HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Moisture content of tea dhool for the scenting process affects the aroma quality and volatile compounds of osmanthus black tea.

To improve the quality of osmanthus black tea, samples produced with different scenting methods were prepared. The sensory quality was assessed and the characteristic aromatic components were explored using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry. According to the results, osmanthus black tea obtained by adding osmanthus scenting in the fermentation process had the strongest floral aroma. The major contributors to the aroma of osmanthus black tea were identified as ß-ionone, dihydro-ß-ionone, benzeneacetaldehyde, citral, geraniol, and linalool by calculating their relative odor activity values. An analysis of the causes revealed that the moisture content of tea dhool significantly affected the adsorption of fresh flower aroma by tea. The experimental results showed that osmanthus black tea produced using tea dhool containing 30% moisture content had the highest content of crucial aroma components, suggesting the tea dhool under this condition had the strongest adsorption capacity for osmanthus aroma.

Effects of natural spring water on the sensory attributes and physicochemical properties of tea infusions.

The sensory quality of tea is influenced by water quality, with natural spring water (NSW) gaining much attention for its natural and healthy qualities. The effects of NSW on the sensory attributes, physicochemical composition, and antioxidant capacity of Chinese tea were investigated. Tea brewed with pure water was the most resistant to oxidation and darkening. NSW with low total dissolved solids (TDS) was most suitable for brewing unfermented or mildly fermented teas, improving their sensory quality. The simulated green tea infusion system was used to investigate further the dramatic darkening of tea infusions in NSW. Exposure of infusions to air promoted the degradation, epimerization, and oxidative polymerization of catechins, and further formed theabrownins which darkened the tea infusions. These findings enabled tea consumers to choose the most suitable NSW for brewing Chinese teas and illustrated the darkening mechanism of tea infusion in high pH/TDS water.

Effects of baking treatment on the sensory quality and physicochemical properties of green tea with different processing methods.

Seven batches of raw tea leaves, processed by different methods (steaming, pan-frying) and from two different harvesting seasons (spring, autumn), were used to investigate the effect of baking treatment on changes in the composition and content of nonvolatile and volatile compounds. The results showed that baking had a greater impact on sensory and flavor quality, which chemically modified some of taste and aroma components. The aroma concentrations of steamed teas (4,168-10,706 µg/L) were significantly higher than those of pan-fried teas (959-2,608 µg/L), and the aroma concentrations of baked green teas (2,608-10,706 µg/L) were significantly higher than those of unbaked teas (959-4,213 µg/L). Based on VIP > 1 and ACI > 1, (E, E)-3,5-octadien-2-one, hexanal, ß-ionone, 5-methylfurfural, ß-cyclocitral, and linalool were identified as the main aroma compounds. Chemical changes resulting from Maillard reaction were greater during baking of steamed, than pan-fried green tea. These results help improve the quality of green tea with baking.

A targeted and nontargeted metabolomics study on the oral processing of epicatechins from green tea.

Oral processing (OP), referring to the whole process of food digestion in human mouth, has a major influence on food flavor perception. This study focused on the compositional changes of the four green tea epicatechins (viz., EC, EGC, ECG, EGCG) during OP, based on targeted and nontargeted metabolomics. It was found that the four epicatechins were all extensively lost through transformation undergoing OP, among which EC was the most stable one, whereas EGCG the least. EGCG was further revealed to be susceptible to human oral cavity in the simulated OP in vitro. It could be converted physically by precipitating with mucin in saliva, and chemically through hydrolysis and dimerization, mediated mainly by the neutral pH condition. The OP of epicatechins also caused salivary composition changes possibly involving health benefits of green tea. These findings could raise awareness of the interactions between epicatechins, or any other food materials, with human mouth.

Effect of Ferrous Ion on Heat-Induced Aroma Deterioration of Green Tea Infusion.

