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Mangiferin is a bioactive substance present in high concentration in mangoes and also in some other fruits. Owing to its potential as a chemopreventive and chemotherapeutic agent against several types of cancer, this unique, significant, and well‐researched polyphenol has received a lot of attention recently. It possesses the ability to treat cancers, including rectal cancer, prostate cancer, ovarian cancer, leukemia, gastric cancer, liver cancer, chronic pancreatitis, and lung cancer. It can control/regulate multiple key signaling pathways, such as signal transducer and activator of transcription 3 (STAT3), second mitochondria‐derived activator of caspases/direct inhibitor of apoptosis (IAP)‐binding protein with low propidium iodide (pl) (Smac/DIABLO) nuclear factor kappa B (NF‐κB), phosphatidylinositol 3 kinase/protein 3 kinase (PI3K/Akt), transforming growth factor beta/suppressor of mothers against decapentaplegic (TGF‐β/SMAD), c‐jun N‐terminal kinase/p38 mitogen‐activated protein kinase (JNK/p38‐MAPK), and phosphor‐I kappa B kinase (p‐IκB), which are crucial to the development of cancers. By triggering apoptotic signals and halting the advancement of the cell cycle, it can also prevent some cancer cell types from proliferating and developing. It has been revealed that mangiferin targets a variety of adhesion molecules, cytokines, pro‐inflammatory transcription factors, kinases, chemokines, growth factors, and cell‐cycle proteins. By means of preventing the onset, advancement, and metastasis of cancer, these targets may mediate the chemopreventive and therapeutic effects of mangiferin. Mangiferin has confirmed potential benefits in lung, cervical, breast, brain, and prostate cancers as well as leukemia whether administered alone or in combination with recognized anticancer compounds. More clinical trials and research investigations are required to completely unleash the potential of mangiferin, which may lower the risk of cancer onset and act as a preventive and therapeutic alternative for a number of cancers. [ABSTRACT FROM AUTHOR]

Mangifera indica peels are a rich source of diverse flavonoids and xanthonoids; however, generally these are discarded. Computational studies revealed that mangiferin significantly interacts with amino acid residues of transcriptional regulators 1IK3, 3TOP, and 4f5S. The methanolic extract of Langra variety of mangoes contained the least phenol concentrations (22.6 ± 0.32 mg/gGAE [gallic acid equivalent]) compared to the chloroform (214.8 ± 0.12 mg/gGAE) and ethyl acetate fractions (195.6 ± 0.14 mg/gGAE). Similarly, the methanolic extract of Sindhri variety contained lower phenol concentrations (42.3 ± 0.13 mg/gRUE [relative utilization efficiency]) compared with the chloroform (85.6 ± 0.15 mg/gGAE) and ethyl acetate (76.1 ± 0.32 mg/gGAE) fractions. Langra extract exhibited significant α‐glucosidase inhibition (IC50 0.06 mg/mL), whereas the ethyl acetate fraction was highly active (IC50 0.12 mg/mL) in Sindhri variety. Mangiferin exhibited significant inhibition (IC50 0.026 mg/mL). A moderate inhibition of 15‐LOX was observed in all samples, whereas mangiferin was least active. In advanced glycation end product inhibition assay, the chloroform fraction of Langra variety exhibited significant inhibition in nonoxidative (IC50 64.4 μg/mL) and oxidative modes (IC50 54.7 μg/mL). It was concluded that both Langra and Sindhri peel extracts and fractions possess significant antidiabetic activities. The results suggest the potential use of peel waste in the management and complications of diabetes. [ABSTRACT FROM AUTHOR]

AbstractThe aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose in high-fat diet (HFD)-fed mice. MG treatment inhibited beta-cell apoptosis in HFD-treated mice. In vitro, MG protected INS-1 cells against apoptosis and impairment of insulin secretion following High glucose/Palmitic acid (HG/PA) treatment. MG treatment enhanced autophagy flux which was blocked by HG/PA treatment. Inhibition of autophagosome formation by 3-Methyladenine or blockade of autolysosome by Chloroquine reversed the protective effects of MG on INS-1 cells. MG treatment increased AMPK phosphorylation and reduced mTOR activation in INS-1 cells. Administration of the AMPK blocker abrogated MG-induced autophagy, and similar results were observed in INS-1 cells after cotreatment with MG and mTOR activator. In conclusion, MG ameliorated pancreatic beta-cell injury induced by glucolipotoxicity through modulation of autophagy via the AMPK-mTOR pathway. [ABSTRACT FROM AUTHOR]

