Женьшень и рак Обзоры Клинические исследования Ginseng & cancer Review



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4.3. Клинические Исследования

Несмотря на распространенное использование женьшеня, только ограниченное число клинических исследований доложены на женьшень-химиотерапевтического агента сочетания (см. табл. 4). На основе традиционной китайской медицины (ткм) рассмотрение, китайский женьшень подготовка Shengmai выбран в качестве тонизирующего средства в комбинации с химиотерапией, например, дополняя qi (означает жизненную энергию) и питает Инь (средства пассивной силы) [40]. Chen et al. оценили эффективность и побочные эффекты Shengmai в сочетании с химиотерапевтическими препаратами в лечении advanced non-small-cell lung cancer (NSCLC) [40]. Это исследование было проведено на 63 больных с гонартрозом III B и IV НМРЛ, получающих navelbine (торговое название Винорелбин, растения алкалоид) и цисплатин химиотерапии. Пациенты были распределены на две группы: 33 пациентов в группе, получавшей лечение Shengmai внутривенно капельно и Gujin гранул (китайское травяное Лекарство в воде растворимых гранул) в устной и 30 пациентов контрольной группы. Среди 61 пациента (33 от лечения в группе и 28 из контрольной группы), которые завершили наблюдательность, скорость реакции была 48.5% (16/33) в лечении и 32,2% (9/28) в контрольной группах, медиана времени выживания 13 месяцев и 9 месяцев соответственно. Это исследование показало, что комбинированное применение женьшеня и противоопухолевого препарата может увеличить краткосрочные терапевтической эффективности НМРЛ. Это исследование, однако, не был ослеплен. Рандомизированное, двойное слепое, плацебо-контролируемое исследование по оценке терапевтической эффективности Shenmai (так же, как Shengmai здесь) у онкологических больных, подвергающихся химиотерапии или лучевой терапии продолжается [43].

В другом рандомизированном контролируемом исследовании, Huang et al. проведена оценка эффективности Shenyi (95% гинзенозиды Rg3) в сочетании с гемцитабин плюс цисплатин 60 пациентов с прогрессирующим раком пищевода. По сравнению с пациентами в контрольной группе с только химиотерапией, результаты показали никаких существенных различий в общую скорость реакции между двумя группами в ходе этапа лечения. После лечения сосудистого эндотелиального фактора роста в лечении группы оказалась ниже, чем в контрольной группе (P < 0,05), что свидетельствует эффект ингибирования ангиогенеза. Кроме того, один-летняя выживаемость в группе лечения была выше по сравнению с контрольной группой (P < 0.05). Shenyi также улучшилось качество жизни пациентов по Карнофски performance status scale [46]. Rg3 было показано, что некоторые противораковые мероприятия, например, антипролиферативное, апоптоза, антиангиогенных, антиметастатической, и анти-инвазивных эффекты, а также регуляции клеточного цикла [8, 11, 12].

5. Резюме и заключение

Женьшень был использован в основном в качестве тонизирующего средства в пользу больных раком, особенно в Азии. На основании нашего обзора опубликованных in vitro, in vivo, и человеческого исследования, женьшень имеет отличный потенциал в качестве адъювантной химиотерапии, из-за его низкой токсичности и многие желательные свойства, такие как antiangiogenesis, antiproliferation, противовоспалительное, антиокислительные, апоптоза и иммунных эффектов модуляции [63]. Хотя есть существенные доказательства, от in vitro и исследования на животных свидетельствуют в пользу женьшень и его активных составляющих в повышении противоопухолевой активностью при использовании в комбинации с другими противоопухолевыми препаратами, недостаточно клинических данных, таких, благо в настоящее время.

Женьшень уже было принято, как натуральный продукт для укрепления здоровья. По этой причине, дальнейшее использование женьшеня вместе с обнадеживающими результатами от in vitro и in vivo исследования на животных (см. таблицы Tables22 и 3)3) могут содержать важные улики, чтобы продемонстрировать будущее клинике благо женьшеня. Дальнейшие исследования женьшеня продукции должна включать в себя контроль качества, таких как использование маркеров активности и активных компонентов, а также определение их фармакокинетики и фармакодинамики. Остается надеяться, что государственная поддержка, а также разработка новых патентов на женьшень станет достаточным стимулом и финансирование проведения хорошо спланированных клинических испытаний, ведущих к нормативно-утверждение женьшеня продукт для химиотерапии, улучшение в будущем.

