iridoids and Brain-Injuries--Traumatic

We aimed to investigate whether geniposide, a main component extracted from Gardenia jasminoides Ellis fruit, could exert neuroprotective functions against traumatic brain injury (TBI). Enzyme-linked immunosorbent assay (ELISA) was used for detection of plasma cytokines. Real-time polymerase chain reaction (RT-PCR) was employed for measurements of mRNA levels of cytokines. Neurological outcomes were evaluated by modified neurological severity score (mNSS) and Rota-Rod. Blood-brain barrier (BBB) integrity and brain edema were assessed. Protein expression was tested by Western blot. The plasma levels of interleukin (IL)-1β, IL-6, IL-8 and IL-10 were all elevated in patients with TBI compared to those of healthy controls. TBI rats treated with geniposide showed lower mNSS and longer fall latency time than untreated TBI rats. BBB integrity was maintained and brain edema was reduced by geniposide treatment in TBI rats. Plasma levels of IL-1β, IL-6 and IL-8 were significantly repressed by geniposide treatment in TBI rats, whereas IL-10 level was upregulated. mRNA expression levels of these cytokines in the brain tissues of TBI rats exhibited the same trends of changes. By testing p38 mitogen-activated protein kinase and NF-κB p65 activities, it was observed that phosphorylated (p)-p38 and p-p65 were dramatically inhibited by geniposide. In conclusion, geniposide exerts neuroprotective functions against TBI by inhibiting p-p38 and p-p65.

Topics: Adolescent; Adult; Animals; Anti-Inflammatory Agents; Blood-Brain Barrier; Brain Edema; Brain Injuries, Traumatic; Cytokines; Female; Humans; Imidazoles; Iridoids; Male; Middle Aged; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Pyrimidines; Rats, Sprague-Dawley; RNA, Messenger; Treatment Outcome; Young Adult

Naozhenning granule is a Chinese herbal formula, which is mainly used in the treatment of concussion, cerebral post-traumatic syndrome. Although its effectiveness has been certified in the clinical use, the mechanism of action and bioactive components of Naozhenning remain unknown. In this study, the ultrahigh performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry was applied to identify the absorbed constituents of Naozhenning in the rat serum. A total of 60 compounds, including 30 prototype components and 30 metabolites were identified. Then the absorbed constituents were subjected to the network pharmacology analysis. The compound-target-disease (CTD) and KEGG pathway analysis revealed that 40 absorbed constituents, 56 target genes and three key pathways such as RAS, PI3K/Akt, MAPK, TGFβ were probably related with the efficacy of Naozhenning against cerebral trauma and cerebral concussion. The results provided a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Naozhenning granule.

Topics: Administration, Oral; Animals; Brain Injuries, Traumatic; Chromatography, Liquid; Drugs, Chinese Herbal; Gene Expression; Iridoids; Male; Mass Spectrometry; Neuroprotective Agents; Rats, Sprague-Dawley; Signal Transduction

We previously developed a biomaterial scaffold that could effectively provide seed cells to a lesion cavity resulting from traumatic brain injury. However, we subsequently found that few transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) are able to migrate from the scaffold to the lesion boundary. Stromal derived-cell factor-1α and its receptor chemokine (C-X-C motif) receptor (CXCR)4 are chemotactic factors that control cell migration and stem cell recruitment to target areas. Given the low expression level of CXCR4 on the hUC-MSC membrane, lentiviral vectors were used to generate hUC-MSCs stably expressing CXCR4 fused to green fluorescent protein (GFP) (hUC-MSCs(CXCR4/GFP)). We constructed a scaffold in which recombinant human brain-derived neurotrophic factor (BDNF) was linked to chitosan scaffolds with the crosslinking agent genipin (CGB scaffold). The scaffold containing hUC-MSCs(CXCR4/GFP) was transplanted into the lesion cavity of a rat brain, providing exogenous hUC-MSCs to both lesion boundary and cavity. These results demonstrate a novel strategy for inducing tissue regeneration after traumatic brain injury.

Topics: Animals; Brain; Brain Injuries, Traumatic; Brain-Derived Neurotrophic Factor; Cell Adhesion; Cell Differentiation; Cell Movement; Cell Proliferation; Chitosan; Gene Expression Profiling; Green Fluorescent Proteins; Humans; Iridoids; Male; Rats; Rats, Sprague-Dawley; Receptors, CXCR4; Tissue Engineering; Tissue Scaffolds