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Background and Objectives: Hyperglycemia is known to undermine the osteointegration process of implants. In this study, the effects of mangiferin (MF) on the post-implant osteointegration process in a type-II diabetes model were investigated molecularly and morphologically. Materials and Methods: Sprague Dawley male rats were divided into three groups: control, diabetes, and diabetes + MF. All animals were implanted in their tibia bones on day 0. At the end of the 3-month experimental period, the animals' blood and the implant area were isolated. Biochemical measurements were performed on blood samples and micro-CT, qRT-PCR, histological, and immunohistochemical measurements were performed on tibia samples. Results: MF significantly improved the increased glucose, triglyceride-VLDL levels, and liver enzymes due to diabetes. By administering MF to diabetic rats, the osteointegration percentage and bone volume increased while porosity decreased. DKK1 and BMP-2 mRNA expressions and OPN, OCN, and OSN mRNA–protein expressions increased by MF administration in diabetic rats. Additionally, while osteoblast and osteoid surface areas increased with MF, osteoclast and eroded surface areas decreased. Conclusions: The findings of our study indicate that MF will be beneficial to the bone-repairing process and osteointegration, which are impaired by type-II diabetes. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is typified by inflammation of dopaminergic neurons leading to the release of various inflammatory mediators. These mediators activate the transcription factor NF-κB, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation. Purpose: This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-κB with low-dose nitric oxide (NO) modulators. Methods: A total of eight Wistar rats weighing 200–250 g were used in each group. Stereotactic surgery was performed to induce 6-hydroxydopamine (6-OHDA) lesions. The treatment period extended from day 14 to day 42, during which time behavioral tests were performed to evaluate the effects of mangiferin and its combination with NO modulators. On day 42, the brains of the rats were removed for biochemical and molecular analyzes. Results: Mangiferin significantly improved locomotor activity and decreased inflammatory chemokines levels in rats with 6-OHDA lesions. Mangiferin therapy decreased myeloperoxidase (MPO) levels and reduced oxidative stress. In particular, caspase-3, caspase-9 and COX-2 activities were significantly reduced after the mangiferin treatment. A combination of 45-µg mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA. Conclusion: In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-α and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-µg mangiferin enhanced the anti-inflammatory and anti-Parkinsonian activity of mangiferin. Consequently, the combination therapy of mangiferin and L-NAME is promising for the treatment of PD. However, clinical trials will be required to evaluate the efficacy of this combination therapy in humans. [ABSTRACT FROM AUTHOR]

Mangiferin is a naturally occurring glucosylxanthone that has shown promising immunomodulatory effects. It is generally isolated from the leaves, peels, bark, and kernels of Mangifera indica Linn. Mangiferin is like a miraculous natural bioactive molecule that has an immunomodulatory function that makes it a potential therapeutic candidate for the treatment of rheumatoid arthritis (RA) and cancer. The anticancer activity of mangiferin acts by blocking NF‐κB, as well as regulating the β‐catenin, EMT, MMP9, MMP2, LDH, ROS, and NO, and also by the activation of macrophages. It has no cytotoxic effect on grown chondrocytes and lowers matrix metalloproteinase levels. Additionally, it has a potent proapoptotic impact on synoviocytes. The precise molecular mechanism of action of mangiferin on RA and malignancies is still unknown. This comprehensive review elaborates on the immunomodulatory effect of mangiferin and its anticancer and anti‐RA activity. This also explained the total synthesis of mangiferin and its in vitro and in vivo screening models. [ABSTRACT FROM AUTHOR]

Chuihao Kong,1,2,* Kaidi Wang,1,2,* Lei Sun,1,3 Hongsu Zhao,1,2 Tongsheng Wang,1 Wuxi Zhou,1 Deling Wu,1,2 Fengqing Xu1,2 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China; 3Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wuxi Zhou; Fengqing Xu, School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan District, Hefei, 230012, People’s Republic of China, Email zhouwuxi@ahtcm.edu.cn; xufengqing@ahtcm.edu.cnBackground: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics.Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo.Results: The results indicated that MC-CDs with a uniform spherical particle size of 1– 5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg.Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs. Keywords: Moutan Cortex, carbon dots, mangiferin, solubility, bioavailability

AbstractInhibition of lipid synthesis in sebocytes is essential for acne treatments. The effects of natural product-derived substances on lipid synthesis are unknown. This study investigated the effects of water extract of Mangifera indica leaves (WEML) on lipid synthesis in human sebocytes. Sebocyte differentiation in low serum conditions increased lipid accumulation and proliferator-activated receptor γ expression. WEML treatment significantly inhibited lipid accumulation and adipogenic mRNA expression in sebocytes. Mangiferin, a bioactive compound in WEML, also reduced lipid accumulation and adipogenic mRNA expression via the AKT pathway. Thus, WEML and mangiferin effectively inhibit lipid synthesis in sebocytes, showing promise for acne treatment. [ABSTRACT FROM AUTHOR]

To enhance Mangiferin (MNG) the brain bioavailability by developed novel polysorbate-80 (P 80) MNG PLGA NPs and examined the quantity of MNG through developed a novel method of LC–MS/MS in the ischemic rat brain treatment. The solvent evaporation method used to develop a novel MNG loaded PLGA NPs followed by their coating from polysorbate-80. Polysorbate-80 (P 80) MNG PLGA NPs developed based on EE, particle size, Zeta Potential, PDI, and loading capacity with their characterization followed by drug release and intranasal permeation to enhance the brain bioavailability and also determined their neurobehavioral as well as biochemical evaluation with the histopathological examination. P 80 MNG PLGA NPs were optimized with their particle size 103.4 ± 2.66 nm, PDI: 0.201 ± 0.008, Zeta Potential (−35.8 ± 2.48), and drug loading 37.16 ± 2.09% with 76.08 ± 4.91% entrapment efficiency showed a sustained and controlled release (83.43 ± 6.47%) with great permeation (> 83%) of MNG. MNG & IS showed retention time (0.756 and 1.258 min) and their m/z (421.20/301.20 and 237.2/179.2), respectively. MNG showed a good linearity range, i.e., 10.0–1000.0 ng mL−1; the results of inter-and-intraday accuracy and CV were found to be (93.01–99.43%) and (2.27–4.02%), respectively. An excellent significant results was showed, i.e., p < 0.001 for (AUC)0–24 & Cmax via i.n. dose delivered. A highly significantly results of P 80 MNG PLGA NPs (i.n.) were found based on the examination of biochemical, neurobehavioral, and histopathological in the developed ischemic MCAO brain rat's model. An excellent significant role of P 80 MNG PLGA NPs for MNG were proved based on enhancement of brain bioavailability of MNG via i.n. delivery of the rats and targeted easily to the brain in the treatment of cerebral ischemia followed by improvement of neuroprotection based on use of a very small dose of MNG. [ABSTRACT FROM AUTHOR]

Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture. [ABSTRACT FROM AUTHOR]

UV irradiation causes skin damage and aging. This study aimed to develop and evaluate a gel formulation loaded with electrospray mangiferin nanoparticles (MNPs) as a double-action product with photoprotective and anti-aging properties. The MNPs were prepared using the electrospraying technique and loaded in a gel formulation. The MNP formulation was evaluated regarding its physical appearance, viscosity, in vitro sun protection factor (SPF), and in vitro anti-oxidant activity and compared with a formulation containing purified mangiferin (PM) at the same concentration of 0.2% (w/v). Moreover, both formulations were analyzed for their in vitro release and ex vivo skin permeation. The MNP formulation had a considerably higher SPF value than the PM formulation at the same concentration (20.43 ± 0.13 and 12.19 ± 0.27, respectively). The in vitro anti-oxidant activities of the formulations with MNPs and PM were 74.47 ± 2.19% and 80.52 ± 1.05%, respectively. The MNP formulation showed potent photoprotective and anti-oxidation activities with acceptable stability in all parameters under accelerated conditions (4 ± 2 °C 48 h/45 ± 2 °C 48 h for 6 cycles) and after 30 days of storage under various conditions. The release profile data of the MNPs showed a controlled release pattern at 76.97 ± 0.06% at 480 min. Furthermore, after using a Franz diffusion cell for 8 h, the MNP formulation showed the release of 37.01 ± 2.61% and 22.39 ± 1.59% of mangiferin content in the skin layer as stratum corneum and viable epidermis, respectively. Therefore, the overall results demonstrate that electrospray MNPs in a gel formulation are suitable for skin and constitute a promising delivery system for mangiferin in developing cosmetics and cosmeceutical products with good potential. [ABSTRACT FROM AUTHOR]

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 RAFLS proliferation, migration, and inflammatory factor release. [ABSTRACT FROM AUTHOR]

Background: Microorganisms are crucial in our ecosystem, offering diverse functions and adaptability. The UNGA Science Summit has underscored the importance of understanding microbes in alignment with the UN Sustainable Development Goals. Bacillus anthracis poses significant challenges among various microorganisms due to its harmful effects on both soil and public health. Our study employed computational techniques to investigate the inhibitory effects of curcumin and mangiferin on Bacillus anthracis, with the aim of presenting a novel bio-based approach to microbial management. Methods: Employing high-throughput screening, we identified potential binding sites on B. anthracis. Molecular docking revealed that curcumin and mangiferin, when synergistically combined, exhibited strong binding affinities at different sites on the bacterium. Our findings demonstrated a significant drop in binding free energy, indicating a stronger interaction when these compounds were used together. Findings: Results of Molecular docking indicated binding energies of -8.45 kcal/mol for mangiferin, -7.68 kcal/mol for curcumin, and a notably higher binding energy of -19.47 kcal/mol for the combination of mangiferin and curcumin with CapD protein. Molecular dynamics simulations further validated these interactions, demonstrating increased stability and structural changes in the bacterium. Conclusion: This study highlights the effectiveness of natural compounds like curcumin and mangiferin in microbial management, especially against challenging pathogens like B. anthracis. It emphasizes the potential of sustainable, nature-based solutions and calls for further empirical research to expand upon these findings. [ABSTRACT FROM AUTHOR]

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents. [ABSTRACT FROM AUTHOR]

