α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood glucose level by delaying the digestion of carbohydrates and diminishing the absorption of monosaccharides. In the process of our endeavor in mining AGS inhibitors from natural sources, the culture broth of two mangrove-derived actinomycetes Streptomyces sp. WHUA03267 and Streptomyces sp. WHUA03072 exhibited an apparent inhibitory activity against AGS. A subsequent chemical investigation into the two extracts furnished 28 secondary metabolites that were identified by spectroscopic methods as two previously undescribed linear polyketides 1–2, four benzenoid ansamycins 3–6, fourteen cyclodipeptides 7–18, one prenylated indole derivative 19, two fusicoccane-type diterpenoids 20–21, two hydroxamate siderophore 22–23, and five others 24–28. Among all of the isolates, 11 and 24 were obtained from actinomycetes for the first time, while 20–21 had never been reported to occur in a marine-derived microorganism previously. In the in vitro AGS inhibitory assay, compounds 3, 8, 9, 11, 14, 16, and 17 exhibited potent to moderate activity with IC₅₀ values ranging from 35.76 ± 0.40 to 164.5 ± 15.5 μM, as compared with acarbose (IC₅₀ = 422.3 ± 8.4 μM). The AGS inhibitory activity of 3, 9, 14, 16, and 17 was reported for the first time. In particular, autolytimycin (3) represented the first ansamycin derivative reported to possess the AGS inhibitory activity. Kinetics analysis and molecular docking were performed to determine the inhibition types and binding modes of these inhibitors, respectively. In the MTT assay, 3, 8, 9, 11, 14, 16, and 17 exhibited no apparent cytotoxicity to the human normal hepatocyte (LO2) cells, suggesting satisfactory safety of these AGS inhibitors.

α-Mangostin (α-M) is a natural xanthone from the pericarp of fruit Garcinia mangostana and possesses versatile biological activities. α-M has a therapeutic potential to treat Alzheimer’s disease (AD) because of its anti-inflammatory, antioxidative, and neuroprotective activities. However, the use of α-M for AD treatment is limited due to its cytotoxic activities and relatively low potency. Modifications of its chemical structure were needed to reduce its cytotoxicity and improve its therapeutic potential against AD. For this purpose, 16 α-M carbamate derivatives were synthesized. An animal model of AD was established, and the effects of AMG-1 on the spatial learning ability and memory ability were evaluated using behavioral tests. The effect on neuropathology was tested by histopathological evaluation, Nissl staining, and silver staining. Computational systems pharmacology analysis using the chemogenomics knowledgebase was applied for network studies. Compound-target, target-pathway, and target-disease networks were constructed, integrating both in silico analysis and reported experimental data. The results show that AMG-1 can demonstrate its therapeutic effects in a one-molecule, multiple-targets manner to remarkably ameliorate neurological changes and reverse behavioral deficits in AD model rats. The improved cognitive function and alleviated neuronal injury can be observed. The ability of AMG-1 to scavenge β-amyloid in the hippocampus was validated in AD model rats.

Previous studies have been reported that the fruit body of wild Phellinus baumii alleviates diabetes, and antioxidants are beneficial to diabetes by protecting the β-cell from damage due to oxidative stress. Large-scale cultivation of P. baumii fruit body has been successful in the past decade. This paper aimed to investigate whether the fruit body of the cultivated P. baumii has the same analogical effects as the wild. The cultivated P. baumii fruit body was extracted by 80% of ethanol extracts, and different fractions were obtained with the successive use of petroleum ether, ethyl acetate (EtOAc), n-butanol (n-BuOH), and water, which yielded 15.98 ± 1.56, 1.74 ± 0.34, 3.31 ± 0.41, 4.12 ± 0.37, and 1.38 ± 0.26% extract recovery, respectively. Results show that the EtOAc fraction exhibits the highest inhibitory effect on α-glucosidase activity (IC₅₀ = 49.05 ± 3.14 μg mL^–1), which is an order of magnitude higher than the positive control (acarbose, IC₅₀ = 645.73 ± 7.86 μg mL^–1). It was mainly composed of phenolic compounds with a purity of 79.45% and characterized by liquid chromatography-mass spectrometry as osmudacetone, hispidin, davallialactone, 2,5-bis(4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)cyclohexa-2,5-diene-1,4-dione, hypholomin B, and inoscavin A. Furthermore, the EtOAc fraction increased the glucose consumption of insulin-resistant HepG2 cells at a concentration range of 25–100 μg mL^–1. The EtOAc fraction also demonstrated antioxidant activities by scavenging 1,1-diphenyl-2-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt, and hydroxyl radicals. In conclusion, the EtOAc fraction of the cultivated P. baumii fruit body exerted effective antidiabetic effects, possibly due to the high content of selective phenolic compounds. Hence, the cultivated fruit body of P. baumii can be a sustainable resource for treating diabetes, and our work also shed some light on its future utilization.

Introduction: Garcinia mangostana L. a widely used tropical fruit, has been historically valued as a medicinal plant. Modern pharmacological research has identified several compounds in its pericarp, such as alkaloids, flavonoids, and phenolic acids, which possess antioxidant and anticancer properties. Recent studies have shown that various medicinal and edible plant-derived nanovesicles (MEPNs) exhibit potent anti-tumor effects. However, the impact of Garcinia mangostana L.-derived exosome-like nanoparticles (GELNVs) in treating glioma remains insufficiently explored. Methods: GELNVs were isolated from the rind of Garcinia mangostana L. using an environmentally sustainable method. The chemical composition of GELNVs was systematically characterized through both qualitative and quantitative analyses via UPLC-MS/MS. Network pharmacology was utilized to identify potential anti-glioma targets, with a focus on the PI3K-Akt signaling pathway. Subsequently, in vitro experiments were conducted to assess the uptake of GELNVs by glioma cells and their anti-tumor effects, including apoptosis induction, cell proliferation suppression, and effects on microglial polarization. Results: Using a sustainable extraction method, GELNVs were successfully isolated and chemically characterized by UPLC-MS/MS. Network pharmacology and molecular docking identified key anti-glioma targets, particularly AKT1 within the PI3K-Akt signaling pathway. In vitro experiments demonstrated that GELNVs were effectively internalized by GL261 glioma and BV2 microglial cells, showing significant anti-glioma activity by inducing apoptosis and inhibiting cell proliferation. Additionally, GELNVs promoted the activation of M1-type microglia while inhibiting M2 polarization induced by IL-4 and glioma cells. This was evidenced by the upregulation of inflammatory mediators, including iNOS, TNF-α, IL-6, and IL-1β at the mRNA level. Conclusion: Our findings demonstrate that GELNVs represent a potential therapeutic strategy for glioma by inducing apoptosis in tumor cells and inhibiting their proliferation through suppression of the PI3K-Akt signaling pathway. Furthermore, GELNVs show promise in modulating microglial polarization, further highlighting their potential as a glioma treatment.