Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Table 3 Anti-cancer effects of herbal formulas against hepatocarcinoma

Herbal formula	Therapeutic principles	Herbs	Models	Effects	Targets/events	Ref.
Fuzheng Yiliu Granule	Tonifying Qi and blood, and dissolving stasis	Hong-Qi (Hedysarum polybotrys), Dang-Gui (Angelica sinensis), Mu-Tou-Hui (Patrinia scabra Bunge), etc.	Mouse H22 hepatocarcinoma bearing mice	Inhibit tumor growth, induce apoptosis	p53, caspase-3, mitochondrial membrane potential	[126,127]
Fuganchun 6	Tonifying Qi and Yin, detoxifying and dissipating mass	Huang-Qi (Astragalus membranaceus), Nü-Zhen-Zi (Ligustrum lucidum Ait), Bai-Hua-She-She-Cao (Hedyotis diffusa Willd), Bie-Jia (Carapax trionycis), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin), etc.	Mouse H22 hepatocarcinoma cells in vitro and in vivo	Inhibite tumor growth and cell proliferation, and induce apoptosis	Enhance proliferation activity of lymphocyte, NK cells activities and IL-2 production	[128,178]
Bushen Jianpi Decoction	Tonifying spleen and kidney	Dang-Shen ( ), Bai-Zhu (Atractylodes macrocephala Koidz.), Fu-Ling (Poria cocos), Shu-Di-Huang (Rehmannia glutinosa), shan-Zhu-Yu (Cornus officinalis), Du-Zhong (Eucommia ulmoides Oliver), etc.	Mouse H22 hepatocarcinoma bearing mice	Inhibit tumor growth, induce apoptosis	VEGF	[129]
Warming Yang and Dispersing Stasis Formula	Warming Yang and dispersing stasis	Fu-Zi (Aconitum carmichaeli Debx.), Huang-Qi (Astragalus membranaceus), Bai-Zhu (Atractylodes macrocephala Koidz.), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin), Bai-Shao (Paeonia lactiflora), etc.	Human BEL-7402 hepatocarcinoma cells	Induce apoptosis	Unknown	[130]
Fufangkushen injection	Clearing heat and removing toxicity	Ku-Shen (Sophora flavescens Ait.), etc.	Human SMMC-7721 hepatocarcinoma cells	Inhibit proliferation, induce apoptosis	Survivin, Bcl-2, caspase-3	[131]
Songyou Yin	Tonifying Qi and blood, dissolving stasis and dissipating mass	Dan-shen (Salvia miltiorrhiza Bge.), Huang-Qi (Astragalus membranaceus Bge.), Gou-Qi (Lycium barbarum L.), Shan-Zha (Crataegus pinnatifida Bge.), and Bie-Jia (Trionyx sinensis Wiegmann)	Human MHCC97H hepatocarcinoma bearing nude mice; activated rat hepatic stellate cells and rat McA-RH7777 hepatoma cells	Induce apoptosis, inhibit tumor growth, prolong survival; inhibit invasion and metastasis	MMP-2, IL-6, TGF-β1, VEGF, epithelial-mesenchymal transition	[132,167]
Huang-lian-jie-du-tang	Clearing heat and removing toxicity	Huang-Lian (C. chinensis Franch), Huang-Qin (Scutellaria baicalensis Georgi), Huang-Bai (P. amurense Rupr) and Zhi-Zi (Gardenia jasminoides Ellis)	Human Hep G2 and PLC/PRF/5 hepatomain cells in vitro and in vivo	Inhibit cell proliferation, induce cell cycle arrest and apoptosis	Cdc2, Cdc25C, cyclin A, cyclin B1, Cdc2, Cdc25C, Bax, Bak, Bcl-2, Bcl-XL, IkappaBalpha	[141]
Bu-Zhong-Yi-Qi-Tang	Invigorating spleen-stomach and replenishing qi	Huang-QI (Astragalus membranaceus), Ren-Shen (Panax ginseng), Gang-Gui (Angelicae sinensis), Sheng-Ma (Cimicifuga foetida L.), Gan-Cao (Glycyrrhiza uralensis), Chen-Pi (Citrus poonensis), Chai-Hu (Bupleurum chinensis), Sheng-Jiang (Zingiber officinale), Da-zhao (Ziziphs jujuba), Bai-Shu (Atractylodes macrocephala KOIDZUMI)	Human hepatoma Hep3B, HepG2 and HA22T cells	Inhibit cell proliferation, induce apoptosis and arrest cell cycle at G0/G1 phase	Unknown	[142]
Jiedu Xiaozheng Yin	Heat-clearing and detoxification	Bai-Hua-She-She-Cao (Hedyotis diffusa Willd), Xia-Ku-Cao (Prunella), Shan-Ci-Gu (Pseudobulbus Cremastrae), Ku-Shen (Sophora flavescens)	Human Hep G2 hepatoma cell in vitro and in vivo	Inhibits the growth of HepG2 cells, arrest cell cycle at the G0/G1 phase	Cyclin D and cyclin E	[143]
Liver Yin Tonifying formula	Tonifying liver-Yin, draining dampness and dissipating stasis	Nü-Zhen-Zi (Ligustrum lucidum Ait), Zhi-Bie-Jia (processed Carapax trionycis) and Hu-Zhang (Polygonum cuspidatum)	Human hepatocarcinoma Bel-7402 cells	Inhibit proliferation, induce apoptosis and cell senescence	Caspases-8, -9 and -3, p16, p21, pRB	[152]