Mangiferin is one of the main bioactive ingredients in leaves of Mangifera indica. But the poor liposolubility and low bioavailability restrict its application. This study aimed to esterify mangiferin with lipase to improve its lipophilicity, and evaluate its antioxidant activity and hypoglycemic properties. Four fatty acids (palmitic acid, lauric acid, stearic acid, oleic acid) were selected for enzymatic esterification with mangiferin by single‐factor experiments. Under the following optimum reaction conditions of tetrahydrofuran (THF):tert‐amyl alcohol (2:1) was used as solvent, water activity was 0.31, TLIM lipase was 45 mg mL–1, The ratio of mangiferin to fatty acid was 1:50, and the substrates were pretreated by ultrasonic for 0.5 h, then reacted at 55°C for 21 h, the resulting conversion rates of mangiferin‐esterified derivatives exceeded 70.0%. Lipophilicity, antioxidant, and PTP1B inhibitory activity of mangiferin‐esterified derivatives were determined. The results demonstrated that compared with mangiferin, the ability to scavenge DPPH radicals decreased by about 9%, but the lipophilicity was increased by 10–30 times, and the lipid antioxidant capacity was also improved significantly. Moreover, the inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) exhibited minimal alteration. This indicates that esterification can not only improve the lipophilicity of mangiferin, but also improve its lipid antioxidant capacity. Practical Applications: In the study, a series of mangiferin‐esterified derivatives were synthesized and their lipophilicity, antioxidant properties, and PTP1B inhibitory activity were determined. The results indicated that, compared with the untreated mangiferin, the mangiferin‐esterified derivatives exhibited superior lipid antioxidant and hypoglycemic activities. Furthermore, the enzymatic esterification method employed in this study offered greater economic and environmental advantages when compared to chemical catalysis. Therefore, the preparation of mangiferin derivatives through enzymatic esterification were deemed feasible with potential application value for enhancing lipid antioxidant capacity in high‐fat foods. [ABSTRACT FROM AUTHOR]

Mangiferin, a prominent phytochemical found abundantly in mango leaves, possesses a wide range of pharmacological properties, including antioxidant, antiviral, anticancer, and antidiabetic effects (Lee, Kim, & Kim, 2019). However, its minted solubility hinders its pharmaceutical applications. This study aimed to optimize the parameters of the spray-drying process to improve the dissolution of mangiferin in Mangiferin indica L. leaf extract and formulate capsules for diabetes treatment. Fourteen experiments were designed using Design Expert software and optimized with BC Pharsoft OPT software. Three independent variables were investigated: the ratio of mangiferin to excipients (X1), the ratio of maltodextrin in spray fluid composition (X2), and inlet air temperature (X3). The dissolution of mangiferin was measured as the percentage released within 5 minutes (Y1), 15 minutes (Y2), and 30 minutes (Y3), and the percentage of hygroscopicity at 25oC (Y4). The results showed that the optimized spray drying process and formula, which included the ratios of mangiferin and maltodextrin in the spray drying solution of 8.30% and 9.63%, respectively, the inlet air temperature of 156.26oC, blowing speed of 50 m3/s, and pump flow of 3 mL/min, possessed a dissolution of mangiferin in the spray drying powder of 91.89 ± 2.43% at 30 minutes, and a percentage hygroscopicity of 0.13 ± 0.13% at 25oC. This study, for the first time, explored the cause-effect relationships and optimization of the formulation of Mangifera indica L. leaf extract powder. The spray-dried powder capsule released more than 90% mangiferin within 30 minutes and showed significant hypoglycemic effects in inhibiting the a-glucosidase enzyme (IC 50 of 36.94 µg/mL equivalent to mangiferin in comparison with the commercial drug Glucobay (acarbose 176.09 µg/mL). In summary, the capsules containing the optimized formula of mangiferin spray-dried powder from Mangifera indica L. leaf extract have been successfully prepared and have potential antidiabetic effects in in-vitro settings. [ABSTRACT FROM AUTHOR]

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1a) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes. [ABSTRACT FROM AUTHOR]

Bersama (Melianthaceae) has been used in traditional medicine for a wide range of ailments, including blood purifier, immune booster, psychotropic medication, and treatment for malaria, hepatitis, infertility, diabetes, impotency, meningitis, and stroke. This review gathers fragmented information from the literature on ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of the Bersama genus. It also explores the therapeutic potential of the Bersama genus in ethnophytopharmacology, allowing for further investigation. All the available information published in the English language on Bersama genus was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search using the following keywords: "Bersama genus," "traditional use," "phytochemistry," "pharmacological effects," and "toxicology". The ethnomedical applications of the Bersama genus have been recorded, and it has been used traditionally for more than 30 different types of ailments. Thus far, more than 50 compounds have been isolated from the genus. Cardiac glycosides and terpenoids are the main compounds isolated from the Bersama genus. Different plant parts of Bersama genus extracts demonstrated a wide range of pharmacological properties, including antioxidant, antimalarial, antidiabetic, antiviral, anti-inflammatory, and cytotoxic activity. Exemplary drug leads from the genus include mangiferin and quercetin-3-O-arabinopyranoside, both of which have antioxidant activities. Bersama genus has long been used to cure a wide range of ailments. Bersama genus extracts and phytochemicals have been found to have promising pharmacological activities. Further study on promising crude extracts and compounds is required to develop innovative therapeutic candidates. [ABSTRACT FROM AUTHOR]

Anxiety and depression are major side effects induced by currently available antiepileptic drugs; apart from this, they also diminish intelligence and language skills which cause hepatic failure, anemia, etc. Hence, in this study, we assessed antiepileptic effect of a phytochemical mangiferin. Epilepsy, a prevalent non communicable neurological disorder, affects infants and older population throughout the world. Epilepsy-induced comorbidities are more severe and if not treated cautiously lead to disability and even worse cases, mortality. The onset and duration of convulsion were observed. Seizure severity score was assessed by provoking kindling with 35 mg/kg PTZ. Prooxidants and antioxidants were measured to assess the antioxidant effect of mangiferin. Inflammatory markers were measured to determine the anti-inflammatory effect of mangiferin. The levels of neurotransmitters and ATPases were quantified to evaluate the neuroprotective effect of mangiferin. Mangiferin significantly decreased the onset and duration convulsion. It also decreased the seizure severity score, locomotor activity, and immobilization effectively. The excitatory neurotransmitter was reduced, and inhibitory neurotransmitter was increased in mice treated with mangiferin. Overall, our results confirm that mangiferin efficiently protects mice from PTZ-induced seizures. It can be subjected to further research to be prescribed as a potent antiepileptic drug. [ABSTRACT FROM AUTHOR]

