[Drug-induced cholestasis].

Total glucosides of paeony: A review of its phytochemistry, role in autoimmune diseases, and mechanisms of action.

Radix Paeoniae Rubra and Radix Paeoniae Alba are the different characteristic forms of Paeonia lactiflora Pall. They are widely used as traditional Chinese medicines in clinical practices. This study analyzes the development history, efficacy, chemical compositions, and pharmacological effects of Radix Paeoniae Rubra and Radix Paeoniae Alba, and explores the causes of the similarities and differences of these two amalgams. It provides a basis for the clinical application of these two Chinese medicinal materials, and lays a foundation for further study of the pharmacological effects and the quality identification of Paeonia lactiflora Pall as it applies to traditional Chinese medicine.

/pdf/efficacy-chemical-constituents-and-pharmacological-actions-1xy88d7eux.pdf

Efficacy, Chemical Constituents, and Pharmacological Actions of Radix Paeoniae Rubra and Radix Paeoniae Alba.

Ethnopharmacological relevance In Traditional Chinese medicine (TCM) theory, ulcerative colitis (UC) is associated with damp-heat, blood stasis, and intestinal vascular ischemia. Kuijieyuan decoction (KD) is a traditional Chinese medicine based on the above theory and used clinically to alleviate UC injury. Methods The main components of KD were analyzed by using high-pressure liquid chromatography (HPLC) and confirmed by UPLC-MS/MS. A UC model was established in rats by using dextran sulfate sodium (DSS) and dead rats (caused by DSS) were excluded from the study. Forty-eight rats were divided into 6 groups, health control (CG), UC model (UG), sulfasalazine (SG), low-dose KD (LG), middle-dose KD (MG), and high-dose KD (HG) groups. UC damage was assessed by hematoxylin and eosin staining and scan electron microscopy. We measured Toll-like receptor 4 (TLR4), p-phosphatidylinositol 3-kinase (PI3K), PI3K, p-Protein kinase B (AKT), AKT, p-nuclear factor kappa B (NF-κB), NF-κB, oxidative stress marker (superoxidase dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), and malondialdehyde) and inflammatory markers (tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6 and IL-10) in UC tissues. Gut microbiota was analyzed through16S rRNA sequencing. Results The main components of KD consist of gallic acid, paeoniflorin, emodin, berberine, coptisine, palmatine, jatrorrhizine, baicalein and baicalin. The UC model was successfully established by causing intestinal barrier injury with the loss of intestinal villi and destructed mitochondria of intestinal epithelial cells. Both sulfasalazine and KD treatment repaired UC injury, reduced the levels of malondialdehyde, TNFα, IL-1, IL-6, TLR4, p-PI3K, p-AKT, and p-NF-κB, and increased the levels of SOD, GPx, CAT, and IL-10. KD showed a protective function for the UC model in a dose-dependent way. The serum levels of paeoniflorin and baicalin had a strong relationship with the levels of inflammatory and oxidative stress biomarkers. KD treatment increased the proportion of Alloprevotella, Treponema, Prevotellaceae, and Prevotella, and reduced the proportion of Escherichia_Shigella and Desulfovibrio in gut microbiota. Conclusions KD improved intestinal barrier injury of ulcerative colitis, antioxidant and anti-inflammatory properties by affecting TLR4-dependent PI3K/AKT/NF-κB signaling possibly through the combination of its main compounds, and improving gut microbiota.

/pdf/kuijieyuan-decoction-improved-intestinal-barrier-injury-of-3r29ojok4r.pdf

Kuijieyuan Decoction Improved Intestinal Barrier Injury of Ulcerative Colitis by Affecting TLR4-Dependent PI3K/AKT/NF-κB Oxidative and Inflammatory Signaling and Gut Microbiota.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. This study sought to evaluate the insulin-sensitizing effect of paeoniflorin (PF) on high-fat diet-induced NAFLD and possible molecular mechanisms. Male Sprague Dawley rats were fed a high-fat diet (HFD) for 10 weeks to establish the NAFLD model, and PF (20 mg/kg/d) was gavaged to the NAFLD rats for another four weeks. Our results demonstrated that HFD resulted in hepatocellular ballooning, micro-/macrovesicular steatosis, and oxidative stress in the liver, accompanied by increased serum total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and homeostasis model of insulin resistance (HOMA-IR) index. PF treatment improved the biochemical and histopathological changes in NAFLD rats. Moreover, we also found that PF could inhibit lipid ectopic deposition via regulating lipid metabolism (inhibiting lipid synthesis of cholesterol and de novo pathway), and exert insulin sensitizing effect by regulating the insulin signaling pathway IRS/Akt/GSK3β and anti-oxidation. The study findings suggest that PF has therapeutic potential against NAFLD and that it acts through multiple signaling pathways.

