Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala.
Animals ; Diet, High-Fat/adverse effects* ; Fibroblast Growth Factors/genetics* ; Mice ; Male ; Panax/chemistry* ; Mice, Inbred C57BL ; Anxiety/etiology* ; Saponins/administration & dosage* ; Brain-Derived Neurotrophic Factor/genetics* ; Humans ; Liver/metabolism* ; Drugs, Chinese Herbal/administration & dosage*

Based on the similarity of chemical constituents between Panax notoginseng flowers and rhizomes, this study investigated their lipid-lowering effects and impacts on the intestinal flora of rats. The main components of P. notoginseng flowers and rhizomes were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) to compare their chemical similarities. A hyperlipidemia rat model was induced using a high-fat diet. After successful modeling, the rats were divided into the blank control group, blank administration group(0.090 g·kg~(-1)), model group, low-(0.045 g·kg~(-1)), medium-(0.090 g·kg~(-1)), high-dose(0.180 g·kg~(-1)) P. notoginseng flower group, P. notoginseng rhizome group(0.270 g·kg~(-1)), and simvastatin group(0.900 mg·kg~(-1)). After modeling, the rats were given intragastric administration for 3 weeks, once daily, while their body weight was recorded regularly. Before the last administration, fresh feces were collected for analysis of changes in intestinal flora using 16S rDNA high-throughput sequencing technology. One hour after the last administration, the rats were anesthetized with 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Serum biochemical indexes were detected using an automatic biochemical analyzer. Organs(heart, liver, spleen, lung, and kidney) were harvested, and organ index were calculated. Liver tissue pathology was assessed through HE staining and oil red O staining. The results indicated that there were 33 identical chemical constituents in P. notoginseng flowers and rhizomes, accounting for 75.00% of the total constituents. After treatment, high-dose P. notoginseng flower group and P. notoginseng rhizome group exhibited similar effects on body weight, serum biochemical indexes, and liver histopathological conditions. Compared with model control group, the abundance of Firmicutes and Actinobacteria increased in high-dose P. notoginseng flower and rhizome groups, while the abundance of Bacteroidetes and Thermodesulfobacteria decreased. Cluster analysis showed no significant difference between the two groups. Both P. notoginseng flowers and rhizomes possess similar chemical components and lipid-lowering effects, and they can regulate the intestinal flora imbalance caused by hyperlipidemia, indicating their potential for use in hyperlipidemia treatment.
Animals ; Hyperlipidemias/microbiology* ; Panax notoginseng/chemistry* ; Rats ; Rhizome/chemistry* ; Male ; Flowers/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/administration & dosage* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Liver/drug effects*

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

Gardeniae Fructus, a traditional Chinese medicine, has significant pharmacological activities such as clearing heat and detoxifying, promoting bile secretion and protecting liver injury. It is widely used in clinical practice for treating conditions like fever-induced restlessness, damp-heat jaundice, dysuria with pain, and fire-toxin sores. Gardeniae Fructus has been included in "list of items that are both food and medicine", so it is also used as an ingredient in food and health products. However, recent toxicological studies have shown that Gardeniae Fructus has certain potential hepatotoxicity, and its improper use may pose a risk. Therefore, it is necessary to clarify the dual regulatory effects and their scientific connotations of Gardeniae Fructus on efficacy and toxicity. Based on the current progress in clinical, pharmacological and toxicological researches, this paper will discuss the characteristics and possible mechanisms of the dual effects of efficacy and toxicity of Gardeniae Fructus, and propose thoughts on the rational clinical use and scientific supervision of Gardeniae Fructus.
Animals ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Fruit/chemistry* ; Gardenia/chemistry* ; Medicine, Chinese Traditional ; Liver/drug effects*

A targeted metabolomics study was conducted on the bile acid profiles in the liver and feces of rats induced by a high-fat diet and intervened by ginsenoside Rb_1, along with the detection of FXR pathway gene expression in the liver, to explore and clarify its mechanism of action. The content of biochemical indicators in the serum were detected using an automatic biochemical analyzer. Hematoxylin and eosin(HE) staining and oil red O staining were used to detect pathological changes and lipid deposition in the liver. RT-PCR was used to detect the mRNA expression of FXR, small heterodimer partner(SHP), cholesterol 7 alpha-hydroxylase(CYP7A1), and sterol regulatory element-binding protein-1c(SREBP-1c) in the liver. Targeted bile acid metabolomics technology was employed to analyze changes in bile acid profiles in liver tissue and feces, and a correlation analysis was performed between key genes such as FXR, SHP, CYP7A1, SREBP-1c and differential bile acid metabolites. The results showed that ginsenoside Rb_1 significantly reduced the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) in the serum, alleviated the large fat vacuoles and lipid deposition in the liver, increased the expression of FXR mRNA in the liver, and decreased the expression of SREBP-1c mRNA. The expression of CYP7A1 and SHP mRNA was increased, but the differences were not statistically significant. Targeted bile acid metabolomics showed that ginsenoside Rb_1 could restore the levels of 9 bile acids in the liver and 8 bile acids in the feces. Ginsenoside Rb_1 also increased the percentage of taurocholic acid(TCA) in the liver(56.78%) and the percentage of 12-ketolithocholic acid(12-KLCA) in the feces(26.10%). Pathway enrichment analysis revealed two pathways involved in bile acid metabolism: primary bile acid biosynthesis and taurine and hypotaurine metabolism. Correlation analysis showed that FXR, SHP, CYP7A1, and SREBP-1c were positively correlated with multiple differential bile acids. These results suggest that ginsenoside Rb_1 may intervene in lipid metabolism disorders induced by a high-fat diet by regulating the FXR pathway and modulating bile acid profiles in the liver and feces.
Animals ; Bile Acids and Salts/metabolism* ; Rats ; Ginsenosides/pharmacology* ; Male ; Receptors, Cytoplasmic and Nuclear/genetics* ; Liver/drug effects* ; Diet, High-Fat/adverse effects* ; Metabolomics ; Rats, Sprague-Dawley ; Feces/chemistry* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Sterol Regulatory Element Binding Protein 1/genetics* ; Humans

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*