Efficacy and safety of Salvia miltiorrhiza (Salvia miltiorrhiza Bunge) and ligustrazine injection in the adjuvant treatment of early-stage diabetic kidney disease: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza and ligustrazine injection is a compound injection composed of the extract from Salvia miltiorrhiza and Ligusticum striatum (Ligusticum striatum DC.), has been frequently used for the adjuvant treatment of early-stage diabetic kidney disease (DKD) in China. Safety and efficacy studies in terms of evidence-based medical practice have become more prevalent in application to Chinese Herbal Medicine. It is necessary to assess the efficacy and safety of Salvia miltiorrhiza and ligustrazine injection in the adjuvant treatment of early-stage diabetic kidney disease by conducting a systematic review and meta-analysis of available clinical data. AIM OF THE STUDY: The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of Salvia miltiorrhiza and ligustrazine injection as an adjunctive therapy to conventional therapies for early-stage DKD. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to structure this study. We searched the English databases PubMed, Cochrane library, and Chinese databases including Chinese journal full text database (CNKI), China Biomedical Documentation Service System (SinoMed), Wanfang digital periodical full text database and Chinese Scientific Journal Database (VIP). Relevant studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed with RevMan 5.3 software after data extraction and the quality of studies assessment. The quality of the evidence was assessed with the Cochrane risk of bias tool. Sensitivity analysis and Egger's test were performed using Stata 15.0 software. RESULTS: A total of 22 trials were included with 1939 patients. Meta-analysis showed that compared with the control group of conventional western medicine alone, Salvia miltiorrhiza and ligustrazine injection combined with conventional western medicine can achieve better efficacy in the treatment of early-stage DKD, reduce urinary albumin excretion rate (12RCTs, 1181 participants; SMD = -1.82, 95% CI [-2.62, -1.01], P < 0.00001), serum creatinine (13RCTs, 1228 participants; MD = -13.21 µmol/L, 95% CI [-19.58, -6.83], P < 0.0001), ß2-microglobulin (9RCTs, 669 participants; SMD = -1.45, 95% CI [-2.43, -0.48], P = 0.003) and reduce interleukin-6 (4RCTs, 331 participants; MD = -6.38 ng/L, 95% CI [-9.03, -3.78], P < 0.00001), interleukin-18 (2RCTs, 177 participants; MD = -29.78 ng/L, 95% CI [-41.51, -18.05], P < 0.00001), tumor necrosis factor-α (4RCTs, 331 participants; MD = -18.03 ng/L, 95% CI [-22.96, -13.09], P < 0.00001), with statistical differences and alleviate the body inflammatory response effectively. CONCLUSION: Based on the existing evidence, that Salvia miltiorrhiza and ligustrazine injection in the adjuvant treatment of early-stage diabetic kidney disease is safe and effective. However, due to the limitation of the quality of the included studies, the above conclusions need to be further verified by more relevant randomized controlled trials with high-quality large samples.

Effectiveness of hypoxia-induced factor prolyl hydroxylase inhibitor for managing anemia in chronic kidney disease: a systematic review and meta-analysis.

PURPOSE: To meta-statistically compare the efficiency of hypoxia-induced factor prolyl hydroxylase inhibitor on hemoglobin, ferritin, hepcidin rate, and adverse events. METHODS: A systematic identification of literature was performed according to PRISMA guidelines on 4 academic databases: MEDLINE, Scopus, EMBASE, and CENTRAL. A meta-analysis evaluating the influence of hypoxia-induced factors was performed for patients undergoing/not undergoing hemodialysis. The analysis evaluated the efficacy of hypoxia-induced factors on hemoglobin, ferritin, hepcidin rate, and the number of adverse events. RESULTS: Out of 1052 records, 15 articles including 2045 patients (mean age 62.1 ± 5.4 years) were included in this review. The systematic review presents a 1a level of evidence supporting the use of hypoxia-induced factor for mediating anemia in patients with chronic kidney disease. The meta-analysis reveals medium to large beneficial effects of the hypoxia-induced factor on hemoglobin rate for patients receiving (0.72) and not receiving (1.04) hemodialysis. Moreover, the administration of hypoxia-induced factors was reported to reduce ferritin rate and the hepcidin rate, and the number of adverse events in patients with chronic kidney disease. CONCLUSION: The current meta-analysis recommends the use of hypoxia-induced factor prolyl hydroxylase inhibitor for managing anemia in chronic kidney disease.

Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine, extracted from Coptis Root and Phellodendron Chinese, has been frequently used for the adjuvant treatment of type 2 diabetes mellitus, hyperlipidemia, and hypertension in China. Safety and efficacy studies in terms of evidence-based medical practice have become more prevalent in application to Chinese Herbal Medicine. It is necessary to assess the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipidemia and hypertension by conducting a systematic review and meta-analysis of available clinical data. MATERIALS AND METHODS: We searched the English databases PubMed, ScienceDirect, Cochrane library, EMbase, etc., and Chinese databases including China biomedical literature database (CBM), Chinese Technology Journal Full-text Database, Chinese journal full text database (CNKI), and Wanfang digital periodical full text database. Relevant studies were selected based on the inclusion and exclusion criteria. Meta-analysis was performed with RevMan5.0 software after data extraction and the quality of studies assessment. RESULTS: Twenty-seven randomized controlled clinical trials were included with 2569 patients. There are seven subgroups in our meta-analysis: berberine versus placebo or berberine with intensive lifestyle intervention versus intensive lifestyle intervention alone; berberine combined with oral hypoglycemic versus hypoglycemic alone; berberine versus oral hypoglycemic; berberine combined with oral lipid lowering drugs versus lipid lowering drugs alone; berberine versus oral lipid lowering drugs; berberine combined with oral hypotensor versus hypotensive medications; berberine versus oral hypotensive medications. In the treatment of type 2 diabetes mellitus, we found that berberine with lifestyle intervention tended to lower the level of FPG, PPG and HbA1c than lifestyle intervention alone or placebo; the same as berberine combined with oral hypoglycaemics to the same hypoglycaemics; but there was no statistical significance between berberine and oral hypoglycaemics. As for the treatment of hyperlipidemia, berberine with lifestyle intervention was better than lifestyle intervention, berberine with oral lipid lowering drugs was better than lipid lowering drugs alone in reducing the level of TC and LDL-C, and raising the level of HDL-C. In the comparative study between berberine and oral lipid lowering drugs, there was no statistical significance in reducing the level of TC and LDL-C, but berberine shows better effect in lowering the level of TG and raising the level of HDL-C. In the treatment of hypertension, berberine with lifestyle intervention tended to lower the level of blood pressure more than the lifestyle intervention alone or placebo did; The same occurred when berberine combined with oral hypotensor was compared to the same hypotensor. Notably, no serious adverse reaction was reported in the 27 experiments. CONCLUSION: This study indicates that berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect. Considering the relatively low cost compared with other first-line medicine and treatment, berberine might be a good alternative for low socioeconomic status patients to treat type 2 DM, hyperlipidemia, hypertension over long time period. Due to overall limited quality of the included studies, the therapeutic benefit of berberine can be substantiated to a limited degree. Better methodological quality, large controlled trials using standardized preparation are expected to further quantify the therapeutic effect of berberine.

[Effect of Curcuma aromatica on epithelial-myofibroblast transdifferentiation of NRK-52E cells induced by TGF-beta1].

OBJECTIVE: To observe the antagonist effect of Curcuma Aromatica (CA) on renal tubular epithelial-myofibroblast transdifferentiation (EMT) induced by transforming growth factor-beta1 (TGF-beta1). METHODS: Normal renal tubular epithelial NRK-52E cells in vitro cultured were randomly divided into 6 groups, i.e., the normal control group (Group C), the TGF-beta1 induced model group (Group T), the low dose CA treated group (Group E1), the moderate dose CA treated group (Group E2), the high dose CA group (Group E3), and the Benazepril Hydrochloride Tablet treated group (Group Y). Except Group C, corresponding medication (with an action of 48 h) was administered to cells in the rest groups after they were induced by TGF-beta1 for 24 h. The morphological changes were observed by inverted phase contrast microscope. The distribution of beta-actin protein was detected by immunohistochemical assay. The mRNA expressions of alpha-smooth muscle actin (alpha-SMA) and E-cadherin (E-cad) were detected by real-time PCR. The concentration of fibronectin (FN) was detected by ELISA. RESULTS: After induced by TGF-beta1 for three days, hypertrophy and elongated cells in fusiform-shape occurred,with increased expressions of beta-actin protein in the cytoskeletal structure (P < 0.05), bundle fibrous structure occurred inside cytoplasm with significantly up-regulated intracellular alpha-SMA mRNA expressions (P < 0.05), E-cad mRNA expression decreased (P < 0.05), the FN content in the supernate increased (P < 0.05) in Group T. Compared with Group T, partial cells in Group E1, E2, and E3 showed fibrous changes, accompanied with decreased expression of beta-actin protein and FN concentration (P < 0.05). The expression of alpha-SMA mRNA increased and the expression E-cad mRNA decreased in Group E2 and E3 (both P < 0.05). But there was no statistical difference in the expression levels of E-cad and alpha-SMA mRNA (P > 0.05). Compared with Group E1, the expression of beta-actin protein and FN concentration decreased in Group E2 and E3 (P < 0.05). The expressions of alpha-SMA mRNA decreased and E-cad mRNA increased in Group E3 (P < 0.05). Compared with Group Y, the expression of beta-actin mRNA and FN concentration increased in Group E1 (P < 0.05); the expression of beta-actin mRNA increased in Group E3 (P < 0.05); the expression of E-cad mRNA decreased in Group E3 (P < 0.05). There was no statistical difference in the expression of alpha-SMA mRNA among Group E1, E2, and E3 (P > 0.05). CONCLUSION: CA could inhibit the occurrence of TGF-beta1 induced EMT, which could be used as an effective drug for treating chronic renal insufficiency.

