Phyllanthus emblica Linn: A comprehensive review of botany, traditional uses, phytonutrients, health benefits, quality markers, and applications.

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.

[Chemical constituents from fruits of Morinda citrifolia and their inhibitory effects on proliferation of synoviocytes in vitro].

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-ß-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-ß-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) µmol·L~(-1).

Human cytomegalovirus infection perturbs neural progenitor cell fate via the expression of viral microRNAs.

Human cytomegalovirus (HCMV) preferentially targets neural progenitor cells (NPCs) in congenitally infected fetal brains, inducing neurodevelopmental disorders. While HCMV expresses several microRNAs (miRNAs) during infection, their roles in NPC infection are unclear. Here, we characterized expression of cellular and viral miRNAs in HCMV-infected NPCs during early infection by microarray and identified seven differentially expressed cellular miRNAs and six significantly upregulated HCMV miRNAs. Deep learning approaches were used to identify potential targets of significantly upregulated HCMV miRNAs against differentially expressed cellular messenger RNA (mRNAs), and the associations with miRNA-mRNA expression changes were observed. Gene ontology enrichment analysis indicated cellular gene targets were significantly enriched in pathways involved in neurodevelopment and cell-cycle processes. Viral modulation of selected miRNAs and cellular gene targets involved in neurodevelopmental processes were further validated by real-time quantitative reverse transcription polymerase chain reaction. Finally, a predicted 3' untranslated region target site of hcmv-miR-US25-1 in Jag1, a factor important for neurogenesis, was confirmed by mutagenesis. Reduction of Jag1 RNA and protein levels in NPCs was observed in response to transient expression of hcmv-miR-US25-1. A hcmv-miR-US25-1 mutant virus (ΔmiR-US25) displayed limited ability to downregulate Jag1 mRNA levels and protein levels during the early infection stage compared with the wild type virus. Our collective experimental and computational investigation of miRNAs and cellular mRNAs expression in HCMV-infected NPCs yields new insights into the roles of viral miRNAs in regulating NPC fate and their contributions to HCMV neuropathogenesis.

Anthraquinones with potential antiproliferative activities from the fruits of Morinda citrifolia.

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.

Adding acupoint identification into the textbook Meridians and Acupoints: preliminary assumption / 中国针灸

To deepen the understanding of the acupoint indications, clarify the targeting of acupoints, and provide a basis for the composition of acupuncture prescriptions, it is suggested to add acupoint identification into the textbook Meridians and Acupoints, and a preliminary assumption that relevant acupoints can be identified by taking the indications, locations, and meridians as the key points is proposed. In this paper, acupoints for treating stomach disease, acupoints of eye region, and five-shu points of lung meridian are taken as examples, combined with ancient literature and modern scientific research achievements, the main indications of acupoint is identified, which is of great significance to the discipline's development, talent training, and achievement transformation.

Construction of glioma prognosis model with n7-methylguanosine related long non-coding RNA based on transcriptome / 中国医师进修杂志

Objective:To investigate the relationship between n7-methylguanosine (m7G) related long non-coding RNA (lncRNA) expression and glioma prognosis, and to construct a prognosis model with m7G-related lncRNA in patients with glioma.Methods:Data related to the test set and validation set were downloaded from the Cancer and Tumor Genome Atlas (TCGA) database and the China Glioma Genome Atlas (CGGA) database. LASSO regression and random forest algorithm were used to establish the glioma prognosis model with m7G related lncRNA. Individualized risk scores were calculated using the weighted expression levels of the 12 extracted lncRNA coefficients, and test set and validation set glioma patients were categorized into high and low risk groups based on median risk score. Kaplan-Meier survival curve was drawn, the comparison method used log rank test. The efficacy of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was evaluated using the receiver operating characteristics (ROC) curve.Results:A total of 12 lncRNA associated with m7G were obtained, with a risk score = 1.026 × AC002454.1 + 1.086 × AC131097.4 + 1.039 × AC147651.3 + 1.01 × AGAP2-AS1 + 1.036 × CRNDE + 0.733 × GDNF-AS1 + 1.321 × HOXD-AS2 + 0.934 × LINC00641 + 1.183 × PAXIP1-AS2 + 1.258 × PVT1 + 0.909 × SOX21-AS1 + 0.754 × TTC28-AS1, with a median risk score of - 0.45 scores. Kaplan-Meier survival curve analysis result showed that the median survival time in high risk group was significantly shorter than that in low risk group (1.98 years vs. 9.51 years, log-rank χ2 = 131.78, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was 0.891, 0.923 and 0.912. In the validation set of glioma patients, Kaplan-Meier survival curve analysis result showed that the median survival time in high risk group was significantly shorter than that in low risk group (1.29 years vs. 6.88 years, log-rank χ2 = 103.27, P<0.01); ROC curve analysis result showed that the AUC of risk score in predicting the 1-, 2- and 5-year survival rate in patients with glioma was 0.724, 0.795 and 0.762. In the test set and validation set, multivariate Cox regression analysis result showed that the risk score was the independent risk factors of prognosis in patients with glioma ( HR = 1.992 and 1.247, P<0.01 or <0.05). Conclusions:A risk score model with m7G related lncRNA based on transcriptome is a novel approach to predict the prognosis of glioma patients.

