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Abstract Spinal cord injury (SCI), characterized by the disruption of neural pathways and an increase in inflammatory cell infiltration, leads to profound and lasting neurological deficits, with a high risk of resulting in permanent disability. Currently, the therapeutic landscape for SCI is notably sparse, with limited effective treatment options available. Methylprednisolone (MP), a widely used clinical anti-inflammatory agent for SCI, requires administration in high doses that are associated with significant adverse effects. In this study, we introduce an innovative approach by substituting cholesterol with MP to engineer a novel Lipid Nanoparticle (MP-LNP). This strategy aims to enhance the localization and concentration of MP at the injury site, thereby amplifying its therapeutic efficacy while mitigating systemic side effects. Furthermore, we explore the integration of C3 transferase mRNA into MP-LNPs. C3 transferase, a potent inhibitor of the RhoA pathway, has shown promise in facilitating neurological recovery in animal models of SCI and is currently being evaluated in clinical trials. The novel formulation, MP-LNP-C3, is designed for direct administration to the injury site during decompression surgery, offering a targeted therapeutic modality for SCI. Our findings reveal several significant advantages of this approach: Firstly, the incorporation of C3 transferase mRNA into MP-LNPs does not compromise the structural integrity of the nanoparticles, ensuring efficient mRNA expression within the spinal cord. Secondly, the MP-LNP formulation effectively attenuates inflammation and reduces the adverse effects associated with high-dose MP treatment in the acute phase of SCI. Lastly, MP-LNP-C3 demonstrates notable neuroprotective properties and promotes enhanced recovery of motor function in SCI mouse models. Together, these results underscore the potential of this innovative LNP-based therapy as a promising avenue for advancing the treatment of clinical SCI. Graphical Abstract

Ziziphus Jujuba cv. Muzao has attracted researchers for a long time, while residue of jujuba after extracted by water still contains many bioactivities. This paper presents the first study on in-depth structure analysis and its antioxidant of a pectic polysaccharide (PZJRP) separated and purified from Ziziphus Jujuba cv. Muzao residue through alkali extraction. Results of structural and morphological characterization according to high-performance gel-permeation chromatography, methylation analysis and partial acid hydrolysis etc. showed that PZJRP was composed of rhamnose, arabinose, glucose, galactose and galacturonic acid. Main chain of PZJRP including 1,2,4-linked rhamnose and 1,4-linked galacturonic acid, branches attached to C-4 of rhamnose, which suggested that PZJRP was a pectin polysaccharide belongs to rhamngalacturonan I type (RG-I). Significant antioxidant activity of PZJRP was revealed by protecting RAW264.7 cells against H2O2-induced oxidative stress. These findings demonstrated the potential of PZJRP to be a functional thickener as a novel food additive.

Ziziphus jujuba cv. Muzao is a plant widely cultivated in the Yellow River Basin of China. It has nutritional and healthcare functions, in which polysaccharides are the main components of its bio-functions. In order to make effective use of Ziziphus jujuba cv. Muzao residue resources and explore new functional food ingredients, the polysaccharide (ZJRP) from Ziziphus jujuba cv. Muzao residues were extracted by sodium hydroxide, and the optimal extraction conditions of ZJRP were obtained by the response surface method. The basic composition and antioxidant effects of ZJRP were determined. The results showed that ZJRP has significant antioxidant activity, mainly reflected in the high DPPH radical scavenging rate, which may be related to their high content of galacturonic acid and the extraction method. In addition, the rheological and thermal properties of ZJRP were respectively determined by a rheometer and differential scanning calorimetry (DSC), indicating that they have shear thinning properties and good thermal stability. Results showed that the alkaline extraction method can be used as a potential technique for extracting ZJRP with high antioxidant activity, and ZJRP can be further explored as a functional food ingredient.