An endophytic fungus Schizophyllum commune isolated from Panax ginseng enhances hairy roots growth and ginsenoside biosynthesis.

Using endophytic fungal elicitors to increase the accumulation of valuable secondary metabolites in plant tissue culture is an effective biotechnology strategy. In this study, a collection of 56 strains of endophytic fungi were isolated from different organs of cultivated Panax ginseng, of which seven strains can be symbiotically co-cultured with the hairy roots of P. ginseng. Further experiments observed that strain 3R-2, identified as endophytic fungus Schizophyllum commune, can not only infect hairy roots but also promote the accumulation of specific ginsenosides. This was further verified because S. commune colonization significantly affected the overall metabolic profile of ginseng hairy roots. By comparing the effects of S. commune mycelia and its mycelia extract (EM) on ginsenoside production in P. ginseng hairy roots, the EM was confirmed to be a relatively better stimulus elicitor. Additionally, the introduction of EM elicitor can significantly enhance the expressions of key enzyme genes of pgHMGR, pgSS, pgSE, and pgSD involved in the biosynthetic pathway of ginsenosides, which was deemed the most relevant factor for promoting ginsenosides production during the elicitation period. In conclusion, this study is the first to show that the EM of endophytic fungus S. commune can be considered as an effective endophytic fungal elicitor for increasing the biosynthesis of ginsenosides in hairy root cultures of P. ginseng.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation.

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis / 中国天然药物

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome.

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Chinese Herbal Medicine Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating Endoplasmic Reticulum Stress.

Myocardial ischemia/reperfusion injury is the main cause of increased mortality and disability in cardiovascular diseases. The injury involves many pathological processes, such as oxidative stress, calcium homeostasis imbalance, inflammation, and energy metabolism disorders, and these pathological stimuli can activate endoplasmic reticulum stress. In the early stage of ischemia, endoplasmic reticulum stress alleviates the injury as an adaptive survival response, but the long-term stress on endoplasmic reticulum amplifies oxidative stress, inflammation, and calcium overload to accelerate cell damage and apoptosis. Therefore, regulation of endoplasmic reticulum stress may be a mechanism to improve ischemia/reperfusion injury. Chinese herbal medicine has a long history of clinical application and unique advantages in the treatment of ischemic heart diseases. This review focuses on the effect of Chinese herbal medicine on myocardial ischemia/reperfusion injury from the perspective of regulation of endoplasmic reticulum stress.

[Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine].

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Metabonomics: A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure.

OBJECTIVE: To reveal the underlying relationships between Chinese medicine (CM) syndromes and ultrafiltration (UF) in the treatment of heart failure based on a metabonomic approach. METHODS: Seventeen acute decompensated heart failure (ADHF) patients were enrolled, and their CM syndromes before and after UF were collected. In addition, their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis. Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples. Partial least-squares to latent structure-discriminant analyses were used for data analysis. RESULTS: An obvious difference was observed pre- and post-treatment. A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine, 1-methylhistidine, phytosphingosine, O-decanoyl-R-carnitine, etc. were screened out, showing a significant change after UF. The major adjusted metabolic pathways were purine metabolism, histidine metabolism, leucine and isoleucine metabolism, arginine and proline metabolism, carnitine shuttle, sphingolipid metabolism and phospholipid metabolism. CONCLUSIONS: Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Thirty-year follow-up observation of the impact of iodine fortification strategy on intellectual development of children / 中华地方病学杂志

