For citation: Qin Y, Wang K, Zhang Z-M, Wu T, Zhang L, Liu J. Ginsenoside Rg3 Induces Apoptosis While Attenuates Collagen Metabolism in Human Vocal Cord Scar Fibroblasts In Vitro. International Journal of Biomedicine. 2026;16(3):372-377. doi:10.21103/Article16(3)_OA7
Originally published September 5, 2026
Background: This study aimed to investigate the effects of ginsenoside Rg3 on apoptosis and collagen metabolism in human vocal cord scar fibroblasts (HVCSFs) and the molecular mechanisms involved.
Methods and Results: HVCSFs were cultured in vitro and treated with different concentrations of ginsenoside Rg3. Cell proliferation inhibition rate was detected by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry and Calcein/PI live/dead cell staining. Cell invasion ability was detected by Transwell assay. Expression levels of apoptosis-related protein caspase-3 and Collagen Type I, Collagen Type Ⅲ (Col Ⅰ, Col Ⅲ) were detected by Western blot and Quantitative real-time polymerase chain reaction (qPCR).
HVCSFs were cultured in vitro and exposed to increasing concentrations of ginsenoside Rg3. Rg3 treatment dose-dependently inhibited HVCSFs proliferation, as shown by the CCK-8 assay (P<0.0001). Flow cytometry and Calcein/PI live/dead staining consistently revealed a significant induction of apoptosis upon Rg3 exposure (P<0.0001). Cell invasion was also effectively suppressed, as assessed by the Transwell assay (P<0.001, P<0.0001). At the protein level, Western blot analysis demonstrated that Rg3 upregulated caspase 3 expression (P<0.01, P<0.001) while downregulating both Col I and Col III (P<0.05, P<0.01). Correspondingly, qPCR results showed elevated mRNA levels of caspase 3 (P<0.05, P<0.01, P<0.0001) and reduced mRNA levels of Col I and Col III (P<0.05, P<0.0001) in response to Rg3 treatment.
Conclusions. Ginsenoside Rg3 may promote the apoptosis of HVCSFs through activating the caspase-3-dependent apoptotic pathway and inhibiting the expression of Col Ⅰ and Col Ⅲ, thereby improving vocal cord scar fibrosis. This study provides experimental evidence for ginsenoside Rg3 as a potential anti-vocal cord scar drug.
- Yang Y, Xu X, Zhuang P. Explore the Pattern of Biomechanical Alterations in Vocal Fold Scar and Its Objective Quantitative Assessment Method. J Voice. 2024 Jul 24:S0892-1997(24)00212-1. doi: 10.1016/j.jvoice.2024.07.003. Epub ahead of print. PMID: 39054187.
- Miura R, Matsuzaki H, Suzuki H, Makiyama K, Oshima T. Effect of a Single Injection of Basic Fibroblast Growth Factor into the Vocal Folds: A 36-Month Clinical Study. J Voice. 2023 May;37(3):444-451. doi: 10.1016/j.jvoice.2021.01.015. Epub 2021 Feb 9. PMID: 33573843.
- Vontela S, Balouch B, Bress E, Brennan MJ, Alnouri G, Martha VV, Sataloff RT. Vocal Fold Paresis and Voice Outcomes following Vocal Fold Mass Excision. J Voice. 2024 Jan;38(1):225-230. doi: 10.1016/j.jvoice.2021.07.014. Epub 2021 Aug 30. PMID: 34474936.
- Kang HT, Park KN, Lee SW. Regenerative Effect of a 532-nm Diode Laser on Vocal Fold Scar in a Rabbit Model. J Voice. 2026 Jan;40(1):160-166. doi: 10.1016/j.jvoice.2023.09.004. Epub 2023 Oct 29. PMID: 37903688.
- Svistushkin MV, Kotova S, Shpichka A, Starostina S, Shekhter A, Bikmulina P, Nikiforova A, Zolotova A, Royuk V, Kochetkov PA, Timashev S, Fomin V, Vosough M, Svistushkin V, Timashev P. Stem cell therapy for vocal fold regeneration after scarring: a review of experimental approaches. Stem Cell Res Ther. 2022 May 3;13(1):176. doi: 10.1186/s13287-022-02853-9. PMID: 35505357; PMCID: PMC9066721.
- John M, Nabizath A, Krishnakumar S, Menon U, Menon D, Nair M. Injectable Tissue Adhesive Microgel Composite Containing Antifibrotic Drug for Vocal Fold Scarring. ACS Appl Bio Mater. 2024 Aug 19;7(8):5237-5246. doi: 10.1021/acsabm.4c00422. Epub 2024 Jul 15. PMID: 39007499.
- Pierce JL, Olson B, Merrill RM, Pierce J, Isom A, Torrecillas V, McCrary H, Aylward A, Smith ME, Ben Christensen M. Amniotic Fluid as a Potential Treatment for Vocal Fold Scar in a Rabbit Model. J Voice. 2025 Jan 3:S0892-1997(24)00445-4. doi: 10.1016/j.jvoice.2024.12.015. Epub ahead of print. PMID: 39755523.
- Halder N, Perkerson R, Kanekiyo T, Rutt AL. Compatibility of Hepatocyte Growth Factor, Adipose-Derived Mesenchymal Stem Cells, and Dermal Fillers for the Treatment of Vocal Fold Scar. Stem Cell Rev Rep. 2025 May;21(4):1131-1133. doi: 10.1007/s12015-025-10862-3. Epub 2025 Feb 28. PMID: 40019729.
- Wu L, Bai L, Dai W, Wu Y, Xi P, Zhang J, Zheng L. Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications. Curr Top Med Chem. 2024;24(10):869-884. doi: 10.2174/0115680266283661240226052054. PMID: 38441023.
