Skip to main content

Advertisement

Log in

Efficacy of ginsenoside Rg3 nanoparticles against Ehrlich solid tumor growth in mice

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Solid tumors are fairly common and face many clinical difficulties since they are hardly surgically resectable and broadly do not respond to radiation and chemotherapy. The current study aimed to fabricate ginsenoside Rg3 nanoparticles (Rg3-NPs) and evaluate their antitumor effect against Ehrlich solid tumors (EST) in mice. Rg3-NPs were fabricated using whey protein isolates (WPI), maltodextrin (MD), and gum Arabic (GA). EST was developed by the injection of mice with Ehrlich ascites cells (2.5 × 106). The mice were divided into a control group, EST group, and the EST groups that were treated orally 2 weeks for with normal Rg3 (3 mg/kg b.w.), Rg3-NPs at a low dose (3 mg/kg b.w.), and Rg3-NPs at a high dose (6 mg/kg b.w.). Serum and solid tumors were collected for different assays. The results revealed that synthesized Rg3-NPs showed a spherical shape with an average particle size of 20 nm and zeta potential of -5.58 mV. The in vivo study revealed that EST mice showed a significant increase in AFP, Casp3, TNF-α, MMP-9, VEGF, MDA, and DNA damage accompanied by a significant decrease in SOD and GPx. Treatment with Rg3 or Rg3-NPs decreased the tumor weight and size and induced a significant improvement in all the biochemical parameters. Rg3-NPs were more effective than Rg3, and the improvement was dose-dependent. It could be concluded that fabrication of Rg3-NPs enhanced the protective effect against EST development which may be due to the synergistic effect of Rg3 and MD, GA, and WPI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig.1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The codes used during the current study are available from the corresponding author on reasonable request.

References

  • Abd Eldaim MA, Tousson E, El Sayed IE, Awd MA (2019) Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon-induced reproductive toxicity in male rats. Environ Toxicol 34(2):150–159

    Article  CAS  Google Scholar 

  • Abdel-Aziem SH, Hassan AM, Abdel-Wahhab MA (2011) Dietary supplementation with whey protein and ginseng extract counteracts the oxidative stress and DNA damage in rats fed aflatoxin-contaminated diet. Mutat Res 723:65–71

    Article  CAS  Google Scholar 

  • Abdel-Wahhab MA, El-Nekeety AA, Hassan NS, Gibriel AA, Abdel-Wahhab KG (2018) Encapsulation of cinnamon essential oil in whey protein enhances the protective effect against single or combined sub-chronic toxicity of fumonisin B1 and/or aflatoxin B1 in rats. Environ Sci Pollu Res 25(29):29144–29161

    Article  CAS  Google Scholar 

  • Abdel-Wahhab MA, Hassan NS, El-Kady AA, Khadrawy YA, El-Nekeety AA, Mohamed SR, Sharaf HA, Mannaa FA (2010) Red ginseng protects against aflatoxin B1 and fumonisin-induced hepatic pre-cancerous lesions in rats. Food Chem Toxicol 48(2):733–742

    Article  CAS  Google Scholar 

  • Abdel-Wahhab MA, Ibrahim AA, El-Nekeety AA, Hassan NS, Mohamed AA (2012) Panax ginseng C.A. Meyer extract counteracts the oxidative stress in rats fed multi-mycotoxins-contaminated diet. Com Sci 3(3):143–153

    Google Scholar 

  • Ahmed AA, Fedail JS, Musa HH, Kamboh AA, Sifaldin AZ, Musa TH (2015) Gum Arabic extracts protect against hepatic oxidative stress in alloxan-induced diabetes in rats. Pathophysiol 22:189–194

    Article  CAS  Google Scholar 

  • Ahmed M, Ehab T, Ahmed NS, Elwan MM, Haneen HM (2019) Antineoplastic activities of grape seed proanthocyanidin extract against Ehrlich solid tumor-bearing mice induced alterations in AFP, CEA, TNF-α and DNA Damage. Asian Oncol Res J 2(1):1–12

    Google Scholar 

  • Aldubayan MA, Elgharabawy RM, Ahmed AS, Tousson E (2019) Antineoplastic activity and curative role of avenanthramides against the growth of Ehrlich solid tumors in mice. Oxid Medi Cell Longev 12:5162687