Objective:To follow up and observe the intellectual development of school children aged 8 to 10 in Baicheng County, Xinjiang Uygur Autonomous Region, which was a severe iodine deficiency disorders region in history, before and after effective control of the disease, in order to evaluate the impact of iodine supplementation on protection of children's intellectual development and provide a theoretical basis for scientific supplements of iodine.Methods:From 1989 to 2018, Combined Raven's Test for Rural in China (CRT-RC) was used to observe the intellectual development status of 660 Uyghur school children aged 8 to 10 in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively. Children's intelligence quotient (IQ) was calculated using CRT-RC's 1987 normal sample of rural children in the same age group; the data of average iodized salt coverage rate (C-IS) and childhood goiter rate (GR) from multiple local surveys and the median urinary iodine (MUIC) of children were collected, combined with the "Criteria for Elimination of Iodine Deficiency Disorders" (GB 16006-2008) and the United Nations International Children's Emergency Fund (UNICEF) recommended standards, the status of iodine deficiency during children's growth (IDG) was divided into complete exposure to iodine deficiency, no exposure, and semi-exposed. The Flynn effect (FE) gain was calculated using norm samples of children aged 8 to 10 in 1987, 1996 and 2006 of CRT-RC, and the differences in children's intellectual development after FE correction before and after IDG reached the standard were compared.Results:The IQ of children were (81.67 ± 14.13), (83.26 ± 14.05), (89.68 ± 13.58), (98.50 ± 14.33) and (103.23 ± 15.25) points in Baicheng County in 1989, 2002, 2006, 2012 and 2018, respectively, the difference between different years was statistically significant ( F = 58.357, P < 0.01). The three indicators of C-IS, GR, and MUIC didn't meet the standards during the IDG evaluation period in the 1989, 2002, and 2006 groups, which were the complete exposure to iodine deficiency; in the 2012 group, only the MUIC met the standard, which was semi-exposed; in the 2018 group, three indicators all met the standard, which was no exposure. The FE gains of 1987 with 1996, 1996 with 2006 were 0.96 points/year and 0.74 points/year, respectively; after FE correction, the actual gains of IQ of 2002 and 2006 compared with 1989, 2012 and 2018 compared with 2006 were - 9.57, - 6.11, 4.38, and 4.67 points, respectively. Conclusions:In iodine deficiency areas, intermittent iodine supplementation (1989 - 2009) for children exposed to iodine deficiency during growth still cannot effectively protect children's intellectual development; continuous and effective iodine supplementation (2010 - 2018) with iodized salt as the core and covering children's growth period has obvious positive effects on protection of children's normal intellectual development. In the future, we will continue to observe the influence of IDG full-cycle suitable iodine nutrition on children's intellectual development.

Relationship between thyroid function, iodine nutrition and autoantibodies in pregnant women / 中华地方病学杂志

Objective:To analyze the relationship between thyroid function, iodine nutrition level and thyroid autoantibodies in pregnant women.Methods:In 2016, pregnant women were selected from different water iodine areas in Tianjin. A disposable urine sample of 25 ml was collected to determine urine iodine, and 3 ml of intravenous non-anticoagulated blood was collected to determine serum thyroid hormones and thyroid autoantibodies. Chemiluminescence immunoassay was used to determine the thyroid function indexes [free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH)], thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody (TgAb) levels in pregnant women. According to serum TSH and FT 4 levels, pregnant women were divided into the euthyroidism group and subclinical hypothyroidism group(referred to as hypothyroidism). Urine iodine arsenic-cerium catalytic spectrophotometry was used to detect the urine iodine level of pregnant women. The correlation between urinary iodine levels and thyroid function indexes of the two groups of pregnant women was analyzed, and single factor and multivariate logistic regression were used to analyze the influencing factors of hypothyroidism. Results:There were 798 pregnant women in the euthyroidism group and 28 pregnant women in the hypothyroidism group. The hypothyroidism detection rate was 3.39% (28/826). In the euthyroidism group and hypothyroidism group, 43.73% (349/798) and 46.43% (13/28) of pregnant women had urine iodine levels < 150 μg/L, respectively. There was no correlation between urine iodine level and serum TSH ( r = 0.038, P > 0.05), and a positive correlation with serum FT 4 ( r = 0.077, P < 0.05). The differences between the euthyroidism group and the hypothyroidism group in the median (interquartile range) of TPOAb and TgAb were statistically significant ( Z = - 3.986, - 3.411, P < 0.05). After logistic regression analysis, TPOAb was a risk factor for hypothyroidism ( OR = 3.428, 95% CI: 1.131 - 10.388). Conclusions:Urine iodine and thyroid autoantibodies should be screened as routine examination items before or during pregnancy. Correct iodine deficiency in time, avoid blindly excessive iodine supplement, and reduce the occurrence of subclinical hypothyroidism in pregnant women, so as to reduce the adverse effects on mothers and their offspring.

