A Case Report of Acute Hepatitis Involving the Medicinal Herb Tinospora cordifolia Along with Other Variables.

This is a 54-year-old woman from Germany of central European origin who developed an acute hepatitis while orally taking Ayurvedic herbal remedies, among those was the medicinal herb Tinospora cordifolia. She took the plant powders from July 1, 2021, to October 1, 2021, with the intention of relieving the symptoms of her subjectively irritated gastrointestinal tract. The patient's main symptoms of acute hepatitis were progressively increasing general fatigue, nausea, and exhaustion. During an inpatient hospital admission from November 4, 2021, to November 9, 2021, she was under clinical observation, but no specific therapeutic measures were deemed necessary; however, blood chemistry showed an acute toxic hepatitis. There was no clinical or laboratory evidence of acute liver failure. Aminotransferase values decreased to normal values on December 14, 2021, by themselves. This case report contributes to the ongoing discussion about the potential risks of triggering an acute hepatitis due to the intake of herbal remedies from the Tinospora genus in rare cases, differentiating other involved risk factors. The case also shows that causality assignments are not trivial in the context of multivariate clinical scenarios. In the case of known hepatic metabolism-associated risk factors, T. cordifolia should be used with more caution based on available case reports. At the same time, no hasty and exaggerated prejudgments should be made about this medicinal herb, which has been very successfully used in traditional South Asian systems of medicine for many centuries.

Drug-induced, mixed-type hepatitis following ingestion of Cordyceps sinensis.

The use of herbal and dietary supplements is increasing worldwide. Consumers consider it as a natural, and therefore safe and healthy alternative to conventional synthetic drugs and do not expect adverse effects. However, numerous herbal and dietary supplements have been associated with adverse hepatic reactions of variable severity. Recognition of adverse hepatic reactions following the ingestion of herbal and dietary supplements is sometimes difficult since clinical presentation can resemble that of other etiologies unrelated to xenobiotics. Pharmacovigilance is based on spontaneous reporting and, thus, many incidents probably remain unrecorded due to lack of awareness among users and prescribers. The present report describes the first case of cholestatic hepatitis after the intake of an herbal supplement containing Cordyceps sinensis. Causality was considered probable after exclusion of alternative causes, a close temporal relationship, and an immediate dechallenge response with a full remission.

Luteolin ameliorates LPS-induced acute liver injury by inhibiting TXNIP-NLRP3 inflammasome in mice.

BACKGROUND: Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases. PURPOSE: The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis. STUDY DESIGN: Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin. METHODS: Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA, qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury. RESULTS: The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1ß (IL-1ß) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA, SOD, and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro. CONCLUSIONS: These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition.

SCOPE: The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. METHODS AND RESULTS: Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increases interleukin-6 and interferon-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon-like peptide-1 (GLP-1) were higher in IL-TPN. Gluconeogenesis is increased in IL-TPN and the nuclear profile of key metabolic transcription factors shows a liver-protective phenotype in OV-TPN. OV-TPN increases insulin sensitivity in the liver and skeletal muscle. CONCLUSION: OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin.

Dietary Fiber from Oat and Rye Brans Ameliorate Western Diet-Induced Body Weight Gain and Hepatic Inflammation by the Modulation of Short-Chain Fatty Acids, Bile Acids, and Tryptophan Metabolism.

SCOPE: Dietary fiber (DF) induces changes in gut microbiota function and thus modulates the gut environment. How this modulation is associated with metabolic pathways related to the gut is largely unclear. This study aims to investigate differences in metabolites produced by the gut microbiota and their interactions with host metabolism in response to supplementation with two bran fibers. METHODS AND RESULTS: Male C57BL/6N mice are fed a western diet (WD) for 17 weeks. Two groups of mice received a diet enriched with 10% w/w of either oat or rye bran, with each bran containing 50% DF. Microbial metabolites are assessed by measuring cecal short-chain fatty acids (SCFAs), ileal and fecal bile acids (BAs), and the expression of genes related to tryptophan (TRP) metabolism. Both brans lowered body weight gain and ameliorated WD-induced impaired glucose responses, hepatic inflammation, liver enzymes, and gut integrity markers associated with SCFA production, altered BA metabolism, and TRP diversion from the serotonin synthesis pathway to microbial indole production. CONCLUSIONS: Both brans develop a favorable environment in the gut by altering the composition of microbes and modulating produced metabolites. Changes induced in the gut environment by a fiber-enriched diet may explain the amelioration of metabolic disturbances related to WD.

