|Table of Contents|

Alleviative effect and mechanism of ginsenoside Rg3 on breast cancer-induced bone pain in rats

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 08
Page:
1397-1401
Research Field:
Publishing date:

Info

Title:
Alleviative effect and mechanism of ginsenoside Rg3 on breast cancer-induced bone pain in rats
Author(s):
LI YachenSHENG GegeWU JiliangZHU Haili
School of Pharmacy,Xianning Medical College,Hubei University of Science and Technology,Hubei Xianning 437100,China.
Keywords:
ginsenoside Rg3cancer-induced bone painspinal inflammationNLRP3 inflammasomemitochondria
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.08.005
Abstract:
Objective:To investigate the alleviative effect and mechanism of ginsenoside Rg3 on breast cancer-induced bone pain in rats.Methods:A rat model of breast cancer-induced bone pain was constructed by inoculation of MRMT-1 rat breast cancer cells into the medullary cavity of tibia in rats.Rats were randomly divided into three groups,including Sham,Model and ginsenoside Rg3 (Rg3) groups.Ginsenoside Rg3 was injected on rats by the tail vein for 3 consecutive days.The changes of pain behavior of rats were detected.Molecular docking analyzed the binding between Rg3 and protein.Immunofluorescence and Western blotting assays were performed to detect the expression of proteins related to inflammation in spinal cord tissue in each group of animals.Results:Bone metastases of breast cancer caused bone damage,induced mechanical pain,thermal hyperalgesia and spontaneous pain of rats.The spinal cord glia cells and NLRP3 inflammasome were activated.The pro-inflammatory factor IL-1β level was increased.The antioxidant factors Nrf2 and GPX4 levels were decreased.The levels of mitochondrial oxidative damage related proteins DHODH and cytochrome C were increased.Ginsenoside Rg3 treatment alleviated the mechanical pain,thermal hyperalgesia and spontaneous pain of rats,inhibited spinal inflammatory reaction,enhanced spinal Nrf2/GPX4-mediated antioxidant responses,decreased spinal mitochondrial oxidative level.In addition,ginsenoside Rg3 combined with Nrf2 assayed by auto-dock.Conclusion:Ginsenoside Rg3 treatment activates Nrf2-mediated antioxidant responses,inhibits inflammatory reaction in the spinal cord,and alleviates cancer-induced bone pain.

References:

[1] COLOSIA A,NJUE A,BAJWA Z,et al.The burden of metastatic cancer-induced bone pain:a narrative review[J].Journal of Pain Research,2022,15:3399-3412.
[2] KAPOOR R,SAXENA AK,VASUDEV P,et al.Cancer induced bone pain:current management and future perspectives[J].Medical Oncology,2021,38(11):134-137.
[3] YONEDA T,HIASA M,OKUI T,et al.Cancer-nerve interplay in cancer progression and cancer-induced bone pain[J].Journal of Bone and Mineral Metabolism,2023,41(3):415-427.
[4] LINNERBAUER M,WHEELER MA,QUINTANA FJ.Astrocyte crosstalk in CNS inflammation[J].Neuron,2020,108(4):608-622.
[5] 王煜嘉,张凤,王柏军,等.2-溴棕榈酸鞘内给药对乳腺癌骨转移大鼠疼痛的作用及机制[J].湖北科技学院学报:医学版,2020,34(4):281-284. WANG YJ,ZHANG F,WANG BJ,et al.Effect and mechanism of intrathecal 2-bromopalmitateon on painin rat with bone metastatic of breast cancer[J].Journal of Hubei University of Science and Technology (Medical Sciences),2020,34(4):281-284.
[6] SWANSON KV,DENG M,TING JPY.The NLRP3 inflammasome:molecular activation and regulation to therapeutics[J].Nature Reviews Immunology,2019,19(8):477-489.
[7] YANG J,LI S,WANG L,et al.Ginsenoside Rg3 attenuates lipopolysaccharide-induced acute lung injury via MerTK-dependent activation of the PI3K/AKT/mTOR pathway[J].Frontiers in Pharmacology,2018,9:850.
[8] KANG S,PARK SJ,LEE AY,et al.Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage polarization[J].Journal of Ginseng Research,2018,42(1):68-74.
[9] SUN Y,SHI S,ZHENG Y,et al.Analgesic effect and related amino acids regulation of ginsenoside Rg3 in mouse pain models[J].Life Sciences,2019,239:117083.
[10] AHN EJ,CHOI GJ,KANG H,et al.Antinociceptive effects of ginsenoside Rg3 in a rat model of incisional pain[J].European Surgical Research,2016,57(3-4):211-223.
[11] WANG J,ZENG L,ZHANG Y,et al.Pharmacological properties,molecular mechanisms and therapeutic potential of ginsenoside Rg3 as an antioxidant and anti-inflammatory agent[J].Frontiers in Pharmacology,2022,13:975784.
[12] NAKHJAVANI M,SMITH E,TOWNSEND AR,et al.Anti-angiogenic properties of ginsenoside Rg3[J].Molecules,2020,25(21):4905.
[13] STAURENGO-FERRARI L,BADARO-GARCIA S,HOHMANN MSN,et al.Contribution of Nrf2 modulation to the mechanism of action of analgesic and anti-inflammatory drugs in pre-clinical and clinical stages[J].Frontiers in Pharmacology,2019,9:1536.
[14] KAUSHIK AS,STRATH LJ,SORGE RE.Dietary interventions for treatment of chronic pain:oxidative stress and inflammation[J].Pain and Therapy,2020,9:487-498.
[15] ZHOU YQ,MEI W,TIAN XB,et al.The therapeutic potential of Nrf2 inducers in chronic pain:Evidence from preclinical studies[J].Pharmacology & Therapeutics,2021,225:107846.
[16] SHAN Y,LI J,ZHU A,et al.Ginsenoside Rg3 ameliorates acute pancreatitis by activating the NRF2/HO-1-mediated ferroptosis pathway[J].International Journal of Molecular Medicine,2022,50(1):1-10.
[17] ZHAO T,YU Z,ZHOU L,et al.Regulating Nrf2-GPx4 axis by bicyclol can prevent ferroptosis in carbon tetrachloride-induced acute liver injury in mice[J].Cell Death Discovery,2022,8(1):380.
[18] AMOS A,AMOS A,WU L,et al.The Warburg effect modulates DHODH role in ferroptosis:a review[J].Cell Communication and Signaling,2023,21(1):1-12.
[19] GUERRA-CASTELLANO A,DAZ-QUINTANA A,PREZ-MEJAS G,et al.Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria[J].Proceedings of the National Academy of Sciences,2018,115(31):7955-7960.
[20] KIM MJ,DO KOO Y,KIM M,et al.Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis in C2C12 myotubes[J].Diabetes & Metabolism Journal,2016,40(5):406-413.

Memo

Memo:
National Natural Science Foundation of China(No.81971066);国家自然科学基金资助项目(编号:81971066)
Last Update: 1900-01-01