Cryptosporidium parvum is a major cause of severe diarrheal disease, yet therapeutic options remain limited. This study integrated host-parasite transcriptomic profiling, GC-MS phytochemical profiling, computational screening, and in vitro experimental validation to evaluate anti-Cryptosporidium phytochemicals from Garcinia mangostana extract (GME). Host epithelial transcriptional responses (GSE2077) during C. parvum infection were analyzed to map infection-associated host reprogramming. A curated library of 30 identified phytochemicals was computationally docked against prioritized parasite-relevant targets: calcium-dependent protein kinase 1 (CDPK1), C. parvum 1-phosphatidylinositol 4-kinase [PI(4)K; cgd8_4500/UniProt Q5CVD3, AlphaFold model AF-Q5CVD3-F1], and cleavage and polyadenylation specificity factor 3 (CPSF3). The anti-Cryptosporidium efficacy of GME was subsequently evaluated in vitro by assessing C. parvum oocyst count and viability over 48 h. Transcriptomic analysis suggested a biphasic pattern of host reprogramming involving inflammatory signaling, sterol metabolism, Wnt signaling, and cell-cycle regulation. GC-MS analysis identified sterols and fatty acid derivatives, including stigmasterol, campesterol, and ethyl iso-allocholate. Molecular docking against the C. parvum PI(4)K model predicted campesterol (NP028) and ethyl iso-allocholate (NP029) as leading PI(4)K-oriented candidates, with mean affinities of - 7.97 ± 0.59 and - 7.72 ± 0.61 kcal/mol, respectively, while NP008 showed a predicted multi-target interaction profile, particularly against CPSF3. In vitro assays showed a significant, concentration- and time-dependent reduction in C. parvum oocyst viability, with an LC50 of 830 µg/mL after 48 h. Overall, the parasite-specific docking and oocysticidal data support GME phytochemicals as promising anti-Cryptosporidium candidates and generate testable hypotheses for CDPK1, PI(4)K, or CPSF3 involvement, while direct intracellular infection assays and recombinant enzyme inhibition studies are required to confirm target engagement.

Currently approved androgen receptor (AR) inhibitors for prostate cancer (PCa) target the ligand-binding domain (LBD) of the AR. These compounds cannot inhibit androgen receptor splice variant 7 (AR-V7), a truncated form of AR that is constitutively active in advanced PCa. Our previous studies demonstrated that α-mangostin, a xanthone derived from the fruit of Garcinia mangostana, promotes degradation of AR and AR-V7 through modulation of the chaperone binding immunoglobulin protein (BiP) in vitro and in vivo. Mangosteen contains more than 80 xanthones, and in this study we investigated whether additional xanthones can induce AR and AR-V7 degradation through direct BiP- engagement. Four fractions (F1-F4) were prepared from mangosteen extract, and their interactions with BiP were determined using surface plasmon resonance (SPR). Among them, F3 showed the highest binding affinity for BiP. We further evaluated additional xanthones isolated from these fractions. Among these compounds, α-mangostin exhibited the strongest binding affinity. Structure-activity relationship (SAR) analysis suggested that hydroxyl groups at C3 and a methoxy group at C7 contribute to BiP engagement. Consistent with these findings, α-mangostin and gartanin promoted degradation of AR and AR-V7 in 22Rv1 AR and AR-V7 HiBiT cells. Although BiP primarily functions through ATPase activity, α-mangostin did not affect its ATPase activity. Molecular docking of α-mangostin identified potential allosteric binding sites on BiP distinct from the ATPase pocket, suggesting that it may act as an allosteric modulator. Together, these findings identify mangosteen-derived xanthones as BiP-engaging compounds capable of promoting the degradation of AR and AR-V7 in PCa cells.

Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor in adults, with current therapies failing to achieve significant clinical advancements. GDPPH1, a natural compound derived from Garcinia mangostana L., is known for its antioxidant properties; however, its anticancer effects and underlying mechanisms remain insufficiently understood. In this study, we demonstrate that GDPPH1 significantly inhibits GBM cell proliferation in a concentration-dependent manner by downregulating CDK4 and Cyclin D1 expression, inducing cell cycle arrest at G1/S checkpoint, and promoting apoptosis. Mechanistically, GDPPH1 reduces the m[6]A methylation of CDK4 and CCND1 through METTL14-YTHDF2-mediated transcript decay, resulting in decreased CDK4/CCND1 expression and subsequent decreased RB phosphorylation levels. Further studies revealed that m[6]A-METTL14-YTHDF2 axis is responsible for GDPPH1-induced downregulation of CDK4 and Cyclin D1. Additionally, the in vivo anti-GBM efficacy of GDPPH1 was confirmed using both xenograft and orthotopic intracranial mouse models. Collectively, these findings provide robust evidence supporting GDPPH1 as a promising therapeutic candidate for GBM and offer novel insights into the role of m[6]A RNA methylation in cell cycle regulation.

