Targets Of Traditional Chinese Medicine Research Articles

Research Progress on Inhibition of Osteoclast Differentiation by Traditional Chinese Medicine

Background: Bone tissue undergoes continuous remodeling to maintain a steady state of bone equilibrium. During this process, osteoblasts actively stimulate bone formation, while osteoclasts continuously engage in bone resorption. The dynamic equilibrium between bone formation and bone resorption is crucial for maintaining bone structure. In a healthy human skeletal structure, the two components are constantly in a state of benign dynamic equilibrium. However, due to factors such as aging, trauma, bone diseases, and other influences, the activity of osteoblasts decreases while the activity of osteoclasts increases. This disrupts the dynamic equilibrium, leading to a decrease in bone metabolism. As a result, bone resorption gradually surpasses bone production, making it challenging to maintain a normal amount of bone mass. The effectiveness of traditional Chinese medicine in treating bone-related disorders is extraordinary, and its molecular biological mechanism has become a widely discussed subject. Objectives: This study aims to unravel the classical signaling pathways and potential targets involved in the effects of traditional Chinese medicine on osteoclast differentiation, and to provide evidence for its clinical efficacy. Methodology: The main keywords chosen for this study were “Traditional Chinese Medicine (TCM)”, “osteoclast differentiation”, “natural plant”, and “medicinal plant”. To gather relevant literature, we utilized multiple online search engines, including PubMed, Web of Science, and CNKI, as well as other publication resources. Results: The results indicated that Traditional Chinese Medicine (TCM) can modulate signaling pathways, including NF-κB, MAPKs, STATs, and Wnt/β-catenin pathways., to influence osteoclast differentiation. This modulation involves maintaining the balance of inflammatory interactions, inhibiting oxidative stress. Conclusion: The impact of traditional Chinese medicine on osteoclast differentiation is reflected on multiple levels and through various pathways. Future research is envisioned to delve deeper from the perspective of precision-targeted therapy, aiming to provide insights for identifying the core targets of traditional Chinese medicine in treating orthopedic diseases.

Transcriptomic analysis reveals the critical role of chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu decoction

Ethnopharmacological relevanceThe process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AimThis study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. Materials and methodsAS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. ResultsAfter ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). ConclusionXuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

Network pharmacology and gut microbiota insights: unraveling Shenling Baizhu powder's role in psoriasis treatment.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood. Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models. Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement. Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP's modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Noncanonical pyroptosis pathway: a promising target of traditional Chinese medicine in the treatment of sepsis-related injury

Noncanonical pyroptosis pathway: a promising target of traditional Chinese medicine in the treatment of sepsis-related injury

Interpreting the pharmacological mechanisms of Juanbi recipe on rheumatoid arthritis through network pharmacology, molecular docking.

Traditional Chinese medicine (TCM) offers the advantage of effectively relieving rheumatoid arthritis (RA) with minimal side effects. The Juanbi recipe is a commonly utilized TCM treatment for RA, yet its pharmacological mechanism remains unclear. Network pharmacology serves as an effective tool for identifying pharmaceutical ingredients and potential therapeutic targets of TCM, thereby uncovering its mechanisms. This study aimed to identify the core target genes and explore the mechanisms underlying the treatment of RA with the Juanbi recipe. This study adopted the method of network pharmacology to filter key gene targets of Juanbi recipe in RA treatment. Single-cell ribonucleic acid (RNA) sequencing data was used to screen the key genes to form the core genes of Juanbi recipe in RA treatment. The molecular docking technique was used to verify the core target genes and explore the mechanisms of Juanbi recipe in RA treatment. The RA model of mice was induced by the collagen-induced arthritis and the effect of Juanbi recipe was evaluated by intragastric administrating of extraction of Juanbi recipe. Enzyme linked immunosorbent assay was used to analysis serum inflammatory factors. Hematoxylin and eosin staining was used to evaluate inflammation and immunohistochemical (IHC) staining was used to evaluate core target genes and pathways in synovium of ankle. This study screened out 281 active molecules in Juanbi recipe, found 105 key target genes of Juanbi recipe in RA treatment, and drew an "ingredient - molecule - gene" diagram. Juanbi recipe reduced the levels of serum interleukin (IL)-1 and IL-6, the inflammatory infiltration in synovium, demonstration that Juanbi recipe reduced both systemic and synovial inflammatory response. Single cell RNA sequencing data were used to select six core target genes and six core active molecules of Juanbi recipe in RA treatment. The pathways of Juanbi recipe in RA treatment involved in activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB) pathway. Results of western blot and IHC staining showed that Juanbi recipe decreased the expressions of c-jun and p65, which demonstrated that Juanbi recipe inhibited the expression of AP-1 and NF-κB pathway in RA. The core active molecules of Juanbi recipe could inhibit key factors of AP-1 and NF-κB pathway to inhibit the inflammation, which played a protective role in RA.

