Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

3.9. Ginseng

The generic term ginseng encloses several species of plants belonging to the genus Panax such as Panax ginsengand Panax japonicus (i.e., Asian ginseng) and Panax quinquefolius L. (American ginseng) [269]. In recent years, ginseng has gained popularity in Western countries and is included in the Pharmacopoeias of Germany, Austria, and United Kingdom [326]; in the United States, ginseng is the second top-selling herbal supplement but it is not a drug approved by the Food and Drug Administration [327–329]. Ginseng presents a complex mixture of various active compounds but the main pharmacologically active ingredients are triterpene saponins known as ginsenosides, which are found in the roots. Therefore, the dried roots are used in traditional medicines due to the variety of beneficial effects, including in breast cancer [330, 331]. However, its clinical significance in breast cancer patients has not been fully investigated and some divergences are reported.

Despite several in vitro studies having proved the promising use of ginseng extract or its active components as anticancer agent in breast cancer [332, 333], no animal studies have been found in literature. The mechanisms by which components of ginseng or metabolites performed their antiproliferative effect are reported in several research studies and resumed in a recent review paper [334]. These compounds can modulate signalling pathways associated with inflammation, oxidative stress, angiogenesis, metastasis, and stem/progenitor-like properties of cancer cells. For example, ginsenoside Rp 1 inhibits the insulin-like growth factor 1 receptor (IGF-1R)/Akt pathway in breast cancer cells [332]. In addition, ginsenoside Rp 1 was also demonstrated to induce cycle arrest and apoptosis. Kwak et al. studied the inhibitory effect of ginseng sapogenins and their derivatives on the proliferation of MDA-MB-231 human breast cancer cells (a model of triple negative breast cancer) [333]. 20(S)-Protopanaxadiol exhibited IC₅₀ (i.e., half maximal inhibitory concentration) comparable to the taxol (chemotherapeutic agent) and acts by stimulating caspase-dependent apoptosis in breast cancer cells. The ability of ginsenoside Rg 3, one of the major active compounds of heat-processed ginseng, to induce apoptosis in MDA-MB 231 cells by blocking NF- ƙB signalling was also verified [335, 336].

A specific effect of ginseng in cancer is increasing the sensitivity of breast cancer cells to various chemical anticancer agents including gemcitabine (an antimetabolite), cisplatin (an alkylating agent), paclitaxel (a taxane agent belonging to a plant alkaloid), and epirubicin (an antibiotics) through downregulation of them RNA level of MDR-1 [337].

Despite popular use of ginseng in cancer patients, only a few clinical studies have been conducted on ginseng-chemotherapeutic agent association. A clinical phase II study using no ginseng alone but in Shengmai formula (i.e., a traditional Chinese ginseng preparation that contains red ginseng, lilyturf root, and magnolia vine fruit) reported immunologic improvements among breast cancer patients [78].

Some beneficial effects related to the use of ginseng in human include maintenance of natural energy, improvements of physical, chemical, and biological performance and enhancement mood and general vitality and immune function [326, 338]. Despite these positive outcomes which are attributed to its “adaptogen” characteristic, findings on the effects of ginseng in breast cancer patients are mixed. Bao et al. [79] conducted the Shanghai Breast Cancer Survival Study to detect some association between quality of life and postdiagnosis ginseng use among breast cancer survivors. The authors did not find any improvements. In another study, Cui and collaborators reported that the use of ginseng had positive quality of life scores, namely, in the psychological and social domains [80]. The authors explained the variability in response to the design of study and the different doses of ginseng use among breast cancer survivors.

Nevertheless, evidence of efficacy is sparse. Well-designed clinical trials are required to provide information for scientists and healthcare consumers. Furthermore, treatment of symptoms and side effects is crucial for people with cancer because of the longevity associated with successful cancer treatment. And regarding this issue, evidence is also required in relation to ginseng use.

Ginseng should be avoided by children and used with some prudence by patients medicated with blood pressure medicines, blood-thinning medications, hormones, or insulin due to possible drug-herb interactions (recommendation performed by American Cancer Society) [3]. Ginseng is relatively nontoxic but in high doses (i.e., superior to 3 g ginseng root daily) can confer adverse symptoms such as insomnia, nervous excitation, headaches, and nausea. Ginseng may present steroid/hormone like effects, so in women who have breast or endometrial cancer special attention to its use is recommended [7, 339].