Down-regulation of P-glycoprotein expression contributes to an increase in Danshensu accumulation in the cerebral ischemia/reperfusion brain

Chong, Yating; Wang, Wenyan; Zhang, Leiming; Li, Chong; Yu, Pengfei; Wang, Hongsheng; Fu, Fenghua

doi:10.3892/mmr.2011.691

Cited by 3 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Danshensu+HSYA group was injected 3 ml of 7.5 mg/kg Danshensu plus 3 mg/kg HSYA diluted with 0.9% sodium chloride injection intraperitoneally. The dose selection in each group was based on previous pharmacodynamics studies [ 37 , 38 ]. The ratio between Danshensu and HSYA in the combined treatment was 2:1.…”

Section: Methodsmentioning

confidence: 99%

Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Ischemic stroke is a common cerebrovascular disease with substantial morbidity and mortality worldwide. However, therapeutic options to minimize the cerebral ischemia-reperfusion (I/R) injury are limited. In China, combination of herb Danshen (Salvia miltiorrhiza Bge) and Honghua (Carthamus tinctorius L.) is effective for stroke treatment in patients but its underlying mechanism requires further investigation. Our study was conducted to evaluate and explore the synergistic effects of two herb ingredients Danshensu and hydroxysafflor yellow A (HSYA) on cerebral ischemia-reperfusion (I/R) injury in rats. Rats were randomly assigned to the following five groups: sham group, model group, Danshensu group, HSYA group, and Danshensu+HSYA group. Under our experimental conditions in vitro, oxygen-glucose deprivation (OGD) model was established to determine the synergistic neuroprotective effects of Danshensu and HSYA. With such methods as neurological deficits scoring, TTC, HE and TUNEL staining, and ELISA detection, the results demonstrated that administration of either Danshensu or HSYA improved neurological defects and alleviated pro-inflammatory and oxidative stress reactions. Notably, combination of Danshensu and HSYA exerted more effective results than that used alone. Furthermore, western blot analysis results showed that Danshensu and HSYA combination displayed synergistic regulation on TLR4/NF-κB and Nrf2/HO-1 pathways. Consistently, Danshensu +HSYA group exhibits better neuroprotection in primary neurons with OGD model compared with Danshensu or HSYA group. Taken together, we found for the first time that Danshensu plus HSYA could achieve remarkable synergistic neuroprotective effects on I/R injury, which is related to the anti-inflammatory and antioxidant pathways.

show abstract

Section: Methodsmentioning

confidence: 99%

Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Furthermore, Tanshinone IIA, a phenolic acid of S. miltiorrhiza, has been shown to markedly reduce the increase in Ca 2+ levels evoked by H 2 O 2 and reverse H 2 O 2 -induced hippocampal LTP impairment (26). Previous studies have demonstrated that the long-term use of S. miltiorrhiza extract can not only decrease the volume of cerebral infarction but also improve learning and memory capacity; the underlying mechanism for these effects may be associated with the antioxidant property of S. miltiorrhiza (27,28). In the present study, S. miltiorrhiza -treated (four weeks, i.p) diabetic rats showed improvements in body weight and blood sugar level and an increased learning and memory capacity, as demonstrated by reductions in escape latency and increased platform-crossing frequency in 120 sec, compared with untreated diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats

Cai

Lian

Wang

et al. 2014

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

The aim of this study was to explore the protective effects of Salvia miltiorrhiza injection against learning and memory impairment in streptozotocin (STZ)-induced diabetic rats and the possible mechanism involved. Sprague Dawley male rats (n=30) were randomized into three groups: Diabetes, diabetes treated with S. miltiorrhiza injection and normal control. Diabetes was induced by an intraperitoneal injection of STZ (65 mg/kg). The S. miltiorrhiza injection-treated rats received an intraperitoneal injection of S. miltiorrhiza (5 ml/kg/day) while the rats of the other two groups were administered an intraperitoneal injection of the same volume of 0.9% saline for four weeks. After four weeks of treatment, the escape latency and search strategies in the rats were assessed by the Morris water maze test. The protein levels of mitogen-activated protein kinase phosphatase-1 (MKP-1) were also assessed by immunohistochemistry. Four weeks after the induction of diabetes, the body weight of the diabetic rats was significantly lower and the blood glucose concentration was significantly higher than that of the control rats. S. miltiorrhiza injection was observed to improve the blood glucose and learning ability (P<0.05). Compared with the control group, the expression of MKP-1 was significantly decreased in the hippocampal area of the diabetes group; S. miltiorrhiza injection-treated rats showed an increased expression compared with the diabetic rats, but the expression remained lower than that of the normal control group (P<0.05). In conclusion, S. miltiorrhiza injection can improve the learning and memory decline of diabetic rats. The changes in expression of MKP-1 under hyperglycemia may play a role in the protective effects of S. miltiorrhiza against dementia in diabetic rats.

show abstract

Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

et al. 2016

Molecules

View full text Add to dashboard Cite

Abstract:The active ingredients of salvia (dried root of Salvia miltiorrhiza) include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I) and hydrophilic (e.g., danshensu and salvianolic acid B) constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS) was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%-80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

show abstract

Down-regulation of P-glycoprotein expression contributes to an increase in Danshensu accumulation in the cerebral ischemia/reperfusion brain

Cited by 3 publications

References 14 publications

Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats

Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats

Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats

Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

Contact Info

Product

Resources

About