Phytomolecules

Rg3 : a rising star in the ginseng world

1. PANAX GINSENG & GINSENOSIDES

Asian ginseng is one of the most famous medicinal plants in the world. Praised for a myriad of health benefits, its roots are widely consumed for nutraceutical and therapeutical purposes. The potency of ginseng root is linked to the presence of specific molecules. Among them, ginsenosides are recognised as the main active constituents. Consequently, ginsenosides content is considered to be a key aspect of ginseng quality and performance.
However, the nature of ginsenosides is equally important. Indeed, not every ginsenoside are "born equal" in terms of potency. For instance, if Rb1 and Rg1 are considered as the most common ginsenosides, they show poor bioavailability. Yet, they are precursors of more bioactive ginsenosides (like Rg3) and are partially converted by gut microflora (ex: Rb1 is converted in Rg3). Alternatively, ginsenosides can be transformed by drying, cooking and other processes. For instance, the steam cooking process applied to produce red ginseng, converts some ginsenosides into more bioavailables ones. It is also true for the process of black ginseng (cooked nine times) that is promoted as a more bioactive version of red ginseng due to a higher convertion rate [1-2].
2. Rg3: A COVETED MOLECULE

2.1. Rg3: a rare ginsenoside

Due to its high health potential, Rg3 is one of the rising star among ginsenosides. Unfortunately, if Rb1 or Rg1 are considered to be ubiquitous, Rg3 is considered to be a rare (frequently called "rares ginsenosides" or "nobles ginsenosides" in the litterature). In fact, Rg3 is almost absent from white ginseng and is generally exclusive of premium cooked ginseng. Wild ginseng is also considered to be more effective than field ginseng through a better ginsenoside profile, however, this depends on growth conditions (some wild ginseng are poor in ginsenosides of interest and some cultivated ginseng are good).

2.2. Ginsenosides bioconversion

As explained before, Rb1 can be "bioactivated" in Rg3 by the gut microflora. However, depending on the microbiota, the converted fraction can be quite low, leading to poor bioavailability and consequently poor health benefits. Due to the rise of interest for the nutraceutical and therapeutical potential of Rg3, it is now highly coveted. Indeed, a lot of energy is devoted to find ways to "bioactivate" classical ginsenosides Rg3.
The investigations about conversion processes involve cooking optimisations. As mentioned, the black ginseng trend is based on this principle. Ginseng fermentation is also an emerging trend that opens the opportunity to "bioactive" ginsenosides [3-4].
More recently, tuning of growth conditions through indoor vertical farming is appearing as an opportunity to optimise ginsenosides content. Combined with cooking optimisation, it leads to the development of ideal ginsenosides profiles with strong nutraceutical and therapeutical potentials.
3. NUTRACEUTICAL POTENTIAL OF Rg3

3.1. Ergogenic

Ginseng is traditionally considered as a natural tonic. Unsurprisingly, it is widely found in energizing food and beverage. These ergogenic and anti-fatigue effects can, at least partially, be explained by the activity of Rg3. Indeed, Rg3 has been reported to have positive impact on fatigue, both from a metabolic standpoint [5] and a neurological perspective [6]. Moreover, Rg3 has been reported to "mimic exercise training" on cardiac mitochondrial system [7], offering new opportunities for sport nutrition.

3.2. Immune booster

In European pharmacies, ginseng is usually combined with vitamins for products destined to support natural defenses against "common cold". This use seems to be related, in part, to Rg3 which has has been reported to not only to potentiate immune response, but also to inhibit virus infection.
Indeed, Rg3 has be highlighted as an immune booster [8-10] to the point that it was even evaluated in a chemotherapy context to support immune defenses recovery [11-12]. It has also been identified as an inhibitor of virus infection [13-16]. Combined with the data on ergogenic properties, Rg3 becomes a true "health booster".

3.3. Neuroprotection

In Shénnóng běncǎo jīng, ginseng benefits are described as follow: "Consumed over a long time, it lightens the body and extends the years". Since then, ginseng roots are considered as a medicinal plant for longevity. Neuroprotection is therefore a core element in ginseng neurological properties.
According to existing data, not only does Rg3 show neuroprotective properties [17-24] but it also has been identified as a "shield" against cognitive deterioration in multiple experimental models [25-26]. Finally, the benefits of Rg3 on Alzheimer related mechanisms is also really promising [27-30].

3.4. Stress & anxiety

Ginseng is rarely considered as a first choice for stress management. However, numerous ginsenosides have shown positive effects on anxiety and depression models. Rg3 is no exception and has been identified as beneficial in multiple experiments [31-36]. Interestingly, Rg3 has shown quicker and stronger effect at lower dosage compared to other ginsenosides [37], illustrating one more time the fact that Rg3 can be considered as a "bioactivated" form of ginsenoside. Finally, it should be noted that Rg3 has been identified as an activator of GABAergic pathway [38] which opens opportunities for products destined to sleep. It should be noted that a growing number of data seem to correlate the anti-stress effect with the nootropic action of ginseng.

3.5. Menopause

Menopause is a complex phenomenon with potential adverse effects (irritability, sleep troubles, hot flashes, etc.) and associated with increased risks of cardiovascular issues, osteoporosis, metabolic syndrom, depression, etc. Even if ginseng is not traditionally considered as an asset on this matter, clinical data indicate that ginseng could be a great asset in supporting menopausal women [39-40]. Moreover, some highlighted biological properties of Rg3 suggest that it could bring an even more global support.