A Systematic Review and Meta-analysis of the Therapeutic Effect of Acupuncture on Migraine.

Background: Migraine is an intractable headache disorder, manifesting as periodic attacks. It is highly burdensome for patients and society. Acupuncture treatment can be beneficial as a supplementary and preventive therapy for migraine. Objectives: This systematic review and meta-analysis aimed to investigate the efficacy and safety of acupuncture for migraine, and to examine transcranial doppler changes after acupuncture. Methods: Reports, conference, and academic papers published before March 15, 2019 in databases including PubMed, Cochrane library, Embase, China National Knowledge Infrastructure, WANFANG Database, Chinese journal of Science and Technology, and China Biomedical were searched. Randomized controlled trials (RCTs) involving acupuncture, sham acupuncture, and medication in migraine were included. The Cochrane Collaboration software, RevMan 5.3, was used for data processing and migration risk analysis. Results: Twenty-eight RCTs were included. 15 RCTs included medication only, 10 RCTs included sham acupuncture only, and 3 RCTs included both. The study included 2874 patients, split into 3 groups: acupuncture treatment group (n = 1396), medication control group (n = 865), and sham acupuncture control group (n = 613). The results showed that treatment was more effective in the acupuncture group than in the sham acupuncture group (MD = 1.88, 95% CI [1.61, 2.20], P < 0.00001) and medication group (MD = 1.16, 95% CI [1.12, 1.21], P < 0.00001). Improvement in visual analog scale (VAS) score was greater in the acupuncture group than in the sham acupuncture group (MD = -1.00, 95% CI [-1.27,-0.46], P < 0.00001; MD = -0.59, 95% CI [-0.81,-0.38], P < 0.00001), and their adverse reaction rate was lower than that of the medication group (RR = 0.16, 95% CI [0.05, 0.52], P = 0.002). The improvement of intracranial blood flow velocity by acupuncture is better than that by medication, but the heterogeneity makes the result unreliable. Conclusions: Acupuncture reduced the frequency of migraine attacks, lowered VAS scores, and increased therapeutic efficiency compared with sham acupuncture. Compared with medication, acupuncture showed higher effectiveness with less adverse reactions and improved intracranial blood circulation. However, owing to inter-study heterogeneity, a prospective, multicenter RCT with a large sample is required to verify these results.

Advances of the effects of iodine on brain development / 中华地方病学杂志

Iodine is an essential element in the synthesis of thyroid hormones. The normal brain development of children depends on thyroid hormone, and the critical period is in the first three years of life. Iodine deficiency is the most influential and preventable factor that is known to cause brain neurodevelopmental disorders in children. Therefore, research on the relationship between iodine nutrition and thyroid function of pregnant women and brain development of offspring has always been a hot spot in the research and prevention of iodine deficiency disorders. However, there has been no clear conclusion on the influence and extent of thyroid dysfunction such as hidden iodine deficiency in pregnant women (urinary iodine is 100-150 μg/L), subclinical hypothyroidism and hypothyroidism on the brain development of offspring. This article reviews the research in this field, the related research on the effects of iodine deficiency, iodine supplementation and iodine overdose on children's brain development, and introduces the preventive and therapeutic effects of iodine and thyroxine supplementation during pregnancy.

Profiling and identification of aqueous extract of Cordyceps sinensis by ultra-high performance liquid chromatography tandem quadrupole-orbitrap mass spectrometry / 中国天然药物

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

Dandelion Chloroform Extract Promotes Glucose Uptake via the AMPK/GLUT4 Pathway in L6 Cells.

