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Open AccessArticle

Study on the Pharmacological Mechanism of Icariin for the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking Techniques

by Dongwei Wang, Jilong Zheng, Xingsheng Sun, Liuwei Xie and Yang Yang

Metabolites 2024, 14(1), 1; https://doi.org/10.3390/metabo14010001 - 19 Dec 2023

Cited by 9 | Viewed by 3355

Abstract

The purpose of this study is to explore the pharmacological mechanism of icariin (ICA) in the treatment of Alzheimer’s disease (AD) based on network pharmacology and network molecular docking technology. In order to investigate the regulatory effect of ICA on the expression level of AD pathological phosphorylation regulatory proteins, this study further explored the possible molecular mechanism of ICA regulating AD autophagy through network pharmacology. Macromolecular docking network was verified by Autodock Vina 1.1.2 software. The main active ingredients of ICA, the physicochemical properties, and pharmacokinetic information of ICA were predicted using online databases and relevant information. The results showed that the targets of MAPK3, AKT1, HSP90AA1, ESR1, and HSP90AA1 were more critical in the treatment of AD. Autophagy, apoptosis, senescence factors, phosphatidylinositide 3-kinase/protein kinase B (P13K/AKT) signaling pathway, MAKP, mTOR, and other pathways were significantly associated with AD. Docking of ICA with HIF-1, BNIP3, PINK1, and Parkin pathway molecules showed that the key targets of the signaling pathway were more stably bound to ICA, which may provide a better pathway for ICA to regulate autophagy by providing a better pathway. ICA can improve AD, and its mechanism may be related to the P13K/AKT, MAKP, and mTOR signaling pathways, thereby regulating autophagy-related proteins. Full article

(This article belongs to the Section Bioinformatics and Data Analysis)

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13 pages, 1534 KB

Open AccessReview

Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i)

by Payal Ganguly, Tom Macleod, Chi Wong, Mark Harland and Dennis McGonagle

Pharmaceuticals 2023, 16(9), 1286; https://doi.org/10.3390/ph16091286 - 12 Sep 2023

Cited by 50 | Viewed by 10059

Abstract

The p38 mitogen-activated protein kinase (p38-MAPK) is a crucial signaling pathway closely involved in several physiological and cellular functions, including cell cycle, apoptosis, gene expression, and responses to stress stimuli. It also plays a central role in inflammation and immunity. Owing to disparate p38-MAPK functions, it has thus far formed an elusive drug target with failed clinical trials in inflammatory diseases due to challenges including hepatotoxicity, cardiac toxicity, lack of efficacy, and tachyphylaxis, which is a brief initial improvement with rapid disease rebound. To overcome these limitations, downstream antagonism of the p38 pathway with a MAPK-activated protein kinase (MAPKAPK, also known as MK2) blockade has demonstrated the potential to abrogate inflammation without the prior recognized toxicities. Such MK2 inhibition (MK2i) is associated with robust suppression of key pro-inflammatory cytokines, including TNFα and IL-6 and others in experimental systems and in vitro. Considering this recent evidence regarding MK2i in inflammatory arthritis, we revisit the p38-MAPK pathway and discuss the literature encompassing the challenges of p38 inhibitors with a focus on this pathway. We then highlight how novel MK2i strategies, although encouraging in the pre-clinical arena, may either show evidence for efficacy or the lack of efficacy in emergent human trials data from different disease settings. Full article

(This article belongs to the Section Pharmacology)

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13 pages, 3475 KB

Open AccessArticle

Low-Level Laser Therapy Induces Melanoma Tumor Growth by Promoting Angiogenesis

by Yi-Yuan Lin, Shin-Yi Lee and Yu-Jung Cheng

Life 2023, 13(2), 320; https://doi.org/10.3390/life13020320 - 23 Jan 2023

Cited by 9 | Viewed by 10622

Abstract

The effects of low-level laser therapy (LLLT) on tumor growth are inconsistent. In this study, we investigated the effects of LLLT on melanoma tumor growth and angiogenesis. C57/BL6 mice were challenged with B16F10 melanoma cells and treated with LLLT for 5 consecutive days; untreated mice were used as controls. Tumor weight, angiogenesis, immunohistochemistry, and protein levels were compared between the treated and untreated mice. In an in vitro experiment, B16F10 cells were treated with LLLT. Proteins were extracted and subjected to Western blot analysis for analyzing signaling pathways. Compared with the findings in the untreated mice, tumor weight substantially increased in the treated mice. Both immunohistochemical and Western blot analyses revealed markedly increased levels of CD31, a biomarker of vascular differentiation, in the LLLT group. In B16F10 cells, LLLT considerably induced the phosphorylation of extracellular signal-regulated kinase (ERK), which, in turn, phosphorylated p38 mitogen-activated protein kinase (MAPK). Furthermore, LLLT induced the expression of vascular endothelial growth factor, but not hypoxia-inducible factor-1α, through the ERK/p38 MAKP signaling pathways. Our findings indicate that LLLT induces melanoma tumor growth by promoting angiogenesis. Therefore, it should be avoided in patients with melanoma. Full article

(This article belongs to the Section Medical Research)

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