Diabetes mellitus, particularly type 2 diabetes mellitus, is a growing global health burden characterized by chronic hyperglycemia and insulin resistance. Alpha-mangostin (AM), a xanthone from Garcinia mangostana pericarp, exhibits antioxidant, anti-inflammatory, and metabolic regulatory properties in preclinical models. We performed a systematic review and meta-analysis of controlled in vivo studies to assess AM's anti-hyperglycemic effects. Fourteen studies (25 comparisons) in rodent models of diabetes or hyperglycemia were included. Primary outcome was blood glucose; secondary outcomes were glycated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Random-effects meta-analysis demonstrated that AM significantly reduced fasting blood glucose (mean difference (MD) = -8.75 mmol/L; 95% CI: -10.73 to -6.78; p < 0.001) and HbA1c (MD = -2.20%; 95% CI: -3.07 to -1.32; p < 0.001). AM did not significantly alter circulating insulin (Hedges' g = 0.43; 95% CI: -0.62 to 1.49; p = 0.42) but improved insulin resistance as measured by HOMA-IR (MD = -0.90; 95% CI: -1.68 to -0.12; p = 0.02). Subgroup, sensitivity, and risk-of-bias analyses supported the robustness of the glucose-lowering association, although substantial between-study heterogeneity was present. Overall, this study provides preclinical evidence that AM exerts significant antihyperglycemic and insulin-sensitizing effects, supporting its potential as a multitarget metabolic modulator. Further standardized and mechanistically informed studies are warranted to facilitate translational progression.

Obesity has emerged as a substantial socioeconomic challenge, imposing considerable burdens on healthcare systems worldwide, thereby necessitating continued efforts to identify effective and sustainable obesity control strategies. Garcinia mangostana (GM) is rich in phenolics with strong antioxidant and anti-inflammatory activities, yet its potential to mitigate obesity and related comorbidities, including hyperglycemia and male reproductive dysfunction, remains unexplored. This present study investigates the hypolipidemic, hypoglycemic, and fertility-enhancing effects of a polyphenol-rich GM pericarp extract in vivo. In this study, male Sprague-Dawley rats except those in the normal control group, were fed with HFD for four weeks to induce obesity prior to streptozotocin (STZ) administration for the induction of type 2 diabetes mellitus. The HFD-STZ-induced obese-diabetic rats were supplemented with orlistat, metformin and GM pericarp extract (150, 300, and 600 mg/kg body weight), respectively. Results showed that GM supplementation for 7 weeks significantly (p < 0.05) reduced Lee's obesity index and improved glycemic control, with blood glucose levels decreasing by 33-50% compared to negative control. The supplementation significantly increased HDL level, ameliorated dyslipidemia, enhanced insulin sensitivity and reproduction health, as evidenced by improved lipid and hormonal profiles and increased sperm quality. Furthermore, the histopathological abnormalities of testis and kidney tissues caused by obesity and diabetes were notably alleviated. Creatinine levels remained within the physiological range upon treatment, suggesting no renal toxicity. GM supplementation demonstrated ameliorative effects against obesity and its associated comorbidities, including diabetes, and impaired male reproductive function. This effect could possibly be mediated by bioactive metabolites with antioxidant and anti-inflammatory properties, suggesting its prospective role in nutraceutical development.

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.