Aroma deterioration is one of the biggest problems in processing tea beverages. The aroma of tea infusion deteriorates fast during heat sterilization and the presence of ferrous ion (Fe2+) aggravates it. The underlying mechanism remains unveiled. In this study, Fe2+ was verified to deteriorate the aroma quality of green tea infusion with heat treatment. Catechins were necessary for Fe2+-mediated aroma deterioration. By enhancing the degradation of catechins, Fe2+ dramatically increased the production of hydrogen peroxide (H2O2). Fe2+ and H2O2 together exacerbated the aroma of green tea infusion with heat treatment. GC-MS analysis revealed that the presence of Fe2+ enhanced the loss of green/grassy volatiles and promoted the formation of new volatiles with diversified aroma characteristics, resulting in a dull scent of green tea infusion. Our results revealed how Fe2+ induced aroma deterioration of green tea infusion with heat treatment and could help guide tea producers in attenuating the aroma deterioration of tea infusion during processing.

Effects of brewing water on the sensory attributes and physicochemical properties of tea infusions.

The effects of brewing water on the sensory attributes and physicochemical properties of tea infusions made from Chinese teas were investigated. The tea infusions brewed in water with higher pH and total dissolved solids (TDS), generally had a darker color and lower overall sensory acceptability. Moreover, those infusions had less catechins, particularly galloylated-catechins, and lower antioxidant capacity. The teas with less fermentation contained more galloylated-catechins and had higher antioxidant capacity, but were much more susceptible to high mineral brewing water. Green tea was proved to be the most susceptible one, whereas dark tea the most stable one. Green tea infusions prepared with higher pH/TDS water were more rapidly oxidized, resulting in a darker color due to polymerization of catechins, when exposed to the air. These findings suggested that low mineral brewing water was better for Chinese tea, both from the sensory and health benefit perspectives.

Zijuan tea- based kombucha: Physicochemical, sensorial, and antioxidant profile.

Zijuan tea is a representative anthocyanin-rich tea cultivar in China. In this study, Zijuan tea was used to produce a novel kombucha beverage (ZTK). The physicochemical, sensory properties, and antioxidant activity of ZTK were compared with that of black tea kombucha (BTK) and green tea kombucha (GTK). Results indicated that after fermentation, the color of ZTK changed from yellowish-brown to salmon-pink, because its anthocyanins (4.5 mg/L) appeared red in acidic conditions. Meanwhile no significant changes of color were observed in BTK and GTK. The dynamic changes of pH, biomass, and concentrations of sugars, amino acids, and main organic acids were similar in three kombucha beverages, except catechins showing different trends. Moreover, ZTK showed the highest overall acceptability score, antioxidant activity, and concentration of volatiles among the three kombucha beverages. Therefore, Zijuan tea is suitable for the preparation of kombucha beverage with attractive color and health benefits.

Discovery of anti-flu substances and mechanism of Shuang-Huang-Lian water extract based on serum pharmaco-chemistry and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Huang-Lian preparation has captured wide attention since its clinical applications for the successful treatment of upper respiratory tract infection. However, its functional basis under actual therapeutic dose in vivo was still unrevealed. AIM OF THE STUDY: This study aimed to reveal the anti-flu substances and mechanism of Shuang-Huang-Lian water extract (SHL) on H1N1 infected mouse model by a strategy based on serum pharmaco-chemistry under actual therapeutic dose and network pharmacology. MATERIALS AND METHODS: H1N1 infected mouse model was employed for evaluation of the anti-flu effects of SHL. A simultaneous quantification method was developed by UPLC-TQ-XS MS coupled switch-ions mode and applied to characterize the pharmacokinetics of the multiple components of SHL under actual therapeutic dose. The potential active ingredients were screened out based on their pharmacokinetic parameters. And then, a compound mixture of these active candidates was re-evaluated for the anti-flu activity on H1N1 infected mouse model. Furthermore, the anti-flu mechanism of SHL was also predicted by network pharmacology coupled with the experimental result. RESULTS: SHL significantly increased the survival rate and prolonged survival days on H1N1 infected mice at a dosage of 20 g crude drug/kg/day by reversing the increased lung index, down-regulating the inflammatory cytokines (TNF-α, IL-1ß, IL-6) and inhibiting the release of IFN-ß in bronchoalveolar lavage fluids (BALF). Concomitantly, the pharmacokinetic parameters of fourteen quantified and twenty-one semi-quantified constituents of SHL were characterized. And then, five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin), which displayed satisfactory pharmacokinetic features, were considered as potential active ingredients. Thus, a mixture of these five ingredients was administered to H1N1-infected mice at a dose of 4.24 mg/kg/day. As a result, the therapeutical effects of the mixture were similar to SHL in terms of survival rate, lung index and the release of cytokines (TNF-α, IL-1ß and IL-6) in BALF. Moreover, network pharmacology analysis indicated that the TNF-signal pathways might play a role in the anti-flu mechanism of SHL. CONCLUSIONS: A mixture of five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin) were the anti-flu substances of SHL. The strategy based on serum pharmaco-chemistry under actual therapeutic dose provided a new sight on exploring in vivo effective substances of TCM.

