Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid

Mao, Zhimin; Shen, Shanmei; Wan, Yi‐Gang; Sun, Wei; Chen, Hao-Li; Huang, Mengmeng; Yang, Jingjing; Wu, Wei; Tang, Haitao; Tang, Renmao

doi:10.1016/j.jep.2015.07.036

Cited by 76 publications

(75 citation statements)

References 32 publications

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“…ASA decreased the phosphorylation of p38 and ERK, but it did not affect the phosphorylation of JNK ( Figure 5A). We are interested in the role of p38 in ASA inhibiting autophagy because of its importance in fibrosis [12,13] . The p38 inhibitor SB203580 increased LC3-II levels in basal and ASA-treated CFs ( Figure 5B), which suggested that p38 regulated autophagy.…”

Section: Asa Alleviates Cf Proliferation By Inhibiting Autophagymentioning

confidence: 99%

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Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

Liu

Sun

et al. 2017

Acta Pharmacol Sin

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Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg -1 ·d -1, ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice. The mechanisms underlying ASA's anti-fibrotic effect were further analyzed in neonatal cardiac fibroblasts (CFs) exposed to hypoxia in vitro. ASA (0.5-5 mmol/L) dose-dependently inhibited the proliferation and Akt phosphorylation in the CFs. In addition, ASA significantly inhibited CF apoptosis, and decreased the levels of apoptosis markers (cleaved caspase 3 and Parp1), which might serve as a side effect of anti-fibrotic effect of ASA. Furthermore, ASA dose-dependently inhibited the autophagy in the CFs, as evidenced by the reduced levels of autophagy marker LC3-II. The autophagy inhibitor Pepstatin A (PepA) promoted the inhibitory effect of ASA on CF proliferation, whereas the autophagy inducer rapamycin rescued ASA-caused inhibition of CF proliferation, suggesting an autophagydependent anti-proliferative effect of ASA. Both p38 inhibitor SB203580 and ROS scavenger N-acetyl-cysteine (NAC) significantly decreased Akt phosphorylation in CFs in the basal and hypoxic situations, but they both significantly increased LC3-II levels in the CFs. Our results suggest that an autophagy-and p38/ROS-dependent pathway mediates the anti-cardiac fibrosis effect of ASA in CFs. As PepA and SB203580 did not affect ASA-caused inhibition of CF apoptosis, the drug combination will enhance ASA's therapeutic effects.

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Section: Asa Alleviates Cf Proliferation By Inhibiting Autophagymentioning

confidence: 99%

“…In addition, p38 activation is involved in the fibrosis of various organs. Inhibition of p38 can attenuate renal fibrosis, and the activation of p38 can promote liver fibrosis [12,13] , although whether p38 participates in the ASAinduced anti-fibrosis process and its relationship with autophagy remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

Liu

Sun

et al. 2017

Acta Pharmacol Sin

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“…Cumulative evidence suggests that these managements can preserve renal function and prevent or slow the progression of DN (15)(16)(17). Isorhamnetin (ISO) is a plant flavonoid abundant in herbal medicinal plants, such as Hippophae rhamnoides L. In recent Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model studies, ISO exhibited strong antioxidant and anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

et al. 2016

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Abstract. The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

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“…Reactive oxygen species (ROS), caused by oxidative stress, play a major part in DN. Regulation focused on oxidative stress and ROS can ameliorate urinary albumin and renal dysfunction including blood urea nitrogen and uric acid in DN rats (Mao et al, 2015). In addition, reduction of oxidative stress attenuates glomerulus hypertrophy and expansion of the mesangial area, swell and effacement of foot process (Cai et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…The nuclear factor erythroid-2-related factor 2 (Nrf2) has been shown to be the important mechanism to alleviate oxidative stress (Ma, 2013). Nrf2 is a transcription factor that regulates the expression of various cytoprotective enzymes.…”

Section: Introductionmentioning

confidence: 99%

Salvia miltiorrhizaLipophilic Fraction Attenuates Oxidative Stress in Diabetic Nephropathy through Activation of Nuclear Factor Erythroid 2-Related Factor 2

Marikar

et al. 2017

Am. J. Chin. Med.

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Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus. To mimic the hyperglycemic conditions in DN patients, we used high glucose (25 mmol/L) media to stimulate mouse mesangial cells (MMCs), and EASM inhibited high glucose-induced reactive oxygen species. We also observed that EASM enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), which mediated the antioxidant response, and its downstream gene heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) with concomitant decrease of expression of kelch-like ECH-associated protein 1 (keap1) both in vitro and in vivo. Taken together, these results suggest that EASM alleviates the progression of DN and this might be associated with activation of Nrf2.

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Huangkui capsule attenuates renal fibrosis in diabetic nephropathy rats through regulating oxidative stress and p38MAPK/Akt pathways, compared to α-lipoic acid

Cited by 76 publications

References 32 publications

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

Aspirin alleviates cardiac fibrosis in mice by inhibiting autophagy

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

Salvia miltiorrhizaLipophilic Fraction Attenuates Oxidative Stress in Diabetic Nephropathy through Activation of Nuclear Factor Erythroid 2-Related Factor 2

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