Salvia Miltiorrhiza Group Research Articles

Effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism

Effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism

Effect of Salvia miltiorrhiza Combined with Aromatic Amino Acids on the Impaired Renal Function in Rats with Chronic Renal Failure

Background and Aim: At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Salvia miltiorrhiza (SM) is a very popular medicinal plant that has been extensively applied to treat various diseases. It also has been reported that lowering the aromatic aminoacids (AAA) in the protein diet can improve renal function in rodents with CRF. This study seeks to employ the use of SM combined with low aromatic amino acid diet (LA-AAD) for treatment of CRF in rats. Methods: Animals were assigned into 3 groups: Control, CRF and Experiment. CRF models were induced by 2.5% adenine administered by gavage for 8 weeks. Control and CRF group received normal protein diet (18.8% proteins, AAA 0.024%), and Experiment group was divided into 3 subgroups, being treated with SM (1.0g/kg/d) and LA-AAD (18% proteins, AAA 0.009%) differently. Proteinuria, blood urine nitrogen (BUN), serum and urine creatinine (Scr, Ucr) were measured and creatinine clearance rate (CCR) was calculated accordingly. Results: Proteinuria, BUN, Scr analyses showed amelioration of functional parameters and increased the CCR significantly in LA-AAD + SM group. Conclusion: These results showed that the combination of SM and LA-AAD could be beneficial to the improvement of renal function in CRF rats and this method can be a novel strategy for CRF treatment.

Salvia miltiorrhiza (SM) Injection Ameliorates Iron Overload-Associated Cardiac Dysfunction by Regulating the Expression of DMT1, TfR1, and FP1 in Rats.

Previous studies have found that Salvia miltiorrhiza (SM) injection have a protective effect on the iron overloaded (IO) heart. However, the mechanisms are not completely known. In the present study, we investigated the underlying mechanisms based on the iron transport-related proteins. The rats were randomly divided into five groups: control, IO group, low-dose SM group, high-dose SM group, and deferoxamine control group. Iron dextran was injected to establish the IO model. After 14 days of treatment, cardiac histological changes were observed by hematoxylin and eosin (H&E) staining. Iron uptake-related proteins divalent metal transporter-1 (DMT-1), transferrin receptor-1 (TfR-1), and iron export-related proteins ferroportin1 (FP1) in the heart were detected by Western blotting. The results showed that SM injection decreased cardiac iron deposition, ameliorated cardiac function, and inhibited cardiac oxidation. Most important of all, SM injection downregulated the expression of DMT-1 and TfR-1 and upregulated FP1 protein levels compared with the IO group. Our results indicated that reducing cardiac iron uptake and increasing iron excretion may be one of the important mechanisms of SM injection reducing cardiac iron deposition and improving cardiac function under the conditions of IO.

Salvia miltiorrhiza Injection Alleviates LPS-Induced Acute Lung Injury by Adjusting the Balance of MMPs/TIMPs Ratio.

Salvia miltiorrhiza injection (SMI) is a classical traditional Chinese medicine, which plays an active role in the treatment of many diseases such as promoting blood circulation, removing blood stasis, reducing inflammatory reaction, and improving acute lung injury (ALI). Previous studies have shown that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathophysiological process of ALI. However, the relationship between SMI and MMPs/TIMPs remains unclear. In this study, Wistar rats were randomly divided into control group (NC), Salvia miltiorrhiza group (SM), lipopolysaccharide group (LPS), and Salvia miltiorrhiza treatment group (Tsm). The four groups were subdivided into four time points (2, 6, 12, and 24 hours), and specimens were collected after animal sacrifice at each time point. Serum TNF-α and IL-6 levels were detected by ELISA. The degree of lung injury was determined by lung tissue hematoxylin-eosin staining, lung wet/dry weight (W/D) ratio, and lung permeability index. The changes in lung MMPs/TIMPs protein and mRNA were detected by Western blot and real-time quantitative PCR. The results showed that rats injected with LPS experience acute lung injury, and the ratio of MMPs/TIMPs in lung tissues increased gradually with time. In the Tsm group, the ratio of MMPs/TIMPs decreased gradually, and likewise, the balance was gradually restored, while indicators related to lung injury were gradually declined. These data suggest that SMI alleviates LPS-induced acute lung injury; this protective effect may be related to regulation of the balance of MMPs/TIMPs ratio.

