[Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder].

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

[Research progress of Curcuma kwangsiensis root tubers and analysis of liver protection and anti-tumor mechanisms based on Q-markers].

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and ß-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.

Analysis on oral medication rules of traditional Chinese medicine prescriptions for prevention of COVID-19.

OBJECTIVE: To analyze the medication rules of traditional Chinese medicine (TCM) preventive oral prescriptions for COVID-19. METHODS: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. RESULTS: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials, Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic TCMs. CONCLUSION: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of "Preventive Treatment of Disease" was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application.

Analysis on application law of dampness-removing traditional Chinese medicines in treatment of coronavirus disease 2019.

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) has been diagnosed as an epidemic disease characterized by cold and dampness pathogens in TCM clinic. Due to many Chinese medicines with different functions were used in the treatment of COVID-19, it is very important to find the law of application of damp-removing traditional Chinese medicine with high frequency application, with view to providing a reference for the use and research of Chinese medicine to further control the pandemic. METHODS: The publicly released diagnosis and treatment programs issued by the National Health Commission and Health Commission of provinces, autonomous regions and municipalities, and Chinese herbs prescription information in these were collected, a database was established, and Excel and Graphpad 8.0 software were used to analyze the frequency of use of various Chinese medicines, the frequency and property characters including five flavors (bitter, pungent, sweet, sour, and salty) and four natures (warm, hot, cool, and cold) and channel tropisms of Chinese medicine for removing dampness. RESULTS: A total of 137 prescriptions of Chinese medicine for treating COVID-19 were collected, including 178 TCMs showing functions of resolving phlegm, relieving cough and asthma, resolving dampness, clearing damp and inducing dieresis, clearing heat, tonifying deficiency, and relieving exterior syndrome, in which the TCMs with the first four functions that we called the dampness-removing TCMs, accounted for 35.78%. Also a number of TCMs in the rest functions showed removing-dampness. The first four functions were divided into subfunctions including aromatic resolving dampness, clearing heat and drying dampness, drying dampness and tonifying spleen qi, drying dampness and removing phlegm, inducing diuresis and relieving swelling, inducing diuresis and relieving exterior syndrome. Among them, the most frequently used TCMs was Ephedrae Herba, followed by Citri Reticulatae Pericarpium, Pogostemonis Herba, Pinelliae Rhizoma, Poria, Scutellariae Radix, and Atractylodis Rhizoma. The property character analysis in the dampness-removing TCMs showed that bitter and pungent were largely present and sour and astringent were absent, warm and hot were dominant; And the lung, spleen, stomach, large intestine, bladder were main channel tropisms. CONCLUSION: Dampness-removing TCMs are the first important type of traditional Chinese medicine to be considered in the treatment of COVID-19 in Chinese medicine. The application of dampness-removing TCMs in the treatment of COVID-19 needs to be combined with its application law. This study may provide meaningful and useful information on further research to investigate the effective compounds from the dampness-removing Chinese medicine with high frequency application, and also provide a reference for the clinical treatment of COVID-19 accurately against dampness evil with dampness-removing traditional Chinese medicines.

Sub-lethal Camphor Exposure Triggers Oxidative Stress, Cardiotoxicity, and Cardiac Physiology Alterations in Zebrafish Embryos.

