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Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group , Blautia , Rs-E47_termite_group , UCG-009, and Clostridia_UCG-014 , were identified as the intrinsic link between GM and metabolites. The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP. [Display omitted] • BX exhibited therapeutic effects in the treatment of osteoporosis (OP). • BX modulated the gut microbiota (GM) composition and metabolism. • Functional correlations between GM and differential metabolites were discovered. • BX regulated purine and tryptophan metabolism-related GM and its metabolites. [ABSTRACT FROM AUTHOR]

Linderae Radix (Lindera aggregata (Sims) Kosterm) is a traditional Chinese medicine known for its capability to regulate qi and relieve pain, particularly in the context of gastrointestinal disorders. While our previous research has demonstrated the efficacy of the Linderae Radix water extract (LRWE) in the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), the precise mechanisms remain elusive. This study aims to provide a comprehensive understanding of the therapeutic effects of LRWE on IBS-D through multi-omics techniques. 16 S rRNA gene sequencing combined with LC-MS metabolomics was employed to investigate the effect of LRWE on the gut microbiota and metabolites of IBS-D rats. Spearman correlation analysis was performed on the gut microbiota and metabolites. LRWE administration significantly ameliorated IBS-D rats' symptoms, including diarrhea, visceral hypersensitivity, and low-grade intestinal inflammation. Gut microbiota analysis revealed that LRWE influenced the diversity of the gut microbiota in IBS-D rats by significantly reducing the relative abundance of Patescibacteria and Candidatus Saccharimonas, while increasing the relative abundance of Jeotgalicoccus. Serum metabolomic analysis identified 16 differential metabolites, associated with LRWE's positive effects on IBS-D symptoms, focusing on glyoxylate and dicarboxylic acid metabolism, and cysteine and methionine metabolism. Spearman analysis demonstrated a strong correlation between cecal microbiota composition and serum metabolite levels. This study elucidates that LRWE plays a crucial role in the comprehensive therapeutic approach to IBS-D by restoring the relative abundance of gut microbiota and addressing the disturbed metabolism of endogenous biomarkers. The identified bacteria and metabolites present potential therapeutic targets for IBS-D. [Display omitted] [ABSTRACT FROM AUTHOR]

Bawei Guben Huashi Jiangzhi Decoction (BGHJ), a traditional Chinese compound formula, comprises eight Chinese medicinal herbs: Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Cassiae Semen, Lysimachiae Herba, Edgeworthiae Gardner Flos, Oryzae Semen cum Monasco, Nelumbinis Folium, and Alismatis Rhizoma. It has the therapeutic effects of improving digestive and absorptive functions of the gastrointestinal tract, reducing cholesterol levels, and helping to lose weight. Therefore, BGHJ is mainly used to treat spleen-deficient obesity (SDO) clinically. This study aims to examine the efficacy and mechanism of BGHJ in a model of SDO in rats, as well as the potentially involved constituents entering the blood and differential metabolites. The SDO rat model was replicated utilizing a high-fat and high-sugar diet in conjunction with exhaustive swimming. Subsequently, the rats were subjected to a six-week intervention comprising varying dosages of BGHJ and a positive control, orlistat. To evaluate the efficacy of BGHJ on SDO model rats, we first measured the rats' body weight, body surface temperature, spleen index, as well as biochemical indicators in the serum and colon, and then assessed the pathological state of the colon and liver. Afterward, we analyzed the 16S rDNA gut microbiota, non-targeted serum metabolomics, and serum pharmacology to study the main active components of BGHJ and its action mechanism against SDO model rats. In addition, we constructed a network diagram for overall visualization and analysis, and experimentally verified the predicted results. Finally, we used quantitative polymerase chain reaction (qPCR) to detect the gene expression of proopiomelanocortin (POMC) and neuropeptide Y (NPY) indicators in rat hypothalamic neurons. We quantitatively targeted the detection of neurotransmitters dopamine (DA), acetylcholine (Ach), 5-hydroxytryptamine (5-HT), and noradrenaline (NA) in rat hypothalamus. The results demonstrated that all dosage regimens of BGHJ exhibited the capacity to moderately modulate parameters including body weight, surface temperature, spleen index, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), 5-HT, interleukin 6 (IL-6) and interleukin 17 (IL-17), while concurrently reducing hepatic lipid droplet deposition and restoring intestinal integrity. Subsequent experimental results showed that we successfully identified 27 blood components of BGHJ and identified 52 differential metabolites in SDO model rats. At the same time, the experiment proved that BGHJ could effectively inhibit the metabolic pathway of arachidonic acid. In addition, BGHJ can also restore the intestinal microbiota composition of SDO model rats. Finally, we also found that BGHJ could regulate the expression of hypothalamic neurons and neurotransmitters. The research revealed the main active ingredients of BGHJ and its mechanism against SDO model rats through gut microbiota, non-target serum metabolomics, and serum drug chemistry. [Display omitted] [ABSTRACT FROM AUTHOR]

Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. To understand the material foundation and liver injury mechanism of STR. Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI. [Display omitted] • A total of 152 compounds were identified in STR by UPLC-Q/TOF MS. • Active components in STR-medicated serum were identified. • Multi-omics approaches were conducted to reveal the mechanism of SILI. • Taurine, hypotaurine, and pyridoxal might be the potential biomarkers in SILI. [ABSTRACT FROM AUTHOR]

Nocardiosis is an uncommon infectious disease that bears certain similarities to tuberculosis, with a continuous increase in its incidence and a poor prognosis. In traditional Chinese medicine, the leaves of Cajanus cajan (L.) Millsp. are employed to treat wounds, malaria, coughs, and abdominal pain. In this study, we investigated the effects and mechanisms of longistylin A (LGA), a natural stilbene isolated from C. cajan , as a potential antibiotic against nocardiosis. LGA was isolated from the leaves of C. cajan and assessed using a minimum bactericidal concentration (MBC) determination against Nocardia seriolae. Multi-omics analysis encompassing genes, proteins, and metabolites was conducted to investigate the impact of LGA treatment on N. seriolae. Additionally, quantitative analysis of 40 cytokinins in N. seriolae mycelium was performed to assess the specific effects of LGA treatment on cytokinin levels. Cryo-scanning electron microscopy was utilized to examine morphological changes induced by LGA treatment, particularly in the presence of exogenous trans-zeatin-O-glucoside (tZOG). The therapeutic effect of LGA was investigated by feeding N. seriolae -infected largemouth bass. LGA exhibited significant efficacy against N. seriolae, with MBC value of 2.56 μg/mL. Multi-omics analysis revealed that LGA disrupted glycerophospholipid metabolism and hormone biosynthesis by notably reducing the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. Treatment with LGA markedly disrupted 12 distinct cytokinins in N. seriolae mycelium. Additionally, the addition of exogenous tZOG counteracted the inhibitory effects of LGA on filamentous growth, resulting in mycelial elongation and branching. Furthermore, LGA treatment improved the survival rate of largemouth bass infected with N. seriolae. We found for the first time that LGA from C. cajan exhibited significant efficacy against N. seriolae by interfering with glycerophospholipid metabolism and cytokinin biosynthesis. [Display omitted] • CJE and LGA displayed a noteworthy anti- N. seriolae efficacy. • LGA interfered glycerophospholipid metabolism and hormone biosynthesis. • LGA notably reduced the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. • LGA disrupted 12 cytokinins in N. seriolae ， tZOG counteracted LGA-elicited inhibition on the filamentous growth. • LGA enhanced the survival rate of largemouth bass infected with N. seriolae. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the mechanisms underlying the action of CXCG in DKD remain unclear. This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics. The chemical compounds of CXCG were identified using ultra-high- performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was performed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes. A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella , Oscillibacter , Anaeroplasma , Anaerotruncus , and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes. This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD. [Display omitted] • Compound Xiancao granule (CXCG), a classic Zhuang medicinal formula, has been clinically shown to be highly effective in treating DKD. • Multiomics was used to analyze the effects of CXCG against DKD rats for the first time. • The mechanisms of CXCG on DKD through remodeling gut microbiota structure and restoring the metabolic homeostasis by regulating carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways. • Microbiota-gut-kidney axis provides a novel insights to reveal the mechanism of CXCG on DKD. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine (TCM) and traditional Korean medicine (TKM), Gwakhyangjeonggi-san (GJS) is an herbal decoction used to treat gastrointestinal disorders and allergic diseases. However, no randomized controlled trials have reported the efficacy and safety of GJS against atopic dermatitis (AD) or its comorbidities. This clinical trial investigated the clinical efficacy and safety of GJS for treating patients with AD who have gastrointestinal symptoms, using a multi-omics approach that included 16S rRNA sequencing and metabolomics. This study was a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Fifty-two patients with AD (age: 19–60) were randomly assigned to receive either the GJS (N = 27) or placebo (N = 25) granules thrice daily for 8 weeks. The primary outcome was measured as the change in the SCORing of Atopic Dermatitis index from baseline to 8 weeks. The secondary outcomes included the eczema area and severity index, dermatology life quality index, EuroQoL 5 dimensions 5 levels (EQ-5D-5L), immunological factors, gastrointestinal status, and safety evaluation. In addition, 16S rRNA sequencing on gut-microbiomes and non-targeted metabolomics approach using mass spectrometry on sera samples were applied to investigate the GJS therapeutic mechanism. After 8 weeks, AD symptoms were reduced in both the GJS and placebo groups without any serious adverse events, but the reduction was not significantly different between the two groups. However, t he EQ-5D-5L scores and gastrointestinal symptom scores , such as bitter-tasting fluid presenting in the mouth, upper abdomen bloating, and nausea, only improved in the GJS group. To further elucidate the effect of GJS on patients with AD who have gastrointestinal symptoms, 16S rRNA sequencing and metabolomics were executed. The GJS group had lower gut microbiome diversity including observed OUT, Ace, Chao1 and Shannon index than the placebo group at enrollment time, while the difference in gut microbiome diversity between GJS and placebo group was eliminated by 8 weeks of treatment. Consistently, the metabolomics results showed that the gut microbiome-derived uremic toxins, including indoxyl sulfate and phenylacetylglutamine, significantly increased in the placebo group, while these in GJS group were maintained without any significant change. These results showed that the GJS had no significant effect on AD compared to the placebo but exerted a beneficial effect on improving the quality of life and gastrointestinal symptoms in patients with AD, and it acted by modulating gut microbiome diversity and gut microbiome-derived uremic toxins. Our findings support the use of GJS for AD comorbidities and also provide evidence that multi-omics approaches can be useful for understanding herbal decoctions in TCM and TKM comprehensively. [Display omitted] • GJS benefits the quality of life and gastrointestinal symptoms in AD patients. • GJS changed the microbiome diversity of AD patients with gastrointestinal symptoms. • GJS regulated the gut microbiome-derived uremic toxins. [ABSTRACT FROM AUTHOR]