Effect of Salvia Miltiorrhiza on Tmmrna Expression in Coronary Artery Tissue of Rats with High Salt Induced Blood Stasis

Objective To understand the effect of Salvia miltiorrhiza on the cardiovascular system by the expression of tissue TMmRNA, and to provide the scientific basis for the use of Salvia miltiorrhiza and a low salt diet for the prevention and treatment of cardiovascular and cerebrovascular diseases caused by high salt intake. Methods Thirty SD rats were randomly divided into a blank group, high salt group and Salvia miltiorrhiza group. The blank group was given intragastric distilled water and the high salt and the Salvia miltiorrhiza groups were treated with intragastric administration of 12% NaCl, for 30 consecutive days. Seven days before finishing this model, sterile water was injected intraperitoneally every afternoon in the blank group and the high salt group while, in the Salvia miltiorrhiza group, an injection of Salvia miltiorrhiza was given every afternoon. Then the animals were killed and the coronary arteries were removed. The expression of thrombomodulin mRNA (TMmRNA) in the coronary arteries of the rats in each experimental group was detected by the RT-PCR technique. Result Compared with the blank group, the expression of TMmRNA in the coronary tissue of the high salt group was obvious (p 0.05). Compared with the high salt group, the expression of TMmRNA in the coronary tissue of the Salvia miltiorrhiza was significantly different (p Conclusion Salvia miltiorrhiza can reduce the expression of TMmRNA in the tissue of blood stasis caused by high salt, promote the repair of blood vessel endothelium and blood movement, and can effectively improve the damaged coronary artery. Acknowledgements Supported by a project grant from Natural Science Foundation of China (Grant No. 81503476).

Salvia miltiorrhiza promotes osteogenic differentiation and proliferation of MC3T3-E1 preosteoblast by the extracellular signal-regulated kinase pathway

Objective To study whether or not Salvia miltiorrhiza (SM) can promote osteogenic differentiation and proliferation of MC3T3-E1 preosteoblast, and examine the relationship between the mechanism and extracellular signal-regulated kinase (ERK) signal pathway. Methods Different groups with different Salvia miltiorrhiza concentration (75, 150, 300 mg/L), the control group without Salvia miltiorrhiza, the proliferation of MC3T3-E1 cell was analyzed by cell counting kit-8 (CCK-8) assy, After 21days culture, the mineralization of MC3T3-E1 was examined by alizarin red staining, and the calcium nodes were counted. The mRNA expressions of bone gla protein (BGP) and runt related transcription factor 2 (Runx2) were examined by real-time fluorescence quantitative PCR (FQ-PCR). MC3T3-E1 cells were treated with SM in high concentration (300 mg/L), the protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) were detected by Western bloting. After added inhibitor of ERK1/2 pathway, the mRNA expressions of BGP and Runx2 were examined by qPCR again. Results Compared to control group, MC3T3-E1 preosteoblasts treated with SM had higher level of proliferation, and SM in 300 mg/L showed extremely significant difference (P=0.006). MC3T3-E1 cells treated with SM in different concentration had more calcium nodes than the control group (P=0.000), the quantity was (11.40±2.30), (21.00±2.24), (35.60±1.52), (6.40±1.14) (control group) respectively. In general, the groups treated with SM had higher level of the mRNA expressions of osteoblasts-related gene BGP and Runx2. For BGP mRNA, the raletive expression were (1.02±0.04), (1.11±0.07), (1.26±0.05)respectively, the two groups (treated with SM in 150 mg/L and 300 mg/L) haded significant statistical differences (P=0.019, P=0.000). For Runx2 mRNA, the raletive expression were (1.38±0.25), (2.28±0.13, (2.48±0.06)respectively, the group treated with SM in 75 mg/L showed significant differences (P=0.012), while the two groups treated with SM in 150 mg/L and 300 mg/L respectively, showed very significant statistical differences (P=0.000). The expression level of protein p-ERK1/2 was also remarkably elevated in SM group compared to the control group (P=0.014), and the quantity were (0.14±0.01), (0.10±0.01)respectively. The two groups were compared (300 mg/L SM, 300 mg/L SM+ PD98059), after added inhibitor of ERK pathway (PD98059), the mRNA expressions of BGP (1.87±0.05, 1.39±0.07)and Runx2 (1.87±0.05, 1.39±0.07) obviously decreased. Conclusion Salvia miltiorrhiza can promote osteogenic differentiation, proliferation and mineralization of MC3T3-E1 preosteoblast by the ERK signal pathway. Key words: Salvia miltiorrhiza; MC3T3-E1 preosteoblast; Extracellular signal-regulated kinase; Signal pathway

Expression of secreted frizzled-related protein-1 in patient with oral submucous fibrosis