Δ9-Tetrahydrocannabinolic Acid markedly alleviates liver fibrosis and inflammation in mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Medicinal cannabis and some neutral cannabinoids have been suggested as a potential therapy for liver diseases. HYPOTHESIS: Δ9-tetrahydrocannabinolic acid (Δ9-THCA), the non-psychotropic precursor of Δ9-THC, is one of the most abundant cannabinoids presents in Cannabis Sativa. However, its biological activities have been poorly investigated. Herein, we studied the antifibrotic and antiinflammatory activities of Δ9-THCA in two different animal models of liver injury, providing a rationale for additional studies on the medicinal use of this cannabinoid in the treatment of liver fibrosis and the management of NAFLD. STUDY DESIGN: The antifibrotic activity of Δ9-THCA in vitro was investigated in the cell lines LX-2 and NIH-3T3-Col1A2-luc. Non-alcoholic liver fibrosis was induced in mice by CCl4 treatment or, alternatively, by 23-week high fat diet (HFD) feeding. Δ9-THCA was administered daily intraperitoneally during the CCl4 treatment or during the last 3 weeks in HFD-fed mice. METHODS: TGFß-induced profibrotic gene expression was analyzed by luciferase and qPCR assays. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose, insulin, leptin and triglyceride levels were measured in HFD mice. RESULTS: Δ9-THCA inhibited the expression of Tenascin C (TNC) and Col3A1 induced by TGFß in LX-2 cells and the transcriptional activity of the Col1A2 promoter in fibroblasts. Δ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration. CONCLUSIONS: Δ9-THCA prevents TGFß-induced fibrotic markers in vitro and liver inflammation and fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, for the treatment of liver fibrosis and the management of NAFLD.

Protective effect of Chushizi (Fructus Broussonetiae) on acetaminophen-induced rat hepatitis by inhibiting the Toll-like receptor 3/c-Jun N-terminal kinase/c-jun/c-fos/janus protein tyrosine kinase/activators of transcription 3 pathway.

OBJECTIVE: To observe the intervention of Chushizi (Fructus Broussonetiae) (CSZ) on drug-induced liver injury (DILI) in rats, as well as indicators of liver function, serum levels of inflammatory cytokines, and expression of proteins and mRNA associated with toll-like receptor 3 (TLR3) and the signal transducer and activator of transcription 3 (STAT3) pathway in the liver [TLR3, janus protein tyrosine kinase 2 (JAK2), c-jun, c-fos, c-Jun N-terminal kinase 2 (JNK2), and STAT3]. METHODS: Forty specified pathogen free grade Sprague-Dawley rats were randomly divided into the control group, the model group, the silybin group and the CSZ group. Rats were given acetaminophen (APAP) to trigger DILI. Histopathology of the liver was observed by hematoxylin-eosin staining. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), direct bilirubin (DBIL), and total bilirubin (TBIL) in serum were detected by a semi-automatic biochemical instrument. Content of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-13, and IL-22 in serum were detected by the enzyme-linked immunosorbent assay, the expression of TLR3, phosphorylation of JAK2 (p-JAK2), while c-jun and c-fos proteins in the liver were determined by immunohistochemistry; expression of JNK2, and STAT3 in the liver were assayed by Western blot and real-time quantitative polymerase chain reaction. P-JNK2 and p-STAT3 in the liver were assayed by Western blot. RESULTS: After treatment, the activity of ALT, AST, and concentrations of TBIL, DBIL, TNF-α, IL-6, as well as IL-13 in serum, were lower than those in the model group, and expression of p-JAK2, TLR3, c-jun, c-fos, p-STAT3, and p-JNK2 could be downregulated. CONCLUSION: Our findings suggest that CSZ is a valid medicine to alleviate APAP-induced DILI, while its partial mechanism may regulate the TLR3/JNK/ c-jun/c-fos/JAK/STAT3 pathway.