Exploring the potential mechanism of Simiao Yongan decoction in the treatment of diabetic peripheral vascular disease based on network pharmacology and molecular docking technology

The study aims to investigate the potential action targets and molecular mechanisms of Simiao Yongan decoction (SMYAD) in treating diabetic peripheral vascular disease (DPVD) by utilizing network pharmacology analysis and molecular docking technology. The components and targets of SMYAD were screened using the TCMSP database, while DPVD-related genes were obtained from the GeneCards, OMIM, and Disgenet databases. After intersecting the gene sets, a Protein-Protein Interaction (PPI) network was established, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. The practical chemical components and core targets identified were molecularly docked using AutoDock software. A total of 126 active compounds were screened from which 25 main components included quercetin, rutoside, hesperidin, naringin, and β-sitosterol were determined to be the active components most associated with the core targets. A total of 224 common target genes were obtained. Among them, JUN, AKT1, MAPK3, TP53, STAT3, RELA, MAPK1, FOS, and others are the expected core targets of traditional Chinese medicine. The top-ranked GO enrichment analysis results included 727 biological processes (BP), 153 molecular functions (MF), and 102 cellular components (CC). KEGG pathway enrichment analysis involved mainly 178 signaling pathways, such as cancer signaling pathway, AGE-RAGE signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, endocrine resistance signaling pathway, cell aging signaling pathway, and so on. The molecular docking results demonstrate that the principal chemical components of SMYAD exhibit considerable potential for binding to the core targets. SMYAD has the potential to treat DPVD through various components, targets, and pathways. Its mechanism of action requires further experimental investigation.

Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Mechanisms of Xiaozheng decoction for anti-bladder cancer effects via affecting the GSK3β/β-catenin signaling pathways: a network pharmacology-directed experimental investigation

PurposeThe combination of Xiaozheng decoction with postoperative intravesical instillation has been shown to improve the prognosis of bladder cancer patients and prevent recurrence. However, the mechanisms underlying the efficacy of this herbal formula remain largely unclear. This research aims to identify the important components of Xiaozheng decoction and explore their anti-bladder cancer effect and mechanism using network pharmacology-based experiments.MethodsThe chemical ingredients of each herb in the Xiaozheng decoction were collected from the Traditional Chinese Medicine (TCM) database. Network pharmacology was employed to predict the target proteins and pathways of action. Disease databases were utilized to identify target genes associated with bladder cancer. A Protein–Protein Interaction (PPI) network was constructed to illustrate the interaction with intersected target proteins. Key targets were identified using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. A compound-target-pathway network was established after molecular docking predictions. In vitro experiments with bladder cancer cell lines were conducted using core chemical components confirmed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to verify the conclusions of network pharmacology.Results45 active compounds were extracted, and their relationships with Traditional Chinese Medicines (TCMs) and protein targets were presented, comprising 7 herbs, 45 active compounds, and 557 protein targets. The intersection between potential TCM target genes and bladder cancer-related genes yielded 322 genes. GO and KEGG analyses indicated that these targets may be involved in numerous cancer-related pathways. Molecular docking results showed that candidate compounds except mandenol could form stable conformations with the receptor. In vitro experiments on three bladder cancer cell lines demonstrated that quercetin and two other impressive new compounds, bisdemethoxycurcumin (BDMC) and kumatakenin, significantly promoted cancer cell apoptosis through the B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/BAX) pathway and inhibited proliferation and migration through the glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway.ConclusionBy employing network pharmacology and conducting in vitro experiments, the mechanism of Xiaozheng decoction’s effect against bladder cancer was tentatively elucidated, and its main active ingredients and targets were identified, providing a scientific basis for future research.

