| Citation: |
LIU Linchen, XU Xiaoyan, SUN Chunmeng, et al. Ginkgolide B inhibits cell proliferation and promotes cell apoptosis of MH7A human fibroblast-like synoviocytes through PI3K/AKT pathway[J]. J China Pharm Univ, 2025, 56(2): 216 − 224. DOI: 10.11665/j.issn.1000-5048.2024091403
|
To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.
| [1] |
Li N, Jiang L, Cai YH, et al. The correlation between interleukin-34 and bone erosion under ultrasound in rheumatoid arthritis[J]. Mod Rheumatol, 2020, 30(2): 269-275. doi: 10.1080/14397595.2019.1593576
|
| [2] |
Romão VC, Fonseca JE. Etiology and risk factors for rheumatoid arthritis: a state-of-the-art review[J]. Front Med (Lausanne), 2021, 8: 689698.
|
| [3] |
Tian XP, Wang Q, Li MT, et al. 2018 Chinese guidelines for the diagnosis and treatment of rheumatoid arthritis[J]. Rheumatol Immunol Res, 2021, 2(1): 1-14. doi: 10.2478/rir-2021-0002
|
| [4] |
Chen YX, Dang JL, Lin XR, et al. RA fibroblast-like synoviocytes derived extracellular vesicles promote angiogenesis by mirna-1972 targeting p53/MTOR signaling in vascular endotheliocyte[J]. Front Immunol, 2022, 13: 793855. doi: 10.3389/fimmu.2022.793855
|
| [5] |
Castrejon I. Evaluation and monitoring of established rheumatoid arthritis[J]. Best Pract Res Clin Rheumatol, 2019, 33(5): 101480. doi: 10.1016/j.berh.2019.101480
|
| [6] |
Zhang Q, Liu J, Zhang MM, et al. Apoptosis induction of fibroblast-like synoviocytes is an important molecular-mechanism for herbal medicine along with its active components in treating rheumatoid arthritis[J]. Biomolecules, 2019, 9(12): 795. doi: 10.3390/biom9120795
|
| [7] |
Meng W, Ye HB, Ma ZF, et al. Perfluorocarbon nanoparticles incorporating ginkgolide b: artificial O2 carriers with antioxidant activity and antithrombotic effect[J]. Chem Med Chem, 2024, 19(1): e202300312. doi: 10.1002/cmdc.202300312
|
| [8] |
Yang JL, Li YX, Wang LL, et al. LncRNA H19 aggravates TNF-α-induced inflammatory injury via TAK1 pathway in MH7A cells[J]. Biofactors, 2020, 46(5): 813-820. doi: 10.1002/biof.1659
|
| [9] |
Mo X, Chen J, Wang X, et al. Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced by TNF-α in human fibroblast-like synoviocyte MH7A cells[J]. Mol Cell Biochem, 2018, 438: 77-84. doi: 10.1007/s11010-017-3115-9
|
| [10] |
Wang Y, Chen S, Du K, et al. Traditional herbal medicine: therapeutic potential in rheumatoid arthritis[J]. J Ethnopharmacol, 2021, 279: 114368. doi: 10.1016/j.jep.2021.114368
|
| [11] |
Xiang YJ, Zhang SY, Lu J, et al. Ginkgolide B protects human pulmonary alveolar epithelial A549 cells from lipopolysaccharide-induced inflammatory responses by reducing TRIM37-mediated NF-κB activation[J]. Biotechnol Appl Biochem, 2020, 67(6): 903-911. doi: 10.1002/bab.1847
|
| [12] |
Chen K, Sun WJ, Jiang Y, et al. Ginkgolide B suppresses TLR4-mediated inflammatory response by inhibiting the phosphorylation of JAK2/STAT3 and p38 MAPK in high glucose-treated HUVECs[J]. Oxid Med Cell Longev, 2017, 2017: 9371602. doi: 10.1155/2017/9371602
|
| [13] |
Wan F, Zang SS, Yu GQ, et al. Ginkgolide B suppresses methamphetamine-induced microglial activation through TLR4-NF-κB signaling pathway in BV2 cells[J]. Neurochem Res, 42 (10): 2881-2891.
|
| [14] |
Xie CM, Jiang J, Liu JP, et al. Ginkgolide B attenuates collagen-induced rheumatoid arthritis and regulates fibroblast-like synoviocytes-mediated apoptosis and inflammation[J]. Ann Transl Med, 2020, 8(22): 1497. doi: 10.21037/atm-20-6420
|
| [15] |
Rahmani F, Ziaeemehr A, Shahidsales S, et al. Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma[J]. J Cell Physiol, 2020, 235(5): 4146-4152. doi: 10.1002/jcp.29333
|
| [16] |
Chen KL, Zhu PF, Chen WH, et al. Melatonin inhibits proliferation, migration, and invasion by inducing ROS-mediated apoptosis via suppression of the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells[J]. Aging (Albany NY), 2021, 13(18): 22502-22515.
|
| [17] |
Zhao YY, Ye X, Chen RF, et al. Sirtuin 7 promotes non-small cell lung cancer progression by facilitating G1/S phase and epithelial-mesenchymal transition and activating AKT and ERK1/2 signaling[J]. Oncol Rep, 202, 44 (3): 959-972.
|
| [18] |
Wei EH, Rao MR, Ji ND, et al. Inhibitory effects of ginkgolide B on proliferation of bovine aortic smooth muscle cells[J]. Acta Pharm Sin, 2002, 37(2): 90-93.
|
| [19] |
Sun R, Zhai R, Ma C, et al. Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/Akt/mTOR pathway[J]. Cancer Med, 2020, 9(3): 1141-1151. doi: 10.1002/cam4.2723
|
| [20] |
Wang LF, Wang N, Zhao Q, et al. Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase/protein kinase B pathway[J]. J Cell Biochem, 2019, 120(9): 15202-15210. doi: 10.1002/jcb.28784
|
| [21] |
Zhou MJ, Tan W, Hasimu H, et al. Euphorbium total triterpenes improve Freund's complete adjuvant-induced arthritis through PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathways[J]. J Ethnopharmacol, 2023, 306: 116146. doi: 10.1016/j.jep.2023.116146
|
| [22] |
Nichani K, Li JZ, Suzuki M, et al. Evaluation of Caspase-3 activity during apoptosis with fluorescence lifetime-based cytometry measurements and phasor analyses[J]. Cytometry A, 2020, 97(12): 1265-1275. doi: 10.1002/cyto.a.24207
|
| [23] |
Chan WH. Ginkgolide B induces apoptosis and developmental injury in mouse embryonic stem cells and blastocysts[J]. Hum Reprod, 2006, 21(11): 2985-2895. doi: 10.1093/humrep/del255
|
| 1. |
鲁双，方名扬，范小燕，薛斌. 使用生物材料治疗毛发相关疾病的研究进展. 中国医疗美容. 2025(02): 95-98 .
| |
| 2. |
钱昕妤，王思梦，王倩. ⅩⅦ型胶原蛋白在脱发治疗中的应用效果. 医药前沿. 2025(15): 65-68 .
|
Supported by: Beijing Renhe Information Technology Co., Ltd. 
Total visits：436990
DownLoad: