Timosaponin A-III: Plant sources, Pharmacological Actions

Rhizoma anemarrhenae is the dry rhizome of Anemarrhena asphodeloides Bge. It is bitter in taste, cold in nature, and attributes to the lungs, stomach and kidney meridians. It has the effects of clearing away heat and purging fire, nourishing yin and moisturizing dryness, quenching thirst and relieving vexation etc. It is clinically used for overabundance of pathogenic heat due to febrile disease with symptoms of high fever and excessive thirst, cough due to lung heat, hyperactivity of fire due to yin deficiency marked by hectic fever, diabetes due to yin deficiency manifested as thirst due to consumption of body fluids and constipation due to dryness of intestine etc. 

The molecular structure of Timosaponin AIII, C39H64O13. Molecular weight: 740.92.

As the main pharmacologically active ingredient of Rhizoma anemarrhenae, timosaponin is about 6% rich in the Rhizoma anemarrhenae. Timosaponin A-III, also known as Xilingsaponin A, is a typical spirostanol saponin, and its nucleus is sarsasapogenin which is a polyglycoside formed by condensation of two fructose and one glucose after dehydrogenation of the hydroxyl group at the C22 position of the saponin. Timosaponin AIII has anti-platelet aggregation, anti-senile dementia, anti-tumor and hypoglycemic effects. In particular, it exerts strong pharmacological activity in control of tumor and has inhibitory effects on colon cancer, cervical cancer and breast cancer.

Cardiovascular system

Anti-platelet aggregation

The molecular mechanisms of anti-platelet aggregation of timosaponin A-III are mainly as follows:

1. It activates platelet P2Y1 receptor coupled to Gq subunit of G protein-coupled receptor, thereby inducing platelet deformation;

2. it inhibits the Gq and G12/G13 subunits coupled to the G protein and prevents its conduction activation signal, thereby inhibiting platelet aggregation in a dose-dependent manner;

3. It activates the Gi signaling pathway, inhibits adenylate cyclase, increases cAMP, and thus inhibits platelet aggregation;

4. It does inhibit the binding of platelets to fibrinogen by inhibiting the activation of integrin αII bβ3, and thuse inhibits the further transmission of aggregated signals.

Vasodilatation effect

Stimulation of Ca2+ influx can stimulate vasodilator (NO) synthase in vascular endothelial cells, thereby promoting the release of NO from endothelial cells, which in turn stimulates the transfer of Ca2+ into endothelial cells, which makes the vasodilating activity of timosaponin AIII Stronger.

Improve memory and learning deficits

It has been found by Bomi etc that 40 mg/kg timosaponin A-III significantly reduced the number of errors in glutamate-induced Alzheimer's model mice in the passive avoidance tests and significantly shortened the error latency. The mechanism of action may be to increase the concentration of norepinephrine, dopamine and serotonin in the brain of dementia mice, and thereby improve the memory of mice, and meanwhile the timosaponin A-III reduces the number of β-APP positive neurons in inner molecular layer of dementia mice and hippocampus. Thus improving the symptoms of Alzheimer's disease in mice.

Hypoglycemic effect

The timosaponin A-III has a hypoglycemic effect and its efficacy is concentration dependent.

Reference

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