Dose-dependent target diversion of Danhong injection on the Glu-GLT-1/Gly-GlyRα dynamic balance module of cerebral ischemia

Xu, Wenjuan; Zhang, Yingying; Yu, Yanan; Li, Bing; Liu, Jun; Wang, Pengqian; Wu, Hongli; Liu, Qiong; Wei, Ziyi; Xiao, Hongbin; Wang, Zhong

doi:10.1016/j.phrs.2018.07.020

Cited by 25 publications

(21 citation statements)

References 28 publications

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“…Existing studies have shown that DSS, SAA, SAB, and HSYA have the ability to scavenge free oxygen radicals, inhibit apoptosis, and prevent inflammation [5][6][7][8][9][10][11][12][13][14][15][16][17][18][25][26][27][28], thereby protecting against cerebral ischemic injury. Over the past few years, the Dan-Hong injection and its ingredients have been widely studied in clinical and basic research [30,[46][47][48]. However, there are few studies evaluating the pharmacokinetic parameters of the active ingredients in the Dan-Hong injection.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Ying

et al. 2019

Eur J Drug Metab Pharmacokinet

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Background and Objective Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. Methods Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. Results The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration-time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. Conclusion Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood-brain barrier during cerebral ischemia-reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

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Section: Discussionmentioning

confidence: 99%

“…Analysis of the components in the Dan-Hong injection and their pharmacodynamic effects has revealed that DSS, SAA, SAB, and HSYA are the main active ingredients [30,46,[49][50][51]. Therefore, a pharmacokinetic study of the these four active ingredients appeared to be reasonable and necessary.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Ying

et al. 2019

Eur J Drug Metab Pharmacokinet

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“…Safflower injection has many pharmacological effects, such as preventing ischemia-reperfusion injury, improving hemodynamics, reducing free radical generation, and increasing nitric oxide (NO) production. It has been widely used in many diseases, including coronary heart disease, heart failure, cerebral infarction, cerebral ischemia, cerebral hemorrhage, vertebral-basal artery ischemic vertigo, diabetic complications, and primary dysmenorrhea [24][25][26][27].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The results indicated that glutamate and glycine (Glu/Gly) was a biomarker, glycine receptor (GlyR)α was identified as an upstream target, and glutamate transporter-1 (GLT-1) was identified as a downstream target. GlyRα is the primary target for low doses of DHI, while GLT-1 is activated at dose accumulation [81]. Nuclear factor (erythrocyte-derived 2)-like 2 (Nrf2, also known as NFE2L2) activation upregulates a battery of cytoprotective genes by binding to antioxidant response elements (AREs) of target genes.…”

Section: Experimental Studies and Molecular Mechanismsmentioning

confidence: 99%

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

Feng

Wang

et al. 2019

Pharmacological Research

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Cardiovascular and cerebrovascular diseases are the main cause of mortality worldwide, currently with less than optimum therapeutic options. Danhong injection (DHI) is a medicinal preparation based on two eminent Chinese herbal medicines, Salviae Miltiorrhizae (Dan Shen; family: Lamiaceae) and Flos Carthami (Hong Hua; family: Compositae/Asteraceae). DHI has been mainly used in the clinical therapy of cardiovascular (such as acute coronary syndrome and angina pectoris) and cerebrovascular diseases (such as stroke) in China for many years. The pharmacological properties of DHI include anti-inflammatory, anti-oxidant, anti-coagulatory, hypolipidemic, anti-apoptotic, vasodilatory, and angiogenesis-promoting actions. DHI offers a safe and effective therapeutic agent against cardiovascular and cerebrovascular diseases by modulating multiple disease-relevant signaling pathways and molecular targets. Herein, we provide a comprehensive review of the phytochemistry, therapeutic effects, molecular mechanisms, and adverse reactions of DHI in cardiovascular and cerebrovascular diseases. We also highlight the latest pharmacological advances and therapeutic potential of this promising herb-derived cardiovascular drug preparation.

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“…TCM is a clinically proven medical practice that has been in existence for thousands of years [12][13][14]. DHI is a mixed extraction of Salvia miltiorrhiza (DS; Dan Shen; family: Lamiaceae) and Carthami Flos (HH; Hong Hua; family: Compositae /Asteraceae) [15][16][17]. DHI has been widely used as an important adjuvant for the treatment of cardiovascular and cerebrovascular diseases in China [14,18,19].…”

Section: Introductionmentioning

confidence: 99%

Investigating the multi-target pharmacological mechanism of danhong injection acting on unstable angina by combined network pharmacology and molecular docking

Guo

Zhou

et al. 2020

BMC Complement Med Ther

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Background: Danhong injection (DHI), which is one of the most well-known Traditional Chinese Medicine (TCM) injections, widely used to treat unstable angina (UA). However, its underlying pharmacological mechanisms need to be further clarified. Methods: In the present study, network pharmacology was adopted. Firstly, the relative compounds were obtained by a wide-scaled literatures-mining and potential targets of these compounds by target fishing were collected. Then, we built the UA target database by DisGeNET, DigSee, TTD, OMIM. Based on data, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were performed and screen the hub targets by topology. Furthermore, evaluation of the binding potential of key targets and compounds through molecular docking. Results: The results showed that 12 ingredients of DHI and 27 putative known therapeutic targets were picked out. By systematic analysis, identified 4 hub targets (TNF, TLR4, NFKB1 and SERPINE1) mainly involved in the complex treating effects associated with coagulation and hemostasis, cell membrane region, platelet alpha granule, NFkappa B signaling pathway and TNF signaling pathway. Conclusion: The results of this study preliminarily explained the potential targets and signaling pathways of DHI in the treatment of UA, which may help to laid a good foundation for experimental research and further clinical application.

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Dose-dependent target diversion of Danhong injection on the Glu-GLT-1/Gly-GlyRα dynamic balance module of cerebral ischemia

Cited by 25 publications

References 28 publications

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential

Investigating the multi-target pharmacological mechanism of danhong injection acting on unstable angina by combined network pharmacology and molecular docking

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