Exploring metabolic responses and pathway changes in CHO-K1 cells under varied aeration conditions and copper supplementations using 1 H NMR-based metabolomics.

The optimization of bioprocess for CHO cell culture involves careful consideration of factors such as nutrient consumption, metabolic byproduct accumulation, cell growth, and monoclonal antibody (mAb) production. Valuable insights can be obtained by understanding cellular physiology to ensure robust and efficient bioprocess. This study aims to improve our understanding of the CHO-K1 cell metabolism using 1 H NMR-based metabolomics. Initially, the variations in culture performance and metabolic profiles under varied aeration conditions and copper supplementations were thoroughly examined. Furthermore, a comprehensive metabolic pathway analysis was performed to assess the impact of these conditions on the implicated pathways. The results revealed substantial alterations in the pyruvate metabolism, histidine metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis, which were especially evident in cultures subjected to copper deficiency conditions. Conclusively, significant metabolites governing cell growth and mAb titer were identified through orthogonal partial least square-discriminant analysis (OPLS-DA). Metabolites, including glycerol, alanine, formate, glutamate, phenylalanine, and valine, exhibited strong associations with distinct cell growth phases. Additionally, glycerol, acetate, lactate, formate, glycine, histidine, and aspartate emerged as metabolites influencing cell productivity. This study demonstrates the potential of employing 1 H NMR-based metabolomics technology in bioprocess research. It provides valuable guidance for feed medium development, feeding strategy design, bioprocess parameter adjustments, and ultimately the enhancement of cell proliferation and mAb yield.

Application of the Analytical Procedure Lifecycle Concept to a Quantitative 1H NMR Method for Total Dammarane-Type Saponins.

Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the analytical procedure lifecycle. In the first stage (analytical procedure design), the Ishikawa diagram and failure mode effects and criticality analysis were used to conduct risk identification and risk ranking. Plackett-Burman design and central composite design were used to screen and optimize critical analytical procedure parameter. Then, the method operable design region was obtained through modeling. In the second stage (analytical procedure performance qualification), the performance of methodological indexes was investigated based on analytical quality by design. As examples of continued procedure performance verification, the method was successfully applied to determine the total DTSs in herbal pharmaceutical preparations and botanical extracts. As a general analytical method to quantify total DTSs in medicinal plants or pharmaceutical preparations, the developed method provides a new quality control strategy for various products containing dammarane-type saponin.

Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.

Previous reports have confirmed that crude saponins (ginsenosides) in Panax ginseng have a preventive effect on chemotherapy-induced intestinal injury. However, the protective effects and possible mechanisms of ginsenoside Re (G-Re, a maker saponin in ginseng) against chemotherapy-induced intestinal damage have not been thoroughly studied. In this work, a series of experiments in vivo and in vitro on the intestinal toxicity caused by cisplatin have been designed to verify the improvement effect of G-Re, focusing on the levels of Wnt3a and [Formula: see text]-catenin. Mice were intragastric with G-Re for 10 days, and intestinal injury was induced by intraperitoneal administration of cisplatin at a dose of 20 mg/kg. Histopathology, gastrointestinal digestive enzyme activities, inflammatory cytokines, and oxidative status were evaluated to investigate the protective effect. Furthermore, in IEC-6 cells, G-Re statistically reverses cisplatin-induced oxidative damage and cytotoxicity. The TUNEL and Hoechst 33258 staining demonstrated that G-Re possesses protective effects in cisplatin-induced apoptosis. Additionally, pretreatment with G-Re significantly alleviated the apoptosis via inhibition of over-expressions of B-associated X (Bax), as well as the caspase family members, such as caspase 3 and 9, respectively, in vivo and in vitro. Notably, western blotting results showed that G-Re treatment decreased Wnt3a, Glycogen synthase kinase [Formula: see text] (GSK-[Formula: see text]), and [Formula: see text]-catenin expression, suggesting that nuclear accumulation of [Formula: see text]-catenin was attenuated, thereby inhibiting the activation of GSK-[Formula: see text]-dependent Wnt/[Formula: see text]-catenin signaling, which was consistent with our expected results. Therefore, the above evidence suggested that G-Re may be a candidate drug for the treatment of intestinal injury.

A multivariate curve resolution-alternating least squares (MCR-ALS) technology assisted 1 H-NMR methodology for multi-component quantitation of Trichosanthis Pericarpium injection.

