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Effect of Huaiqihuang Granules Combined with Comprehensive Nursing on Children with  Primary Nephrotic Syndrome.  

J Healthc Eng. 2022 Jan 15(IF 3.822)

;2022:3279503. doi: 10.1155/2022/3279503. eCollection 2022. 

Yang G(1), Yang H(1), Cui S(2), Shan J(1). 

Author information: 

(1)Child Health Care Department, Zhangqiu Maternity and Child Care Hospital, Jinan  250200, China. 

(2)Department of Paediatrics, Zhangqiu Maternity and Child Care Hospital, Jinan 250200,  China. 

BACKGROUND: To observe the effect of Huaiqihuang granules combined with  comprehensive nursing intervention on children with primary nephrotic syndrome (PNS) and  its effect on renal function index. 

METHODS: A total of 104 patients were included, and the patients were randomly divided  into two groups, with 52 cases in each group. The control group was treated with  glucocorticoid, and the study group was treated with Huaiqihuang granules. The  clinicalefficacy of the two groups was observed. The levels of TG, TC, EGFR, 24 h UTP, BUN,  

Scr, IgA, IgG, IgM, IFN-γ and TNF-α were compared between two groups before and after  treatment. The incidence of adverse reactions and recurrence rate after treatment were  compared between the two groups. 

RESULTS: The effective rate of the study group (94.23%) was significantly higher than that  of the control group (78.85%). Before treatment, there was no significant difference in TG  and TC levels between the two groups. After treatment, the levels of TG and TC in both  groups were decreased, and the decrease was more obvious in the study group. Compared  with before treatment, the levels of 24 h UTP, BUN, Scr, IFN-γ, and TNF-α in both groups  were significantly decreased after treatment, while EGFR, IgA, IgG, and IgM levels were  significantly increased. Compared with the control group, the changes of each index in the  study group were more obvious after treatment. After treatment, the incidence of adverse  reactions and recurrence rate in the study group were significantly lower than those in the  control group.

CONCLUSIONS: Huaiqihuang granules combined with comprehensive nursing treatment in  children with PNS can reduce the occurrence of recent recurrence and adverse reactions and  improve the cellular immune function and renal function. 

Copyright © 2022 Guiyun Yang et al. 

DOI: 10.1155/2022/3279503 

PMCID: PMC8783717 

PMID: 35075385 [Indexed for MEDLINE] 

Conflict of interest statement: The authors have no conflicts of interest to declare.

Systematic Review of the Efficacy and Safety of Traditional Chinese Medicine Granules  Associated with Hormone When Treating Primary Nephrotic Syndrome in Children.  

Contrast Media Mol Imaging. 2022 Sep 27(IF 3.009)

;2022:2520367. doi: 10.1155/2022/2520367. eCollection 2022. 

Zhang L(1), Chen L(2). 

Author information: 

(1)Department of Pediatrics, Qilu Medical University, Zibo, Shandong, China. (2)Department of Surgery, Qilu Medical University, Zibo, Shandong, China. 

OBJECTIVE: To systematically evaluate the efficacy and safety of traditional Chinese  medicine (TCM) granules associated with hormones when treating primary nephrotic  syndrome (PNS) in children. 

METHODS: Search online databases such as PubMed, EMBASE, ScienceDirect, Cochrane  Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang  Database, and China Biomedical Literature Database (CBM) to search for information on the  use of hormone-related Chinese medicine granules in the treatment of children with PNS  controlled trials. Retrieval time was limited to the period from the date the database was  established to the present. Separately, two researchers gathered the data. Statistical software  RevMan5.4 was adopted to estimate bias risk in accordance with the Cochrane Handbook 5.3  standard.