On one hand, Rg3 could potentially be beneficial in case of hypertension (a frequent condition in menopausal women) [41] and has been identified as cardioprotective [42] and vasculoprotective [43]. It also has been identified in experimental models as beneficial in cases of atherosclerosis [44-45]. On the other hand, Rg3 seems to have beneficial effect on osteoporis-related mechanisms [46-48].
4. THERAPEUTIC PERSPECTIVES OF Rg3

But, beyond nutraceutical benefits, the real cause of "Rg3 rush" is more than probably related to its potential therapeutical properties.

4.1. Diabetes

Ginseng is usually considered in phytotherapy to have a balancing effect on blood sugar. Scientific data on Rg3 seem to not only validate this virtue [49-52] but also to have potential benefits on complications related to the condition [53-56]. Obviously, this does not means that Rg3 is a treatment against diabetes. However, these results invites to consider it as a adjuvant treatment or a support tool for glycemic balance.

4.2. Oncology

Oncology is probably the most studied topic for Rg3. It would be too long to make a exhaustive compendium of every cancer model where Rg3 where evaluated (see main examples below). Even from a general perspective, Rg3 is involved through many physiological processes (Epigenetical impact [57], Angiogenesis inhibition [58], etc.). Its interest has been evaluated in lots of different cancer models:

  • Colon Cancers: Rg3 has shown fascinating results on different cell lines of colon cancers. The identified effects range from direct antiproliferative effects [59-62] to inhibition of angiogenesis [63] and migration [64-65]. Rg3 has also been shown to potentiate treatments like docetaxel [66] or radiotherapy [67].

  • Breast Cancers: Rg3 has been reported to have significant impact on different breast cancer models [68-70] (including triple negative [71]) through multiple mechanisms [72-73]. Like data on colon cancer, that includes impact on migration [74] and potantiation of treatments like paclitaxel [75] or capecitabine [76].

  • Liver Cancers: Rg3 has been evaluated in the context of liver cancers through different models. Like other types of cancer described above, Rg3 seems to inhibit proliferation/stimulate apoptosis of cancer cells [77-82], limit migration [83] and potentiate treatments like sorafenib [84] and Doxorubicin [85].

  • Lung Cancers: Rg3 has shown results in lung cancers [86-87] including impact on invasiveness [88-90]. Moreover, there is a lot of studies on the potentiation of other treatment using Rg3 like osimertinib [91], icotinib [92], gefitinib [93], cisplatin [94-95], gemcitabine [96], cyclophosphamide [97] and even radiation treatment [98].

These are only some examples among many other like skin cancers [99-103], ovarian cancers [104-108] or brain cancers [109-112]. Like the data on diabetes, this does not mean that Rg3 can be considered as a cancer treatment. However, the health potential of the molecule begs to investigate the opportunity of using it to support patients.
5. CONCLUSIONS

Rg3 is widely considered as the flagship molecule of Panax ginseng roots both for nutraceutical and therapeutical applications. However, even if it is present in very limited quantities in red ginseng and in reasonnable quantities in black ginseng, Rg3 is still a rare ginsenoside. Based on this premise, a lot of industrial actors are looking to produce pure Rg3 by other means, thereby giving up on the beneficial properties of other constituents of ginseng roots.
BOTALYS is exploring another path. By applying a unique indoor vertical farming approach to ginseng culture, it has total control over growth conditions and has optimized them to produce a red ginseng naturally rich in Rg3 (>15 mg/g) among other rare ginsenosides like Rg5 & Rk1.
REFERENCES