    Google Scholar 

  • Ali BH, Beegam I, Al-Lawati M, Waly MI, Al Za’abi MA, Nemmar A, (2013) Comparative efficacy of three brands of gum acacia on adenine-induced chronic renal failure in rats. Physiol Res 62(62):47–56

    Article  CAS  Google Scholar 

  • Ali NE, Kaddam LA, Alkarib SY, Kaballo BG, Khalid SA, Higawee A, Abd Elhabib A, Alaa Aldeen A, Phillips AO, Saeed AM (2020) Gum Arabic (Acacia Senegal) augmented total antioxidant capacity and reduced C-reactive protein among haemodialysis patients in phase II trial. Int J Nephrol 2020:7214673. https://doi.org/10.1155/2020/7214673

    Article  CAS  Google Scholar 

  • Bachmann J, Friess H, Martignoni ME (2008) Molecular mechanisms and its clinical impact in cancer cachexia. Z Gastroenterol 46(12):1384–1392

    Article  CAS  Google Scholar 

  • Basuony M, Hafez E, Tousson E, Massoud A, Elsomkhraty S, Eldakamawy S (2015) Beneficial role of Panax ginseng root aqueous extract against cisplatin-induced blood toxicity in rats. Am J Biol Chem 3(1):1–7

    Google Scholar 

  • Bayrama T, Pekmez M, Arda N, Yalcın AS (2009) Antioxidant activity of whey protein fractions isolated by gel exclusion chromatography and protease treatment. Talanta 75:705–709

    Article  CAS  Google Scholar 

  • Benedict B, van Harn T, Dekker M, Hermsen SA, Kucukosmanoglu A, Pieters W, Delzenne-Goette E, Dorsman JC, Petermann E, Foijer F, TeRiele H (2018) Loss of p53 suppresses replication-stress-induced DNA breakage in G1/S checkpoint deficient cells. Elife 7:e37868. https://doi.org/10.7554/eLife.37868

    Article  Google Scholar 

  • Blasiak J, Sikora A, Czechowska A, Drzewoski J (2003) Free radical scavengers can modulate the DNA-damaging action of alloxan. Acta Biochim Pol 50(1):205–210

    Article  CAS  Google Scholar 

  • Bray F, Laversanne M, Weiderpass E, Soerjomataram I (2021) The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 127(16):3029–3030

    Article  Google Scholar 

  • Chen H, Yang H, Fan D, Deng J (2020) The anticancer activity and mechanisms of ginsenosides: an updated review. Food 1(3):226–241

    Google Scholar 

  • Chen W, Balan P, Popovich DG (2019a) Review of ginseng anti-diabetic studies. Molecules 24(24):4501. https://doi.org/10.3390/molecules24244501

    Article  CAS  Google Scholar 

  • Chen XJ, Zhang XJ, Shui YM, Wan JB, Gao JL (2016) Anticancer activities of protopanaxadiol- and protopanaxatriol-type ginsenosides and their metabolites. Evid Based Complement Alternat Med 2016:5738694. https://doi.org/10.1155/2016/5738694

    Article  Google Scholar 

  • Chen Z, Wei X, Shen L, Zhu H, Zheng X (2019b) 20(S)-ginsenoside-Rg3 reverses temozolomide resistance and restrains epithelial-mesenchymal transition progression in glioblastoma. Cancer Sci 110(1):389–400

    Article  CAS  Google Scholar 

  • Cheng LY, Sun XM, Hu CM, Jin R, Sun BS, Shi YM, Zhang L, Cui WG, Zhang YG (2013) In vivo inhibition of hypertrophic scars by implantable ginsenosideRg3-loaded electrospun fibrous membranes. Acta Biomater 9(12):9461–9473

    Article  CAS  Google Scholar 

  • Cheng LY, Sun XM, Zhao X, Wang L, Yu J, Pan GQ, Li B, Yang HL, Zhang YG, Cui WG (2016) Surface biofunctional drug-loaded electrospun fibrous scaffolds for comprehensive repairing hypertrophic scars. Biomaterials 83:169–181

    Article  CAS  Google Scholar 

  • Choi WT, Kakar S (2017) Immunohistochemistry in the diagnosis of hepatocellular carcinoma. Gastroenterol Clin 46(2):311–325