INTRODUCTION: Trichosanthis Pericarpium injection (TPI) is a traditional Chinese medicine preparation obtained from Trichosanthis Pericarpium by extraction, purification and sterilisation. It contains amino acids, alkaloids, nucleotides and other components. Existing quantitative methods only analyse a few components in injections, so this study intends to develop a method for comprehensive analysis of TPI components. OBJECTIVE: To develop a method for quantification of components in TPI by multivariate curve resolution-alternating least squares (MCR-ALS) assisted proton nuclear magnetic resonance (1 H-NMR). METHODS: A 1 H-NMR method was developed for the quantification of components in TPI. For components with independent signals, 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid sodium salt (TSP) was used as an internal standard to calculate the component contents. For components with overlapping signals, the method of MCR-ALS was used. RESULTS: A total of 36 components were identified in TPI, of which 33 were quantified. Methodological validation results showed that the developed 1 H-NMR method has good linearity, accuracy, precision, robustness and specificity. CONCLUSION: The use of 1 H-NMR provides a reliable and universal method for the TPI components identification and quantification. Also, it can be used as a powerful tool for analysing the contents in a complex mixture as a quality control measure.

Collagenase-I decorated co-delivery micelles potentiate extracellular matrix degradation and hepatic stellate cell targeting for liver fibrosis therapy.

Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo, CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization. Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. STATEMENT OF SIGNIFICANCE: A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.

Quantitative profiling of comprehensive composition in compound herbal injections: An NMR approach applied on Shenmai injection.

INTRODUCTION: Compound herbal injections (CHIs) can be regarded as a significant innovation in the modernisation of herbal medicine. Therefore, improving the quality control level of CHIs has always been an active research topic in traditional herbal medicine. OBJECTIVES: In this study, Shenmai injection was used as a representative sample for investigating the ability of proton nuclear magnetic resonance (1 H NMR) in the quality evaluation of CHIs. METHODS: A quantitative 1 H NMR method was developed to simultaneously determine the contents of total ginsenosides, polysorbate 80, and 20 primary metabolites in Shenmai injection. Multivariate statistical analysis was combined to compare differences between samples from different manufacturers. RESULTS: It was found that the combined measurement uncertainty of each component is less than 1.61%, which demonstrates the reliability of the method. Furthermore, the components determined by this method account for up to 92.64% of the total solids, which is an unprecedented success in the analysis of Shenmai injection. In the end, the method was applied to the quality comparison of Shenmai injection from six manufacturers. The results showed that the differences among the samples from the six manufacturers were reflected in multiple types of components. CONCLUSION: This study fully demonstrates the superiority of the quantitative 1 H NMR method in comprehensive composition profiling of CHIs, which is conducive to improving the quality control level of Shenmai injection. Further, the present study can be used as a reference study for the research on the quality and safety of CHIs.

Development of a comprehensive method based on quantitative 1H NMR for quality evaluation of Traditional Chinese Medicine injection: a case study of Danshen Injection.

OBJECTIVES: This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections. METHODS: A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection. KEY FINDINGS: A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis. CONCLUSION: It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections.

[Fingerprint of Shenmai Injection based on ~1H-NMR technique].

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

[~1H-qNMR quantification of total ginsenosides in Shenmai Injection].

A content determination method based on ~1H-qNMR was developed for the determination of total ginsenosides in Shenmai Injection. The parameters were optimized with CD_3OD as the solvent, dimethyl terephthalate as the internal standard, the peak at δ 8.11 as the internal standard peak, and the peaks at δ 1.68 and δ 0.79 as quantitative peaks of total ginsenosides. The developed ~1H-qNMR-based method was validated methodologically. The results showed that the method could achieve accurate measurement of total ginsenosides in Shenmai Injection in the range of 0.167 6-3.091 1 mmol·L~(-1). The developed ~1H-qNMR-based method for total ginsenosides is simple in operation, short in analysis time, strong in specificity, independent of accompanying standard curve, and small in sample volume, which can serve as a reliable mean for the quality control of Shenmai Injection. This study is expected to provide new ideas for the development of quantification methods of total ginsenosides.

[NMR method for simultaneous determination of 21 chemical components in Danhong Injection].

Danhong Injection, a compound Chinese medicine injection prepared from Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, is used in the clinical treatment of coronary heart disease, cerebral thrombosis, myocardial infarction, angina pectoris and other cardiovascular and cerebrovascular diseases. In this study, a quantitative method for simultaneous determination of multiple components in Danhong Injection was developed based on ~1H-qNMR technology and then methodological verification was carried out. The results showed that the established method had good methodological indexes. This method can simultaneously determine the content of 21 chemical components including 6 amino acids, 4 small molecular organic acids, 5 sugars and their derivatives, 1 nucleoside, and 5 aromatic compounds in Danhong Injection. The total content accounted for about 85% of the total solid mass, which reflected the great advantage of ~1H-qNMR method in the analysis of Chinese medicine injections. The ~1H-qNMR method for simultaneous determination of multiple components in Danhong Injection developed in this study has simple operation, short analysis time, and wide application range, which has practical significance for the quality evaluation of Danhong Injection and provides reference for the development of quality control methods for Chinese medicine injections.

