Bioassay-Guided and DeepSAT-Driven Precise Mining of Monoterpenoid Coumarin Derivatives with Antifeedant Effects from the Leaves of Ailanthus altissima.

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

Isolation of four new monoterpenes from Ailanthus altissima (mill.) Swingle and their enzyme inhibitory effects.

A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.

Discovery of Michael reaction acceptors from the leaves of Ailanthus altissima by a modified tactic.

Structural characteristics-guided investigation of Ailanthus altissima (Mill.) Swingle resulted in the isolation and identification of seven undescribed potential Michael reaction acceptors (1-7). Ailanlactone A (1) possesses an unusual 1,7-epoxy-11,12-seco quassinoid core. Ailanterpene B (6) was a rare guaianolide-type sesquiterpene with a 5/6/6/6-fused skeleton. Their structures were determined through extensive analysis of physiochemical and spectroscopic data, quantum chemical calculations, and single crystal X-ray crystallographic technology using Cu Kα radiation. The cytotoxic activities of isolates on HepG2 and Hep3B cells were evaluated in vitro. Encouragingly, ailanaltiolide K (4) showed significant cytotoxicity against Hep3B cells with IC50 values of 1.41 ± 0.21 µM, whose covalent binding mode was uncovered in silico.

Chouchunsteride A-D, four new steroids from the leaves of Ailanthus altissima (Mill.) Swingle.

Four new steroids, chouchunsteride A-D (1-4), together with four known steroids (5-8), were isolated from the leaves of Ailanthus altissima (Mill.) Swingle. Their structures were elucidated based on spectroscopic data analysis, while the relative and absolute configurations were determined via acetonide analysis and quantum chemical ECD calculations. All isolated steroids were evaluated for their cytotoxic activity against two hepatoma carcinoma cell lines (HepG2, Hep3B). Among them, 1 exhibited the most potent cytotoxicity against HepG2 cells with an IC50 value of 4.03 µM.

In Situ Regulation of Macrophage Polarization to Enhance Osseointegration Under Diabetic Conditions Using Injectable Silk/Sitagliptin Gel Scaffolds.

As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected at the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered that sitagliptin induces macrophage polarization to the M2 phenotype and alleviates the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner. The silk gel scaffolds loaded with sitagliptin elicite a stronger recruitment of M2 macrophages to the sites of Ti implants and a significant promotion of osteointegration, as compared to oral sitagliptin administration. The results suggest that injectable silk/sitagliptin gel scaffolds can be utilized to modulate the immune responses at the bone-implant interface, thus enhancing bone regeneration required for successful implantation of orthopedic and dental devices in diabetic patients.

All-Aqueous-Processed Injectable In Situ Forming Macroporous Silk Gel Scaffolds for Minimally Invasive Intracranial and Osteological Therapies.

Hydrogels are widely utilized in regenerative medicine for drug delivery and tissue repair due to their superior biocompatibility and high similarity to the extracellular matrix. For minimally invasive therapies, in situ forming gel scaffolds are desirable, but technical challenges remain to be overcome to achieve the balance between tissue-like strength and cell-sized porosity, especially for intracranial and osteological therapies. Here, a new method-inspired by the liquid crystalline spinning process in natural silk fibers-is reported for preparing injectable silk gel scaffolds with favorable preclinical efficacy and unique characteristics including 1) in situ gelling for minimally invasive surgeries, 2) controllable porosity for efficient cellular infiltration and desirable degradation, 3) resilient and tunable mechanical properties that are compatible with the modulus regime of native soft tissues, and 4) all-aqueous processing that avoids toxic solvents and enables facile loading of bioactive agents. Moreover, hierarchically structured heterogeneous silk gel scaffolds with variable porosity and bioactive agent gradients within 3D matrices can be achieved for sustained drug release and guided tissue regeneration. Preclinical efficacy studies in rodent models show efficient bacterium and glioma inhibition and positive effects on bone regeneration and vascularization.