The effects of kangxianling on renal fibrosis as assessed with a customized gene chip.

OBJECTIVE: To determine the mechanisms by which kangxianling (KXL) treats renal interstitial fibrosis using a customized gene chip. METHODS: Twelve out of 18 specific pathogen-free sprague dawley (SPF SD) rats underwent a unilateral ureteral occlusion. These rats were then randomly assigned into either the model unilateral ureteral obstruction (UUO) or kangxianling (KXL) group. The other six rats were assigned to the sham-operated group. The UUO and sham-operated groups were given normal saline via intragastric administration, whereas the KXL group was given KXL via intragastric administration. All rats were sacrificed for renal tissue collection (i.e., left nephridial tissue), and the detection of genetic changes with the customized chip. RESULTS: Compared to the sham-operated group, transforming growth factor-beta (TGF-beta), Smad2, and Smad3 genes were significantly up-regulated in the UUO group, with >1.5-fold rise (P < 0.01). The Smad7 gene was significantly reduced in the UUO versus sham-operated group, with a down-regulation of >1.5-fold (P < 0.01). In the KXL group, TGF-beta1, Smad2, and Smad3 genes were significantly reduced compared to the UUO group, with a down-regulation of >1.5-fold (P < 0.01), whereas the Smad7 gene was significantly increased compared to the UUO group, with an up-regulation of > 1.5-fold (P < 0.01). CONCLUSION: It was found that KXL can significantly reduce the gene levels of TGF-beta1, Smad2, and Smad3. Immunohistochemistry findings also revealed significantly lower TGF-beta1/Smads-mediated gene transcription activity. These findings suggest that KXL may negatively regulate the TGF-beta1/Smads signal pathway to inhibit the occurrence of renal fibrosis.

CXCL16 recruits bone marrow-derived fibroblast precursors in renal fibrosis.

Although fibroblasts are responsible for the production and deposition of extracellular matrix in renal fibrosis, their origin is controversial. Circulating fibroblast precursors may contribute to the pathogenesis of renal fibrosis, but the signaling mechanisms underlying the recruitment of bone marrow-derived fibroblast precursors into the kidney in response to injury are incompletely understood. Here, in the unilateral ureteral obstruction model of renal fibrosis, tubular epithelial cells upregulated the chemokine CXCL16 in obstructed kidneys, and circulating fibroblast precursors expressed the CXCL16 receptor, CXCR6. Compared with wild-type mice, CXCL16-knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors in obstructed kidneys. CXCL16-knockout mice also exhibited significantly fewer CD45-, collagen I-, and CXCR6-triple-positive fibroblast precursors in injured kidneys. Furthermore, targeted deletion of CXCL16 inhibited myofibroblast activation, reduced collagen deposition, and suppressed expression of collagen I and fibronectin. In conclusion, CXCL16 contributes to the pathogenesis of renal fibrosis by recruiting bone marrow-derived fibroblast precursors.

The clinical research on serum cystatin-C alteration on stage II chronic kidney disease with gubenquduyishen decoction treatment.

AIM OF THE STUDY: Gubenquduyishen (GBQDYS) decoction, the modified remedy of a classical Chinese prescription named Liuweidihuang decoction, has been clinically employed to treat nephrotic syndrome and chronic nephritis in chronic kidney disease (CKD). The present study was designed to examine whether GBQDYS decoction has a protective effect on renal function associated with the raised level of cystatin-C (Cys-C), serum creatinine (Scr), blood urea nitrogen (BUN) and decreased Glomerular filtration rate (GFR) in stage-II CKD. MATERIALS AND METHODS: A total of 68 stage-II CKD patients were randomly divided into two groups, the control group and the treatment group who received GBQDYS decoction as an additional therapy supplement. RESULTS: Following up on a period of 48 months, levels of serum Cys-C, Scr, and BUN were significantly reduced by the treatment of GBQDYS decoction and GFR was elevated in the treated group. Whereas not achieved in the control group, suggesting the nephro-protective activity of GBQDYS decoction. CONCLUSIONS: Taken together, these results demonstrated that GBQDYS decoction is able to protect renal function by delaying the progression of renal failure, and this may be used as an effective alternative treatment for CKD patients.

The change-over of yin-yang and gene regulation in kidney deficiency syndromes.

The present paper studies gene regulation in kidney deficiency syndromes from the simple Nephrotic Syndrome and with the principle of positive-negative regulation to control the change-over of yin-yang, the modern molecular biological techniques can be used, such as gene chip, representational difference analysis (RDA) and gene sequence analysis, so as to investigate the inner relationship between the genes and kidney deficiency syndromes and prove the effect given by these genes on the pathophysiological status of change-over of yin-yang in kidney deficiency syndromes. This philosophical approach and method can also be adopted for studies of the related genes in other TCM syndromes.