Potential for treating SPG20
This review of Icariin, a biologically active substance found in the plant Epimedii herba, was done in conjunction with development of a protein-protein interaction network and functional enrichment analyses to predict the therapeutic actions of Icariin. This resulted in identifying SPG20 as a potential treatment target.
Icariin is a biologically active substance in Epimedii herba that is used for the treatment of neurologic disorders. However, a comprehensive analysis of the molecular mechanisms of icariin is lacking. In this review, we present a brief history of the use of icariin for medicinal purposes; describe the active chemical components of Epimedii herba; and examine the evidence from experimental studies that have uncovered molecular targets of icariin in different diseases. We also constructed a protein-protein interaction network and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to predict the therapeutic actions of icariin in nervous system diseases including Alzheimer disease, Parkinson disease, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, and hereditary spastic paraplegias. The results of our analyses can guide future studies on the application of icariin to the treatment of neurologic disorders.
Hereditary spastic paraplegias are a genetically heterogeneous group of neurodegenerative disorders characterized by length-dependent corticospinal tract and dorsal column degeneration.205 Patients present the core clinical features of bilateral lower limb spasticity, hyperreflexia, and extensor plantar responses.206 Hereditary spastic paraplegias can emerge in infancy, childhood, adolescence, or adulthood and are usually associated with autosomal dominant or recessive or X-linked modes of inheritance.207
There is currently no direct evidence that icariin has therapeutic effects in spastic paraplegia; however, a possibly link through aldehyde dehydrogenase 18 family member A1 (ALDH18A1) and EGFR was suggested by our network pharmacology analysis. ALDH18A1 mutations cause dominant (SPG9A) or recessive (SPG9B) spastic paraplegia. Troyer syndrome, a hereditary spastic paraplegia, is an autosomal recessive disease characterized by pathogenic mutations in the SPG20 gene that result in degradation of the protein and a loss-of-function phenotype that includes length-dependent axonopathy of corticospinal motor neurons.208 Methylation-induced SPG20 silencing was reported to activate the EGFR/MAPK signaling pathway.209 Spartin, a multifunctional protein encoded by SPG20, is involved in the endocytic trafficking of EGFR;209 as icariin inhibits EGFR signaling, icariin may alleviate hereditary spastic paraplegia by interfering with the function of spartin.
SOURCE: Drug Des Devel Ther. 2021; 15: 3619–3641. Published online 2021 Aug 20. doi: 10.2147/DDDT.S310686 PMID: 34447243 © 2021 Wang et al.
Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review
Shuangqiu Wang # 1 2 3 , Jiarui Ma # 4 , Yanqi Zeng # 5 , Guowei Zhou 6 , Yuxuan Wang 1 2 3 , Wenjuan Zhou 5 , Xiaohe Sun 5 , Minghua Wu 1 5
1. Department of Neurology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, People’s Republic of China.
2. Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, 210046, People’s Republic of China.
3. State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, People’s Republic of China.
4. Provincial Key Laboratory of Drug Target and Drug for Degenerative Disease, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, People’s Republic of China.
5. First Clinical Medical School, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, People’s Republic of China.
6. Department of General Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, People’s Republic of China.
#. Contributed equally.