How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways

Yu, Jin-Gao; Guo, Jianming; Zhu, Kevin Y.; Tao, Weiwei; Chen, Yanyan; Liu, Pei; Hua, Yongqing; Tang, Yuping; Duan, Jin‐Ao

doi:10.1038/s41598-017-03201-1

Cited by 13 publications

(11 citation statements)

References 58 publications

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“…Prior chemical studies have shown that Genkwa flos encompasses various types of constituents involving flavonoids, diterpenoids, lignans, and coumarins [ 100 ]. Current emerging evidence indicates that severe lesions to cardiac, renal, hepatic, and cutaneous tissues can be identified by excessive and prolonged administration of Genkwa flos [ 101 , 102 , 103 , 104 ]. Hepatotoxicity of Genkwa flos treatment have shown in HL-7702 liver cells, such as the increased hepatic serum makers of ALT, AST, and MDA, and downregulated oxidative stress indexes of CAT and GSH.…”

Section: Molecular Mechanisms Involved In Tcm-induced Oxidative Hementioning

confidence: 99%

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

Zhang

Wang

et al. 2018

IJMS

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Oxidative stress, defined as a disequilibrium between pro-oxidants and antioxidants, can result in histopathological lesions with a broad spectrum, ranging from asymptomatic hepatitis to hepatocellular carcinoma in an orchestrated manner. Although cells are equipped with sophisticated strategies to maintain the redox biology under normal conditions, the abundance of redox-sensitive xenobiotics, such as medicinal ingredients originated from herbs or animals, can dramatically invoke oxidative stress. Growing evidence has documented that the hepatotoxicity can be triggered by traditional Chinese medicine (TCM) during treating various diseases. Meanwhile, TCM-dependent hepatic disorder represents a strong correlation with oxidative stress, especially the persistent accumulation of intracellular reactive oxygen species. Of note, since TCM-derived compounds with their modulated targets are greatly diversified among themselves, it is complicated to elaborate the potential pathological mechanism. In this regard, data mining approaches, including network pharmacology and bioinformatics enrichment analysis have been utilized to scientifically disclose the underlying pathogenesis. Herein, top 10 principal TCM-modulated targets for oxidative hepatotoxicity including superoxide dismutases (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), glutathione peroxidase (GPx), Bax, caspase-3, Bcl-2, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nitric oxide (NO) have been identified. Furthermore, hepatic metabolic dysregulation may be the predominant pathological mechanism involved in TCM-induced hepatotoxic impairment.

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Section: Molecular Mechanisms Involved In Tcm-induced Oxidative Hementioning

confidence: 99%

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

Zhang

Wang

et al. 2018

IJMS

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“…System pharmacology is emerging as a holistic and efficient tool to study the role of TCM due to its capable of describing complex interactions between drugs and biological systems including the human body, organs, and diseases from a network perspective (Kloft et al, 2016 ; Zhang et al, 2016 ). Combined with pharmacology and pharmacodynamics, it has been successfully applied to interpret the synergistic mechanisms of herb combinations at molecular network level (Zhou et al, 2016 ; Yu et al, 2017 ; Yue et al, 2017 ). In the present study, we tried to establish the compound-target (C-T), target-pathway (T-P), and target-organ (T-O) networks by the system pharmacology model based on chemical, pharmacokinetic and pharmacological data at the system, organ, and molecular levels (Supplementary Figure S2 ), so as to uncover the underlying synergistic mechanisms of Huangqi and Huanglian for treating DM.…”

Section: Introductionmentioning

confidence: 99%

System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus

et al. 2017

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The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.

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“…The urinary excretion volume was mainly determined by the urine concentrating ability, including urine and its electrolyte reabsorption [13, 16]. In this study, we explored the diuretic activity of LS and its four fractions (LSA, LSB, LSC, and LSD) compared with that produced by furosemide in normal rats.…”

Section: Discussionmentioning

confidence: 99%

Diuretic and Antidiuretic Activities of Ethanol Extract and Fractions of Lagopsis supina in Normal Rats

Yang

et al. 2019

BioMed Research International

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Lagopsis supina is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of L. supina (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na+ excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K+ excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na+ and K+ excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na+-K+-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF-α and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process.

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How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways

Cited by 13 publications

References 58 publications

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus

Diuretic and Antidiuretic Activities of Ethanol Extract and Fractions of Lagopsis supina in Normal Rats

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