[1] Xu XF, Gao Y, Xu SY, Liu H, Xue X, Zhang Y, Zhang H, Liu MN, Xiong H, Lin RC, Li XR (2017) – “Remarkable impact of steam temperature on ginsenosides transformation from fresh ginseng to red ginseng.” J Ginseng Res. 2018 Jul;42(3):277-287. doi: 10.1016/j.jgr.2017.02.003. Epub 2017 Feb 27.
[2] Jin Y, Kim YJ, Jeon JN, Wang C, Min JW, Noh HY, Yang DC (2015) – “Effect of white, red and black ginseng on physicochemical properties and ginsenosides.” Plant Foods Hum Nutr. 2015 Jun;70(2):141-5. doi: 10.1007/s11130-015-0470-0.
[3] Kim JH, Doo EH, Jeong M, Kim S, Lee YY, Yang J, Lee JS, Kim JH, Lee KW, Huh CS, Byun S (2019) – “Enhancing Immunomodulatory Function of Red Ginseng Through Fermentation Using Bifidobacterium animalis Subsp. lactis LT 19-2.” Nutrients. 2019 Jun 28;11(7). pii: E1481. doi: 10.3390/nu11071481.
[4] Park B, Hwang H, Lee J, Sohn SO, Lee SH, Jung MY, Lim HI, Park HW, Lee JH (2017) – “Evaluation of ginsenoside bioconversion of lactic acid bacteria isolated from kimchi.” J Ginseng Res. 2017 Oct;41(4):524-530. doi: 10.1016/j.jgr.2016.10.003. Epub 2016 Oct 10.
[5] Yang QY, Lai XD, Ouyang J, Yang JD (2018) – “Effects of Ginsenoside Rg3 on fatigue resistance and SIRT1 in aged rats.” Toxicology. 2018 Nov 1;409:144-151. doi: 10.1016/j.tox.2018.08.010. Epub 2018 Aug 23.
[6] Xu Y, Zhang P, Wang C, Shan Y, Wang D, Qian F, Sun M, Zhu C (2013) – “Effect of ginsenoside Rg3 on tyrosine hydroxylase and related mechanisms in the forced swimming-induced fatigue rats.” J Ethnopharmacol. 2013 Oct 28;150(1):138-47. doi: 10.1016/j.jep.2013.08.016. Epub 2013 Aug 28.
[7] M, Huang C, Wang C, Zheng J, Zhang P, Xu Y, Chen H, Shen W (2013) – “Ginsenoside Rg3 improves cardiac mitochondrial population quality: mimetic exercise training.” Biochem Biophys Res Commun. 2013 Nov 8;441(1):169-74. doi: 10.1016/j.bbrc.2013.10.039. Epub 2013 Oct 15.
[8] Xin C, Kim J, Quan H, Yin M, Jeong S, Choi JI, Jang EA, Lee CH, Kim DH, Bae HB (2019) – “Ginsenoside Rg3 promotes Fc gamma receptor-mediated phagocytosis of bacteria by macrophages via an extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent mechanism.” Int Immunopharmacol. 2019 Dec;77:105945. doi: 10.1016/j.intimp.2019.105945. Epub 2019 Oct 20.
[9] Choi YJ, Kang LJ, Lee SG (2014) – “Stimulation of DDX3 expression by ginsenoside Rg3 through the Akt/p53 pathway activates the innate immune response via TBK1/IKKε/IRF3 signalling.” Curr Med Chem. 2014;21(8):1050-60.
[10] Wei X, Chen J, Su F, Su X, Hu T, Hu S (2012) – « Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice.” Int Immunol. 2012 Jul;24(7):465-71. doi: 10.1093/intimm/dxs043. Epub 2012 Mar 16.
[11] X, Zhang Z, Liu J, Wang Y, Zhou Q, Wang S, Wang X (2019) – “Ginsenoside Rg3 improves cyclophosphamide-induced immunocompetence in Balb/c mice.” Int Immunopharmacol. 2019 Jul;72:98-111. doi: 10.1016/j.intimp.2019.04.003. Epub 2019 Apr 8.
[12] Park D, Bae DK, Jeon JH, Lee J, Oh N, Yang G, Yang YH, Kim TK, Song J, Lee SH, Song BS, Jeon TH, Kang SJ, Joo SS, Kim SU, Kim YB (2011) – “Immunopotentiation and antitumor effects of a ginsenoside Rg₃-fortified red ginseng preparation in mice bearing H460 lung cancer cells.” Environ Toxicol Pharmacol. 2011 May;31(3):397-405. doi: 10.1016/j.etap.2011.01.008. Epub 2011 Mar 8.
[13] Wright S, Altman E (2020) – “Inhibition of Herpes Simplex Viruses, Types 1 and 2, by Ginsenoside 20(S)-Rg3.” J Microbiol Biotechnol. 2020 Jan 28;30(1):101-108. doi: 10.4014/jmb.1908.08047.
[14] Yang H, Oh KH, Kim HJ, Cho YH, Yoo YC (2018) – “Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice.” J Microbiol Biotechnol. 2018 Mar 28;28(3):391-396. doi: 10.4014/jmb.1801.01006.
[15] Kim SJ, Jang JY, Kim EJ, Cho EK, Ahn DG, Kim C, Park HS, Jeong SW, Lee SH, Kim SG, Kim YS, Kim HS, Kim BS, Lee J, Siddiqui A (2017) – “Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation.” Hepatology. 2017 Sep;66(3):758-771. doi: 10.1002/hep.29177. Epub 2017 Aug 1.
[16] Kang LJ, Choi YJ, Lee SG (2013) – “Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication.” Int J Biochem Cell Biol. 2013 Nov;45(11):2612-21. doi: 10.1016/j.biocel.2013.08.016. Epub 2013 Sep 1.
[17] Hou J, Xue J, Wang Z, Li W (2018) – “Ginsenoside Rg3 and Rh2 protect trimethyltin-induced neurotoxicity via prevention on neuronal apoptosis and neuroinflammation.” Phytother Res. 2018 Dec;32(12):2531-2540. doi: 10.1002/ptr.6193. Epub 2018 Oct 2.
[18] Park SM, Choi MS, Sohn NW, Shin JW (2012) – “Ginsenoside Rg3 attenuates microglia activation following systemic lipopolysaccharide treatment in mice.” Biol Pharm Bull. 2012;35(9):1546-52.
