Mangiferin Attenuates Prostatic Fibrosis in Benign Prostate Hyperplasia by Regulating miRNA-483-3p / 医药导报

Objective This study was to investigate the ameliorative effects of mangiferin on prostatic fibrosis in benign prostatic hyperplasia(BPH)and the mechanism of action of regulating microRNA(miRNA)-483-3p.Methods The male mice were randomly divided into five groups:normal control group,BPH model control group,finasteride group,mangiferin group,and mangiferin+miRNA-483-3p antagonist group.The mice model of BPH was induced by castration and subcutaneous injection of tes-tosterone propionate.After 30 days,the prostatic collagen deposition was observed by masson and sirius red stain,and the level of hydroxyproline was detected.Prostatic mRNA levels of transforming grouth factor-β1(TGF-β1),mitogen-activated protein kinase 2(MK2),and mitogen-activated protein kinase kinase 6(MKK6),as well as the level of miRNA-483-3p,were detected by quantita-tive real-time PCR.Prostatic protein levels of TGF-β1,MK2,phosphorylated MK2(p-MK2),MKK6,and p-MKK6 were detected by western blotting.Finally,the binding effect of miRNA-483-3p on MK2 was evaluated by luciferase assay.Results Compared to normal control group,the prostatic collagen deposition,mRNA levels of TGF-β1,MK2,and MKK6,as well as protein levels of TGF-β1,p-MK2,and p-MKK6 were significantly increased(P＜0.01),while the miRNA-483-3p level was significantly decreased in BPH model control group(P＜0.01).Compared with BPH model control group,the mangiferin group was able to up-regulate the level of miRNA-483-3p,reduce the mRNA levels of TGF-β1,MK2,and MKK6,as well as the protein levels of TGF-β1,p-MK2,and p-MKK6,and alleviate prostatic collagen deposition.When compared to the mangiferin group,mangiferin+miRNA-483-3p antagomir significantly decreased the miRNA-483-3p level,increased the prostatic collagen deposition,mRNA levels of TGF-β1,MK2,and MKK6,as well as protein levels of TGF-β1,p-MK2,and p-MKK6(P＜0.01).Luciferase assay showed that miRNA-483-3p could tar-get binding with MK2.Conclusion Mangiferin can attenuate prostatic fibrosis by regulating miRNA-483-3p and inhibiting MK2.

Mangiferin inhibits proliferation,migration and inflammatory factor expression of fibroblast-like synoviocytes in rheumatoid arthritis / 中国组织工程研究

BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.

A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications / 中西医结合学报

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.

Research on effect and mechanism of mangiferin on pancreatic cancer by regulating MMP9-mediated macrophage M2 polarization / 中国免疫学杂志

Objective:To investigate effect and mechanism of mangiferin on regulation of M2-type macrophage polarization tar-geting MMP9 in pancreatic cancer.Methods:In vivo,therapeutic effect of mangiferin on pancreatic cancer was evaluated by drawing tumor growth curves and immunohistochemical staining.M2-type macrophages expression in pancreatic cancer was detected by immu-nofluorescence and ELISA.Effects of mangiferin on expression of MMP9 and downstream M2 macrophage polarization-related signaling pathways were detected by immunofluorescence,ELISA,Western blot and qRT-PCR.In vitro,MTT assay was utilized to detect effect of mangiferin on M2-type macrophage and therapeutic effect of mangiferin on pancreatic cancer.ELISA was used to detect effect of mangiferin on M2-type polarized macrophages.Effects of mangiferin on expression of MMP9 and its downstream signalling pathway were detected by immunofluorescence and Western blot.Results:Mangiferin had potential to inhibit growth of pancreatic cancer in mice pancreatic model,and could prevent expression of M2-polarized macrophages in pancreatic cancer in addition.At the same time,mangiferin could inhibit expression of MMP9 and downstream M2 macrophage polarization related signaling pathways in pancreatic cancer.Mangiferin inhibited proliferation of pancreatic cancer cells in a M2 type polarized macrophage-pancreas cancer cell co-culture model,inhibited macrophage M2 polarization,at the same time,expression of MMP9 and downstream M2 macrophage polarization related signaling pathway was inhibited.Conclusion:Mangiferin can inhibit macrophage M2 polarization by inhibiting MMP9 and its downstream signaling pathway,and play a role in pancreatic cancer therapy.

