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Inhibition 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]

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin's effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia , Coprococcus , Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis. [ABSTRACT FROM AUTHOR]

Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses. The protective effects of mangiferin on macrophages in a hyperglycemic environment were assessed by examining the expression of Nrf2, NF-κB, NLRP3, HO-1, CAT, COX-2, IL-6, and IL-10 through gene and protein expression analyses using qPCR and immunoblotting, respectively. The mangiferin-mediated nuclear translocation of Nrf2 was evidenced, leading to a robust antioxidant response in macrophages exposed to a hyperglycemic microenvironment. This activation suppressed NF-κB signaling, reducing the expression of pro-inflammatory mediators such as COX-2 and IL-6. Additionally, mangiferin decreased NLRP3 inflammasome activation and reactive oxygen species accumulation in hyperglycemia exposed macrophages. Our findings revealed that mangiferin alleviated hyperglycemia-induced reductions in AKT phosphorylation, highlighting its potential role in modulating key signaling pathways. Furthermore, mangiferin significantly enhanced the invasiveness and migration of macrophages in a hyperglycemic environment, indicating its potential to improve wound healing. In conclusion, this study suggests that mangiferin may offer a promising therapeutic approach for managing inflammation and promoting wound healing in diabetic patients by regulating Nrf2 activity in hyperglycemia-induced macrophages. [ABSTRACT FROM AUTHOR]

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]

Purpose: Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro. Materials and Methods: The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms. Results: MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1β in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells. Conclusion: CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation. [ABSTRACT FROM AUTHOR]

Introduction: Mango fruit and its by-products represent a very diverse and abundant source of sugars and components with anti-inflammatory and antioxidant properties, such as dietary fiber, vitamins, and polyphenols. Consuming mango pulp might reduce health disorders caused by inflammatory and oxidative processes such as obesity related diseases. Mango and its by-products contain compounds that can either promote or neutralize inflammatory and oxidative environments; variations in their composition may directly influence the degree of bioactivity. This work aimed to analyze the nutritional and nutraceutical profiles presented in the three different mango by-products to know their possible nutraceutical potential. Objective: This work aimed to analyze the nutritional and nutraceutical profiles presented in the three different mango by-products to know their possible nutraceutical potential. Methods: Ripe Ataulfo mango products (pulp, peel, and peel fiber) were evaluated for nutritional composition by AOAC methods. β-carotene and ascorbic acid were analyzed by UV-Vis liquid chromatography (LC), while mangiferin, phenolics and flavonoids by LC coupled to mass spectrometer detector. The antioxidant capacity was correlated to each of the bioactive compounds. Results: Ripe Ataulfo mango products (pulp, peel, and peel fiber) were evaluated for nutritional, antioxidant, and phytochemical characteristics. All the by-products demonstrated significant differences (P ≤ 0.05) in nutritional and chemical composition. Mango peel had the highest β-carotene, vitamin C, and mangiferin values. Mango pulp had the highest values for free sugars (73 g 100 g-1), but low phytochemicals values, contrasting the peel fiber with 81% of total dietary fiber but minimum values of free sugars and β-carotene and no vitamin C. The highest antioxidant capacity was presented for mango peel. Results obtained from this study indicate that the mango Ataulfo pulp and by-products are divergent and represent a good source of bioactive compounds. Conclusions: Mango peel composition is a natural combination of high concentrations of mangiferin, flavonoids, phenolic acids, vitamin C, provitamin A, and dietary fiber, all involved with inflammation and cell oxidative stress-related disease control and prevention. However, mango peel exhibited the most significant nutraceutical potential due to its high antioxidant capacity. [ABSTRACT FROM AUTHOR]

This study evaluated the performance of two techniques – conventional solvent extraction (CSE) and ultrasound-assisted extraction (UAE) – using different solvents (50% methanol, 50% ethanol, 70% acetone) for the extraction of phenolics from mango peel. For each mango peel extract (MPE), a further purification step was performed on an OASIS HLB 6 cc VAC-packed column. Subsequently, the phenolic compound profile was quantified using Ultra Performance Liquid Chromatography accoupled with a Photodiode Array (UPLC-PDA), and the antioxidant activity was also assessed. The results indicated that using 50% methanol as an extraction solvent yielded more significant phenolics, such as mangiferin, gallic acid, quercetin, and rutin. Additionally, the extracts obtained by UAE with different solvents showed a higher phenolic compound content, with mangiferin being the most predominant, mainly when methanol was used (222.34 mg/100 g DW) and higher antioxidant activity than extracts obtained by CSE, especially when acetone was used (364.00 ± 13.00 µmol Trolox/g DW). Overall, the results indicate the potential use of these mango by-products as a source of natural ingredients for the development of functional food. [ABSTRACT FROM AUTHOR]