[19] He B, Chen P, Yang J, Yun Y, Zhang X, Yang R, Shen Z (2012) – “Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats.” Neurosci Lett. 2012 Sep 27;526(2):106-11. doi: 10.1016/j.neulet.2012.08.022. Epub 2012 Aug 19.
[20] Kim SO, You JM, Yun SJ, Son MS, Nam KN, Hong JW, Kim SY, Choi SY, Lee EH (2010) – “Ginsenoside rb1 and rg3 attenuate glucocorticoid-induced neurotoxicity.” Cell Mol Neurobiol. 2010 Aug;30(6):857-62. doi: 10.1007/s10571-010-9513-0. Epub 2010 Mar 25.
[21] Tian J, Zhang S, Li G, Liu Z, Xu B (2009) – “20(S)-ginsenoside Rg3, a neuroprotective agent, inhibits mitochondrial permeability transition pores in rat brain.” Phytother Res. 2009 Apr;23(4):486-91. doi: 10.1002/ptr.2653.
[22] Joo SS, Yoo YM, Ahn BW, Nam SY, Kim YB, Hwang KW, Lee DI (2008) – “Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation.” Biol Pharm Bull. 2008 Jul;31(7):1392-6.
[23] Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH, Lee JH, Pyo MK, Lee SM, Chung JM, Kim S, Rhim H, Oh JW, Nah SY (2007) – “Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus.” Brain Res. 2007 Mar 9;1136(1):190-9. Epub 2006 Dec 22.
[24] Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W, Wang C, Liu K (2005) – “Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats.” Neurosci Lett. 2005 Feb 10;374(2):92-7.
[25] Kim J, Shim J, Lee S, Cho WH, Hong E, Lee JH, Han JS, Lee HJ, Lee KW (2016) – “Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice.” BMC Complement Altern Med. 2016 Feb 18;16:66. doi: 10.1186/s12906-016-1050-z.
[26] Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M, Shim I, Lee H, Hahm DH (2013) – “Ginsenoside rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats.” Biomol Ther (Seoul). 2013 Sep 30;21(5):381-90. doi: 10.4062/biomolther.2013.053.
[27] Zhang Y, Yang X, Wang S, Song S (2019) – “Ginsenoside Rg3 Prevents Cognitive Impairment by Improving Mitochondrial Dysfunction in the Rat Model of Alzheimer's Disease.” J Agric Food Chem. 2019 Sep 11;67(36):10048-10058. doi: 10.1021/acs.jafc.9b03793. Epub 2019 Aug 27.
[28] Jang SK, Yu JM, Kim ST, Kim GH, Park DW, Lee DI, Joo SS (2015) – “An Aβ42 uptake and degradation via Rg3 requires an activation of caveolin, clathrin and Aβ-degrading enzymes in microglia.” Eur J Pharmacol. 2015 Jul 5;758:1-10. doi: 10.1016/j.ejphar.2015.03.071. Epub 2015 Apr 4.
[29] Kang MS, Baek SH, Chun YS, Moore AZ, Landman N, Berman D, Yang HO, Morishima-Kawashima M, Osawa S, Funamoto S, Ihara Y, Di Paolo G, Park JH, Chung S, Kim TW (2013) – “Modulation of lipid kinase PI4KIIα activity and lipid raft association of presenilin 1 underlies γ-secretase inhibition by ginsenoside (20S)-Rg3.” J Biol Chem. 2013 Jul 19;288(29):20868-82. doi: 10.1074/jbc.M112.445734. Epub 2013 May 30.
[30] Yang L, Hao J, Zhang J, Xia W, Dong X, Hu X, Kong F, Cui X (2009) – “Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin.” J Pharm Pharmacol. 2009 Mar;61(3):375-80. doi: 10.1211/jpp/61.03.0013.
[31] Xu JN, Chen LF, Su J, Liu ZL, Chen J, Lin QF, Mao WD, Shen D (2018) – “The anxiolytic-like effects of ginsenoside Rg3 on chronic unpredictable stress in rats.” Sci Rep. 2018 May 17;8(1):7741. doi: 10.1038/s41598-018-26146-5.
[32] Kang A, Xie T, Zhu D, Shan J, Di L, Zheng X (2017) – “Suppressive Effect of Ginsenoside Rg3 against Lipopolysaccharide-Induced Depression-Like Behavior and Neuroinflammation in Mice.” J Agric Food Chem. 2017 Aug 16;65(32):6861-6869. doi: 10.1021/acs.jafc.7b02386. Epub 2017 Aug 7.
[33] Zhang H, Zhou Z, Chen Z, Zhong Z, Li Z (2017) – “Ginsenoside Rg3 exerts anti-depressive effect on an NMDA-treated cell model and a chronic mild stress animal model.” J Pharmacol Sci. 2017 May;134(1):45-54. doi: 10.1016/j.jphs.2017.03.007. Epub 2017 Apr 12.
[34] You Z, Yao Q, Shen J, Gu Z, Xu H, Wu Z, Chen C, Li L (2017) – “Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade.” J Nat Med. 2017 Apr;71(2):367-379. doi: 10.1007/s11418-016-1066-1. Epub 2016 Dec 24.
[35] Kim TW, Choi HJ, Kim NJ, Kim DH (2009) – “Anxiolytic-like effects of ginsenosides Rg3 and Rh2 from red ginseng in the elevated plus-maze model.” Planta Med. 2009 Jun;75(8):836-9. doi: 10.1055/s-0029-1185402. Epub 2009 Mar 5.
[36]Lee SH, Jung BH, Kim SY, Lee EH, Chung BC (2006) – “The antistress effect of ginseng total saponin and ginsenoside Rg3 and Rb1 evaluated by brain polyamine level under immobilization stress.” Pharmacol Res. 2006 Jul;54(1):46-9. Epub 2006 Mar 10.