Multiple mycotoxins in feed threaten animal health and food safety, demanding sustainable mitigation strategies. This study evaluated acid-modified mangosteen peel (AMP), an agricultural by-product, as a potential multi-mycotoxin adsorbent. Physicochemical characterization using scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area analysis, and Fourier transform infrared spectroscopy (FTIR) analyses demonstrated that acid modification increased surface area (1.9 to 9.03 m2/g), pore volume (0.005 to 0.027 cm3/g), and surface negativity, indicating enhanced adsorption properties. In vitro binding experiments assessed adsorption of aflatoxin B1 (AFB1), zearalenone (ZEA), ochratoxin A (OTA), T-2 toxin, deoxynivalenol (DON) and fumonisin B1 (FB1) under different pH conditions. AMP exhibited high adsorption efficiencies for AFB1, ZEA, OTA, and T-2 toxin, particularly at pH 3, whereas DON and FB1 showed limited binding. Adsorption behavior was dose-dependent and best described by Langmuir and Freundlich isotherm models. Simulated gastrointestinal digestion indicated stable binding of AFB1 and ZEA under gastric conditions, with partial release of some toxins at neutral pH. Cytotoxicity assessment in porcine intestinal epithelial cells (IPEC J2) showed no apparent cytotoxic effects at 0.25-1 mg/mL. Therefore, AMP demonstrated improved multi-mycotoxin adsorption compared to the untreated material and showed no apparent cytotoxic effects in vitro within the tested concentration range, indicating its potential as a promising feed additive candidate.

Garcinia mangostana L. (mangosteen), a tropical fruit native to Southeast Asia, has garnered significant attention for its xanthone-rich pericarp, traditionally discarded as waste but now recognized for its potent bioactive potential. This review offers a critical, integrative synthesis of the phytochemistry, pharmacology, and food-science relevance of mangosteen, with a focus on sustainable valorization pathways. Unlike previous reviews focused narrowly on either phytochemistry or pharmacological activity, this work bridges therapeutic mechanisms with functional food innovation and green extraction science. Special emphasis is placed on green extraction technologies, such as microwave-assisted (yielding 121 mg/g α-mangostin), supercritical CO2 (>90% xanthone recovery), and enzymatic methods which offer eco-efficient routes for pericarp utilization. Mechanistic insights have been drawn from its pharmacological activities, including antioxidant and anti-inflammatory effects as well as antidiabetic and neuroprotective effects. Further, the review evaluates cutting-edge delivery platforms, including exosome-like nanoparticles (GELNVs), nanoemulsions, and solid lipid carriers, which improve solubility and bioavailability (2-5-fold) for both pharmaceutical and functional food formulations. Beyond therapeutics, the review explores food-relevant applications, such as oxidative stabilization in lipids, microbial shelf-life extension (5-7 days), and anti-inflammatory effects in human trials. Mangosteen could be a promising model for circular innovation, potentially transforming agro-industrial waste into high-value functional ingredients for sustainable health solutions.

This study systematically investigated the antibacterial activity and underlying mechanism of garcinone D, a xanthone isolated and purified from mangosteen, against B. cereus. The results demonstrated that garcinone D exhibited significant inhibitory activity, with a MIC90 of 3.12 μg/mL, which is markedly lower than that of the commercial preservative ε-polylysine (MIC90 = 25 μg/mL). Furthermore, garcinone D produced a larger inhibition zone diameter. In a rice preservation model, garcinone D effectively reduced the total bacterial count. Mechanistic studies revealed that garcinone D exerts its antibacterial activity primarily by disrupting cell membrane integrity. Specifically, it increased membrane permeability, leading to the leakage of intracellular components such as nucleic acids and proteins. PI staining further confirmed the loss of membrane integrity. Additionally, garcinone D induces ROS accumulation accompanied by a significant increase in MDA content, indicating that membrane lipid peroxidation exacerbates membrane damage. RNA-seq transcriptomic analysis and KEGG pathway enrichment indicated that DEGs were significantly enriched in categories related to cell envelope and transport, particularly the ABC transporter pathway, as well as in central metabolic pathways and QS/virulence-related pathways. Subsequent experiments confirmed that garcinone D markedly reduced intracellular ATP levels and inhibited the hemolytic activity of B. cereus toxins. RT-qPCR validated the expression changes of genes related to these functions. In the 5000 mg/kg acute toxicity test, garcinone D did not cause any deaths or adverse effects on general behavior and body weight, indicating good tolerance in mice under this exposure condition and providing acute safety data for the preliminary application of garcinone D. In conclusion, garcinone D will be developed into a highly effective and safe natural antibacterial agent. Which has broad application prospects in controlling food contamination and relating foodborne diseases caused by B. cereus.

