Search Results (125)

Xanthones from mangosteen pericarp (MP) are bioactive compounds with promising pharmaceutical and nutraceutical applications. However, their efficient and selective extraction using environmentally friendly solvents remains a challenge. This study aimed to evaluate tricaprylin (C8) and tricaprin (C10) as novel green co-extractants in supercritical carbon dioxide (scCO₂) extraction for the recovery of xanthones from MP, using a mass ratio of C8:C10 = 0.64:0.36, hereafter referred to as C8/C10, and to model extraction kinetics for process design and scale-up. Extraction performance was investigated using different C8/C10–MP mass ratios and scCO₂ conditions at temperatures of 60 °C and 70 °C and pressures of 250 bar, 350 bar, and 450 bar. A pseudo-first-order kinetic model was applied to describe the extraction profile, and the kinetic parameters were generalized using second-order polynomial functions of temperature and pressure. The highest xanthone yield (39.93 ± 0.37%) and total xanthone content (51.44 ± 2.22 mg/g) were obtained at a 40% C8/C10–MP ratio under 70 °C and 350 bar, where the C8/C10 mixture outperformed other tested co-extractants in both efficiency and selectivity, particularly for α-mangostin. The extraction profiles were well described by the pseudo-first-order kinetic model, and the generalized model predicted the extraction yield with an uncertainty of 2.3%. C8/C10 is a highly effective and scalable co-extractant for scCO₂ extraction of xanthones, offering a foundation for industrial applications in food, nutraceutical, and pharmaceutical sectors. Full article

Feline infectious peritonitis virus (FIPV), caused by a mutated form of feline coronavirus, poses a significant threat to feline health worldwide, with limited therapeutic options available. This study investigated the antiviral potential of α-mangostin (α-MG) and its enriched extracts (AMEs), obtained via microwave-assisted extraction, against FIPV. We evaluated their cytotoxicity, direct virucidal activity, and antiviral activity in CRFK cells. Both α-MG and AMEs demonstrated significant antiviral activity, with EC₅₀ values from 2.71 to 2.88 μg/mL and favorable selectivity indices (3.25–3.66). Notably, AMEs exhibited direct virucidal effects, effectively reducing viral titers. Furthermore, treatment with these compounds significantly reduced inflammatory cytokine expression (IFN-β, TNF-α, and IL-6 mRNA levels) and decreased viral loads in FIPV-infected cells. Drug combination studies using the ZIP model revealed enhanced cooperative effects when AMEs and α-MG were combined with GC-376 or GS-441524, with GC-376 combinations showing particularly strong synergistic potential. These findings suggest that α-MG and AMEs are promising candidates for FIPV treatment, either as monotherapy or in combination therapy. This study provides insights into developing novel therapeutic strategies to combat FIPV infections and offers a foundation for future veterinary antiviral drug development. Full article

Background/Objectives: The present study aimed to synthesize folate-conjugated poloxamers and develop polymeric micelles for the dermal delivery of irinotecan and alpha-mangostin for the treatment of melanoma using poloxamer 188 and poloxamer 184, which have never been synthesized with folate before. Methods: Poloxamer 188 and poloxamer 184 were synthesized with folate by esterification. The in vitro skin penetration enhancement of irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles was evaluated. The skin penetration pathway of folate-conjugated polymeric micelles was investigated by colocalization of multiple fluorescently labeled particles using confocal laser scanning microscopy (CLSM). Results: Folate-conjugated poloxamer 188 and poloxamer 184 were successfully synthesized. The prepared irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles from poloxamer 188 and poloxamer 184 had particle sizes of approximately 180 and 150 nm, respectively, indicating a positive charge with a narrow size distribution which could be easily taken up into cells. An in vitro skin penetration study revealed that folate-conjugated polymeric micelles from poloxamer 184 significantly enhanced the skin penetration of irinotecan and alpha-mangostin to a greater extent than the solution. CLSM visualization revealed that folate-conjugated polymeric micelles penetrated through the skin by the transfollicular pathway as the major penetration pathway, whereas penetration by the intercluster pathway, transcellular pathway and intercellular pathway constituted a minor pathway. Conclusions: Folate-conjugated poloxamer 184 polymeric micelles are promising candidates for the dermal delivery of anticancer drugs by the transfollicular pathway as the major skin penetration pathway. Full article