    Article  Google Scholar 

  • Comoli P, Chabannon C, Koehl U, Lanza F, Urbano-Ispizua A, Hudecek M, Ruggeri A, Secondino S, Bonini C, Pedrazzoli P (2019) Development of adaptive immune effector therapies in solid tumors. Ann Oncol 30(11):1740–1750

    Article  CAS  Google Scholar 

  • Cruz FD, Matushansky I (2012) Solid tumor differentiation therapy-is it possible? Oncotarget 3(5):559–567

    Article  Google Scholar 

  • Dai L, Zhu W, Si C, Lei J (2018) Nano-ginseng for enhanced cytotoxicity against cancer cells. Int J Mol Sci 19(2):627. https://doi.org/10.3390/ijms19020627

    Article  CAS  Google Scholar 

  • Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, Brun A, Mehta K (2002) Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene 21(57):8843–8851

    Article  CAS  Google Scholar 

  • Dogan D, Can C, Kocyigit A, Dikilitas M, Taskin A, Bilinc H (2011) Dimethoate induced oxidative stress and DNA damage in Oncorhynchus mykiss. Chemosphere 84(1):39–46

    Article  CAS  Google Scholar 

  • Dugan LL, Quick KL (2005) Reactive oxygen species and aging: evolving questions. Sci Aging Knowl Environ 2005(26):pe20

    Article  Google Scholar 

  • Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, Nedaeinia R, Haghjooy Javanmard S, Taherian M, Ahmadlou M, Salehi R, Sadeghi B, Manian M (2021) The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int 21(1):62. https://doi.org/10.1186/s12935-020-01719-5

    Article  CAS  Google Scholar 

  • Eratte D, Wang B, Dowling K, Barrow CJ, Adhikari BP (2014) Complex coacervation with whey protein isolate and gum Arabic for the microencapsulation of omega-3 rich tuna oil. Food Funct 5:2743–2750

    Article  CAS  Google Scholar 

  • Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 147(4):742–758

    Article  CAS  Google Scholar 

  • Gad AS, Khadrawy YA, El-Nekeety AA, Mohamed SR, Hassan NS, Abdel-Wahhab MA (2011) Antioxidant activity and hepatoprotective effects of whey protein and spirulina in rats. Nutr 27(5):582–589

    Article  CAS  Google Scholar 

  • Ganesan P, Ko HM, Kim IS, Choi DK (2015) Recent trends of nano bioactive compounds from ginseng for its possible preventive role in chronic disease models. RSC Adv 5(119):98634–98642

    Article  CAS  Google Scholar 

  • Gavhane YN, Shete AS, Bhagat AK, Shinde VR, Bhong KK, Khairnar GA, Yadav AV (2011) Solid tumors: facts, challenges and solutions. Int J Pharm Sci Res 2(1):1–12

    Google Scholar 

  • Giono LS, Manfredi JS (2006) The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol 209:13–20

    Article  CAS  Google Scholar 

  • Gopi J, Gopinath M, Banerjee A, Rupert S, Vennila R, Pathak S (2021) Nanomedicines for solid tumors: current status, challenges, and future prospects. In Nanomedicine for Cancer Diagnosis and Therapy (pp. 81–96). Springer, Singapore

  • Gu JW, Makey KL, Tucker KB, Chinchar E, Mao X, Pei I, Thomas EY, La M (2013) EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression. Vascular Cell 5(1):1–10

    Article  CAS  Google Scholar 

  • Gueta I, Altman A, Shoenfeld Y (2010) The effect of blocking TNF-alpha in patients with cancer-related cachexia and anorexia. Harefuah 149(8):512–514

    Google Scholar 

  • Hafez E, Masoud A, Barnous M, Tousson E (2015) Apoptotic marker alternations in the spleen of experimentally hyperthyroid and hypothyroid rat. J Biosci Appl Res 1(5):234–242

    Article  Google Scholar 

  • Haris CC (1996) Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J Nat Can Inst 88(20):1442–1455

    Article  Google Scholar 

  • Hassan AM, Abdel-Azeim SH, El-Nekeety AA, Abdel-Wahhab MA (2015) Panax ginseng extract modulates oxidative stress, DNA fragmentation and up-regulate gene expression in rats sub chronically treated with aflatoxin B1 and fumonisin B1. Cytotechnology 67:861–871