Experimental Study on the Mechanism of Mangiferin Inhibiting Malignant Biological Characteristics of Multiple Myeloma and Exerting Anticancer Effect / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy.@*METHODS@#U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family.@*RESULTS@#Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05).@*CONCLUSION@#Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.

Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4 / 中国药房

OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）. METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl- 2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2- induced myocardial cells were investigated. RESULTS Compared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜ 0.05）. CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway / 中草药·英文版

OBJECTIVE@#Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs.@*METHODS@#MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis.@*RESULTS@#The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.@*CONCLUSION@#Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Effects of mangiferin on obesity complicated with type 2 diabetes in MKR mice / 中国药理学通报

Aim To investigate the mechanism of the effect of mangiferin on obesity complicated with type 2 diabetes mellitus in MKR transgenic mice. Methods MKR mice were randomly divided into model group,metformin group(0.11 g·kg-1),mangiferin low-dose group(25 mg·kg-1),mangiferin medium-dose group(50 mg·kg-1),and mangiferin high-dose group(100 mg·kg-1); FVB/N mice of the same age were used as control group. The mice were given intragastric administration for five weeks,the body weight and fasting glucose of mice were measured every week,the oral glucose tolerance(OGTT)was detected on 30th day of administration,and the insulin tolerance(ITT)was detected on 33rd day,and serum metabolic indexes were detected after administration. HE staining,oil-red O staining and Masson staining were used to observe the changes of liver morphology in mice. HE staining was used to observe the changes of fat morphology in mice. Western blot was used to detect the protein expression changes of TNF-α,IL-6,IL-1β in adipose tissues. Results High-dose mangiferin significantly reduced body weight,decreased fasting blood glucose,increased insulin content,and improved OGTT and ITT; it decreased serum triglyceride,alanine aminotransferase and aspartate aminotransferase levels; it also decreased the expression of serum IL-6 and TNF-α; it significantly reduced the expression of inflammatory factors in adipose tissues. Conclusions Mangiferin has therapeutic effects on obese MKR mice with type 2 diabetes,which is related to reducing the inflammatory response in adipose tissues.

Stability study and manufacture process optimization for Zhibai Anshen oral liquid / 药学实践杂志

Objective To optimize the manufacture process for Zhibai Anshen oral liquid. Methods The orthogonal designed experiments were conducted to monitor the effects of three factors on the content of mangiferin. The three factors included the amount of water, extraction time and alcohol precipitation concentration. Six month accelerated stability study and twelve month long term stability study were performed. Results Optimum percolation process was boiling the mixture with 10 times of water for 1 hour, followed by deposition with 60% alcohol. Conclusion This optimized process can be used for mass production.

Mangiferin attenuates IL / 中南大学学报(医学版)

OBJECTIVES@#Chondrocyte apoptosis is an important process in the pathogenesis of osteoarthritis. Mangiferin exerts multiple pharmacological effects such as anti-inflammatory and anti-apoptosis. However, the role of mangiferin in chondrocyte apoptosis is not clear. In this study, we aimed to explore the role of mangiferin in IL-1β-induced chondrocyte apoptosis.@*METHODS@#ATDC5 cells were randomly divided into a control group, a IL-1β group, a MFN-L group, a MFN-M group, a MFN-H group and a MFN+LY294002 group. Cells in the control group were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN-L group, the MFN-M group and the MFN-H group were pretreated with 5, 10 and 20 μmol/L mangiferin for 1 h respectively, and then they were treated with IL-1β (10 ng/mL) for 24 h; cells in the MFN+LY294002 group were treated with LY294002 (25 μmol/L) for 1 h, then mangiferin (20 μmol/L) and IL-1β (10 ng/mL) for 1 h and 24 h, respectively. Cell viability was detected by CCK-8 assay and cell apoptosis was measured by flow cytometry. Colorimetric assay was conducted to measure the caspase-3 activity. The protein levels of Bcl-2, Bax, and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway related proteins were detected by Western blotting.@*RESULTS@#Compared to the control group, cell viability was significantly decreased; cell apoptosis, caspase-3 activity and Bax protein expression were significantly increased; the protein levels of Bcl-2, p-PI3K, and p-Akt were significantly decreased in the IL-1β group (all @*CONCLUSIONS@#Mangiferin could attenuate IL-1β-induced apoptosis of the mice chondrocytes, which is mediated by the activation of PI3K/Akt signaling pathway.

