A review on the efficacy and mechanism of action of Shenkang injection against chronic kidney disease

Zou, Junju; Zhou, Xiao-Tao; Chen, Yan-Kun; Liu, Jialu; Wang, Cheng; Ma, Yue‐Rong; Wang, Li

doi:10.1016/j.biopha.2020.110833

Cited by 24 publications

(19 citation statements)

References 71 publications

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“…Therefore, the ER stress-mediated apoptosis signaling pathway is one of the important mechanisms of RIF. 3 BioMed Research International miltiorrhizae Bunge), and safflower (Carthamus tinctorius L.) [56]. Studies have found that certain Chinese medicines appear to be effective for RIF by intervening in the apoptosis signaling pathway mediated by ER stress.…”

Section: Er Stress-mediated Apoptosis In Rifmentioning

confidence: 99%

“…One such formula is Shenkang injection, which contains the extracts of four medicinal plants: rhubarb root and rhizome ( Rheum palmatum L.), astragalus root ( Astragalus membranaceus (Fisch.) Bunge), salvia root ( Salviae miltiorrhizae Bunge), and safflower ( Carthamus tinctorius L.) [ 56 ]. Studies have found that certain Chinese medicines appear to be effective for RIF by intervening in the apoptosis signaling pathway mediated by ER stress.…”

Section: Mechanisms Of Tcms In Treating Rif By Affecting the Er Stress-mediated Apoptosis Pathwaymentioning

confidence: 99%

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A Review of Traditional Chinese Medicine in Treating Renal Interstitial Fibrosis via Endoplasmic Reticulum Stress-Mediated Apoptosis

Liu

Chen

Han

et al. 2021

BioMed Research International

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Renal interstitial fibrosis (RIF) is the main pathological manifestation of end-stage renal disease. Recent studies have shown that endoplasmic reticulum (ER) stress is involved in the pathogenesis and development of RIF. Traditional Chinese medicine (TCM), as an effective treatment for kidney diseases, can improve kidney damage by affecting the apoptotic signaling pathway mediated by ER stress. This article reviews the apoptotic pathways mediated by ER stress, including the three major signaling pathways of unfolded protein response, the main functions of the transcription factor C/EBP homologous protein. We also present current research on TCM treatment of RIF, focusing on medicines that regulate ER stress. A new understanding of using TCM to treat kidney disease by regulating ER stress will promote clinical application of Chinese medicine and discovery of new drugs for the treatment of RIF.

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Section: Er Stress-mediated Apoptosis In Rifmentioning

confidence: 99%

Section: Mechanisms Of Tcms In Treating Rif By Affecting the Er Stress-mediated Apoptosis Pathwaymentioning

confidence: 99%

A Review of Traditional Chinese Medicine in Treating Renal Interstitial Fibrosis via Endoplasmic Reticulum Stress-Mediated Apoptosis

Liu

Chen

Han

et al. 2021

BioMed Research International

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“…Shenkang injection (SKI), approved by the State Food and Drug Administration of China (CFDA) in 1999, was used to treat CKD. SKI is composed of Rhei Radix et Rhizoma (Dahuang), Salviae Miltiorrhizae Radix et Rhizoma (Danshen), Astragali Radix (Huangqi), and Carthami Flos (Honghua) ( Zou et al, 2020 ). Dahuang possessed anti-inflammatory, anti-bacterial, anti-cancer, and anti-fibrotic effects ( Wang et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, it could be speculated that their anti-inflammatory and anti-oxidative effects were associated with CKD treatment of SKI. Recently, clinical studies have demonstrated that SKI could improve renal function in CKD, peritoneal dialysis patients with chronic renal failure (CRF), and diabetic nephropathy ( Zhang et al, 2017 ; Song et al, 2019 ; Wang et al, 2020a ; Qin et al, 2020 ; Zou et al, 2020 ; Ma, 2021 ). A seminal publication has highlighted that SKI treatment protected against CRF and symptoms related to CKD following treatment with traditional Chinese medicine was 73.05 and 98.00%, respectively, in a clinical trial of 2200 patients ( Qin et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways

Luo

Suo²,

Ren³

et al. 2021

Front. Pharmacol.