High-starch diets may lead to growth retardation, liver damage and lipid accumulation in fish. Although mangiferin (MGF) can regulate triglyceride metabolism and protect liver health in mammals, studies on its role in fish are limited. The largemouth bass (Micropterus salmoides) were fed four different groups of diets, including a control diet (NCD), a high-starch diet (HSD), a high-starch diet supplemented with 100 mg/kg MGF (100 MGF) and a high-starch diet supplemented with 500 mg/kg MGF (500 MGF). After 8 weeks of feeding, weight gain and specific growth rate were significantly higher in the 500 MGF group than in the HSD group. Feeding rate was significantly higher in the 100 MGF group than in the HSD group. Feed conversion ratio was significantly higher in the 100 MGF group than in the HSD group. MGF reduced HSI, ALT, AST and liver vacuolization, compared with HSD group. In addition, MGF significantly reduced plasma GLU and TG levels and increased plasma HDL levels in largemouth bass. Compared to the HSD group, MGF significantly reduced TG levels in the liver, as well as reduced hepatic lipid droplet area. MGF significantly increased the relative expressions of glycolysis-related gene (pfk1), pentose phosphate pathway-related genes (g6pd, pgd and tktb) and mitochondrial oxidative phosphorylation-related gene (ndufa2, sdhb, sdhaf3, sdhaf4 and cox4). MGF significantly decreased the relative expressions of gluconeogenesis-related gene (pepck and g6pc). MGF significantly decreased the transcriptional levels of key relative expressions of triglyceride metabolism (srebf1), fatty acid synthesis-related genes (acc1, fasn and scd1) and triglyceride synthesis-related genes (gpat2, agpat2, agpat3, agpat5, dgat1a and dgat2). MGF significantly increased the relative expressions of triglyceride catabolism-related genes (pnpla2 and lipeb). The results indicated that MGF reduced lipid accumulation and alleviated high starch diet-induced liver damage by regulating triglyceride metabolism in largemouth bass.

Abstract Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti‐inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word “Cancer” depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard.

Abstract Studies suggest that mangiferin (MAF) has good therapeutic effects on chronic bronchitis and hepatitis. Also, it is one of the antiviral ingredients in Anemarrhena asphodeloides Bunge. However, its effect on the LPS‐induced inflammation and intestinal flora during sepsis remains unclear yet. In the present study, LPS‐stimulated inflammation RAW264.7 cells and LPS‐induced sepsis mice were used to evaluate the efficacy of MAF in vitro and in vivo. 16S rDNA sequencing was performed to analyze the characteristics of intestinal flora of the sepsis mice. It has been demonstrated that MAF (12.5 and 25 μg/mL) significantly inhibited protein expressions of TLR4, MyD88, NF‐κB, and TNF‐α in the LPS‐treated cells and reduced the supernatant TNF‐α and IL‐6 levels. In vivo, MAF (20 mg/kg) markedly protected the sepsis mice and reduced the serum TNF‐α and IL‐6 levels. Also, MAF significantly downregulated the protein expressions of TLR4, NF‐κB, and MyD88 in the livers. Importantly, MAF significantly attenuated the pathological injuries of the livers and small intestines. Further, MAF significantly increased proportion of Bacteroidota and decreased the proportions of Firmicutes, Desulfobacterota, Actinobacteriota, and Proteobacteria at phylum level, and it markedly reduced the proportions of Escherichia‐Shigella, Pseudoalteromonas, Staphylococcus at genus level. Moreover, MAF affects some metabolism‐related pathways such as citrate cycle (TCA cycle), lipoic acid metabolism, oxidative phosphorylation, bacterial chemotaxis, fatty acid biosynthesis, and peptidoglycan biosynthesis of the intestinal flora. Thus, it can be concluded that MAF as a treatment reduces the inflammatory responses in vitro and in vivo by inhibiting the TLR4/ MyD88/NF‐κB pathway, and corrects intestinal flora imbalance during sepsis to some degree.

Abstract Background The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0. Methods Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe −/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein. Results The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe −/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis. Conclusions Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

This study aimed to explore the process of ultrasound-assisted extraction of mangiferin from mango kernels. Through single factor experiments and Box-Behnken response surface design, investigated the effects of five factors: Material liquid ratio, ethanol concentration, ultrasound temperature, ultrasound time, and ultrasound power on the extraction rate of mangiferin. The results showed that the optimal extraction parameters were as follows: Ethanol concentration of 75%, liquid-to-solid ratio of 1:50 g/mL, ultrasonic temperature of 45 ℃, ultrasonic time of 40 min, and ultrasonic power of 288 W. Under this optimal process condition, the yield of mangiferin was 4.78%, with a predicted value of 4.75%. This study can provide a theoretical reference for the extraction of mangiferin from mango kernels.