Clinical application of the new classification criteria in children with Miller Fisher syndrome and clinical characteristics analysis of different types of Miller Fisher syndrome / 中华实用儿科临床杂志

Objective:To investigate the clinical application of the new classification criteria in children with Miller Fisher syndrome (MFS), and to analyze clinical characteristics of different types of MFS.Methods:Clinical data of MFS patients hospitalized in the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2019 were collected and analyzed retrospectively, including demographic characteristics, clinical symptoms, neurological examination findings, laboratory examination data, diagnosis and treatment, and prognosis.The counting data was described by percentage, and the measurement data was described by median.Results:A total of 23 patients were included in the research, including 14 males and 9 females, with a median age of 4 years and 8 months.There were 3 cases of pure MFS; 5 cases of incomplete MFS, including 1 case of acute ptosis and 4 cases of acute ataxia neuropathy; 15 cases of overlapping syndrome, including 13 cases of MFS/Guillain Barre syndrome (GBS), 1 case of MFS/pharyngocervical brachial variant GBS(PCB GBS)and 1 case of MFS/GBS/Bickertaff brainstem encephalitis (BBE). In addition to Ⅲ, Ⅳ and Ⅵ cranial nerve palsy, 11 cases had the involvement of other cra-nial nerves, including 2 cases in pure MFS, 8 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Autonomic nervous dysfunction occurred in 6 cases.Respiratory muscle paralysis occurred in 6 cases, including 5 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Graded by the Hughes scoring system (HG score), 3 cases with pure MFS were graded 4 points; 1 case with acute ptosis was graded 0; 3 cases with acute ataxia neuropathy were graded 2 points, and the other one was graded 3 points; 1 case with MFS/PCB GBS was graded 3 points; 10 cases with MFS/GBS were graded 4 points, 1 case was graded 3 points, and the other 2 cases were graded 2 points; 1 case with MFS/GBS/BBE was graded 4 points.Twenty-two patients were treated with intravenous immunoglobulin.The HG of all patients at discharge decreased at varying degree, which was graded 0 at 6 months of follow-up.Conclusions:The clinical application of the new diagnostic classification method is helpful to the accurate diagnosis of different types of MFS.More than half of MFS cases will develop into the overlapping syndrome.The overlapping of MFS and GBS or BBE is prone to the involvement of cranial nerves except for the external ophthalmic muscles, autonomic nerve dysfunction and respiratory muscle paralysis.The disease course of MFS varies, and its diagnosis should be comprehensively made.All cases of MFS in this study have a satisfactory prognosis.

CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of CO2 laser moxibustion on endometriosis related pelvic pain of cold coagulation and blood stasis.@*METHODS@#A total of 76 patients with endometriosis related pelvic pain of cold coagulation and blood stasis were randomized into a laser moxibustion group and a sham laser moxibustion group, 38 cases in each group. In the laser moxibustion group, moxibustion was applied at bilateral Zigong (EX-CA 1) using CO2 laser moxibustion instrument. In the sham laser moxibustion group, the manipulation of moxibustion was same as the laser moxibustion group, without laser output. The treatment was given once every other day, 30 min each time, 3 times a week for 4 weeks in both groups. Before and after treatment and follow-up of 3 months after treatment, the scores of Gracely box scale (GBS) and visual analogue scale (VAS) were observed, the usage of non-steroidal anti-inflammatory drug for the duration of the treatment and the average days of taking drugs were recorded in both groups.@*RESULTS@#Compared before treatment, the GBS and VAS scores were decreased after treatment and during follow-up in the laser moxibustion group (P<0.05), while those in the sham moxibustion group had no significant differences (P>0.05). Compared with the sham moxibustion group, the GBS and VAS scores were decreased after treatment and during follow-up (P<0.05), the cases and average days of taking drugs were less in the laser moxibustion group (P<0.05).@*CONCLUSION@#CO2 laser moxibustion can improve the pain symptom in patients with endometriosis related pelvic pain of cold coagulation and blood stasis, and reduce the use of analgesic drugs.

Effect of a Template Case Report Based on Cognitive Task Analysis on Emergency Thinking Ability of Resident Doctors in Standardized Training.