Camphor is a terpene ketone with aromatic and volatile properties in nature derived from the bark of Cinnamomum camphora or synthesized from turpentine. Camphor exhibits various biological properties such as anti-microbial, anti-viral, anti-coccidial, and anti-cancer. It is also used as a form of topical medication for skin irritation, joint pain, and as a relief for itching from insect bites. However, even though the high dose of camphor has been documented to be toxic/lethal in humans in different studies, camphor's developmental toxicity has not yet been explored, and its extensive mechanism of action is still unclear. In the present study, we aimed to assess the toxic effects of camphor in zebrafish embryos in the initial developmental stages. The obtained results demonstrated that a sub-lethal dose of camphor caused a decrease in hatching rate, body length, and substantial elevation in malformation rate on zebrafish embryos. On further observation, in the following time frame, curved body and pericardial edema of zebrafish were also observed. Furthermore, exposure to a sub-lethal dose of camphor was also able to trigger cardiotoxicity in zebrafish larvae. Later, on subsequent biochemical analysis, it was found that the antioxidant capacity inhibition and oxidative stress elevation that occurred after camphor exposure might be associated with the inhibition of total superoxide dismutase (SOD) activity and an increase in reactive oxygen species (ROS) and malondialdehyde (MDA) concentration. In addition, compared to the control group, several apoptotic cells in treated zebrafish were also found to be elevated. Finally, after further investigation on marker gene expressions, we conclude that the developmental toxicity of camphor exposure might be associated with apoptosis elevation and oxidative stress. Taken together, the current study provides a better understanding of the developmental toxicity of camphor on zebrafish, a promising alternative animal model to assess the developmental toxicity of chemical compounds.

Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish.

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti-ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE-induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose-dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

Chemical constituents and pharmacological effects of durian shells in ASEAN countries: A review.

Durio zibethnus is mainly distributed in Southeast Asia. Traditional Chinese medicine believes that durian shells have the effects of clearing heat and purging fire, nourishing yin and moisturizing dryness. Therefore, it is often used as a pharmaceutic food in the Chinese folk to assist treating diseases. At present, the chemical constituents isolated from durian shell include phenolic acids, phenolic glycosides, flavonoids, coumarins, triterpenes, simple glycosides and other compounds. Modern pharmacological studies show that durian shell has many pharmacological activities, such as antioxidant, anti-inflammatory, regulation of glucose and lipid metabolism. The chemical composition and pharmacological effects of durian shells are summarized in order to provide references for the further research and application of durian shell.

Genipin induces developmental toxicity through oxidative stress and apoptosis in zebrafish.

Genipin, an iridoid substance, is mainly derived from Gardenia jasminoides Ellis of the traditional Chinese medicine and is widely used in raw materials for the food additive gardenia blue and biological materials. The developmental toxicity of genipin has not been investigated, and its underlying mechanism is unclear. Therefore, in this study we attempt to investigate the potential developmental toxicity of genipin in zebrafish embryos/larvae. The results showed zebrafish embryos treated with 50 µg/ml dose of genipin display inhibited hatching rates and body length. The pericardial edema was observed. It was also found that genipin could induce cardio-toxicity, hepatotoxicity and nephrotoxicity in zebrafish larvae. After genipin treatment, the suppression of antioxidant capacity and increase of oxidative stress were showed for the triggered generation of ROS and MDA, and decreased activity of SOD. Compared with the 0.5% DMSO group, a number of apoptotic cells in zebrafish were increased after genipin exposure. By measuring marker gene expression with the using of qRT-PCR, we proposed that developmental toxicity after genipin treatment might be associated with oxidative stress and apoptosis increase. Our research offers a better understanding for developmental toxicity of genipin.

Chemical constituents from Jasminum pentaneurum Hand.-Mazz and their cytotoxicity against human cancer cell lines.

Chemical investigation of Jasminum pentaneurum Hand.-Mazz led to the isolation and identification of 12 compounds, which included one new secoiridoid glycoside, 10-(3-hydroxy-4-methoxy-benzoate)-ligustroside (4), three secoiridoid glycosides (1-3), and eight phenols (5-12). All compounds were reported for the first time from this plant. Their structures were elucidated based on extensive spectroscopic data analysis, including HR-ESI-MS, UV, IR, 1 D, and 2 D NMR. The absolute configuration of the new one (4) was further elucidated by comparison of its experimental and calculated quantum chemical electronic circular dichroism (ECD) spectra. All the isolates were assayed for their inhibitory activity on four human cancer cells. Compound 11 exhibited inhibitory effects against three human cancer cells SK-MES-1, SMMC-7721 and SGC-7901 with IC50 values ranging from 83.0 to 172.0 µM.