Effect of baking on the flavor stability of green tea beverages.

Flavor stability is important for the quality of tea beverages. Baking is a typical processing technology to improve the flavor of tea leaves. In present study, seven raw tea materials, including steamed spring and autumn tea leaves, pan-fired spring tea leaves, and their corresponding baked tea leaves, were used to investigate the effect of baking on flavor stability of green tea beverages. The results showed that tea beverages prepared with baked tea had better flavor stability. The baking process obviously changed the concentrations of some important flavor substances, especially the aromatic pyrrole substances from 0 (unbaked) to 338.13 µg/L (baked) in tea beverages. Heat treatment had little influence on the flavor of tea beverages prepared from baked tea, but caused great changes in non-volatile and volatile components in those prepared from unbaked leaves. These results could help guide the processing of tea beverages which would improve their flavor quality stability.

Quantitative analyses of the bitterness and astringency of catechins from green tea.

Bitterness and astringency are two important quality attributes of green tea infusion, and catechins are the main contributor to the bitterness and astringency. The aim of this work was to quantitatively analyse the bitterness and astringency of green tea infusion according to the concentrations of catechins. The concentration-taste curves of catechins showed a pattern that fit the cubic functions, and their R2 values were higher than 0.956. The bitterness of green tea was highly correlated with the concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate (ECG) (R2 = 0.7769, p < 0.01), and the astringency (R2 = 0.7878, p < 0.01) was highly correlated with the concentrations of ECG and flavonol glycosides (myricetin 3-O-galactoside and quercetin-3-O-rutinoside). Taste interactions between different catechins and between catechins and other substances were determined. These results may enhance the understanding of tea chemistry for improving the taste of products from green tea.

Effect of extraction methods on the chemical components and taste quality of green tea extract.

The physicochemical properties of tea extracts are significantly affected by the extraction method. The aim of this study was to compare the effects of static and dynamic extractions on the concentrations of chemical components and taste quality of green tea extracts. Our results show that extraction of chemical components using static extraction follows a pseudo-second-order reaction, while that of dynamic extraction follows a first-order reaction. The concentrations of the solids, polyphenols, and free amino acids in green tea extract prepared by dynamic extraction were much higher, although the overall yields were not significantly different between the two extraction methods. Green tea extracts obtained via dynamic extraction were of lower bitterness and astringency, as well and higher intensities of umami and overall acceptability. These results suggest that dynamic extraction is more suitable for the processing of green tea concentrate because of the higher concentration of green tea extract.

System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus.

The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.

Effect of the type of brewing water on the chemical composition, sensory quality and antioxidant capacity of Chinese teas.