The increasing morbidity of various types of cancer in the world’s population and the limited number of universal methods of their treatment contribute to the growth in research into the development of new treatment strategies. Most of this research focuses on treatments that target specific factors in cancer cell signalling pathways. There is also great interest in drugs derived from natural substances, as these represent one of the largest sources of potential pharmaceuticals. In our analysis, we focused on the action of α-mangostin and gambogic acid, which are natural xanthones or their synthetic derivatives. We studied their influence on the expression of STAT3 and NANOG, which play a confirmed role in different stages of cancer development. For this purpose, we applied RNAi-mediated gene silencing of NANOG and STAT3 to enhance the efficacy of xanthone-based anticancer treatment in HeLa cell cultures. After stimulating the cells with xanthones, we determined the expression of the tested transcription factors and the ROS level. In addition, we determined the cytotoxicity and apoptosis of the cells. Our research results confirm the anticancer efficacy of the analysed xanthones and demonstrate the role of the tested transcription factors. Silencing these factors makes cancer cells more susceptible to xanthone treatment. Full article

Alpha-mangostin ($\alpha$-MG) is a prenylated xanthone extracted from the pericarp of the mangosteen tree (Garcinia mangostana) fruit. The compound exhibits a broad range of therapeutic properties, such as anti-inflammatory, antioxidative, and antimicrobial activity. This review highlights new findings in antibacterial studies involving $\alpha$-MG, demonstrates its potent activity against Gram-positive bacteria, including Staphylococcus and Enterococcus genera, and describes the antibacterial mechanisms involved. Most cited literature comes from 2020 to 2025, highlighting the topic’s relevance despite limited new publications in this period. The primary antibacterial mechanism of $\alpha$-MG consists of the disruption of the bacterial membrane and increased bacterial wall permeability, leading to drug accumulation and cell lysis. Other mechanisms include genomic interference and enzyme activity inhibition, which impair metabolic pathways. $\alpha$-MG can also disrupt biofilm formation, facilitate its removal, and prevent its maturation. Furthermore, $\alpha$-MG presents strong synergistic action with common antibiotics and other phytochemicals, even against drug-resistant strains, facilitating infection treatment and allowing for reduced drug dosage. The main challenge in developing $\alpha$-MG-based drugs is their low aqueous solubility; therefore, nanoformulations have been explored to improve its bioavailability and antibacterial stability. Extended research in this direction may enable the development of effective antibacterial and anti-biofilm therapies based on $\alpha$-MG. Full article

Hyperlipidemia is a major risk factor for cardiovascular and metabolic diseases. Although pharmacologic treatments are effective, their adverse effects have spurred interest in natural alternatives. Alpha-mangostin (AM), a xanthone from Garcinia mangostana, has shown lipid-lowering effects in animal studies, but its overall efficacy remains unclear. This systematic review and meta-analysis, conducted in accordance with PRISMA 2020 guidelines, evaluated AM’s impact on lipid profiles in hyperlipidemic animal models. Databases including Scopus, PubMed, ScienceDirect, Cochrane Library, and Web of Science were searched for relevant controlled studies. Nine studies (N = 226 animals) met inclusion criteria, reporting data on triglycerides (TG), total cholesterol (TC), LDL-C, and HDL-C. Risk of bias, assessed using the Cochrane RoB 2 tool, was generally low-to-moderate. Meta-analysis using a random-effects model revealed that AM significantly reduced TG, TC, and LDL-C, while increasing HDL-C. Stronger effects were observed at doses <50 mg/kg/day. Subgroup and sensitivity analyses confirmed robustness and highlighted the influence of species, region, and treatment duration. These findings suggest that AM is a promising lipid-lowering agent in animal models. Further clinical trials are needed to validate efficacy in humans and determine optimal dosing. Full article