[Traditional medicinal plants for arthropod-borne diseases of five countries in Lancang-Mekong region:a review].

Arthropod-borne diseases, such as malaria and dengue fever, have frequently beset five countries(Cambodia, Vietnam, Laos, Myanmar, and Thailand) in the tropical rainy Lancang-Mekong region, which pose a huge threat to social production and daily life. As a resort to such diseases, chemical drugs risk the resistance in plasmodium, non-availability for dengue virus, and pollution to the environment. Traditional medicinal plants have the multi-component, multi-target, and multi-pathway characteristics, which are of great potential in drug development. Exploring potential medicinals for arthropod-borne diseases from traditional medicinal plants has become a hot spot. This study summarized the epidemiological background of arthropod-borne diseases in the Lancang-Mekong region and screened effective herbs from the 350 medicinal plants recorded in CHINA-ASEAN Traditional Medicine. Based on CNKI, VIP, and PubMed, the plants for malaria and dengue fever and those for killing and repelling mosquitoes were respectively sorted out. Their pharmacological effects and mechanisms were reviewed and the material basis was analyzed. The result is expected to serve as a reference for efficient utilization of medicinal resources, development of effective and safe drugs for malaria and dengue fever, and the further cooperation between China and the other five countries in the Lancang-Mekong region.

Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study.

CONTEXT: Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. OBJECTIVE: This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. MATERIALS AND METHODS: The VD model was established by the ligation of the bilateral common carotid artery in Sprague-Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. RESULTS: Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p < 0.05). It also decreased malondialdehyde (MDA) (27.53%) and nitric oxide (NO) (20.41%) while increasing superoxide dismutase (SOD) (11.26%) and glutathione peroxidase (GSH-Px) (20.38%) content in hippocampus tissues. Proteomic analysis revealed 45 differentially expressed proteins (DEPs) in marinoid J-treated VD rats, which included angiotensin-converting enzyme (ACE), keratin 18 (KRT18), cluster of differentiation 34 (CD34), and synaptotagmin II (SYT2). CONCLUSIONS: Marinoid J played a role in protecting hippocampal neurons by regulating a set of proteins that influence oxidative stress and apoptosis, this effect may thereby alleviate the symptoms of VD rats. Thus, pharmacological manipulation of marinoid J may offer a novel opportunity for VD treatment.

Carry forward advantages of traditional medicines in prevention and control of outbreak of COVID-19 pandemic.

Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper mainly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10 + 3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation.

Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway.

Objective: The study was designed to assess the beneficial role of mangiferin (MGN) in lead (Pb)-induced neurological damages in the activation of Nrf2-governed enzymes, genes and proteins. Methods: A total of 96 weaned Wistar rats (48 males and 48 females, 26- to 27-day-old), weighing 50-80 g were used. The experiment was performed in six groups: normal group (control, n = 16), model group (chronic Pb exposed, n = 16), Dimercaptosuccinic acid (DMSA)-treated group (positive control, Pb + DMSA, n = 16), three MGN-treated groups with different doses (Pb + MGN, n = 48). Normal group freely had access to purified water. DMSA-treated group was given DMSA, which was clinically used as the standard treatment for moderate Pb poisoning, at 50 mg/kg (2 mL suspension with purified water) by intragastric gavage (ig) 4 continual days a week for 4 weeks, MGN-treated groups were given MGN at 50, 100, or 200 mg/kg (2 mL suspension with purified water) by ig daily for 4 weeks. At the end of the treatment, all rats were sacrificed and the brain samples were collected. The haematoxylin and eosin (H&E) staining was used for observation of histopathology. Commercial kit, real-time quantitative polymerase chain reaction (RT-qPCR), Western-blot and immunohistochemistry (IHC) detection were used to detect the mRNA and protein expression. Results: Eight weeks exposure to Pb-containing water resulted in pathological alterations, anti-oxidative system disorder in the brain, all of which were blocked by MGN in a Nrf2-dependent manner. Nrf2 downstream enzymes such as HO-1, NQO1, γ-GCS were activated. Nrf2, GCLC, GCLM, HO-1 mRNA and total Nrf2, Nuclear Nrf2, γ-GCS, HO-1 protein expression were affected too. Conclusion: MGN ameliorated morphological damage in the hippocampus. Its neuroprotective effects were achieved by the activation of the Nrf2 downstream genes. The data from this in vitro study indicates that MGN targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with Pb exposure. Thus, MGN could be an effective candidate agent for the Pb-induced oxidative stress and neurotoxicity in the human body.