RESULTS: Finally, 7 articles were selected with a total sample size of 487 cases. The infection  rate, recurrence rate, and adverse reaction rate after treatment were analyzed by meta-analysis.  The infection rate and recurrence rate in the study group were notably lower, and the  difference was statistically significant (P < 0.05). However, the incidence of adverse reactions  exhibited not notably different (P > 0.05). The levels of albumin and blood cholesterol  after treatment indicated no statistical difference between the levels (P > 0.05). Meta-analysis  was performed on the time to negative urine protein and the time to edema subsidence after  treatment. The urine protein negative time and edema subsidence time of the study group  were shorter after treatment, but the difference exhibited not notable (P > 0.05). Meta analysis was performed on the dosage of glucocorticoids after treatment. The dosage of  glucocorticoid in the study group was notably lower, and the difference was statistically  significant (P < 0.05). The levels of T lymphocytes after treatment were analyzed by meta. T  lymphoid level in the study group was notably better after treatment, and the difference was  statistically significant (P < 0.05). Further subgroup analysis indicated that the levels of  CD3+ and CD4+ in the study group were higher after treatment (P < 0.05), and there  exhibited no statistical difference in the levels of CD8+, CD4/CD8+, and CD19 (P > 0.05).  Immunoglobulin levels in the study group after treatment were notably better, and the  difference was statistically significant (P < 0.05). Further subgroup analysis indicated that the  levels of IgA, IgM, and IgG in the study group were notably higher after treatment, and the  difference was statistically significant (P < 0.05). 

CONCLUSION: Huai Qi Huang can reduce the recurrence rate of PNS children and  theincidence of infection and the dosage of prednisone. A long-term application can improve  the cellular and humoral immune function of children with PNS. It has high treatment safety  and has no notable effect on plasma cholesterol levels, so it is suitable for clinical application. 

Copyright © 2022 Li Zhang and Lei Chen. 

DOI: 10.1155/2022/2520367 

PMCID: PMC9532136 

PMID: 36247855 [Indexed for MEDLINE] 

Conflict of interest statement: The authors declare that they have no conflicts of interest.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of  Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.  

Biomed Res Int. 2022 Nov 4(IF 3.246)

;2022:2798217. doi: 10.1155/2022/2798217. eCollection 2022.

Liu Q(1), Liu J(2), Du Y(1), Guo W(3), Mi J(4), Guo Y(1). 

Author information: 

(1)Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu  Hospital, Air Force Medical University, Xi’an, Shaanxi 710038, China. (2)Department of Clinical Laboratory, Xi’an Children’s Hospital, Xi’an, Shaanxi 710003,  China. 

(3)Department of Pharmacy, The First Hospital of Xi’an, Xi’an, Shaanxi 710002, China. (4)Department of Pharmacy, Xi’an Children’s Hospital, Xi’an, Shaanxi 710003, China. 

OBJECTIVE: Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of  chronic renal failure and is the most common secondary glomerular disease in children.  Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects  against HSPN in clinical practice. However, the potential molecular targets and mechanisms  underlying HSPN treatment remain unclear. 

METHODS: By constructing a protein-protein interaction (PPI) network, core targets  related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto  Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways  related to HSPN based on the core targets. To screen the main active ingredients of HQH  against HSPN, an ingredient-target-pathway network was constructed using the top 10 main  pathways associated with HSPN. Then, molecular docking was performed to explore the  interactions and binding patterns between molecules and proteins. 

RESULTS: Clinical data showed that HQH combined with conventional medicine  significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and  erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15  potential core targets were identified. The top 10 main pathways showed higher enrichment  ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to  NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and  molecular docking, we revealed that five active ingredients of HQH had good affinities with  three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. 

CONCLUSIONS: The study preliminarily explored the active ingredients, targets, and  pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be 

attributed to the modulation of inflammatory response, immune response, and oxidative  stress. Combined with clinical data, our results indicate that HQH is highly effective in  treating HSPN. 

Copyright © 2022 Qingqing Liu et al. 

DOI: 10.1155/2022/2798217 

PMCID: PMC9652090 

PMID: 36389115 [Indexed for MEDLINE] 

Conflict of interest statement: All authors report no competing interests regarding the  publication of this manuscript.

