Efficacy and safety evaluation of adjuvant auricular acupuncture for smoking cessation: A study protocol of randomized, assessor-blinded, pragmatic pilot trial.

BACKGROUND: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation. METHODS: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events). RESULTS: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation. CONCLUSION: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (registration number: KCT0007212).

Korean Medicine Clinical Practice Guidelines for Lumbar Herniated Intervertebral Disc in Adults: Based on Grading of Recommendations Assessment, Development and Evaluation (GRADE)

A significant number of individuals suffer from low back pain throughout their lifetime, and the medical costs related to low back pain and disc herniation are gradually increasing in Korea. Korean medicine interventions have been used for the treatment of lumbar intervertebral disc herniation. Therefore, we aimed to update the existing Korean medicine clinical practice guidelines for lumbar intervertebral disc herniation. A review of the existing guidelines for clinical treatment and analysis of questionnaires targeting Korean medicine doctors were performed. Subsequently, key questions on the treatment method of Korean medicine used for disc herniation in actual clinical trials were derived, and drafts of recommendations were formed after literature searches using the Grading of Recommendations, Assessment, Development and Evaluation. An expert consensus was reached on the draft through the Delphi method and final recommendations were made through review by the development project team and the monitoring committee. Fifteen recommendations for seven interventions for lumbar disc herniation were derived, along with the grade of recommendation and the level of evidence. The existing Korean medicine clinical practice guidelines for lumbar intervertebral disc herniation have been updated. Continuous updates will be needed through additional research in the future.

Oral Administration of Gintonin Protects the Brains of Mice against Aß-Induced Alzheimer Disease Pathology: Antioxidant and Anti-Inflammatory Effects.

The study was aimed at analyzing the protective effects of gintonin in an amyloid beta- (Aß-) induced Alzheimer's disease (AD) mouse model. For the development of the Aß-induced AD mouse model, the amyloid-ß (Aß 1-42) peptide was stereotaxically injected into the brains of mice. Subsequently, gintonin was administered at a dose of 100 mg/kg/day/per oral (p.o) for four weeks daily, and its effects were evaluated by using western blotting, fluorescence analysis of brain sections, biochemical tests, and memory-related behavioral evaluations. To elucidate the effects of gintonin at the mechanistic level, the activation of endogenous antioxidant mechanisms, as well as the activation of astrocytes, microglia, and proinflammatory mediators such as nuclear factor erythroid 2-related factor 2 (NRF-2) and heme oxygenase-1 (HO-1), was evaluated. In addition, microglial cells (BV-2 cells) were used to analyze the effects of gintonin on microglial activation and signaling mechanisms. Collectively, the results suggested that gintonin reduced elevated oxidative stress by improving the expression of NRF-2 and HO-1 and thereby reducing the generation of reactive oxygen species (ROS) and lipid peroxidation (LPO). Moreover, gintonin significantly suppressed activated microglial cells and inflammatory mediators in the brains of Aß-injected mice. Our findings also indicated improved synaptic and memory functions in the brains of Aß-injected mice after treatment with gintonin. These results suggest that gintonin may be effective for relieving AD symptoms by regulating oxidative stress and inflammatory processes in a mouse model of AD. Collectively, the findings of this preclinical study highlight and endorse the potential, multitargeted protective effects of gintonin against AD-associated oxidative damage, neuroinflammation, cognitive impairment, and neurodegeneration.

Oral Administration of Alpha Linoleic Acid Rescues Aß-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice.

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aß1-42 (Aß1-42, 5 µL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aß1-42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aß1-42-injected mice to a greater extent than the Aß1-42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aß1-42 infused mouse brains; interestingly, these markers were significantly reduced in the Aß + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aß1-42-treated mouse brains, whereas these markers were markedly reduced in the Aß + ALA-cotreated group. Moreover, Aß1-42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aß1-42) in the mouse brains, whereas these proteins were markedly reduced in the Aß + ALA-cotreated group. We also checked the effects of ALA against Aß-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aß-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aß + ALA-cotreated mouse brains.

Natural Dietary Supplementation of Curcumin Protects Mice Brains against Ethanol-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment via Nrf2/TLR4/RAGE Signaling.

The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.

Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway.

Gintonin, a ginseng-derived glycolipoprotein isolated from ginseng, has been shown to be neuroprotective in several neurological disorders such as Alzheimer's disease models and depressive-like behaviors. In this study, we sought to investigate the potential protective mechanisms of gintonin in an in vivo MPTP and in vitro MPP+-mediated Parkinson's disease (PD) model. We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP+ models of PD. Our in vivo and in vitro findings suggest that the neuroprotective effects of gintonin were associated with the regulation of the Nrf2/HO-1 pathway, which regulated the expression of proinflammatory cytokines and nitric oxide synthase and apoptotic markers in the substantia nigra and striatum of the mice. Moreover, the neuroprotective effects of gintonin were also associated with a reduction in α-synuclein accumulation in the mouse substantia nigra and striatum. The neuroprotective effects of gintonin were further validated by analyzing the effects of gintonin on MPP+-treated SH-SY5Y cells, which confirmed the protective effects of gintonin. It remains for future basic and clinical research to determine the potential use of gintonin in Parkinson's disease. However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. We believe that gintonin might be explored as an important therapeutic agent in the treatment of PD.