Modified Yi Guan Jian	Tonifying liver and kidney-Yin, draining dampness and dissipating stasis	Bei-Sha-Shen (Glehnia littoralis), Mai-Dong (Ophiopogon japonicus), Dang-Gui (Angelica sinensis), Shu-Di (dried Rehmannia glutinosa), Gou-Qi (Lycium barbarum), Chuan-Lian-Zi (Melia toosendan Sieb fruit), and Hu-Zhang (Polygonum cuspidatum)	Human hepatocarcinoma Bel-7402 cells	Inhibit proliferation, induce anoikis	Caspases-3, -8 and -9, p38 MAPK	[156]
Blejiajian Pill	Tonifying Qi, detoxifying and dissipating mass	Bie-Jia-Jiao(Carapacis trionycis-shell glue), E-Jiao(Colla Corii Asini), Feng-Fang (beehives), Chai-Hu (Bupleurum chinense), Huang-Qin (Scutellaria baicalensis), Ban-Xia (Pinellia ternate), Dang-Shen(Codonopsis pilosula), etc.	Human Hep G2 hepatoma cells	Inhibit cell proliferation, adhesion and invasion	Unknown	[168]
Compound Astragalus and Salvia miltiorrhiza extract	Tonifying Qi and dissipating stasis	Astragalosides, astragalus polysaccharide and salvianolic acids	Human Hep G2 hepatoma cells	Inhibit TGF-β1 mediated invasion	TGF-β/Smad signaling	[169]
Shehuang Xiaoliu Fang	Tonifying spleen, dissolving stasis and detoxifying	She-Xiang (musk), Niu-Huang (Cow-Bezoar), Dan-shen (Salvia miltiorrhiza Bge.), Bai-Zhu (Atractylodes macrocephala Koidz.), Ban-Zi-Lian (Sculellaria barbata), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin), etc.	Human SMMC-7721 hepatocarcinoma cells	Inhibit invasive and adhesive	nm23-h1 and ICAM-1	[170]
Xiaochaihu Decoction	Relief liver for smooth Qi	Chai-Hu (Bupleurum chinense), Huang-Qin (Scutellaria baicalensis Georgi), Sheng-Jiang (Zingiber officinale), Ban-Xia (Pinellia ternata), Da-Zao (Ziziphus jujuba), Ren-Shen (Panax ginseng), Gan-cao (Glycyrrhiza uralensis)	Mouse H22 hepatocarcinoma bearing mice	Inhibit tumor growth	Increase T lymphocytes proliferation, NK cells activities and IL-2	[175]
Mylabris Mixture	Detoxifying and dissipating mass	Ban-Mao (Mylabris), Chen-Pi (Citrus reticulata Blanco), Gu-Ya (Setaria italica), etc.	Mouse H22 hepatocarcinoma bearing mice	Inhibit tumor growth	Increase CD4+, CD8+ lymphocytes and NK cells, and IFN-γ and IL-4 production	[176]
Fuzheng Yiliu Granule-2	Tonifying Qi and tonifying Yin	Huang-Qi (Astragalus membranaceus), Nü-Zhen-Zi (Ligustrum lucidum Ait), Ling-Zhi (Ganoderma lucidum), and Shan-Yao (Dioscorea opposita)	Mouse H22 hepatocarcinoma cells in vitro and in vivo	Inhibite tumor growth and cell proliferation, and induce apoptosis	Increase CD4+ lymphocyte, IL-2 and TNF-α, and NK cells	[177]
Fu-Zheng-Kang-Ai-Tang	Strengthening body resistance and anti-cancer	Ren-Shen (Panax ginseng), Huang-Qin (Scutellaria baicalensis Georgi), Ling-Zhi (Ganoderma lucidum), Huang-Qi (Astragalus membranaceus), etc.	Human Bel-7402 hepatocarcinoma bearing nude mice	Inhibit angiogenesis and tumor growth	VEGF and bFGF	[188]
Delisheng	Tonifying Qi and resolving masses	Ren-Shen (Panax ginseng), Huang-Qi (Astragalus membranaceus), Cantharidium, etc.	Human Hep G2 hepatoma cells	Inhibit tumor growth	Endostatin	[189]
QHF	Detoxifying, dissolving stasis and strengthening body resistance	Cinobufagin, Ginsenoside Rg3, Panax Notoginseng Saponins, lentinan	Mouse H22 hepatocarcinoma bearing mice	Inhibit angiogenesis and tumor growth, enhance anti-cancer effects DDP	VEGF, EGFR and MMP-2	[190,196]
Erbie San	Resolving masses	Bie-Jia (Carapax trionycis), etc.	Wistar rats bearing Walker-256 liver cancer	Inhibit tumor growth	VEGF and endostatin	[191]
Chaiqiyigan Granula	Tonifying spleen, soothing liver, dissolving stasis and detoxifying	Chai-Hu (Bupleurum chinense), Huang-Qi (Astragalus membranaceus), etc.	Human hepG2/EGFP hepatoma bearing nude mice	Enhance anti-cancer effects of Taxol	Bax, p53 and VEGF	[195]
Shengmai Injection	Tonifying Qi and Yin	Ren-Shen (Panax ginseng), Mai-Dong (Ophiopogon japonicus), etc.	Mouse H22 hepatocarcinoma bearing mice	Enhance anti-tumor efficacy and reduce toxicity of 5-Fu	Unknown	[197]

TGF: Transforming growth factor; IL-2: Interleukin-2; ICAM-1: Intercellular adhesion molecule 1; TNF: Tumor necrosis factor; VEGF: Vascular endothelial growth factor; MMP2: Matrix metalloproteinase-2; bFGF: Basic fibroblast growth factor; NK: Natural killer; IFN-γ: Interferon-γ; MAPK: Mitogen-activated protein kinases; Bcl-2: Bcl2-associated X protein; Cdc25B: Cell division cycle 25B.