OBJECTIVE: To explore the effect of a template case report based on cognitive task analysis on the emergency thinking ability of resident doctors in standardized training. METHODS: The doctors were split into two groups, according to the date they joined the emergency department (n = 40, each group): the observation and control groups. In the observation group, the resident doctors' teachers in standardized training adopted the cognitive task analysis method to determine the primary links of emergency thinking, made case templates, and carried out training based on the case template report. In the control group, traditional teaching methods were used by the teachers. RESULTS: In the observation and control groups, the scores at departure were 88.10 ± 3.88 and 75.23 ± 7.19, respectively (P < 0.05), and the student's ability improvement rates were 92.5% and 75.0% (P < 0.01). In addition, the awareness rate of "know how to study" and "know how to work in emergency" in the observation group was 90% and 90%, respectively. The rate of doctors that considered "missed diagnosis and misdiagnosis can be reduced" was 85%, and the rate of doctors that considered "help to learn in other departments in the future" was 80%. CONCLUSION: Template case reports based on the cognitive task analysis for emergency thinking training can help resident doctors in standardized training improve their emergency thinking ability.

Observation of the Effectiveness of a Diagnostic Model for Acute Abdominal Pain Based on the Etiology Checklist and Process Thinking.

OBJECTIVE: The present study aimed to explore the effectiveness of the etiology checklist and process thinking in the differential diagnosis for acute abdominal pain. METHODS: A retrospective design was used to include 5,403 patients with acute abdominal pain in the Emergency Department of Hebei Provincial People's Hospital. The patients with acute abdominal pain between July and December 2017 in whom the etiology checklist and process thinking were not implemented were selected as the traditional group. Those with acute abdominal pain between July and December 2018 in whom the etiology checklist and process thinking were implemented were selected as the process thinking group. The clinical data, such as the emergency length of stay, hospitalization expenses, hospitalization length of stay, diagnostic accuracy, and outcome, were compared between the two groups. RESULTS: For patients at emergency level 2 and above, the average emergency length of stay was shorter in the process thinking group than in the traditional group, while the average emergency length of stay was longer for patients at emergency level 3. For hospitalized patients at emergency level 2 and above and patients at emergency level 3, those in the process thinking group had improved diagnostic accuracy, shorter average hospitalization length of stay, reduced average hospital expenses, and improved outcomes. In the comparison among six physicians, the results in the traditional group were inconsistent and statistically different in terms of the average emergency length of stay and diagnostic accuracy, while the results in the process thinking group tended to be consistent. The differences were not statistically different. CONCLUSION: The diagnostic model for acute abdominal pain based on the etiology checklist and process thinking could improve the diagnostic accuracy and outcomes for patients with acute abdominal pain.

Carbazole alkaloids from the fruits of Clausena anisum-olens with potential PTP1B and α-glucosidase inhibitory activities.

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.

Research progress in immune regulation mechanism of Polygonati Rhizoma polysaccharide / 中国药理学与毒理学杂志