Evid Based Complement Alternat Med. 2014; 2014: 168940.

Published online Apr 30, 2014. doi: 10.1155/2014/168940

PMCID: PMC4021740



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

Shihong Chen, 1 , 2 Zhijun Wang, 2 Ying Huang, 3 Stephen A. O'Barr, 3 Rebecca A. Wong, 2 Steven Yeung, 2 and Moses Sing Sum Chow 2 ,*

Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

1. Introduction

The concept of herb-herb or herb-drug combination to enhance therapeutic benefit has been utilized and practiced in China according to Chinese medicine principles for more than 2000 years [1]. Recently, herbs in combinations with anticancer drugs have been found to be capable of resensitizing the chemoresistance developed from repeated use of the anticancer drug [2]. Thus, the use of herb-drug combination to enhance therapeutic effect is of great interest, especially in cancer chemotherapy.

Among many herbs touted to improve cancer treatment, none has probably enjoyed as much worldwide reputation and interest as ginseng. Ginseng is widely used and is included in the pharmacopoeias in China, Japan, Germany, France, Austria, and the United Kingdom. In Asian countries and Western Europe, it is widely available as an over-the-counter drug and also commonly used as an adjuvant for cancer therapy [3, 4]. In the US, ginseng is one of the most frequently purchased herbs; it is available and used as a dietary or an herbal supplement but not as a drug approved by the Food and Drug Administration [5]. It is consumed regularly by more than 6 million Americans [6], as the second top-selling herbal supplement (US $62 million in annual sales in 2000 and about US $83 million in 2010) [7, 8]. In 2002, a national survey of men and women in the US has estimated that 4-5% of those aged 45–64 years had used ginseng [9].

Although ginseng consumption is not limited for in cancer patients, its benefit in cancer appears to be well accepted. Common reasons for the use of ginseng by cancer patients are to improve clinical outcomes, enhance quality of life, treat cancer-related symptoms, reduce adverse effects of chemotherapy, and potentially enhance the effects of chemotherapeutic agents. In addition, ginseng may exert a chemopreventive action: an epidemiological study has shown that patients taking ginseng had a 50% lower risk of cancer recurrence compared to patients not taking ginseng [10].

In view of its wide usage and potential benefit when used in combination with anticancer drugs, the present paper intends to critically review the evidence of such benefit as well as potential mechanisms involved. Although numerous reviews on ginseng-drug interaction have been already published [47, 48], no article has critically reviewed ginseng-anticancer drug combination for improvement of chemotherapy.

Both English and Chinese publications on ginseng and anticancer drug combination to improve cancer chemotherapy were searched from the Medline database (1990~2013) and China Academic Journals Database (1983~2013), respectively. All articles from in vitro, in vivo animal models, and human studies on the combination of ginseng or its active components with chemotherapeutic agent for anticancer effect were included. Because there are several types of ginseng with different active components, their general properties are briefly discussed to provide relevant background information before reviewing the specific combination in order to provide better understanding of the rationale of such combination.



2. Different Types of Ginseng and Its Preparation

Ginseng is a perennial herb that belongs to the Araliaceae family and Panax genus [49]. The root is the preferred part of the plant due to the presence of active components (see below), and the species most commonly used are Panax ginseng C.A. Meyer (Asian ginseng or Korean ginseng) and Panax quinquefolius (American ginseng). Panax ginseng C.A. Meyer is usually cultivated in China and Korea and has been used as a medicinal herb in China, Japan, and Korea for thousands of years. Its commonly claimed health benefits include immunity enhancement, stress relief, and prevention of aging. Panax quinquefolius, originally grown in United States and Canada, has been used by Native Americans for hundreds of years. So far, majority of research on ginseng has been on Panax ginseng C.A. Meyer [5, 17].

Panax ginseng C.A. Meyer is usually harvested after 4 to 6 years of cultivation and is classified into three types based on processing methods: (1) fresh (less than 4 years old, consumed in its fresh state), (2) white ginseng (4 to 6 years old, typically air or oven dried after peeling), (3) red ginseng (6 years old, steamed prior to drying, without peeling). These processing methods are intended to improve efficacy, safety, and preservation [50]. Recently, a new heat-processed ginseng, called Sun ginseng (SG), has been prepared by steaming with white ginseng at high temperature and pressure. Sun ginseng has been reported to contain more unique ginsenosides than the red ginseng. A preparation containing Sun ginseng extract with specific standardization is now available as functional food in Korea [21, 22, 24].