Effect of Huaiqihuang Granules Combined with Comprehensive Nursing on Children with Primary Nephrotic Syndrome 

J Healthc Eng. 2022 Jan 15;2022:3279503. doi: 10.1155/2022/3279503. eCollection 2022.  IF 2.682

Authors 

Guiyun Yang  1 Huanqin Yang  1 Shifang Cui  2 Jinling Shan  1 

Affiliations 

  • 1 Child Health Care Department, Zhangqiu Maternity and Child Care Hospital, Jinan 250200, China.
  • 2 Department of Paediatrics, Zhangqiu Maternity and Child Care Hospital, Jinan 250200, China.
  • PMID: 35075385 
  • PMCID: PMC8783717 
  • DOI: 10.1155/2022/3279503 

Free PMC article

Abstract 

Background: To observe the effect of Huaiqihuang granules combined with comprehensive nursing intervention on children with primary nephrotic syndrome (PNS) and its effect on renal function index. 

Methods: A total of 104 patients were included, and the patients were randomly divided into two groups, with 52 cases in each group. The control group was treated with glucocorticoid, and the study group was treated with Huaiqihuang granules. The clinical efficacy of the two groups was observed. The levels of TG, TC, EGFR, 24 h UTP, BUN, Scr, IgA, IgG, IgM, IFN-γ and TNF-α were compared between two groups before and after treatment. The incidence of adverse reactions and recurrence rate after treatment were compared between the two groups. 

Results: The effective rate of the study group (94.23%) was significantly higher than that of the control group (78.85%). Before treatment, there was no significant difference in TG and TC levels between the two groups. After treatment, the levels of TG and TC in both groups were decreased, and the decrease was more obvious in the study group. Compared with before treatment, the levels of 24 h UTP, BUN, Scr, IFN-γ, and TNF-α in both groups were significantly decreased after treatment, while EGFR, IgA, IgG, and IgM levels were significantly increased. Compared with the control group, the changes of each index in the study group were more obvious after treatment. After treatment, the incidence of adverse reactions and recurrence rate in the study group were significantly lower than those in the control group. 

Conclusions: Huaiqihuang granules combined with comprehensive nursing treatment in children with PNS can reduce the occurrence of recent recurrence and adverse reactions and improve the cellular immune function and renal function. 

Copyright © 2022 Guiyun Yang et al. 

Conflict of interest statement 

The authors have no conflicts of interest to declare.

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation 

Pharm Biol. 2021 Dec;59(1):1425-1431. doi: 10.1080/13880209.2021.1990356.  IF 3.503

Authors 

Yueming Zhang  1 Jian Chang  2 Huan Gao  1 Xiaoyu Qu  1 Jinghui Zhai  1 Lina Tao  1 Jingmeng Sun  1 Yanqing Song  1 

Affiliations 

Free PMC article

Abstract 

Context: Severe nephrotoxicity greatly limits the clinical use of the common effective chemotherapeutic agent cyclophosphamide (CYP). Huaiqihuang (HQH) is a Chinese herbal complex with various pharmacological activities, widely used for treating kidney disease. 

Objective: This study estimates the protective effect of HQH against CYP-induced nephrotoxicity in rats. 

Materials and methods: Four groups of 10 Sprague-Dawley rats were pre-treated with once-daily oral gavage of 3 and 6 mg/kg HQH for 5 days before receiving a single dose of CYP (200 mg/kg i.p.) on the 5th day; the control group received equivalent dose of saline. Renal function indices, morphological changes, oxidative stress, apoptosis and inflammatory mediators were measured. In addition, phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were analysed. 

Results: Both doses of HQH reduced the levels of serum creatinine (31.27%, 43.61%), urea nitrogen (22.66%, 32.27%) and urine protein (12.87%, 15.98%) in the CYP-treated rats, and improved histopathological aberrations. Additionally, HQH decreased the production of MDA (37.02%, 46.18%) and increased the activities of antioxidant enzyme CAT (59.18%, 112.25%) and SOD (67.10%, 308.34%) after CYP treatment. HQH protected against CYP-induced nephrotoxicity by modulating apoptosis-related protein and suppressing the inflammatory responses. Furthermore, the phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were significantly boosted in CYP-treated rats, which was also abrogated by HQH treatment. 

Conclusions: HQH effectively protected against CYP-induced nephrotoxicity, which was associated with regulating oxidative stress, apoptosis and inflammation, and so HQH may be a useful agent for treating nephrotoxicity caused by CYP. 

Keywords: Chinese medicine; apoptosis; chemotherapeutic agent; inflammation; oxidative stress. 

Conflict of interest statement 

No potential conflict of interest was reported by the author(s).

Chinese patent herbal medicine Huaiqihuang for Henoch-Schonlein purpura nephritis in children: a systematic review of randomized controlled trials 

BMC Complement Med Ther. 2021 Nov 8;21(1):278. doi: 10.1186/s12906-021-03415-x.  IF 3.78

Authors 

Xue Xue  1   2 Xue-Han Liu  2 Chun-Li Lu  2 Xin-Yan Jin  2 Qiang Liu  1 Xiao-Qin Wang  1 Jian-Ping Liu  3 

Affiliations 

  • 1 Hubei University of Traditional Chinese Medicine, The first clinical college and affiliated hospital, Wuhan, 430061, Hubei, China.
  • 2 Beijing University of Chinese Medicine, Centre for Evidence-Based Chinese Medicine, Beijing, 100029, China.
  • 3 Beijing University of Chinese Medicine, Centre for Evidence-Based Chinese Medicine, Beijing, 100029, China. Liujp@bucm.edu.cn.
  • PMID: 34743723 
  • PMCID: PMC8573979 
  • DOI: 10.1186/s12906-021-03415-x 

Free PMC article

Abstract 

Background: Henoch-Schönlein purpura nephritis (HSPN) is listed as the most common secondary glomerular diseases among children. Approximately 15 to 20% of children eventually could develop into chronic renal failure. Chinese patent herbal medicine Huaiqihuang (HQH) has been widely used in children with HSPN. This study aimed to evaluate the effectiveness and safety of HQH for HSPN in children, so as to provide evidence for clinical use. 

Methods: Randomized controlled trials (RCTs) on HQH for HSPN in children were searched in eight Chinese and English databases from their inception to December 2020. We included children with HSPN received HQH combined with conventional medicine. Cochrane “Risk of bias” tool was used to assess methodological quality, and “Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach” to summarize the certainty of evidence for main findings. Effect estimates were presented as risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) in meta-analyses using RevMan 5.3. Data not suitable for statistical pooling were synthesized qualitatively. 

Results: In total seven RCTs were identified. Compared with conventional medicine alone, HQH plus conventional medicine showed the better effect in improving clinical cure rate (RR 1.58; 95%CI 1.17 to 2.14; n = 6) and total effective rate (RR 1.34; 1.16 to 1.54; n = 6); reducing urine sediment erythrocyte count (MD -9.23; – 10.76 to – 7.69; n = 3) and urine β2 micro-globulin level (MD -0.09; – 0.12 to – 0.06; n = 2). No serious adverse event was recorded in all included trials. 

Conclusions: Limited evidence showed HQH combined with conventional medicine had a beneficial effect for children with HSPN, and the side effects were mild. HQH may be a promising complementary therapy. However, long term follow-up, high quality and multicenter RCTs are required to confirm the findings. 

Keywords: Children; Chinese patent herbal medicine; Henoch-Schonlein purpura nephritis; Huaiqihuang; Randomized controlled trials; Systematic review. 

© 2021. The Author(s). 

Conflict of interest statement 

All authors declare that they have no competing interests.