Mangiferin inhibited neuroinflammation through regulating microglial polarization and suppressing NF-κB, NLRP3 pathway / 中国天然药物

Inflammation plays important roles in the progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Microglia is responsible for the homeostasis of the central nervous system (CNS), and involved in the neuroinflammation. Therefore, it could be potential in treatment of neurodegenerative diseases to suppress the microglia-mediated neuroinflammation. Mangiferin, a major glucoside of xanthone in Anemarrhena Rhizome, has anti-inflammatory, anti-diabetes, and anti-oxidative properties. However, the effect of mangiferin on the inflammatary responses of microglia cells are still poorly understand. In this study, we investigated the mechanism by which mangiferin inhibited inflammation in LPS-induced BV

Effects of Mangiferin on Glucose and Lipid Metabolism of Insulin-resistant HepG2 Cells / 中国药房

OBJECTIVE：To analyze the effects of mangiferin （MGF）on glucose and lipid metabolism in insulin resistance （IR）HepG2 cells，and to explore the potential mechanism. METHODS ：Using human hepatoma HepG 2 cells as research objects ， 1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG 2 cell model. Using metformin hydrochloride as positive control ，the effects of low-concentration ，medium-concentration and high-concentration MGF （125，250，500 μmol/L）on the corrected glucose consumption ，the contents of triglyceride （TG）and total cholesterol （TC）in IR-HepG 2 cells were detected. The mRNA expression of APN ，AdipoR2，APPL1，AMPK in the upstream of AMPK signaling pathway and IRS- 1，Akt and GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was detected by Western blot assay. RESULTS ：Compared with control group ，corrected glucose consumption ，mRNA expression of APN，AdipoR2，APPL1，AMPK，IRS-1 and GLUT 4，as well as the phosphorylation level of AMPK protein were decreased significantly in model group ，while the contents of TG and TC were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ， corrected glucose consumption ， mRNA expression of APN （except for MGF medium-concentration and high-concentration groups ），AdipoR2，APPL1，AMPK（except for MGF medium-concentration and high-concentration groups ）， IRS-1（except for MGF medium-concentration and high-concentration groups ），Akt（except for positive control group ），GLUT4 （except for MGF high-concentration group ）were increased significantly in administration groups ，while the contents of TG and TC were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Mangiferin may activate APN ，which is the upstream target of pathway ，and then regulate AMPK signaling pathway ，so as to promote glucose uptake of IR-HepG 2 cells，reduce TG and TC contents，and improve IR and abnormal glucose and lipid metabolism.

Effects of compatibility on pharmacokinetics of mangiferin in INS-1 cells and its intracellular distribution / 中国药理学通报

Aim To investigate the effect of compatibility of phellodendron amurense on the pharmacokinetics of mangiferin(MGF) in INS-1 cells, and the distribution of mangiferin in normal and oxidatively damaged INS-1 cells. Methods INS-1 cells were administered in equal doses of mangiferin, anemarrhena and anemarrhena-phellodendron herb pair. LC-MS/MS was used to determine the content of MGF in INS-1 cells. The normal and model groups (INS-1 cells were treated with 140 μmol · L

Mangiferin exerts neuroprotective activity against lead-induced toxicity and oxidative stress via Nrf2 pathway / 中草药·英文版

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.

Effect of mango (Mangifera indica) cv. azúcar juice consumption on plasma antioxidant capacity and oxidative stress biomarkers / Efecto del consumo del jugo de mango (Mangifera indica) variedad azúcar sobre la capacidad antioxidante del plasma y biomarcadores de estrés oxidativo

Background: Mango (Mangifera indica L.) is one of the world's most consumed fruit, and it is also a rich source of antioxidants that may prevent oxidative stress. Objectives: This study aimed to determine if mango (cv. Azúcar) juice can improve the antioxidant status of healthy individuals with low consumption of vegetables and fruit. Methods: This was a cross-over single-blind study carried out with 16 healthy individuals for 73 days. Participants were randomly assigned to either a mango juice period or a placebo period. Total phenolic content, antioxidant capacity, mangiferin, thiobarbituric acid reactive substances (TBARS), total glutathione, and 8 hydroxydeoxyguanosine levels were determined in plasma. Results: Plasma antioxidant activity was significantly higher in the juice consumption period than the placebo consumption period; however, total phenolic content, total glutathione, TBARS, and 8-hydroxydeoxyguanosine levels did not show significant differences between juice period and placebo period. Mangiferin was detected in every participant after juice consumption. Conclusions: Mango (cv. Azúcar) juice daily consumption improves plasma antioxidant capacity.