    Article  CAS  Google Scholar 

  • Hassan ME, Hassan RR, Diab KA, El-Nekeety AA, Hassan NS, Abdel-Wahhab MA (2021) Nanoencapsulation of thyme essential oil: a new avenue to enhance its protective role against oxidative stress and cytotoxicity of zinc oxide nanoparticles in rats. Environ Sci Pollut Res Int 28:52046–52063

    Article  CAS  Google Scholar 

  • Hong C, Wang D, Liang J, Guo Y, Zhu Y, Xia J, Qin J, Zhan H, Wang J (2019) Novel ginsenoside-based multifunctional liposomal delivery system for combination therapy of gastric cancer. Theranostics 9(15):4437–4449

    Article  CAS  Google Scholar 

  • Huang CY, Ju DT, Chang CF, Muralidhar Reddy P, Velmurugan BK (2017) A review on the effects of current chemotherapy drugs and natural agents in treating non-small cell lung cancer. Biomedicine 7(4):23. https://doi.org/10.1051/bmdcn/2017070423

    Article  Google Scholar 

  • Huang H (2018) Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: recent advances. Sensors 18(10):3249

    Article  CAS  Google Scholar 

  • Huang Q, Zhang H, Bai LP, Law BYK, Xiong H, Zhou X, Xiao R, Qu YQ, Mok SWF, Liu L, Wong VKW (2020) Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism. Cell Death Dis 11(8):621. https://doi.org/10.1038/s41419-020-02881-4

    Article  CAS  Google Scholar 

  • Hwang E, Park SY, Yin CS, Kim HT, Kim YM, Yi TH (2017) Antiaging effects of the mixture of Panax ginseng and Crataegus pinnatifida in human dermal fibroblasts and healthy human skin. J Ginseng Res 41(1):69–77

    Article  Google Scholar 

  • Jan R, Chaudhry GE (2019) Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Adv Pharm Bull 9(2):205–218

    Article  CAS  Google Scholar 

  • Jinapong N, Suphantharika M, Jamnong P (2008) Production of instant soymilk powders by ultrafiltration, spray drying and fluidized bed agglomeration. J Food Eng 84(2):194–205

    Article  Google Scholar 

  • Kamal E, Kaddam LA, Dahawi M, Osman M, Salih MA, Alagib A, Saeed A (2018) Gum arabic fibers decreased inflammatory markers and disease severity score among rheumatoid arthritis patients, phase II Trial. Int J Rheumatol. https://doi.org/10.1155/2018/4197537.

  • Kang SH, Kwon JY, Lee JK, Seo YR (2013) Recent advances in in vivo genotoxicity testing: prediction of carcinogenic potential using comet and micronucleus assay in animal models. J Cancer Prev 18:277–288

    Article  Google Scholar 

  • Kelly K, Ras A, Helm S (2016) A comprehensive evaluation of solid tumor analysis in the clinical space. J. Next Generat. Sequnce. Applic 3. https://doi.org/10.4172/2469-9853.1000129

  • Kennedy L, Sandhu JK, Harper ME, Cuperlovic-Culf M (2020) Role of glutathione in cancer: from mechanisms to therapies. Biomolecules 10(10):1429. https://doi.org/10.3390/biom10101429

    Article  CAS  Google Scholar 

  • Khafaga AF, Shamma RN, Abdeen A, Barakat AM, Noreldin AE, Elzoghby AO, Sallam MA (2021) Celecoxib repurposing in cancer therapy: molecular mechanisms and nanomedicine-based delivery technologies. Nanomed (lond) 16(19):1691–1712. https://doi.org/10.2217/nnm-2021-0086

    Article  CAS  Google Scholar 

  • Khalid A, Khan R, Ul-Islam M, Khan T, Wahid F (2017) Bacterial cellulose-zinc oxide nanocomposites as a novel dressing system for burn wounds. Carbohydr Polym 164:214–221

    Article  CAS  Google Scholar 

  • Khalil WKB, Hassan AM, Ahmed KA, Park MH, Kim Y, Park HH, Abdel-Wahhab MA (2008) Inhibitory effects of Panax ginseng extract standardized with ginsenoside Rg3 against EDTA-induced toxicity in male rats. Arch Toxicol 82(3):183–195

    Article  CAS  Google Scholar 

  • Kim JH, Yi YS, Kim MY, Cho JY (2017) Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 41(4):435–443