Codonopsis pilosula (DS), a traditional Chinese medicine, had been used to regulate the immune, digestive and circulatory systems of the human, as well as protect the gastrointestinal tract, improve lung function. The aim of study was to explore the effects and mechanism of Codonopsis pilosula aqueous extract (DS) intervention in improving ulcerative colitis (UC). UC model rats were established using combination of TNBS and ethanol. Tissue samples were collected for transcriptome and metabolomics analysis. Network pharmacology was performed on DS to identify bioactive compounds. Western blot was used to detect the key proteins involved in UC pathogenesis and PI3K/AKT pathways. DS exerted the preventive and therapeutic effects in improving UC via inhibiting abnormal inflammatory responses and promoting antioxidant capacity. Levels of intestinal barrier, oxidative stress and inflammatory mediators were improved to nearly normal level in vivo by DS. Metabolome profiles showed that DS could restore the metabolic disorders associated with the UC pathogenesis. Further transcriptome results showed that DS mainly alleviate UC through inhibiting PI3K/Akt signaling pathway, and various related genes that dramatically expressed in UC Model rats were downregulated by DS. Typically, network pharmacology analysis identified that Glycitein was the hub compounds that involved in the mechanism of DS in improving UC. The results show that Codonopsis pilosula (DS) was an potential excellent material in treating of UC depending on its suitable concentration. Possible therapeutic mechanisms of the DS involved in mitigating colonal inflammation, restoring metabolic disorders, promoting antioxidant capacity, and especially blocking the activation of PI3K/Akt pathway. [Display omitted] • Codonopsis pilosula aqueous extract(DS)alleviates abnormal inflammatory responses and promotes antioxidant capacity. • DS could restore metabolic disorders associated with the UC pathogenesis. • Glycitein is the bioactive compounds of DS in improving UC. • DS mainly alleviate UC through inhibiting PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine theory believes that qi deficiency and blood stasis are the key pathogenesis of heart failure with preserved ejection fraction (HFpEF). As a representative prescription for replenishing qi and activating blood, QiShenYiQi dripping pills (QSYQ) has been used for treating heart diseases. However, the pharmacological mechanism of QSYQ in improving HFpEF is not well understood. The objective of the study is to investigate the cardioprotective effect and mechanism of QSYQ in HFpEF using the phenotypic dataset of HFpEF. HFpEF mouse models established by feeding mice combined high-fat diet and Nω-nitro-L-arginine methyl ester drinking water were treated with QSYQ. To reveal causal genes, we performed a multi-omics study, including integrative analysis of transcriptomics, proteomics, and metabolomics data. Moreover, adeno-associated virus (AAV)-based PKG inhibition confirmed that QSYQ mediated myocardial remodeling through PKG. Computational systems pharmacological analysis based on human transcriptome data for HFpEF showed that QSYQ could potentially treat HFpEF through multiple signaling pathways. Subsequently, integrative analysis of transcriptome and proteome showed alterations in gene expression in HFpEF. QSYQ regulated genes involved in inflammation, energy metabolism, myocardial hypertrophy, myocardial fibrosis, and cGMP-PKG signaling pathway, confirming its function in the pathogenesis of HFpEF. Metabolomics analysis revealed fatty acid metabolism as the main mechanism by which QSYQ regulates HFpEF myocardial energy metabolism. Importantly, we found that the myocardial protective effect of QSYQ on HFpEF mice was attenuated after RNA interference-mediated knock-down of myocardial PKG. This study provides mechanistic insights into the pathogenesis of HFpEF and molecular mechanisms of QSYQ in HFpEF. We also identified the regulatory role of PKG in myocardial stiffness, making it an ideal therapeutic target for myocardial remodeling. [Display omitted] [ABSTRACT FROM AUTHOR]