Efficacy and safety of Huaiqihuang granule as adjuvant treatment for primary nephrotic syndrome in children: a meta-analysis and systematic review 

World J Pediatr. 2021 Jun;17(3):242-252. doi: 10.1007/s12519-020-00405-w. Epub 2021 Jun 1.  IF 2.764

Authors 

Jiao Lin  1 Li-Min Huang  1 Jing-Jing Wang  1 Jian-Hua Mao  2 

Affiliations 

  • 1 Department of Nephrology, National Clinical Research Center For Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
  • 2 Department of Nephrology, National Clinical Research Center For Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. maojh88@zju.edu.cn.
  • PMID: 34075551 
  • DOI: 10.1007/s12519-020-00405-w 

Abstract 

Background: Huaiqihuang (HQH) granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome (PNS) for many years. However, the effectiveness and safety of HQH have not been systematically discussed. This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS. 

Methods: The following databases were searched from inception to Mar 2019: MEDLINE, Cochrane Library, EMBASE, CNKI, Wanfang Database, the Chinese Scientific Journal Database and the Chinese biomedical literature service system. All the randomized controlled trials (RCTs) eligible for inclusion were included. The primary outcomes were relapse, infection, remission and adverse events. The secondary outcomes included serum immunoglobulin levels (IgA, IgG or IgM), T-lymphocyte subtype (CD3+ , CD4+ , CD8+ , CD4+ /CD8+), IL-10, TNF-α, TNF-γ, total cholesterol and time of proteinuria turning negative. 

Results: Fourteen RCTs (885 patients) were identified. Treatment with HQH reduced the chance of relapse [relative risk (RR): 0.47; 95% CI: 0.34, 0.66; P < 0.001] and infections (RR: 0.47; 95% CI: 0.35, 0.62; P < 0.001). No significant difference was found in adverse events. HQH also increased the serum levels of IgA [weighted mean difference (WMD): 0.40; 95% CI: 0.20, 0.60; P < 0.001] and IgG (WMD: 1.58; 95% CI: 1.38-1.78; P < 0.001), as well as CD4+ [standard mean difference (SMD): 0.90; 95% CI: 0.12-1.68; P = 0.02], CD3+ (WMD: 4.04; 95% CI: 3.27-4.82; P < 0.001), and the CD4+/CD8+ratio (WMD: 0.31; 95% CI: 0.21-0.41; P < 0.001), but decreased the level of CD8+ cells (WMD: -3.39; 95% CI: -5.73-1.05; P = 0.004). No statistically significant difference was found in IgM (WMD: 0.05; 95% CI: -0.13, 0.24; P = 0.57). 

Conclusions: HQH could reduce the rate of relapse and the frequency of infection in children with PNS. No apparent adverse effects were found. Moreover, the beneficial influence of HQH may act through immunomodulation. Additional multi-center, large-sample, high-quality studies are needed to confirm the effectiveness and safety of HQH. 

Keywords: Children Huaiqihuang; Meta-analysis; Nephrotic syndrome. 

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study 

Zhongguo Dang Dai Er Ke Za Zhi. 2021;23(9):877-881. doi: 10.7499/j.issn.1008-8830.2106028.  IF 0.36

[Article in English, Chinese] 

Authors 

Hui-Min Wang  1 Chuan-He Liu  1 Chang-Shan LiuYing WangZhi-Ying HanXin SunXing ChenShu-Hua AnMuzhapaer DuolikunAi-Ping LuMin WangYan ChengXiao-Mei YinHan-Min LiuHong WangShan HuaLi DongYing HuangYi JiangJian-Xin XiongSheng-Gang DingShun-Ying ZhaoJin-Rong WangGui-Min Huang  1 Jing-Hui Mu  1 Yu-Zhi Chen  1 

Affiliation 

Free PMC article

Abstract 

in English, Chinese 

Objectives: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. 

Methods: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. 

Results: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). 

Conclusions: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation. 