The number of patients with type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Glucose transporter 4 (GLUT4) is one of the main proteins that transport blood glucose into the cells and is a target in the treatment of T2DM. In this study, we investigated the mechanism of action of dandelion chloroform extract (DCE) on glucose uptake in L6 cells. The glucose consumption of L6 cell culture supernatant was measured by a glucose uptake assay kit, and the dynamic changes of intracellular GLUT4 and calcium (Ca2+) levels were monitored by laser scanning confocal microscopy in L6 cell lines stably expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM) was traced via myc-GLUT4-mOrange. GLUT4 expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), protein kinase C (PKC), and phosphorylation levels were determined by performing western blotting. GLUT4 mRNA expression was detected by real-time PCR. DCE up-regulated GLUT4 expression, promoted GLUT4 translocation and fusion to the membrane eventually leading to glucose uptake, and induced AMPK phosphorylation in L6 cells. The AMPK inhibitory compound C significantly inhibited DCE-induced GLUT4 expression and translocation while no inhibitory effect was observed by the phosphatidylinositol 3-kinase (PI3K) inhibitor Wortmannin and PKC inhibitor Gö6983. These data suggested that DCE promoted GLUT4 expression and transport to the membrane through the AMPK signaling pathway, thereby stimulating GLUT4 fusion with PM to enhance glucose uptake in L6 cells. DCE-induced GLUT4 translocation was also found to be Ca2+-independent. Together, these findings indicate that DCE could be a new hypoglycemic agent for the treatment of T2DM.

Ethanolic Extract of Folium Sennae Mediates the Glucose Uptake of L6 Cells by GLUT4 and Ca2.

In today's world, diabetes mellitus (DM) is on the rise, especially type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. T2DM has high morbidity, and therapies with natural products have attracted much attention in the recent past. In this paper, we aimed to study the hypoglycemic effect and the mechanism of an ethanolic extract of Folium Sennae (FSE) on L6 cells. The glucose uptake of L6 cells was investigated using a glucose assay kit. We studied glucose transporter 4 (GLUT4) expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), and protein kinase C (PKC) phosphorylation levels using western blot analysis. GLUT4 trafficking and intracellular Ca2+ levels were monitored by laser confocal microscopy in L6 cells stably expressing IRAP-mOrange. GLUT4 fusion with plasma membrane (PM) was observed by myc-GLUT4-mOrange. FSE stimulated glucose uptake; GLUT4 expression and translocation; PM fusion; intracellular Ca2+ elevation; and the phosphorylation of AMPK, Akt, and PKC in L6 cells. GLUT4 translocation was weakened by the AMPK inhibitor compound C, PI3K inhibitor Wortmannin, PKC inhibitor Gö6983, G protein inhibitor PTX/Gallein, and PLC inhibitor U73122. Similarly, in addition to PTX/Gallein and U73122, the IP3R inhibitor 2-APB and a 0 mM Ca2+-EGTA solution partially inhibited the elevation of intracellular Ca2+ levels. BAPTA-AM had a significant inhibitory effect on FSE-mediated GLUT4 activities. In summary, FSE regulates GLUT4 expression and translocation by activating the AMPK, PI3K/Akt, and G protein⁻PLC⁻PKC pathways. FSE causes increasing Ca2+ concentration to complete the fusion of GLUT4 vesicles with PM, allowing glucose uptake. Therefore, FSE may be a potential drug for improving T2DM.

[Study on fragmentation pathways of three ginkgolides by mass spectrometry].

The fragmentation pathways of the three ginkgolides (ginkgolides A, ginkgolides B, ginkgolides C) have been studied with high resolution and high mass accuracy using quadrupole time-of-flight mass spectrometry in negative ion mode in this paper. The results indicate that the three ginkgolides have similar fragmentation pathways, including four kinds of common cleavage pathways and one common characteristic ion. In high quality regions, the typical fragmentation pathways of the three ginkgolides are lactone ring opening with continuous loss of CO, CO2,and loss of H2O. In low quality regions, the common characteristic fragment ion of the three ginkgolides at m/z72.993 6 is formed by C rings cleavage. Also, the common fragment ions of ginkgolides A and ginkgolides B at m/z141.018 8, 125.023 8, 113.024 0, 97.029 1 are formed by A rings cleavage. The study of fragmentation pathways could be adopted for the structural identification of the ginkgolides and their metabolites.