Many ginseng products are available on the market as fresh slices, juice, extract (tincture or boiled), powder, tea, tablet, capsule, and other forms. Two-year-old fresh ginseng is also used as an ingredient in Korean chicken-ginseng soup (boiled chicken with young ginseng root), samketang [51]. The traditional Chinese ginseng preparation widely used clinically in China is Shengmai which consists of red ginseng, lilyturf root, and magnolia vine fruit [28, 40].

The quality of ginseng is believed to vary with the age at harvest. When ginseng is harvested at the time of 5 to 6 years, it is considered the “best” with ginsenoside content at its highest [52]. According to several laboratory investigations, the quality of commercially available ginseng products can vary considerably. Negative trial results may be due to poor product quality rather than lack of efficacy [35]. Thus, evaluation of study results must take product quality control into consideration.

3. Active Components of Ginseng Relevant to Anticancer Effect

Ginseng contains various active components including ginsenosides, polysaccharides, flavonoids, volatile oils, amino acid, and vitamins. Of these active components, ginsenosides and ginseng polysaccharides appear to be responsible for the anticancer effect [8].

Ginsenosides are the main pharmacologically active ingredients responsible for the four major actions of ginseng: vasorelaxation, antioxidation, anti-inflammation, and anticancer effect. Ginsenosides, being amphipathic in nature, are steroidal saponins that contain four transring rigid steroid skeleton. They differ from each other mainly by the number, type, and location of their sugar moieties. Thus far, more than 40 different ginsenosides have been identified and isolated. Ginsenosides can be classified into three groups based on the chemical structure of aglycones: (1) protopanaxadiol group (PPD) or diols, for example, Rb1, Rb2, Rb3, Rc, Rd, Rg3, and Rh2; (2) protopanaxatriol group (PPT) or triols, for example, Re, Rf, Rg1, Rg2, and Rh1; (3) oleanane group: only Ro (0.6% of all ginsenosides) [53, 54]. The total percentage of ginsenosides (w/w) can vary from 1.9% to 8.1% in ginseng root preparations [17]. Red ginseng can possess higher activity than white ginseng, due to the presence of unique ginsenosides (Rg3, Rg5, Rg6, Rh2, Rh3, Rh4, Rs3, and F4) produced during steaming method [15, 18, 24]. The relative amounts of ginsenosides may also be used to differentiate Panax species. For example, American ginseng has little or no Rf, and Panax ginseng has higher levels of Rg1 but lower levels of Rb1 (or higher ratio of Rg1/Rb1) compared to those of American ginseng [5, 49, 55, 56]. Ginsenosides are also used as marker compounds for ginseng quality control, of which Rg1, Rc, Rd, Re, Rb1, and Rb2 are quantitatively the most important and prevalent. According to a Ginseng Evaluation Program led by the American Botanical Council of Austin, Texas, Rb1, Rb2, Rc, Rd, Re, and Rg1 account for >90% of the total ginsenoside content of the Panax ginseng root, whereas, Rb1, Rb3, Rc, Rd, Re, and Rg1 make up more than 70% of total ginsenoside content in American ginseng [8]. Each ginsenoside may differ in pharmacology and mechanisms due to its different chemical structure.

Researchers are now focusing on using purified individual ginsenosides to reveal the specific mechanism of action instead of using whole ginseng root extracts. The most commonly studied ginsenosides are Rb1, Re, Rg1, Rg3, and Rh1 [5]. The relevant ginsenosides (Rb1, Rg1, Rg3, and Rh1) for anticancer activity and corresponding molecular mechanisms are listed in Table 1.

Besides ginsenosides, ginseng polysaccharides also possess antitumor effect through modulation of innate immunity. Ginseng polysaccharides (present in 15% of ginseng root), including neutral and acidic polysaccharides, are water-soluble. It has been reported that Panax ginseng polysaccharides contain starch-like polysaccharide and pectin and can be fractionated into two neutral (WGPN and WGPA-N) and six acidic fractions (WGPA-1-RG, WGPA-2-RG, WGPA-1-HG, WGPA-2-HG, WGPA-3-HG, and WGPA-4-HG) by a combination of ethanol precipitation, ion exchange, and gel permeation chromatographies [57]. Many immunological studies have been performed with crude polysaccharide fractions, which are usually prepared by ethanol precipitation after extracting ginseng root with hot water. These polysaccharides have been reported to exert antitumor activity by regulating the immune response of the host organism. Using lymphocyte proliferation assays, both polysaccharides have been found to be potent B and T cell stimulators [57]. The acidic polysaccharides (10,000–150,000 MW), being readily soluble in water, are thought to be more active than neutral ones [27, 31, 32]. Ginseng pectin has also been shown to inhibit the actions of galectin-3, a β-galactoside-binding protein associated with cancer progression [58]. Nonsaponin constituents (immunomodulating polysaccharides) and the harmonizing constituents still remain to be explored.

