Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway

Li, Lei; Huang, Wenxiang; Wang, Shoukai; Sun, Kecheng; Zhang, Wenxue; Ding, Yanmei; Zhang, Le; Tumen, Bayaer; Ji, Lili; Liu, Chang

doi:10.3390/molecules23082032

Cited by 46 publications

(24 citation statements)

References 29 publications

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“…In traditional Chinese formula, AR is often used for the treatment of liver fibrosis [ 10 ]. Although the protective effects of AR on liver injury and related mechanisms have been reported [ 9 , 11 ], the studies on the effect and mechanism of AR on liver fibrosis are still lacking. More importantly, toxicological study has confirmed the high safety of AR.…”

Section: Introductionmentioning

confidence: 99%

Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

Wen

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Astragali Radix (AR), the dried root of Astragali Radix membranaceus (Fisch.) Bge. or Astragali Radix membranaceus (Fisch.) Bge. var. mongholicus (Bge) Hsiao, is a commonly used traditional Chinese medicine for the treatment of liver diseases. This study aimed to comprehensively evaluate the pharmacological action and explore the potential mechanism of AR on liver fibrosis. Rats were administered with carbon tetrachloride for eight weeks, followed by oral treatment with AR for six weeks. The efficacy was confirmed by measuring liver function and liver fibrosis levels. The underlying mechanisms were explored by detecting the expression of related proteins. AR significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (COL-IV), hyaluronic acid (HA), laminin (LN), and precollagen type III (PCIII). In addition, AR inhibited the deposition of collagen and the activation of hepatic stellate cells. Those data strongly demonstrated that AR alleviated liver fibrosis by CCl4. In order to illustrate the potential inflammatory, the mRNA levels of IL-6, TNF-α, and IL-1β were detected. Subsequently, immunohistochemistry analysis was performed to further verify the expression of type I collagen. Finally, the expression of key proteins in the inflammatory signaling pathway was detected. AR significantly reduced the expression of high-mobility group box 1 (HMGB1), TLR4, Myd88, RAGE, and NF-κ B p65 genes and proteins. In addition, western blotting showed AR decreased the protein expression of RAGE, p-MEK1/2, p-ERK1/2, and p-c-Jun. Taken together, our data reveal that AR significantly inhibits liver fibrosis by intervening in the HMGB1-mediated inflammatory signaling pathway and secretion signaling pathway. This study will provide valuable references for the in-depth research and development of Astragali Radix against liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

Wen

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…However, NAC has its limits, such as the short administration period post APAP toxicity (6-8 h). In recent years, a lot of effort has been made to investigate the preventive and therapeutic method for APAP toxicity, especially Chinese herbal medicines (4)(5)(6) and some accepted old drugs.…”

mentioning

confidence: 99%

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Zhang

Jiang

et al. 2021

J Nutr Sci Vitaminol

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Acetaminophen (N-acetyl-p-aminophenol, APAP) overdose causes hepatotoxicity, even liver failure, and oxidative stress plays pivotal role in its pathogenesis. Nicotinic acid (NA) is one form of vitamin B3, which has been used to treat a series of diseases in clinic for decades. To date, several studies have evidenced that NA has anti-oxidative property. Therefore, NA may have the hepatoprotective potential against APAP-induced toxicity. Here, our aim was to investigate the beneficial effect of NA against hepatotoxicity induced by APAP and its mechanism in vivo. BALB/c mice were intraperitoneally injected with NA (100 mg/kg) 3 times at 24, 12 and 1 h before APAP (600 mg/kg or 400 mg/kg) challenge. The results showed that pretreatment of NA markedly improved the survival rate, alleviated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and mitigated the histopathological injuries compared to APAP-exposed mice. Furthermore, NA significantly elevated the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) content, while reduced malondialdehyde (MDA) level. Finally, the signaling pathway was probed. The western blot revealed that NA up-regulated Sirtuin1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase-1 (NQO-1) expression and down-regulated Kelch-like ECH-associated protein 1 (Keap1) level in liver followed APAP exposure, implying Sirt1/Nrf2 axis exerted an essential role in the protective mechanism of NA on APAP toxicity. In brief, pretreatment of NA effectively protects liver against hepatotoxicity due to overdose of APAP through an antioxidant dependent manner modulated by Sirt1/Nrf2 signaling pathway.

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“…The most common used drugs for inducing ALF mainly include D-galactosamine (D-gal) [7,22], acetaminophen (APAP) [26][27][28][29], thioacetamide (TAA) [30], and carbon tetrachloride (CCl 4 ) [31]. In most drug models of ALF, there are nephrotoxicity, cardiotoxicity and other organ damage besides hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Acute Liver Failure Model in Tibet Miniature Pig and Verified by a Non-bioartificial Liver

Liu

Wang

et al. 2021

Preprint

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Background and aims Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality. Animal model is very important to research ALF. This study aimed to establish a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF and verified by a non-bioartificial liver (NBAL).Methods Thirteen Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after central venous catheterization, then D-galactosamine (D-gal) at 0.45, 0.40 and 0.35g/kg body weight were injected through the central venous catheter in group A, B, C. While in group D, D-gal at 0.35g/kg body weight was injected and treated by a NBAL at 48 h after D-gal administration. Vital signs, blood index values were recorded at every 12 h after D-gal administration and every 2 h during NBAL treatemnt. Meanwhile, clinical manifestations, survival times and results of H&E staining, Tunel, Ki67, Masson assays and Picrosirius red staining were performed.Results Tibet miniature pigs developed different degrees of debilitation, loss of appetite and jaundice after D-gal administration. Survival times of groups A, B, C and D were 39.7±5.9 h, 53.0±12.5 h, 61.3±8.1 h and 61±7 h, respectively. Blood levels of ALT, AST, TBIL, Cr, BUN, Amm, PT and inflammation factors (such as TNF-α, IL-1β, IL-6) levels significantly increased compared with baseline in different groups (Ps < 0.05). Pathological results showed obvious liver cell necrosis positively correlated to the dose of D-gal. However, the NBAL did not increase the survival times of ALF, neither Amm and liver cell necrosis, it just decreased some biochemistry indexes (such as TBIL, ALT, AST).Conclusions: We successfully established a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF, the NBAL did not improve the survival times of ALF and we think the dosage of 0.35 g/kg is optimal.

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Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway

Cited by 46 publications

References 29 publications

Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

Nicotinic Acid against Acetaminophen-Induced Hepatotoxicity via Sirt1/Nrf2 Antioxidative Pathway in Mice

Establishment of Acute Liver Failure Model in Tibet Miniature Pig and Verified by a Non-bioartificial Liver

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