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Oxidative stress and inflammation are important and critical mediators in the development and progression of chronic kidney disease (CKD) and its complications. Shenkang injection (SKI) has been widely used to treat patients with CKD. Although the anti-oxidative and anti-inflammatory activity was involved in SKI against CKD, its bioactive components and underlying mechanism remain enigmatic. A rat model of adenine-induced chronic renal failure (CRF) is associated with, and largely driven by, oxidative stress and inflammation. Hence, we identified the anti-oxidative and anti-inflammatory components of SKI and further revealed their underlying mechanism in the adenine-induced CRF rats. Compared with control rats, the levels of creatinine, urea, uric acid, total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum were significantly increased in the adenine-induced CRF rats. However, treatment with SKI and its three anthraquinones including chrysophanol, emodin, and rhein could reverse these aberrant changes. They could significantly inhibit pro-fibrotic protein expressions including collagen I, α-SMA, fibronectin, and vimentin in the kidney tissues of the adenine-induced CRF rats. Of note, SKI and rhein showed the stronger inhibitory effect on these pro-fibrotic protein expressions than chrysophanol and emodin. Furthermore, they could improve dysregulation of IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways. Chrysophanol and emodin showed the stronger inhibitory effect on the NF-κB p65 protein expression than SKI and rhein. Rhein showed the strongest inhibitory effect on p65 downstream target gene products including NAD(P)H oxidase subunits (p47phox, p67phox, and gp91phox) and COX-2, MCP-1, iNOS, and 12-LO in the kidney tissues. However, SKI and rhein showed the stronger inhibitory effect on the significantly downregulated anti-inflammatory and anti-oxidative protein expression nuclear Nrf2 and its target gene products including HO-1, catalase, GCLC, and NQO1 in the Keap1/Nrf2 signaling pathway than chrysophanol and emodin. This study first demonstrated that SKI and its major components protected against renal fibrosis by inhibiting oxidative stress and inflammation via simultaneous targeting IƙB/NF-ƙB and Keap1/Nrf2 signaling pathways, which illuminated the potential molecular mechanism of anti-oxidative and anti-inflammatory effects of SKI.

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“…Shenkang injection (SKI) has been approved by the National Medical Products Administration for the treatment of chronic kidney disease (CKD) as a modern preparation of Chinese patent medicine (Z20040110) and has been widely used in China to treat renal tubulointerstitial fibrosis (TIF) in patients with CKD for almost 20 years ( Song et al, 2019 ; Zou et al, 2020 ). In a previous study, Xu et al reported that SKI, and its major active component emodin, can inhibit the proliferation and apoptosis of mesangial cells induced by high glucose (HG) conditions ( Xu et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Renal Tubular Epithelial Mesenchymal Transition and Endoplasmic Reticulum Stress-Induced Apoptosis with Shenkang Injection Attenuates Diabetic Tubulopathy

et al. 2021

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Background: The proximal renal tubule plays a critical role in diabetic kidney disease (DKD) progression. Early glomerular disease in DKD triggers a cascade of injuries resulting in renal tubulointerstitial disease. These pathophysiological responses are collectively described as diabetic tubulopathy (DT). Thus, therapeutic strategies targeting DT hold significant promise for early DKD treatment. Shenkang injection (SKI) has been widely used to treat renal tubulointerstitial fibrosis in patients with chronic kidney disease in China. However, it is still unknown whether SKI can alleviate DT. We designed a series of experiments to investigate the beneficial effects of SKI in DT and the mechanisms that are responsible for its effect on epithelial-to-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress-induced apoptosis in DT.Methods: The modified DKD rat models were induced by uni-nephrectomy, streptozotocin intraperitoneal injection, and a high-fat diet. Following the induction of renal injury, these animals received either SKI, rosiglitazone (ROS), or vehicle, for 42 days. For in vitro research, we exposed NRK-52E cells to high glucose (HG) and 4-phenylbutyric acid (4-PBA) with or without SKI or ROS. Changes in parameters related to renal tubular injury and EMT were analyzed in vivo. Changes in the proportion of apoptotic renal tubular cells and ER stress, and the signaling pathways involved in these changes, were analyzed both in vivo and in vitro.Results: SKI and ROS improved the general condition, the renal morphological appearance and the key biochemical parameters, and attenuated renal injury and EMT in the rat model of DKD. In addition, SKI and ROS alleviated apoptosis, inhibited ER stress, and suppressed PERK-eIF2α-ATF4-CHOP signaling pathway activation both in vivo and in vitro. Notably, our data showed that the regulatory in vitro effects of SKI on PERK-eIF2α-ATF4-CHOP signaling were similar to those of 4-PBA, a specific inhibitor of ER stress.Conclusion: This study confirmed that SKI can alleviate DT in a similar manner as ROS, and SKI achieves this effect by inhibiting EMT and ER stress-induced apoptosis. Our findings thereby provide novel information relating to the clinical value of SKI in the treatment of DT.

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A review on the efficacy and mechanism of action of Shenkang injection against chronic kidney disease

Cited by 24 publications

References 71 publications

A Review of Traditional Chinese Medicine in Treating Renal Interstitial Fibrosis via Endoplasmic Reticulum Stress-Mediated Apoptosis

A Review of Traditional Chinese Medicine in Treating Renal Interstitial Fibrosis via Endoplasmic Reticulum Stress-Mediated Apoptosis

Shenkang Injection and Its Three Anthraquinones Ameliorates Renal Fibrosis by Simultaneous Targeting IƙB/NF-ƙB and Keap1/Nrf2 Signaling Pathways

Inhibition of Renal Tubular Epithelial Mesenchymal Transition and Endoplasmic Reticulum Stress-Induced Apoptosis with Shenkang Injection Attenuates Diabetic Tubulopathy

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