Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen.

Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.

Eucommiae Folium and Active Compounds Protect Against Mitochondrial Dysfunction-Calcium Overload in Epileptic Hippocampal Neurons Through the Hypertrophic Cardiomyopathy Pathway.

Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy.

Omics combined with network pharmacology reveal the neuroprotective mechanism of Sophora tonkinensis based on the biolabel research pattern: The treatment of Parkinson's disease against oxidative stress and neuroexcitatory toxicity.

Based on the biolabel research pattern, omics and network pharmacology were used for exploring the neuroprotection of Sophora tonkinensis (ST) in the treatment of brain diseases. Multi-omics were applied to investigate biolabels for ST intervention in brain tissue. Based on biolabels, the therapeutic potential, mechanism and material basis of ST for treating brain diseases were topologically analyzed by network pharmacology. A Parkinson's disease (PD) mouse model was used to validate biolabel analysis results. Four proteins and three metabolites were involved in two key pathways (alanine, aspartate and glutamate metabolism and arginine biosynthesis) and considered as biolabels. Network pharmacology showed that ST has the potential to treat some brain diseases, especially PD. Eight compounds (including caffeic acid, gallic acid and cinnamic acid) may serve as the material basis of ST treating brain diseases via the mediation of three biolabels. In the PD model, ST and its active compounds (caffeic acid and gallic acid) may protect dopaminergic neurons (maximum recovery rate for dopamine, 49.5%) from oxidative stress (E3 ubiquitin-protein ligase parkin, reactive oxygen species, nitric oxide, etc.) and neuroexcitatory toxicity (glutamate dehydrogenase, glutamine, glutamic acid, etc.). These findings indicated that omics and network pharmacology may contribute to the achievement of the objectives of this study based on the biolabel research pattern.

Biolabel-led research pattern reveals serum profile in rats after treatment with Herba Lysimachiae: Combined analysis of metabonomics and proteomics.

In traditional Chinese medicine, Herba Lysimachiae (HL) is mainly used to treat rheumatic arthralgia. Current pharmacological studies also showed that HL has therapeutic potential for synovial diseases. HL is an oral drug, whose compounds need to enter the blood circulation before reaching the injured tissue, thus potentially causing activity or toxicity to the blood system. In this study, the biolabel-led research pattern was used to analyze the serum profile after HL intervention, based on which the safety and efficacy of HL were explored. Metabonomics and proteomics were combined to analyze the biolabels responsible for the interventions of HL in serum. Bioinformatics databases were used to screen for the material basis that may interfere with biolabels. Omics analysis showed that differentially expressed proteins (19) and metabolites (5) were identified and considered as the potential biolabels, which were involved in 8 biochemical processes (platelet activation and aggregation, blood glucose release, immune and inflammatory regulation, oxidative stress, endoplasmic reticulum stress, tumor progression, blood pressure regulation, and uric acid synthesis). Thirty-one compounds may be the material basis to interfere with 11 biolabels. The present research reveals that the potential activities and toxicities of HL can be explored based on the biolabel-led research pattern.

The active ingredients analysis of Herba Lysimachiae treating osteoarthritis based on the LC-MS/MS technology and public bioinformatics platforms.

Herba Lysimachiae inhibits synovial damage in osteoarthritis via regulating two bio labels (integrin alpha 2b/beta 3). However, the relevant active ingredients are still unknown. Here, the active ingredients of herbal medicines were analyzed based on the liquid chromatography-tandem mass spectrometry technology and public bioinformatics platforms. The liquid chromatography-tandem mass spectrometry technology was used for compound analysis, and public databases (PubChem BioAssay and STRING) were applied to establish the links between herbal compounds and both bio labels, and identify which herbal compounds may regulate these bio labels. Subsequently, the osteoarthritis model was used to confirm the results. Totally, ninety compounds in Herba Lysimachiae were identified based on the liquid chromatography-tandem mass spectrometry technology. Bioinformatics analysis showed that five compounds (myricetin, fisetin, esculetin, 7-hydroxycoumarin-4-acetic acid, and caffeic acid) may synergistically regulate bio labels through 11 targets, which may be the active ingredients of Herba Lysimachiae for osteoarthritis treatment. In the verification experiments, five compounds markedly suppressed the overexpression of bio labels in the synovium of the osteoarthritis model. In conclusion, the present study effectively and rapidly analyzed the active ingredients of Herba Lysimachiae for osteoarthritis treatment.