目的: 察槐杞黄助治儿童支气管哮喘的效。方法: 采取多中心、前瞻性、登注册的真世界研究方法,于全国21家医院门依序入已明确断支气管哮喘、年2~5、采用以下两种治方案之一的患儿:使用哮喘期控制物,即吸入激素和/或白三受体拮抗,但未使用槐杞黄粒(控制治疗组n=390);使用哮喘期控制物,同加用槐杞黄粒(合治疗组n=1 014)。收集所有患儿的个人及料,于治后第4812202836行门电话访。随访内容包括哮喘作情况、鼻炎症状等,并访观察指统计学分析。: 前两患儿哮喘作次数、天数及鼻炎作天数比差异均无统计学意P>0.05)。后,合治疗组患儿每月哮喘作天数、重度哮喘作次数及鼻炎作天数均著少于控制治疗组P<0.05)。两患儿不良反应发生率比差异无统计学意P=0.667)。结论: 在使用哮喘期控制物治上加用槐杞黄粒能够改善支气管哮喘患儿的床症状及伴的鼻炎症状,提高哮喘控制水平,且在治疗过程中使用安全,无明不良反。 引用格式. 

Keywords: Adjuvant therapy; Bronchial asthma; Child; Huaiqihuang granules. 

Conflict of interest statement 

所有作者均声明不存在利益冲突。

The Effect of Chinese Traditional Medicine Huaiqihuang (HQH) on the Protection of Nephropathy 

Oxid Med Cell Longev. 2020 Jun 16;2020:2153912. doi: 10.1155/2020/2153912. eCollection 2020.  IF 6.543

Authors 

Xueyan Zhang  1 Yiyu Cheng  1 Qian Zhou  1 Haojie Huang  1 Yinmiao Dong  1 Yang Yang  1 Mingyi Zhao  1 Qingnan He  1 

Affiliation 

Free PMC article

Abstract 

Kidney disease is one of the common diseases with high morbidity and high mortality, which brings a huge burden to the society and the patient’s family. The pathogenesis, treatment, and prognosis of kidney diseases are related to oxidative stress, inflammation, mitochondrial damage, and immune dysfunction. However, existing treatments always cause some damage to the kidneys. Kidney disease and immunosuppressant used together often lead to drug toxicity, patients with weakened immunity, organic rupture of the normal structure of the kidney, damage to the physiological function of the kidney, etc. Huaiqihuang is a kind of traditional Chinese medicine with a history of more than one thousand years. According to research, Robinia pseudoacacia can regulate the immune function by regulating oxidative stress, calcium inflow, and mitochondrial ATP. At the same time, it is also involved in regulating the ways of cell death, such as apoptosis, autophagy, ferroptosis, pyroptosis, and clockophagy, to reduce kidney damage, which has important clinical value. This article reviews the exact mechanism and clinical application of Huaiqihuang in different types of nephropathy. The aim is to provide new ideas for the treatment of clinical nephropathy. 

Copyright © 2020 Xueyan Zhang et al. 

Conflict of interest statement 

The authors declare that they have no conflicts of interest.

Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in Ph + Leukemia Cells 

Curr Med Sci. 2020 Apr;40(2):354-362. doi: 10.1007/s11596-020-2181-5. Epub 2020 Apr 26.  IF 2.135

Authors 

Wen-Fu Xu  1 Zhu-Jun Wang  1 Kun Li  1 Ya-Qing Shen  1 Ke Lu  1 Xue-Yan Lv  1 Yu-Xi Wen  1 Run-Ming Jin  2 

Affiliations 

  • 1 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. jinrunm@qq.com.
  • PMID: 32337697 
  • DOI: 10.1007/s11596-020-2181-5 

