as time went by. The expression quantitation of ACE2 and Mas protein at the end of week 16 was lower in the M group than in the C group (P < 0.05). Compared with the M group, ACE2 expression of the Z group and Mas of the I and Z groups increased more significantly (P < 0. 05). CONCLUSION: CHSRCD could play a role in renal protection for diabetic nephropathy rats by up-regulating the mRNA and protein expression of ACE2 and Mas, promoting the ACE2-Ang-(1-7)-Mas axis, and lowering urinary protein.

Relationship between urinary nephrin and urinary albumin changes in diabetic rats and effects of yiqiyangyinhuayutongluo recipe.

OBJECTIVE: To investigate the dynamic changes of urinary nephrin, and the relationship between it and urinary albumin excretion rate (UAER) in a diabetic rat model, as well the effects of yiqiyangyinhuayutongluo recipe. METHODS: Diabetic model was induced by high fat diet combined with low-dose Streptozotocin (STZ) in rats. Normal group (NG), model group (MG), and yiqiyangyinhuayutongluo recipe treated group (YHTG) were set. Gastrointestinal Yiqiyangyi-nhuayutongluo recipe was administered once daily for 32 w. At the end of the 2nd w (2 w), 8 w, 16 w, and 32 w, fasting blood glucose (FBG), UAER and 24h urinary nephrin (U-nephrin) were detected. RESULTS: Compared with NG, FBG in MG increased notably (P < 0.05). Compared with MG, FBG of YHTG (P < 0.05) since 16 w. U-nephrin and UAER in MG increased significantly from 2 w, peaked at 16 w, lessened in different degree at 32 w, but were still higher than NG. The correlation analysis showed that there was a significant positive correlation between U-nephrin and UAER at different time, the correlation coefficient as r > 0.9, and P < 0.05. Compared with MG, U-nephrin and UAER in YHTG decreased markedly (P < 0.05) except for U-nephrin at 8 w. CONCLUSIONS: U-nephrin and UAER in diabetic rat model have a positive linear correlation. Yiqiyangyinhuayutongluo recipe can reduce UAER markedly, and preventing the lose of nephrin in urine maybe one of the mechanisms.

[Effect of supplementing Qi-nourishing Yin-dispersing blood stasis-dredging collateral herbs on p38 MAPK signaling pathway in kidney of early diabetic rats].

OBJECTIVE: To study the effect of supplementing Qi-nourishing Yin and dispersing blood stasis-dredging collateral herbs on p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in the kidney of early diabetic rats. METHOD: Dividing SD rats randomly into 6 groups: Simple nephrectomy group, model group, irbesatan group, traditional Chinese medicine (TCM) low dose group, TCM middle dose group and TCM high dose group. Each group of rats was fed with the corresponding dose of medicine. After 6 weeks, detecting 24 h urine protein (UPro) level, renal function, p38 MAPK mRNA and p-p38 MAPK protein level. RESULT: UPro levels of irbesatan group, TCM low group and TCM middle dose group decreased significantly (P < 0.05) , compared with that of the model group. Renal function of the treated groups was improved greatly and their p38 MAPK mRNA and p-p38MAPK protein levels decreased significantly (P < 0.05), compared with those of the model group. CONCLUSION: Supplementing Qi-nourishing Yin-dispersing blood stasis-dredging collateral herbs could treat DN rats effectively by inhibiting the expression of p38 MAPK signaling pathway.