The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on D-galactose-induced liver and kidney aging and injury.

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.

Panax quinquefolium saponins protect against cisplatin evoked intestinal injury via ROS-mediated multiple mechanisms.

BACKGROUND: Cisplatin is one of the most common chemotherapeutic drugs. Cisplatin-induced toxicity gives rise to gastrointestinal cell damage, subsequent diarrhea and vomiting, leading to the discontinuation of its clinical application in long-term cancer chemotherapy. Panax quinquefolium L., also known as American ginseng, has many pharmacological activities such as improving immunity, anti-tumor, anti-radiation and blood sugar lowering. PURPOSE: Previously, our laboratory reported that American ginseng berry extract could alleviate chemotherapeutic agents-induced renal damage caused by cisplatin. Hence, this study further explored the protective effect of P. quinquefolium saponins (PQS) on cisplatin-induced intestinal injury in mice and the possible molecular mechanisms. METHODS: Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze intestinal injury based on various molecular mechanisms. RESULTS: We demonstrated the destruction of the intestinal barrier caused by cisplatin exposure by detecting the activity of diamine oxidase (DAO) and the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Meanwhile, cisplatin exposure changed SOD and MDA levels in the small intestine, causing oxidative damage to the intestinal mucosa. The inflammation associated-intestinal damage was further explored by the measurement of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and analysis of nuclear factor-kappa B (NF-κB) inflammatory pathway protein expression. Moreover, apoptotic cells labeled with TUNEL staining-positive cells and activated caspase family proteins suggest that cisplatin induces intestinal apoptosis. Interestingly, PQS pretreatment significantly reversed these situations. CONCLUSION: These evidences clearly suggest that PQS can alleviate cisplatin-induced intestinal damage by inhibiting oxidative stress, reducing the occurrence of inflammation and apoptosis, and improving intestinal barrier function.

Association of Mindfulness-Based Interventions With Anxiety Severity in Adults With Cancer: A Systematic Review and Meta-analysis.

Importance: Mindfulness-based interventions (MBIs), grounded in mindfulness, focus on purposely paying attention to experiences occurring at the present moment without judgment. MBIs are increasingly used by patients with cancer for the reduction of anxiety, but it remains unclear if MBIs reduce anxiety in patients with cancer. Objective: To evaluate the association of MBIs with reductions in the severity of anxiety in patients with cancer. Data Sources: Systematic searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and SCOPUS were conducted from database inception to May 2019 to identify relevant citations. Study Selection: Randomized clinical trials (RCTs) that compared MBI with usual care, waitlist controls, or no intervention for the management of anxiety in cancer patients were included. Two reviewers conducted a blinded screening. Of 101 initially identified studies, 28 met the inclusion criteria. Data Extraction and Synthesis: Two reviewers independently extracted the data. The Cochrane Collaboration risk-of-bias tool was used to assess the quality of RCTs, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Summary effect measures were reported as standardized mean differences (SMDs) and calculated using a random-effects model. Main Outcomes and Measures: Our primary outcome was the measure of severity of short-term anxiety (up to 1-month postintervention); secondary outcomes were the severity of medium-term (1 to ≤6 months postintervention) and long-term (>6 to 12 months postintervention) anxiety, depression, and health-related quality of life of patients and caregivers. Results: This meta-analysis included 28 RCTs enrolling 3053 adults with cancer. None of the trials were conducted in children. Mindfulness was associated with significant reductions in the severity of short-term anxiety (23 trials; 2339 participants; SMD, -0.51; 95% CI, -0.70 to -0.33; I2 = 76%). The association of mindfulness with short-term anxiety did not vary by evaluated patient, intervention, or study characteristics. Mindfulness was also associated with the reduction of medium-term anxiety (9 trials; 965 participants; SMD, -0.43; 95% CI, -0.68 to -0.18; I2 = 66%). No reduction in long-term anxiety was observed (2 trials; 403 participants; SMD, -0.02; 95% CI, -0.38 to 0.34; I2 = 68%). MBIs were associated with a reduction in the severity of depression in the short term (19 trials; 1874 participants; SMD, -0.73; 95% CI; -1.00 to -0.46; I2 = 86%) and the medium term (8 trials; 891 participants; SMD, -0.85; 95% CI, -1.35 to -0.35; I2 = 91%) and improved health-related quality of life in patients in the short term (9 trials; 1108 participants; SMD, 0.51; 95% CI, 0.20 to 0.82; I2 = 82%) and the medium term (5 trials; 771 participants; SMD, 0.29; 95% CI, 0.06 to 0.52; I2 = 57%). Conclusions and Relevance: In this study, MBIs were associated with reductions in anxiety and depression up to 6 months postintervention in adults with cancer. Future trials should explore the long-term association of mindfulness with anxiety and depression in adults with cancer and determine its efficacy in more diverse cancer populations using active controls.

