Network pharmacology oriented study reveals inflammatory state-dependent dietary supplement hepatotoxicity responses in normal and diseased rats

Tu, Can; Niu, Ming; Li, Chunyu; Liu, Zhenjie; He, Qin; Li, Ruisheng; Zhang, Yaming; Xiao, Xiaohe; Wang, Jiabo

doi:10.1039/c8fo01974f

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…Under liver fibrosis (immune tolerance), AQs showed therapeutic effect. While in normal state (immune activated), liver is more sensitive to AQs damage, which is related to Kupffer cells (liver macrophages) [157]. This exposes a shortcoming in the current research, that is, the in vitro effects and mechanism studies are relatively isolated and cannot fully simulate the in vivo pathological state, which may lead to contradictory results between in vitro and in vivo studies.…”

Section: Discussionmentioning

confidence: 97%

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

Xin

Zhou

et al. 2022

Molecules

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The anthraquinones (AQs) and derivatives are widely distributed in nature, including plants, fungi, and insects, with effects of anti-inflammation and anti-oxidation, antibacterial and antiviral, anti-osteoporosis, anti-tumor, etc. Inflammation, including acute and chronic, is a comprehensive response to foreign pathogens under a variety of physiological and pathological processes. AQs could attenuate symptoms and tissue damages through anti-inflammatory or immuno-modulatory effects. The review aims to provide a scientific summary of AQs on immune responses under different pathological conditions, such as digestive diseases, respiratory diseases, central nervous system diseases, etc. It is hoped that the present paper will provide ideas for future studies of the immuno-regulatory effect of AQs and the therapeutic potential for drug development and clinical use of AQs and derivatives.

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Section: Discussionmentioning

confidence: 97%

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

Xin

Zhou

et al. 2022

Molecules

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“…Rhein exerts pro-inflammatory actions by increasing the interleukin-1 beta (IL-1β) and high-mobility group box-1(HMGB1) release, while downstream pro-inflammatory cytokines will, in turn, promote upstream intracellular signaling cascades and result in positive feedback pro-inflammatory signaling pathways. This amplifying mechanism of inflammatory signal pathways will eventually lead to further liver injury [ 39 ]. In this study, MA regulates inflammatory response through IL-2 and downstream PI3K-Akt signaling pathway and MAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Chen

Zhang

Jiao

et al. 2022

Toxins

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Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

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“…Routine toxicological studies have shown that no substantial hepatotoxicity has been observed in either raw or processed products or in different extracts within the range of the maximum tolerated dose in animal experiments, suggesting that it is safe to use Polygoni Multiflori Radix for people under normal circumstances [21,22] .…”

Section: Adverse Reactions and Safety Evaluation Of Polygoni Multiflo...mentioning

confidence: 99%

Guidelines for safe use of Polygoni Multiflori Radix

Xiao,

Wang,

Song

et al. 2024

Acupuncture and Herbal Medicine

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Polygoni Multiflori Radix is a Chinese medicine widely used in clinical treatment and preventive healthcare. However, recently there have been frequent reports of liver injury caused by Polygoni Multiflori Radix and its related preparations, and some patients have serious adverse outcomes, attracting wide attention worldwide. The risk of liver damage caused by preparations containing Polygoni Multiflori Radix or Polygoni Multiflori Caulis has been repeatedly reported by the Chinese Food and Drug Administration. Fortunately, substantial progress has recently been made in revealing the basic properties, main causes, material basis, and molecular mechanism of Polygoni Multiflori Radix-related liver injury. The basic characteristics and biomarkers of susceptible people have been identified, indicating that Polygoni Multiflori Radix has the risk of inducing liver injury only in a few specific populations and is safe for most populations. This study provides a scientific basis for a correct and objective understanding of liver injury caused by Polygoni Multiflori Radix, and a reasonable formulation of safe medication measures for Polygoni Multiflori Radix and related preparations. The China Association of Chinese Medicine organized experts in relevant fields across the country to draft and formulate the “Guidelines for Safe Use of Polygoni Multiflori Radix,” with the aim of helping the public and relevant institutions at home and abroad to scientifically understand, evaluate, and avoid the risk of liver injury; guide the rational use; protect the health rights and interests of consumers; and promote the healthy and sustainable development of Polygoni Multiflori Radix and related preparations. These guidelines were issued by the China Association of Chinese Medicine (No.T/CACM 1328-2019).

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Network pharmacology oriented study reveals inflammatory state-dependent dietary supplement hepatotoxicity responses in normal and diseased rats

Abstract: Rhubarb, a well-used herbal and dietary supplement, has been widely used as a laxative in many countries.

Cited by 10 publications

References 46 publications

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Guidelines for safe use of Polygoni Multiflori Radix

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