Buyang Huanwu Decoction (BYHW) is a classic representative formula for treating qi deficiency and the blood stasis syndrome of stroke in the Qing Dynasty physician Wang Qingren's Correction on the Errors of Medical Works. However, the research on the mechanism of BYHW in the treatment of stroke is not systematic and comprehensive. Combined with multi-omics analysis methods to explore the potential targets of BYHW in the treatment of cerebral ischemia-reperfusion (I/R). The rat middle cerebral artery occlusion (MCAO) model was established to study the effect of BYHW on cerebral I/R injury in rats. Then, the potential targets and pathways of BYHW in the treatment of cerebral I/R injury were analyzed by proteomic, transcriptomic, and metabolomic methods. Finally, 4D-PRM was used to validate potential targets. BYHW effectively improved the neurological function scores of MCAO rats and significantly reduced the rate of cerebral infarction in MCAO rats. Multi-omics analysis had identified 15 potential targets and 4 potential signaling pathways. The results of 4D-PRM targeted proteomics verification showed that Pde1b was reversed up-regulated, and Aprt, Gpd1, Glb1, HEXA, and HEXB were reversed down-regulated. BYHW may improve cerebral I/R through Aprt, Pde1b, Gpd1, Glb1, HEXA and HEXB targets, and Glycerophospholipid metabolism, Purine metabolism and Glycosphingolipid biosynthesis - globoseries pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Dengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated. To investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology. A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds. In MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3- O -glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment. DZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis. [Display omitted] • The mechanism of DZSM against IS was clarified by multi-omics and network pharmacology. • The antithrombotic and neuroprotection activities of DZSM were firstly validated in vitro. • A significantly decreased of 2-oxoglutarate was detected in DZSM treated group. • NF-κB pathway and its downstream NO, cytokines contributed to the activity of DZSM. [ABSTRACT FROM AUTHOR]

Marsdenia tenacissima (Roxb.) Moon, (M. tenacissima) a traditional herbal medicine, has been used for thousands of years. It is noted in Dian Nan Ben Cao that M. tenacissima is bitter in flavor and cold in property, and extracts possess diverse pharmacological effects, including immunomodulation and anti-tumor activities. The anti-tumor effects of M. tenacissima extracts (MTE) have been repeatedly confirmed, and this medicine has also been extensively applied in cancer treatment or prognostic adjuvant therapy, with significant curative effect. This study aims to comprehensively analyze the anti-tumor mechanism of M. tenacissima starting from the key features of traditional Chinese medicine and by studying the main active components individually to identify anti-tumor targets in the context of hepatocellular carcinoma. Molecular network profiling and multi-omic joint analyses were conducted using an H22 mouse model of hepatocellular carcinoma to determine the main active ingredients in MTE and the underlying anti-tumor mechanisms. Tenacissosides I, H, and G (TI,TH and TG) were found to be the likely active ingredients of MTE in the treatment of hepatocellular carcinoma. These compounds were shown to promote apoptosis, inhibit angiogenesis and improve immune function through targeting P53, JAK-1 and HIF1α, respectively. For the first time, based on the theory that multiple components and multiple targets synergistically exert the beneficial effects of a traditional Chinese medicine, this paper comprehensively analyzes the mechanisms of action of M. tenacissima and provides a novel strategy for the subsequent development of anti-tumor therapies. [Display omitted] [ABSTRACT FROM AUTHOR]