4. Effects of Ginseng in Combination with Anticancer Drugs

4.1. In Vitro Studies

A number of in vitro studies have shown an enhanced anticancer effect when the ginseng extract or its active component is combined with a chemotherapeutic agent (see Table 2). One specific effect is increasing the cytotoxicity of chemotherapeutic agents.

Ginseng extracts, including ginsenosides, have been found to enhance the cytotoxicity of several chemotherapeutic agents such as 5-fluorouracil (5-FU, an antimetabolite), irinotecan (a plant alkaloid), mitomycin C (an antibiotics), docetaxel (a taxane agent belonging to a plant alkaloid), cisplatin (an alkylating agent), and others at the concentration range of 0.1–300μg/mL (see Table 2). One ginsenoside, Rg3, has been found to inhibit growth of various human tumor cells, such as prostate cancer cells (LNCaP, PC-3, and DU145), Lewis lung cancer cells, colon cancer cells (SW620 and HCT116), and B16 melanoma cells. Ginseng has been also found to enhance the cytotoxicity of docetaxel, cisplatin, and doxorubicin at low doses [21, 22]. Inhibition of nuclear factor-kappa (NF-κB) may be one of the potential mechanisms of the observed effect. NF-κB mediates tumor promotion, angiogenesis, metastasis, and resistance to chemotherapeutics through the expression of genes participating in malignant transformation and tumor promotion. Kim and coworkers have found that Rg3 can suppress the expression of several antiapoptosis genes (Bcl-2, Cox-2, c-Fos, c-Jun, cyclin D1, etc.) via inhibiting NF-κB and thus enhancing the susceptibility of colon cancer cells to docetaxel and other chemotherapeutics [21, 22].

Also, panaxadiol, a pseudoaglycone of diol-type ginsenoside, has been found to enhance the anticancer effects of some anticancer drugs through the regulation of cell cycle transition and the induction of apoptotic cells. Apoptosis, highly regulatory process of programmed death involving the caspase protease family, is considered to be a key factor. Apoptosis may play an important role in the panaxadiol enhanced antiproliferative effects of irinotecan on human colorectal cancer cells as well as when used in combination with 5-FU [18, 20].

Furthermore, the synergistic inhibitory effect of Panax ginseng when combined with 5-FU has been observed in human gastric cancer cell line BGC823 [16]. This appears to involve NO which has been found to directly suppress the growth of BGC823 cells by inducing G0/G1 phase arrest through the regulation of Akt signaling pathway. Ginsenosides may increase NO production by inducing endothelial nitric oxide synthase (eNOS) phosphorylation via the ER-mediated PI3-kinase/Akt pathway [16].

One major difficulty in cancer chemotherapy is the development of broad anticancer drug resistance by tumor cells. This phenomenon has been termed multidrug resistance (MDR) [8]. The overexpression of P-glycoprotein (Pgp) or the multidrug resistance-associated proteins (MRPs) confer MDR to cancer cells. Ginseng extracts may induce chemosensitization of conventional anticancer agents via downregulation of MDR-1 expression (Pgp inhibition) [26, 28]. Choi et al. found that protopanaxatriol ginsenosides can potentially reverse Pgp-mediated MDR by increasing the intracellular accumulation of drugs through competitive inhibition of Pgp [26]. In addition, Shengmai can enhance the sensitivity of cancer cells (human lung carcinoma A549, gastric carcinoma SGC-7901, breast carcinoma MCF-7, and hepatocellular carcinoma HepG-2) to various anticancer drug such as gemcitabine (an antimetabolite), cisplatin, paclitaxel (a taxane agent belonging to a plant alkaloid), and epirubicin (an antibiotics) via downregulation of the mRNA level of MDR-1 [28].