Polygonati Rhizoma is the dry rhizome of Liliaceae plants Polygonatum kingianum coil ethemsl, Polygona?tum sibiricum Redoute and Polygonatum cyrtonem Hua. It tastes sweet and has a flat nature. It belongs to the spleen, lung and kidney channels. Polygonati Rhizoma contains a variety of chemical components, including polysaccharides, alkaloids, steroidal saponins, lignans, phytosterols, and so on. Polygonati Rhizoma polysaccharide (PSP) is one of the main bioactive components of Polygonati Rhizoma. It is widely used. It has the effects of enhancing immunity, anti-inflammatory, anti-virus and regulating blood lipid. In recent years, the immunomodulatory function of PSP has been paid more and more attention by researchers. PSP can play an immunomodulatory role through a variety of mecha?nisms. (1) Effects of PSP on innate immunity. ① Macrophages have a strong ability to phagocytize and clear foreign bodies. When polysaccharides bind to macrophage specific membrane receptors, the immune response will be officially activated. RAW264.7 cells can be activated by PSP MR and TLR4 mediated signal pathway to improve the pinocytosis and phagocytosis of RAW264.7 cells. ② Natural killer cell (NK cell) is a very important immune cell in the body. It is a non-specific immune killer cell naturally existing in the body. It has the dual functions of immune regulation and cytotoxic?ity. It was found that the signal pathway mediated by PSP CR3 and TRL2 may play a major role in the stimulation of NK cells. (2) Effects of PSP on adaptive immune response. ① Lymphocytes can be divided into two forms: T cells and B cells due to different differentiation and maturation sites. T lymphocytes are the general name of thymus dependent lym?phocytes. B lymphocytes differentiate and mature from animal bone marrow cells and exert their humoral immune func?tion by secreting different antibodies. It was found that PSP could activate T/B lymphocytes and increase the ratio of CD4+/CD8+in lymph cells to promote the regulation of immune system.②Thymus and spleen index refers to the level of body immunity through the development of immune organs and the functional status of immune cells. The higher the index of thymus and spleen, the higher the immune activity. A large number of studies have found that PSP can improve immune activity by promoting the proliferation of spleen lymphocytes and regulating organ index, so as to increase the weight and index of thymus and spleen induced by CY. ③ Antibody is a glycoprotein secreted by B cells after antigen stimulation and a series of proliferation and differentiation into plasma cells. Antibody production level is one of the main indicators of nonspecific immune function. PSP can not only improve the serum antibody level of mice by regulating the phagocytosis of mouse macrophages and the level of serum hemolysin, but also enhance the concentration of IL-2 secreted by spleen lymphocytes in vitro to increase the level of antibody response, and then improve the humoral immune function of the body. (3) Effect of PSP on cytokines. ① A large number of experiments have proved that PSP has a significant effect on promoting the production of interleukin (IL). PSP can combine with specific receptors on the surface of immune cells to activate various intracellular signal transduction pathways, enhance the secretion of cytokines such as IL-2, IL-4, IL-6 and IL-10 by spleen lymphocytes in vitro, make them directly kill target cells and regulate the immune function of the body at the molecular level. ② Interferon (IFN) is a special protein or glycoprotein produced by human or animal cells in response to various stimuli. It plays an important role in anti-virus, immune regulation and cell proliferation control. It was found that PSP could increase IFN-γsecreted by T cells and NK cells, activate macrophages to regulate immune function. ③ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response.④ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response. PSP can promote the proliferation and phagocytic activity of macro?phage RAW264.7 to reduce its apoptosis rate. By increasing the secretion of TNF-α, PSP can promote the dissociation between NF-κВprotein and IκВp65 protein after phosphorylation, so as to start the expression and transcription of related immune genes. In conclusion, PSP can improve immunity and has a good application prospect in the development of immunomodulatory drugs.

Research progress in mulberry leaf polysaccharide in treating diabetic nephropathy / 中国药理学与毒理学杂志

Diabetic nephropathy (DN) is one of the most common complications of diabetes. It is an important cause of diabetes disability and death. DN is a systemic metabolic syndrome. In its pathogenesis, the interaction of various cell activities and a large number of cytokine biological activities, the activation of signal pathways and so on are involved in the development of DN. At present, the clinical treatment of DN is mainly Western medicine, but it has limitations such as strong toxicity, high side effects and poor compliance. Therefore, the discovery of natural anti-DN substances has also become an important means to treat DN. Mulberry leaves are the dry leaves of Morus alba L. It is not only a tradi?tional Chinese medicine, but also a dual-purpose medicinal material for medicine and food. It has the effects of dispelling wind and clearing heat, cooling blood and brightening eyes, tonifying and so on. Mulberry leaf polysaccharide (MLP) is a kind of high molecular compound in mulberry leaves. It has many pharmacological effects, such as hypoglycemic, antiox?idant, anti-stress, anti-virus and so on. Therefore, the pharmacological effects of mulberry leaf polysaccharides on dia?betic nephropathy are reviewed in this paper, so as to provide references for further research and application. The patho?genesis of DN is complex, and the mechanism of renal injury has not been completely clarified. The current studies believe that DN is closely related to heredity, abnormal glucose metabolism, abnormal lipid metabolism, microcirculation disorder, cytokine action, oxidative stress and so on. Relevant studies show that the pharmacological effects of mulberry leaf polysaccharide in the prevention and treatment of DN mainly include: ① Effect on transforming factor-β1 (TGF-β1):TGF-β1 has become an important cytokine involved in the formation of renal fibrosis by regulating cell proliferation and differentiation and the production of extracellular matrix (ECM). MLP can significantly inhibit TGF-β1 protein, and then inhibit the synthesis of extracellular matrix by renal interstitial fibroblasts and inhibit the realization of fibrosis.②Effect on insulin receptor substrate (IRS-1): IRS-1 is an important signal molecule at the beginning of IR signal transduction. The decrease of IRS-1 gene expression or the decrease of expression can affect the effective transmission of IR signal and lead to the development and deterioration of diabetes. MPL can significantly increase the expression of IRS-1 mRNA in liver tissue of DN rats, so as to prevent and treat DN. ③ Effect on the expression of resistin protein in adipose tis?sue. Resistin is a secretory polypeptide derived from adipose tissue and is specifically expressed in white adipose tissue and is closely related to type 2 diabetes mellitus (T2DM). Experimental studies show that MLP can effectively reduce the expression of resistin protein in white adipose tissue of T2DM rats, indicating that MLP may reduce the level of IR by inhibiting the expression of resistin in adipose tissue, thereby reducing the insulin resistance state of T2DM rats, so as to achieve the goal of treating diabetes.④Effect on adiponectin receptor 1 (AdipoR1):adiponectin can improve insulin resistance, reduce blood glucose and lipid. AdipoR1 is mainly expressed in skeletal muscle and kidney. Studies have shown that AdipoR1 is closely related to the occurrence and development of DN. The results showed that MLP could reduce the blood glucose and blood lipid level and up regulate the expression of AdipoR1 mRNA in DN rats, suggesting that MLP may delay the occurrence and development of DN. This article reviewed the pharmacological effects of mulberry leaf polysaccharides on diabetic nephropathy, and provided a useful basis for further development and utilization of mul?berry leaf polysaccharides in the treatment of DN.

