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      Radix Puerariae and Fructus Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K

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          Abstract

          Background

          Radix puerariae (RP) is a herbal medicines for diabetes, mainly because of anti-oxidative, insulin resistance and hypoglycemic effect. Fructus crataegi (FC) also possesses strong antioxidant activity in vitro. This study focused on the effects of herbal mixture of RP and FC (RPFC) on renal protection through a diabetic rat model.

          Methods

          Type 2 Diabetic model was established with high fat diet followed by injecting rats a low dose of STZ (25 mg/kg body weight). Rats were randomly divided into five groups: normal, high fat diet, diabetes mellitus, high fat diet plus RPFC prevention, and RPFC prevention before diabetes mellitus. RPFC was given to rats daily by intragastric gavage. The blood bio-chemical index and renal pathological changes were examined. The later includes hematoxylin and eosin staining, periodic acid schiff staining, and Masson trichrome staining. Protein levels of were determined by Western blot and immunohistochemical staining. mRNA levels were detected by RT-PCR.

          Results

          Rats prevented with RPFC resulted in decreasing blood glucose with corresponding vehicle treated rats. Glomerulus mesangial matrix expansion, renal capsule constriction, and renal tubular epithelial cell edema were less severe following RPFC prevention. Moreover, RPFC prevention reduced protein levels of PI3K, AKT, α-SMA and collagen IV in the kidney of diabetic rats.

          Conclusion

          Combined prevention with RPFC may inhibit the PI3K/AKT pathway in the kidney, thereby prevent renal injury in diabetic rats.

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          Most cited references29

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          Expression and cellular distribution of TLR4, MyD88, and NF-κB in diabetic renal tubulointerstitial fibrosis, in vitro and in vivo.

          Inflammation and extracellular matrix hyperplasia are crucial in the pathogenesis of tubulointerstitial fibrosis (TIF) involved in diabetic nephropathy (DN). Macrophage accumulation plays a major role, but whether immune factors contribute to DN pathogenesis is not well understood. This study aimed to investigate TLR4-MyD88-NF-κB-dependent pathway's involvement in TIF pathogenesis.
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            Effects of puerarin in STZ-induced diabetic rats by oxidative stress and the TGF-β1/Smad2 pathway.

            The present study aimed to investigate the effects of pueraria on streptozotocine (STZ)-induced renal damage and its possible mechanisms. Wistar rats were randomly divided into five groups: the normal control group, diabetes untreated model group, two dosages (140 and 200 mg per kg bw per day) of puerarin treatment groups and a positive control group. Rats were studied 30 days after the STZ treatment, and the diabetes untreated model group presented significantly higher kidney index, blood glucose, triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), interferon-γ (IFN-γ), and IFN-γ/IL-4 levels, lower body weight, fasting blood insulin (FPI), IL-4, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels and worse renal function (higher blood urea nitrogen (BUN), serum creatinine (SCr), urine protein (UP) levels and glomerular extracellular matrix (relative area)) compared with the normal control group (p < 0.05). Furthermore, RT-FQ-PCR and western blot analyses showed that TGF-β1, Smad2, CTGF and FN protein and mRNA expression was significantly increased in the diabetes untreated model group compared with the normal control group. In contrast, the puerarin treatment dose-dependently significantly decreased the kidney index, blood glucose, TG, TC, MDA, IFN-γ, and IFN-γ/IL-4 levels, increased the body weight, FPI, IL-4, SOD, CAT, GSH-Px and NO levels and improved the renal function (lower BUN, SCr, UP levels and glomerular extracellular matrix (relative area)) in puerarin treatment groups (p < 0.05). In addition, the mRNA and protein expression of TGF-β1, Smad2, CTGF and FN was downregulated. It can be concluded that puerarin exerted its anti-diabetic effect on the STZ-treated rats through the inhibition of the TGF-β1/Smad2 pathway.
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              Puerarin Attenuated Early Diabetic Kidney Injury through Down-Regulation of Matrix Metalloproteinase 9 in Streptozotocin-Induced Diabetic Rats

              Radix puerariae, a traditional Chinese herbal medication, has been used successfully to treat patients with early stage of diabetic nephropathy. However, the underlined mechanism of this renal protective effect has not been determined. In the current study, we investigated the effects and the mechanism of puerarin in Streptozotocin (STZ)-induced diabetic rats. We treated STZ-rats with either puerarin or losartan, an angiotensin II receptor blocker, as compared to those treated with vehicle. We found that both puerarin and losartan attenuated kidney hypertrophy, mesangial expansion, proteinuria, and podocyte foot process effacement in STZ rats. In addition, both puerarin and losartan increased expression of podocyte slit diaphragm proteins such as nephrin and podocin. Interestingly, we found that puerarin treatment induced a more pronounced suppression of oxidative stress production and S-nitrosylation of proteins in the diabetic kidneys as compared to losartan treatment. Furthermore, we found that matrix metalloproteinase-9 (MMP-9), which is known to be activated by oxidative stress and S-nitrosylation of proteins, was also suppressed more extensively by puerarin than losartan. In conclusion, these data provide for the first time the potential mechanism to support the use of puerarin in the treatment of early diabetic nephropathy.
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                Author and article information

                Contributors
                15888025580@139.com
                934194887@qq.com
                547147188@qq.com
                364289549@qq.com
                1205854932@qq.com
                345680508@qq.com
                liuyuanping666@126.com
                wqwz126@126.com
                zhuyabin@nbu.edu.cn
                luolin@nbu.edu.cn
                baobeiyan2007@sina.com
                bushizhong@nbu.edu.cn
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                8 September 2017
                8 September 2017
                2017
                : 17
                : 454
                Affiliations
                [1 ]Division of Nephrology, Ningbo Urology and Nephrology Hospital, 998 Qianhe North Road, Ningbo City, 315192 Zhejiang People’s Republic of China
                [2 ]ISNI 0000 0000 8950 5267, GRID grid.203507.3, Runliang Diabetes Laboratory, Diabetes Research Center, , School of Medicine, Ningbo University, ; 818 Fenghua Road, Ningbo City, 315211 Zhejiang People’s Republic of China
                [3 ]ISNI 0000 0000 8950 5267, GRID grid.203507.3, School of Medicine, Ningbo University, ; 818 Fenghua Road, Ningbo City, 315211 Zhejiang, People’s Republic of China
                Article
                1945
                10.1186/s12906-017-1945-3
                5591499
                28886733
                a62d7b0e-ff89-45e1-b8e1-62e040f279c1
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 November 2016
                : 22 August 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 281370165
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004731, Natural Science Foundation of Zhejiang Province;
                Award ID: Y13H050021
                Award Recipient :
                Funded by: Public Welfare Technology Application Studies Program of Zhejiang
                Award ID: 2015C33309
                Award Recipient :
                Funded by: Ningbo Science and Technology Innovation Team Program
                Award ID: 2014B82002, 2015B11050
                Award Recipient :
                Funded by: Fang Runhua Fund of Hong Kong and K. C. Wong Magna Fund in Ningbo University
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Complementary & Alternative medicine
                type 2 diabetes,radix puerariae,fructus crataegi,renal injury,pi3k/akt

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