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction.

Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5-1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug-likeness properties will be further studied and developed. Therefore, the herbal compounds with anti-RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti-inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-RA drug discovery.

Microarray Expression Analysis for the Paradoxical Roles of Acanthopanax senticosus Harms in Treating α-Synucleinopathies.

α-Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α-synuclein overexpression and toxicity. Identifying the RNAs related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non-coding RNAs (lncRNAs) and mRNAs was undertaken in control non-transgenic and human α-synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α-synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti-α-synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α-synuclein group, which may cause potential neurotoxicity analogous to α-synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α-synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions.

Metabonomic Study of the Effects of Acanthopanax senticosus on Peripheral System of Rats.

Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application.

[Study on potential effect of Dioscorea nipponica in intervening peripheral system of rats based on metabonomic analysis].

To study the potential effect of Dioscorea nipponica(DN) in intervening peripheral system of rats based on metabolomic analysis. The identification of the potential intervention targets of DN in peripheral system may facilitate its safe application and therapeutic potential exploitation. Totally 20 male SD rats were randomly divided into the blank group and the DN-treated groups, with 10 rates in each group. The DN-treated group was orally administrated with DN extracts once a day for 5 days, with the dose of 80 mg x kg(-1) (equivalent to 15 g crude drug in human), and the blank group was given equal volume of saline once a day for 5 days. Heart, liver, spleen, lung, and kidney tissues and serum samples were collected from each rat 24 h later after the last administration. The ultra-performance liquid chromatography/quadrupole time-of-flight-mass spectrometry based metabolomics was used to investigate the effect of DN in intervening peripheral system of rats. After the treatment with DN, 5 modulated metabolites in heart tissue, 6 in liver tissue, 5 in spleen tissue, 3 in lung tissue, 5 in kidney tissue and 6 in serum sample were identified and considered as the potential intervention targets of DN. Effect of DN in regulating some endogenous metabolites was beneficial for protecting peripheral system, while that in other endogenous metabolites produced potential toxicity to peripheral system. The metabolomic analysis revealed the coexistence of protective and toxic effects of DN on peripheral system, which may be a practical guidance for its safe application and beneficial to the expansion of its application scope.

Therapeutic effect of Rhizoma Dioscoreae Nipponicae on gouty arthritis based on the SDF-1/CXCR 4 and p38 MAPK pathway: an in vivo and in vitro study.

Rhizoma Dioscoreae Nipponicae (RDN) is a widely used traditional Chinese herb, which is used to treat arthroncus, arthrodynia and arthritis. As is known to us, inflammatory mechanisms have played an important role in the occurrence, course and prognosis of gouty arthritis (GA). The aim of this study was to determine the characteristic expressed proteins of synovium in GA rat and synovial cell. The rat model of GA was induced by monosodium urate (MSU) crystal. Tissue samples were assayed by immunohistochemical method. The effects of RDN on Stromal cell-derived factor 1 (SDF-1), CXCR 4 and p38 mitogen-activated protein kinase (MAPK) were investigated in MSU crystal-induced rat. The levels of SDF-1 and mitogen-activated kinase kinase (MKK) 3/6 were measured by Western Blot in interleukin-1ß (IL-1ß) incubated fibroblast-like synoviocytes (FLS). A significant increase in the levels of SDF-1, CXCR 4 and p38 MAPK were observed in MSU crystal-induced rat. The increased SDF-1 and MKK 3/6 levels were observed in IL-1ß incubated FLS. With the treatment of RDN, the above changes were reverted back to near normal levels. RDN might have some therapeutic effects on GA through SDF-1/CXCR 4 and p38 MAPK pathway, and dioscin may be the active compound in RDN to exert therapeutic effect on GA.

Sophora tonkinensis and active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency in myocardial ischemia mice through regulating the vesicle-mediated transport pathway.

Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1ß, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.

Liver protein and metabolite biolabels reveal hepatoprotective effects and active compounds of Eucommiae folium: Exploration of new application of herb based on multi-omics and bioinformatics.

