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Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

Fan HY, Yang MY, Qi D, Zhang ZK, Zhu L, Shang-Guan XX, Liu K, Xu H, Che X - Sci Rep (2015)

Bottom Line: Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury.Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology.The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Yantai University, 264005 Yantai, Shandong Province, China.

ABSTRACT
Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

No MeSH data available.


Related in: MedlinePlus

The effect of SAA on podocin, p-IκBα, IκBα and NF-κB p65 protein expressions.a and b: Protein bands; c–f: podocin, p-IκBα, IκBα and NF-κB p65 protein expressions relative densities to β-actin. Data are expressed as mean ± SD (n = 3, and n = 4 for NF-κB p65). #P < 0.05 vs. Control; *P < 0.05 vs. DOX alone. Full-length blots are presented in Supplementary Figure 5a and 5b.
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f5: The effect of SAA on podocin, p-IκBα, IκBα and NF-κB p65 protein expressions.a and b: Protein bands; c–f: podocin, p-IκBα, IκBα and NF-κB p65 protein expressions relative densities to β-actin. Data are expressed as mean ± SD (n = 3, and n = 4 for NF-κB p65). #P < 0.05 vs. Control; *P < 0.05 vs. DOX alone. Full-length blots are presented in Supplementary Figure 5a and 5b.

Mentions: As shown in Fig. 5, after DOX administration, p-IκBα and NF-κB p65 protein levels in the DOX-only rats were increased as compared with the control rats, while IκBα expression was decreased, which suggested the activation of NF-κB. In contrast, treatment with SAA down-regulated the expression of p-IκBα and NF-κB p65 while up-regulating the IκBα expression. In addition, a lower expression of podocin, an important podocyte protein involves in the development of proteinuria25, was also found in DOX-only rat. SAA significantly recovered the expression level of podocin (P = 0.046).


Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

Fan HY, Yang MY, Qi D, Zhang ZK, Zhu L, Shang-Guan XX, Liu K, Xu H, Che X - Sci Rep (2015)

The effect of SAA on podocin, p-IκBα, IκBα and NF-κB p65 protein expressions.a and b: Protein bands; c–f: podocin, p-IκBα, IκBα and NF-κB p65 protein expressions relative densities to β-actin. Data are expressed as mean ± SD (n = 3, and n = 4 for NF-κB p65). #P < 0.05 vs. Control; *P < 0.05 vs. DOX alone. Full-length blots are presented in Supplementary Figure 5a and 5b.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508635&req=5

f5: The effect of SAA on podocin, p-IκBα, IκBα and NF-κB p65 protein expressions.a and b: Protein bands; c–f: podocin, p-IκBα, IκBα and NF-κB p65 protein expressions relative densities to β-actin. Data are expressed as mean ± SD (n = 3, and n = 4 for NF-κB p65). #P < 0.05 vs. Control; *P < 0.05 vs. DOX alone. Full-length blots are presented in Supplementary Figure 5a and 5b.
Mentions: As shown in Fig. 5, after DOX administration, p-IκBα and NF-κB p65 protein levels in the DOX-only rats were increased as compared with the control rats, while IκBα expression was decreased, which suggested the activation of NF-κB. In contrast, treatment with SAA down-regulated the expression of p-IκBα and NF-κB p65 while up-regulating the IκBα expression. In addition, a lower expression of podocin, an important podocyte protein involves in the development of proteinuria25, was also found in DOX-only rat. SAA significantly recovered the expression level of podocin (P = 0.046).

Bottom Line: Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury.Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology.The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Yantai University, 264005 Yantai, Shandong Province, China.

ABSTRACT
Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

No MeSH data available.


Related in: MedlinePlus