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A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy.

ABSTRACT: Traditional Chinese medicine (TCM) has been widely used in treating various diseases in eastern Asia for several thousand years, and is becoming increasingly popular in western countries. Gubentongluo (GBTL) decoction, as a classic TCM formula, is commonly applied to treat IgA Nephropathy (IgAN) in China. To date, however, the pharmacological/molecular mechanisms of GBTL have not been fully elucidated.In the present study, we used a system biological approach to explore these mechanisms acting on IgAN.First, we found 3876 potential target proteins for GBTL (based on TCMID) and 25 known IgAN associated biomarkers (based on the OMIM or IPA database).16 of the latter biomarkers were direct targets of 6 of the 9 herbs in GBTL, suggesting that these components play a vital role in treating IgAN. Second, we showed that these 6 herbs mainly regulate the immune system and renin-angiotensin system, imbalance in which is the main factor leading to IgAN. Importantly, HUANG QI links with 14 biomarkers, indicating that it is the most important herb in GBTL for treating IgAN. Also, relationships of other herbs with IgAN were explored. Third, we demonstrated that the remaining 9 IgAN associated proteins are responses to biological processes, such as antigen processing, protein ubiquitination and cell cycle regulation, which are crucial for IgAN development. Finally, we found that GBTL could induce a significant increase in the levels of two target gene: TNF and NOS2.Further studies are called to develop/modify the formula of GBTL, in order to enhance its effect on IgAN.

SUBMITTER: Shen P

PROVIDER: S-EPMC4997663 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy.

Shen Peicheng P Shen Jiaojiao J Sun Chuan C Yang Xuejun X He Liqun L

BMC complementary and alternative medicine 20160824 1

<h4>Background</h4>Traditional Chinese medicine (TCM) has been widely used in treating various diseases in eastern Asia for several thousand years, and is becoming increasingly popular in western countries. Gubentongluo (GBTL) decoction, as a classic TCM formula, is commonly applied to treat IgA Nephropathy (IgAN) in China. To date, however, the pharmacological/molecular mechanisms of GBTL have not been fully elucidated.<h4>Method</h4>In the present study, we used a system biological approach to ...[more]

PMID: 27558012

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Project description:IntroductionRenin-angiotensin system (RAS) blockade using angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) is first-line therapy for IgA nephropathy (IgAN). There is a paucity of information on the predictors and magnitude of response to this treatment.MethodsIn a prospective study, treatment-naive patients with IgAN with urinary protein ≥ 1 g/d and estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m2 received supportive treatment including ACEi (ramipril) or ARB (losartan) in patients intolerant to ACEi, and optimal blood pressure (BP) control to ≤130/80 mm Hg, with a follow-up of 6 months. The primary outcome was remission of proteinuria. Complete remission (CR) was defined as proteinuria < 0.5 g/d and partial remission (PR) as proteinuria < 1g/d with at least a 50% decline from the baseline with stable renal function (≤ 25% reduction in eGFR).ResultsA total of 96 patients were analyzed, with a mean age of 33.3 ± 10.2 years, baseline eGFR 74.0 ± 30.9 ml/min per 1.73 m2, and urinary protein 2.6 ± 1.2 g/d. In all, 71.9% patients received ≥ 75% of the maximum approved dose of ACEi/ARB. Remission was observed in 36.5% (CR, 6.3%) patients at 3 months and in 55.2% (CR, 31.3%) at 6 months. Patients who failed to achieve remission had lower baseline eGFR (P = 0.002) and serum albumin levels (P< 0.001), asymptomatic hyperuricemia (P < 0.001), and higher proteinuria (P = 0.076). E1 (P= 0.053) and T1/T2 (P = 0.009) lesions were more frequent on histology. The ACEi/ARB had to be discontinued in 17 (17.7%) patients. These patients were older (P= 0.085) with lower eGFR (P < 0.002) and serum albumin levels (P = 0.001) and more E1 (P = 0.012) and T1/T2 (P = 0.001) lesions on histology.ConclusionMeticulous supportive therapy with optimal use of ACEi/ARB achieved remission in half of IgAN patients in this study. Increasing the treatment duration to 6 months improved remission rates. Patients with severe clinical and histological disease were less likely to tolerate and respond to treatment with RAS blockade.

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A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy.

Publications

A system biology approach to understanding the molecular mechanisms of Gubentongluo decoction acting on IgA Nephropathy.

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