Research progress in pharmacological effects of polyphenols in Areca catechu L / 中国药理学与毒理学杂志

Betel nut is the dry and mature seed of Areca catechu L., which is originated in Malaysia and cultivated in Yunnan, Hainan and Taiwan and other tropical areas of China. It is also known as big belly, binmen, olive seed, green seed and so on. Betel nut is a dual-use resource for medicine and food, which was first contained in LI Dang's Pharma?ceutical Record. Betel nut tastes bitter, pungent, warm in nature, and belongs to the stomach and large intestine meridian. It contains a variety of chemical components such as alkaloids, phenolic compounds, polysaccharides, fatty acids, amino acids, flavonoids, minerals, terpenoids, and steroids. It has the advantages of promoting digestion, lowering blood pres?sure, anti-depression, anti-oxidation, anti-inflammatory, and anti-parasites, antibacterial and other activities. The content of total phenols in fresh fruits of areca nut was 31.1％, mainly including catechin, isorhamnetin, chrysopanthoxanthin, luteolin, tannin and other polyphenols. The commonly used methods for determination of polyphenols in areca are vanil?lin titration potassium permanganate titration and potassium ferricyanide spectrophotometry. The main activities and mechanisms of areca polyphenols include: ① Antidepressant effect: polyphenols bind to monoamine oxidase type A (MAO-A) receptors that inhibit the production of neurotransmitters, thereby increasing the content of amine transmitters in the brain and playing a therapeutic effect on depression. ② Antioxidant effect: polyphenols contain multiple adjacent hydroxyl groups, which are easily oxidized and can effectively remove superoxide anion free radical, hydroxyl free radi?cal, 1,1-diphenyl-2-picrylhydrazyl radical, showing good antioxidant activity.③Bacteriostatic effect:polyphenols can spe?cifically bind to the surface of bacteria, thus achieving bacteriostatic effect. Studies have found that betel nut polyphenols have varying degrees of inhibitory effects on a variety of bacteria. ④ Inducing apoptosis of lymphocytes: polyphenols deplete the mercaptan in lymphocytes and make them unable to survive, thus inducing apoptosis of lymphocytes.⑤Anti-aging effect: polyphenols have the effect of anti-hyaluronidase and anti-elastase, so as to protect elastin fiber and pro?mote collagen synthesis.⑥Anti-allergic effect:studies have found that polyphenols can reduce ovalbumin induced aller?gic reactions.⑦Other functions:betel nut can freshen breath, eliminate bad breath, and resist the activity of cobra venom. At present, domestic and foreign scholars' research on betel nut mainly focuses on arecoline and its carcinogenicity, mutagenicity, effects on reproductive function, addiction and toxicity to the nervous system, and there are few studies on the positive effects of betel nut, especially on it. There is less research on phenolic ingredients. Therefore, this article reviews the polyphenolic chemical constituents of betel nut, and fully excavates its pharmacological activity to provide a reasonable basis for the scientific use of betel nut.

Research progress in mechanism of curcumin in treatment of Parkinson disease / 中国药理学与毒理学杂志