Another benefit of ginseng when used with the anticancer drug is a potential reduction in drug induced toxicity. Baek et al. have found ginsenosides Rh4 and Rk3, the active principles of Sun ginseng (SG), to significantly reduce the cisplatin-induced nephrotoxicity in LLC-PK1 cells in a dose-dependent manner. The mechanisms of function and structure-activity relationships with other ginsenosides remain to be investigated [24]. Ginsenoside Rd may also ameliorate cisplatin-induced renal injury, a process in which apoptosis may play a central role [25].

A critical concern in the above in vitro studies is the relatively high concentration of ginseng extract/active components used (up to 300μg/mL). Such a high concentration is likely not achievable in vivo, as the Cmax of some ginsenosides following oral administration in rats has shown to be less than 0.7μg/mL [59, 60]. Verification of in vitro benefit from lower concentrations of ginseng or from in vivo studies will be essential.

4.2. In Vivo Animal Studies

A number of positive benefits have been delineated with ginseng and anticancer drug combinations. They include increase of drug exposure, inhibition of the angiogenesis and metastasis, survival benefit, reduction of side effects of anticancer drugs, and therapeutic improvement (see Table 3).

A pharmacokinetic interaction leading to enhancement of certain anticancer drugs has been reported. After pretreatment with 3.0mg/kg Panax ginseng extract orally twice daily for ten consecutive days, the elimination half-life of 5-FU has been shown to significantly increase by approximately 58.8% (79.17 versus 125.72). The increase in t1/2 caused by Panax ginseng extract can result in a higher drug exposure of 5-FU, which may lead to a longer drug effect [16]. The specific mechanism however is not known. Ginseng may increase the exposure of other drugs including docetaxel. In vitro studies using human liver microsomes have suggested that ginseng as well as its various ginsenosides, at clinically relevant concentrations, can moderately inhibit CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 [61].

Angiogenesis, the process of pathological vascular in-growth critical for tumor expansion, is now known to play an important role in both growth and metastasis of some cancers. Ginsenoside Rg3 has been found to inhibit tumor angiogenesis. Combined therapy with Rg3 and low-dose gemcitabine or cyclophosphamide has been found to produce significant antiangiogenic effect without overt toxicity. The combined therapy has been shown to decrease vascular endothelial growth factor (VEGF) expression and microvascular density as well as blood flow in tumors (by color Doppler flow imaging) and peak systolic velocity when compared with the control mice. The combined therapy may have selectively enhanced the damage or cytotoxic effects of chemotherapy on newly formed blood vessels while simultaneously reduced Ki-67, VEGF, bcl-2, and P53 gene expression which may partially be responsible for their antiangiogenic and antitumor effects [11, 34, 36].



Survival benefit has been reported with the combination of ginseng or its active components with anticancer agents. In one study, combination treatment with paclitaxel (5 or 15mg/kg) and acidic polysaccharide (25mg/kg) has resulted in a 28.6 or 42.8% increase in 30-day life span of ICR mice bearing sarcoma 180 tumor cells, compared to paclitaxel treatment alone [27]. In another study, up to 53% of the BALB/c mice treated with combination of cyclophosphamide and an acidic polysaccharide (25mg/kg) have shown an increase in survival rate compared with only 10% with cyclophosphamide alone [32]. At least 3 positive survival studies have been reported with ginsenoside Rg3 alone or in combination with anticancer drug: (1): treatment with Rg3, cyclophosphamide, or their combination in athymic mice bearing human ovarian cancer SKOV-3 has been found to improve survival 23.72, 25.90, and 27.12 days, respectively, compared to 13.6 days with the control [34]. (2): combination with gemcitabine has been found to increase survival rate (100%) compared with control or gemcitabine (60% or 70%) in 18 days after treatments [11]. (3): in 50% mice that survived cancer cell implantation, cyclophosphamide (low-dose), Rg3 alone, and their combination treatment groups result in 70, 77, and 95 days compared to only 29 days survival in the control group. The Rg3 anticaner drug combination treatment has shown to induce the longest survival [36]. The mechanism of such benefit however is not clear.