Objective: To investigate the concentrations and clinical significance of secreted frizzled-related protein-1(SFRP1) insaliva and gingival crevicular fluid of patients with oral submucous fibrosis (OSF) as well as the expression of SFRP1 in patients' OSF buccal mucosa. Methods: Twenty OSF patients aged 20 to 40 years old were recruited and randomly divided into two experimental groups, of which were triamcinolone acetonide group and combined triamcinolone acetonide and salvia miltiorrhiza group, respectively. Ten healthy volunteers matchable in sex and age with the patients were recruited as control group. Concentrations of SFRP1 in saliva and gingival crevicular fluid were detected by enzyme-linked immunosorbent assay before and after a continuous treatment of 4 weeks. The visual analogue scale(VAS) pain scores and opening size were also recorded. The expression of SFRP1 in samples from OSF patients' buccal mucosa was also detected using immunohistochemical method. SPSS 16.0 was applied to analyze the results of the experiments. Results: The concentrations of SFRP1 in saliva and gingival crevicular fluid before treatment were (105.8±27.6) ng/L and (84.7±33.2) ng/L in triamcinolone acetonide group, and (86.6±23.2) ng/L and (97.0±23.2) ng/L in combining group, which were both significantly lower(P<0.01) than that in normal group([153.0±32.8] ng/L and [157.5±31.1] ng/L), respectively. The positive expression rate of SFRP1 in OSF group(10%[2/20]) was significantly lower than that of the control group(10/10)(P<0.01). After the treatment for 4 weeks, the concentrations of SFRP1 increased to (141.2±35.3) ng/L and (130.6±31.3) ng/L in triamcinolone acetonide group, and to (148.5±65.9) ng/L and (123.0±27.4) ng/L in combining group, which were both significantly higher than those of pre-treatment, respectively(P<0.01). Conclusions: The concentrations of SFRP1 in saliva and gingival crevicular fluid of OSF patients, which positively corelated to the expression of SFRP1 in OSF patients' buccal mucosa, were significantly lower than that of normal individuals and increased significantly after treatments of local injections of triamcinolone acetonide only or combined with salvia miltiorrhiza.

Effect of Salvia miltiorrhiza on retinopathy

ObjectiveTo explore the effect of Salvia miltiorrhiza on diabetic retinopathy (DR). MethodsDiabetic mice of natural incidence type with monogenic inheritance were selected. Alloxan was injected into the caudal vein of mice once to induce DR. The structural changes of retina tissue in normal mice, DR mice and mice with high, medium and low dose of Salvia miltiorrhiza injection were observed under microscope. Then the blood glucose concentration and malonaldehyde (MDA) content were detected. ResultsThere were some microaneurysms in retina of DR group, number of gangliocyte was decreased significantly, and cells were sparse and in disorder. After modeling, the blood glucose level of high-dose Salvia miltiorrhiza group (SM III group) was significantly different from DR group (P<0.01). Till the tenth week, the blood glucose level of all SM groups was decreased significantly compared with DR group (P<0.01). The effective rates of three SM groups were 93.8%, 76.4% and 50.3%, respectively. After ten weeks, MDA content of DR group was significantly higher than those of the normal control group and SM group (P<0.01), and medium and low dose SM groups had significantly higher MDA than that of normal control group (P<0.01). ConclusionsSalvia miltiorrhiza had certain protective effect on DR mice through the blood-ocular barrier.

Protective effects of Salvia miltiorrhiza against cisplatin-induced ototoxicity in guinea pigs

Objective The aim of the study was to investigate the protective effects of Salvia miltiorrhiza (SM) against cisplatin-induced ototoxicity in guinea pigs. Methods Thirty-nine guinea pigs were randomly divided into 3 groups. The first group (control group) received physiologic saline by intraperitoneal (i.p.) injection for 5 days. The second group (cisplatin group) was treated with cisplatin (2 mg/kg per day, i.p. injection) for 5 days. The third group (SM group) was given SM (8 g/kg per day, i.p. injection) for 2 days and then was given SM (8 g/kg per day, i.p. injection) and cisplatin (2 mg/kg per day, i.p. injection) for 5 days. Auditory brain stem response (ABR) and cochlea blood flow measurement were used to evaluate cochlea function. The structures of cochlea were observed by light microscope, scanning electron microscope, transmission electron microscope (TEM), and immunohistochemical examination. Results Cisplatin could cause severe acoustic damages including significant elevation of ABR threshold, substantial losses of outer hair cells and inner hair cells, and severe damage on the stria vascularis and spiral ganglion cells (SGCs). Although in SM group, the increased tendency of threshold was milder than that in cisplatin group. The damages in cochlea and stria vascularis were also less severe than those in cisplatin group. The expression of induced nitric oxide synthase in the cochlea and SGC in SM group was lower than that in cisplatin group. Conclusions Salvia miltiorrhiza can significantly reduce the cisplatin-induced side effects.