Prevention and treatment of inflammatory arthritis with traditional Chinese medicine: Underlying mechanisms based on cell and molecular targets.

Inflammatory arthritis, primarily including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, is a group of chronic inflammatory diseases, whose general feature is joint dysfunction with chronic pain and eventually causes disability in older people. To date, both Western medicine and traditional Chinese medicine (TCM) have developed a variety of therapeutic methods for inflammatory arthritis and achieved excellent results. But there is still a long way to totally cure these diseases. TCM has been used to treat various joint diseases for thousands of years in Asia. In this review, we summarize clinical efficacies of TCM in inflammatory arthritis treatment after reviewing the results demonstrated in meta-analyses, systematic reviews, and clinical trials. We pioneered taking inflammatory arthritis-related cell targets of TCM as the entry point and further elaborated the molecular targets inside the cells of TCM, especially the signaling pathways. In addition, we also briefly discussed the relationship between gut microbiota and TCM and described the role of drug delivery systems for using TCM more accurately and safely. We provide updated and comprehensive insights into the clinical application of TCM for inflammatory arthritis treatment. We hope this review can guide and inspire researchers to further explore mechanisms of the anti-arthritis activity of TCM and make a great leap forward in comprehending the science of TCM.

Identification of glycogen phosphorylase L as a potential target for lung cancer.

Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.

Role of the HIF-1α/BNIP3 Signaling Pathway in Recurrent Hepatocellular Carcinoma and the Mechanism of Traditional Chinese Medicine.

Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.

Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review.

Mycotoxin contamination has become one of the biggest hidden dangers of food safety, which seriously threatens human health. Understanding the mechanisms by which mycotoxins exert toxicity is key to detoxification. Ferroptosis is an adjustable cell death characterized by iron overload and lipid reactive oxygen species (ROS) accumulation and glutathione (GSH) depletion. More and more studies have shown that ferroptosis is involved in organ damage from mycotoxins exposure, and natural antioxidants can alleviate mycotoxicosis as well as effectively regulate ferroptosis. In recent years, research on the treatment of diseases by Chinese herbal medicine through ferroptosis has attracted more attention. This article reviews the mechanism of ferroptosis, discusses the role of ferroptosis in mycotoxicosis, and summarizes the current status of the regulation of various mycotoxicosis through ferroptosis by Chinese herbal interventions, providing a potential strategy for better involvement of Chinese herbal medicine in the treatment of mycotoxicosis in the future.

Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification

This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 μg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.

Network pharmacology implicates traditional Chinese medicine in regulating systemic homeostasis to benefit Alzheimer's disease.

Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and biological systems coordination, which meet the criteria of the network pharmacological application. Therefore, using network pharmacology to discover the relationship between TCM, diseases, and cellular responses is easily achievable. Aging-induced imbalanced homeostasis is a risk factor for Alzheimer's disease (AD), a neuronal disease regulated by multiple genes. Meta-analysis of TCM in metabolic regulation to improve symptoms of AD helps understand the pharmacological effects. The drug targets of TCM can be investigated using a holistic network pharmacology approach to find potential modulators involved in AD-related metabolic pathways. Based on the theoretical prediction of TCM for AD, experimental validation is needed to develop pure compounds for specific treatments.

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis.

Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.

"Liver-gut" axis: A target of traditional Chinese medicine for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) occurs when fat accumulates in the liver even without excessive alcohol intake. Among the current therapeutic approaches for NAFLD, lifestyle modification with dietary changes and regular exercise is the mainstay treatment. With the rise of intestinal microecology, regulation of the "liver-gut" axis can be an effective treatment for NAFLD. This review aimed to assess the modulation of the liver-gut microbiota axis with traditional Chinese medicine (TCM) as a therapeutic approach to NAFLD and further explored its application in the newly discovered therapeutic avenues beyond NAFLD treatment.

