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

Table 1 Herbal formulas for hepatocarcinoma prevention

Herbal formula	Therapeutic principles	Herbs	Models/patients	Effects	Targets/events	Ref.
Ren-shen-bie-jia-jian	Tonifying Qi and dissolving stasis	Ren-Shen (Panax ginseng), Bie-Jia (Carapax trionycis), Tao-Ren (Peach seed) and other herbs	DMN induced hepatic precancerous lesion in rats	Inhibit hepatocarcinogenesis	Down-regulation of TGF-βIIR	[13]
Xiao-chai-hu-tang	Soothing liver-Qi stagnation	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)	NNM induced hepatocarcinogenesis in rats; patients with cirrhosis	Inhibit hepatocarcinogenesis, prevent hepatocarcinogenesis in patients	Increase helper T lymphocytes	[14,49]
Shi-quan-da-bu-tang	Tonifying Qi-Blood	Ren-Shen (Panax ginseng), Bai-Zhu (Atractylodes macrocephala Koidz.), Fu-Ling (Poria cocos), Gan-cao (Glycyrrhiza uralensis), Chuan-Xiong (Ligusticum chuanxiong), Dang Gui (Angelica sinensis), Shu-Di-Huang (Rehmannia glutinosa), Bai-Shao (Paeonia lactiflora), Huang Qi (Astragalus membranaceous), Rou-Gui (Cinnamomum cassia Presl)	NNM induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Increase IL-2 receptor-positive lymphocytes	[15]
Nourishing Yin Decoction	Tonifying liver Yin	Bei-Sha-Shen (Glehnia littoralis), Dang-Gui (Angelica sinensis), Bai-Shao (Paeonia lactiflora), Gou-Qi (Lycium barbarum), etc.	AFB1 induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Unknown	[16]
Removing Toxic Heat Decoction	Detoxifying and tonifying liver Yin	Ban-Zi-Lian (Sculellaria barbata), Ban-Bian-Lian (Lobelia chinensis Lour.), Mo-Han-Lian (Eclipta prostrata), Gu-Ya (rice sprout), etc.	AFB1 induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Unknown	[16]
A-L tonic capsule	Tonifying liver-Yin and nourishing Qi	Nü-Zhen-Zi (Ligustrum lucidum Ait.) and Huang-Qi (Astragalus membranaceous)	DEN induced hepatocarcinogenesis in rats	Inhibit DNA content and improve DNA distribution	Unknown	[17]
Bu Shen formula	Tonifying kidney	Ba-Ji-Tian (Morinda officinalis), Tu-Si-Zi (Cuscuta chinensis Lam), Qing-Pi (Cuscuta chinensis Lam) and other herbs	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Unknown	[18]
Fu-zheng-hua-yu formula	Strengthening body resistance and dissolving stasis	Dong-Chong-Xia-Cao (Cordyceps sinensis), Tao-Ren (Peach seed), Dan-shen (Salvia miltiorrhiza) and other herbs	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Inhibit cell cycle S phase	[19]
Huqi San	Tonifying kidney, nourishing Qi, and dissolving stasis	Hu-Ji-Sheng (Viscum coloratum), Huang-Qi (Astragalus membranaceus), Yu-Jin (Radix Curcumae), Dan-shen (Salvia miltiorrhiza) and other herbs	DEN and 2-acetylaminofluorene induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Down-regulation of c-jun, c-fos and c-myc, up-regulation of G-6-Pase, SDH and ATPase	[20,21]
Ganfujian	Strengthening spleen	Shan-Yao (Rhizoma Dioscoreae), Shan-Zha (Fructus Crataegi) and Da-Zao (Fructus Ziziphi Jujubae)	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Down-regulation of CDK4, cyclin D1 and PCNA	[22]
SRRS recipe	Strengthening spleen, regulating Qi, removing heat, and softening hard lumps and resolving phlegm	Tai-Zi-Shen (Pseeudostellaria heterophylla), Zhu-Zi-Shen (Panax japonicus), Bai-Zhu (Atractylodes macrocephala Koidz.), Fu-Ling (Poria cocos), Sheng-Mu-Li (raw oyster shell) other herbs	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Unknown	[23]
Jianpi Jiedu Recipe	Strengthening spleen and detoxifying	Huang-Qi (Astragalus membranaceous), Bai-Zhu (Atractylodes macrocephala Koidz.), Zhu-Ling (Polyporus umbrellatus), Ba-Yue-Zha (Akebia trifoliata), Shi-Jian-Chuan (Salvia chinensis), Ye-Pu-Tao-Teng (Wild grape stem), Yi-Yi-Ren (Coix lacryma-jobi L.) other herbs	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Down-regulating miR-199a and AKT/PI3K, and up-regulating p70s6k	[24,25]