Curcumin (Cur) is an important bioactive component of polyphenols in the rhizomes of Curcuma longa L., Tulipa gesneriana L. and other Curcuma plants. It has a wide range of pharmacological effects such as anti-tumor, anti-atherosclerosis, anti-inflammatory, and neuroprotection. Parkinson disease (PD) is a neurodegenerative disease that often occurs in the elderly. Its main pathological characteristics are the characteristic loss of substantia nigra dopaminer?gic neurons, the decrease of dopamine content in the striatum, and the formation of Lewy bodies. At present, the main methods of clinical treatment of PD include drug therapy and surgical operation, but due to its complicated pathogene?sis, they can only play a role in relieving, but cannot be completely cured. Modern pharmacological studies have shown that Cur has certain effects in the treatment of PD. ① Anti-oxidative stress: oxidative stress is closely related to the degeneration of dopaminergic neurons. Studies have found that Cur can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) content, thereby reducing oxidative stress damage and protecting dopaminergic neuron.②Reduce inflammation in brain tissue:neuroinflammation plays an impor?tant role in the development of PD. Reducing the level of inflammatory factors can have a certain therapeutic effect on PD. Studies have shown that high-dose Cur can reduce the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis fac?tor-α (TNF-α) in brain tissue, reduce inflammation, inhibit further neuronal damage, improve learning and memory, and exert neuroprotective effects. ③ Activation of autophagy: the abnormal accumulation of α-Synuclein (α-Syn) in Lewy bodies is closely related to PD, and autophagy dysfunction leads to α-Syn clearance obstacles and an important factor of abnormal aggregation. Cur can increase the expression of microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) and lysosome-associated membrane protein 2A (LAMP2A), and reduce the protein and mRNA expression of α-Syn. It can be seen that Cur promotes the elimination ofα-Syn and protects neurons from damage by activating autophagy.④Inhi?bition of mitochondrial dysfunction:mitochondria plays a central regulatory role in the process of cell apoptosis, and mito?chondrial dysfunction is related to reactive oxygen species, energy and mitochondrial membrane potential, which may cause substantia nigra striatal neuropathy. Experiments have shown that Cur can reduce the active oxygen content in PC12 cells induced by MPP+, maintain the normal membrane potential of mitochondria, thereby stabilizing mitochondrial function and inhibiting PC12 cell apoptosis. This study summarized the action mechanism of Cur in the treatment of PD, and clarified the basis of its pharmacodynamics, providing a reference for the clinical research and new drug develop?ment research of Cur in the treatment of PD.

Study on pharmacological effect of Chuanxiong Rhizoma on vascular neuropathic headache / 中国药理学与毒理学杂志

Chuanxiong Rhizoma is the dry rhizome of Ligusticum chuanxiong in the umbelliferae family. Chuanxiong Rhizoma pungent, warm, go to liver, gallbladder and pericardium. Effective in promoting blood circulation, promoting Qi, dispelling wind and relieving pain, it could treat chest pain, tingling pain in chest and flank, lump, irregular menstruation, amenorrhea, symptomatic abdominal pain, headache and rheumatic pain. Neurovascular headache is a primary disease caused by dysregulation of intracranial vascular movement and nerve function. It has the characteristics of long course, intermittent recurrent attacks, lingering and difficult to heal. Attacks are often accompanied by many plant nervous sys?tem symptoms, such as rapid breathing, accelerated heart rate, vomiting, and gastrointestinal dysfunction. Vascular nerve headache is a common clinical disease, frequently bidity. Studies have shown that Chuanxiong Rhizoma has good pharmacological effects in the treatment of vascular neuropathic headache.① The action of Qi and blood circula?tion: vascular and neurovascular headache is caused by the evil of external wind and cold and damp heat, which leads to the disconnection of the veins, the disorder of Qi and blood, the obstruction of Qi and blood channels, the loss of brain collateral, and finally causes migraine. Modern Chinese medicine points out that"wind, blood stasis, deficiency, phlegm"are the key factors of the disease. Chuanxiong Rhizoma is the medicine of Qi in the blood. It is pungent and warm. It is good at activating blood and promoting Qi, dispelling wind, relieving pain and dispelling cold, so as to achieve the effect of treating vascular headaches. ② Improve brain circulation: angioneurotic headache is caused by dysfunction of the central nervous system related to the regulation of vascular movement, which causes vasospasm or extreme vasodi?lation, and the decrease of intracranial blood flow causes cerebral ischemia and hypoxia. Sodium ferulate is a chemical component in Chuanxiong Rhizoma. It has a relatively good inhibitory effect on platelet aggregation and the release of 5-HT from platelets. It can ensure the normal contraction of intracranial and extracranial blood vessels, improve the patient's brain circulation and nerve function, so as to achieve the effect of treating angioneurotic headaches.③Sedative and analgesic effect:the volatile oil and water decoction of Chuanxiong Rhizoma have sedative and analgesic effects, and the water decoction can counteract the excitatory effect of caffeine. Studies have shown that the ATP activa?tion current of rat dorsal root ganglion neurons can be inhibited by ligustrazine in a non-competitive way, which also indi?cates that Chuanxiong Rhizoma has a good analgesic effect. In this study, the effects of Chuanxiong Rhizoma on angoneeurotic headache were reviewed, and the pharmacological effects of Chuanxiong Rhizoma were further elucidated, providing basis for clinical application and new drug development of Chuanxiong Rhizoma in the treatment of angoneeu?rotic headache.

