Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. In PC12 cells, Aβ-induced tau protein hyperphosphorylation is inhibited by CBD. This inhibition is associated with a downregulation of p-GSK-3β, an inhibitor of Wnt pathway. CBD may also increase Wnt/β-catenin by stimulation of PPARγ, inhibition of Aβ and ubiquitination of amyloid precursor protein. CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. CBD suppresses, through activation of PPARγ, pro-inflammatory signaling and may be a potential new candidate for AD therapy.

Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine., a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells.To investigate the effect ofon osteosarcoma cells and its mechanism.Osteosarcoma MG63 and U2-OS cells were treated with, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect ofon Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay.inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed thatsuppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover,blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated.Our results suggest thatbroadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.

Wnt signaling pathways are the group of signaling transduction controlling the embryonic development, cell proliferation, cell migration, cell fate specification, and body axis pattern. Nuclear accumulation ofβ-catenin in Wnt signaling is a widely recognized marker of poor cancer prognosis which regulates fat and glucose metabolism. Ganoderic acid is a triterpene isolated from fungus Ganoderma lucidum renowned for its pharmacological effects. The present study revealed the mechanistic study of β-catenin with 50 isoforms of ganoderic acid by molecular docking using Maestro 9.6 (Schrödinger Inc) in Wnt signaling pathway. Molecular docking reveals the binding interaction of β-catenin and ganoderic acid A with GScore (-9.44), kcal/mol, lipophilic EvdW (-2.86), electro (-0.72), Glide emodel (-50.401), MM-GBSA (-87.441), H bond (-1.91) with Lys 180 and Asn 220 residues involved in hydrogen bonding. Qikprop analyzed the absorption, distribution, metabolism, excretion, and toxicity and confirmed that most of the isoforms satisfies Lipinski rule but needs little modifications in their structure. The ganoderic acid A is the best-docked isoforms which inhibits the proliferation, viability, and intracellular ROS of pancreatic cancer RIN-5F cells in a dose-dependent manner.

Electroacupuncture (EA) has been demonstrated to promote the functional recovery of neurons following spinal cord injury (SCI); however, the mechanisms underlying its effects have yet to be elucidated. The Wnt/β-catenin signaling pathway has been implicated in the regulation of the balance between growth, proliferation and differentiation of neural precursor cells. The present study aimed to investigate the effects of EA therapy on Wnt/β‑catenin‑regulated gene expression and neuronal recovery in rats with SCI. The Allen method was used to establish SCI in rats, and alterations in Wnt1 and Nestin mRNA and protein expression levels in response to SCI were determined on days 1, 3, 7 and 14 post‑injury using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. To evaluate the effects of EA treatment on SCI, the following four treatment groups were employed: SCI, SCI + EA, SCI + lithium chloride (LiCl) and SCI + LiCl + EA. The protein expression levels of Wnt1, Nestin and nuclear β‑catenin were evaluated on day 3 post‑treatment, and neuronal nuclearantigen (NeuN) protein expression levels were evaluated on day 21 post‑treatment using western blot analysis. The Basso, Beattie and Bresnahan scoring method was used to evaluate spinal cord recovery on day 28 post‑treatment across the four treatment groups. EA therapy at the Dazhui and Mingmenacupuncture points significantly increased the expression levels of Wnt1, Nestin, β‑catenin and NeuN, thus suggesting that EA therapy may promote spinal cord recovery following injury. The underlying mechanism was demonstrated to involve enhanced Wnt/β‑catenin signaling, which may promote theproliferation and differentiation of neural stem cells. However, further studies are required to elucidate the detailed effects and underlying molecular mechanisms of EA therapy on SCI.