Gan Zheng oral solution	Detoxifying and dissolving stasis	Ban-Zi-Lian (Sculellaria barbata), Bai-Hua-She-She-Cao (Hedyotis diffusa Willd.), San-Leng (Sparganium stoloniferum), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin) and other herbs	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Down-regulating ICAM-1	[26]
Zao Lian mixture	Detoxifying, dissolving stasis, strengthening spleen, and soothing liver	Zao-Xiu (Paris Polyphylla), Ban-Zi-Lian (Sculellaria barbata), Hu-Zhang (Polygonum cuspidatum), Jiang-Huang (Carcuma longa), Huang-Qi (Astragalus membranaceous), Bai-Zhu (Atractylodes macrocephala Koidz.), Fu-Ling (Poria cocos), etc.	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Improve liver function	[27]
Sb/Bs Remedy	Clearing heat and discharging fire, eliminating dampness and detoxifying, and soothing liver	Huang-Qin (Scutellaria baicalensis Georgi) and Chai-Hu (Bupleurum scorzonerifolfium Willd)	N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters	Inhibit hepatocarcinogenesis	Increase TNF-alpha, TGF-beta1, caspase-3 and apoptosis, decrease 8-OHdG expression	[28]
Qing Re Fang	Clearing heat and detoxifying	Ban-Zi-Lian (Sculellaria barbata), Bai-Hua-She-She-Cao (Hedyotis diffusa Willd.) and Pu-Gong-Ying (Taraxacum mongolicum)	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Up-regulate GAP, down-regulate Ras and Raf1	[29-31]
Huo Xue Fang	Promoting circulation and removing stasis	Chai-Hu (Bupleurum chinense), Dan-Shen (Salvia miltiorrhiza), Chi-Shao (Paeonia lactiflora Pall. or P. veitchii Lynch), Ba-Yue-Zha (Caulis Akebiae), Yin-Chen-Hao (Artemisia capillaris Thunb.), Yu-Jin ( Radix Curcumae)	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Up-regulate GAP, down-regulate Ras, Grb-2 and Raf 1	[29-31]
Jian Pi Fang	Strengthening spleen	Huang-Qi (Astragalus membranaceus), Bai-Zhu (Atractylodes macrocephala Koidz.), Bai-Shao (Paeonia lactiflora), Yi-Yi-Ren ( Semen Coicis), Shen-Qu (medicated leaven), Ban-Xia (Pinellia ternata) and Fu-Ling (Poria cocos)	DEN induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Up-regulate GAP, down-regulate Ras and SOS	[29-31]
Herbal Compound 861	Dissolving stasis and tonifying Qi	Dan-Shen (Salvia miltiorrhiza), Huang-Qi (Astragalus membranaceus), Ji-Xue-Teng (Spatholobus suberectus) and other herbs	DEN and 2-acetylaminofluorene induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Unknown	[32]
New Anti-tumor formula	Tonifying qi, soothing liver and dissolving stasis	Huang-Qi (Astragalus membranaceus), Chai-Hu (Bupleurum chinense), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin) and other herbs	AFB1 and HBV induced hepatocarcinogenesis in rats	Inhibit hepatocarcinogenesis	Activate SOD and GST, decrease MDA	[33]
Jian-Pi-Huo-Xue Formula	Strengthening spleen and dissolving stasis	Huang Qi (Astragalus membranaceous), Chi-Shao (Paeonia anomala), Dang-Shen (Codonopsis pilosula), Dang-Gui (Angelica sinensis), E-Zhu (Curcuma kwangsiensis or Curcuma phaeocaulis or Curcuma wenyujin) and other herbs	Patients with hepatitis, hepatic cirrhosis and low level of AFP	Prevent hepatocarcinogenesis in patients	Unknown	[47]

DMN: Dimethylnitrosamine; NNM: N-nitrosomorpholine; AFB1: Aflatoxin B1; DEN: Diethylnitrosamine; HBV: Hepatitis B virus; AFP: Radiofrequency ablation; TGF-βIIR: Alpha fetoprotein; transforming growth factor-β type II receptor; IL-2: Interleukin-2; PCNA: Proliferating cell nuclear antigen; CDK4: Cyclin-dependent kinase 4; PI3K/AKT: Phosphatidylinositol-4,5-bisphosphate 3-kinaseV-akt murine thymoma viral oncogene homolog; ICAM-1: Intercellular adhesion molecule 1; TNF: Tumor necrosis factor; Grb-2: Growth factor receptor-bound protein 2; GAP: GTPase-activating protein; SOS: Son of sevenless; SOD: Superoxide dismutase; GST: Glutathione S-transferase; MDA: Malondialdehyde.