Search Results (115)

Mangosteen peel (Garcinia mangostana L.) is widely recognized as a rich source of xanthone derivatives, particularly α-mangostin, which exhibits diverse pharmacological activities and is increasingly utilized in herbal medicines and nutraceutical formulations. This study aimed to develop an integrated chemical fingerprinting approach combining chromatographic quantification and spectroscopic profiling to discriminate and evaluate the quality of GMP (Garcinia mangostana peel) extract collected from different Indonesian provinces. Ethanolic extracts of GMP, originating from ten distinct geographical regions, were subjected to high-performance liquid chromatography (HPLC) for the quantitative determination of α-mangostin. Fourier transform infrared (FTIR) spectroscopy was employed to generate characteristic fingerprint profiles and assess the functional group patterns present in the extracts. The correlation between chromatographic data and spectroscopic signatures was evaluated to elucidate regional variability. The geographical origin of the GMP extract significantly influences its phytochemical composition and α-mangostin content. The combined FTIR–HPLC approach offers a robust and practical framework for extract differentiation, preliminary estimation of α-mangostin content, and quality assurance of mangosteen-derived raw materials intended for 6a-standardized herbal and nutraceutical products. Full article

Background/Objectives: α-Mangostin, a natural product from Garcinia mangostana L, presents very strong antibacterial activity in plant flavonoids against Staphylococcus aureus. Recently, it was reported that the quinone pool is a key target of α-mangostin against Gram-positive bacteria. Here, the detail centering this action mechanism of α-mangostin killing S. aureus was further explored. Methods: The interactions between α-mangostin and type II NADH:quinone oxidoreductase (NDH-2), a key enzyme in the respiratory chain, were explored through the enzyme kinetic experiments, fluorescence analyses, and molecular simulation. Simultaneously, the effect of α-mangostin on membrane potential was also investigated as a possible non-enzymatic mechanism. Results: it was found that α-mangostin mainly competes the menaquinone-binding sites of NDH-2 with menaquinone, and the half-maximal inhibitory concentration (IC₅₀) of α-mangostin on NDH-2 is 4.95 μM. Fluorescence analyses indicated that α-mangostin can spontaneously bind to NDH-2 to form an α-mangostin–NDH-2 complex. Subsequently, molecular simulation further showed that α-mangostin can dock to the menaquinone-binding sites of NDH-2. In addition, non-enzymatic mechanism showed that α-mangostin can cause membrane potential depolarization and disrupt the proton motive force balance, thereby promoting the cell-membrane destruction of S. aureus. Conclusions: α-Mangostin can mainly interact with the amino acid residues at the menaquinone-binding pocket of NDH-2 to block the electron transfer at the quinone pool in the respiratory chain of S. aureus, which will hinder the energy supply and act synergistically with cell membrane damage, ultimately leading to the death of S. aureus. Simultaneously, it once again proves that the quinone pool is a key target of plant flavonoids against Gram-positive bacteria. Full article

Jacareubin (2), nujiangexanthone A, and α-mangostin display the highest anti-allergic effects among the active xantones through still not well-known mechanisms. This study investigates the SAR of jacareubin, its precursor xanthone V (1) and their peracetylated (1a and 2a), permethylated (1b and 2b) derivatives and their anti-allergic and anti-inflammatory effects. To characterize the inhibitory effect of jacareubin, 2a and 2b on the anaphylactic reaction, we first utilized in vitro models of bone marrow derived mast cells (BMMCs), determining their capacity of inhibiting the IgE/Antigen-induced degranulation, myeloperoxidase (MPO), and xanthine oxidase (XO) activation. Also, we utilized in vivo models of passive cutaneous anaphylaxis (PCA) and TPA-induced ear edema. In vitro tests showed that the compound 2b was more effective than jacareubin in the inhibition of BMMCs degranulation. Besides, in vivo models of PCA revealed that the fourth cyclized ring of jacareubin is the critical structural element for anti-allergic efficacy, as compound 1 was less effective. Additionally, hydroxyl groups were found to be essential for inhibiting MPO. Jacareubin was the only tested xanthone that directly inhibited XO, a result supported by molecular docking. Overall, jacareubin represents a promising multi-target scaffold that could be used for developing new treatments for inflammatory and allergic diseases. Full article

