Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

Table 3

In  vivo studies of ginseng in combination with other anticancer drugs.

Ginseng products	Source	Animals	Dose	Anticancer drug	Direct action (inhibit tumor growth)	Indirect action	Reference
Panax ginseng extracts	Tongrentang Pharmacy, Beijing, China, major Rg1, Rb1, Rd	Rat	3.0 mg/kg po., bid, 10 days	5-FU	N/A	(1) Increase drug elimination half-life: 𝑡1/2(𝑘𝑒) of control and ginseng treated group 79.17 and 125.72 min, respectively (𝑃<0.05); (2) Reduce drug-induced weight loss;	[16]
	Korean ginseng, Ginseng Nonghyup, Keum-san, Korea	Rat	12.5~100 mg/kg, po.,	cisplatin	N/A	Reduce drug-induced nausea and vomiting	[29]
	Korean red ginseng, Korea Ginseng Cooperation, Daejeon, Korea	Ferret	3 g/kg, po.,				[30]
acidic; polysaccharides	Korean red ginseng, Korea Ginseng Cooperation, Daejeon, Korea	ICR mice bearing sarcoma 180; C57BL/6 mice bearing B16 melanoma	25, and 100 mg/kg, ip., 7 days	paclitaxel	Yes	(1) Improve survival rate (ICR mice bearing sarcoma 180): 28.6 and 42.8% increase in 30-day life-span, while no obvious effect seen on drug-treatment alone.; (2) Reduce drug-induced immunosuppression: increase NK cell cytotoxicity (C57BL/6 mice)	[27]
	Korean red ginseng, Korean Tobacco, and Ginseng company	BALB/c mice	33~300 mg/kg; po., 3 wks	Cyclophosphamide (CP)	N/A	Reduce drug-induced: (1) weight loss; (2) immunosuppression: (i) increase spleen weight; (ii) restore splenocyte proliferation; (iii) increase macrophage activity (NO production); (iv) increase NK cell cytotoxicity; (v) increase serum IL-12, IFN-𝛾 and CRP (C-reactive protein) level	[31]
	Korean ginseng	BALB/c mice: C57BL/6 mice bearing mouse lung carcinoma LLC cells	100 mg/kg, i.p.	Cyclophosphamide (CP)	Yes	(1) Improve survival rate (BALB/c mice): 53% of post-treated group increased in the 30-day life-span compared with only 10% in the drug alone treated group.; (2) Reduce drug-induced immunosuppression.; (i) Accelerate recovery of bone marrow cells and blood neutrophils; (ii) Stimulate splenocyte proliferation and maintain its cytotoxicity.; (iii) Increase cytokine mRNA expression (TNF-𝛼, IL-1𝛽, IL-6, SCF and GM-CSF).	[32]
neutral polysaccharides	Panax ginseng, Changbai Mountain, Jilin, China	ICR mice bearing Sarcoma 180	25~150 mg/kg, po., 10 days	5-FU	Yes	Reduce drug-induced immunosuppression: (i) increase spleen weight,; (ii) stimulate lymphocyte proliferation,; (iii) increase NK cell cytotoxicity,; (iv) enhance macrophage activity (phagocytosis and NO production),; (v) increase serum TNF-a level	[33]
Ginsenoside Rg3	American ginseng; ≥99.5%, provided by Department of Medicinal Chemistry of Preclinical Medicine of Jilin University, China	Athymic mice bearing human ovarian cancer SKOV-3	3.0 mg/kg, ip., 10 days	Cyclophosphamide (CP)			[34]
	Panax red ginseng, from Northeast China, ≥99.5%, YaTai Pharmaceutical Company, China	C57/BL6 mice with Lewis lung carcinoma	20 mg/kg, po. 18 days	gemcitabine	Yes: (1) Decrease tumor weight; (2) Inhibit tumor cell proliferation [19]; (3) Increase tumor necrosis rate [20]	(1) Improve survival: (i) Rg3, CP, and combination group had longer survival (23.72, 25.90, and 27.12 days, respectively) compared with control group (13.61 days, 𝑃<0.05) (𝑛=7) [19]; (ii) 18 days after treatments, combination group resulted in increased survival rate (100%) compared with control or gemcitabine group (60% or 70%, 𝑃<0.05) (𝑛=10) [20]; (iii) Control group, low-dose CP or Rg3 alone group, and combination group had 29, 70 or 77, and 95 days of 50% survival rate from implantation, respectively. (𝑛=20) [35]; (2) Improve life quality; (3) Reduce drug-induced: weight loss, leucopenia, limited motility, and skin discoloration.; (4) Inhibit tumor angiogenesis: (i) decrease microvascular density; (ii) decrease vascular endothelial growth factor expression	[11]
			10 mg/kg, po. 21 days	Cyclophosphamide (CP)			[36]
Ginsenoside Rg1	Panax ginseng, provided by Takeda Chemical Industries, Osaka.	BALB/c mice	10 mg/kg, i.p. 3 days	Cyclophosphamide	N/A	Reduce drug-induced immunosuppression	[37]
Ginsenoside Rd	Panax ginseng	Rat	1 and 5 mg/kg, po. 30 days	cisplatin		Reduce drug-induced renal toxicity	[23]
Shengmai (Chinese herbal preparation consisting red ginseng, lilyturf root and magnolia vine fruit)	Jilin Province Ji’an Yisheng Pharmaceutical Co. Ltd., China	Rat	3 mL/kg, i.p., pre and during treatment, 4 wks	doxorubicin (DOX)	N/A	Reduce drug-induced diaphragm muscle toxicity	[38]
	Shanghai Hutchison Pharmaceuticals	Mice bearing hepatoma	3.5~14 mL/kg/d, 14 days	5-FU	Yes	(1) Improve immunological function; (2) Reduce drug induced adverse reaction: (i) protective effect on liver and renal function; (ii) increase WBC and PLT counts	[39]