A biolabel-led research based on multi-omics and bioinformatics was applied to analyze the application value of Eucommiae folium (EF) in liver cirrhosis, as well as the mechanism of action and material basis. Multi-omics were used to analyze the biolabels and key pathways of EF intervention in liver tissue. Subsequently, based on the information, bioinformatics was used to analyze the application value of EF in liver disease, as well the mechanism of action and material basis. Finally, histopathological and target expression analyses in an animal model were used to verify biolabels analysis results. Multi-omics showed that 18 proteins and 10 metabolites involved in five key pathways were screened as biolabels. Bioinformatics suggested that the application value of EF for liver cirrhosis may be the highest among the liver diseases that it may treat. Additionally, EF and five active compounds (curcumol, eucalyptol, (+)-catechin, naringenin, and quercetin) may protect the cirrhotic liver against the excessive energy expenditure and hepatic stellate cells activation through suppressing the oxidative phosphorylation pathway in a CCl4-induced mouse model. This study provides reference and evidence for the application value of EF in liver diseases, especially liver cirrhosis.

Drug-repurposing by virtual and experimental screening of PFKFB3 inhibitors for pancreatic cancer therapy.

Pancreatic cancer (PC) is the most frequently occurring cancer, with few effective treatments and a 5-year survival rate of only about 11%. It is characterized by stiff interstitium and pressure on blood vessels, leading to an increased glycolytic metabolism. PFKFB3 plays an important role in glycolysis, and its products (fructose-2,6-bisphosphate), which are allosteric PFK1 activators, limit the glycolytic rate. In this study, 14 PFKFB3 inhibitors were obtained by virtually screening the FDA-approved compound library. Subsequently, the in-vitro investigations confirmed that Lomitapide and Cabozantinib S-malate exhibit the excellent potential to inhibit PFKFB3. The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

Cardioprotection of Eucommiae Folium: the extract and pharmaceutically active compounds attenuate hyperglycemia, mitochondrial dysfunction, calcium dyshomeostasis, insulin resistance, and oxidative stress in diabetic cardiomyopathy db/db mice.

OBJECTIVES: A biolabel research based on multi-omics, informatics, molecular docking, and experimental verification was used to investigate the cardioprotective effect and pharmaceutically active compounds of Eucommiae Folium (EF). KEY FINDINGS: Based on the biolabel research pattern, metabonomics, proteomics, and bioinformatics indicated that EF has a therapeutic potential for a variety of heart diseases, especially cardiomyopathy, and the most critical mechanism involved is the diabetic cardiomyopathy pathway. Bioinformatics, cheminformatics, and molecular docking showed that 24 EF compounds may play a therapeutic role in diabetic cardiomyopathy via this pathway. Among which, four compounds (kaempferol, esculetin, (+)-catechin, and astragalin) showed appropriate pharmacokinetic parameters and formed stable binding with biolabels in the pathway. In diabetic cardiomyopathy db/db mice, histopathological analysis, mitochondrial swelling and membrane potential assay, ELISA, and biochemical analysis demonstrated that EF and four active compounds had obvious hypoglycemic effects and attenuated myocardial damage and related pathological processes, such as mitochondrial dysfunction, calcium dyshomeostasis, insulin resistance, and oxidative stress. CONCLUSIONS: This study provides new evidence and insights into the effect, mechanism, and material basis of EF in treating diabetic cardiomyopathy.

Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy.

Purpose: Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility. Methods: In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed. Results: In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment. Conclusion: The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.

Sophorae tonkinensis radix et rhizome-induced pulmonary toxicity: A study on the toxic mechanism and material basis based on integrated omics and bioinformatics analyses.

The root and rhizome of Sophora tonkinensis Gagnep. (ST) are widely used for the treatment of tonsillitis, sore throats, and heat-evil-induced diseases in traditional Chinese medicine. However, the clinical application of ST is relatively limited due to its toxicity. The mechanism and material basis of ST-induced pulmonary toxicity are still unclear. In the present research, integrated omics and bioinformatics analyses were used to investigate the toxic mechanism and material basis of ST in lung tissue. Proteomics and metabonomics were integrated to analyze the differentially expressed proteins and metabolites. Joint pathway analysis was used to analyze the significantly dysregulated pathways. PubChem and the Comparative Toxicogenomics Database were applied for the screen of toxic targets and compounds. Integrated omics revealed that 323 proteins and 50 metabolites were differentially expressed after treating with ST, out of which 19 proteins and 1 metabolite were significantly enriched in seven pathways. Bioinformatics showed that 15 compounds may indirectly affect the expression of 9 toxic targets of ST. Multiple toxic targets of ST-induced pulmonary injury were found in the study, whose dysregulation may trigger pulmonary cancer, dyspnea, and oxidative stress. Multiple compounds may be the toxic material basis in response to these effects.