This study investigated the effects of dietary supplementation with α-mangostin (α-Ma), a bioactive xanthone derived from mangosteen pericarp, on production performance and egg quality in late-phase laying hens. The experiment was conducted using a completely randomized design. In total, 576 healthy 51-week-old Beinong No. 2 laying hens were randomly assigned to 4 dietary treatments (n = 12): a basal diet (CON) or the basal diet supplemented with 80, 120, or 160 mg/kg α-Ma. The experiment lasted for 4 weeks, after which production performance, egg quality, serum biochemical and antioxidant parameters, inflammatory markers, and uterine gene expression were evaluated. Dietary supplementation with α-mangostin, particularly at 120 mg/kg, significantly improved feed efficiency (p < 0.05), as evidenced by a reduced feed-to-egg ratio from week 2 onward, without affecting average daily feed intake or egg production rate. After 4 weeks, hens receiving 120 mg/kg α-Ma exhibited significantly greater egg weight and eggshell strength (p < 0.05). Serum and hepatic antioxidant capacities were significantly enhanced, with increased glutathione peroxidase and catalase activities, elevated total antioxidant capacity, and decreased malondialdehyde levels (p < 0.05). Moreover, α-Ma at 120 mg/kg specifically lowered the concentration of the pro-inflammatory cytokine interleukin-1β in both serum and uterine tissue (p < 0.05). At the molecular level, this dosage significantly upregulated uterine genes essential for eggshell formation (p < 0.05), including calcium transporters (TRPV6, ATP2B2), the matrix protein gene OC-116, and other key genes (LYZ, CA2, SLC4A9, and ATP6V0D2). In conclusion, dietary supplementation with 120 mg/kg α-Ma effectively enhances feed efficiency, strengthens antioxidant and anti-inflammatory defenses, and upregulates uterine genes involved in biomineralization, thereby improving eggshell quality in aging laying hens. These findings support α-Ma as a promising plant-based feed additive for maintaining productivity and egg quality in antibiotic-free layer production systems. Full article

Background: Prostate cancer remains a leading cause of male cancer-related mortality, largely driven by the dysregulated activation of the androgen receptor (AR) signaling pathway. The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the discovery of innovative therapeutic approaches. This systematic review aims to consolidate contemporary evidence regarding natural products as bioactive alternatives capable of targeting the AR signaling axis. Methods: Adhering to PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and ScienceDirect databases. The review identified and qualitatively analyzed 15 original research studies that investigated the efficacy and mechanisms of various natural compounds in modulating AR signaling. Results: The analysis reveals that natural products deactivate the AR signaling axis through diverse mechanisms. Neoisoliquiritin and α-terthienyl were found to suppress AR expression, activity, and nuclear translocation. Notably, α-mangostin facilitates the degradation of the AR-V7 splice variant, a key driver of treatment resistance. Manzamine A inhibits AR biosynthesis by targeting the transcription factor E2F8. Furthermore, alternative pathways are modulated through 5-α-reductase inhibition (Annona muricata compounds) and the activation of the non-classical membrane receptor ZIP9 by (-)-epicatechin to induce apoptosis. Conclusions: The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the exploration of innovative therapeutic approaches. This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation. Full article

Background/Objectives: Xanthones from the tropical fruit mangosteen (Garcinia mangostana) have been reported to modulate oxidative stress and inflammatory responses. This work explored the anti-inflammatory potential of mangosteen in the form of tinctures. Methods: Tinctures were prepared from the pericarp and leaves, characterized for their major constituents, and evaluated for their in vitro, anti-inflammatory and antioxidant potential. Results: HPLC analysis revealed eight major isoprenylated xanthones whose concentrations increased with an increasing alcohol percentage. α-Mangostin and γ-mangostin, two major xanthones present in the tinctures, were stable for 12 weeks at room and elevated (40 °C) temperatures, indicating stability of the tincture. In vitro luciferase reporter assays using HepG2-ARE revealed an alcohol concentration-dependent activation of Nrf2 by pericarp and leaf tinctures. The tinctures inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and reactive oxygen species (ROS) in RAW264.7 cells. Garcinone C (GarC) and garcinone D (GarD) caused significant inhibition of LPS-induced NO production and iNOS expression. GarC and GarD also induced nuclear translocation of Nrf2 and upregulated heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione S-transferase Pi 1 (GSTP1) in RAW264.7 cells. Conclusions: Taken together, mangosteen tinctures are a significant source of prenylated xanthones with anti-inflammatory and antioxidant potential. Full article