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

An electrically active ceramic composite of Ca10(PO4)6(OH)2 and BaSrTiO3 was studied for its possible therapeutic applications. This study offers an in-depth investigation into the material science aspects of composites, including their biological properties and dielectric interactions. The weight ratio of the mixed hydroxyapatite and ferroelectric barium strontium titanate was 60:40. The microstructure and phase composition of the composites were both characterized using X-ray diffraction analysis and scanning electron microscopy (SEM). As part of the in vitro study, mangiferin (MANG) was included in both unpolarized and polarized HA-BST composites. The MTT assay for cell viability showed enhanced osteoblast activity of the specimens. The polarized composite was found to be more effective than the unpolarized specimen in inhibiting the growth and attachment of Staphylococcus aureus. As a result, the polarized HA-BST-MANG composite has shown to be an effective bone substitute in encouraging osteoblast production and preventing bacterial infection. [ABSTRACT FROM AUTHOR]

Studies suggest that mangiferin (MAF) has good therapeutic effects on chronic bronchitis and hepatitis. Also, it is one of the antiviral ingredients in Anemarrhena asphodeloides Bunge. However, its effect on the LPS‐induced inflammation and intestinal flora during sepsis remains unclear yet. In the present study, LPS‐stimulated inflammation RAW264.7 cells and LPS‐induced sepsis mice were used to evaluate the efficacy of MAF in vitro and in vivo. 16S rDNA sequencing was performed to analyze the characteristics of intestinal flora of the sepsis mice. It has been demonstrated that MAF (12.5 and 25 μg/mL) significantly inhibited protein expressions of TLR4, MyD88, NF‐κB, and TNF‐α in the LPS‐treated cells and reduced the supernatant TNF‐α and IL‐6 levels. In vivo, MAF (20 mg/kg) markedly protected the sepsis mice and reduced the serum TNF‐α and IL‐6 levels. Also, MAF significantly downregulated the protein expressions of TLR4, NF‐κB, and MyD88 in the livers. Importantly, MAF significantly attenuated the pathological injuries of the livers and small intestines. Further, MAF significantly increased proportion of Bacteroidota and decreased the proportions of Firmicutes, Desulfobacterota, Actinobacteriota, and Proteobacteria at phylum level, and it markedly reduced the proportions of Escherichia‐Shigella, Pseudoalteromonas, Staphylococcus at genus level. Moreover, MAF affects some metabolism‐related pathways such as citrate cycle (TCA cycle), lipoic acid metabolism, oxidative phosphorylation, bacterial chemotaxis, fatty acid biosynthesis, and peptidoglycan biosynthesis of the intestinal flora. Thus, it can be concluded that MAF as a treatment reduces the inflammatory responses in vitro and in vivo by inhibiting the TLR4/ MyD88/NF‐κB pathway, and corrects intestinal flora imbalance during sepsis to some degree. [ABSTRACT FROM AUTHOR]

Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti‐inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word "Cancer" depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard. [ABSTRACT FROM AUTHOR]

Mangiferin, a key bioactive constituent in Gentiana rhodantha, has a favorable impact on reducing blood sugar. A selective and sensitive UPLC MS/MS approach was developed for determining mangiferin in diabetic rats. Employing acetonitrile protein precipitation, chromatographic separation utilized a 2.1x50 mm, 3.5 µm C18 column with a mobile phase of 0.1% formic acid aqueous and 5 mM ammonium acetate (A, 45%) and acetonitrile (B, 55%) at a 0.5 mL min-1 flow rate. Quantification, employing the multiple reaction monitoring (MRM) mode, focused on precursor-toproduct ion transitions at m/z 447.1→271.1 for baicalin m/z and 421.0→301.0 for mangiferin. Calibration curves demonstrated linearity in the 1.00~100 ng/mL range, with a lower quantification limit for rat plasma set at 1.00 ng/mL. Inter- and intra-day accuracies spanned -9.1% to 8.5%, and mangiferin mean recovery varied from 82.3% to 86.7%. The adeptly utilized UPLC-MS/MS approach facilitated the exploration of mangiferin pharmacokinetics in diabetic rats. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) represents a considerable clinical and public health burden worldwide. Mangiferin (MF), a flavonoid compound present in diverse species such as mango (Mangifera indica L.), papaya (Pseudocydonia sinensis (Thouin) C. K. Schneid.), zhimu (Anemarrhena asphodeloides Bunge), and honeybush tea (Cyclopia genistoides), boasts a broad array of pharmacological effects. It holds promising uses in nutritionally and functionally targeted foods, particularly concerning MetS treatment. It is therefore pivotal to systematically investigate MF's therapeutic mechanism for MetS and its applications in food and pharmaceutical sectors. This review, with the aid of a network pharmacology approach complemented by this experimental studies, unravels possible mechanisms underlying MF's MetS treatment. Network pharmacology results suggest that MF treats MetS effectively through promoting insulin secretion, targeting obesity and inflammation, alleviating insulin resistance (IR), and mainly operating via the phosphatidylinositol 3 kinase (PI3K)/Akt, nuclear factor kappa-B (NF- κ B), microtubule-associated protein kinase (MAPK), and oxidative stress signaling pathways while repairing damaged insulin signaling. These insights provide a comprehensive framework to understand MF's potential mechanisms in treating MetS. These, however, warrant further experimental validation. Moreover, molecular docking techniques confirmed the plausibility of the predicted outcomes. Hereafter, these findings might form the theoretical bedrock for prospective research into MF's therapeutic potential in MetS therapy. [ABSTRACT FROM AUTHOR]