The combination of ginseng and various anticancer drugs have been found to lessen the reduction of weight loss, nausea/vomiting, diaphragm muscle toxicity, immunosuppression, and liver and renal function deterioration (see Table 3). Ginseng extract may decrease the side effect of weight loss from anticancer drugs by increasing the protein and RNA contents of muscles and liver in rats [11, 16, 31, 36, 62]. In addition, Ge and coworkers have found the effect of Shengmai (Chinese herbal preparation consisting of red ginseng, lilyturf root, and magnolia vine fruit) to be capable of protecting diaphragm muscles from doxorubicin induced toxicity which appears to be correlated with a decrease in expression of iNOS and lipid peroxidation [39]. Furthermore, Shengmai has been found to also protect liver and renal function and increase white blood cell, platelet counts, and serum alanine aminotransferase [38]. Also, ginseng is known to modulate the immune system and thus may improve chemotherapy by an “indirect effect.” Shim et al. have shown Korean ginseng can increase the expression level of the cytokines, such as TNF-α, IL-1β, IL-6, SCF and, GM-CSF [32]. Polysaccharides may also improve drug-induced immunosuppression. They can significantly increase relative spleen weight (spleen weight/100g of bodyweight, e.g., frm 2.89% cyclophosphamide alone to 3.42% combined use), stimulate lymphocyte proliferation, NK cell cytotoxicity, and macrophage activity, increase serum TNF-α, IL-12, IFN-γ, and CRP (serum C-reactive protein) levels, and so forth [27, 31, 33]. However whether the degree of elevation of these cytokines by ginseng can improve chemotherapy outcome needs further investigated.

4.3. Clinical Studies

Despite popular use of ginseng, only a limited number of clinical studies have been reported on ginseng—chemotherapeutic agent combination (see Table 4). On the basis of the traditional Chinese medicine (TCM) consideration, the Chinese ginseng preparation Shengmai is selected as a tonic in combination with chemotherapy, for example, supplementing qi (means vital energy) and nourishing yin (means passive force) [40]. Chen et al. have evaluated the efficacy and side effects of Shengmai combined with chemotherapeutic agents in treating advanced non-small-cell lung cancer (NSCLC) [40]. This study was conducted on 63 patients with stages III B and IV NSCLC receiving navelbine (trade name of Vinorelbine, a plant alkaloid) and cisplatin chemotherapy. The patients were assigned to two groups: 33 patients in the treatment group receiving Shengmai by intravenous drip and Gujin Granule (a Chinese herbal remedy in water soluble granule) orally and 30 patients in the control group. Among the 61 patients (33 from the treatment group and 28 from the control group) who completed the observation, the response rate was 48.5% (16/33) in the treatment and 32.2% (9/28) in the control groups, with a median survival time of 13 months and 9 months, respectively. This study indicated that the combined use of ginseng and anticancer drug might enhance the short-term therapeutic efficacy of NSCLC. This study however was not blinded. A randomized, double-blind, placebo-controlled trial evaluating the therapeutic efficacy of Shenmai (same as Shengmai here) in cancer patients undergoing chemotherapy or radiotherapy is ongoing [43].

In another randomized controlled trial, Huang et al. evaluated the efficacy of Shenyi (95% ginsenoside Rg3) in combination with gemcitabine plus cisplatin in 60 patients with advanced esophageal cancer. Compared to patients in the control group with chemotherapy alone, the results showed no significant difference in total response rate between the two groups during the treatment phase. After treatment, the vascular endothelial growth factor in the treatment group was found to be lower than that in the control group (P < 0.05), suggesting an effect of inhibiting angiogenesis. In addition, one-year survival rate in the treatment group was higher compared with the control group (P < 0.05). Shenyi also improved the patients' quality of life according to the Karnofsky performance status scale [46]. Rg3 had been shown to have some anticancer activities like antiproliferative, apoptotic, antiangiogenic, antimetastatic, and anti-invasive effects as well as cell cycle regulation [8, 11, 12].

5. Summary and Conclusion

Ginseng has been used primarily as a tonic to benefit cancer patients, especially in Asia. Based on our review of published in vitro, in vivo, and human studies, ginseng has excellent potential as a chemotherapy adjuvant, because of its low toxicity and many desirable properties such as antiangiogenesis, antiproliferation, anti-inflammation, antioxidation, apoptosis, and immune modulation effects [63]. Although there are substantial evidence from in vitro and animal studies showing the benefit of ginseng and its active constituents in enhancing antitumor activity when used in combination with other anticancer drugs, there is insufficient clinical evidence of such benefit at present.

Ginseng has already been accepted as a natural product for health promotion. For this reason, continued use of ginseng together with encouraging results from the in vitro and in vivo animal studies (see Tables ​Tables22 and ​and3)3) may provide important clues to demonstrate future clinic benefit of ginseng. Further studies of ginseng products should include quality control such as the use of activity markers and active components, as well as determination of their pharmacokinetics and pharmacodynamics. It is hoped that government support as well as development of new process patents for ginseng will provide sufficient incentive and funding to conduct well designed clinical trials leading to regulatory approval of a ginseng product for chemotherapy enhancement in the future.