Protective Effects of Black Raspberry (Rubus occidentalis) Extract against Hypercholesterolemia and Hepatic Inflammation in Rats Fed High-Fat and High-Choline Diets.

Choline is converted to trimethylamine by gut microbiota and further oxidized to trimethylamine-N-oxide (TMAO) by hepatic flavin monooxygenases. Positive correlation between TMAO and chronic diseases has been reported. Polyphenols in black raspberry (BR), especially anthocyanins, possess various biological activities. The objective of this study was to determine the effects of BR extract on the level of choline-derived metabolites, serum lipid profile, and inflammation markers in rats fed high-fat and high-choline diets. Forty female Sprague-Dawley (SD) rats were randomly divided into four groups and fed for 8 weeks as follows: CON (AIN-93G diet), HF (high-fat diet), HFC (HF + 1.5% choline water), and HFCB (HFC + 0.6% BR extract). Serum levels of TMAO, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and cecal trimethylamine (TMA) level were significantly higher in the HFC than in the HFCB. BR extract decreased mRNA expression of pro-inflammatory genes including nuclear factor-κB (NF-κB), interleukin (IL)-1ß, IL-6, and cyclooxygenase-2 (COX-2), and protein expression of NF-κB and COX-2 in liver tissue. These results suggest that consistent intake of BR extract might alleviate hypercholesterolemia and hepatic inflammation induced by excessive choline with a high-fat diet via lowering elevated levels of cecal TMA and serum TMAO in rats.

Green tea polyphenols mitigate the plant lectins-induced liver inflammation and immunological reaction in C57BL/6 mice via NLRP3 and Nrf2 signaling pathways.

Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including hepatitis, inflammatory bowel disease, diabetes, and celiac disease. In this present study, we aimed to assess whether green tea polyphenols (GTPs) exerts protective effects against plant lectins-induced liver inflammation and immunological reaction in mice. The C57BL/6 mice received intragastric GTPs (200 mg/kg b.w.) once per day for 7 consecutive days prior to plant lectins stimulation (50 mg/kg b.w., intraperitoneally). GTPs supplementation alleviated the histopathological changes of liver and the disorder of serum biochemical parameters in plant lectins-challenged mice. GTPs supplementation also alleviated plant lectins-induced oxidative stress and liver inflammation, decreasing protein contents and gene expression levels of pro-inflammatory cytokines in the plasma and hepatic tissue and increasing antioxidant capacity in the liver. GTPs decreased the protein expression levels of myeloperoxidase, F4/80 and neutrophil, as determined by immunohistochemical analysis, and T lymphocytes (CD4 and CD8) contents as determined by immunofluorescence analysis, in the liver. Moreover, we found that GTPs inhibited Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome expression and increased nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in the liver tissues of plant lectins-challenged mice. Taken together, these results show that GTPs alleviates hepatic inflammatory damage and immunological reaction after plant lectins challenge, and GTPs (or green tea intake) supplements can be beneficial for people exposed to plant lectins.

Vitamin D Deficiency Induces Insulin Resistance and Re-Supplementation Attenuates Hepatic Glucose Output via the PI3K-AKT-FOXO1 Mediated Pathway.

