Study on the mechanism of puerarin against osteoarthritis from ferroptosis based on network pharmacology and bioinformatics.

Network pharmacology and bioinformatics were used to study puerarin's molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using "Osteoarthritis" as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilß levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin's anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin's multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.

Traditional Chinese medicine Master XIONG Jibo’s medication experience in treating arthralgia syndrome through data mining / 数字中医药（英文）

@#Objective This study aimed to examine and propagate the medication experience and group formula of traditional Chinese medicine (TCM) Master XIONG Jibo in diagnosing and treating arthralgia syndrome (AS) through data mining. Methods Data of outpatient cases of Professor XIONG Jibo were collected from January 1, 2014 to December 31, 2018, along with cases recorded in A Real Famous Traditional Chinese Medicine Doctor: XIONG Jibo's Clinical Medical Record 1, which was published in December 2019. The five variables collected from the patients’ data were TCM diagnostic information, TCM and western medicine diagnoses, syndrome, treatment, and prescription. A database was established for the collected data with Excel. Using the Python environment, a customized modified natural language processing (NLP) model for the diagnosis and treatment of AS by Professor XIONG Jibo was established to preprocess the data and to analyze the word cloud. Frequency analysis, association rule analysis, cluster analysis, and visual analysis of AS cases were performed based on the Traditional Chinese Medicine Inheritance Computing Platform (V3.0) and RStudio (V4.0.3). Results A total of 610 medical records of Professor XIONG Jibo were collected from the case database. A total of 103 medical records were included after data screening criteria, which comprised 187 times (45 kinds) of prescriptions and 1 506 times (125 kinds) of Chinese herbs. The main related meridians were the liver, spleen, and kidney meridians. The properties of Chinese herbs used most were mainly warm, flat, and cold, while the flavors of herbs were mainly bitter, pungent, and sweet. The main patterns of AS included the damp heat, phlegm stasis, and neck arthralgia. The most commonly used herbs for AS were Chuanniuxi (Cyathulae Radix), Huangbo (Phellodendri Chinensis Cortex), Cangzhu (Atractylodis Rhizoma), Qinjiao (Gentianae Macrophyllae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangqi (Astragali Radix), and Chuanxiong (Chuanxiong Rhizoma). The most common effect of the herbs was “promoting blood circulation and removing blood stasis”, followed by “supplementing deficiency (Qi supplementing, blood supplementing, and Yang supplementing)”, and “dispelling wind and dampness”. The data were analyzed with the support ≥ 15% and confidence = 100%, and after de-duplication, five second-order association rules, 39 third-order association rules, 39 fourth-order association rules, and two fifth-order association rules were identified. The top-ranking association rules of each were “Cangzhu (Atractylodis Rhizoma) → Huangbo (Phellodendri Chinensis Cortex)” “Cangzhu (Atractylodis Rhizoma) + Chuanniuxi (Cyathulae Radix) → Huangbo (Phellodendri Chinensis Cortex)” “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) + Gancao (Glycyrrhizae Radix et Rhizoma) → Qinjiao (Gentianae Macrophyllae Radix)” and “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) +Gancao (Glycyrrhizae Radix et Rhizoma) + Huangbo (Phellodendri Chinensis Cortex) → Qinjiao (Gentianae Macrophyllae Radix)”, respectively. Five clusters were obtained using cluster analysis of the top 30 herbs. The herbs were mainly drying dampness, supplementing Qi, and promoting blood circulation. The main prescriptions of AS were Ermiao San (二妙散), Gegen Jianghuang San (葛根姜黄散), and Huangqi Chongteng Yin (黄芪虫藤饮). The herbs of core prescription included Cangzhu (Atractylodis Rhizoma), Chuanniuxi (Cyathulae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangbo (Phellodendri Chinensis Cortex), Mugua (Chaenomelis Fructus), Qinjiao (Gentianae Macrophyllae Radix), Danggui (Angelicae Sinensis Radix), and Yiyiren (Coicis Semen). Conclusion Clearing heat and dampness, relieving collaterals and pain, and invigorating Qi and blood are the most commonly used therapies for the treatment of AS by Professor XIONG Jibo. Additionally, customized NLP model could improve the efficiency of data mining in TCM.

Sijunzi decoction may decrease apoptosis via stabilization of the extracellular matrix following cerebral ischaemia-reperfusion in rats.

Neurons undergo degeneration, apoptosis and death due to ischaemic stroke. The present study investigated the effect of Sijunzi decoction (SJZD), a type of traditional Chinese medicine known as invigorating spleen therapy, on anoikis (a type of apoptosis) in rat brains following cerebral ischaemia-reperfusion. Rats were randomly divided into sham, model, nimodipine and SJZD low/medium/high dose groups. A middle cerebral artery occlusion model was established. Neurobehavioural scores were evaluated after administration for 14 days using a five-grade scale. Blood-brain barrier permeability and apoptotic rate were detected using Evans blue (EB) extravasation and TUNEL staining, respectively. Tissue inhibitor of metalloproteinase 1 (TIMP-1), matrix metalloproteinase 9 (MMP-9) and collagen IV (COL IV) were determined using immunohistochemistry. Neurobehavioural scores decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.05). Compared with the sham group, EB extravasation was higher in the model group (P<0.01). The amount of EB extravasation decreased in the SJZD high dose and nimodipine groups compared to the model group (P<0.01), and extravasation in the SJZD high dose group was lower than the SJZD low and medium dose groups (P<0.01). TIMP-1 and MMP-9 expression and apoptotic rate increased, but COL IV decreased significantly in the hippocampus of the model group compared to the sham group (P<0.01). TIMP-1 and COL IV expression increased significantly and MMP-9 and apoptotic rate decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.01). TIMP-1 and COL IV expression decreased, but MMP-9 expression and apoptotic rate increased in the SJZD low and medium dose groups compared to the SJZD high dose group (P<0.01). SJZD rescued neurons and improved neurobehavioural function in rats following cerebral ischaemia-reperfusion, especially when used at a high dose. The mechanism may be related to protection of the extracellular matrix followed by anti-apoptotic effects.