Advances in metal-organic framework-based nanozymes in ROS scavenging medicine.

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.

Structurally diverse isoquinoline alkaloids from the barks of Alangium salviifolium (L. f.) Wangerin and their cytotoxicity.

Eleven undescribed isoquinoline alkaloids (1-8, 14, 15, and 24), along with 19 analogues (9-13, 16-23, and 25-30) were isolated from the barks of Alangium salviifolium. The structures of the undescribed compounds were elucidated through the analysis of their HR-ESI-MS, 1D and 2D NMR, IR, UV, and X-ray diffraction. The absolute configuration of 8 was established via the ECD calculation. Notably, compounds 1/2 and 3/4 were two pairs of C-14 epimers. The isolated alkaloids were evaluated for their cytotoxicity against various cancer cell lines, including SGC-7901, HeLa, K562, A549, BEL-7402, HepG2, and B16, ß-carboline-benzoquinolizidine (14-22) and cepheline-type (24-28) alkaloids exhibited remarkable cytotoxicity, with IC50 values ranging from 0.01 to 48.12 µM. Remarkably, compounds 17 and 21 demonstrated greater cytotoxicity than the positive control doxorubicin hydrochloride. Furthermore, a significant proportion of these bioactive alkaloids possess a C-1' epimer configuration. The exploration of their structure-activity relationship holds promise for directing future investigations into alkaloids derived from Alangium, potentially leading to novel insights and therapeutic advancements.

Anti-inflammatory and α-glucosidase inhibitory constituents from Dendrobium nobile Lindl.

Four new compounds ((±)-1-3), including one pair of enantiomers ((±)-1), along with 11 known bibenzyls (4-14) were isolated from Dendrobium nobile. The structures of the new compounds were elucidated by spectroscopic methods including 1D and 2D NMR as well as HRESIMS. The configurations of (±)-1 were established via the electronic circular dichroism (ECD) calculations. Compounds (+)-1 and 13 displayed pronounced α-glucosidase inhibitory activities with IC50 values of 16.7 ± 2.3 and 13.4 ± 0.2 µM, respectively, which were comparable to that of genistein (IC50, 8.54 ± 0.69 µM). Kinetic studies revealed that (+)-1 and 13 were non-competitive inhibitors against α-glucosidase and molecular docking simulations illuminated their interactions with α-glucosidase. All the isolates were also evaluated for their anti-inflammatory activities. Compounds 4, 5, and 11 exhibited superior inhibition activity with IC50 values ranging from 9.2 to 13.8 µM to that of quercetin (IC50, 16.3 ± 1.1 µM).

Triterpenoids as bivalent and dual inhibitors of acetylcholinesterase/butyrylcholinesterase from the fruiting bodies of Inonotus obliquus.

Inonotus obliquus, an edible and medicinal mushroom parasitic on birches, has been used in human diet and for traditional therapies in the high latitude regions of Europe and Asia for a long time. Our phytochemical study of this fungus led to the identification of fourteen triterpenoids including four undescribed ones, and two pairs of undescribed phenolic enantiomers. The undescribed compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, quantum chemical NMR and ECD calculations, as well as single-crystal X-ray diffraction analysis. Bioassays revealed that eight compounds showed dual inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values ranging from 2.40 ± 0.05 to 28.72 ± 0.46 µM, while 3ß-hydroxy-lanosra-8,24-dien-21-al and trametenolic acid only presented BuChE inhibitory activities with IC50 values of 22.21 ± 1.01 and 7.68 ± 0.13 µM, respectively. In the kinetic studies, the most active three compounds acted as non-competitive inhibitors for both cholinesterases. Furthermore, molecular docking simulations revealed that three compounds demonstrated dual-sites bounding to AChE/BuChE. These triterpenoids emerged as bivalent and dual inhibitors of AChE/BuChE and could be effective drug candidates to prevent and treat Alzheimer's disease in the future.

Phenolic compounds from the sclerotia of Inonotus obliquus.

Three phenolic compounds (±1 and 2) including a pair of new enantiomers were isolated from the sclerotia of Inonotus obliquus. Their structures were assigned by extensive spectroscopic analyses. All the compounds were evaluated for the neuroprotective activity against oxidative damage on human neuroblastoma SH-SY5Y cells induced by H2O2. Compound 2 showed remarkable neuroprotective effect and significantly improved the cell viability of SH-SY5Y cells treated by H2O2.

2-(2-Phenylethyl)chromone derivatives: Promising α-glucosidase inhibitors in agarwood from Aquilaria filaria.

Twelve undescribed 2-(2-phenylethyl)chromone derivatives, including one pair of enantiomers, together with eleven known ones, were isolated from the EtOAc extract of agarwood originating from Aquilaria filaria. All structures were elucidated by spectroscopic (NMR, UV, IR, MS) methods and compared with reported data in literatures. Twenty-one compounds were assessed for α-glucosidase inhibitory activity, which showed inhibition of α-glucosidase with IC50 values ranging between 7.8 ± 0.3 to 137.7 ± 3.0 µM (Acarbose, 743.4 ± 3.3 µM; Genistein, 8.3 ± 0.1 µM). Our results expanded the structural diversity of 2-(2-phenylethyl)chromones from agarwood, and revealed the potential of 2-(2-phenylethyl)chromones as α-glucosidase inhibitors.

[Molecular analysis of an avian influenza virus isolate of H5N2 subtype from parrot].

In 2005, an avian influenza virus stain was isolated from Parrot in Guangdong, which was then genotyped as H5N2 subtype and designated as A/Parrot/Guangdong/268/2005. According to the current OIE definition on the low-pathogenicity of avian influenza virus, the strain was recognized as a low pathogenic avian influenza virus due to the presence of one basic amino acid residue at the HA cleavage site. Some molecular characteristics of the virus, such as potential glycosylation sites in HA and NA, receptor binding sites of HA, and drug resistance site of NA, showed no variations. To analyze molecular evolution of this strain, we selected the sequences of H5N2 subtype AIVs from GenBank and established the phylogenetic trees. Our results indicated that this strain shared the highest homologies with the H5N2 LPAI isolate A/Pheasant/NJ/1355/1998-like. Phylogenic analysis revealed the isolate, together with A/Chicken/Pennsylvania/1/1983 (H5N2), belonged to America lineages and clustered with A/Pheasant/NJ/1355/1998-like.