Synergistic Effects of Salvianolic Acid B and Puerarin on Cerebral Ischemia Reperfusion Injury

Ischemic stroke (IS) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It has been a worldwide critical disease threatening to the health and life of human beings. Despite significant progresses achieved, effective treatment still remains a formidable challenge due to the complexity of the disease. Salvianolic acid B (Sal-B) and Puerarin (Pue) are two active neuroprotectants isolated from traditional Chinese herbs, Salvia miltiorrhiza and Kudzu root respectively, which have been used for the prevention and treatment of IS for thousands of years in China. The activities of two compounds against cerebral ischemia reperfusion injury have been confirmed via various pathways. However, the therapeutic efficacy of any of the two components is still unsatisfied. In the present study, the effect of the combination of Sal-B and Pue on IS was evaluated and validated in vitro and in vivo. The ratio of two compounds was firstly optimized based on the results of CoCl₂ damaged PC12 cells model. The co-administration exhibited significantly protective effect in CoCl₂ induced PC12 cells injury model by reducing ROS, inhibiting apoptosis and improving mitochondrial membrane potential in vitro. Moreover, Sal-B + Pue significantly relieved neurological deficit scores and infarct area than Sal-B or Pue alone in vivo. The results indicated that neuroprotection mechanism of Sal-B + Pue was related to TLR4/MyD88 and SIRT1 activation signaling pathway to achieve synergistic effect, due to the inhibition of NF-κB transcriptional activity and expression of pro-inflammatory cytokine (TNF-α, IL-1β, IL-6). In conclusion, the combination of Sal-B and Pue exerted much stronger neuroprotective effect than Sal-B or Pue alone, which provides a potential new drug and has great significance for the treatment of IS.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Molecules (Basel, Switzerland) - 23(2018), 3 vom: 02. März

Sprache:

Englisch

Beteiligte Personen:

Ling, Chengli [VerfasserIn]
Liang, Jianming [VerfasserIn]
Zhang, Chun [VerfasserIn]
Li, Ruixiang [VerfasserIn]
Mou, Qianqian [VerfasserIn]
Qin, Jin [VerfasserIn]
Li, Xiaofang [VerfasserIn]
Wang, Jianxin [VerfasserIn]

Links:

Volltext

Themen:

3G0H8C9362
Benzofurans
C1GQ844199
Cobalt
Cobaltous chloride
Combination
Drug Combinations
EVS87XF13W
IL1B protein, rat
Inflammation
Interleukin-1beta
Interleukin-6
Ischemia stroke
Isoflavones
Journal Article
Myd88 protein, rat
Myeloid Differentiation Factor 88
NF-kappa B
Neuroprotective Agents
Puerarin
Reactive Oxygen Species
Salvianolic acid B
Synergistic effect
Tlr4 protein, rat
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
Z9W8997416

Anmerkungen:

Date Completed 30.08.2018

Date Revised 07.12.2018

published: Electronic

Citation Status MEDLINE

doi:

10.3390/molecules23030564

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM281558817