Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation.

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

Luteolin attenuates neutrophilic oxidative stress and inflammatory arthritis by inhibiting Raf1 activity.

Neutrophils play a significant role in inflammatory tissue injury. Activated neutrophils produce reactive oxygen species (ROS), release proteases, and form neutrophil extracellular traps (NETs), significantly affecting the pathogenesis of inflammatory arthritis. We examined the therapeutic effects of luteolin, a flavone found in many plants, in neutrophilic inflammation and on acute inflammatory arthritis. Luteolin significantly inhibited superoxide anion generation, ROS production, and NET formation in human neutrophils. The increase in elastase release, CD11b expression, and chemotaxis was also inhibited by luteolin. Luteolin significantly suppressed phosphorylation of extracellular signal-regulated kinase (Erk) and mitogen-activated protein kinase kinase-1 (MEK-1), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Analysis of the molecular mechanism further revealed that luteolin acts as a Raf-1 inhibitor. In mice with complete Freund's adjuvant-induced arthritis, luteolin ameliorated neutrophil infiltration as well as the thickness of paw edema and ROS production. In conclusion, in addition to its known ROS scavenging effect, this study is the first to provide evidence that luteolin diminishes human neutrophil inflammatory responses by inhibiting Raf1-MEK-1-Erk. Our results focused on the importance of neutrophil activation in inflammatory tissue injury and offer opportunities for the development of luteolin's therapeutic potential to attenuate neutrophilic inflammatory diseases.

The aqueous extract of Glycyrrhiza inflata can upregulate unfolded protein response-mediated chaperones to reduce tau misfolding in cell models of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) and several neurodegenerative disorders known as tauopathies are characterized by misfolding and aggregation of tau protein. Although several studies have suggested the potential of traditional Chinese medicine (TCM) as treatment for neurodegenerative diseases, the role of TCM in treating AD and tauopathies have not been well explored. MATERIALS AND METHODS: Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of repeat domain of tau (ΔK280 tauRD) with DsRed. The ΔK280 tauRD-DsRed fusion gene was then used to generate Tet-On 293 and SH-SY5Y cell clones as platforms to test the efficacy of 39 aqueous extracts of TCM in reducing tau misfolding and in neuroprotection. RESULTS: Seven TCM extracts demonstrated a significant reduction in tau misfolding and reactive oxidative species with low cytotoxicity in the ΔK280 tauRD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ΔK280 tauRD-DsRed SH-SY5Y neuronal cell model. G. inflata further rescued the upregulation of ERN2 (pro-apoptotic) and downregulation of unfolded-protein-response-mediated chaperones ERP44, DNAJC3, and SERP1 in ΔK280 tauRD-DsRed 293 cells. CONCLUSION: This in vitro study provides evidence that G. inflata may be a novel therapeutic for AD and tauopathies. Future applications of G. inflata on animal models of AD and tauopathies are warranted to corroborate its effect of reducing misfolding and potential disease modification.

Aqueous extract of Glycyrrhiza inflata inhibits aggregation by upregulating PPARGC1A and NFE2L2-ARE pathways in cell models of spinocerebellar ataxia 3.

Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 and dentatorubropallidoluysian atrophy, as well as Huntington disease, are a group of neurodegenerative disorders caused by a CAG triplet-repeat expansion encoding a long polyglutamine (polyQ) tract in the respective mutant proteins. The cytoplasmic and nuclear aggregate formation, a pathological hallmark of polyQ diseases, is probably the initial process triggering the subsequent pathological events. Compromised oxidative stress defense capacity and mitochondrial dysfunction have emerged as contributing factors to the pathogenesis of polyQ diseases. The roots of licorice (Glycyrrhiza species) have long been used as an herbal medicine. In this study, we demonstrate the aggregate-inhibitory effect of Glycyrrhiza inflata herb extract and its constituents licochalcone A and ammonium glycyrrhizinate (AMGZ) in both 293 and SH-SY5Y ATXN3/Q75 cells, SCA3 cell models. The reporter assay showed that G. inflata herb extract, licochalcone A, and AMGZ could enhance the promoter activity of peroxisome proliferator-activated receptor γ, coactivator 1α (PPARGC1A), a known regulator of mitochondrial biogenesis and antioxidative response genes. G. inflata extract, licochalcone A, and AMGZ upregulated PPARGC1A expression and its downstream target genes, SOD2 and CYCS, in the 293 ATXN3/Q75 cell model. The expression of nuclear factor erythroid 2-related factor 2 (NFE2L2), the principal transcription factor that binds to antioxidant-responsive elements (AREs) to promote ARE-dependent gene expression when the cells respond to oxidative stress, and its downstream genes, HMOX1, NQO1, GCLC, and GSTP1, was also increased by G. inflata herb extract, licochalcone A, and AMGZ. Knockdown of PPARGC1A increased aggregates in ATXN3/Q75 cells and also attenuated the aggregate-inhibiting effect of the tested compounds. G. inflata extract and its constituents significantly elevated GSH/GSSG ratio and reduced reactive oxidative species in ATXN3/Q75 cells. The study results suggest that the tested agents activate PPARGC1A activity and NFE2L2-ARE signaling to increase mitochondrial biogenesis, decrease oxidative stress, and reduce aggregate formation in SCA3 cellular models.