    Article  Google Scholar 

  • Kim YJ, Zhang D, Yang DC (2015) Biosynthesis and biotechnological production of ginsenosides. Biotechnol Adv 33(6 Pt 1):717–735

    Article  CAS  Google Scholar 

  • Kong H, Yang J, Zhang Y, Fang Y, Nishinari K, Phillips GO (2014) Synthesis and antioxidant properties of gum Arabic-stabilized selenium nanoparticles. Int J Biol Macromol 65:155–162

    Article  CAS  Google Scholar 

  • Kumaravel TS, Jha AN (2006) Reliable comet assay measurements for detecting DNA damage induced by ionizing radiation and chemicals. Mutat Res 605:7–16

    Article  CAS  Google Scholar 

  • Li H, Ding F, Xiao L, Shi R, Wang H, Han W, Huang Z (2017) Food-derived antioxidant polysaccharides and their pharmacological potential in neuro-degenerative diseases. Nutrients 9:778. https://doi.org/10.3390/md17120674

    Article  CAS  Google Scholar 

  • 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 46:775–781

    Article  CAS  Google Scholar 

  • Li X, Yao F, Fan H, Li K, Sun L, Liu Y (2018) Intraconversion of polar ginsenosides, their transformation into less-polar ginsenosides, and ginsenoside acetylation in ginseng flowers upon baking and steaming. Molecules 23(4):759. https://doi.org/10.3390/molecules23040759

    Article  CAS  Google Scholar 

  • Li Y, Yang T, Li J, Hao HL, Wang SY, Yang J, Luo JM (2016) Inhibition of multiple myeloma cell proliferation by ginsenoside Rg3 via reduction in the secretion of IGF-1. Mol Med Rep 14:2222–2230

    Article  CAS  Google Scholar 

  • Liang Y, Zhang T, Jing S, Zuo P, Li T, Wang Y, Xing S, Zhang J, Wei Z (2021) 20(S)-ginsenoside Rg3 inhibits lung cancer cell proliferation by targeting EGFR-mediated Ras/Raf/MEK/ERK pathway. Am J Chinese Med 49(03):753–765

    Article  CAS  Google Scholar 

  • Liu C, Gong Q, Chen TJ, Feng Z, Liu P, Deng Z (2018) Treatment with 20(S)-ginsenoside Rg3 reverses multidrug resistance in A549/DDP xenograft tumors. Oncol Lett 4:4376–4382

    Google Scholar 

  • Liu H, Pan H, Yang H, Wang J, Zhang K, Li X, Zheng Z (2015) LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression. J Orthop Res 33(3):294–303

    Article  CAS  Google Scholar 

  • 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. 120. https://doi.org/10.1016/j.biopha.2019.109483

  • Mannaa FA, Abdel-Wahhab MA, Ahmed HH, Park MH (2006) Protective role of Panax ginseng extract standardized with ginsenoside Rg3 against acrylamide-induced neurotoxicity in rats. J Appl Toxicol 26(3):198–206

    Article  CAS  Google Scholar 

  • Mansour S, Anis L (2010) Possible effect of 5, 6-dimethyl-4 isothiocyanate thieno [2, 3-d] pyrimidine and I or irradiation on Ehrlich carcinoma in mice. J Rad Res Appl Sci 3:599–618

    Google Scholar 

  • Mathiyalagan R, Kim YJ, Wang C, Jin Y, Subramaniyam S, Singh P, Wang D, Yang DC (2016) Protopanaxadiol aglycone ginsenoside-polyethylene glycol conjugates: synthesis, physicochemical characterizations, and in vitro studies. Artif Cells Nanomed Biotechnol 44(8):1803–1809

    Article  CAS  Google Scholar 

  • Medhat D, Hussein J, El-Naggar ME, Attia MF, Anwar M, Latif YA, Booles HF, Morsy S, Farrag AR, Khalil WKB, El-Khayat Z (2017) Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations. Biomed Pharmacother 91:1006–1016

    Article  CAS  Google Scholar 

  • Metawea ORM, Abdelmoneem MA, Haiba NS, Khalil HH, Teleb M, Elzoghby AO, Khafaga AF, Noreldin AE, Albericio F, Khattab SN (2021) A novel ‘smart’ PNIPAM-based copolymer for breast cancer targeted therapy: synthesis, and characterization of dual pH/temperature-responsive lactoferrin-targeted PNIPAM-co-AA. Colloids Surf B Biointerfaces 202:111694. https://doi.org/10.1016/j.colsurfb.2021.111694