Progress in protective effect and mechanism of 6-gingerol on myocardial ischemia/reperfusion injury / 中国药理学与毒理学杂志

The morbidity and mortality of cardiovascular diseases are very high, which has attracted more and more attention all over the world. Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting, which can quickly restore blocked coronary blood flow and reduce the infarct size. However, the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow, its pathological mechanism is complicated, and the Western medicine countermeasures are very limited. Among the current drugs for the treatment of cardiovascular diseases, traditional Chinese medicine has become a research hotspot due to its multiple targets, safety, and low side effects. Ginger is the fresh rhizome of Zingiber offici?nale Rosc., a perennial herbaceous plant in the ginger family. It is a dual-purpose resource of medicine and food. Ginger has the functions of relieving the appearance and dispelling cold, warming up and relieving vomiting, resolving phlegm and relieving cough, and relieving fish and crab poison. The chemical components of ginger mainly include volatile oil, gingerol, diphenylheptane, etc.. Among them, 6-gingerol, as the main active component of gingerols, has obvious phar?macological effects in myocardial protection, anti-oxidation, anti-inflammatory, etc.. Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress, anti-inflammatory, inhibiting cell apoptosis, and preventing cal?cium influx. ① Anti-oxidative stress: oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance, and it is also an important factor leading to myocardial damage. Many studies have confirmed that 6-gingerol has an antioxidant effect, and it is considered a natural antioxidant. 6-gingerol can significantly reduce the degree of oxi?dative stress and the level of reactive oxygen species caused by cardiomyocyte damage, and has a significant cardiopro?tective effect. ② Anti-inflammatory: inflammation can cause substantial cell damage and organ dysfunction, which is another important cause of myocardial damage. 6-gingerol can reduce the levels of inflammatory factors such as inter?leukin-6, interleukin-1β, and tumor necrosis factor-αin cardiomyocytes, and at the same time inhibit the TLR4/NF-κB sig?naling pathway, an important regulatory pathway of inflammation, showing that it may improve myocardial damage through anti-inflammatory effects. ③ Inhibition of apoptosis: apoptosis is a complex and orderly process in the autono?mous biochemical process of cells, and one of the main mechanisms of myocardial injury. This process can be roughly divided into three pathways: mitochondria, endoplasmic reticulum, and death receptors. Among them, the mitochondrial pathway plays an important role, and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane. Studies have found that the preventive application of 6-gingerol can reduce cell damage, reduce the number of apoptotic cells, reduce the activity of Bax and caspase-3, and increase the expression of Bcl-2. Therefore, 6-gingerol pretreatment can reduce the damage of cardio?myocytes, and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury, which may be related to excessive contracture, arrhythmia, and mitochondrial Ca2+accumulation that impairs myocardial function. 6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current, thereby reducing extracellular Ca2+ influx, thereby avoiding calcium overload and playing a cardioprotective effect. In summary, 6-gingerol can effectively treat and improve myocardial isch?emia/reperfusion injury, and it has great development potential in the fields of medicine and health products.

Pharmacological effects of Schisandra Chinensis Fructus polysaccharide on intestinal protection / 中国药理学与毒理学杂志

Schisandra Chinensis Fructus (SCF) is the fruit of Schisandra chinensis (Turcz.) Baill., a perennial vine. It was first recorded in Shen Nong's herbal classic and has a long application history. Studies have shown that SCF has anti-inflammatory, protective liver, antioxidant, antibacterial and other pharmacological effects. Ancient prescriptions are commonly used in the treatment of chronic diarrhea and other intestinal diseases and diabetes. Modern clinical phar?macology features of SCF polysaccharide (SCFP) in diabetes, liver diseases, enteritis and other aspects have achieved excellent results. Gut is an important digestive organ of human body, but intestinal diseases are varied, including Crohn's disease, ulcerative colitis, intestinal flora imbalance, etc.. It is a chronic and non-specific inflammatory disease. The disease is persisted for a long time and the incidence rate is expected to rise. Most of the symptoms are recurrent diarrhea, bloody stool and abdominal pain. It is considered by the World Health Organization as a refractory disease. At present, there is little possibility of complete cure, which is closely related to complex environmental factors, eating hab?its and heredity. In recent years, clinical studies have found that SCFP has a variety of pharmacological effects on intes?tinal protection.①Reduce inflammatory factors:intestinal mucositis is a common adverse reaction in patients with chemo?therapy. The development of mucositis is related to pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, Interferon-γ(IFN-γ). SCFP can significantly reduce IL-6 TNF-α, IL-1β, and IL-8, as well as the accumulation of T cells in the process of resisting apoptosis, reduce the inflammatory reaction and protect the dam?age to villi and crypts, improve the symptoms of small intestinal mucositis caused by weight loss and diarrhea. ② Pro?mote immunoglobulin A secretion: intestinal mucosal immunity is the first line of defense of the body's immune system. Its main antibody is secretory immunoglobulin A, which can destroy and phagocytize microorganisms, bacteria and viruses. SCFP can improve intestinal immunity by increasing the number and activity of T lymphocytes, promoting the secre?tion of secretory immunoglobulin A, and affecting the activity of a variety of cytokines. ③ Regulation of intestinal flora:the flora in the intestine has the functions of auxiliary nutrient absorption, biological antagonism and immune regulation, and can form a natural barrier for the host's intestine. When the human intestinal flora is disordered, probiotics will be greatly reduced, harmful bacteria will proliferate and destroy the intestinal environment. Under these conditions, the intake of SCFP significantly increased the number of beneficial bacteria such as bifidobacteria and lactobacillus, and sig?nificantly decreased the number of conditional pathogens such as enterococcus and escherichia coli, indicating that SCFP can indeed regulate the intestinal disorder caused by lincomycin hydrochloride to a certain extent. This may be because beneficial bacteria in the intestine metabolize polysaccharides produce short chain fatty acids such as lactic acid and acetic acid, which reduces the pH value in the intestine and inhibits the growth of enterococcus and Escherichia coli. In conclusion, SCFP can treat and protect intestinal diseases to a certain extent, which provides a favorable basis for the treatment of intestinal diseases.