BACKGROUND: Pandemic vitamin D deficiency is associated with insulin resistance and type 2 diabetes. Vitamin D supplementation has been reported to have improved glucose homeostasis. However, its mechanism to improve insulin sensitivity remains unclear. METHODS AND RESULTS: Male C57BL/6J mice are fed with/without vitamin D control (CD) or Western (WD) diets for 15 weeks. The vitamin-D-deficient lean (CDVDD) and obese (WDVDD) mice are further subdivided into two groups. One group is re-supplemented with vitamin D for 6 weeks and hepatic insulin signaling is examined. Both CD and WD mice with vitamin D deficiency developed insulin resistance. Vitamin D supplementation in CDVDD mice significantly improved insulin sensitivity, hepatic inflammation, and antioxidative capacity. The hepatic insulin signals like pAKT, pFOXO1, and pGSK3ß are increased and the downstream Pepck, G6pase, and Pgc1α are reduced. Furthermore, the lipogenic genes Srebp1c, Acc, and Fasn are decreased, indicating that hepatic lipid accumulation is inhibited. CONCLUSION: The results demonstrate that vitamin D deficiency induces insulin resistance. Its supplementation has significant beneficial effects on pathophysiological mechanisms in type 2 diabetes but only in lean and not in the obese phenotype. The increased subacute inflammation and insulin resistance in obesity cannot be significantly alleviated by vitamin D supplementation. This needs to be taken into consideration in the design of new clinical trials.

The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis.

Recent evidence suggests herbal-induced liver injury (HILI) to account for 20% of cases among the U.S. Drug-Induced-Liver-Injury-Network. To define injury patterns of HILI, we reviewed the clinical data of 413 patients exposed to 53 HDS products by considering the evidence for HILI and its grades of severity. Outstandingly, females developed HILI more rapidly (p = 0.018) and the time to recovery was significantly increased (p = 0.0153). > 90% of reported cases were severe and half of HDS products caused acute liver failure (ALF) requiring liver transplantation or resulted in fatal outcomes. Liver biopsies of 243 patients defined 13 histological features; two-thirds of products elicited immune-mediated hepatitis and included 154 Hy's law positive cases. The histological injury patterns were confirmed among unrelated patients, while accidental re-challenges evidenced culprits as causative. Furthermore, one-fifth of patients presented elevated autoantibody titres indicative of autoimmune-like HILI, and one-third of the products were linked to chronic hepatitis and cholestatic injuries not resolving within 6 months. Lastly, INR and TBL are critical laboratory parameters to predict progression of severe HILI to ALF. Our study highlights the need for a regulatory framework to minimize the risk for HILI. Better education of the public and a physician-supervised self-medication plan will be important measures to abate risk of HILI.

Protective effect of phenolic acids from Chebulae Fructus immaturus on carbon tetrachloride induced acute liver injury via suppressing oxidative stress, inflammation and apoptosis in mouse.

Chebulae Fructus immaturus, a traditional Tibetan medicine, originated from the immature fruit of Terminalia chebula Retz., has been proven to have antioxidat function. However, its protection to injury liver cell caused by carbon tetrachloride (CCl4) has not been clarified. This study evaluated the effect of phenolic acid from Chebulae Fructus immaturus (PATC) on CCl4-induced acute liver injury in mice and related molecular mechanisms. Our data showed that PATC had convincing protective effects on the CCl4-induced acute liver injury by enhancing the anti-oxidative defense system, ameliorating inflammation and inhibiting the hepatocyte apoptosis.

Anti-inflammatory and Antioxidant Effects of Lotus corniculatus on Paracetamol-induced Hepatitis in Rats.