- Yao ZW, Zhu H. Pharmacological mechanisms and drug delivery systems of ginsenoside Rg3: A comprehensive review. Pharmacol Res. 2025 Jun;216:107799. doi: 10.1016/j.phrs.2025.107799. Epub 2025 May 23. PMID: 40414584.
- Tian ZF, Hu RY, Wang Z, Wang YJ, Li W. Molecular mechanisms behind the inhibitory effects of ginsenoside Rg3 on hepatic fibrosis: a review. Arch Toxicol. 2025 Feb;99(2):541-561. doi: 10.1007/s00204-024-03941-w. Epub 2024 Dec 27. PMID: 39729114.
- Chen Y, Peng Y, Li P, Jiang Y, Song D. Ginsenoside Rg3 induces mesangial cells proliferation and attenuates apoptosis by miR-216a-5p/MAPK pathway in diabetic kidney disease. Aging (Albany NY). 2024 Jun 7;16(11):9933-9943. doi: 10.18632/aging.205907. Epub 2024 Jun 7. PMID: 38850526; PMCID: PMC11210261.
- Yun E, Kwon BS, Kim J, Lee A. Ginsenoside Rg3 attenuates pulmonary fibrosis by inhibiting endothelial to mesenchymal transition. Anim Cells Syst (Seoul). 2023 Aug 4;27(1):159-170. doi: 10.1080/19768354.2023.2244549. PMID: 37554358; PMCID: PMC10405771.
- Tang M, Bian W, Cheng L, Zhang L, Jin R, Wang W, Zhang Y. Ginsenoside Rg3 inhibits keloid fibroblast proliferation, angiogenesis and collagen synthesis in vitro via the TGFβ/Smad and ERK signaling pathways. Int J Mol Med. 2018 Mar;41(3):1487-1499. doi: 10.3892/ijmm.2018.3362. Epub 2018 Jan 4. PMID: 29328420; PMCID: PMC5819908.
- Naba A. Mechanisms of assembly and remodelling of the extracellular matrix. Nat Rev Mol Cell Biol. 2024 Nov;25(11):865-885. doi: 10.1038/s41580-024-00767-3. Epub 2024 Sep 2. PMID: 39223427; PMCID: PMC11931590.
- Eskandari E, Eaves CJ. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J Cell Biol. 2022 Jun 6;221(6):e202201159. doi: 10.1083/jcb.202201159. Epub 2022 May 12. PMID: 35551578; PMCID: PMC9106709.
- Liang Z, Chen Y, Gu R, Guo Q, Nie X. Asiaticoside Prevents Oxidative Stress and Apoptosis in Endothelial Cells by Activating ROS-dependent p53/Bcl-2/Caspase-3 Signaling Pathway. Curr Mol Med. 2023;23(10):1116-1129. doi: 10.2174/1566524023666221024120825. PMID: 36284389.
- Wang Z, Tan Y, Xu F. Zonisamide improves Fas/FasL-mediated apoptosis and inflammation in a degenerative cervical myelopathy rat model. Tissue Cell. 2023 Apr;81:102024. doi: 10.1016/j.tice.2023.102024. Epub 2023 Jan 13. PMID: 36669388.
- Choi RJ, Mohamad Zobir SZ, Alexander-Dann B, Sharma N, Ma MKL, Lam BYH, Yeo GSH, Zhang W, Fan TP, Bender A. Combination of Ginsenosides Rb2 and Rg3 Promotes Angiogenic Phenotype of Human Endothelial Cells via PI3K/Akt and MAPK/ERK Pathways. Front Pharmacol. 2021 Feb 10;12:618773. doi: 10.3389/fphar.2021.618773. PMID: 33643049; PMCID: PMC7902932.
- Wan J, Cheng W, Xing X, He Y, Tang P, Feng Y, Liu S, Lu X, Zhong L. A SERS-Based Dual-Parameter Monitoring Nanoprobe of ROS and PI3K/Akt during Ginsenoside Rg3-Induced Cell Apoptosis. Biosensors (Basel). 2023 Jan 31;13(2):212. doi: 10.3390/bios13020212. PMID: 36831977; PMCID: PMC9953484.
- Tao D, Li F, Zhang X, Guo H, Yang R, Yang Y, Zhang L, Shen Z, Teng J, Chen P, He B. 20(R)-ginsenoside Rg3 protects against focal cerebral ischemia‒reperfusion injury by suppressing autophagy via PI3K/Akt/mTOR signaling pathway. Neuropharmacology. 2025 Feb 1;263:110226. doi: 10.1016/j.neuropharm.2024.110226. Epub 2024 Nov 16. PMID: 39557153.
- Wang X, He R, Geng L, Yuan J, Fan H. Ginsenoside Rg3 Alleviates Cisplatin Resistance of Gastric Cancer Cells Through Inhibiting SOX2 and the PI3K/Akt/mTOR Signaling Axis by Up-Regulating miR-429. Front Genet. 2022 Mar 3;13:823182. doi: 10.3389/fgene.2022.823182. PMID: 35309116; PMCID: PMC8927288.
- Xu H, Miao H, Chen G, Zhang G, Hua Y, Wu Y, Xu T, Han X, Hu C, Pang M, Tan L, Liu B, Zhou Y. 20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways. J Ginseng Res. 2023 Nov;47(6):743-754. doi: 10.1016/j.jgr.2023.06.007. Epub 2023 Jul 3. PMID: 38107395; PMCID: PMC10721484.
Received July 1, 2026.
Accepted August 8, 2026.
© 2026 The Author(s). International Journal of Biomedicine is published by IMRDC. This is an open access article under the CC BY-NC-ND 4.0 license.