Waste products from agricultural crops can become valuable if their benefits are discovered. Mangosteen, known as the “queen of fruits”, has a pericarp extract that has been reported to possess various biological activities, including antioxidation, anti-inflammation, antimicrobial activity, and UVB protection (in vitro and in vivo). In this work, we revealed that mangosteen pericarp extract (MPE) exhibits photoprotective properties in primary human dermal fibroblasts (PHDFs) exposed to ultraviolet A (UVA). The α-mangostin content, a major compound in MPE, was determined to be 60.9 ± 1.2% using HPLC. In an in vitro, cell-based assay, we first assessed the cytotoxicity of MPE on PHDFs using the MTT assay. The highest concentration of MPE that showed no cytotoxicity was 50.0 µg/mL. For antioxidative effects, MPE reduced intracellular ROS levels induced by H₂O₂, compared to H₂O₂-treated PHDFs. To assess the photoprotective effect of MPE, cells were pretreated with MPE for 24 h before exposure to UVA at an intensity of 5 J/cm². Our data demonstrated that MPE pretreatment reduced the accumulation of senescent cells compared to UVA-induced senescent cells (7.1 ± 2.4% vs. 12.0 ± 0.2%, respectively). In addition, we examined key aging-related markers, including matrix metalloproteinase 1 (MMP-1) and collagen type I. The expression level of MMP-1 levels was 23,873.4 ± 5498.1 pg/mL in MPE-treated, UVA-induced PHDFs, compared to 38,929.1 ± 6971.4 pg/mL in untreated UVA-induced PHDFs. Meanwhile, procollagen type I in MPE-pretreated PHDFs was 56,443.3 ± 3623.8 pg/mL, compared to 37,137.4 ± 4614.8 pg/mL in UVA-induced PHDFs. These experimental results highlight the photoprotective properties of Garcinia mangostana peel extract, which contains α-mangostin as a major compound, and suggest its potential as an active ingredient in cosmeceuticals for protecting against UVA-induced aging. To the best of our knowledge, this is the first study to report the photoprotective effects of MPE on UVA-induced senescent cells. Full article

α-Mangostin, a bioactive xanthone derived from the Garcinia mangostana L. Clusiaceae (G. mangostana) fruit, has demonstrated significant anti-inflammatory and immunomodulatory properties. Chronic inflammation plays a critical role in the pathogenesis of various diseases, including metabolic disorders, autoimmune conditions, and cancer. Conventional anti-inflammatory therapies, such as non-steroidal anti-inflammatory drugs (NSAIDs), often carry undesirable side effects, prompting the need for safer, natural alternatives. This review consolidates the existing literature on the mechanisms by which α-mangostin exerts its anti-inflammatory effects, including the suppression of pro-inflammatory cytokines, modulation of immune cell activity, and inhibition of key signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, α-mangostin exhibits immunomodulatory properties by influencing both innate and adaptive immune responses, affecting macrophage polarization, T cell differentiation, and cytokine production. Its efficacy has been observed in numerous disease models, including joint disorders, digestive and metabolic conditions, hepatic diseases, neurological disorders, and respiratory ailments. The potential therapeutic applications of α-mangostin as an anti-inflammatory agent warrant further investigation through preclinical and clinical studies to validate its efficacy and safety. Full article

Several plant-associated microbes have the capability of ameliorating the adverse effects of salinity stress in plants. Such microbes produce metabolites, including proline, glycine betaine, and secondary compounds, like melatonin, traumatic acid, and β-estradiol, which have been found to have a role in reducing salinity-induced damage in plant cells. While the effects of these metabolites have been studied, their application-related aspects remain underexplored. In this study, we investigated the salinity-stress-alleviating potential of metabolites derived from the endophytic bacterium Bacillus safensis BTL5. The microbial metabolites were extracted using the hexane–chloroform fraction method and identified through LC-HRMS analysis. Four metabolites (traumatic acid, β-estradiol, arbutin, and α-mangostin), along with a fifth compound, melatonin, were initially screened for their salinity alleviation potential. Subsequently, two metabolites, i.e., arbutin and β-estradiol, were evaluated for their impact on growth parameters and enzymatic antioxidant activities under 200 mM salt stress. The results revealed that arbutin and β-estradiol significantly improved plant growth, chlorophyll content, and enzymatic activities while reducing oxidative damage. The dose-dependent effects highlighted optimal concentrations for maximum efficacy from these compounds under elevated salinity. This study signifies the potential of microbial metabolites in enhancing crop resilience to salinity, highlighting their role in sustainable agriculture. The outcomes of this study provide a baseline for the applied use of such microbial metabolites under field conditions. Full article