The effect of Salvia miltiorrhiza on vasoactive substance and hepatic function in severe acute pancreatitis

Objective To explore the changes of TXA2,PGI1 and hepatic function as well as effects of salvia miltiorrhiza on the patiente with server acute pancreatitis hepatic injury. Methods 57 patitnts with SAP were randomly divided ito control group and salvia miltiorrhiza treatment group. Patientes in control group received routine treatment, and the patients in salvia miltiorrhiza treatment group received additional salvia miltiorrhiza. The changes of plasma TXA2, PGI1 and hepatic function were conitored and compared between them. Results Plasma TXA2, the ratio of TXA2/PGI1 were significantly lower in the salvia miltiorrhiza group as compared with the control group on the 3,7,14 d after treatment( P ＜ 0.05 or P ＜ 0.01 ) ;but there were no obvious difference in the plasma PGI1 levels at each time point. The hepatic function in the salvia miltiorrhiza group were change normal after 14 days,which had signification difference than those in the control gruop P ＜ 0.05orP ＜0.01). Conclusion The salvia miltiorrhiza had a significant efficacy to treated the SAP hepatic injure. salvia miltiorrhiza may correct the imbalance between constrictionand factor and relaxation factor to improve the microcirculation of hepatic, and this was one of the mechanisms of salvia miltiorrhiza in treatment of SAP hepatic injure. Key words: Server acute pancreatitis; Hepatic injure; Salvia miltiorrhiza; TXA2/PGI1

Salvia miltiorrhiza inhibits intimal hyperplasia and monocyte chemotactic protein-1 expression after balloon injury in cholesterol-fed rabbits.

Antioxidants that prevent low density lipoproteins (LDL) from oxidation may inhibit atherosclerosis and post-angioplasty restenosis. Salvia miltiorrhiza (SM) has been shown to inhibit LDL oxidation and reduce atherosclerosis in cholesterol-fed rabbits. The effects of SM on neointimal hyperplasia and monocyte chemotactic protein-1 (MCP-1) expression after balloon injury were studied. Male New Zealand white rabbits were fed a 2% cholesterol diet together with daily SM (4.8 gm/kg body wt.) treatment (SM; n=10) or without SM as a control (C; n=9) for 6 weeks. Probucol-treated (0.6 gm/kg body wt.) rabbits (P; n=9) were used as a positive control group. A balloon injury of the abdominal aorta was performed at the end of the third week. Aortas were harvested at the end of 6 weeks. The plasma cholesterol levels were lowered in SM group. The neointimal hyperplasia in abdominal aortas was significantly inhibited in SM group [neointima/media area ratio: 0.63+/-0.05 (SM) versus 0.78+/-0.05 (C); P < 0.05] and in P group [0.45+/-0.02 (P) versus 0.78+/-0.05 (C); P < 0.05] when compared with C group. SM treatment significantly reduced MCP-1 mRNA and protein expression in balloon-injured abdominal aorta. These inhibitory effects on intimal response after balloon injury might be attributed to antioxidant capacity and cholesterol lowering effect of SM. SM treatment may offer some protection against post-angioplasty restenosis.

Effect of Salvia Miltiorrhiza on coronary collateral circulation in dogs with experimental acute myocardial infarction.

To evaluate the effect of Salvia Miltiorrhiza on coronary collateral circulation in dogs with experimental acute myocardial infarction, 12 dogs were randomly divided into Salvia Miltiorrhiza group (group D) and control group (group C). Acute myocardial infarction model was established in all dogs, Salvia Miltiorrhiza or saline was administered to the 2 groups respectively for 21 days. Coronary angiography was performed before and after ligation of coronary artery. The capillaries and distribution vessel density in tissue sections of myocardia were assessed. Angiography 2 h and 22 days after ligation of coronary artery revealed significant augmentation of collateral vessels, and capillaries and distribution vessel density in ischemic zone on day 22 showed statistically significant augmentation in group D as compared with that of controls (P < 0.05 and P < 0.01). It is concluded that Salvia Miltiorrhiza might improve the opening and formation of coronary collateral circulation of ischemic myocardia in dogs and thereby protecting myocardia from ischemia.