[37] Zhang H, Li Z, Zhou Z, Yang H, Zhong Z, Lou C (2016) – “Antidepressant-like effects of ginsenosides: A comparison of ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K, and 20(S)-protopanaxadiol in mice models of despair.” Pharmacol Biochem Behav. 2016 Jan;140:17-26. doi: 10.1016/j.pbb.2015.10.018. Epub 2015 Oct 31.
[38] Lee BH, Kim HJ, Chung L, Nah SY (2013) – “Ginsenoside Rg₃ regulates GABAA receptor channel activity: involvement of interaction with the γ₂ subunit.” Eur J Pharmacol. 2013 Apr 5;705(1-3):119-25. doi: 10.1016/j.ejphar.2013.02.040. Epub 2013 Mar 13.
[39] Ghorbani Z, Mirghafourvand M, Charandabi SM, Javadzadeh Y (2019) – “The effect of ginseng on sexual dysfunction in menopausal women: A double-blind, randomized, controlled trial.” Complement Ther Med. 2019 Aug;45:57-64. doi: 10.1016/j.ctim.2019.05.015. Epub 2019 May 22.
[40] Lee HW, Choi J, Lee Y, Kil KJ, Lee MS (2016) – “Ginseng for managing menopausal woman's health: A systematic review of double-blind, randomized, placebo-controlled trials.” Medicine (Baltimore). 2016 Sep;95(38):e4914. doi: 10.1097/MD.0000000000004914.
[41] Nagar H, Choi S, Jung SB, Jeon BH, Kim CS (2016) – “Rg3-enriched Korean Red Ginseng enhances blood pressure stability in spontaneously hypertensive rats.” Integr Med Res. 2016 Sep;5(3):223-229. doi: 10.1016/j.imr.2016.05.006. Epub 2016 Jun 3.
[42] Jiang Y, Li M, Lu Z, Wang Y, Yu X, Sui D, Fu L (2017) – “Ginsenoside Rg3 induces ginsenoside Rb1-comparable cardioprotective effects independent of reducing blood pressure in spontaneously hypertensive rats.” Exp Ther Med. 2017 Nov;14(5):4977-4985. doi: 10.3892/etm.2017.5198. Epub 2017 Sep 22.
[43] Min JK, Kim JH, Cho YL, Maeng YS, Lee SJ, Pyun BJ, Kim YM, Park JH, Kwon YG (2006) – “20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway.” Biochem Biophys Res Commun. 2006 Oct 27;349(3):987-94. Epub 2006 Aug 30.
[44] Guo M, Xiao J, Sheng X, Zhang X, Tie Y, Wang L, Zhao L, Ji X (2018) – “Ginsenoside Rg3 Mitigates Atherosclerosis Progression in Diabetic apoE-/- Mice by Skewing Macrophages to the M2 Phenotype.” Front Pharmacol. 2018 May 9;9:464. doi: 10.3389/fphar.2018.00464. eCollection 2018.
[45] Guo M, Guo G, Xiao J, Sheng X, Zhang X, Tie Y, Cheng YK, Ji X (2018) – “Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell proliferation and migration in diabetic atherosclerosis.” J Cell Mol Med. 2018 Jun;22(6):3202-3214. doi: 10.1111/jcmm.13601. Epub 2018 Mar 22.
[46] Zhang X, Chen K, Wei B, Liu X, Lei Z, Bai X (2016) – “Ginsenosides Rg3 attenuates glucocorticoid-induced osteoporosis through regulating BMP-2/BMPR1A/Runx2 signaling pathway.” Chem Biol Interact. 2016 Aug 25;256:188-97. doi: 10.1016/j.cbi.2016.07.003. Epub 2016 Jul 5.
[47] Siddiqi MH, Siddiqi MZ, Kang S, Noh HY, Ahn S, Simu SY, Aziz MA, Sathishkumar N, Jiménez Pérez ZE, Yang DC (2015) – “Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7 Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of Cathepsin K: An In Silico and In Vitro Study.” Phytother Res. 2015 Sep;29(9):1286-1294. doi: 10.1002/ptr.5374. Epub 2015 Jun 8.
[48] Siddiqi MZ, Siddiqi MH, Kim YJ, Jin Y, Huq MA, Yang DC (2015) – “Effect of Fermented Red Ginseng Extract Enriched in Ginsenoside Rg3 on the Differentiation and Mineralization of Preosteoblastic MC3T3-E1 Cells.” J Med Food. 2015 May;18(5):542-8. doi: 10.1089/jmf.2014.3251. Epub 2015 Mar 12.
[49] Kim KS, Jung Yang H, Lee IS, Kim KH, Park J, Jeong HS, Kim Y, Seok Ahn K, Na YC, Jang HJ (2015) – “The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice.” Sci Rep. 2015 Dec 17;5:18325. doi: 10.1038/srep18325.
[50] Niu J, Pi ZF, Yue H, Yang H, Wang Y, Yu Q, Liu SY (2012) – “Effect of 20(S)-ginsenoside Rg3 on streptozotocin-induced experimental type 2 diabetic rats: a urinary metabonomics study by rapid-resolution liquid chromatography/mass spectrometry.” Rapid Commun Mass Spectrom. 2012 Dec 15;26(23):2683-9. doi: 10.1002/rcm.6392.
[51] Kim M, Ahn BY, Lee JS, Chung SS, Lim S, Park SG, Jung HS, Lee HK, Park KS (2009) – “The ginsenoside Rg3 has a stimulatory effect on insulin signaling in L6 myotubes.” Biochem Biophys Res Commun. 2009 Nov 6;389(1):70-3. doi: 10.1016/j.bbrc.2009.08.088. Epub 2009 Aug 21.
[52] Park MW, Ha J, Chung SH (2008) – “20(S)-ginsenoside Rg3 enhances glucose-stimulated insulin secretion and activates AMPK.” Biol Pharm Bull. 2008 Apr;31(4):748-51.
