Rb1-KO Mouse

Rb1, short for retinoblastoma susceptibility gene, is a prototype tumor suppressor gene. It plays a key role in restraining cell cycle entry, and its pathway alterations occur in most human cancers, often having prognostic value. RB1, along with its family members, regulates numerous cellular processes and impacts cell response to various stimuli, determining cell fate [2,4,8].

In ischemic stroke, ginsenoside Rb1 (not to be confused with the Rb1 gene) inhibits astrocyte activation by blocking reverse electron transport-derived ROS production from mitochondrial complex I, and promotes transfer of astrocytic mitochondria to neurons, which seems to be a means for neuronal survival and function [1]. In myocardial ischemia/reperfusion injury, ginsenoside Rb1 inhibits cardiomyocyte autophagy via the PI3K/Akt/mTOR signaling pathway, reducing such injury [3]. It also protects ovarian granulosa cells from oxidative stress-induced injury through the Akt-FoxO1 interaction [5], and reduces H2O2-induced HUVEC dysfunction by stimulating the sirtuin-1/AMP-activated protein kinase pathway [6]. Additionally, ginsenoside Rb1 attenuates myocardial ischemia/reperfusion injury by inhibiting ROS production from mitochondrial complex I [7], and attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis [9].

In conclusion, while the Rb1 gene is crucial in tumor suppression and cell cycle regulation, ginsenoside Rb1 shows potential in treating various conditions related to oxidative stress, autophagy, and mitochondrial function, such as ischemic stroke, myocardial ischemia/reperfusion injury, and doxorubicin induced cardiotoxicity. These studies provide insights into potential therapeutic strategies targeting these pathways [1,3,5-7,10].

References:

1. Ni, Xue-Chun, Wang, Hong-Fei, Cai, Yuan-Yuan, Li, Jia, Huang, Feng-Qing. 2022. Ginsenoside Rb1 inhibits astrocyte activation and promotes transfer of astrocytic mitochondria to neurons against ischemic stroke. In Redox biology, 54, 102363. doi:10.1016/j.redox.2022.102363. https://pubmed.ncbi.nlm.nih.gov/35696763/

2. Yao, Yiran, Gu, Xiang, Xu, Xiaofang, Ge, Shengfang, Jia, Renbing. 2022. Novel insights into RB1 mutation. In Cancer letters, 547, 215870. doi:10.1016/j.canlet.2022.215870. https://pubmed.ncbi.nlm.nih.gov/35964818/

3. Qin, Guo-Wei, Lu, Pan, Peng, Li, Jiang, Wei. 2021. Ginsenoside Rb1 Inhibits Cardiomyocyte Autophagy via PI3K/Akt/mTOR Signaling Pathway and Reduces Myocardial Ischemia/Reperfusion Injury. In The American journal of Chinese medicine, 49, 1913-1927. doi:10.1142/S0192415X21500907. https://pubmed.ncbi.nlm.nih.gov/34775933/

4. Linn, Paing, Kohno, Susumu, Sheng, Jindan, Watanabe, Yoshihiro, Takahashi, Chiaki. 2021. Targeting RB1 Loss in Cancers. In Cancers, 13, . doi:10.3390/cancers13153737. https://pubmed.ncbi.nlm.nih.gov/34359636/

5. Zhou, Ping, Deng, Feng, Yang, Zi, Li, Rong, Yu, Yang. 2022. Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction. In Science China. Life sciences, 65, 2301-2315. doi:10.1007/s11427-021-2080-x. https://pubmed.ncbi.nlm.nih.gov/35661967/

6. Zheng, Zhenda, Wang, Min, Cheng, Cailian, Zhu, Jieming, Qian, Xiaoxian. 2020. Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway. In Molecular medicine reports, 22, 247-256. doi:10.3892/mmr.2020.11096. https://pubmed.ncbi.nlm.nih.gov/32377712/

7. Jiang, Lujing, Yin, Xiaojian, Chen, Ya-Hui, Qi, Lian-Wen, Li, Jia. 2021. Proteomic analysis reveals ginsenoside Rb1 attenuates myocardial ischemia/reperfusion injury through inhibiting ROS production from mitochondrial complex I. In Theranostics, 11, 1703-1720. doi:10.7150/thno.43895. https://pubmed.ncbi.nlm.nih.gov/33408776/

8. Indovina, Paola, Pentimalli, Francesca, Conti, Daniele, Giordano, Antonio. 2019. Translating RB1 predictive value in clinical cancer therapy: Are we there yet? In Biochemical pharmacology, 166, 323-334. doi:10.1016/j.bcp.2019.06.003. https://pubmed.ncbi.nlm.nih.gov/31176618/

9. Zhai, Yafei, Bai, Jinmeng, Peng, Ying, Dong, Jianzeng, Zhao, Xiaoyan. 2024. Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis. In Biochemical and biophysical research communications, 710, 149910. doi:10.1016/j.bbrc.2024.149910. https://pubmed.ncbi.nlm.nih.gov/38593619/