Antecedentes: El mango (Mangifera indica L.) es una de las frutas más consumidas en el mundo y también es una fuente rica en antioxidantes los cuales pueden prevenir el estrés oxidativo. Objetivos: El objetivo de este estudio fue determinar si el mango (c.v Azúcar) puede mejorar el estado antioxidante de individuos sanos con un bajo consumo de frutas y vegetales. Métodos: Se llevó a cabo un estudio cruzado, simple-ciego en 16 individuos sanos durante 73 días. Los participantes fueron asignados aleatoriamente al período del consumo del jugo o del placebo. Se determinó el contenido fenólico total, la capacidad antioxidante y los niveles de sustancias reactivas al ácido tiobarbiturico (TBARS), mangiferina, glutatión total y 8-hidroxi-guanosina, en el plasma obtenido de los participantes. Resultados: La capacidad antioxidante en plasma fue mayor en el período del consumo del jugo en comparación con el período del consumo del placebo; sin embargo, el contenido fenólico total, y los niveles de glutation total, 8-hidroxideoxiguanosina y TBARS no mostraron diferencias significativas entre el período del jugo y el período del placebo. La mangiferina se detectó en todos los individuos después del consumo del jugo. Conclusiones: El consumo diario de jugo de mango variedad Azúcar mejora la capacidad antioxidante en plasma.

El Sistema de Endocannabinoides como regulador de la lipogénesis y su posible modulación por la Mangiferina

RESUMEN Actualmente es innegable la participación del sistema endocannabinoides (SEC) en la regulación metabólica; ya que su sobre estimulación ha sido relacionada con varias patologías entre las que se encuentran obesidad, diabetes mellitus, retinopatía e hígado graso no alcohólico. Éstas se relacionan mutuamente a través de alteraciones del metabolismo de los lípidos, como lo es una sobre estimulación de la síntesis de ácidos grasos, una disminución en la beta-oxidación, hiperglicemia causada por un aumento de la gluconeogénesis, así como en la glucólisis; procesos en los cuales se ha descrito al SEC como un participante crucial. Por otro lado, algunos compuestos fitoquímicos, tales como la mangiferina (MGF), han probado sus efectos farmacológicos en el metabolismo de lípidos a nivel hepático y en el control glicémico. Hasta el momento se desconoce el efecto de la mangiferina sobre los receptores de endocannabinoides, por lo que esta revisión aborda la regulación a nivel sistémico (órganos y tejidos) y central (sistema nervioso) de la lipogénesis por el SEC y la regulación negativa que tiene la mangiferina sobre éste. Finalmente se sugiere, con base en la información publicada hasta el momento, una relación entre el posible efecto que pueden tener la MGF sobre el SEC.

ABSTRACT Currently, the participation of the endocannabinoid system in metabolic regulation is undeniable; because its hyperactivation has been related to several pathologies such as obesity, diabetes mellitus, retinopathy and non-alcoholic fatty liver, and others. These pathologies are related through alterations in lipid metabolism, e.g. over stimulation of fatty acid synthesis, beta-oxidation decrease, hyperglycemia increase, all these changes are caused by increase in gluconeogenesis, as well as glycolysis, processes in which the SEC has been described as a main character. On the other hand, some phytochemicals such as mangiferin (MGF) have shown their pharmacological effects on lipid metabolism, as well as glycemic control. So far, the effect of mangiferin on cannabinoid receptors is unknown. In this review, we try to demonstrate how mangiferin and these receptors participate in the opposite manner in the adaptation of lipid metabolism in many organs like as liver, tissue adipose and SN (nervous system). In addition, we suggest, based on the published information to until now, a relationship between the MGF´s effect on the SEC.