Mangosteen (Garcinia mangostana L.) has long been used in traditional Southeast Asian medicine to treat inflammatory-related conditions. In this study, three new compounds, including garcimangone A (1), garcimangone B (2), and the S-form of garcimangone C (3), and 18 known compounds were isolated and investigated for their anti-inflammatory properties and effects on M1- and M2-associated markers. Among the isolated components, γ-mangostin (5), garcinone D (6), morusignin J (15), and fuscaxanthone C (16) showed the most potent NO-inhibitory effects in LPS-stimulated RAW264.7 cells. SAR study revealed that chromeno moiety at C-3,4, oxygen substituents at C-1,3,6,7, and isoprenyl groups at C-2,8 are key structural features that promoted anti-inflammatory activity. Cytokine analysis results indicated that morusignin J (15) and fuscaxanthone C (16) could modulate the production of pro-inflammatory cytokines, such as TNF-α and IL-6, while modulating the anti-inflammatory cytokine IL-10. Western blot results demonstrated that morusignin J (15) modulated the inflammatory response through NF-κB and MAPK signaling and increased the expression of M2-associated markers KLF4 and arginase-1 in LPS-induced RAW264.7 macrophages. Further molecular docking analysis confirmed the high binding affinity of morusignin J (15) with key iNOS residues, such as Gln257, Pro344, Glu371, and Hem901, and the in silico prediction supported its potent oral bioavailability and drug-likeness. These in vitro and in silico findings highlight that pericarps of G. mangostana possess potential as promising natural sources for functional extracts and bioactive constituents for the development of antioxidative and anti-inflammatory candidates, and warrant further in vivo investigation in the future. Full article

Phosphodiesterase 4 (PDE4) is a key enzyme responsible for the hydrolysis of cyclic adenosine monophosphate (cAMP), thereby regulating essential signaling pathways involved in inflammation and immune modulation. Structural studies have demonstrated a high degree of conservation within the catalytic domains of PDE4 isoforms, accompanied by subtle conformational variations that underlie their selectivity and tissue-specific distribution. Elucidating these structural features has been instrumental in guiding the rational design of PDE4 inhibitors. Although synthetic PDE4 inhibitors such as roflumilast and apremilast exhibit significant therapeutic efficacy, their clinical application is often limited by dose-dependent adverse effects. These effects primarily arise from insufficient isoform selectivity, as current inhibitors tend to target multiple PDE4 subtypes indiscriminately, resulting in off-target pharmacological actions and reduced tolerability. In contrast, natural products—including flavonoids, terpenoids, and related polyphenolic compounds such as curcumin, α-mangostin, and their derivatives—have emerged as promising molecular scaffolds. Their lower toxicity, favorable biocompatibility, and structural diversity enable fine-tuning of potency and selectivity through rational modification. Integrating structural insights derived from crystallographic and computational studies with the optimization of natural compounds offers a sustainable and effective strategy for the development of safer, isoform-selective PDE4-targeted therapies. Full article

Acute kidney injury (AKI) is characterized by rapid loss of renal function due to oxidative stress, inflammation, and apoptosis, with limited targeted therapies. Alpha-mangostin (AM), a natural compound from Garcinia mangostana, exhibits antioxidant and anti-inflammatory properties in preclinical studies, but its efficacy in AKI has not been reviewed. This systematic review and meta-analysis, registered on the Open Science Framework and adhering to PRISMA guidelines, analyzed in vivo and in vitro studies on AM’s effects in AKI models through searches of PubMed, Scopus, Embase, and Web of Science. Primary outcomes included serum creatinine and cell viability, while secondary outcomes encompassed oxidative stress markers (malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS)), inflammatory cytokines, apoptosis indicators, and histopathology. Data were extracted independently and assessed using the Toxicological Data Reliability Assessment Tool (ToxRTool). AM significantly reduced serum creatinine (mean difference (MD) = −0.67 mg/dL; 95% confidence interval (CI): −1.28 to −0.06; p = 0.03) and improved cell viability (MD = 28.26%; 95% CI: 17.25 to 39.26; p < 0.0001). It markedly decreased MDA and ROS, increased GSH, and enhanced antioxidant enzymes (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD)). In vivo, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were lowered, and histopathology showed reduced tubular necrosis and structural damage. Subgroup analyses indicated dose- and model-dependent effects, with lower doses often yielding greater benefits. Sensitivity analyses confirmed robustness despite heterogeneity. Preclinical evidence supports AM’s nephroprotective potential and underscores the need for dose optimization, mechanistic validation, and clinical translation. Full article