/pdf/beneficial-effects-of-paeoniflorin-on-non-alcoholic-fatty-2crr7heyvl.pdf

Beneficial effects of paeoniflorin on non-alcoholic fatty liver disease induced by high-fat diet in rats

Saikosaponin-D Prevents Acute Renal Injury via Inhibition of NLRP3 Inflammasome By SIRT1

Background Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Materials and methods Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. Results Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, γ-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. Conclusion The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis.

/pdf/paeonia-lactiflora-pall-protects-against-anit-induced-294nyybbxd.pdf

Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway

BACKGROUND
A Pueraria lobata (Willd.) Ohwi (PL) has been used in China to detoxify alcohol and protect the liver for millennia, however, its mechanism of liver protection has not been elucidated; and fermentation is considered to be one of the effective ways to enhance the efficacy of traditional Chinese medicine. The aim of this study was to investigate the hepatoprotective mechanism of probiotic-fermented Pueraria lobata (Willd.) Ohwi (FPL). SD rats were administered with FPL followed by gavage of alcohol for 7 consecutive days, following that, liver injury levels were evaluated in rats.


RESULTS
Probiotic-fermented Pueraria lobata (Willd.) Ohwi (FPL) ameliorated lipid accumulation and inflammation levels in rats. Meanwhile, the levels of ethanol dehydrogenase (ADH)、acetaldehyde dehydrogenase (ALDH) and cytochrome P4502E1 (CYP2E1) were elevated by FPL treatment. It was observed that the levels of Catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated, and the expression of Nrf2 and HO-1 genes and proteins were increased by FPL treatment, it demonstrated that Nrf2-mediated signal pathways was activated. Furthermore, FPL restored the composition of the gut microbiota with an increase in the abundances of Firmicutes and Lactobacillus and a decrease in the abundances of Bacteroidota and Akkermansia. Additionally, a strong correlation was found between the gut microbiota and the antioxidant parameters.


CONCLUSION
The results indicate that probiotic-fermented Pueraria lobata (Willd.) Ohwi possesses an excellent protective effect in alcoholic liver injury. Our findings are beneficial to the development of hepatoprotective nutraceuticals for alcoholics. This article is protected by copyright. All rights reserved.

Probiotic-fermented Pueraria lobata (Willd.) Ohwi alleviates alcoholic liver injury by enhancing antioxidant defense and modulating gut microbiota.

Liver-related disease caused by alcohol is a frequent disorder of the hepatic tract. Heavy consumption of alcohol in a short period causes oxidative damage to the liver. Sea cucumber is abundant in nutrients and its various extracts have been studied for antioxidant properties. One peptide was isolated and identified from Apostichopus japonicus in our recent study. We investigated the benefits of the peptide in a model of acute ethanol-induced male C57BL/6J mice. Dietary intake of the peptide could attenuate hepatomegaly, hepatitis and the accumulation of lipid droplets, and increase antioxidant enzyme activities in mice with acute alcoholic liver injury. The results indicated that a 20 mg/kg peptide supplement could activate the Nrf2/HO-1 pathway and block the nuclear translocation of NF-κB to alleviate oxidative stress and inflammation. In addition, the preventive effects of peptide supplementation may be related to autophagy. This study suggests that dietary supplementation with a sea cucumber-derived peptide is one of the potential candidates to alleviate acute alcoholic liver injury.

/pdf/a-peptide-hepfygnegalr-from-apostichopus-japonicus-dparxqf2.pdf

A Peptide HEPFYGNEGALR from Apostichopus japonicus Alleviates Acute Alcoholic Liver Injury by Enhancing Antioxidant Response in Male C57BL/6J Mice

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Papers

Saikosaponin-D Prevents Acute Renal Injury via Inhibition of NLRP3 Inflammasome By SIRT1

Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway

Probiotic-fermented Pueraria lobata (Willd.) Ohwi alleviates alcoholic liver injury by enhancing antioxidant defense and modulating gut microbiota.

A Peptide HEPFYGNEGALR from Apostichopus japonicus Alleviates Acute Alcoholic Liver Injury by Enhancing Antioxidant Response in Male C57BL/6J Mice