Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (SM) is an outstanding herbal medicine with various traditional effects, especially promoting blood circulation to remove blood stasis. It has been widely used for centuries to treat blood stasis syndrome (BSS)-related diseases. BSS is one of the basic pathological syndromes of diseases such as cardiovascular and cerebrovascular diseases in traditional East Asian medicine, which is characterized by disturbance of blood circulation. However, the bioactive components and mechanisms of SM in the treatment of BSS have not been systematically reviewed. Therefore, this article outlines the anti-BSS effects of bioactive components of SM, concentrating on the molecular mechanisms. AIM OF THE REVIEW: To summarize the bioactive components of SM against BSS and highlight its potential targets and signaling pathways, hoping to provide a modern biomedical perspective to understand the efficacy of SM on enhancing blood circulation to remove blood stasis. MATERIALS AND METHODS: A comprehensive literature search was performed to retrieve articles published in the last two decades on bioactive components of SM used for BSS treatment from the online electronic medical literature database (PubMed). RESULTS: Phenolic acids and tanshinones in SM are the main bioactive components in the treatment of BSS, including but not limited to salvianolic acid B, tanshinone IIA, salvianolic acid A, cryptotanshinone, Danshensu, dihydrotanshinone, rosmarinic acid, protocatechuic aldehyde, and caffeic acid. They protect vascular endothelial cells by alleviating oxidative stress and inflammatory damage and regulating of NO/ET-1 levels. They also enhance anticoagulant and fibrinolytic capacity, inhibit platelet activation and aggregation, and dilate blood vessels. Moreover, lowering blood lipids and improving blood rheological properties may be the underlying mechanisms of their anti-BSS. More notably, these compounds play an anti-BSS role by mediating multiple signaling pathways such as Nrf2/HO-1, TLR4/MyD88/NF-κB, PI3K/Akt/eNOS, MAPKs (p38, ERK, and JNK), and Ca2+/K+ channels. CONCLUSIONS: Both phenolic acids and tanshinones in SM may act synergistically to target different signaling pathways to achieve the effect of promoting blood circulation.

Research Progress in the Study of Startle Reflex to Disease States.

The startle reflex is considered a primitive physiological reflex, a defense response that occurs in the organism when the body feels sudden danger and uneasiness, characterized by habituation and sensitization effects, and studies on the startle reflex often deal with pre-pulse inhibition (PPI) and sensorimotor gating. Under physiological conditions, the startle reflex is stable at a certain level, and when the organism is in a pathological state, such as stroke, spinal cord injury, schizophrenia, and other diseases, the reflex undergoes a series of changes, making it closely related to the progress of disease. This paper summarizes the startle reflex in physiological and pathological states by reviewing the databases of PubMed, Web of Science, Cochrane Library, EMBASE, China Biology Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, Wanfang Data, and identifies and analyzes the startle reflex and excessive startle reaction disorder.

Comparison of Cognitive Performance and Cardiac Function Between Three Different Rat Models of Vascular Dementia.

PURPOSE: Establishing an ideal animal model is essential for studying the pathogenesis, prevention and treatment of vascular dementia (VD). The present study was designed to compare the differences of behavior, cerebral blood flow (CBF), cardiac output and the levels of myocardial enzyme of three different VD rat models. METHODS: The rats were randomly divided into sham-operated group (SHAM), permanent bilateral common carotid artery occlusion group (BCCAO), BCCAO combined with sodium nitroprusside (2.0mg·kg-1) group (BCCAO+2.0SNP) and BCCAO combined with sodium nitroprusside (2.5mg·kg-1) group (BCCAO+2.5SNP). After operation, Morris water maze test, echocardiographic evaluation and the measurement of CBF were performed, then the levels of myocardial enzymes in serum were assessed during euthanasia. RESULTS: Compared with SHAM rats, the three VD model rats showed different degrees of cognitive impairment, lower cardiac output and CBF, and BCCAO rats showed higher levels of myocardial enzymes. Compared with BCCAO rats, the spatial learning ability of BCCAO+2.0SNP rats and BCCAO+2.5SNP rats was more severely impaired, while the levels of myocardial enzymes of BCCAO+2.0SNP rats were lower. Compared with BCCAO+2.0SNP rats, BCCAO+2.5SNP rats showed no significant difference in cognitive function and cardiac function. CONCLUSION: Our present study demonstrated that all of the three different VD rat models exhibited cognitive and cardiac function impairment. The BCCAO+2.0SNP model and BCCAO+2.5SNP model damaged the spatial learning ability more seriously. The BCCAO+2.5SNP model caused more comprehensive cognitive impairment. In addition, the BCCAO+2.0SNP model and BCCAO+2.5SNP model might cause more serious damage to cardiac function.

Improving Collateral Circulation: A Potential Adjunctive Strategy to Prevent or Slow the Progression of Vascular Dementia.

Vascular dementia (VaD), a cognitive disorder caused by cerebrovascular pathologies, is the most common cause of dementia in the elderly, being second only to Alzheimer's disease. Researches have shown that adequate cerebral blood flow (CBF) is the first condition for maintaining the structural integrity and normal function of the brain, and VaD is generally considered to be resulted from neuronal loss due to reduced CBF. Collateral circulation, a compensation mechanism for CBF, provides an alternative vascular pathway for blood to reach ischemic tissues, which has been confirmed to be associated with better clinical outcomes of ischemic diseases. At present, considerable effort has been devoted to enhancing the functional prognosis of acute ischemic stroke by improving collateral circulation. Since ischemic stroke is the primary contributor to VaD, it is necessary to explore whether improving collateral circulation is beneficial to prevent or slow the progression of VaD. This article reviews the compensatory characteristics of different levels of cerebral collateral circulation, addresses the relationship between collateral circulation and VaD, and highlights that improving collateral circulation may be a potential adjunctive strategy in preventing and slowing the progression of VaD.

Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro.

Vasomotor dysfunction is one of the key pathological aspects of shock and heart failure (HF). Shenfu injection (SFI) has been widely used for the treatment of shock and HF in China. Pharmacological studies have suggested that SFI can reduce peripheral circulation resistance and improve microcirculation. However, whether it has a regulatory effect on macrovascular has not been elucidated. In this study, we used thoracic aorta rings isolated from Wistar rats and the human umbilical vein cell line (EA.hy926) to explore the vasodilative activity of SFI and its potential mechanisms. The relaxation due to SFI was measured after pre-treatment with selective soluble guanylate cyclase (sGC) inhibitor or cyclooxygenase (COX) inhibitor and compared with the vasodilation effect of SFI only treated with norepinephrine (NE). The contents of NO, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), COX-1, 6-K-PGF1α, and caveolin-1 were evaluated respectively. Additionally, the level of eNOS mRNA and total eNOS and its phosphorylation were studied to investigate the potential mechanisms involved. Experimental results showed that SFI markedly attenuated NE-induced vasoconstriction but that this effect was significantly eliminated after pre-incubation with the selective sGC inhibitor 1-H-[1, 2, 4] oxadiazolo [4, 3-α] quinoxaline-1-one (ODQ), instead of the COX inhibitor indomethacin (INDO). SFI significantly increased the eNOS content and up-regulated the eNOS mRNA expression, while it did not affect the content of COX-1 and 6-K-PGF1α. SFI also markedly increased NO content but significantly reduced the content of ET-1 and caveolin-1 in the cell supernatant. Furthermore, it promoted the expression of total eNOS and the phosphorylation of eNOS at serine (Ser) 1177 but inhibited the phosphorylation at threonine (Thr) 495, which was significantly reversed by PI3K-specific inhibitor LY294002. In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications.