Mango peel extracts and mangiferin chromatographic Fourier-transform infrared correlation with antioxidant, antidiabetic, and advanced glycation end product inhibitory potentials using in silico modeling and in vitro assays.

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.

Mangiferin, a component of Mangifera indica leaf extracts, inhibits lipid synthesis in human sebocytes.

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.

Mangiferin: A natural bioactive immunomodulating glucosylxanthone with potential against cancer and rheumatoid arthritis.

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 ß-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.

Supplementation of Mangiferin to a High-Starch Diet Alleviates Hepatic Injury and Lipid Accumulation Potentially through Modulating Cholesterol Metabolism in Channel Catfish (Ictalurus punctatus).

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.

Valorisation of raw mango pickle industry waste into antimicrobial agent against postharvest fungal pathogens.

In mango pickle industry, a significant quantity of mango seed kernels is discarded as solid wastes. These seed kernels can be an ideal source for obtaining extracts rich in bioactive polyphenolic compounds with good antioxidant properties. The potential of mango kernel phenolic extract (MKPE) was investigated as a natural and effective antimicrobial agent for controlling major postharvest fungal pathogen infections, a significant threat to global food supply chains. Fungal pathogens contribute to the deterioration of fruits, vegetables, and grains during storage and transportation, leading to economic losses and compromised food safety. MKPE was obtained from pickling variety 'Ramkela' raw mango kernels, and its phenolic composition was characterized using LC-MS. The in vitro antifungal activity of MKPE against Botrytis cinerea, Colletotrichum gloeosporoides, and Rhizopus stolonifer was evaluated in vitro. A concentration-dependent inhibition of fungal radial growth against all three pathogens was observed, exhibiting the potential of MKPE as a valuable natural resource for addressing postharvest losses caused by fungal pathogens. The extraction process yielded a total phenolic content of 2128 mg GAE/100 g. Major polyphenolic bioactive compounds present were mangiferin, quercetin, and rhamnetin. The in-vitro antimicrobial assay showed reduction in the radial growth and inhibition percent of the pathogens. EC50 values of MKPE for B. cineria, C. gloeosporoides, and R. stolonifer was found to 364.17, 963.8 and 926 ppm, respectively. Our results demonstrate an economical, sustainable, and eco-friendly approach to manage post-harvest diseases rendered by fungi using mango MKPE from pickling industry waste.

HPLC-DAD quantification of mangiferin, antioxidant potential and essential oil composition of the leaves of five varieties of Mangifera indica L. of North India.

Mangifera indica L. (Mango), native of tropical Asia, has enormous genetic diversity. Comparative phytochemical analysis of leaves of five varieties of Mangifera indica viz. Dashahri, Chausa, Langra, Lucknow Safeda and Gola grown in North India was carried out. Mangiferin content (using HPLC) was found to vary from 0.96 g to 3.00 g per 100 g of dry leaves. Essential oil composition (through GC-MS) showed the major components of all the five varieties to be caryophyllene (4.14-46.26%), humulene (3.19-30.45%), caryophyllene oxide (2.98-17.23%) and humulene epoxide 2 (1.56-4.73%). Results indicated that there was a direct relationship between total phenolic and flavonoid contents and DPPH radical scavenging activities. Our studies indicate that M. indica leaves, which are a form of biomass waste, could be used as an economical and renewable source of antidiabetic compound mangiferin as well as other biologically active phytoconstituents having nutraceutical as well as pharmaceutical applications.

Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats.

