Letter to the editor

A recent overview on ginsenosides as microRNA modulators in the treatment of human diseases

Tae Kyung Hyun1[*]

1Department of Industrial Plant Science and Technology, College of Agricultural, Life and Environmental Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea

EXCLI J 2021;20:Doc1453


Dear Editor,

MicroRNAs (miRNAs) are short (20-22 nucleotides) and highly conserved noncoding transcripts that play a crucial role in the regulation of gene expression, guiding the RNA-induced silencing complex to target mRNAs (Treiber et al., 2019[26]). Under normal physiological conditions, miRNAs are involved in feedback and feedforward loops, which have widespread functions in diverse biological processes, including cell proliferation, differentiation, and apoptosis (Tsang et al., 2007[27]; Reddy, 2015[23]). Since the human disease-related miR15 and miR16, located at chromosome 13q14, were first characterized in chronic lymphocytic leukemia (Calin et al., 2002[4]), much attention has been directed towards the function of miRNAs in a number of disorders such as cancer, viral infections, diabetes, immune-related diseases, and neurodegenerative disorders (Condrat et al., 2020[12]). In addition, accumulating evidence suggests that miRNA-mediated control of gene expression is important for the treatment of various diseases (Ali Syeda et al., 2020[1]; Condrat et al., 2020[12]; Zhang et al., 2020[37]; Wang et al., 2021[31]).

Ginsenosides are a class of steroid glycosides and triterpene saponins that account for the medical effects of ginseng (Panax ginseng). Among more than a hundred ginsenosides in ginseng, the most abundant ginsenosides are Rb1, Rb2, Rc, Rd, Re, and Rg1, all of which belong to the protopanaxadiol or protopanaxatriol saponins (Chen et al., 2019[5]). A growing body of evidence indicates that ginsenosides act as antioxidant, antimicrobial, anti-inflammatory, anti-cancer, anti-diabetic, and anti-aging agents, although each ginsenoside exhibits a different pharmacological action (Bai et al., 2018[2]; Zheng et al., 2018[39]; Wang and Roh, 2020[29]). The molecular targets of these effects contain various signaling pathways, including the Ras/Raf/MEK/ERK, PI3K/Akt, NF-κB, and PPARγ/HO-1 signaling pathways (Bai et al., 2018[2]; Zheng et al., 2018[38]). In addition, increasing focus on ginsenosides as miRNA modulators continues to contribute to advances in clinical trials.

In this letter, we present a review of recent clinical findings on the miRNA-mediated pharmacological role of ginsenosides (Table 1(Tab. 1); References in Table 1: Cai et al., 2019[3]; Cheng and Xing, 2019[10]; Chen et al., 2018[6][7], 2019[9], 2021[8]; Chu et al., 2019[11]; Gao and Zheng, 2018[13]; Jia et al., 2019[14]; Jiang et al., 2021[15]; Kim et al., 2017[17], 2021[16]; Lee et al., 2020[18]; Li et al., 2019[19]; Liang et al., 2019[20]; Liu et al., 2020[21]; Paik et al., 2019[22]; Shi et al., 2018[25], 2019[24]; Wang et al., 2018[30], 2021[28]; Wilkes et al., 2021[32]; Xue et al., 2018[33]; Yang et al., 2019[34]; Yi et al., 2019[35]; Yu et al., 2018[36]; Zheng et al., 2018[38]; Zhou et al., 2018[40]). We believe that this letter provides a solid foundation for further evaluation of ginsenosides as miRNA modulators in the prevention and treatment of a number of chronic diseases in humans.

Conflict of interest

The authors declare no conflict of interest.



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32. Wilkes Mc, Jung K, Lee BE, Saxena M, Sathianathen RS, Mercado JD, et al. The active component of ginseng, ginsenoside Rb1, improves erythropoiesis in models of Diamond Blackfan Anemia by targeting Nemo-like Kinase. J Biol Chem. 2021;297(3):100988.
33. Xue LP, Fu XL, Hu M, Zhang LW, Li YD, Peng YL, et al. Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway. Biochem Biophys Res Commun. 2018;501:827-32.
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35. Yi G, Liu L, Lv C, Wei Y, Yan T. Ginsenoside Rg1 defenses PC-12???cells against hydrogen peroxide-caused damage via up-regulation of miR-216a-5p. Life Sci. 2019;236:116948.
36. Yu H, Fan C, Yang L, Yu S, Song Q, Wang P, et al. Ginsenoside Rg1 prevents chronic stress-induced depression-like behaviors and neuronal structural plasticity in rats. Cell Physiol Biochem. 2018;48:2470-82.
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38. Zheng HZ, Fu XK, Shang JL, Lu RX, Ou YF, Chen CL. Ginsenoside Rg1 protects rat bone marrow mesenchymal stem cells against ischemia induced apoptosis through miR-494-3p and ROCK-1. Eur J Pharmacol. 2018;822:154-67.
39. Zheng M, Xin Y, Li Y, Xu F, Xi X, Guo H, et al. Ginsenosides: A potential neuroprotective agent. Biomed Res Int. 2018;2018:8174345.
40. Zhou Y, Zheng X, Lu J, Chen W, Li X, Zhao L. Ginsenoside 20(S)-Rg3 inhibits the warburg effect via modulating DNMT3A/ MiR-532-3p/HK2 pathway in ovarian cancer cells. Cell Physiol Biochem. 2018;45:2548-59.

Table 1: Recent studies on the modulation of microRNAs by ginsenosides as potential therapeutics

[*] Corresponding Author:

Tae Kyung Hyun, Department of Industrial Plant Science and Technology, College of Agricultural, Life and Environmental Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea; Phone: +82-43-261-2520, Fax: +82-43-271- 0413, eMail: taekyung7708@chungbuk.ac.kr