The physicochemical characteristics, sensory quality, and antioxidant activity of tea infusions prepared with purified water (PW), mineral water (MW), mountain spring water (MSW), and tap water (TW) from Hangzhou were investigated. The results showed that the taste quality, catechin concentration, and antioxidant capacity of green, oolong, and black tea infusions prepared using MW and TW were significantly lower than those prepared using PW. Extraction of catechins and caffeine was reduced with high-conductivity water, while high pH influenced the stability of catechins. PW and MSW were more suitable for brewing green and oolong teas, while MSW, with low pH and moderate ion concentration, was the most suitable water for brewing black tea. Lowering the pH of mineral water partially improved the taste quality and increased the concentration of catechins in the infusions. These results aid selection of the most appropriate water for brewing Chinese teas.

Association between Recreational Physical Activity and the Risk of Upper Urinary Calculi.

OBJECTIVE: Upper urinary calculi (UUC) is considered to be a comprehensive disease associated with many risk factors, but the role of physical activity (PA) is undefined. Here, we conducted a cross-sectional study to investigate this relationship in Asian populations. MATERIALS AND METHODS: Patients diagnosed with UUC were the subjects of study and those who participated in a health examination in local medical center were included as controls. Information was collected through the same standard questionnaire. A metabolic equivalent score (METs) was measured for each kind of activity. OR of UUC in categories of PA were determined by logistic regression. RESULTS: A total of 1,782 controls and 1,517 cases were enrolled. People who took higher PA (5-9.9, 10-19.9, 20-29.9 and >30 METs/wk) weekly were associated with lower risks of UUC than those took lower PA (<4.9 METs/wk) after adjusting for age, ethnicity, body mass index, systolic blood pressure, water intake, history of gout, history of diabetes mellitus, history of supplemental calcium use and history of hypertension (adjusted OR 0.11, 0.32, 0.24, 0.34; 95% CI 0.08-0.15, 0.23-0.43, 0.15-0.40, 0.22-0.53, respectively; p value <0.001). CONCLUSIONS: In our cross-sectional study, PA was associated with UUC.

Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation.

Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (ß-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2, ß-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain.

Improving the sweet aftertaste of green tea infusion with tannase.

The present study aims to improve the sweet aftertaste and overall acceptability of green tea infusion by hydrolyzing (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) with tannase. The results showed that the intensity of the sweet aftertaste and the score of overall acceptability of the green tea infusion significantly increased with the extension of the hydrolyzing treatment. (-)-Epigallocatechin (EGC) and (-)-epicatechin (EC) were found to be the main contributors for the sweet aftertaste, based on a trial compatibility with EGCG, ECG, EGC, and EC monomers, and a synergistic action between EGC and EC to sweet aftertaste was observed. A 2.5:1 (EGC/EC) ratio with a total concentration of 3.5 mmol/L gave the most satisfying sweet aftertaste, and the astringency significantly inhibited the development of the sweet aftertaste. These results can help us to produce a tea beverage with excellent sweet aftertaste by hydrolyzing the green tea infusion with tannase.

WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling.

Warm­supplementing kidney yang (WSKY) is an herbal prescription that has been used in Traditional Chinese Medicine for the treatment of psychiatric conditions. A previous study by our group found that WSKY significantly improved cognitive function of schizophrenia patients. In the present study, the effects of WSKY on cognitive function and their underlying mechanisms were investigated. WSKY was administered to an MK­801­induced rat model of chronic schizophrenia for 14 days. Memory performance was assessed using the Morris water maze (MWM) test. The expression of brain­derived neurotrophic factor (BDNF), activation of cAMP response element binding protein (pCREB/CREB) and activation of extracellular signal­regulated kinase (pERK/ERK) in the hippocampus was detected using western blot analysis. In the acquisition phase of the MWM test, the escape latency was significantly increased in the MK­801­treated group compared with the normal control group (P<0.01). Treatment with WSKY for 14 days at doses of 100 or 250 mg/kg rescued this cognitive impairment (P<0.05). In the probe test, 250 mg/kg WSKY treatment increased the time spent in the target quadrant (P<0.05) and number of platform crossings (P<0.01). Western blot analysis demonstrated that the levels of BDNF expression in the hippocampus of rats without behavioral tests were elevated following 14 days of WSKY treatment, and the effect of WSKY treatment on hippocampal BDNF expression was presented in an inverted U­shaped dose­response pattern. The pERK1/2 in the hippocampus was significantly enhanced following 100 mg/kg (P<0.01) and 250 mg/kg (P<0.01) WSKY treatment, while only 250 mg/kg WSKY increased the phosphorylation of CREB (P<0.01). The results of the present study indicated that WSKY enhances cognitive performance via the upregulation of BDNF/ERK/CREB signaling, and that WSKY has potential therapeutic implications for cognitive impairment of schizophrenia.