INTRODUCTION: Mangiferin is a Chinese herbal extract with multiple biological activities. Mangiferin can penetrate the blood‒brain barrier and has potential in the treatment of nervous system diseases. These findings suggest that mangiferin protects the neurological function in ischemic stroke rats by targeting multiple signaling pathways. However, little is known about the effect and mechanism of mangiferin in alleviating poststroke cognitive impairment. METHODS: Cerebral ischemia/reperfusion (I/R) rats were generated via middle cerebral artery occlusion. Laser speckle imaging was used to monitor the cerebral blood flow. The I/R rats were intraperitoneally (i.p.) injected with 40 mg/kg mangiferin for 7 consecutive days. Neurological scoring, and TTC staining were performed to evaluate neurological function. Behavioral experiments, including the open field test, elevated plus maze, sucrose preference test, and novel object recognition test, were performed to evaluate cognitive function. Metabolomic data from brain tissue with multivariate statistics were analyzed by gas chromatography‒mass spectrometry and liquid chromatography‒mass spectrometry. RESULTS: Mangiferin markedly decreased neurological scores, and reduced infarct areas. Mangiferin significantly attenuated anxiety-like and depression-like behaviors and enhanced learning and memory in I/R rats. According to the metabolomics results, 13 metabolites were identified to be potentially regulated by mangiferin, and the differentially abundant metabolites were mainly involved in lipid metabolism. CONCLUSIONS: Mangiferin protected neurological function and relieved poststroke cognitive impairment by improving lipid metabolism abnormalities in I/R rats.

A Multifunctional Hydrogel Fabricated by Direct Self-Assembly of Natural Herbal Small Molecule Mangiferin for Treating Diabetic Wounds.

Clinical studies have continually referred to the involvement of drug carrier having dramatic negative influences on the biocompatibility, biodegradability, and loading efficacy of hydrogel. To overcome this deficiency, researchers have proposed to directly self-assemble natural herbal small molecules into a hydrogel without any structural modification. However, it is still a formidable challenge due to the high requirements on the structure of natural molecules, leading to a rarity of this type of hydrogel. Mangiferin (MF) is a natural polyphenol of C-glucoside xanthone with various positive health benefits, including the treatment of diabetic wounds, but its poor hydrosolubility and low bioavailability significantly restrict the clinical application. Inspired by these, with heating/cooling treatment, a carrier-free hydrogel (MF-gel) is developed by assembling the natural herbal molecule mangiferin, which is mainly governed through hydrogen bonds and intermolecular π-π stacking interactions. The as-prepared hydrogel has injectable and self-healing properties and shows excellent biocompatibility, continuous release ability, and reversible stimuli-responsive performances. All of the superiorities enable the MF-based hydrogel to serve as a potential wound dressing for treating diabetic wounds, which was further confirmed by both the vitro and vivo studies. In vitro, the MF-gel could promote the migration of healing-related cells from peripheral as well as the angiogenesis and displays the capacity of mediating inflammation response by scavenging the intracellular ROS. In vivo, the MF-gel accelerates wound contraction and healing via inflammatory adjustment, collagen deposition, and angiogenesis. This study provides a facile and effective method for diabetic wound management and emphasizes the direct self-assembly hydrogel from natural herbal small molecule.

Mangiferin attenuates lipopolysaccharide-induced neuronal injuries in primary cultured hippocampal neurons.

Mangiferin, a naturally occurring potent glucosylxanthone, is mainly isolated from the Mangifera indica plant and shows potential pharmacological properties, including anti-bacterial, anti-inflammation, and antioxidant in sepsis-induced lung and kidney injury. However, there was a puzzle as to whether mangiferin had a protective effect on sepsis-associated encephalopathy. To answer this question, we established an in vitro cell model of sepsis-associated encephalopathy and investigated the neuroprotective effects of mangiferin in primary cultured hippocampal neurons challenged with lipopolysaccharide (LPS). Neurons treated with 20 µmol/L or 40 µmol/L mangiferin for 48 h can significantly reverse cell injuries induced by LPS treatment, including improved cell viability, decreased inflammatory cytokines secretion, relief of microtubule-associated light chain 3 expression levels and several autophagosomes, as well as attenuated cell apoptosis. Furthermore, mangiferin eliminated pathogenic proteins and elevated neuroprotective factors at both the mRNA and protein levels, showing strong neuroprotective effects of mangiferin, including anti-inflammatory, anti-autophagy, and anti-apoptotic effects on neurons in vitro.

Mangiferin: A comprehensive review on its extraction, purification and uses in food systems.

