Deans' stroke musings: Timosaponin B-II attenuates cerebral ischemia injury by enhancing Parkin-mediated mitophagy

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Sunday, November 30, 2025

Timosaponin B-II attenuates cerebral ischemia injury by enhancing Parkin-mediated mitophagy

Sounds important for our recovery. Do you really think your incompetent? doctor and hospital will ensure human testing gets done? Competent entities would do that!

Timosaponin B-II attenuates cerebral ischemia injury by enhancing Parkin-mediated mitophagy

https://doi.org/10.1016/j.phymed.2025.157580 Get rights and content

Abstract

Background

Ischemic stroke (IS) is linked to dysregulated mitophagy. Timosaponin B-II (TBII), a complex furostan steroid saponin extracted from Anemarrhena asphodeloides Bunge, has been demonstrated to play a crucial role in regulating autophagy. However, whether TBII exerts therapeutic effects in cerebral ischemia through the regulation of autophagy, particularly Parkin-dependent pathways remained unexplored.

Purpose

The present study investigated whether TBII can alleviate cerebral ischemic injury by enhancing Parkin-dependent mitophagy.

Methods

We evaluated TBII’s effects on cerebral ischemic injury using permanent middle cerebral artery occlusion (pMCAO) in mice and oxygen-glucose deprivation (OGD)-treated neurons. Mitophagy and mitochondrial function were assessed by Western blot, transmission electron microscopy (TEM), and immunofluorescence techniques. Parkin knockdown (shPrkn lentivirus) and the mitophagy inhibitor Mdivi-1 were employed to validate TBII’ mechanisms.

Results

Intragastrical (i.g.) administration of TBII (10, 20, 40 mg/kg) for 7 days significantly reduced cerebral infarction volume, brain water content, and neurological deficits in pMCAO mice, while attenuating neuronal death in vivo and in vitro. Molecular docking, cellular thermal shift assays (CETSA), drug affinity responsive target stability (DARTS), and molecular dynamics simulations confirmed that TBII specifically binds and stabilizes to Parkin, suggesting its potential to enhance mitophagy. TBII mitigated the impairment of mitophagy by upregulating Parkin and p-Parkin (Ser65), promoting the ubiquitination of mitochondria, the degradation of autophagy substrate SQSTM1 and damaged mitochondria after IS. TBII also preserved mitochondrial membrane potential (MMP), suppressed oxidative stress, and restored mitochondrial function and ultrastructure. These benefits were reversed by the mitophagy inhibitor Mdivi-1 and Parkin knockdown.

Conclusion

The present study demonstrates that TBII reduces oxidative stress, preserves mitochondrial function, and ultimately attenuates ischemic brain injure by enhancing Parkin-dependent mitophagy. Our study provides the first evidence supporting TBII as a promising therapeutic agent for IS.