Ginsenoside Rb1 is a ginsenoside found in Panax ginseng and Panax japonicus var. major that is ginsenoside Rd in which the beta-D-glucopyranoside group at position 20 is replaced by a beta-D-glucopyranosyl-beta-D-glucopyranoside group. It has a role as a neuroprotective agent, an anti-obesity agent, an anti-inflammatory drug, an apoptosis inhibitor, a radical scavenger and a plant metabolite. It is a ginsenoside, a glycoside and a tetracyclic triterpenoid. It is functionally related to a ginsenoside Rd. Ginsenoside Rb1 is one of the primary constituents of traditional Chinese medicine, Ginseng. It belongs to the group of triterpene saponins called ginsenosides and pharmacologically, it is one of the most active dammarane-type ginsenosides. It is known to have anti-tumor, anti-oxidant, anti-inflammatory, and cytoprotective properties.

Neuroprotective Mechanisms of Ginsenoside Rb1

Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. Triterpenoid is constituted mainly by ginsenoside Rb1, ginsenoside Rb2, and notoginsenoside R1, among which ginsenoside Rb1 takes up a tremendous part. Ginsenoside is a kind of steroids, also known as triterpenoid saponins. All the ginsenosides have the similarity in the basic structure, containing sterane steroid nuclei arranged into four rings by 30 carbon atoms. What’s more, treatment with ginsenoside Rb1 attenuated tumor necrosis factor-α (TNF-α)-induced inflammation by inhibiting the activation of c-Jun N-terminal kinase (JNK) and p38 pathways in human umbilical vein endothelial cells and further suppressed the nuclear factor-kappa B (NF-κB) signaling and downregulated the expression of inflammatory factors. CNSDs, including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury, which are always difficult to cure clinically. Therapeutic drugs used clinically fail to block the development of diseases or are proved to produce severe side effects.[1]

Changhong and others found that ginsenoside Rb1 treatment could serve as an activator of peroxisom proliferator-activated receptor-γ (PPARγ) and reduce the level of cholesterol and further lowered the cytotoxicity of Aβ25-35 in PC12 cells . Interestingly, ginsenoside Rb1 mitigated the isoflurane/surgery-induced cognitive impairment- and synapse dysfunction via decreasing levels of ROS, TNF-α and IL-6 in the mice hippocampus, suggesting that the mechanisms refer to inhibiting oxidative stress and neuroinflammation. Ischemic stroke is one of the leading causes of adult disability and death all over the world. Cerebral ischemia, caused by a significant blockage in cerebral blood flow, results in various pathological events such as oxidative stress, neuroinflammation response, excitatory neurotransmitter release and energy failure, which eventually lead to neuronal apoptosis and brain tissue necrosis. Ginsenoside Rb1 could effectively reduce the levels of oxidative stress to protect against cerebral ischemia-induced neuronal injury. In summary, current studies have demonstrated that ginsenoside Rb1 exerts neuroprotective roles through inhibiting oxidative stress, apoptosis and neuroinflammation and regulating the autophagy in neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury.

Ginsenoside Rb1 in cardiovascular and cerebrovascular diseases

With the improvement of economic level and the change of human lifestyle, the prevalence of CCVDs continues to increase. Ginseng (Panax ginseng C. A. Mey.) was widely used in traditional diseases due to its supposed tonic properties. Ginsenoside Rb1 (G-Rb1) is the most abundant active ingredient with multiple pharmacological effects extracted from ginseng. Up to now, nearly 400 ginsenosides have been reported. Ginsenoside-Rb1 (G-Rb1) is considered to be one of the main ginsenosides, which has many pharmacological activities due to its steroid structure, such as anti-inflammatory, anti-oxidant, regulating lipid abnormalities, restoring autophagy. In addition to their therapeutic potential was proven in chronic diseases such as nervous system, cardiovascular system and diabetes, Ginsenoside Rb1 has been used in clinical medicine around the world and may provide the basis for the development of novel drugs.[2]

As the incidence of CCVDs increases year by year, it has led many to advocate for more widespread use of statins for rapid treatment. However, they found only a slight reduction in the risk of events CCVDs after statin use. However, it has been reported that G-Rb1 alleviated acute liver injury caused by acetaminophen (APAP), showing significant liver protection. Therefore, new drug formulations of G-Rb1 such as Ginsenoside Rb1 nanocapsule, G-Rb1-paclitaxel self-assembled nanoparticles, G-Rg3-G-Rb1 assembled nanoparticles can well solve the problem of low bioavailability, and achieve a better effect of slow release. Despite the promising preclinical findings, further research is warranted to translate the therapeutic potential of Ginsenoside Rb1 into clinical applications. Clinical trials are needed to evaluate the efficacy, safety, and optimal dosage regimens of G-Rb1 in CCVDs patients. Moreover, elucidating the pharmacokinetic profile and bioavailability of G-Rb1 will facilitate its clinical development and therapeutic use.

Ginsenoside Rb1 exerts neuroprotective effects

Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Until now, the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 has not been well understood. In the present study, we aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying neuroprotective mechanisms of Ginsenoside Rb1 in rats subjected to I/R-induced focal cerebral injury.  In the present study, all concentrations at 1 h, 6 h, and 24 h were found to be much lower than 100 ng/g, and the Rb1 concentration ratios of brain to plasma were far lower than 0.1. Effects of Rb1 on cerebral infarct volume; neurological deficit score; and levels of IL-1, IL-6, and TNF-α in I/R rats were attenuated by coadministering an antibiotic cocktail. Thus, the gut microbiota plays a key role in mediating neuroprotective effects of Ginsenoside Rb1.[3]

Overall, the findings of the present study suggest that I/R surgery downregulates the population of certain probiotics (Bif.L, Bif.D, Lac.B, Lac.H, and Lac.R). After pretreatment with Ginsenoside Rb1, the relative abundance of specific probiotics can be significantly enhanced, and Lac.H is upregulated far more that the other studied probiotics. Enhanced Lac.H levels can then upregulate the expression of GABAA (α2, β2, and γ2) and GABAB (1b and 2) receptor subunits in the rat hippocampus and striatum. Upregulation of GABAA receptors may play a crucial role in mediating neuroprotective effects of Ginsenoside Rb1 and Lac.H.

References

[1]Gong L, Yin J, Zhang Y, Huang R, Lou Y, Jiang H, Sun L, Jia J, Zeng X. Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases. Front Pharmacol. 2022 Jun 2;13:914352. doi: 10.3389/fphar.2022.914352. PMID: 35721176; PMCID: PMC9201244.

[2]Song, Yueqin et al. “Ginsenoside Rb1 in cardiovascular and cerebrovascular diseases: A review of therapeutic potentials and molecular mechanisms.” Chinese herbal medicines vol. 16,4 489-504. 16 Sep. 2024, doi:10.1016/j.chmed.2024.09.006

[3]Chen H, Shen J, Li H, Zheng X, Kang D, Xu Y, Chen C, Guo H, Xie L, Wang G, Liang Y. Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABAA receptor expression. J Ginseng Res. 2020 Jan;44(1):86-95. doi: 10.1016/j.jgr.2018.09.002. Epub 2018 Sep 19. PMID: 32095096; PMCID: PMC7033341.