Research progress in traditional Chinese medicine in the treatment of Alzheimer's disease and related dementias.

Alzheimer's disease (AD) is the world's leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.

Integrated analysis of comprehensive metabolomics and network pharmacology to reveal the mechanisms of abelmoschus manihot (L.) medik. in the treatment of cisplatin-induced chronic kidney disease.

Background: Abelmoschus manihot (L.) Medik ("Huangkui" in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated. Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology. Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP >1, p < 0.01, and FC > 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other. Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD. Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.

Identifying Potential Gene Defect Patterns Related to COVID-19 Based on Pharmacological and Bioinformatics Analysis for Lung Adenocarcinoma.

BackgroundCoronavirus disease 2019 (COVID-19) greatly affects cancer patients, especially those with lung cancer. This study aimed to identify potential drug targets for lung adenocarcinoma (LUAD) patients with COVID-19.MethodsLUAD samples were obtained from public databases. Differentially expressed genes (DEGs) related to COVID-19 were screened. Protein–protein interactions among COVID-19-related genes, the traditional Chinese medicine (TCM) and TCM target genes were analyzed by CytoScape. The correlation between tumor microenvironment and COVID-19 target genes were assessed by Pearson correlation analysis. Unsupervised consensus clustering was conducted to categorize molecular subtypes.ResultsWe filtered 26 COVID-19 target genes related to TCM for LUAD. Interleukin (IL)-17 signaling pathway and tumor necrosis factor (TNF) signaling pathway were significantly enriched in these 26 genes. A strong correlation was found between COVID-19 target genes and tumor microenvironment (TME), cell death. Importantly, interleukin-1beta (IL1B) was identified as a core gene in the protein–protein interactions (PPI) network. Based on the 26 target genes, two molecular subtypes showing distinct overall survival, TME and response to target therapy were developed.ConclusionsThis study explored 26 COVID-19 target genes, which could serve as potential therapeutic drug targets for LUAD. IL1B was verified as a critical target for developing new molecular drugs. Furthermore, two novel molecular subtypes showed the potential to guide personalized therapies in clinical practice.

Treatment of refractory acute gout by invigorating spleen, raising Yang, dehumidifying, and dredging collaterals: A metabolomics study

ObjectiveThis study aimed to use proton nuclear magnetic resonance technology to analyze the metabolic pathways of invigorating the spleen and promoting Yang dehumidification and dredging collaterals (Cassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction) in treating the acute attack of refractory gout and to find the target of traditional Chinese medicine (TCM). MethodForty patients with acute refractory gout of spleen deficiency and dampness-heat type were recruited and randomly divided into TCM group and the Western medicine group, with 20 patients in each group. Serum samples were collected before and after 10 days of treatment for comparative analysis, and the metabolic pathways were identified. Combined with the results of TCM syndrome score, inflammatory indexes (C reactive protein, erythrocyte sedimentation rate), and creatinine, adiponectin, and cytokine (interleukin-6, tumor necrosis factor-α) levels before and after treatment, the mechanism of TCM action was analyzed. ResultsCassia twig Peony Anemarrhenae and Rise Yang Dehumidification Decoction were found to be better than Western medicine in alleviating joint swelling and pain, localized as well as systemic fever, and bitter and dry mouth. Furthermore, inflammatory indicators, cytokines, creatinine, and adiponectin levels were better in the TCM group than in the Western medicine group. In terms of metabolic pathways, the treatment of an acute attack of refractory gout with our TCM compounds resulted in better improvements in branched-chain amino acid (BCAA) metabolism, glycine, serine, and threonine metabolism, tyrosine metabolism, taurine, and low taurine metabolism, glycolysis/sugar dysplasia, synthesis and degradation of ketone body, D-glutamine metabolism, citric acid cycle (TCA cycle), glyceride metabolic pathways, etc., than the use of Western medicine. ConclusionTCM compounds may improve the metabolic network of refractory acute gout by stimulating the above metabolic pathways to inhibit the inflammatory response, relieve joint pain, and augment glucose metabolism, energy metabolism, and lipid metabolism. These compounds are hence worthy of promotion.