Efficacy and Safety of Abelmoschus manihot for Primary Glomerular Disease: A Prospective, Multicenter Randomized Controlled Clinical Trial

Zhang, Li; Li, Ping; Xing, Changying; Zhao, Jiuyang; He, Yong; Wu, Xiongfei; Liu, Zhangsuo; Zhang, Aiping; Lin, Hongli; Ding, Xiaoqiang; Yin, Aiping; Yuan, Fang; Fu, Ping; Hao, Li; Miao, Lining; Xie, Ruiqin; Wang, Rong; Zhou, Chunhua; Guan, Guangju; Hu, Zhao; Lin, Song; Ming, Chang; Zhang, Miao; He, Liqun; Mei, Changlin; Wang, Li; Chen, Xiangmei

doi:10.1053/j.ajkd.2014.01.431

Cited by 102 publications

(80 citation statements)

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“…Recently, a first randomized controlled clinical trial was organized to assess the efficacy and the safety of A. manihot in patients with primary glomerular disease. New data from this trial suggest that A. manihot is more effective than the angiotensinreceptor blocker losartan in reducing proteinuria in patients with primary glomerular disease (Carney, 2014;Zhang et al, 2014). Flavonoids are the main active components of A. manihot for treating CKD (Chen, 2006).…”

Section: Introductionmentioning

confidence: 99%

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Guo

Shang

et al. 2015

Pharmaceutical Biology

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Objective: Flavonoids are main active components of A. manihot, which can be transformed into glucuronide/sulfate conjugates in vivo. Exploring the pharmacokinetic profile of these conjugates is necessary to further elucidate the mechanism of action. Material and method: Flavonoid fraction of A. manihot (FFA) was extracted from A. manihot flower with ethanol. FFA (400 mg/kg) was orally given to normal rats and chronic kidney disease (CKD) model rats. Blood samples were collected at 5, 15, 30, 45, 60, 90, 120, 240, 360, and 720 min after administration. The plasma concentrations of quercetin and isorhamnetin glucuronide/sulfate conjugates were analyzed by UPLC-MS/MS. Results: In normal rats, AUC of quercetin-glucuronide conjugates, isorhamnetin-glucuronide conjugates, quercetin-sulfate conjugates, and isorhamnetin-sulfate conjugates was 459. 45 ± 192.70, 1153.01 ± 697.04, 417.81 ± 220.31, and 2475.19 ± 1085.22 mmol h/L, respectively. While AUC of quercetin and isorhamnetin was 5.47 ± 2.54 and 30.73 ± 25.95 mmol h/L. AUC of the glucuronide-sulfate conjugates of quercetin and isorhamnetin is 125-times higher than that of aglycone (quercetin and isorhamnetin), showing that glucuronide/sulfate conjugates represent the major circulating forms of A. manihot flavonoid in vivo. AUC of isorhamnetinglucuronide conjugates and quercetin-sulfate conjugates was 719.65 ± 619.22 and 275.49 ± 1 60.95 mmol h/L, indicating that less conjugated metabolites were formed in CKD rats compared with normal rats. The ratio of AUC glucuronide/sulfate /AUC aglycone decreased from 125 to 104, which implied the impaired phase II metabolism ability in CKD rat. Discussion and conclusion: Glucuronide-sulfate conjugates provide an important clue for further elucidating the activity of conjugated metabolites and their relationship with the nephroprotective efficacy of A. manihot. It is necessary to take caution when extrapolating pharmacokinetics parameters from healthy animals in designing pharmacological studies.

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Section: Introductionmentioning

confidence: 99%

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Guo

Shang

et al. 2015

Pharmaceutical Biology

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“…a medicinal plant Zhang et al, 2014). Over the past 20 years, huangkui capsule (HKC, the local name in China), a Chinese patent medicine extracted from AM, has been approved by the China State Food and Drug Administration (Z19990040) for the conventional therapy of chronic nephritis.…”

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confidence: 99%

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

Mao

Shen

Wan

et al. 2015

Journal of Ethnopharmacology

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“…For the mechanistic studies, AM has shown to improve kidney inflammation and glomerular injury in rats with doxorubicin-induced nephropathy through inhibition of the p38 MAPK signaling pathway and TGF-β1 protein expression [23]. The results of our previous study have shown that AM significantly reduced proteinuria and maintained kidney function in patients with primary glomerular disease, non-nephrotic-range proteinuria and normal kidney function [11]. AM even showed a better therapeutic effect on reducing proteinuria than losartan (50 mg/d) after 24 weeks of treatment [24].…”

Section: Discussionmentioning

confidence: 99%

“…The clinical research enrolled a total of 417 patients from 26 hospitals who had been diagnosed with primary glomerular disease by renal biopsy. The results showed that AM can significantly reduce urinary protein in patients with primary kidney disease (CKD stages 1–2) and its effect is better than that of losartan potassium (50 mg/d) [11]. Since IgAN was the most common primary glomerular disease and the design of the former study had some limitations, such as not using a blind method, the low dose of losartan potassium (50 mg/d) used, and a short observation time (24 weeks), we conducted this prospective, double-blind, double-dummy randomized controlled study to evaluate efficacy and safety of AM in the treatment of IgAN.…”

Section: Introductionmentioning

confidence: 99%

Abelmoschus manihot – a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial

Chen

Lin

et al. 2017

Trials

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BackgroundIgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN.MethodsWe will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks.DiscussionThis study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN.Trial registrationClinicalTrials.gov, identifier: NCT02231125. Registered on 30 August 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1774-6) contains supplementary material, which is available to authorized users.

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Efficacy and Safety of Abelmoschus manihot for Primary Glomerular Disease: A Prospective, Multicenter Randomized Controlled Clinical Trial

Abstract: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Cited by 102 publications

References 21 publications

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

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

Abelmoschus manihot – a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial

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