Acetyl-11-keto-beta-boswellic acid modulates macrophage polarization and Schwann cell migration to accelerate spinal cord injury repair in rats.

BACKGROUND: Inhibiting secondary inflammatory damage caused by glial cells and creating a stable microenvironment is one of the main strategies to investigate drugs for the treatment of spinal cord injury. Acetyl-11-keto-beta-boswellic acid (AKBA) is the active component of the natural drug boswellia, which has anti-inflammatory and antioxidant effects and offers a possible therapeutic option for spinal cord injury. METHODS: In this study, a spinal cord injury model was established by crushing spinal cord, respectively, to detect the M1 macrophage inflammatory markers: iNOS, TNF-α, IL-1ß, and the M2 macrophage markers CD206, ARG-1, IL-10, and the detection of antioxidant enzymes and MDA. In vitro, macrophages were cultured to verify the main mechanism of the macrophage switch from Nrf2/HO-1 to M2 type by flow cytometry, immunofluorescence, and other techniques. Macrophage and Schwann cell co-culture validated the migration mechanism of Schwann cells promoted by AKBA. RESULTS: AKBA significantly enhanced the antioxidant enzyme activities of CAT, GSH-Px, T-AOC, and SOD, reduced MDA content, and reduced oxidative damage caused by spinal cord injury via the Nrf2/HO-1 signaling pathway; AKBA mediates Nrf2/HO-1/IL-10, converts macrophages from M1 to M2 type, reduces inflammation, and promotes Schwann cell migration, thereby accelerating the repair of spinal cord injury in rats. CONCLUSIONS: Our work demonstrates that AKBA can attenuate oxidative stress as well as the secondary inflammatory injury caused by macrophages after SCI, promote Schwann cell migration to the injury site, and thus accelerate the repair of the injured spinal cord.

TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb.

In recent years, olfactory dysfunction has attracted increasingly more attention as a hallmark symptom of neurodegenerative diseases (ND). Deeply understanding the molecular basis underlying the development of the olfactory bulb (OB) will provide important insights for ND studies and treatments. Now, with a genetic knockout mouse model, we show that TRIM67, a new member of the tripartite motif (TRIM) protein family, plays an important role in regulating the proliferation and development of mitral cells in the OB. TRIM67 is abundantly expressed in the mitral cell layer of the OB. The genetic deletion of TRIM67 in mice leads to excessive proliferation of mitral cells in the OB and defects in its synaptic development, resulting in reduced olfactory function in mice. Finally, we show that TRIM67 may achieve its effect on mitral cells by regulating the Semaphorin 7A/Plexin C1 (Sema7A/PlxnC1) signaling pathway.

Acetyl-11-Keto-ß-Boswellic Acid Accelerates the Repair of Spinal Cord Injury in Rats by Resisting Neuronal Pyroptosis with Nrf2.

The primary aim of this study is to delve into the potential of Acetyl-11-keto-ß-boswellic acid (AKBA) in ameliorating neuronal damage induced by acute spinal cord injury, as well as to unravel the intricate underlying mechanisms. A cohort of 40 Sprague-Dawley rats was meticulously categorized into four groups. Following a seven-day oral administration of AKBA, damaged spinal cord samples were meticulously procured for Nissl staining and electron microscopy to assess neuronal demise. Employing ELISA, immunofluorescence, Western blot (WB), and quantitative polymerase chain reaction (qPCR), the modulatory effects of AKBA within the context of spinal cord injury were comprehensively evaluated. Furthermore, employing an ex vivo extraction of spinal cord neurons, an ATP + LPS-induced pyroptotic injury model was established. The model was subsequently subjected to Nrf2 inhibition, followed by a battery of assessments involving ELISA, DCFH-DA staining, flow cytometry, immunofluorescence, and WB to decipher the effects of AKBA on the spinal cord neuron pyroptosis model. By engaging the Nrf2-ROS-NLRP3 pathway, AKBA exerted a repressive influence on the expression of the pyroptotic initiator protein Caspase-1, thereby mitigating the release of GSDMD and alleviating pyroptosis. Additionally, AKBA demonstrated the ability to attenuate the release of IL-18 and IL-1ß, curbing neuronal loss and expediting the restorative processes within the context of spinal cord injury. Our study elucidates that AKBA can reduce spinal cord neuronal apoptosis, providing a basis for the development of AKBA as a clinical treatment for spinal cord injury.

AKBA Promotes Axonal Regeneration via RhoA/Rictor to Repair Damaged Sciatic Nerve.