Может Женьшень Облегчить Связанные С Раком Усталость?

Как многие из вас уже, наверное, заметили, JADPRO обзор серии 2013 года было сосредоточено на темах, связанных интегративной медицины. Мы рассмотрели гипноз в качестве метода для некоторых пациентов с раком, от использования сенсорных и энергетических лечебным, и дополнительные стратегии для побочные эффекты лучевой терапии, среди других. Хотя использование интегративной терапии и природных агентов не был принят во всех гематологии и онкологии параметров, исследование этих интригующих процедуры продолжается. Ясно одно: дальнейшее тщательное исследование необходимо, чтобы определить безопасность и терапевтическую ценность таких мероприятий в нашей популяции пациентов.



Женьшень и усталость

Целебные свойства натурального агента, в частности, женьшеня, был расхваливали на протяжении тысячелетий. Одно недавно опубликованное исследование делает многое для того, чтобы проверить использование женьшеня у больных с особенно разрушительной симптом: рака, связанных с усталостью. Бартон и его коллеги опубликовали свои результаты использования Висконсин женьшень большие испытания 364 пациентов из 40 различных учреждений (Barton et al., 2013). Их результаты показали положительные результаты в борьбе с этим распространенным, но часто изнурительных симптомов.

Усталость, которая влияет на более чем 60% до 90% пациентов с раком, как правило, более тяжелые, как болезнь прогрессирует (Lawrence, Kupelnick, Миллер, Дивайн, & Лау, 2004). National comprehensive Cancer Network описывает, связанных с раком неприятной усталости и стойких; истощение, связанных рака или лечения рака, препятствует обычного функционирования (Piper & Cella, 2010). В одном ретроспективном исследовании 1,778 пациентов, 84% выводится с умеренной или сильной усталости, боли и изменение аппетита, будучи наиболее значимыми предикторами этот симптом (Yennu, Urbauer, & Bruera, 2012).

Бартон и его коллеги сообщили о своих многоузловой суда (N07C2) в Журнал Национального института рака (2013). Исследование было двойным слепым методом, в котором 364 усталость, перенесших онкологические заболевания были рандомизированы для приема 2000 мг американского женьшеня по сравнению с плацебо в течение в общей сложности 8 недель. Первичной конечной точкой исследования была 4-недельного измерения усталости на общие подшкала многомерного симптом усталости инвентаризации-краткая форма (УМФИ-SF), с изменениями от исходного уровня отмечено у 4 и 8 недель и оцениваются путем двусторонней, двухвыборочный t-тест.



Интригующие Результаты Исследования

Результаты сообщили Бартон и его коллеги показали, что изменения в УМФИ-SF оценка по базовой линии до 4 недель были 14.4 (стандартное отклонение [SD] = 27.1) для пациентов, получавших женьшеня по сравнению с плацебо (8.2 с SD = 24.8; p = .07). В 8 недель, статистически значимых различий также не видел женьшень группы, с изменением счетом 20 (SD = 27), в то время как в группе плацебо забил 10.3 (SD = 26.1; p = .003). Пациенты, которые получали активную терапию по своему заболеванию имели лучшие результаты, чем пациенты, которые уже закончили терапию. Токсичности были сходны между группами.



Что Такое Женьшень?

Несколько видов женьшеня существует, хотя Тип наиболее часто используется в травяных препаратов азиатский женьшень. Исследование обсуждалось здесь используется американский женьшень. Женьшень, как сообщается, имеют много различных эффектов, включая сонливость, антидепрессивной активностью, диурез, и свойствами афродизиаков (Sparreboom, Кокс, Ачарья, и Фигг, 2004). Отчеты исследований, показывающих соотношения доза-ответ между женьшень и снижение рака были опубликованы (Yun & Цой, 1998).

Активной составляющей в экстракты женьшеня - гинзенозиды, которые могли бы вызвать лекарственных взаимодействий, которые могут возникнуть при использовании этого продукта (Sparreboom et al., 2004). Поскольку токсичность видел в N07C2 судебное заседание не отличаются статистически между двумя оружия, можно предположить, что значимые лекарственные взаимодействия не происходят в настоящем исследовании; это важный факт, как неблагоприятные события могут быть проблемы, если соединение мешал или повлекли за собой дополнительные побочные эффекты.