[53] Saba E, Kim SH, Kim SD, Park SJ, Kwak D, Oh JH, Park CK, Rhee MH (2018) – “Alleviation of diabetic complications by ginsenoside Rg3-enriched red ginseng extract in western diet-fed LDL-/- mice.” J Ginseng Res. 2018 Jul;42(3):352-355. doi: 10.1016/j.jgr.2017.04.004. Epub 2017 Apr 24.
[54] Kim YJ, Park SM, Jung HS, Lee EJ, Kim TK, Kim TN, Kwon MJ, Lee SH, Rhee BD, Kim MK, Park JH (2016) – “Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress.” Islets. 2016 Apr 18;8(3):57-64. doi: 10.1080/19382014.2016.1161874.
[55] Sun HQ, Zhou ZY (2010) – “Effect of ginsenoside-Rg3 on the expression of VEGF and TNF-α in retina with diabetic rats.” Int J Ophthalmol. 2010;3(3):220-3. doi: 10.3980/j.issn.2222-3959.2010.03.09. Epub 2010 Sep 18.
[56] Kang KS, Yamabe N, Kim HY, Park JH, Yokozawa T (2008) – “Therapeutic potential of 20(S)-ginsenoside Rg(3) against streptozotocin-induced diabetic renal damage in rats.” Eur J Pharmacol. 2008 Sep 4;591(1-3):266-72. doi: 10.1016/j.ejphar.2008.06.077. Epub 2008 Jun 27.
[57] Ham J, Jeong D, Park S, Kim HW, Kim H, Kim SJ (2019) – “Ginsenoside Rg3 and Korean Red Ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1.” J Ginseng Res. 2019 Oct;43(4):625-634. doi: 10.1016/j.jgr.2019.02.004. Epub 2019 Feb 28.
[58] Kim JW, Jung SY, Kwon YH, Lee JH, Lee YM, Lee BY, Kwon SM (2012) – “Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells.” Cancer Biol Ther. 2012 May;13(7):504-15. doi: 10.4161/cbt.19599. Epub 2012 May 1.
[59] Yang X, Zou J, Cai H, Huang X, Yang X, Guo D, Cao Y (2017) – “Ginsenoside Rg3 inhibits colorectal tumor growth via down-regulation of C/EBPβ/NF-κB signaling.” Biomed Pharmacother. 2017 Dec;96:1240-1245. doi: 10.1016/j.biopha.2017.11.092. Epub 2017 Nov 21.
[60] Yuan HD, Quan HY, Zhang Y, Kim SH, Chung SH (2010) – “20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway.” Mol Med Rep. 2010 Sep-Oct;3(5):825-31. doi: 10.3892/mmr.2010.328. Epub 2010 Jul 8.
[61] He BC, Gao JL, Luo X, Luo J, Shen J, Wang L, Zhou Q, Wang YT, Luu HH, Haydon RC, Wang CZ, Du W, Yuan CS, He TC, Zhang BQ (2011) – “Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling.” Int J Oncol. 2011 Feb;38(2):437-45. doi: 10.3892/ijo.2010.858. Epub 2010 Dec 3.
[62] Lee SY, Kim GT, Roh SH, Song JS, Kim HJ, Hong SS, Kwon SW, Park JH (2009) – “Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines.” Biosci Biotechnol Biochem. 2009 Apr 23;73(4):811-6. Epub 2009 Apr 7.
[63] Tang YC, Zhang Y, Zhou J, Zhi Q, Wu MY, Gong FR, Shen M, Liu L, Tao M, Shen B, Gu DM, Yu J, Xu MD, Gao Y, Li W (2018) – “Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo.” Int J Oncol. 2018 Jan;52(1):127-138. doi: 10.3892/ijo.2017.4183. Epub 2017 Nov 1.
[64] Li J, Qi Y (2019) – “Ginsenoside Rg3 inhibits cell growth, migration and invasion in Caco-2 cells by downregulation of lncRNA CCAT1.” Exp Mol Pathol. 2019 Feb;106:131-138. doi: 10.1016/j.yexmp.2019.01.003. Epub 2019 Jan 8.
[65] Junmin S, Hongxiang L, Zhen L, Chao Y, Chaojie W (2015) – “Ginsenoside Rg3 inhibits colon cancer cell migration by suppressing nuclear factor kappa B activity.” J Tradit Chin Med. 2015 Aug;35(4):440-4.
[66] Kim SM, Lee SY, Yuk DY, Moon DC, Choi SS, Kim Y, Han SB, Oh KW, Hong JT (2009) – “Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel.” Arch Pharm Res. 2009 May;32(5):755-65. doi: 10.1007/s12272-009-1515-4. Epub 2009 May 27.
[67] Liu T, Duo L, Duan P (2018) – « Ginsenoside Rg3 Sensitizes Colorectal Cancer to Radiotherapy through Downregulation of Proliferative and Angiogenic Biomarkers.” Evid Based Complement Alternat Med. 2018 Mar 18;2018:1580427. doi: 10.1155/2018/1580427. eCollection 2018.
[68]Oh J, Yoon HJ, Jang JH, Kim DH, Surh YJ (2019) – “The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling.” J Ginseng Res. 2019 Jul;43(3):421-430. doi: 10.1016/j.jgr.2018.05.004. Epub 2018 May 17.
[69] Nakhjavani M, Hardingham JE, Palethorpe HM, Tomita Y, Smith E, Price TJ, Townsend AR (2019) – “Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer.” Medicines (Basel). 2019 Jan 23;6(1). pii: E17. doi: 10.3390/medicines6010017. Review.
[70] Kim BM, Kim DH, Park JH, Na HK, Surh YJ (2013) – “Ginsenoside Rg3 Induces Apoptosis of Human Breast Cancer (MDA-MB-231) Cells.” J Cancer Prev. 2013 Jun;18(2):177-85.
[71] Nakhjavani M, Palethorpe HM, Tomita Y, Smith E, Price TJ, Yool AJ, Pei JV, Townsend AR, Hardingham JE (2019) – “Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models.” Pharmaceuticals (Basel). 2019 Aug 1;12(3). pii: E117. doi: 10.3390/ph12030117