Synergism and rules of the new combination drug Yiqijiedu formulae (YQJD) on ischemic stroke based on amino acids (AAs) metabolism.

The use of combination drugs is considered to be a promising strategy to control complex diseases such as ischemic stroke. The detection of metabolites has been used as a versatile tool to reveal the potential mechanism of diverse diseases. In this study, the levels of 12 endogenous AAs were simultaneously determined quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen as the potential biomarkers, and using PLS-DA analysis, the effects of the new combination drug YQJD, which is composed of ginsenosides, berberine, and jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid, homocysteine, methionine, and tryptophan, which changed significantly in the YQJD-treated groups compared to the vehicle groups (P < 0.05), were identified and designated as the AAs to use to further explore the synergism of YQJD. The result of a PCA showed that the combination of these three drugs exhibits the strongest synergistic effect compared to other combination groups and that ginsenosides might play a pivotal role, especially when combined with jasminoidin. We successfully explored the synergetic mechanism of multi-component and provided a new method for evaluating the integrated effects of combination drugs in the treatment of complex diseases.

[A correlation research on Chinese medical syndromes of chronic heart failure and various complications].

OBJECTIVE: To study the correlation between various complications of chronic heart failure (CHF) patients and Chinese medical syndromes, thus indicating distribution laws of Chinese medical syndromes in various complications of CHF patients. METHODS: Chinese medical syndrome typing was performed in 630 CHF patients by cross-sectional study of the demographic data, history of present diseases, related information on Chinese medical four diagnostic methods, and the distribution of complications. Logistic regression analysis was used to determine the correlation of various complications of CHF patients and Chinese medical syndromes. RESULTS: In this study, recruited were common complications such as hypertension, diabetes, arrhythmia, hyperlipemia, and cerebral vascular accident, and so on. Main syndromes were sequenced as qi deficiency syndrome, blood stasis syndrome, water retention syndrome, yin deficiency syndrome, phlegm turbid syndrome, yang deficiency syndrome. Results of Logistic regression analysis indicated that correlation existed between common complications and Chinese medical syndromes. In CHF complicated hypertension patients, Logistic regression analysis showed qi deficiency syndrome and yang deficiency syndrome were negatively correlated with hypertension (P < 0.05). In CHF complicated diabetes patients, Logistic regression analysis showed phlegm turbid syndrome and water retention syndrome were positively correlated with diabetes (P < 0.05). In CHF complicated arrhythmia patients, there was no statistical difference in the distribution of each syndrome (P > 0.05). In CHF complicated hyperlipemia patients, Logistic regression analysis showed qi deficiency syndrome and water retention syndrome were negatively correlated with hyperlipemia (P < 0.05), while blood stasis syndrome, yin deficiency syndrome, and phlegm turbid syndrome were positively correlated with hyperlipemia (P < 0.01). In CHF complicated cerebral vascular accident patients, Logistic regression analysis showed qi deficiency syndrome and yang deficiency syndrome were negatively correlated with cerebral vascular accident (P < 0.01, P < 0.05). CONCLUSIONS: There existed certain correlations between complications of CHF and the distribution of main Chinese medical syndromes. It could be used as guidance for treating CHF and its various complications by Chinese medicine and pharmacy.