Efficacy and safety evaluation of black ginseng (Panax ginseng C.A. Mey.) extract (CJ EnerG): broad spectrum cytotoxic activity in human cancer cell lines and 28-day repeated oral toxicity study in Sprague-Dawley rats

Abstract

Background Ginseng (Panax ginseng C.A. Mey.) has been used as a valuable ingredient in traditional medicine for thousands of years mostly in Asian countries due to its therapeutic effects in various diseases. Among the processed ginseng products, black ginseng is produced by a repeated steaming and drying process of ginseng roots and has been known for its superior efficacy based on high accumulation of minor ginsenosides as recently discovered. Despite its popularity and increasing use, the toxicity information on black ginseng still remained largely lacking, raising safety concerns. This study was therefore carried out to determine the repeated oral toxicity of black ginseng extract (BGE; CJ EnerG) with evaluation of cytotoxic activity as validation of its pharmacological activity for toxicity testing. Methods Prior to the toxicity test, we examined the cytotoxicity of BGE in six cancer cell lines derived from distinct human tissues in comparison with red ginseng extract (RGE), ginsenosides Rg5 and 20(S)-Rg3, and then assessed 28-day repeated oral toxicity in Sprague-Dawley (SD) rats using daily administration of up to 2000 mg/kg BGE. Results BGE showed higher cytotoxicity than RGE in all the cell lines used in this study. Interestingly, the efficacy of BGE closely resembled the cytotoxic pattern of Rg5, suggesting Rg5 as the main effector in the cytotoxic activity of BGE. During the toxicity study, BGE-treated groups showed no noticeable abnormality in clinical signs, body weight gain, food and water consumption and urinalysis. Furthermore, hematological, serum biochemical and histopathological analyses did not find any BGE-related toxicity. Conclusion Our findings demonstrated that BGE has broad-spectrum in vitro cytotoxic activity, and that NOAEL of BGE in SD rats is > 2000 mg/kg, providing the essential safety information for human consumption.

Safety and efficacy of a feed additive consisting of a tincture derived from the roots of Panax ginseng C.A.Mey. (ginseng tincture) for horses, dogs and cats (FEFANA asbl)

“…Although none of the studies was performed with the additive under assessment, some of the studies were considered relevant as P. ginseng roots were extracted with hot water or 80% ethanol resulting in concentrations of ginsenosides in the test items comparable or higher (from 2% to 10.9%) than in the additive under assessment (1%). From these studies (oral exposure: 28 days up to 2 years), no observed adverse effect level (NOAEL) values were identified in the range 2000–5000 mg/kg bw per day for the test item, ginseng extracts containing 2%–10.9% ginsenosides (Jeong et al., 2016 ; Lee et al., 2019 ; NTP, 2011 ; Park et al., 2013 , 2018 , 2022 ).…”

Anti-prostate cancer mechanism of black ginseng during the "nine steaming and nine sun-drying" process based on HPLC analysis combined with vector space network pharmacology

“…Black ginseng is made by processing ginseng under "nine steaming and nine sun-drying" to produce rare saponins with potent anticancer activity [3]. Recent studies have shown that black ginseng has anticancer [4], antioxidant [5], and immunomodulatory effects [6]. Black ginseng has a better impact against prostate cancer, according to previous research on the variations in the composition of ginseng, red ginseng, and black ginseng [7,8].…”

Quality assessment of black ginseng materials utilizing chemometrics and modeling inflammation in Zebrafish

“…The potential biological effectiveness of black ginseng, such as anti-tumor, anti-inflammatory, antioxidant, anti-aging, and anti-diabetic activities is believed to surpass that of ginseng products derived from other processing procedures (Huang et al, 2023). However, it is worth noting that black ginseng may exhibit increased cytotoxicity in laboratory settings, which could be attributable to the unique properties of certain saponin components present in black ginseng (Park et al, 2022). No apparent abnormalities were observed in the physiological indicators, blood biochemistry, and histopathology analyses following the administration of black ginseng extract, as determined through tests conducted on rat models (Park et al, 2022).…”

“…However, it is worth noting that black ginseng may exhibit increased cytotoxicity in laboratory settings, which could be attributable to the unique properties of certain saponin components present in black ginseng (Park et al, 2022). No apparent abnormalities were observed in the physiological indicators, blood biochemistry, and histopathology analyses following the administration of black ginseng extract, as determined through tests conducted on rat models (Park et al, 2022). The chemical composition of black ginseng, particularly ginsenosides, shows significant alterations during nine steaming and drying cycles, resulting in corresponding modifications to the biological activity of black ginseng (Huang et al, 2023).…”