Magnesium lithospermate B improves renal hemodynamics and reduces renal oxygen consumption in 5/6th renal ablation/infarction rats

Abstract

BackgroundMagnesium lithospermate B (MLB) can promote renal microcirculation. The aim of the current project was to study whether MLB improves renal hemodynamics, oxygen consumption and subsequently attenuates hypoxia in rats induced by 5/6th renal Ablation/Infarction(A/I).MethodsChronic renal failure (CRF) was induced in male SD rats by the 5/6 (A/I) surgery. 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) + vehicle group (CRF group) and 5/6 (A/I) + MLB (CRF + MLB) group. 28 days after the surgery, rats were given with saline or 100 mg/kg MLB by i.p. injection for 8 weeks. The 24-h urinary protein (24hUp), serum creatinine (Scr), blood urine nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The protein expression of Fibronectin (FN), Collagen-I (Col-I), Connective Tissue Growth Factor(CTGF) and Interleukin-6 (IL-6) were measured by Western blot. Renal blood flow (RBF) and renal O2 consumption (QO2) indicated as sodium reabsorption (QO2/TNa) were detected before sacrifice. Renal hypoxia was assessed by measuring the protein expression of nNOS, HIF-1α and VEGF.ResultsMLB significantly reduced 24hUp, Scr, BUN, SBP and DBP levels in rats with CRF. The expression of FN, Col-I, CTGF and IL-6 were down-regulated by MLB treatment in rats with CRF. In comparison to sham operated rats, 5/6 (A/I) rats had significantly lower RBF, and MLB significantly increased RBF in rats with CRF. Moreover, QO2/TNa was higher in the CRF group as compared to that in the sham group, and it was significantly attenuated in the CRF + MLB group. MLB reversed the expression of nNOS (neuronal nitric oxide synthase), HIF-1α (hypoxia inducible factor-1) and VEGF in rats with CRF.ConclusionsMLB improves renal function, fibrosis and inflammation in CRF rats induced by 5/6 (A/I), which is probably related to the increase in RBF, reduction of oxygen consumption and attenuation of renal hypoxia in the remnant kidney with CRF.

Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling

“…Therefore, the inhibition of TGF-β signaling has received attention as a potential and useful therapy for pulmonary fibrosis [ 40 , 41 ]. Magnesium lithospermate B (MLB) has been reported to have anti-inflammatory, antioxidative and antifibrotic effects, especially in experimental models of liver fibrosis and renal or cardiovascular diseases, with great safety and tolerance [ 27 , 30 , 42 ]. More alternatives to treatments for pulmonary fibrosis will be provided if MLB is validated for alleviating pulmonary fibrosis.…”

“…Our previous research reported the protective and anti-inflammation effects of MLB on hepatic ischemia/reperfusion [ 28 ]. Other previous studies have shown that MLB might effectively attenuate liver or renal fibrosis by inhibiting the TGF-β pathway [ 29 , 30 , 31 ]. The severity and mortality of IPF patients are worse than those of patients with other forms of tissue fibrosis because of the high risk of the acute exacerbation of IPF and subsequent respiratory failure [ 32 ], and more alternatives for pulmonary fibrosis therapies will be available if MLB can effectively alleviate pulmonary fibrosis [ 33 ].…”

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

“…Compared with intravenous injection and conventional liposomes, long-circulating liposomes of Sal B prolong the retention time and drug concentration of Sal B in liver, kidney, and brain, showing higher bioavailability ( Pi et al, 2015 ). Sustained release of Sal B using scaffolds has also shown to enhance the osteogenic differentiation and osteogenesis of MSCs during spinal fusion or repair of bone tissue defects ( Li et al, 2016 ; Lin et al, 2019 ). The current multidisciplinary research provides more possibilities for improving the bioavailability of Sal B, which needs more cooperation in disciplines such as biomaterials and medicinal chemistry.…”

Mechanisms and Efficacy of Chinese Herbal Medicines in Chronic Kidney Disease

“…The officinal parts of Salvia miltiorrhiza Bunge are the root and rhizome. Salvia miltiorrhiza Bunge and its extractions have been shown to reduce proteinuria and attenuate kidney injury in several animal models of kidney disease, including 5/6th renal ablation/infarction ( Lin et al, 2019a ), renal ischemic reperfusion injury ( Ma et al, 2017 ), diabetic nephropathy ( Hou et al, 2017 ), and doxorubicin-induced nephropathy ( Liu et al, 2011 ). These effects associated with anti-inflammatory and antioxidative mechanisms have been observed in conjunction with these observed beneficial effects.…”