Review Article

Preclinical Models for Investigation of Herbal Medicines in Liver Diseases: Update and Perspective

Table 4

Animal models of liver cancers used to investigate the effect of herbal medicines.

ModelExperiment durationsHerbal medicineMechanism involvedReference

Implantation (ectopic)

H22 cells5 daysFuzheng-Yiliu granuleInduced cell apoptosis. Antitumour effect after combined with 5-FU. Restored decreased level of WBC and lymphocytes. [150]

H22 cells5 daysFuzheng-Yiliu granuleInduced apoptosis and CD3, CD4, and NK cells in peripheral blood. Increased serum IL-2 and TNFα levels.[49]

H22 cells5 daysTagalsinUpregulated wild type p53 and reduced Bcl-2. [151]

H22 cells10 daysGlycyrrhiza polysaccharideInduced apoptosis via P53/PI3K/AKT pathway. [152]

H22 cells10 daysMacrothelypteris viridifronsInhibited expressions of VEGF and CD34. [153, 154]

Hepa 1–6 cells14 daysYupingfeng powderReduced MDA, SOD activities in liver and lung.[155]

H22 cells14 daysEupolyphaga sinensis WalkerIncreased TNFα and IFN-γ and Bax/Bcl-2 ratio; activated caspase-3.[48]

H22 cells14 daysRadix Glycyrrhizae polysaccharideReduced Treg population and Foxp3. Increased serum Th1/Th2 cytokine. [156]

H22 cells15 daysToosendanin, from Melia toosendan Sieb. et Zucc.Reduced Bcl-2; increased Bax and Fas. [157]

Hep3B cells15 daysAndrographolide, from Andrographis paniculataReduced GSH; increased p-JNK, ASK1, MKK4, and c-Jun. [158]

S180 and H22 ascites cells15 daysDioscorea bulbifera L. rhizome[159]
20 daysJiedu Xiaozheng YinIncreased expressions of cyclin D and cyclin E.[49, 154]

Bel-7402 cells25 daysSulfated glycopeptide from Gekko swinhonis Guenther Inhibited bFGF production. [152, 160]

HepG2 cells3 wkspennogenyl saponins from rhizoma paridisDecreased Bcl-2 and increased Bax, cleaved caspase-8, and cleaved caspase-3; decreased ERK1/2 and Akt phosphorylation and increased p38 and JNK phosphorylation.[161]

SMMC-7721 cells4 wksLuteoloside from Gentiana macrophyllaDecreased ROS and NLRP3 inflammasome. Inactivated caspase-1 and IL-1β.[162]

MHCC97L cells4 wksCoptidis rhizoma aqueous extract Increased phosphorylation of eEF2. [48, 51]

MHCC97L cells4 wksHuanglian Jiedu decoctionInactivated eEF2, induced eEF2k and AMPK. [52]

MHCC97-H cells5 wksCorilaginActivated p-p53-p21(Cip1) -cdc2/cyclin B1.[156, 163]
Hedyotis diffusa Willd.Downregulated expressions of CDK2, cyclin E, and E2F1.[157, 164]
Jiedu Xiaozheng YinInhibited expressions of expression of Bmi1 and Wnt/beta-catenin. [158, 165]
Triptolide from Tripterygium wilfordiiIncreased ROS and caspase-3 activity; induced Bax and inhibit Bcl-2 after addition of 5-FU.[166]
Invigorating spleen and detoxification decoctionIncreased MHC I/MHC II expression.[167]
Livistona chinensis seedsInhibited angiogenesis via reduction of VEGF-A and VEGFR-2 and inhibited Notch, Dll4, and Jagged1.[168]

H22 cellsPinus massoniana bark extractInduced apoptosis via caspase-dependent pathways.[169]

Walker-256 cellsAitongxiao recipeReduced Bcl-2, survivin. [170]

H22 cellsXiaoai Jiedu RecipeReduced CCL3, CXCL2. [171]

Hep3B cellsPiper betle leaf extractsInduced MAPK-p73 pathway.[172]

H22 cellsCiji Hua’ai Baosheng granule formula[173]

H22 cellsOxytropis falcata[174]

H22 cellsCorn silk polysaccharidesImproved serum IL-2, IL-6, and TNFα levels. [175]

HepG2/EGFP cellsChaiqiyigan granulaIncreased Bax; reduced p53 and VEGF combined with taxol.[50]

Primary hepatic carcinomaBushen jianpi decoctionReduced VEGF expression.[176]

Implantation (orthotopic)

HepG2 cells expressing red fluorescent protein 25 daysCelastrus orbiculatus Thunb.Inhibited VEGF.[53]

MHCC97H cells35 daysBaicaleinReduced MMP-2, MMP-9, and u-PA; increased TIMP-1 and TIMP-2 expressions through ameliorated phosphorylation of ERK. [177]

Bel-7402 cells10 wksJianpijiedu FangIncreased PTEN, pFAK; and reduced PI3K. [178]

MHCC97L cellsSongyou yinRestored E-cadherin and reduced N-cadherin.[179]

Transgenic mice model

X15-myc mice12 mthThapring Reduced Bcl2 and overexpression of p21Waf1.[45]

Others

25% CCl4 injection, 8% ethanol solution as drinking fluid for 4 weeks, and 20 weeks of 0.5% CCl4-8% ethanol solution as drinking fluid 8 wksXiaochaihu decoctionReduced ONOO, MDA, VMA, LPS-P, and ALP-C; increased ALP-A.[180]

N-Methyl-N-nitrosourea28 wksAegle marmelos leaf extractDecreased IL-1β, IL-6, Bcl-2, and c-jun; increased p53 and IL-4. [181]

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