The existing studies by our team demonstrated the pro-recovery effect of 3-Acetyl-11-keto-beta-boswellic acid (AKBA) on a sciatic nerve injury. To further investigate the role of AKBA in peripheral nerve injury repair, The TMT quantitative proteomics technique was used to obtain differentially significant proteins in a Sham group, Model group, and AKBA group. After that, three time points (5, 14, and 28 d) and four groups (Sham + AKBA, Sham, Model, and AKBA) were set up, and immunoblotting, immunofluorescence, and cellular assays were applied to investigate the expression of CDC42, Rac1, RhoA, and Rictor in the sciatic nerve at different time points for each group in more depth. The results showed that AKBA enriched the cellular components of the myelin sheath and axon regeneration after a sciatic nerve injury and that AKBA upregulated CDC42 and Rac1 and downregulated RhoA expression 5 d after a sciatic nerve injury, promoting axon regeneration and improving the repair of a sciatic nerve injury in rats. Rictor is regulated by AKBA and upregulated in PC12 cells after AKBA action. Our findings provide a new basis for AKBA treatment of a peripheral nerve injury.

Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism.

Previous studies showed that acetyl-11-keto-beta-boswellic acid (AKBA), the active ingredient in the natural Chinese medicine Boswellia, can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation. However, the underlying molecular mechanism remains poorly understood. In this study, we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days. We found that the phagosome pathway was related to AKBA treatment, and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated. We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway. Myeloperoxidase expression in the phagosome pathway was markedly decreased, and brain-derived neurotrophic factor, nerve growth factor, and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased. Additionally, expression levels of the inflammatory factors CD68, interleukin-1ß, pro-interleukin-1ß, and tumor necrosis factor-α were also decreased. Myelin basic protein- and ß3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased. These findings suggest that, at the molecular level, AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions, which could promote myelin sheath and axon regeneration in the injured sciatic nerve.

Dracorhodin Perchlorate Regulates the Expression of Inflammatory Cytokines through the TLR4 Pathway and Improves Skin Wound Healing in Diabetic Rats.

Background: Dragon's blood is a natural medicine with hemostatic and blood-activating effects and is used to promote wound healing. Dracorhodin perchlorate (DP) is a stable form of dracarhod and is used as a substitute for cochinchinenin. DP promotes the proliferation of rat fibroblasts and promotes wound healing in rats. Methods: DP ointment (0.2 mg/mL) was applied to the skin wounds of nondiabetic and diabetic rats, and the skin of the wound was collected. Wound healing rate, H&E staining, Masson staining, TLR4 pathway, related inflammatory factors, nitric oxide synthase, and so forth were detected. Results: DP treatment alleviated the prolonged inflammatory cell infiltration time and the increase in the TLR4 pathway and inflammatory factors caused by diabetes. DP also promoted wound healing by increasing eNOS protein expression and NO content in the later stage of wound healing. Conclusion: DP promotes wound healing in diabetic rats by regulating the TLR4 pathway and related inflammatory factors. Therefore, adjuvant treatment of DP can be developed for diabetic wound healing.

Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves.

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.

Aristolochic acid induces mitochondrial apoptosis through oxidative stress in rats, leading to liver damage.

Aristolochic acid (AA) are persistent soil pollutants in the agricultural fields of the Balkan Peninsula. Preparations containing aristolochic acid are widely used for anti-inflammatory, diuretic, etc. To study the hepatotoxicity of aristolochic acid, 80 healthy SD rats were selected and divided into 20 mg/kg- AA group, 4 mg/kg-AA group, and 2 mg/kg-AA group and blank group, 20 rats per group. Mainly tested the body weight, liver function, liver tissue oxidative stress and pathological changes of liver tissue in rats. The ALT and AST activities in the serum of the rats in the administration groups were increased compared with the blank group. The activity of MDA in the administration groups was higher than that in the blank group; the activities of SOD, T-AOC and GSH-PX were significantly lower than those in the blank group. HE tissue sections also found that the administration groups showed varying degrees of hepatocyte boundary blur, nuclear fragmentation, and fibrosis tendency. Transmission electron microscopy showed that the mitochondria of the rat liver became more and more severely damaged with the increase of dose. Compared with the blank group, the mRNA expression of Bax, Caspase-9 and Caspase-3 in the administration groups were determined, while the mRNA expression of the Bcl-2 was increased. And compared with the blank control group, the expression levels of apoptotic proteins caspase-9 and caspase-3 increased significantly in the 20 mg/kg-AA group. Aristolochic acid can induce liver injury in rats through oxidative stress pathway and mitochondrial apoptosis pathway.