Objectives: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. Methods: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. Key findings: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-β-D-glucosaminidase activity and nitrite levels. Conclusion: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone. Graphical Abstract [ABSTRACT FROM AUTHOR]

This review aims to provide an in-depth analysis of the pharmacological properties of mangiferin, focusing primarily on its bioavailability and mechanisms of action, and its potential therapeutic applications, especially in the context of chronic diseases. We conducted a comprehensive examination of in vitro and in vivo studies, as well as clinical trials involving mangiferin or plant extracts containing mangiferin. The primary source of mangiferin is Mangifera indica, but it's also found in other plant species from the families Anacardiaceae, Gentianaceae, and Iridaceae. Mangiferin has exhibited a myriad of therapeutic properties, presenting itself as a promising candidate for treating various chronic conditions including neurodegenerative disorders, cardiovascular diseases, renal and pulmonary diseases, diabetes, and obesity. Despite the promising results showcased in many in vitro studies and certain animal studies, the application of mangiferin has been limited due to its poor solubility, absorption, and overall bioavailability. Mangiferin offers significant therapeutic potential in treating a spectrum of chronic diseases, as evidenced by both in vitro and clinical trials. However, the challenges concerning its bioavailability necessitate further research, particularly in optimizing its delivery and absorption, to harness its full medicinal potential. This review serves as a comprehensive update on the health-promoting and therapeutic activities of mangiferin. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a major health concern contributing to most of diabetic cases worldwide. Mangiferin and its congeners are known for their diverse pharmacological properties. This study sought to investigate the inhibitory property of naturally occurring mangiferin congeners on sodium-glucose co-transporter 2 protein (SGLT-2) using comprehensive computational methods. The naturally occurring mangiferin congeners were subjected to molecular docking, molecular dynamics (MDs) simulation (100 ns), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy, density functional theory calculations (B3LYP 6-31G basis set), and ADMET approaches to identify potential SGLT-2 inhibitor. The molecular docking studies revealed neomangiferin (−9.0 kcal/mol) as the hit molecule compared with dapagliflozin (−8.3 kcal/mol). Root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) plots from the MD simulations established that neomangiferin stabilizes SGLT-2 better than the dapagliflozin, a standard drug. The MM-PBSA binding free energy calculations showed that neomangiferin (−26.05 kcal/mol) elicited better binding affinity than dapagliflozin (−17.42 kcal/mol). The electronic studies showed that neomangiferin (3.48 eV) elicited high electrophilicity index compared with mangiferin (3.31 eV) and dapagliflozin (2.11 eV). Also, the ADMET properties showed that the hit molecule is safe when administered to diabetic subjects. The current in silico studies suggest that neomangiferin could emerge as a promising lead molecule as a SGLT-2 inhibitor. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20 kcal/mol, Akt at -15.16 kcal/mol, and mTOR at -10.24 kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nanoformulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/ Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage. [ABSTRACT FROM AUTHOR]

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Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the β-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults. [ABSTRACT FROM AUTHOR]

Background. Muscle fatigue is defined as a decrease in maximal force or power production in response to contractile activity, which can cause muscle damage and limit athletic performance. A mass of phytochemicals were certified feasibly in relieving exercise-induced fatigue. Mangiferin, a multifactorial pharmacological phytochemical, was a promising candidate in theory; nonetheless, the potential molecular mechanisms of mangiferin on exercise-induced fatigue need to be elucidated. Methods. In this research, a mouse fatigue model was induced by forced swimming 4 weeks, and mangiferin was supplied in 100 mg/kg. The protective effects of mangiferin were illustrated by rotating rod test, serum biochemical indicators (LA, CK, BUN, ALT, and AST), and gastrocnemius morphology. Then, the targets of mangiferin against exercise-induced fatigue were predicted using network pharmacology through a comprehensive search and analysis with STITCH, PharmMapper Serve, STRING, and AutoDock Vina. Furthermore, predicted target genes were verified in gastrocnemius by immunohistochemistry. Results. Mangiferin has a significant antifatigue effect by prolonging the rotating time of the rod test. Serum biochemical indicators were mitigated (LA, CK, BUN, ALT, and AST), and gastrocnemius injury was easing. Network pharmacology was used to find that mangiferin might alleviate exercise-induced fatigue through regulating NFκB, PTGS2, TNF-α, and CCL2, and those aberrant expressions were verified in gastrocnemius. Molecular docking indicated that NFκB may be the most important molecule locking with mangiferin. Furthermore, the levels of IL-1β, TNF-α, IL-6, and MDA were significantly upregulated, while SOD and GSH-PX were downregulated in serum of fatigue mice, which were reversed with mangiferin treatment. Conclusion. Mangiferin is a feasible treatment to mitigate exercise-induced fatigue by anti-inflammation and antioxidative stress, through regulating the expression of NFκB and its downstream molecules. [ABSTRACT FROM AUTHOR]