Abstract 

Imatinib mesylate (IM) is the first-line treatment for Philadelphia (Ph) chromosomal positive leukemia by inhibiting phosphorylation of substrates via binding to the ABL kinase domain. Because of the drug resistance, side effects and the high cost of IM, it is necessary to find anti-cancer drugs with relatively low toxicity and cost, and enhanced efficacy, such as traditional Chinese medicines (TCMs). As one of TCMs, Huai Qi Huang (HQH) was chosen to treat BV173 and K562 cells. Various concentrations of HQH were added to cells for 24-72 h. Co-treatment of HQH and trametinib, an MEK inhibitor, was used to verify the synergistic effects on cell viability and apoptosis. Knockdown and overexpression of mitogen-activated protein kinase kinase 4 (MEK4) were implemented to demonstrate the role of MEK in cell apoptosis. Cell viability and apoptosis were measured by cell counting kit-8 assay (CCK8) and flow cytometry, respectively. Western blotting and real-time quantitative PCR (RT-qPCR) were used to assess protein and mRNA expression levels, respectively. The results showed that HQH inhibited survival and promoted apoptosis of BV173 and K562 cells in a dose-dependent manner, accompanied with down-regulation of PRKCH mRNA as well as CRAF, MEK4, phospho-ERK (pERK) and BCL2 proteins, and up-regulation of cleaved caspase3 protein. Co-treatment of HQH and trametinib had a synergistic effect on inhibiting survival and promoting apoptosis. MEK4 knockdown increased apoptosis, and had a synergistic effect with HQH. In contrast, MEK4 overexpression decreased apoptosis, and had the opposite effect with HQH. Collectively, the results of this study may identify a therapeutic mechanism of HQH on promoting apoptosis, and provide a potential option for treatment of Ph+ leukemia. 

Keywords: BCR-ABL; Huai Qi Huang; RAF/MEK/ERK; apoptosis; leukemia. 

Huai Qi Huang Potentiates Dexamethasone-Mediated Lethality in Acute Lymphoblastic Leukemia Cells by Upregulating Glucocorticoid Receptor α 

Med Sci Monit. 2020 Feb 17;26:e921649. doi: 10.12659/MSM.921649.  IF 2.649

Authors 

Wenfu Xu  1 Zhujun Wang  1 Kun Li  1 Runming Jin  1 

Affiliation 

Free PMC article

Abstract 

BACKGROUND Glucocorticoids are important components of a number of chemotherapeutic regimens used to treat pediatric acute lymphoblastic leukemia (ALL). A primary cause of treatment failure of ALL is acquired resistance to glucocorticoids. Recently, traditional Chinese medicines were effectively used to treat solid tumors. Thus, the aim of this study was to investigate whether Huai Qi Huang (HQH), a traditional Chinese medicine, increased the efficacy of glucocorticoids in the treatment of ALL, and if so, to determine the underlying mechanism. MATERIAL AND METHODS Various concentrations of HQH were used to treat Jurkat and Nalm-6 cells for 24 to 72 hours. Subsequently, cells were co-treated with HQH and the glucocorticoid receptor agonist, dexamethasone (DEX), or a MEK inhibitor (PD98059) to verify the synergistic effects on apoptosis in Jurkat and Nalm-6 cells for 24 hours. Cell Counting Kit-8 assay and flow cytometry were used to measure cell viability and apoptosis, respectively. Protein and mRNA expression levels were assessed using western blotting and quantitative polymerase chain reaction. RESULTS The results revealed that cell survival was reduced and apoptosis was increased as the HQH concentration was increased, and this was accompanied with increases in the levels of BAX, cleaved-caspase-3 and glucocorticoid receptor alpha (GRalpha) and decreases in the levels of Bcl-2 and phospho-ERK (pERK). Glucocorticoid receptor ß (GRß) and total ERK (t-ERK) had no significant changes. Combined treatment with HQH and DEX or PD98059 increased apoptosis in Jurkat and Nalm-6 cells, and concurrently increased BAX, cleaved-caspase-3, GILZ, NFKBIA, and GRalpha and decreased Bcl-2 and pERK. CONCLUSIONS HQH enhanced the sensitivity of ALL cells to glucocorticoids by increasing the expression of GRalpha and inhibiting the MEK/ERK pathway, thus providing a rational foundation for the treatment of ALL with HQH. 

Conflict of interest statement 

Conflict of interests

None.

