Delving into the Latest Updates on Salvianolic acid A with Synapse

AbstractVPS34 is a sole member of class III phosphoinositide 3‐kinase involved in endosomal trafficking and autophagosome formation, making it an interesting target for cancer treatment. Here, we investigated 5,774 natural products using structure‐based virtual screening against human VPS34. 10 natural products identified by virtual screening were purchased and tested in VPS34 ADP‐Glo assay, yielding several potential VPS34 inhibitors. Amongst, Salvianolic acid A (4) and Ellagic acid (8) inhibited VPS34 with IC50 values of 2.46 and 3.12 μM, respectively, more potent than the positivity control 3‐MA. Moreover, in vitro assays demonstrated that both of the compounds suppressed vesicle trafficking in cell‐based assay. Significantly, Salvianolic acid (4) effectively prevented autophagy in Hela cells induced either by starvation or Rapamycin, an mTOR inhibitor. In addition, in silico analysis was done to elucidate the binding mechanisms of the ligand in complex with VPS34. Overall, this study highlights the efficacy of structure‐based virtual screening and presents several natural products as VPS34 inhibitors that modulate autophagy.

01 Mar 2025·Journal of Molecular Structure

Identification of Salvianolic acid A as a potent inhibitor of PDEs to enhance proliferation of human neural stem cells

Author: Li, Ya-Lin ; Tian, Xiu-Fen ; Mao, Jun ; Ren, Ji-Xia ; Song, Hao

The inhibition of phosphodiesterases (PDEs) is a promising therapeutic strategy for treating central nervous system (CNS) disorders due to its capacity to facilitate neuroplasticity.Salvianolic acid A (SAA) shows promise in treating CNS disorders, but its specific targets are still unclear.This study has discovered that SAA directly targets PDEs to promote the proliferation of neural stem cells (NSCs).A pharmacophore model for PDE9 inhibitors was developed and validated to screen a compound database, leading to the discovery of SAA as an active agent.Further investigation into the anti-PDEs activity of SAA has revealed that it is a broad-spectrum PDEs inhibitor, with IC₅₀ values of 28.26, 34.18, and 31.68 μM for PDE4, PDE5, and PDE9, resp.Furthermore, the proliferation of human NSCs (H9) was significantly enhanced by 30-90 μM SAA.This study also provides comprehensive elucidations of signaling pathways associated with direct targeting of PDEs for neuroplasticity in stroke.Furthermore, mol. dynamics (MD) simulations revealed that SAA effectively interacts with the crucial amino acid residues of PDE9.The decomposition of binding free energy for acid residues offers further insight into the interactions between SAA and these key amino acids, thus providing more information for understanding the mechanism of SAA bound to PDE9.

19 Feb 2025·ACS Chemical Neuroscience

Acute Treatment with Salvianolic Acid A Produces Neuroprotection in Stroke Models by Inducing Excitatory Long-Term Synaptic Depression

Article

Author: Mao, Rongrong ; Yang, Chunxian ; Jiao, Chunxiang ; Li, Jinnan ; Xu, Lin ; Tang, Xun ; Huang, Qi ; Ding, Yuqiang ; Zhou, Qixin ; Shan, Baoci ; Liu, Weilin ; Wang, Niya

Acute ischemic stroke (AIS) is a significant brain disease with a high mortality and disability rate. Additional therapies for AIS are urgently needed, and neuroplasticity mechanisms by agents are expected to be neuroprotective for AIS. As a major active component of Salvia miltiorrhiza, salvianolic acid A (SAA) has shown potential for preventing cardiovascular diseases. However, there is no evidence of the long-term effect of SAA on ischemic injury or its mechanism. Therefore, using rats and mice, we systematically investigated the impact of SAA on AIS from the perspective of neuroprotective and neuroplasticity. Here, we report that SAA induces a long-term depression (LTD)-like process in synapses. This antiexcitotoxicity action supports the SAA effect, including alleviating infarction and promoting blood circulation in photothrombosis and middle cerebral artery occlusion (MCAO) models. Furthermore, repeated positron emission tomography/computed tomography (PET/CT) imaging and behavioral assessments two months after AIS induction reveal that acute treatment of SAA promotes recovery from disrupted whole-brain glucose metabolism and impaired spatial memory. These data suggest that acute treatment of SAA is neuroprotective by improving long-term functional outcomes through a synaptic LTD-like process, providing a promising adjunct to current therapies to enable better recovery for AIS.

100 Deals associated with Salvianolic acid A

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic peripheral neuropathy	Phase 2	China	Institute of Materia Medica	11 May 2021
Acute Chest Syndrome	Phase 1	China	Shanghai Pharmaceuticals Holding Co., Ltd.	21 Jul 2022
Diabetic Nephropathies	Phase 1	-	Chinese Academy of Medical Sciences	-
Peripheral Nervous System Diseases	Phase 1	-	Chinese Academy of Medical Sciences	-
Endothelial dysfunction	Preclinical	China	Zhejiang Chinese Medical University	24 May 2024
Diabetic peripheral neuropathy	Discovery	China	Chinese Academy of Medical Sciences	11 May 2021
Angina Pectoris	Discovery	China	Beijing Bencao Tianyuan Medicine Research Institute	29 Nov 2018
Angina Pectoris	Discovery	China	Chia Tai Qingchunbao Pharmaceutical Co., Ltd.	29 Nov 2018
Angina Pectoris	Discovery	China	Shanghai Pharmaceuticals Holding Co., Ltd.	29 Nov 2018