Background: The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0. Methods: Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe−/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein. Results: The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe−/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis. Conclusions: Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy. [ABSTRACT FROM AUTHOR]

A polycationic organohalloysite (H‐polyQ22) prepared by the sequential grafting of methylamine and 1,4‐butanediol diglycidyl ether in the interlayer space of (3‐aminopropyl)trimethoxysilane grafted halloysite is herein employed as a carbon paste electrode (CPE) modifier for the electrochemical determination of mangiferin, a bioactive molecule. When H‐polyQ22 was used as CPE modifier, the cyclic voltammetric response of mangiferin increased by ca. 8‐fold. This electrochemical response enhancement was shown to be the result of the great preconcentration capacity of H‐polyQ22. Since the H‐polyQ22 modified CPE proved to be a good signal enhancer, a new methodology for the sensitive determination of mangiferin was developed using square wave voltammetry. Under optimised conditions, a linear correlation between peak current and mangiferin concentration was obtained in the range from 0 to 2775.67 nM. A detection limit of 5.47×10−10 M was obtained based on a signal to noise ratio of 3, with a sensitivity of 193.58 μA/μM. The ability of some possible interferents such as human serum albumin, L‐cystine, ascorbic acid, glucose, dopamine and phenol to perturb the electrochemical signal of mangiferin in real sample analysis was alsoinvestigated. [ABSTRACT FROM AUTHOR]

Photochemical damage to retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of age-related macular degeneration. This study investigated the protective effect of mangiferin on RPE cells subjected to blue light-induced damage. Using human-derived acute RPE 19 (ARPE-19) cells as an in vitro model, we incubated ARPE-19 cells with mangiferin and subsequently subjected those cells to damage-inducing blue light irradiation. Cell viability was measured by Cell Counting Kit-8. Intracellular reactive oxygen species (ROS) level was analyzed using flow cytometry. The results indicate that mangiferin can protect ARPE-19 cell growth after blue light-induced damage. However, the preincubation of ARPE-19 cells with lutein did not demonstrate the same protective effect against photo-induced damage. Lutein increased ROS generation and reduced cell viability (72 h), but mangiferin reduced the ROS level compared with the blank control. Our results demonstrate that mangiferin had a protective effect on blue light-induced RPE cell damage. [ABSTRACT FROM AUTHOR]

Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves (Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them. [ABSTRACT FROM AUTHOR]

BackgroundMicroorganisms are crucial in our ecosystem, offering diverse functions and adaptability. The UNGA Science Summit has underscored the importance of understanding microbes in alignment with the UN Sustainable Development Goals. Bacillus anthracis poses significant challenges among various microorganisms due to its harmful effects on both soil and public health. Our study employed computational techniques to investigate the inhibitory effects of curcumin and mangiferin on Bacillus anthracis, with the aim of presenting a novel bio-based approach to microbial management.MethodsEmploying high-throughput screening, we identified potential binding sites on B. anthracis. Molecular docking revealed that curcumin and mangiferin, when synergistically combined, exhibited strong binding affinities at different sites on the bacterium. Our findings demonstrated a significant drop in binding free energy, indicating a stronger interaction when these compounds were used together.FindingsResults of Molecular docking indicated binding energies of −8.45 kcal/mol for mangiferin, −7.68 kcal/mol for curcumin, and a notably higher binding energy of −19.47 kcal/mol for the combination of mangiferin and curcumin with CapD protein. Molecular dynamics simulations further validated these interactions, demonstrating increased stability and structural changes in the bacterium.ConclusionThis study highlights the effectiveness of natural compounds like curcumin and mangiferin in microbial management, especially against challenging pathogens like B. anthracis. It emphasizes the potential of sustainable, nature-based solutions and calls for further empirical research to expand upon these findings.

This study aimed to develop and optimize mangiferin-loaded solid lipid nanoparticles (MG-SLNs) using the microemulsion technique and ultrasonication. The MG-SLNs were composed of Labrafil M 2130 CS, MG, ethanol, Tween 80, and water. The optimized MG-SLNs exhibited a particle size of 138.37 ± 3.39 nm, polydispersity index of 0.247 ± 0.023, entrapment efficiency of 84.37 ± 2.43 %, and zeta potential of 18.87 ± 2.42 mV. Drug release studies showed a two-fold increase in the release of MG from SLNs compared to the solution. Confocal images indicated deeper permeation of MG-SLNs, highlighting their potential. Molecular docking confirmed mangiferin's inhibitory activity against α-amylase, consistent with previous findings. In vitro studies showed that MG-SLNs inhibited α-amylase activity by 55.43 ± 6.11 %, α-glucosidase activity by 68.76 ± 3.14 %, and exhibited promising antidiabetic activities. In a rat model, MG-SLNs significantly and sustainably reduced blood glucose levels for up to 12 h. Total cholesterol and triglycerides decreased, while high-density lipoprotein cholesterol increased. Both MG-SOL and MG-SLNs reduced SGOT and SGPT levels, with MG-SLNs showing a more significant reduction in SGOT compared to MG-SOL. Overall, the biochemical results indicated that both formulations improved diabetes-associated alterations. In conclusion, the study suggests that loading MG in SLNs using the newly developed approach could be an efficient oral treatment for diabetes, offering sustained blood glucose reduction and positive effects on lipid profiles and liver enzymes.