Pharmacological effects of volatileoil from Alpinia officinaruim in treating cardiovascular diseases / 中国药理学与毒理学杂志

Galangal (Alpinia officinaruim Hance) is the rhizome of the perennial herb belonging to Zingiberaceae family. There are many active components in galangal, such as volatile oil, flavonoids, terpenoids, phenylpropanoids and glycosides, among which the content of volatile oil is higher. The bioactivities of galangal volatile oil on health effect includesanti-inflammatory, anti-hypertension, anti-oxidation and prevention of cardiovascular diseases. Cardiovascular disease (CVD) is a kind of diseases related to circulatory system, which is also called circulatory system diseases. Over the past decade, the number of people dying from CVD has increased by 12.5％ worldwide, and it is now the leading cause of human death worldwide. Studies have shown that galangal volatile oil has good pharmacological effects in treating CVD. ① Regulation of glucose and lipid metabolism: studies have found that abnormal lipid metabolism can lead to obesity, diabetes, CVD and other diseases. The serum total triglyceride (TG) content in liver and serum will increase in patients with abnormal fat metabolism. The results showed that the volatile oil of galangal could increase the excretion of neutral cholesterol, significantly reduce liver TG and serum TG, and thus regulate glucose and lipid metabo?lism, prevent lipid deposition and prevent CVD. ② Improving insulin resistance (IR): inhibition of inflammatory cytokines such as IL-1, IL-6 activation and expression of TNF-α, improves IR, thereby protecting myocardium from IR-mediated damage. Through the establishment of endothelial cell injury model induced by high glucose in vitro, it was found that the volatile oil of galangal can significantly reduce the secretion of pro-inflammatory cytokines TNF-αand IL-8, and inhib?it the expression of ICAM-1 and VCAM-1 induced by high glucose, suggesting that it has protective effect on endothelial dysfunction and inflammation induced by high glucose.③Regulate blood oxygenation:during acute myocardial hypoxia, the activity of free radical scavenging system is decreased, and oxygen free radicals are produced in large quantity, which reacts with unsaturated fatty acids on the cell membrane and forms lipid peroxidation, resulting in myocardial structural damage. The results showed that the water extract of Galangal could reduce the content of MDA in blood and protect the SOD activity of ischemic and hypoxic myocardium.④ Protective effect of vascular endothelial cells (ES):ES injury is the pathological basis of some cardiovascular diseases. The results showed that the volatile oil of galangal had a protective effect on ES apoptosis. Compared with the morphology and activity of ES treated with oxidized LDL, galan?gal volatile oil could ameliorate these morphological changes and improve cell viability. ⑤ Antiplatelet agglutination:inhibit platelet aggregation and thromboxane release, improve blood circulation, and have obvious anti-thrombotic effect, which has a good effect on the treatment and prevention of cardiovascular diseases. The results showed that the volatile oil of galangal had inhibitory effect on platelet aggregation and anticoagulant effect. In conclusion, the volatile oil of galangal can be used to prevent and treat cardiovascular diseases. Based on the mechanism of CVD, this study summa?rized the role of the essential oil of Alpinia officinaruim in CVD, providing basis for the clinical application of alpiniaoffici?nalis essential oil in the prevention and treatment of CVD and the development of new drugs.