Pharmacokinetics of Three Kinds of Mangiferin Polymorphs in Rats / 医药导报

Objective To study the mangiferin absorption process of mangiferin polymorphs in SD rats thus to find out the optimal crystal form and explore the factors that may affect the clinical effects of mangiferin. Methods Each rat was given one of three crystal forms of mangiferin. Plasma concentration of mangiferin were determined by HPLC-MS method. After liquidliquid extraction by ethyl acetate, the chromatographic separation was carried out on an Agilent ZORBAX SB-C18 (2.1 mm× 100 mm,3.5 μm) with a mobile phase consisting of methanol-0.1％ formic acid aqueous solution (30:70) . Mass spectrometry were performed in positive ion mode. Ion mass-to-charge ratio was set at 445 and 447 for mangiferin and, cefuroxime sodium (internal standard) respectivel for quantitive analysis. Results The main pharmacokinetic parameters of mangiferin form II, Ⅴ, Ⅵ were as follows: AUC(0-24 h) were (1323. 27 ± 218. 07) ,(1974. 34 ± 469. 24) ,(1737. 79 ± 623. 06) ng · mL-1 · h, respectively; Cmax were (321.92±85.18) ,(455.83±277.07) ,(319.92±86.07) μg·L-1, respectively; tmax were (0.70±0.45) , (0.50±0.32) ,(0.50± 0.34) h, respectively; t1/2z were (2.78± 1.72) ,(5.29± 2.67) ,(5.31± 2.82) h, respectively. Conclusion The main pharmacokinetic parameters of mangiferin polymorphs in plasma of rats are different, and mangiferin form Ⅴ has the hightest AUC(0-24 h) and Cmax.

Interventional effect of mangiferin on carbon tetrachloride-induced hepatic fibrosis in mice / 临床肝胆病杂志

ObjectiveTo investigate the interventional effect of mangiferin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice and the potential mechanism. MethodsA total of 45 male C57BL/6 mice were randomly divided into three groups: normal control group (NC group), liver fibrosis model group (CCl4 group), and mangiferin pretreatment group (CCl4+M group), with 15 mice in each group. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); HE staining and Masson staining were performed to observe liver pathological changes; ELISA was used to measure the serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα); Western Blot was used to measure the protein expression of α-smooth muscle actin (α-SMA), nuclear factor-kappa B (NF-κB), IL-1β, p62, and microtubule-associated protein 1 light chain 3 (LC3) in the liver; quantitative real-time PCR was used to measure the mRNA expression of type I collagen (Col-I) and α-SMA in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsHE staining and Masson staining showed a low proportion of mice with hepatocyte degeneration and necrosis and a significant reduction in collagen fibers in the CCl4+M group. Compared with the CCl4 group, the CCl4+M group had significant reductions in the serum levels of ALT and AST (both P＜001). ELISA showed that compared with the CCl4 group, the CCl4+M group had significant reductions in the serum levels of IL-1β, IL-6, and TNF-α (all P＜0.01). Western Blot showed that compared with the CCl4 group, the CCl4+M group had significant reductions in the protein expression of α-SMA, NF-κB, IL-1β, and LC3-II/I in the liver (P＜0.01, P＜0.05, P＜0.01, and P＜0.05) and a significant increase in the protein expression of p62 (P＜0.05). Quantitative real-time PCR showed that compared with the CCl4 group, the CCl4+M group had significant reductions in the mRNA expression of Col-I and α-SMA (P＜0.05 and P＜0.01). ConclusionMangiferin can alleviate CCl4-induced hepatic fibrosis in mice, possibly by reducing inflammation to protect liver function and inhibiting autophagy to reduce the activation of hepatic stellate cells.

Effects of association state on decocting rate of mangiferin in Pingfei Decoction by using low-field and high-field NMR / 中草药

Objective: To study the effects of association complexes on extraction and separation behavior of mangiferin in Pingfei Decoction by low-field and high-field NMR. Methods Using the T2 relaxation time and chemical shifts value of hydrogen as index, and group DNJ-citric acid as control, the relaxation characteristrics of hydrogen in association state was analyzed by low field NMR to verify the structure of association complexes combined with high-field NMR. Results DNJ and mangiferin existed in the form of association state with larger molecular weight, which inhibited the migration of components from medicinal materials to solution and caused lower transmittance. And the T2 peak shifted to the left in the spectrum, and the chemical shift in the high field nuclear magnetic field also changed. Conclusion This experiment clarified the mechanism of the effect of presence of components on extraction and separation behavior of mangiferin and provided technical support for studying the decocting method and mechanism of Chinese herbal compound.