Polyphenolic compounds are widely explored for health benefits, including hypertension, but their active ingredients, molecular targets, and mechanisms remain poorly defined. We identify the xanthone Mangostin from Garcinia mangostana as a potent modulator of several potassium channels, with large-conductance K+ (BK) channels as its primary target for vasorelaxation. Mangostin-activated BK channels as α subunits alone, in complexes with vascular β1 subunits, and in reconstituted BKα/β1-Cav nanodomains. It shifted BK voltage activation to more negative potentials by antagonizing channel closure and promoting channel opening without markedly altering Ca²+ sensitivity. Docking, competition, single-channel analysis, and mutagenesis localized the binding site in the pore cavity below the SF, involving gating-critical S6 residues I308, L312, and A316, and suggest that Mangostin stays bound in closed and open states. These findings establish BK channel activation as the core molecular mechanism driving Mangostin's vascular effects and define its structural mode of action, informing nutraceutical safety assessment and BK-targeted drug design.

The study aimed to evaluate the impact of Zinc oxide nanoparticles (ZnO-NPs) on growth performance, carcass traits, meat color, antioxidant activity, and insuline-like growth factor-1 (IGF-1) gene expression in broiler chickens. This study used 200 Cobb500 broiler chicks aged two days. The observation was conducted for 5 weeks and used a completely randomized design with 4 treatments and 5 replications (10 chicks, each replicates). The treatment were: Control (basal diet); ZnO-NPs 50 (control + 50 mg Zn/kg); ZnO-NPs 75 (control + 75 mg Zn/kg); ZnO-NPs 100 (control + 100 mg Zn/kg). Performance, carcass traits, Zn content and antioxidant activity, meat color, and IGF-1 gene expression were observed. Supplementation of ZnO-NPs (d 1-14) significantly (P < 0.05) increased body weight and improved feed-to-gain ratio, whereas no effects (P > 0.05) were observed on average daily gain, average daily feed intake, or feed-to-gain ratio during days 15-35. Zinc oxide nanoparticles (ZnO-NPs) also significantly (P < 0.05) increased the hue (h*) value while reducing the lightness (L*) and redness (a*) of the breast. Supplementation enhanced Zn deposition and SOD enzyme activity, accompanied by a decrease in MDA concentration in the breast. However, ZnO-NPs did not affect (P > 0.05) carcass traits (percentage of breast, back, thigh, and drumstick meat), nor did the yellowness (b*) and chromaticity (c*) of breast meat and IGF-1 gene expression in the small intestine. Overall, the addition of ZnO-NPs at levels up to 100 mg Zn/kg in broiler chicken feed during the growth phase leads to optimal improvements in performance parameters. Mechanistically, ZnO-NPs function as redox modulators rather than direct antioxidants, eliciting dose-dependent pro-oxidant and antioxidant responses in broiler chickens. This modulatory effect contributes to enhanced antioxidant status, a tendency to support the IGF-1 gene expression profile, and a reduction in oxidative stress. Furthermore, breast meat derived from chickens supplemented with ZnO-NPs demonstrates potential as a functional food with added health benefits.

Background/Objectives: Neurodegenerative diseases like Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis (ALS) share common molecular pathways, including neuroinflammation and oxidative stress, which complicate the effectiveness of single-target treatments. Garcinia mangostana L. (mangosteen) has shown neuroprotective properties, but previous studies focused on lipophilic xanthones, which have poor bioavailability and uncertain blood-brain barrier permeability. Methods: In the current study, polar metabolites from G. mangostana peel aqueous extract (GMPE) were assessed for potential multi-target interactions via UHPLC-QTOF-MS-based metabolomics, systems pharmacology, and molecular docking analysis. Further, in silico ADMET screening and network-based analyses assessed for overlap between GMPE compounds and genes associated with neurodegeneration (AD, PD, ALS). Results: Analysis of genes linked to AD, PD, and ALS revealed 121 common molecular targets influenced by GMPE metabolites. Network and enrichment analyses indicated that the compounds derived from GMPE may be involved in common pathways related to oxidative stress, neuroinflammation, and neuronal survival. Molecular docking analyses suggest that selected metabolites are likely to exhibit moderate binding affinities to their respective protein targets. Conclusions: The results presented in this study provide evidence that GMPE may possess potential multi-target interactions within common neurodegenerative pathways. However, since the data are based on computational and predictive approaches, these results should be considered hypothesis-generating and warrant further experimental validation.