[72] Ham J, Lee S, Lee H, Jeong D, Park S, Kim SJ (2018) – “Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3.” Am J Chin Med. 2018;46(6):1333-1355. doi: 10.1142/S0192415X18500702. Epub 2018 Aug 27.
[73] Zou M, Wang J, Gao J, Han H, Fang Y (2018) – “Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells.” Oncol Lett. 2018 Mar;15(3):2889-2898. doi: 10.3892/ol.2017.7654. Epub 2017 Dec 19.
[74] Chen XP, Qian LL, Jiang H, Chen JH (2011) – “Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line.” Int J Clin Oncol. 2011 Oct;16(5):519-23. doi: 10.1007/s10147-011-0222-6. Epub 2011 Apr 1.
[75] Yuan Z, Jiang H, Zhu X, Liu X, Li J (2017) – “Ginsenoside Rg3 promotes cytotoxicity of Paclitaxel through inhibiting NF-κB signaling and regulating Bax/Bcl-2 expression on triple-negative breast cancer.” Biomed Pharmacother. 2017 May;89:227-232. doi: 10.1016/j.biopha.2017.02.038. Epub 2017 Feb 20.
[76] Zhang Q, Kang X, Yang B, Wang J, Yang F (2008) – “Antiangiogenic effect of capecitabine combined with ginsenoside Rg3 on breast cancer in mice.” Cancer Biother Radiopharm. 2008 Oct;23(5):647-53. doi: 10.1089/cbr.2008.0532.
[77] Hu S, Zhu Y, Xia X, Xu X, Chen F, Miao X, Chen X (2019) – “Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis.” Anal Cell Pathol (Amst). 2019 Aug 26;2019:3815786. doi: 10.1155/2019/3815786. eCollection 2019.
[78] Li X, Tsauo J, Geng C, Zhao H, Lei X, Li X. (2018) – “Ginsenoside Rg3 Decreases NHE1 Expression via Inhibiting EGF-EGFR-ERK1/2-HIF-1α Pathway in Hepatocellular Carcinoma: A Novel Antitumor Mechanism.” Am J Chin Med. 2018;46(8):1915-1931. doi: 10.1142/S0192415X18500969. Epub 2018 Dec 10.
[79] Teng S, Wang Y, Li P, Liu J, Wei A, Wang H, Meng X, Pan D, Zhang X (2017) – “Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells.” Mol Med Rep. 2017 Apr;15(4):2029-2038. doi: 10.3892/mmr.2017.6255. Epub 2017 Feb 28.
[80] Park HM, Kim SJ, Kim JS, Kang HS (2012) – “Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways.” Food Chem Toxicol. 2012 Aug;50(8):2736-41. doi: 10.1016/j.fct.2012.05.027. Epub 2012 May 22.
[81] Zhang C, Liu L, Yu Y, Chen B, Tang C, Li X (2012) – « Antitumor effects of ginsenoside Rg3 on human hepatocellular carcinoma cells.” Mol Med Rep. 2012 May;5(5):1295-8. doi: 10.3892/mmr.2012.808. Epub 2012 Feb 23.
[82] Jiang JW, Chen XM, Chen XH, Zheng SS (2011) – “Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway.” World J Gastroenterol. 2011 Aug 21;17(31):3605-13. doi: 10.3748/wjg.v17.i31.3605.
[83] Sun MY, Song YN, Zhang M, Zhang CY, Zhang LJ, Zhang H (2019) – “Ginsenoside Rg3 inhibits the migration and invasion of liver cancer cells by increasing the protein expression of ARHGAP9.” Oncol Lett. 2019 Jan;17(1):965-973. doi: 10.3892/ol.2018.9701. Epub 2018 Nov 15.
[84] Lu M, Fei Z, Zhang G (2018) – “Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway.” Biomed Pharmacother. 2018 Jan;97:1282-1288. doi: 10.1016/j.biopha.2017.11.006. Epub 2017 Dec 14.
[85] Kim DG, Jung KH, Lee DG, Yoon JH, Choi KS, Kwon SW, Shen HM, Morgan MJ, Hong SS, Kim YS (2014) – “20(S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin.” Oncotarget. 2014 Jun 30;5(12):4438-51.
[86] Liu T, Zuo L, Guo D, Chai X, Xu J, Cui Z, Wang Z, Hou C (2019) – « Ginsenoside Rg3 regulates DNA damage in non-small cell lung cancer cells by activating VRK1/P53BP1 pathway.” Biomed Pharmacother. 2019 Dec;120:109483. doi: 10.1016/j.biopha.2019.109483. Epub 2019 Oct 16.
[87] Xie Q, Wen H, Zhang Q, Zhou W, Lin X, Xie D, Liu Y (2017) – “Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell.” Biomed Pharmacother. 2017 Jan;85:16-21. doi: 10.1016/j.biopha.2016.11.096. Epub 2016 Dec 5.
[88] Ahmmed B, Kampo S, Khan M, Faqeer A, Kumar SP, Yulin L, Liu JW, Yan Q (2019) – “Rg3 inhibits gemcitabine-induced lung cancer cell invasiveness through ROS-dependent, NF-κB- and HIF-1α-mediated downregulation of PTX3.” J Cell Physiol. 2019 Jul;234(7):10680-10697. doi: 10.1002/jcp.27731. Epub 2019 Jan 9.
[89] L, Shen D, Li X, Shan X, Wang X, Yan Q, Liu J (2016) – “Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.” Oncotarget. 2016 Jan 12;7(2):1619-32. doi: 10.18632/oncotarget.6451.
[90] Kim YJ, Choi WI, Jeon BN, Choi KC, Kim K, Kim TJ, Ham J, Jang HJ, Kang KS, Ko H (2014) – “Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance.” Toxicology. 2014 Aug 1;322:23-33. doi: 10.1016/j.tox.2014.04.002. Epub 2014 May 2.
[91] Tan Q, Lin S, Zeng Y, Yao M, Liu K, Yuan H, Liu C, Jiang G (2020) – “Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells.” Environ Toxicol. 2020 Jan 9. doi: 10.1002/tox.22899.