Four New Cyclohexylideneacetonitrile Derivatives from the Hypocotyl of Mangrove (Bruguiera gymnorrhiza).

Four new cyclohexylideneacetonitrile derivatives 1-4, named menisdaurins B-E, as well as three known cyclohexylideneacetonitrile derivatives--menisdaurin (5), coclauril (6), and menisdaurilide (7)--were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures of the isolates were elucidated on the basis of extensive spectroscopic analysis. Compounds 1-7 showed anti-Hepatitis B virus (HBV) activities, with EC50 values ranging from 5.1 ± 0.2 µg/mL to 87.7 ± 5.8 µg/mL.

[Mangiferin protects rats against chronic bronchitis via regulating NF-kappaB (P65) and IkappaBalpha expression in mononuclear cells].

This study is to investigate the protective effect of mangiferin on NF-kappaB (P65) and IkappaBalpha expression in peripheral blood mononuclear cell (PBMC) in rats with cigarette smoke induced chronic bronchitis. The rat model with chronic bronchitis was established by cigarette smoke. Real-time fluorescence RT-PCR was executed for evaluating the NF-kappaB (P65) and IKkappaBalpha gene expression in mononuclear cell, and flow cytometry for their protein expression. The serum hs-CRP (high-sensitivity C-reactive proteins) and TNF-alpha (tumor necrosis factor-alpha) were detected by enzyme-linked immunosorbent assay. The histopathological score was obtained from lung tissue HE staining slides of lung tissue. The results showed that mangiferin could markedly suppress the NF-kappaB (P65) mRNA and protein expression in mononuclear cell, while promote the IkappaBalpha mRNA and protein expression. Furthermore, mangiferin could lower serum hs-CRP and TNF-alpha level, and reduce the chronic inflammatory damage of bronchiole. These results suggested that mangiferin could notably ameliorate chronic bronchiole inflammation induced by cigarette smoke, and this protective effect might be linked to the regulation of NF-kappaB (P65) and IkappaBalpha expression in mononuclear cell.

Mangiferin attenuates TH1/TH2 cytokine imbalance in an ovalbumin-induced asthmatic mouse model.

Mangiferin is a major bioactive ingredient in Mangifera indica Linn. (Anacardiaceae) leaves. Aqueous extract of such leaves have been used as an indigenous remedy for respiratory diseases like asthma and coughing in traditional Chinese medicine. However, underlying molecular mechanisms of mangiferin on anti-asthma remain unclear. In our present study, we investigated the anti-asthmatic effect of mangiferin on Th1/Th2 cytokine profiles and explored its underlying immunoregulatory mechanism in mouse model of allergic asthma. Mangiferin significantly reduced the total inflammatory cell counts and eosinophil infiltration, decreased the production of ovalbumin-specific IgE in serum and PGD2 in BALF. The antibody array analysis showed that mangiferin down-regulated the levels of one group of cytokines/chemokines including Th2-related IL-4, IL-5, IL-13, and others IL-3, IL-9, IL-17, RANTES, TNF-α, but simultaneously up-regulated Th1-related IFN-γ, IL-2 and IL-10 and IL-12 expression in serum. Thus it attenuates the imbalance of Th1/Th2 cells ratio by diminishing the abnormal mRNA levels of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4, IL-5 and IL-13). Finally, mangiferin substantially inhibited the activation and expression of STAT-6 and GATA-3 in excised lung tissues. Our results suggest that mangiferin can exert anti-asthmatic effect. The underlying mechanism may attribute to the modulation of Th1/Th2 cytokine imbalance via inhibiting the STAT6 signaling pathway.