In order to cure a range of ailments, scientists have investigated a number of bioactive antioxidant compounds produced from natural sources. Mangiferin, a C-glycosyl xanthone-structured yellow polyphenol, is abundant in mangoes and other dietary sources. In-depth examinations found that it is effective in the treatment of a variety of disorders due to its antiviral, anti-inflammatory, antiproliferative, antigenotoxic, antiatherogenic, radioprotective, nephroprotective, antihyperlipidemic, and antidiabetic properties. However, it is recognised that mangiferin's poor bioavailability, volatility, and limited solubility restrict its therapeutic usefulness. Over time, effective solutions to these problems have arisen in the shape of effective delivery methods. The current articles present a summary of the several researches that have updated Mangiferin's biopharmaceutical characteristics. Additionally, strategies for enhancing the bioavailability, stability, and solubility of this phytodrug have been discussed. This review provides detailed information on the development of innovative Mangiferin delivery methods such as nanoparticles, liposomes, micelles, niosomes, microspheres, metal nanoparticles, and complexation, as well as its therapeutic applications in a variety of sectors. This article provides effective guidance for researchers who desire to work on the formulation and development of an effective delivery method for improved magniferin therapeutic effectiveness. [ABSTRACT FROM AUTHOR]

One of the main factors in the pathophysiology of amyotrophic lateral sclerosis is oxidative stress. Mangiferin (MF), a natural plant polyphenol, has anti‐inflammatory and antioxidant effects. The aim of our study was to investigate the protective effects and mechanisms of MF in the hSOD1‐G93A ALS cell model. Our result revealed that MF treatment reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased oxidative damage, and reduced apoptosis. Additionally, it was observed that MF significantly increased the synthesis of the antioxidant genes hemeoxygenase‐1 and NAD(P)H: quinone oxidoreductase 1, which are downstream of the Nrf2 signaling pathway, and increased the expression and activation of nuclear factor erythroid 2‐related factor 2 (Nrf2). Nrf2 knockdown greatly promoted apoptosis, which was reversed by MF treatment. To summarize, MF promoted the Nrf2 pathway and scavenged MDA and ROS to protect the ALS cell model. [ABSTRACT FROM AUTHOR]

Caixing Shi,1 Yueyao Li,2 Zhidong You,3 Yiran Tian,4 Xiaoyu Zhu,4 Hao Xu,4 Menghan Yang,4 Yutong Zhang,4 Rui Dong,4 Huirong Quan,4 Yongyi Shang,4 Xiaojin Li1 1School of Basic Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 2College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 3School of Nursing, Jining Medical University, Jining, 272067, People’s Republic of China; 4School of Clinical Medicine, Jining Medical University, Jining, 272067, People’s Republic of ChinaCorrespondence: Xiaojin Li, School of Basic Medicine, Jining Medical University, No. 133 hehua Road, Taibai Lake New District, Jining, 272067, People’s Republic of China, Tel +8615265775150, Email jinli10221@163.comPurpose: Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro.Materials and Methods: The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms.Results: MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1β in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells.Conclusion: CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation.Keywords: mangiferin, liver injury, oxidative stress, inflammation, Nrf2

