RESUMEN
Objective:To analyze the compatibility rules of prescriptions containing Forsythiae Fructus based on data mining and explore the anti-inflammatory mechanism of Forsythiae Fructus based on network pharmacology，so as to provide reference for the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines. Method:The prescriptions containing Forsythiae Fructus in the<italic> Dictionary of Traditional Chinese Medicine Prescriptions</italic> were collected，based on which a clinical prescription database was constructed. The Chinese herbs combined with Forsythiae Fructus and the corresponding indications were subjected to frequency statistics，association rule analysis，and complex network analysis using SPSS Statistics 26，IBM SPSS Modeler 18.0，and Gephi 9.2. The active components and targets of Forsythiae Fructus for anti-inflammation were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），BATMAN-TCM，and SEA，and the targets related to anti-inflammation from GeneCards，Online Mendelian Inheritance in Man （OMIM），CTD，and GenCLiP3. Following the analysis of protein-protein interactions （PPI） with STRING，a PPI network was constructed. The enrichment analysis was performed using Metascape，and the active component-anti-inflammation target-signaling pathway network of Forsythiae Fructus was constructed by Cytoscape 3.8.2. Result:According to the inclusion and exclusion criteria，2 245 prescriptions containing Forsythiae Fructus were harvested，involving 512 Chinese herbs，with a total usage frequency of 27 314. The Chinese herbs that were most frequently combined with Forsythiae Fructus （>800 times） were Glycyrrhizae Radix et Rhizoma （1 483 times），Scutellariae Radix （964 times），and Angelicae Sinensis Radix （842 times）. Hence，the herbal pairs "Forsythiae Fructus-Scutellariae Radix" and "Forsythiae Fructus-Angelicae Sinensis Radix" were further explored. The prescriptions containing Forsythiae Fructus could be utilized for the treatment of 29 kinds of diseases，and three representative disease categories including "carbuncle，gangrene，sores and ulcers"，"ophthalmic diseases and syndromes" and "epidemic diseases" are selected for data mining. There were 19 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Lonicerae Japonicae Flos-Angelicae Sinensis Radix" as the core herb combination for "carbuncle，gangrene，sores and ulcers". The clustering analysis revealed one multi-herb clustering group，four herbal pairs，and single herb Lonicerae Japonicae Flos，the complex network analysis four herbal modules，and the factor analysis six common factors. There were 23 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Scutellariae Radix-Angelicae Sinensis Radix" as the core herb combination for "ophthalmic diseases and syndromes". The clustering analysis revealed two multi-herb clustering groups and four herbal pairs，the complex network analysis four herbal modules，and the factor analysis five common factors. There were 28 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Menthae Haplocalycis Herba-Lonicerae Japonicae Flos" as the core herb combination for "epidemic diseases". The clustering analysis revealed three multi-herb clustering groups，one herbal pair，and two single herbs Forsythiae Fructus and Glycyrrhizae Radix et Rhizoma，the complex network analysis four herbal modules，and the factor analysis five common factors. As demonstrated by network pharmacology-based analysis，the core anti-inflammation components of Forsythiae Fructus were quercetin，luteolin，and kaempferol，and the core targets were phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1），protein kinase B 1 （Akt1），and epidermal growth factor receptor（EGFR）. The biological pathways were mainly concentrated in proteoglycans in cancer，pathways in cancer，and PI3K/Akt signaling pathway，with such functions as inhibition of transcription factors，regulation of enzyme activity，and inflammation-related gene expression involved. Conclusion:This study employed a variety of data mining techniques to objectively，intuitively，and scientifically uncover the compatibility rules of Forsythiae Fructus in the treatment of high-frequency diseases. It has been found that Forsythiae Fructus is often combined with heat-clearing herbs，tonifying herbs，exterior-releasing herbs，and blood-activating and stasis-resolving herbs for diverse diseases and syndromes. Under the premise of clearing heat and removing toxin，reinforcing healthy Qi and dredging stagnation are also emphasized. According to the degree of internal heat exuberance，the heat-clearing herbs with different merits are combined. This study has revealed the unique advantages of Forsythiae Fructus in the treatment of specific diseases and syndromes as well as its multi-component，multi-target，and multi-pathway mechanisms in anti-inflammation，breaking through the limitations in modern clinical and experimental research of Forsythiae Fructus. These findings are of great significance for guiding the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines，thus better accelerating the development of Chinese medicine health industry.
RESUMEN
<p><b>Background</b>Dandelion is commonly used in traditional Chinese medicine with several active compounds found in extracts. It has a variety of pharmacological effects, such as a reduction in swelling and inflammation, and detoxification. The mechanism by which dandelion extract inhibits the inflammatory response in skeletal muscle cells remains unknown; therefore, the aim of this study was to investigate the effects of dandelion extract root on the proliferation of skeletal muscle cells and the alleviation of lipopolysaccharide (LPS)-induced inflammatory response in vitro.</p><p><b>Methods</b>Rat skeletal muscle cells were isolated from Sprague-Dawley rat and cultured in vitro which were cultured in basal medium, or medium containing LPS or dandelion extract. Cell counting kit-8 (CCK-8) was employed to measure cell proliferation; meanwhile, the optimal concentration of dandelion extract and treatment time were selected. Crystal violet staining was used to detect the proliferation of muscle cells. Western blotting analysis was used to detect the levels of inflammatory factors, myogenic factor, and p-AKT protein expression.</p><p><b>Results</b>The optimal concentration and treatment time of dandelion extract for the following study were 5 mg/ml and 4 days, respectively. Dandelion extract was found to increase proliferation of rat skeletal muscle cells (t = 3.145, P < 0.05), with the highest effect observed at 5 mg/ml. LPS was found to decrease proliferation of skeletal muscle cells (t = -131.959, P < 0.001), and dandelion extract could against this affection (t = 19.466, P < 0.01). LPS could induce expression of inflammatory factors, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α (IL-1β: t = 9.118, P < 0.01; IL-6: t = 4.346, P < 0.05; TNF-α: t = 15.806, P < 0.05), and dandelion extract was shown to reduce LPS-induced expression of IL-1β, IL-6 and TNF-α (IL-1β: t = -2.823, P < 0.05; IL-6: t = -3.348, P < 0.01; and TNF-α: t = -3.710, P < 0.01). Furthermore, LPS was also shown to decrease expression of myogenic factor, including myod1 and myogenin (MyoD1: t = 4.039, P < 0.05 and myogenin: t = 3.300, P < 0.01), but dandelion extract was shown to against this effect of LPS (MyoD1: t = -3.160, P < 0.05 and myogenin: t = -3.207, P < 0.01). And then, LPS was found to increase expression of p-AKT protein (p-AKT/AKT: t = 4.432, P < 0.05). Moreover, expression of p-AKT protein was found to decrease, with 5 mg/ml of dandelion extract (p-AKT/AKT: t = -3.618, P < 0.05).</p><p><b>Conclusions</b>The findings indicate that dandelion extract plays an important role in skeletal muscle cells viability regulation, promote cells proliferation by increasing level of p-AKT protein expression, and reduce LPS-induced expression of inflammatory factors, inhibiting the inflammatory response of rat skeletal muscle cells.</p>