Biolabel-led research pattern positions the effects and mechanisms of Sophorae Tonkinensis radix et rhizome on lung diseases: A novel strategy for computer-aided herbal medicine research based on omics and bioinformatics.

Previous studies have shown that Sophorae Tonkinensis radix et rhizome (ST) can be used to treat some lung diseases. However, the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST treatment of lung diseases remain unclear. Thus, the aim of this study was to carry out an integrated analysis based on the biolabel-led research pattern. Proteomics and metabonomics were applied to explore the biolabels responsible for the effect of ST on lung tissue. Based on the biolabels, a bioinformatics database was used to topologically analyze the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST in treating lung diseases. Four human lung-cancer cell models were used to validate the results of the biolabel analysis. In total, 45 proteins and 3 metabolites were significantly enriched in 13 pathways and were considered as biolabels. Bioinformatics revealed that the therapeutic potentials of ST involved a variety of lung diseases, especially lung neoplasms. Under the mediation of 40 biolabels, 29 compounds may be the material basis of ST in treating lung diseases. In a verification experiment, ST had a significant inhibitory effect on the H226 cell line (lung squamous cell carcinoma), which ranks first in morbidity and mortality among lung cancers in China. Additionally, five biolabels (CPS1, CKM, CPT1B, COX5B, and COX4I1) were involved in the anti-lung cancer mechanism of ST and 3 compounds (gallic acid, betulinic acid, and caffeic acid). These findings indicate that the biolabel-led research pattern was helpful in achieving the objectives of this study.

A biolabel research based on metabonomics reveals the therapeutic potentials of Herba Lysimachiae in synovial diseases: The dual effects on synovial platelet aggregation by prostaglandin E1/E2.

Previous research has demonstrated that Herba Lysimachiae (HL) exerts the dual effects on platelet aggregation in the synovium, which may contribute to its protection against synovial lesions under different situations. However, the mechanism is unclear. In the present experiment, a biolabel research based on metabonomics was used to mine the information about the intervention of HL on synovium at the metabolite level, which may help to analyze the regulation of HL on synovial platelet aggregation and its possible treatment in synovial diseases. Synovial metabolic profiling was analyzed using a Shimadzu Nexera UHPLC LC-30A system and an AB SCIEX Triple TOF 4600 mass spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to verify the biolabels analysis results in the healthy and osteoarthritis rats. Totally, thirteen common metabolites were differentially expressed after treating with HL, and implicated in 2 key pathways (arachidonic acid metabolism and glycerophospholipid metabolism). ELISA showed that HL regulated the expression of prostaglandins E1 and E2 in synovial tissues of the healthy and osteoarthritis rats. This study reveals that HL may regulate synovial platelet aggregation through prostaglandin E1/E2. Additionally, HL is suitable for treating synovial diseases, especially osteoarthritis, which may be associated with platelet aggregation, apoptosis, inflammation, angiogenesis, and carcinogenesis processes.

A Review of Pharmacological and Toxicological Effects of Sophora tonkinensis with Bioinformatics Prediction.

Sophora tonkinensis Gagnep. (ST) (Fabaceae) is distributed chiefly in south-central and southeast China and Vietnam. In traditional Chinese medicine theory, the root and rhizome of ST are toxic and mainly used in the treatment of pharyngeal and laryngeal diseases. Modern studies provide new insights into the pharmacological and toxicological aspects of ST. The pharmacological and toxicological properties of ST were reviewed in this paper based on the literature from Google Scholar and CNKI, and the bioinformatics platforms were applied to explore the pharmacological and toxicological potentials of ST. The results of the literature analysis showed that ST has hepatoprotective, immunomodulatory, and anticancer effects and produces obvious toxicity to the liver and nervous and cardiovascular system. The results of bioinformatics showed that the compounds from ST may be applied to the treatment of cancer and digestive and nervous system diseases and show the possibility to cause hematotoxicity, neurotoxicity, and immunotoxicity. The present review demonstrates that attention should be paid to the potential toxicity of ST in the treatment of diseases and provides the reference for the subsequent pharmacological toxicological studies on the mechanism and chemical basis of ST.