Non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations have brought great challenges to the medical treatment in the world. Current treatment strategies, such as EGFR tyrosine kinase inhibitors (TKIs), have reached certain achievements, however, patients inevitably experienced resistance after undergoing a period of treatment with these drugs. Hence, more novel therapy strategies need to be urgently developed. Natural compounds have become popular topics in drug development. α-Mangostin, which is derived from mangosteen, possesses multiple biological properties, yet the antitumor mechanism against NSCLC has not been further elucidated. In this study, an MTT assay, Western blotting, a colony formation assay, and flow cytometry were performed to detect the antitumor activity of α-Mangostin on NSCLC cell NCI-H1975. Molecular docking and molecular dynamics simulations were performed to analyze the interactions between α-Mangostin and the core target proteins. The results indicated that α-Mangostin exerts its antitumor activity by inhibiting cell proliferation and migration, reducing cell cycle arrest, promoting cell apoptosis, and regulating the phosphorylation expression levels of EGFR and signal transducer and activator of transcription 3 (STAT3). Moreover, the results of the molecular simulation study revealed the potential binding mode of α-Mangostin to EGFR and STAT3. In summary, we characterized that α-Mangostin may be used as a potent pro-drug against NSCLC via the EGFR/STAT3 pathway. Full article

Background/Objectives: Fructose-driven metabolic disorders, such as obesity, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes, are significant global health challenges. Ketohexokinase C (KHK-C), a key enzyme in fructose metabolism, is a promising therapeutic target. α-Mangostin, a naturally occurring prenylated xanthone, has been identified as an effective KHK-C inhibitor, prompting exploration of its analogs for enhanced efficacy. This study aimed to identify α-Mangostin analogs with improved inhibitory properties against KHK-C to address these disorders. Methods: A library of 1383 analogs was compiled from chemical databases and the literature. Molecular docking, binding free energy calculations, pharmacokinetic assessments, molecular dynamics simulations, and quantum mechani–cal analyses were used to screen and evaluate the compounds. α-Mangostin’s binding affinity (37.34 kcal/mol) served as the benchmark. Results: Sixteen analogs demonstrated binding affinities superior to α-Mangostin (from −45.51 to −61.3 kcal/mol), LY-3522348 (−45.36 kcal/mol), and reported marine-derived inhibitors (from −22.74 to −51.83 kcal/mol). Hits 7, 8, 9, 13, and 15 not only surpassed these benchmarks in binding affinity, but also exhibited superior pharmacokinetic properties compared to α-Mangostin, LY-3522348, and marine-derived inhibitors, indicating strong in vivo potential. Among these, hit 8 emerged as the best performer, achieving a binding free energy of −61.30 kcal/mol, 100% predicted oral absorption, enhanced metabolic stability, and stable molecular dynamics. Conclusions: Hit 8 emerged as the most promising candidate due to its superior binding affinity, favorable pharmacokinetics, and stable interactions with KHK-C. These findings highlight its potential for treating fructose-driven metabolic disorders, warranting further experimental validation. Full article

Multidrug-resistant bacteria represent a significant challenge in the treatment of bacterial infections, often leading to therapeutic failures. This issue underlines the need to develop strategies that improve the efficacy of conventional antibiotic therapies. In this study, we aimed to assess whether a plant-derived compound, α-mangostin, and photodynamic therapy (PDT) could enhance the antibacterial activity of ciprofloxacin against uropathogenic strains of Escherichia coli and Staphylococcus aureus. Using nanopore sequencing technology, we confirmed that the clinical strains tested were classified as multidrug-resistant. Digital holotomography (DHT) was used to examine α-mangostin-induced changes in the bacterial cells’ penetration by a photosensitizer. A scanning confocal fluorescence microscope was used to visualize photosensitizer penetration into bacterial cells and validate DHT results. A synergistic effect between α-mangostin and ciprofloxacin was observed exclusively in S. aureus strains, while no enhancement of ciprofloxacin’s antibacterial activity was detected in E. coli strains when combined with α-mangostin. Notably, photodynamic therapy significantly potentiated the antibacterial effects of ciprofloxacin and its combination with α-mangostin compared to untreated controls. In addition, morphological changes were observed in bacterial cells exposed to these antimicrobials. In conclusion, our findings suggest that α-mangostin and PDT may serve as valuable adjuncts to ciprofloxacin, improving the eradication of uropathogens. Full article

