Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells

Abstract

BackgroundVascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time. Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently, it has been reported that SAL have an obvious hypoglycemic effect in diabetes and show a beneficial activity in diabetic vascular dysfunction. However, it remains unknown whether or not SAL treatment could directly reduce blood pressure in diabetes. Furthermore, it is not clear what is the molecular mechanism underlying the vascular protection of SAL treatment in diabetes.MethodsMale diabetic Goto-Kakizaki (GK) and non-diabetic control Wistar-Kyoto (WKY) rats were administrated with different dosages of SAL (50, 100 and 200 mg/kg/day) for 4 weeks. Contractile responsiveness of cerebral artery to KCl or 5-HT was investigated by Pressure Myograph System. The activity of CaL channel was investigated by recording whole-cell currents, assessing the expressions of CaL channel α1C-subunit and its downstream kinase, MLCK, at protein or mRNA levels.ResultsWe showed that administration of 100 mg/kg/day SAL for 4 weeks not only lowered blood glucose, but also reduced blood pressure and alleviated cerebrovascular contractile activity in diabetic GK rats, which suggested that SAL treatment may provide a combinational therapy for lowering blood glucose and reducing blood pressure in diabetes at the same time. Furthermore, SAL treatment markedly inhibited the function and expression of CaL channel in cerebral VSMCs isolated from diabetic GK rats or when exposed to hyperglycemia condition, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.ConclusionsThe present study provided evidences that SAL contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic GK rats by inhibition of CaL channel in smooth muscle cells, which may provide a novel approach to treat vascular complications in diabetic patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0135-8) contains supplementary material, which is available to authorized users.

Salidroside inhibits platelet function and thrombus formation through AKT/GSK3β signaling pathway

“…Salidroside is the main bioactive component in Rhodiola rosea and possesses several biological and pharmacological properties, such as anti-inflammatory, anti-oxidative, anti-aging, anti-cancer, anti-depressant, neuroprotective, and hepatoprotective activities [13,14]. In addition, salidroside has been shown to reduce blood pressure and alleviate cerebrovascular contractile activity in diabetic Rats [15], and attenuate oxidized low-density lipoprotein-induced endothelial cell injury [16] or vascular endothelial dysfunction [17]. Furthermore, salidroside has also been demonstrated to decrease atherosclerotic plaque formation in mice with deficiency of low-density lipoprotein receptor [18] and ameliorate chronic hypoxia-induced pulmonary arterial hypertension in mice [19].…”

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

“…The content of salidroside in the crude FLL power determined by HPLC ranges from 5.7 to 6.9 mg/g [ 42 ]. Currently, there are more than 400 publications investigating the biological activities of salidroside, including anti-diabetes [ 43 ], anti-obesity [ 44 ], anti-cancer [ 44 , 45 ], anti-osteoporosis [ 46 ], anti-arthritis-induced brain cognition deficits [ 47 ], anti-hypertension [ 48 , 49 ], and cardioprotective effects [ 50 ].…”

Inhibition of autophagy enhances synergistic effects of Salidroside and anti-tumor agents against colorectal cancer

“…Autophagy confers protective effect against toxicity of anti-tumor agents, thus it, to some extent, inhibits apoptosis of cancerous cells and results in chemo-resistance [ 17 ]. Sal has been emerged as an important plant extracts for the treatments of cancer and age-related diseases [ 18 ]. Our data showed that Sal inhibited cell viability of CRC, but only exerted modest effect on the apoptosis at a moderate concentration (1 μg/mL).…”

“…Previous study has demonstrated that Sal exerts anti-proliferative and pro-apoptotic effects against cancer cells [ 18 ]. However, the present study found that Sal also triggered autophagy of CRC cells, which counteracts the anti-tumor effects of Sal alone or in combination with anti-tumor agents (as shown in Fig.…”