Background/Objective: Dendritic cells (DCs) act as sentinels bridging innate and adaptive immunity, and their functions are strongly influenced by dietary and environmental factors. Phytochemicals such as α-Mangostin (A phytochemical, a xanthone derivative from Garcinia mangostina, known for its anti-inflammatory and antioxidant properties) are widely recognized for their antioxidant and anti-inflammatory effects, but their potential to modulate antiviral pattern recognition pathways remains unclear. This study investigated whether phytochemicals activate retinoic acid–inducible gene I (RIG-I: DDX58, a cytosolic receptor recognizing viral RNA and inducing antiviral responses)–dependent signaling in human monocyte-derived dendritic cells (MoDCs) and affect downstream T cell responses. Methods: MoDCs were generated from peripheral blood and stimulated with selected phytochemicals. RIG-I pathway–related transcripts were quantified by qPCR, and protein expression was assessed by Western blotting, intracellular flow cytometry, and immunofluorescence staining. Functional outcomes were evaluated by co-culturing MoDCs with T cells, followed by phenotypic analysis via flow cytometry and measurement of IFN-γ production by ELISA. Results: α-Mangostin stimulation increased RIG-I (DDX58) mRNA levels in MoDCs and induced time-dependent changes in intracellular protein expression. In co-culture, α-Mangostin–treated MoDCs tended to increase the proportion of OX40⁺ 4-1BB⁺ CD4⁺ T cells, accompanied by a significant elevation of IFN-γ levels in supernatants. Experiments with CpG-ODN (synthetic oligodeoxynucleotides mimicking bacterial DNA that activate TLR9) suggested context-dependent crosstalk between the TLR9 and RIG-I signaling axes. Conclusions: Phytochemicals, exemplified by α-Mangostin, prime antiviral responses in human DCs through upregulation of RIG-I and promote Th1-dependent immune responses. These findings suggest that phytochemicals may represent promising nutritional strategies to enhance antiviral immunity while mitigating excessive inflammation under infectious conditions. Full article

Narrowband ultraviolet B (NB-UVB) phototherapy, used for treating skin diseases, can induce skin aging, cause inflammation, and reduce cell viability due to reactive oxygen species (ROS) generation. To mitigate these adverse effects, a multi-target polyherbal mixture for topical application was developed. This study investigated the effects of a polyherbal combination comprising Zingiber officinale (ZH), Garcinia mangostana (GE), and Centella asiatica (CAEw) extracts against NB-UVB-induced damage in HaCaT cells. Extracts were prepared to obtain high levels of specific biomarkers (compound D, α-mangostin, and asiaticoside). They were characterized for total phenolic and total flavonoid content, antioxidant properties, and anti-collagenase activity. The ability to enhance HaCaT cell viability after NB-UVB exposure was evaluated to determine the optimal polyherbal mixture ratios. Both the individual extracts and polyherbal formulations significantly improved irradiated HaCaT cell viability. Subsequent treatment with 100 µg/mL of the polyherbal mixture ZH:GE:CAEw (1:1:1) increased cell viability from 62.3% to 80.1% and decreased intracellular ROS (63.6%) without reducing cell apoptosis. It also downregulated the gene expression of cyclooxygenase-2, inducible nitric oxide synthase, matrix metalloproteinase-1 (MMP-1), and MMP-9, allowing their expression to reach the normal level of the non-irradiated cells. In conclusion, the polyherbal mixture effectively attenuated NB-UVB-induced damage and premature aging in HaCaT keratinocytes. Full article

Curcumin (CUR), atractylodin (ATD), α-mangostin (αMG), ethyl-p-methoxycinnamate (EPMC), ligustilide (LIG), and β-eudesmol (BEU) are commonly used in Thai traditional medicine formulations. This study evaluated the cytotoxic effects of these compounds in HepG2 liver cancer cells and ReNcell VM neural progenitor cells using the resazurin assay, as well as their potential for hERG inhibition in hERG-overexpressing HEK293 cells, utilizing the automated patch-clamp technique. αMG and CUR significantly reduced HepG2 cell viability (IC₅₀ = 5.5 and 21 µM, respectively). In undifferentiated ReNcell VM cells, αMG was the most potent inhibitor of cell viability (IC₅₀ = 2.1 µM), followed by CUR (IC₅₀ = 21.1 µM), while in differentiated ReNcell VM cells, only αMG exhibited significant neurotoxicity (IC₅₀ = 6.0 µM). Other compounds showed no significant effects on these cells. ATD, BEU, LIG, and EPMC demonstrated low inhibition of hERG channels (IC₅₀ = 26.4, 33.4, 37.3, and 53 µM, respectively), while CUR and αMG displayed weak inhibitory effects (IC50 > 100 µM). αMG may have cytotoxic effects on hepatocytes and neurons at concentrations much higher than when used as medicine or food supplements. At regular clinical doses, αMG, ATD, BEU, EPMC, LIG, and CUR are unlikely to cause significant side effects. However, if these compounds are considered for drug development, their potential effects on hERG channels should be carefully assessed to avoid possible cardiotoxicity. Pharmacokinetics, both preclinical and clinical studies, are necessary to understand the relationship between the plasma concentration profile of EPMC and its potential risks for hepatotoxicity, neurotoxicity, cardiotoxicity, and drug interactions. Full article

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

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