Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma Mitigate Renal Fibrosis： A Review / 中国实验方剂学杂志

Renal fibrosis， the final pathological outcome of end-stage chronic kidney diseases， is associated with inflammation， oxidative stress， epithelial-mesenchymal transdifferentiation （EMT）， and extracellular matrix deposition. It belongs to the categories of edema， ischuria， anuria and vomiting， and consumptive disease in traditional Chinese medicine （TCM）， with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides， polysaccharides， calycosin， salvianolic acid， and tanshinone， with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis， this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier， inhibiting EMT and mesangial cell proliferation， improving renal hemodynamics， and protecting renal function. Furthermore， the mechanisms were summarized. Specifically， Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism， alleviate endoplasmic reticulum stress and autophagy disorders， and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2 （Nrf2）/PTEN-induced kinase 1 （Pink1）， Nrf2/antioxidant response element （ARE）， tumor necrosis factor-α （TNF-α）/nuclear transcription factor-κB （NF-κB）， miR-21/Smad7/transforming growth factor beta （TGF-β）， Wnt/β-catenin， long non-coding RNA-taurine up-regulated gene 1 （lncRNA-TUG1）/tumor necrosis factor receptor-associated factor 5 （TRAF5）， Ras-related C3 botulinum toxin substrate 1 （Rac1）/cell division cycle protein 42 （CDC42）， Ras homolog （Rho）/Rho-associated coiled-coil containing protein kinase （ROCK）， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， peroxisome proliferator-activated receptor α （PPARα）/peroxisome proliferator-activated receptor γ coactivator l alpha （PGC-1α）， and p38 mitogen-activated protein kinase （p38 MAPK）. This review aims to provide references for the relevant research， give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma， and provide guidance for the clinical treatment of renal fibrosis.

Shenhua Tablet inhibits mesangial cell proliferation in rats with chronic anti-Thy-1 nephritis

BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.

Effect of Native and Modified Lipoproteins, and Albumin on Human Mesangial Cell Proliferation / 대한신장학회잡지

BACKGROUND: Modified lipoproteins may be involved in nephro- and glomerulosclerosis. Diabetic nephropathy-like lesions have also been induced in a rat model by glycated and glycoxidized albumin. In cultured rat or human mesangial cells, enhanced cell proliferation and production of mesangial matrix in response to lipoproteins and their modified forms have been demonstrated by [3H]-thymidine incorporation and cell counting assays. But these methods are relatively complex and most of them have used only one or two of the lipoprotein, albumin and their modified forms. METHODS: We investigated the effects of native and modifed lipoproteins, and albumin on cultured human mesangial cell proliferation using non-radioactive colorimetric method by MTS/PMS assay. Lipoproteins added were low density lipoprotein(LDL), high density lipoprotein(HDL), very low density lipoprotein(VLDL), oxidized LDL(oxidation with copper sulfate in vitro) and glycated LDL and we also used albumin, glycated albumin, and interleukin-1beta as a positive control. RESULTS: Interleukin-1beta promoted the proliferation of cultured human mesangial cells up to concentration 20 ng/mL. LDL induced the proliferation of mesangial cells in a concentration-dependent manner up to concentration 100 microgram/mL. HDL and VLDL had no significant proliferative effect. Oxidized LDL caused the proliferation of mesangial cells at low concentration up to concentration 25 microgram/mL. Addition of glycated LDL resulted in a concentration- dependent inhibition of mesangial cells. Albumin and glycated albumin inhibited the proliferation of mesangial cells at low concentration of 100 microgram/mL, but cell growth was increased at higher concentrations. CONCLUSION: We demonstrated the effects of the single and modified proteins on the proliferation of cultured human mesangial cell by relatively simple colorimetric method. Results were almostly identical to those of previous studies obtained by radioactive method or cell counting assay.

Regulation of recombinant interleukin-6 antisense RNA on glomerular mesangial cell / 中华肾脏病杂志

Objective To determine whether the recorabinant murine interleukin-6 antisense RNA (IL-6 RNAAS) can regulate the proliferation of murine glomerular mesangial cell (MC) and the expression of protein and IL-6 mRNA that derived from the MC. Methods IL-6 RNAAS was led into the package cell PA31; by lipofect AMINE. Presence of IL-6 RNAAS in the supernatant of the cultural PA3n cells was assured by G4u screening and PCR check. The MC proliferation, IL-6 activity and IL-6 mRNA expressionin of MC were detected by 3 H-thymidine, KD3,7 cell line and Northern blot respectively. Results The pse.udovirus liter in the PA317 cell supernatant reached 1 ?107 CFU/ml. The IL-6 RNAAS could incorporate into MC and was expressed. The 3H-thymidine incorporation, IL-6 mRNA expression and MC-derived IL-6 were significantly lower than that in control group. Conclusion IL-6 RNAAScan inhibit MC proliferation and regulate downward the secretion and expression of IL-6 in MC.

Experimental study on the inhibitory effect of IL-4 on IL-1?-induced mesangial cells proliferation in rat / 解放军医学杂志

Objective To observe the inhibitory effect of IL-4 on the IL-1?-induced rat mesangial cell proliferation, the release of PGE 2, and on the COX-2 mRNA and protein expression, so as to explore the related mechanism of anti-glomerulosclerosis. Methods Rat mesangial cell (MC) was cultured in vitro and the IL-1? -induced proliferation of MC was detected by MTT method. ELISA method was employed to measure the contents of PGE 2 in blank control group, IL-1? group, IL-4+IL-1? group, NS-398 group, NS-398+IL-1? group, indomethacin group, indomethacin+IL-1? group. The expression of mRNA and protein of COX-1 and COX-2 gene were detected by RT-PCR and Western blot, respectively. Results IL-1? could induce the proliferation of MC when the concentration was 0.1-100ng/ml in 12h, 24h and 48h. When its concentration was 2ng/ml, it had the strongest effect in 24h. All the IL-4, NS-398, indomethacin could inhibit IL-1? to induce MC producing PGE 2. The inhibitory rates are in proper order as: IL-4 (84.9%), NS-398(56.5%), and indomethacin(41.2%). Both IL-4 and NS-398 could obviously inhibit the expression of COX-2 mRNA and protein proved by RT-PCR and Western blot. Indomethacin could strongly inhibit the expression of COX-1 mRNA and protein, while only shew a weak inhibition on the expression of COX-2 mRNA and protein. Conclusion IL-4 could markedly inhibit the IL-1? -induced MC proliferation, down-regulate COX-2 gene, decrease the production of PGE 2, and thus take effect on anti-glomerulosclerosis.