В качестве поддержки результатов, используя этот метод лечения рака, связанных с усталостью, онкологии опытных практиков могли бы рассмотреть женьшень вариант терапии для своих пациентов, испытывающих усталость. Однако требуется продолжение исследований, чтобы окончательно изучить роль женьшеня в лечении онкологических заболеваний, связанных с усталостью, симптом, который является распространенным и разрушительным для многих наших пациентов. На Barton et al. исследование представляет собой важное дополнение к этому органу исследований.

J Adv Pract Oncol. 2013 Nov-Dec; 4(6): 392–393.

Published online Nov 1, 2013.

PMCID: PMC4093449

Can Ginseng Alleviate Cancer-Related Fatigue?

Pamela Hallquist Viale, RN, MS, CS, ANP, AOCNP®

Copyright and License information ►

As many of you have probably noticed, JADPRO’s review series for 2013 has focused on topics related to integrative medicine. We’ve covered hypnosis as a modality for selected patients with cancer, the use of touch and energy healing therapies, and complementary strategies for the side effects of radiation therapy, among others. Although the use of integrative therapies and natural agents has not been adopted in all hematology and oncology settings, the study of these intriguing treatments continues. One thing is clear: Further rigorous research is needed to determine the safety and therapeutic value of these interventions in our patient population.



Ginseng and Fatigue

The healing properties of one natural agent in particular, ginseng, have been touted for millennia. One recently published study does much to validate the use of ginseng in patients with a particularly devastating symptom: cancer-related fatigue. Barton and colleagues published their results of the use of Wisconsin ginseng in a large trial of 364 patients from 40 different institutions (Barton et al., 2013). Their findings showed positive results in combating this common yet often debilitating symptom.

Fatigue, which affects over 60% to 90% of patients with cancer, is usually more severe as the disease progresses (Lawrence, Kupelnick, Miller, Devine, & Lau, 2004). The National Comprehensive Cancer Network describes cancer-related fatigue as distressing and persistent; exhaustion related to cancer or cancer treatment interferes with usual functioning (Piper & Cella, 2010). In one retrospective study of 1,778 patients, 84% presented with moderate to severe fatigue, with pain and appetite changes being the most significant predictors of this symptom (Yennu, Urbauer, & Bruera, 2012).

Barton and colleagues reported on their multisite trial (N07C2) in the Journal of the National Cancer Institute (2013). The study was a double-blind one in which 364 fatigued cancer survivors were randomized to receive 2,000 mg of American ginseng vs. a placebo for a total of 8 weeks. The primary endpoint of the study was the 4-week measurement of fatigue on the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), with changes noted from baseline at 4 and 8 weeks and evaluated by a two-sided, two-sample t-test.



Intriguing Study Results

The results reported by Barton and colleagues showed that changes in MFSI-SF score from baseline to 4 weeks were 14.4 (standard deviation [SD] = 27.1) for the patients receiving ginseng vs. placebo (8.2 with SD = 24.8; p = .07). At 8 weeks, a statistically significant difference was also seen for the ginseng group, with a change score of 20 (SD = 27), whereas the placebo group scored 10.3 (SD = 26.1; p = .003). Patients who were receiving active therapy for their disease had better scores than the patients who had already completed therapy. Toxicities were similar between groups.



What Does Ginseng Do?

Several types of ginseng exist, although the type most commonly used in herbal preparations is Asian ginseng. The study discussed here used American ginseng. Ginseng has been reported to have many different effects, including sedation, antidepressant activity, diuresis, and aphrodisiac properties (Sparreboom, Cox, Acharya, & Figg, 2004). Reports of research showing a dose-response relationship between ginseng and a decrease in cancer have been published (Yun & Choi, 1998).

The active constituent in extracts of ginseng is ginsenoside, which could possibly cause the drug interactions that may occur with the use of this product (Sparreboom et al., 2004). Since the toxicities seen in the N07C2 trial did not differ statistically between the two arms, it may be presumed that significant drug-drug interactions did not occur in this study; this is an important fact, as adverse events could be problematic if the compound interfered with or caused additional side effects.

As the results support using this treatment for cancer-related fatigue, oncology advanced practitioners could consider ginseng therapy an option for their patients experiencing fatigue. However, continued research is needed to definitively study the role of ginseng in the treatment of cancer-related fatigue, a symptom that is prevalent and devastating to so many of our patients. The Barton et al. study represents an important addition to that body of research.





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