Red ginseng protects against cisplatin-induced intestinal toxicity by inhibiting apoptosis and autophagy via the PI3K/AKT and MAPK signaling pathways.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg-1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg-1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

The PI3K/Akt and NF-κB signaling pathways are involved in the protective effects of Lithocarpus polystachyus (sweet tea) on APAP-induced oxidative stress injury in mice.

Acetaminophen (APAP)-induced acute liver injury (ALI) is a health issue that has gradually attracted attention, and is often regarded as a model of drug-induced hepatotoxicity. The leaves of Lithocarpus polystachyus Rehd. (named as "sweet tea", ST) usually serve as tea drink and folk medicine for healthcare in the southwest part of China. In previous reports, it has been proven to protect various animal models, except for APAP-induced liver injury model. Therefore, this study initially explored the protective effect of ST leaf extract (STL-E) on hepatotoxicity induced by APAP in ICR mice. STL-E of 50 and 100 mg kg-1 were given to each group for 7 days. ALI was intraperitoneally induced by APAP treatment (i.p. 250 mg per kg body weight). Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze the inflammation and apoptosis of liver tissues. Interestingly, the treatment with STL-E significantly attenuated APAP-induced liver injury (p < 0.05). Moreover, STL-E partially mitigated APAP-induced liver injury by effectively activating the PI3K/Akt pathway and inhibiting the NF-κB pathway. In a word, STL-E protected liver against APAP-induced hepatotoxicity by inhibiting the PI3K/Akt-mediated apoptosis signal pathway and inhibiting the NF-κB-mediated signaling pathway.

Maltol (3-Hydroxy-2-methyl-4-pyrone) Slows d-Galactose-Induced Brain Aging Process by Damping the Nrf2/HO-1-Mediated Oxidative Stress in Mice.

Maltol, a maillard reaction product from ginseng (Panax ginseng C. A. Meyer), has been confirmed to inhibit oxidative stress in several animal models. Its beneficial effect on oxidative stress related brain aging is still unclear. In this study, the mouse model of d-galactose (d-Gal)-induced brain aging was employed to investigate the therapeutic effects and potential mechanisms of maltol. Maltol treatment significantly restored memory impairment in mice as determined by the Morris water maze tests. Long-term d-Gal treatment reduced expression of cholinergic regulators, i.e., the cholineacetyltransferase (ChAT) (0.456 ± 0.10 vs 0.211 ± 0.03 U/mg prot), the acetylcholinesterase (AChE) (36.4 ± 5.21 vs 66.5 ± 9.96 U/g). Maltol treatment prevented the reduction of ChAT and AChE in the hippocampus. Maltol decreased oxidative stress levels by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production in the brain and by elevating antioxidative enzymes. Furthermore, maltol treatment minimized oxidative stress by increasing the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1). The above results clearly indicate that supplementation of maltol diminishes d-Gal-induced behavioral dysfunction and neurological deficits via activation of the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway in brain. Maltol might become a potential drug to slow the brain aging process and stimulate endogenous antioxidant defense capacity. This study provides the novel evidence that maltol may slow age-associated brain aging.

[Experimental studies on hypoglycemic effects of total flavonoid from Toona sinensis].

OBJECTIVE: To study hypoglycemic effects of total flavonoid from Toona sinensis (TSTF) on diabetic mice model. METHODS: To confect alloxan 0.02 g/ml with NS and injected alloxan into abdominal cavity to induce diabetic model, and all rats were fed bid with glucose for 2 consecutive days, then the blood glucose was detected by glucose oxidizes, when hypoglycemic point >11.00 mmol/L the rats were successful model made. 100 model rats were divided into 5 groups as contrast groups (distilled water), model control control groups, hight doses group (0.12 g/kg) and low doses group (0.6 g/kg) of TSTF, positive control groups of phenformin (0.10 g/kg); In addition to set 20 natural rats (distilled water), and all groups were fed qd for 15 consecutive days, and then the blood glucose were detected by glucose oxidizes in the sixteenth day. RESULTS: The blood glucose levels of the diabetic rats in TSTF groups significantly decreased. CONCLUSION: TSTF can significantly decrease the blood glucose levels of diabetic mice induced by alloxan.