Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study.

Background: Escin is the main active component in Aesculus hippocastanum. It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP). Methods: The Swiss Target Prediction and the Pharm Mapper database were employed for predicting the targets of escin. Also, the candidate targets of NP were gathered via the databases including Therapeutic Targets, DisGeNet, GeneCards, DrugBank, and OMIM. Subsequently, the network of protein-protein interaction was screened for the key targets by the software Cytoscape 3.8.0. Then, the intersection of these targets was analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, we further investigated the ligand-target interactions by molecular docking and molecular dynamics simulations. Results: In total, 94 escin targets were predicted by network pharmacology. Among them, SRC, MMP9, PTGS2, and MAPK1 were the core candidate targets. Subsequently, the analysis of GO and KEGG enrichment revealed that escin affected NP by regulating protein kinase C, MAP kinase, TRP channels, the T-cell receptors signaling pathway, and the TNF signaling pathway. The results of molecular docking and molecular dynamics simulation confirmed that escin not only had a strong binding activity with the four core target proteins but also stably combined in 50 ns. Conclusions: Our study revealed that escin acts on the core targets SRC, MMP9, PTGS2, MAPK1, and associated enrichment pathways to alleviate neuronal inflammation and regulate the immune response, thus exerting anti-NP efficacy. This study provided innovative ideas and methods for the promising treatment of escin in relieving NP.

Anti-Inflammatory and Anti-Osteoclastogenesis Activities of Different Kinds of Zanthoxylum bungeanum Seed Oil in Vitro.

Our previous study has exhibited that one kind of Zanthoxylum bungeanum seed oil (ZSO), extracted from Zanthoxylum bungeanum seed, had inhibitory effects on osteoclastogenesis. However, the anti-osteoclastogenesis activities of different kinds of ZSO are scarcely reported. Since inflammation is related to bone loss and osteoporosis, in this study, three kinds of ZSO, Zanthoxylum schinifolium Siebold et Zucc seed oil (ZSSO), Zanthoxylum armatum DC. seed oil (ZDSO) and Zanthoxylum bungeanum maximum seed oil (ZBSO), were obtained with Soxhlet extraction and their fatty acid constituents were detected by GC-FID. RAW264.7 macrophages induced by lipopolysaccharide (LPS) were used to evaluate the inhibitory effects of three kinds of ZSO on inflammation via detecting the expression levels of inflammatory factors by RT-qPCR. Moreover, RANKL-induced osteoclastogenesis was applied to demonstrate the anti-osteoclastogenesis activities of them through tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR. The GC-FID results exhibited that the highest constituent in ZSSO and ZDSO was oleic acid (OA) and palmitoleic acid (PLA), respectively. While linoleic acid (LA) and α-Linolenic acid (ALA) in ZBSO were dominant. At the concentration of 0.5 µL/mL, all three kinds of ZSO could decrease the expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) in LPS-induced macrophages. At the concentration of 0.25 µL/mL, only ZSSO could decrease the expression levels of iNOS and COX-2, which implied the inhibitory effects of ZSSO were stronger than other ZSOs. The number of RANKL-induced osteoclasts and the expressions of nuclear factor kappa-B (NF-κB), TNF-α and IL-6 in the cells were decreased after being treated with ZSOs at the concentration of 0.5 µL/mL, while the number of RANKL-induced osteoclasts after treated with ZBSO were less than those treated with other ZSOs, this indicated that the anti-osteoclastogenesis effect of ZBSO were stronger than other ZSOs. In conclusion, the fatty acid compositions of three major kinds of ZSO were compared and the content of unsaturated fatty acids especially ω-3 polyunsaturated fatty acids in ZBSO were the highest among them. All ZSOs tested had anti-inflammatory and anti-osteoclastogenesis activities. And their anti-osteoclastogenesis effects might be related to the suppression of the NF-κB pathway.

Comprehensive treatment of Cronkhite-Canada syndrome: A case report and literature review.

INTRODUCTION: Cronkhite-Canada syndrome (CCS) is currently considered to be a non-hereditary disease, which is relatively rare clinically. It is also known as polyposis hyperpigmentation alopecia nail dystrophy syndrome, it is a syndrome characterized by gastrointestinal polyposis and ectodermal changes, the main manifestations are gastrointestinal symptoms, skin pigmentation, alopecia, and hypothyroidism. CASE PRESENTATION: In this paper, the clinical characteristics, diagnosis and treatment of a case of CCS admitted to Huanghe Sanmenxia Hospital were analyzed. In the course of treatment, traditional Chinese medicine was used, but no hormone, and the patient's clinical symptoms were greatly relieved. CONCLUSIONS: CCS is rare, there is no specific treatment, and traditional Chinese medicine may can greatly relieve the clinical symptoms of patients. However, it's still having to be verified by a large sample, multi-center, long-term treatment follow-up studies.