[92] Wang XJ, Zhou RJ, Zhang N, Jing Z (2019) – “20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy.” Eur J Pharmacol. 2019 May 5;850:141-149. doi: 10.1016/j.ejphar.2019.02.023. Epub 2019 Feb 14.
[93] Dai Y, Wang W, Sun Q, Tuohayi J (2019) – “Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines.” Exp Ther Med. 2019 Jan;17(1):953-959. doi: 10.3892/etm.2018.7001. Epub 2018 Nov 21.
[94] Wang J, Tian L, Khan MN, Zhang L, Chen Q, Zhao Y, Yan Q, Fu L, Liu J (2018) – “Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness.” Cancer Lett. 2018 Feb 28;415:73-85. doi: 10.1016/j.canlet.2017.11.037. Epub 2017 Dec 2.
[95] Jiang Z, Yang Y, Yang Y, Zhang Y, Yue Z, Pan Z, Ren X (2017) – “Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune.” Biomed Pharmacother. 2017 Dec;96:378-383. doi: 10.1016/j.biopha.2017.09.129. Epub 2017 Oct 12.
[96] Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL, Song HB, Yi C (2009) – “Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice.” BMC Cancer. 2009 Jul 23;9:250. doi: 10.1186/1471-2407-9-250.
[97] Zhang Q, Kang X, Zhao W (2006) – “Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma.” Biochem Biophys Res Commun. 2006 Apr 14;342(3):824-8. Epub 2006 Feb 20.
[98] Wang L, Li X, Song YM, Wang B, Zhang FR, Yang R, Wang HQ, Zhang GJ (2015) – “Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway.” Mol Med Rep. 2015 Jul;12(1):609-14. doi: 10.3892/mmr.2015.3397. Epub 2015 Feb 27.
[99] Meng L, Ji R, Dong X, Xu X, Xin Y, Jiang X (2019) – “Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways.” Int J Oncol. 2019 Jun;54(6):2069-2079. doi: 10.3892/ijo.2019.4787. Epub 2019 Apr 16.
[100] Shan X, Tian LL, Zhang YM, Wang XQ, Yan Q, Liu JW (2015) – “Ginsenoside Rg3 suppresses FUT4 expression through inhibiting NF-κB/p65 signaling pathway to promote melanoma cell death.” Int J Oncol. 2015 Aug;47(2):701-9. doi: 10.3892/ijo.2015.3057. Epub 2015 Jun 18.
[101] Shan X, Aziz F, Tian LL, Wang XQ, Yan Q, Liu JW (2015) – “Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.” Int J Oncol. 2015 Apr;46(4):1667-76. doi: 10.3892/ijo.2015.2886. Epub 2015 Feb 10.
[102] Shan X, Fu YS, Aziz F, Wang XQ, Yan Q, Liu JW (2014) – “Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation.” PLoS One. 2014 Dec 18;9(12):e115401. doi: 10.1371/journal.pone.0115401. eCollection 2014.
[103] Chen J, Peng H, Ou-Yang X, He X (2008) – “Research on the antitumor effect of ginsenoside Rg3 in B16 melanoma cells.” Melanoma Res. 2008 Oct;18(5):322-9. doi: 10.1097/CMR.0b013e32830b3536.
[104] Zhao L, Shou H, Chen L, Gao W, Fang C, Zhang P (2019) – “Effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells.” Oncol Rep. 2019 Jun;41(6):3209-3218. doi: 10.3892/or.2019.7115. Epub 2019 Apr 12.
[105] Zheng X, Zhou Y, Chen W, Chen L, Lu J, He F, Li X, Zhao L (2018) – “Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells.” Cell Physiol Biochem. 2018;51(3):1340-1353. doi: 10.1159/000495552. Epub 2018 Nov 27.
[106] Li J, Liu T, Zhao L, Chen W, Hou H, Ye Z, Li X (2015) – “Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells.” Int J Oncol. 2015 Feb;46(2):775-81. doi: 10.3892/ijo.2014.2767. Epub 2014 Nov 18.
[107] Wang JH, Nao JF, Zhang M, He P (2014) – “20(s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways.” Tumour Biol. 2014 Dec;35(12):11985-94. doi: 10.1007/s13277-014-2497-5. Epub 2014 Aug 29.
[108] Zhou Y, Zheng X, Lu J, Chen W, Li X, Zhao L (2018) – “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(6):2548-2559. doi: 10.1159/000488273. Epub 2018 Mar 16.
[109] Hou J, Kim S, Sung C, Choi C (2017) – “Ginsenoside Rg3 Prevents Oxidative Stress-Induced Astrocytic Senescence and Ameliorates Senescence Paracrine Effects on Glioblastoma.” Molecules. 2017 Sep 10;22(9). pii: E1516. doi: 10.3390/molecules22091516.
[110] Sun C, Yu Y, Wang L, Wu B, Xia L, Feng F, Ling Z, Wang S (2016) – “Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitro.” J Exp Clin Cancer Res. 2016 Feb 13;35:32. doi: 10.1186/s13046-015-0274-y.
[111] Choi YJ, Lee HJ, Kang DW, Han IH, Choi BK, Cho WH (2013) – “Ginsenoside Rg3 induces apoptosis in the U87MG human glioblastoma cell line through the MEK signaling pathway and reactive oxygen species.” Oncol Rep. 2013 Sep;30(3):1362-70. doi: 10.3892/or.2013.2555. Epub 2013 Jun 20.
[112] Sin S, Kim SY, Kim SS (2012) – “Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells.” Int J Oncol. 2012 Nov;41(5):1669-74. doi: 10.3892/ijo.2012.1604. Epub 2012 Aug 23.