Myocarditis is a major cause of heart failure and death, particularly in young individuals. Current treatments are mainly symptomatic, but emerging therapies focus on targeting inflammation and fibrosis pathways. Natural bioactive compounds like flavonoids and phenolic acids show promising anti-inflammatory and antioxidant properties. Corticosteroids are frequently employed in the treatment of autoimmune myocarditis and appear to lower mortality rates compared to conventional therapies for heart failure. This study aims to explore the effects of Mangiferin on pro-inflammatory cytokine levels, nitro-oxidative stress markers, histopathological alterations, and cardiac function in experimental myosin-induced autoimmune myocarditis. The effects were compared to Prednisone, used as a reference anti-inflammatory compound, and Trolox, used as a reference antioxidant. The study involved 30 male Wistar–Bratislava rats, which were randomly divided into five groups: a negative control group (C−), a positive control group with induced myocarditis using a porcine myosin solution (C+), three groups with induced myocarditis receiving Mangiferin (M), Prednisone (P), or Trolox (T) as treatment. Cardiac function was evaluated using echocardiography. Biochemical measurements of nitro-oxidative stress and inflammatory markers were conducted. Finally, histopathological changes were assessed. At echocardiography, the evaluation of the untreated myocarditis group showed a trend toward decreased left ventricular ejection fraction (LVEF) but was not statistically significant, while all treated groups showed some improvement in LVEF and left ventricular fraction shortening (LVFS). Significant changes were seen in the Mangiferin group, with lower end-diastolic left ventricular posterior wall (LVPWd) by day 21 compared to the Trolox group (p < 0.001). In the first week of the experiment, levels of interleukins (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were significantly higher in the myosin group compared to the negative control group (p < 0.001, p < 0.001, p < 0.01), indicating the progression of inflammation in this group. Treatment with Mangiferin, Prednisone, and Trolox caused a significant reduction in IL-1β compared to the positive control group (p < 0.001). Notably, Mangiferin resulted in a superior reduction in IL-1β compared to Prednisone (p < 0.05) and Trolox (p < 0.05). Furthermore, Mangiferin treatment led to a statistically significant increase in total oxidative capacity (TAC) (p < 0.001) and a significant reduction in nitric oxide (NOx) levels (p < 0.001) compared to the negative control group. Furthermore, when compared to the Prednisone-treated group, Mangiferin significantly reduced NOx levels (p < 0.001) and increased TAC levels (p < 0.001). Mangiferin treatment significantly lowered creatine kinase (CK) and aspartate aminotransferase (AST) levels on day 7 (p < 0.001 and p < 0.01, respectively) and reduced CK levels on day 21 (p < 0.01) compared to the untreated group. In the nontreated group, the histological findings at the end of the experiment were consistent with myocarditis. In the group treated with Mangiferin, only one case exhibited mild inflammatory infiltrates, represented by mononucleated leukocytes admixed with few neutrophils, with the severity graded as mild. Statistically significant correlations between the grades (0 vs. 1–2) and the study groups have been highlighted (p < 0.005). This study demonstrated Mangiferin's cardioprotective effects in autoimmune myocarditis, showing reduced oxidative stress and inflammation. Mangiferin appears promising as a treatment for acute myocarditis, but further research is needed to compare its efficacy with other treatments like Trolox and Prednisone. [ABSTRACT FROM AUTHOR]

Stress degradation of mangiferin and gallic acid was induced to establish the stability indicating power of the validated high performance thin layer chromatography method. Mangiferin is a C-glycosyl xanthone derivative with many health-endorsing biological activities such as hypoglycaemic, antioxidant, and anti-inflammatory. Similarly, gallic acid a phenolic compound possesses antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective, gastroprotective, and neuroprotective effects. To elucidate the intrinsic stability, both molecules were subjected to a forced degradation process under conditions more severe than accelerated ones, generating degradation products for further study. Forced degradation studies were performed according to stability guidelines by International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Q1(R2) and Q1B. Accordingly, mangiferin and gallic acid were exposed to oxidation, acid hydrolysis, alkaline hydrolysis, photolysis, as well as hydrolytic and thermal degradation experiments. Forced degradation results show that mangiferin was less susceptible to acidic and hydrolytic conditions and moderately susceptible to dry heat and photostability conditions. Mangiferin was highly susceptible to alkali and oxidative conditions. Gallic acid was less susceptible to photostability conditions and moderately susceptible to alkali, hydrolytic, and dry heat conditions. Gallic acid was highly susceptible to acid and oxidative conditions. [ABSTRACT FROM AUTHOR]

Mangifera pajang Kosterm., or 'Bambangan,' a fruit known for its rich phytochemical content, was investigated for the effects of ultrasound‐assisted osmotic dehydration (UAOD) on pretreated M. pajang fruit pulp (PMPF) and drying at different temperatures (40, 50, 60, 70, and 80°C). Thin‐layer drying kinetics were analyzed using six models, with the Midilli and Kucuk model being the most suitable, showing optimal effective moisture diffusivity and activation energy. PMPF dried at 50°C, using natural deep eutectic solvents (NADES) as the extraction solvent, exhibited the highest extraction yield (64.13 ± 1.08%), mangiferin content (0.5818 ± 0.00164 mg/g), total phenolic content (146.2081 ± 1.33 mg GAE/g DW), total flavonoid content (2.4737 ± 0.06 mg RE/g DW), and DPPH inhibition activity (95.87 ± 0.16%), along with the best color retention compared to untreated M. pajang fruit pulp. This highlights its potential for nutraceutical and functional food applications, with UAOD as pretreatment effectively preserving food quality and color. Practical Applications: This article provides new insights into the drying and pretreatment of Mangifera pajang fruits. Rich in phytochemicals, M. pajang offers numerous health benefits. Pretreatment methods such as ultrasound‐assisted osmotic dehydration (UAOD) and oven drying at different temperatures significantly enhance the retention of bioactive compounds like phenolics and flavonoids, as well as antioxidant activity and color stability. The study identified optimal drying temperatures, conditions, drying rates, and activation energy to maximize these qualities. Using mathematical models for drying kinetics, this research offers practical guidance for the food processing industry. It provides an operational tool for manufacturers to optimize the drying process, reduce operational costs, and ensure the preservation of chemical qualities while extending the shelf life of M. pajang fruits. This work supports the development of high‐quality nutraceutical and functional food ingredients, promoting their commercialisation and use in health‐focused markets. [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]

