Rhubarb Enema Attenuates Renal Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Alleviating Indoxyl Sulfate Overload

Lu, Zhaoyu; Zeng, Yuqun; Lu, Fuhua; Liu, Xusheng; Zou, Chuan

doi:10.1371/journal.pone.0144726

Cited by 28 publications

(23 citation statements)

References 23 publications

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“…33 Previous studies have indicated that Rhubarb has a promising protective effect against lung and renal fibrosis. 34,35 AE is an active compound in the plant rhubarb, 36 which is a traditional medicine used widely in the treatment of a variety of diseases in China. 37 Our study showed for the first time that AE protected against renal injury in a UUO model.…”

Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

Dou

Liu

et al. 2019

Rejuvenation Research

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Fibrosis is the major pathological feature of chronic kidney disease (CKD). Aloe-emodin (AE), one of the main active compounds in Rhubarb, is widely used for renal protection. However, mechanisms implied in the modulation of kidney fibrosis after AE treatment for CKD remain elusive. Here, we explored the protective effects of AE for renal fibrosis and the involved mechanisms in vivo and in vitro. The renal fibrosis mice model was established by unilateral ureteral obstruction (UUO). We found that AE administration significantly ameliorated UUO-induced impairment of kidney, evidenced by improved histopathological abnormalities, body weight, and abnormal renal function in mice model. Immunohistochemical staining showed that TGF-β1 and Fibronectin expressions were significantly decreased in UUO mice compared with sham group. Meanwhile, we found that AE suppressed the activation of the PI3K/Akt/mTOR pathway induced by TGF-β1 in vivo. AE improved cell survival and decreased the level of fibrosis-related proteins under TGF-β1-induced fibrosis in HK-2 cells as well as in vitro. Furthermore, both wortmannin, an inhibitor of PI3K, and short-hairpin RNAs of PI3K knockdown abrogated TGF-β1-induced phosphorylation of Akt and mTOR, and decreased the suppression of fibrosis. These findings indicated that AE alleviated fibrosis by inhibiting PI3K/Akt/mTOR pathway in vivo and in vitro, which may provide a potential therapeutic option for CKD.

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Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

Dou

Liu

et al. 2019

Rejuvenation Research

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“…Gubenxiezhuo is a mixture of Chinese medicine, including prepared rhubarb, monkshood, red ginseng, concha ostreae, carthamus tinctorious, and dandelion. The previous study has been documented that rhubarb decrease the renal tubulointerstitial in 5/6 neophrectomized rat via decreasing indoxyl sulfate overload (Lu, Zeng, Lu, Liu, & Zou, ). Red ginseng decreases pro‐inflammatory mediators in LPS‐treated macrophage to against endotoxic shock (Yayeh et al, ).…”

Section: Discussionmentioning

confidence: 96%

Influence of colonic dialysis using Gubenxiezhuo on the distribution of gut microflora in uremia rats

Tang

et al. 2018

Journal Cellular Physiology

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Objective This study aimed to explore the underlying function of Gubenxiezhuo dialysis on the distribution of gut microflora uremia. Methods A uremia rat model was constructed, and the morphology of renal tissue was determined using the hematoxylin‐eosin (H&E) staining. Moreover, the blood samples were collected and the expression of IL‐1β, IL‐6, and CRP was determined using enzyme‐linked immunosorbent assay. Following these experiments, the gut tissues of rats were collected and the distribution of gut microbiota was explored using real‐time PCR. Results Compared with the control group, inflammatory infiltration, apoptosis, and bleeding were significantly upregulated in kidney of uremia rats, and Gubenxiezhuo dialysis could obviously ameliorate these changes. Expression of IL‐1β, IL‐6, and CRP were significantly elevated in uremic rats and Gubenxiezhuo could significantly attenuate these elevations (p < 0.01). In addition, Gubenxiezhuo dialysis also could attenuate the upregulations of Acinetobacter, Bacillus cereus, Proteus vulgaris, Shigella flexneri, and Escherichia coli , and the downregulation of Bifidobacterium, Lactobacillus, and Helicobacter in the uremia rats ( p < 0.05). Conclusion Gubenxiezhuo dialysis could significantly ameliorate the inflammatory to modulate the distribution of gut microbiota in uremia.

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“…In TCM, it has been considered that prepared rhubarb can clear heat away and discharge turbidity, and promote blood circulation and purging. One previous study indicated that prepared rhubarb inhibited renal tubulointerstitial fibrosis, and ameliorated renal oxidative stress and inflammatory injury [20]. When used in prescription in TCM, peach kernel can promote blood circulation and eliminate blood stasis.…”

Section: Discussionmentioning

confidence: 99%

Shenduning Granule Attenuates Renal Injury from Oxidative Stress through the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway

Xiaojun¹,

Hu²

2019

Pharmacology

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Background: Systemic oxidative stress has been reported to play a central role in the pathogenesis of kidney function decline. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is one of the important endogenous antioxidant stress pathways in cells. This study aims to investigate whether shenduning granule can ameliorate oxidative stress in kidney tissues by activating the Nrf2/ARE pathway, and explores the detailed underlying mechanism. Methods: A total of 120 male Sprague-Dawley rats were randomly assigned to the sham-operated and operation groups. Rats in the operation group underwent 5/6 nephrectomy. Two weeks later, rats in the operation group were further randomly divided into 5 groups: model group, low-dose, medium-dose and high-dose shenduning granule groups, and losartan group. Rats in each group were given the same volume of corresponding liquid orally. Serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein, malondialdehyde (MDA) and superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl-cysteine synthetase (γ-GCS) were determined. Results: Shenduning granule could markedly elevate HO-1, NRF2, γ-GCS and SOD (p < 0.05), and significantly decreased MDA, 24-h urinary protein, SCr and BUN in rats (p < 0.05). Conclusion: Shenduning granule can improve renal antioxidative stress activity in rats, exhibiting a renoprotective effect. The potential mechanism is likely exerted by the activation of the Nrf2/ARE pathway.

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Rhubarb Enema Attenuates Renal Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Alleviating Indoxyl Sulfate Overload

Cited by 28 publications

References 23 publications

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

Influence of colonic dialysis using Gubenxiezhuo on the distribution of gut microflora in uremia rats

Shenduning Granule Attenuates Renal Injury from Oxidative Stress through the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway

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