    Article  CAS  Google Scholar 

  • Mirghani MES, Elnour AAM, Kabbashi NA, Alam MZ, Musa KH, Abdullah A (2018) Determination of antioxidant activity of gum Arabic: an exudation from two different locations. Sci Asia 44:179–186

    Article  CAS  Google Scholar 

  • Mohammed KAA, Ahmed HMS, Sharaf HA, El-Nekeety AA, Abdel-Aziem SH, Mehaya FM, Abdel-Wahhab MA (2020) Encapsulation of cinnamon oil in whey protein counteracts the disturbances in gene expression and diabetic complications in rats. Environ Sci Pollut Res 27:2829–2843

    Article  CAS  Google Scholar 

  • Mohanan P, Subramaniyam S, Mathiyalagan R, Yang DC (2017) The molecular signaling of ginsenosides Rb1, Rg1, Rg3 and their mode of actions. J Ginseng Res. https://doi.org/10.1016/j.jgr.2017.01.008

    Article  Google Scholar 

  • 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) 6(1):17. https://doi.org/10.3390/medicines6010017

    Article  CAS  Google Scholar 

  • Nakhjavani M, Smith E, Townsend AR, Price TJ, Hardingham JE (2020) Anti-angiogenic properties of ginsenoside Rg3. Molecules 25(21):4905. https://doi.org/10.3390/molecules25214905

    Article  CAS  Google Scholar 

  • Nourazarian AR, Kangari P, Salmaninejad A (2014) Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev 15(12):4745–4751

    Article  Google Scholar 

  • 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 31:397–405

    Article  CAS  Google Scholar 

  • Peng Y, Zhang R, Yang X, Zhang Z, Kang N, Bao L, Shen Y, Yan H, Zheng F (2019) Ginsenoside Rg3 suppresses the proliferation of prostate cancer cell line PC3 through ROS-induced cell cycle arrest. Oncol Lett 17(1):1139–1145

  • Perry MJ (2008) The chemotherapy source book. Wolters Kluwer Health/Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  • Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616

    Article  CAS  Google Scholar 

  • Rodzik A, Pomastowski P, Sagandykova GN, Buszewski B (2020) Interactions of whey proteins with metal ions. Int J Mol Sci 21(6):2156. https://doi.org/10.3390/ijms21062156

    Article  CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191

    Article  CAS  Google Scholar 

  • Song JH, Eum DY, Park SY, Jin YH, Shim JW, Park SJ, Kim MY, Park SJ, Heo K, Choi YJ (2020) Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells. PLoS ONE 15(10):e0240533. https://doi.org/10.1371/journal.pone.0240533

    Article  CAS  Google Scholar 

  • Sun HY, Lee JH, Han YS, Yoon YM, Yun CW, Kim JH, Song YS, Lee SH (2016) Pivotal roles of ginsenoside Rg3 in tumor apoptosis through regulation of reactive oxygen species. Anticancer Res 36:4647–4654

    Article  CAS  Google Scholar 

  • Sun M, Ye Y, Xiao L, Duan X, Zhang Y, Zhang H (2017) Anticancer effects of ginsenoside Rg3. Int J Mol Med 39(3):507–518

    Article  CAS  Google Scholar 

  • Sun X, Cheng L, Zhu W, Hu C, Jin R, Sun B, Shi Y, Zhang Y, Cui W (2014) Use of ginsenoside rg3-loaded electrospun PLGA fibrous membranes as wound cover induces healing and inhibits hypertrophic scar formation of the skin. Colloid Surf B-Biointerfaces 115:61–70

    Article  CAS  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249

    Article  Google Scholar 

  • Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M (2003) Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 31(8):1065–1071

    Article  Google Scholar 

  • 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 15:2029–2038

    Article  CAS  Google Scholar 

  • Tiwari V, Wilson DM (2019) DNA damage and associated DNA repair defects in disease and premature aging. Am J Hum Genet 105(2):237–257

    Article  CAS  Google Scholar 

  • Tousson E, Alm-Eldeen A, El-Moghazy M (2011) p53 and Bcl-2expression in response to boldenone induced liver cells injury. Toxicol Ind Health 27(8):711–718. https://doi.org/10.1177/0748233710395350