[Study on the regulation role of semen persicae to cAMP-PKA signal pathway in the rats with cold and heat blood stasis syndrome].

OBJECTIVE: To study the regulation role of with neutral property to cAMP-PKA pathway in the rats with cold and heat blood stasis syndromes and it's mechanism. METHODS: 60 rats were randomly divided into normal control group, model control group, Semen Persicae group, radix salvia miltiorrhiza group, rhizoma chuanxiong group, 12 rats per group. The three herb groups were orally given relative herbs decoction, whose dosages were equal to 10 times the human clinical dose, normal and model control groups were orally given water, 2 times/day, 20 mL/kg, for 7 days. Experiments in rats with cold and heat blood stasis syndromes were carried on respectiverly. In heat blood stasis syndromes, except normal control group, the other groups were intraperitoneally injected 10% carrageenan, 5 mL/kg, 1 times/day, for 3 days;24 hours after the last injection, subcutaneously injected 20% dry yeast suspension, 10 mL/kg. In cold blood stasis syndromes, except normal control group, the other groups were put into fridge, temperature--(18 +/- 2) degrees C, 2 hours/ times, 2 times/day, for 7 days. Separately draw 5 ml abdominal aortic blood and taken abdominal aorta, 6 hours and 12 hours after finishing the model in the two syndromes. Tested the cAMP content by elisa, tested the PKA protein expression by Western blot. RESULTS: Semen Persicae with neutral property, could decrease the content of cAMP in plasma (P < 0.01), inhibit the expression of protein PKA (P < 0.05) in rats with heat stagnation and blood stasis syndrome, increase the plasma content of cAMP (P < 0.01) and increase the expression of protein PKA (P < 0.01) in rats with cold stagnation and blood stasis syndrome. Semen Persicae had two-way adjustment action on CAMP-PKA signal pathway. CONCLUSION: In different internal environment of heat stagnation and blood stasis syndrome, cold stagnation and blood stasis syndrome, Semen Persicae with neutral property has two-way adjustment to cAMP-PKA signaling channel, which may be one of the mechanism of it's two-way application.

Synthesis and hypoglycemic activity of esterified-derivatives of mangiferin.

AIM: To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. METHODS: Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. RESULTS: 7, 2', 3', 4', 6'-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2', 3', 4', 6'-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2', 3', 4'-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS,(1)H, (13)C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg(-1)), HPM group (0.5, 0.25 mmol·kg(-1)), and HBM group (0.5, 0.25, 0.125 mmol·kg(-1)) mice showed strong hypoglycemic activity (P < 0.01); mangiferin group (1, 0.5 mmol·kg(-1)), PAM group (0.125 mmol·kg(-1)) and HPM group (0.125 mmol·kg(-1)) showed marginal hypoglycemic activity (P < 0.05); mangiferin group (0.25 mmol·kg(-1)) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. CONCLUSION: Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.

Synthesis and anti-tumor activity evaluation of gallic acid-mangiferin hybrid molecule.

To improve the anti-tumor effects of gallic acid and mangiferin, a gallic acid-mangiferin hybrid molecule (GAMA) was synthesized from gallic acid with mangiferin in the presence of ionic liquid ChC1(choline chloride)·2SnC12. Chemical and spectroscopic methods, such as (1)H and (13)C NMR spectroscopy, and HR-ESIMS were used for the structure identification of GA-MA. Using the cell counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared between GA-MA, gallic acid and mangiferin on human hepatoma HepG2, human nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK-OV-3, and human cervical cancer Hela cells. The results showed that the half inhibitory concentration (IC50) of GA-MA on HepG2, CNE, NCI-H460, SK-OV-3, and Hela cells was significantly lower than that of gallic acid or mangiferin. This showed that GA-MA has a better in vitro anti-tumor effect than gallic acid and mangi-ferin.