With the target of fabricating healthier products, food manufacturing companies look for natural-based nutraceuticals that can potentially improve the physicochemical properties of food systems while being nutritive to the consumer and providing additional health benefits (biological activities). In this regard, Mangiferin joins all these requirements as a potential nutraceutical, which is typically contained in Mangifera indica products and its by-products. Unfortunately, knowing the complex chemical composition of Mango and its by-products, the extraction and purification of Mangiferin remains a challenge. Therefore, this comprehensive review revises the main strategies proposed by scientists for the extraction and purification of Mangiferin. Importantly, this review identifies that there is no report reviewing and criticizing the literature in this field so far. Our attention has been targeted on the timely findings on the primary extraction techniques and the relevant insights into isolation and purification. Our discussion has emphasized the advantages and limitations of the proposed strategies, including solvents, extracting conditions and key interactions with the target xanthone. Additionally, we report the current research gaps in the field after analyzing the literature, as well as some examples of functional food products containing Mangiferin.

Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H2O2). The results showed that mangiferin attenuated H2O2-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H2O2-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H2O2-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

The ethnomedicine, phytochemistry, and pharmacological properties of the genus Bersama: current review and future perspectives.

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.

Effects of Maturation on Antibacterial Properties of Vietnamese Mango (Mangifera indica) Leaves.

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.

A novel front in sustainable microbial management: computational analysis of curcumin and mangiferin's synergistic action against Bacillus anthracis.

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.

Mangiferin improves early porcine embryonic development by reducing oxidative stress.

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, PGC1α) 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.

Structure-based virtual screening of mangiferin derivatives with antidiabetic action: a molecular docking and dynamics study and MPO-based drug-likeness approach.

Extracts from Mangifera indica leaves and its main component, mangiferin, have proven antidiabetic activity. In this study, mangiferin and its natural derivatives Homomangiferin (HMF), Isomangiferin (IMF), Neomangiferin (NMF), Glucomangiferin (GMF), Mangiferin 6'-gallate (MFG), and Norathyriol (NRT) were compared regarding their action on Diabetes mellitus (DM), employing docking and molecular dynamics (MD) simulations to analyze interactions with the aldose reductase enzyme, the precursor to the conversion of glucose into sorbitol. Notably, HMF showed significant affinity to residues in the active site of the enzyme, including Trp 79, His 110, Trp 111, Phe 122, and Phe 300, with an energy of - 7.2 kcal/mol, observed in the molecular docking simulations. MD reinforced the formation of stable complexes for HMF and MFG with the aldose reductase, with interaction potential energies (IPE) in the order of - 300.812 ± 52 kJ/mol and - 304.812 ± 52 kJ/mol, respectively. The drug-likeness assessment, by multiparameter optimization (MPO), highlighted that HMF and IMF have similarities with polyphenols and glycosidic flavonoids recently patented as antidiabetics, revealing that high polarity (TPSA > 180 Å2) is a favorable property for subcutaneous administration, especially because of the gradual passive cell permeability values in biological tissues, with Papp values estimated at < 10 × 10-6 cm/s. These compounds are metabolically stable against metabolic enzymes, resulting in a low toxic incidence by metabolic activation, corroborating with a lethal dose (LD50) greater than 2000 mg/kg. In this way, HMF showed a systematic alignment between predicted pharmacokinetics and pharmacodynamics, characterizing it as the most favorable substance for inhibiting aldose reductase. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03978-9.

Inhibition of macrophage MAPK/NF-κB pathway and Th2 axis by mangiferin ameliorates MC903-induced atopic dermatitis.

Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.

Novel Carbon Dots Derived from Moutan Cortex Significantly Improve the Solubility and Bioavailability of Mangiferin.

Background: 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.

Regulatory effects of mangiferin on LPS-induced inflammatory responses and intestinal flora imbalance during sepsis.

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.

Therapeutic potential of mangiferin in cancer: Unveiling regulatory pathways, mechanisms of action, and bioavailability enhancements - An updated review.

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.