    Article  CAS  Google Scholar 

  • Ushida K, Hatanaka H, Inoue R, Tsukahara T, Phillips GO (2011) Effect of long-term ingestion of gum Arabic on the adipose tissues of female mice. Food Hydrocoll 25(5):1344–1349

    Article  CAS  Google Scholar 

  • Wang JQ, Hu SZ, Nie SP, Yu Q, Xie MY (2016) Reviews on mechanisms of in vitro antioxidant activity of polysaccharides. Oxid Med Cell Longev 2016:5692852. https://doi.org/10.1155/2016/5692852

    Article  CAS  Google Scholar 

  • 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 12:609–614

    Article  CAS  Google Scholar 

  • Warren MA, Shoemaker SF, Shealy DJ, Bshara W, Ip MM (2009) Tumor necrosis factor deficiency inhibits mammary tumor genesis and a tumor necrosis factor neutralizing antibody decreases mammary tumor growth in neu/erbB2 transgenic mice. Mol Cancer Ther 8(9):2655–2663

    Article  CAS  Google Scholar 

  • WHO (2020) World Health Organization .Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and by Region, 2000–2019. WHO; 2020. Accessed December 11, 2020. who.int/data/gho/data/themes/mortality-andglobal-health-estimates/ghe-leadingcauses-of-death

  • Wong AS, Che CM, Leung KW (2015) Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview. Nat Prod Rep 32(2):256–272

    Article  CAS  Google Scholar 

  • Yahia D, Ali MF, Abd El-Maguid DS (2019) Estimation of bone marrow DNA damage induced by Lambda cyhalothrin and dimethoate insecticides using alkaline comet assay. J Adv Vet Res 9(1):23–28

    Google Scholar 

  • Yin SY, Wei WC, Jian FY, Yang NS (2013) Therapeutic applications of herbal medicines for cancer patients. Evid. Based Complement. Alternat. Med. 302426. https://doi.org/10.1155/2013/302426

  • Zhang YH, Li HD, Li B, Jiang SD, Jiang LS (2014) Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells. Oncol Rep 31:919–925

    Article  CAS  Google Scholar 

  • Zhao J, Duan Z, Ma X, Liu Y, Fan D (2020) Recent advances in systemic and local delivery of ginsenosides using nanoparticles and nanofibers. Chinese J. Chem. Eng. 30. https://doi.org/10.1016/j.cjche.2020.11.012

  • Zheng X, Chen W, Hou H, Li J, Li H, Sun X, Zhao L, Li X (2017) Ginsenoside 20 (S)-Rg3 induced autophagy to inhibit migration and invasion of ovarian cancer. Biomed Pharmacother 85:620–626

    Article  CAS  Google Scholar 

  • Zhong Q, Wei B, Wang S, Ke S, Chen J, Zhang H, Wang H (2019) The antioxidant activity of polysaccharides derived from marine organisms: an overview. Mar Drugs 17(12):674. https://doi.org/10.3390/md17120674

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Research Centre, Dokki, Cairo, Egypt (the Department of Medical Biochemistry and Food Toxicology & Contaminants, project # 12050305) and the Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.

Author information

Authors and Affiliations

Authors

Contributions

This work was carried out in collaboration between all authors. Authors MA El-Banna, OM Hendawy, and AA El-Nekeety carried out the experimental work, managed the literature searches, and shared in writing the first draft of the manuscript. Authors MA Abdel-Wahhab and MA El-Banna wrote the protocol, managed the project, managed the analyses of the study, performed the statistical analysis, and wrote the final draft of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mosaad A. Abdel-Wahhab.

Ethics declarations

Ethics approval

The protocol of the current study was approved by the ethics Animal Care and Use Committee of the National Research Center, Dokki, Cairo, Egypt (approval # 12050305/2019).

Consent for publication

Not applicable.

Consent to participate

Not applicable.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible Editor: Lotfi Aleya

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Banna, M.A., Hendawy, O.M., El-Nekeety, A.A. et al. Efficacy of ginsenoside Rg3 nanoparticles against Ehrlich solid tumor growth in mice. Environ Sci Pollut Res 29, 43814–43825 (2022). https://doi.org/10.1007/s11356-022-19019-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-022-19019-y

Keywords

Navigation