Effect of Huai Qi Huang on asthma in rats and the mechanism research

Zhongguo Dang Dai Er Ke Za Zhi. 2020 Feb;22(2):171-176. doi: 10.7499/j.issn.1008-8830.2020.02.016.  IF 0.36

[Article in Chinese] 

Authors 

Na Lu  1 Yan BaiChen ZhaoLi TianXia WanRun-Ming Jin

Affiliation 

Free PMC article

Abstract 

in English, Chinese 

Objective: To study the role and mechanism of action of Huai Qi Huang (HQH) in the rat model of asthma. 

Methods: Forty Sprague-Dawley rats were randomly divided into a control group, an asthma model group, a budesonide group, and an HQH group, with 10 rats in each group. A rat model of asthma was established by ovalbumin sensitization and challenge. The budesonide group was given budesonide aerosol 2 mg before each challenge. The HQH group was given HQH 4 g/kg dissolved in water by gavage before each challenge. Hematoxylin and eosin staining was used to observe the pathological changes of lung tissues. The percentage of eosinophils in bronchoalveolar lavage fluid (BALF) was measured. Enzyme-linked immunosorbent assay was used to determine the levels of interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), interferon gamma (INF-γ), and immunoglobulin E (IgE) in BALF. Flow cytometry was used to determine T-helper type 1 (Th1)/T-helper type 2 (Th2) ratio in peripheral blood and the spleen. RT-PCR and Western blot were used to measure the mRNA and protein expression of T-bet and GATA-3 in lung tissue. 

Results: Compared with the control group, the asthma model group showed significant increases in the degree of airway inflammation, the percentage of eosinophils in BALF, and the levels of IL-3, IL-4, IL-5 and IgE in BALF (P<0.05), however, the asthma model group showed significant reductions in the levels of IL-10 and INF-γ in BALF (P<0.05). The asthma model group had significantly lower percentage of Th1 cells but significantly higher percentage of Th2 cells in peripheral blood and the spleen compared with the control group (P<0.05). The mRNA and protein expression of T-bet in lung tissue was significantly lower, but the mRNA and protein expression of GATA-3 in lung tissue was significantly higher in the asthma group than those in the control group (P<0.05). Both HQH and budesonide significantly improved airway inflammation and the above markers in asthmatic rats (P<0.05), with comparable effects between them. However, there were still significant differences in these indices between the control group and the HQH or budesonide group (P<0.05). 

Conclusions: HQH can reduce the airway inflammation of asthmatic rats and alleviate the symptoms of asthma, possibly by regulating the levels of related cytokines and Th1/Th2 ratio through the T-bet/GATA-3 pathway. 

目的: 探索槐杞黄在哮喘大鼠模型中的作用及相关机制。 

方法: 40Sprague-Dawley大鼠随机分为对、哮喘模型、布地奈德和槐杞黄n=10)。通卵白蛋白致敏并激建立哮喘大鼠模型,布地奈德在每次激前以布地奈德2 mg化,槐杞黄在每次激前以槐杞黄4 g/kg溶于水中灌胃。木精染色察各大鼠肺组织病理化;数肺泡灌洗液(BALF)中嗜酸性粒胞比例;ELISA检测BALF胞因子IL-3IL-4IL-5IL-10INF-γIgE度;流式术检测外周血及脾Th1/Th2胞比例;RT-PCR检测组织T-betGATA-3 mRNA达;Western bolt检测组织T-betGATA-3蛋白表达。 

: 相比,哮喘大鼠气道炎症程度明增加;BALF中嗜酸性粒胞比例著升高;IL-3IL-4IL-5IgE著升高,而IL-10INF-γ度明下降;外周血及脾Th1胞比例明降低,Th2胞比例明升高;肺组织T-bet mRNA及其蛋白表达水平明降低,GATA-3 mRNA及其蛋白表达水平明升高(P < 0.05)。槐杞黄及布地奈德均能明改善哮喘大鼠气道炎症及上述指水平(P < 0.05),且效果相当;但与,差异仍有统计学意P < 0.05)。 

结论: 槐杞黄能改善哮喘大鼠气道炎症,解哮喘症状,其机制可能与调节相关胞因子水平及Th1/Th2比例有关,一作用可能T-betGATA-3通路控。