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]

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Objective: To discuss the effect of mangiferin (MGF) on the healing of hip fracture in the rats by regulating the Wnt/β -catenin signaling pathway, and to clarify the mechanism. Methods: The hip fracture model in the SD rats was established. After successful modeling, the rats were divided into model group, MGF group, and MGF+XAV-939(Wnt/β-catenin signaling pathway inhibitor) group, and sham operation group was set up, and there were 15 rats in each group. From the first day after surgery, the rats in each group received MGF or XAV-939 interventions every two days, totally for 14 times. Lane-Sandhu X-ray scoring method was used to detect the fracture healing in the second and fourth weeks after surgery; micro CT was used to detect the microstructural parameters of the bone, such as bone volume (BV), number of bone trabeculae (Tb. N), bone volume fraction (BV/TV), and bone trabecular thickness (Tb. Th); HE staining was used to observe the morphology of callus tissue of the rats in various groups; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of osteogenic markers bone alkaline phosphatase (BALP) and type Ⅰ procollagen N-terminal propeptide (PINP) and bone resorption markers tartrate resistant acid phosphatase-5b (TRACP-5b) and Carboxy-terminal terminalpeptide of type Ⅰ collagen (CTX) in serum of the rats in various groups; Western blotting method was used to detect the expression levels of β -catenin, Runt-associated transcription factor 2(Runx2), and bone morphogenetic protein-2(BMP-2) in callus tissue of the rats in various groups. Results: Compared with sham operation group, the rats in model group showed distinct fracture lines, an abundance of fibrous tissue at the fracture site, and no bony callus at the 2nd and 4th weeks after fracture, the Lane-Sandhu X-ray scores and microstructural parameters BV, Tb. N, BV/TV, and Tb. Th of the rats in model group were decreased (P<0. 05), the serum level of BALP was decreased (P<0. 05), while the levels of PINP, TRACP-5b, and CTX were increased (P<0. 05), and the expression levels of β -catenin, Runx2, and BMP-2 proteins in callus tissue were decreased (P<0. 05). Compared with model group, the rats in MGF group showed significantly increased new bone callus at 2nd weeks after fracture, almost no visible fracture line at the 4th weeks, faster fracture healing, and replacement of fibrous tissue by bone tissue at the fracture site, the Lane-Sandhu X-ray scores and microstructural parameters BV, Tb. N, BV/TV, and Tb. Th of the rats in MGF group were increased (P<0. 05), the serum level of BALP was increased (P< 0. 05), the levels of PINP, TRACP-5b, and CTX were decreased (P<0. 05), and the expression levels of β -catenin, Runx2, and BMP-2 proteins in callus tissue were increased (P<0. 05). Compared with MGF group, the rats in MGF+XAV-939 group showed only a small amount of new bone callus at the fracture site at 2nd and 4th weeks after fracture, with no formation of the marrow cavity, and the LaneSandhu X-ray scores and microstructural parameters BV, Tb. N, BV/TV, and Tb. Th of the rats in MGF+XAV-939 group were decreased (P<0. 05), the serum level of BALP was decreased (P<0. 05), the levels of PINP, TRACP-5b, and CTX were increased (P<0. 05), and the expression levels of β -catenin, Runx2, and BMP-2 proteins in callus tissue were decreased (P<0. 05). Conclusion: MGF can promote the healing of hip fracture in the rats, and its mechanism may be related to activation of Wnt/β-catenin signaling pathway. [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,&ast; Kaidi Wang,1,2,&ast; 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&ast;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

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]

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin’s effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia, Coprococcus, Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis.

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 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.

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]

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]

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]