Background: Alpha mangostin (AM) has demonstrated significant potential as an anticancer agent, owing to its potent bioactivity. However, its clinical application is limited by poor solubility, which hampers its bioavailability and effectiveness. Amorphous solid dispersion (ASD) presents a promising technique to enhance the solubility and stability of AM. Molecular dynamics simulation offers a rapid, efficient, and precise method to evaluate and optimize ASD formulations before production. Aim of Study: In this study, we conducted molecular dynamics simulations to explore the ASD development of AM with poloxamer and pullulan. Result: Our results revealed that AM–poloxamer complexes exhibit superior interaction characteristics compared to AM–pullulan, with a 1:5 ratio of AM to poloxamer and a cooling rate of 1 °C/ns demonstrating the most favorable outcomes. This combination showed enhanced hydrogen bonding, a more compact molecular structure, and higher stability, making it the optimal choice for ASD formulation. Conclusion: The integration of molecular dynamics simulation into ASD development significantly accelerates the formulation process and provides critical insights into achieving a stable and effective AM dispersion. The AM–poloxamer complex, particularly at a 1:5 ratio with a 1 °C/ns cooling rate, offers the best potential for improving AM solubility and therapeutic efficacy. Full article

α-Mangostin, a xanthone derivative extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.), has garnered significant attention for its potential as a natural anti-cancer agent. This review provides a comprehensive analysis of the current literature on the anti-cancer properties of α-mangostin across various cancer types. Through an extensive analysis of in vitro and in vivo studies, this review elucidates the multifaceted mechanisms underlying α-mangostin’s cytotoxicity, apoptosis induction through both intrinsic and extrinsic pathways, and modulation of key cellular processes implicated in cancer progression in a diverse array of cancer cells. It causes mitochondrial dysfunction, activates caspases, and regulates autophagy, endoplasmic reticulum stress, and oxidative stress, enhancing its anti-cancer efficacy. Moreover, α-mangostin exhibits synergistic effects with conventional chemotherapeutic agents, suggesting its utility in combination therapies. The ability of α-mangostin to inhibit cell proliferation, modulate cell cycle progression, and induce apoptosis is linked to its effects on key signaling pathways, including Akt, NF-κB, and p53. Preclinical studies highlight the therapeutic potential and safety profile of α-mangostin, demonstrating significant tumor growth inhibition without adverse effects on normal cells. In summary, understanding the molecular targets and mechanisms of action of α-mangostin is crucial for its development as a novel chemotherapeutic agent, and future clinical investigations are warranted to explore its clinical utility and efficacy in cancer prevention and therapy. Full article

The epithelial-to-mesenchymal transition (EMT) plays a key role in the pathogenesis of kidney fibrosis, and kidney fibrosis is associated with an adverse renal prognosis. Beta-mangostin (β-Mag) is a xanthone derivative obtained from mangosteens that is involved in the generation of antifibrotic and anti-oxidation effects. The purpose of this study was to examine the effects of β-Mag on renal tubulointerstitial fibrosis both in vivo and in vitro and the corresponding mechanisms involved. As shown through an in vivo study conducted on a unilateral ureteral obstruction mouse model, oral β-Mag administration, in a dose-dependent manner, caused a lesser degree of tubulointerstitial damage, diminished collagen I fiber deposition, and the depressed expression of fibrotic markers (collagen I, α-SMA) and EMT markers (N-cadherin, Vimentin, Snail, and Slug) in the UUO kidney tissues. The in vitro part of this research revealed that β-Mag, when co-treated with transforming growth factor-β1 (TGF-β1), decreased cell motility and downregulated the EMT (in relation to Vimentin, Snail, and N-cadherin) and phosphoryl-JNK1/2/Smad2/Smad3 expression. Furthermore, β-Mag co-treated with SB (Smad2/3 kinase inhibitor) or SP600125 (JNK kinase inhibitor) significantly inhibited the TGF-β1-associated downstream phosphorylation and activation of JNK1/2-mediated Smad2 targeting the Snail/Vimentin axis. To conclude, β-Mag protects against EMT and kidney fibrotic processes by mediating the TGF-β1/JNK/Smad2 targeting Snail-mediated Vimentin expression and may have therapeutic implications for renal tubulointerstitial fibrosis. Full article