BACKGROUND: Herbal medicines have been used in the treatment of liver diseases for a long time. The current study was elaborated to evaluate in vitro and in vivo antioxidant and anti-inflammatory effects of Lotus corniculatus (L. corniculatus) butanolic extract. METHODS: The in vitro antioxidant and anti-inflammatory properties of L. corniculatus were investigated by employing DPPH radical scavenging, H2O2 scavenging and BSA denaturation assays. In vivo antioxidant and anti-inflammatory effects of L. corniculatus were evaluated against paracetamol (APAP)-induced hepatitis in rats. L.corniculatus at doses of 100 and 200 mg/kg was administered orally once daily for seven days. Serum transaminases (AST and ALT) and lactate dehydrogenase (LDH), total bilirubin levels, liver malondialdehyde (MDA), reduced glutathione (GSH), glutathione S- transferase (GST) and superoxide dismutase (SOD) levels and inflammatory markers, such as serum Creactive protein (CRP), circulating and liver myeloperoxidase (MPO) levels were investigated. Further histopathological analysis of the liver sections was performed to support the effectiveness of L. corniculatus. RESULTS: L. corniculatus exhibited strong antioxidant and anti-inflammatory effects in vitro. In the in vivo study, our findings demonstrate that L. corniculatus (100 and 200 mg/kg) administration led to an amelioration of APAP effects on liver histology, liver functions parameters (AST, ALT, LDH, and total bilirubin levels) and liver oxidative stress markers (MDA, GSH, GST and SOD levels). Furthermore, serum CRP, circulating MPO and liver MPO levels were declined by both doses of L. corniculatus extract. The best benefits were observed with 200 mg/kg of L. corniculatus extract. CONCLUSION: Antioxidant and anti-inflammatory effects of L. corniculatus extract may be due to the presence of active components.

[Severe hepatitis caused by green tea intoxication in a child. Case report]. / Hepatitis grave producida por intoxicación con té verde en un niño. Presentación de un caso.

Herb-induced liver injury is a type of adverse drug reaction related to using herbal medicine, and now is a segment of druginduced liver injury. The use of herbal products has increased significantly, because it is generally regarded as safe and natural by the public. In the United States, the incidence reaches 9 % and, in the countries of Asia, 19-63 % of the total cases of druginduced liver injury. Green tea is obtained from the leaves of the Camellia sinensis. Freshly harvested leaves are stabilized by dry heating to inactivate the polyphenol enzyme and then dried quickly. Its consumption has increased in recent years and has been reported with hepatotoxic reactions. We present a case of severe hepatitis related to the consumption of green tea in a 2-year-old child.

El daño hepático inducido por hierbas es una reacción adversa relacionada con el uso de medicina herbaria, incluida en el grupo de daño hepático inducido por drogas. El uso terapéutico de hierbas medicinales es cada vez más frecuente por la creencia de que los productos naturales o hierbas son siempre seguros. En Estados Unidos, la incidencia de toxicidad alcanza un 9 % y, en países de Asia, un 19-63 % de los casos totales de daño hepático inducido por drogas. El té verde es obtenido de las hojas de la Camellia sinensis. Las hojas recién cosechadas son estabilizadas por calentamiento en seco para inactivar la enzima polifenol y luego se secan rápidamente. Su consumo ha aumentado en los últimos años, y se han documentado reacciones hepatotóxicas. Se presenta un caso de hepatitis aguda grave asociada al consumo de té verde en un niño de 2 años.

Preparation and antagonistic effect of ACE inhibitory peptide from cashew.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides were found to alleviate acute hepatitis significantly. In this study, we purified and identified ACE inhibitory peptide from cashew to evaluate its protective role on alcohol-induced acute hepatitis in mice. RESULTS: The ACE inhibitory peptides were purified by using consecutive chromatographic techniques. One of these peptides (FETISFK) exhibited the highest ACE inhibition rate (91.04 ± 0.31%). In vivo, the results showed that ACE inhibitory peptide decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by alcohol exposure. Moreover, it could increase the activities of superoxide dismutase (SOD) and glutathione (GSH), and decrease the level of malondialdehyde (MDA). It was also found to down-regulate markedly the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It could also decrease the expression of ACE, angiotensin II (AngII) and angiotensin II type 1 receptor (AT1 R). CONCLUSION: These findings support the view that the ACE inhibitory peptide alleviated acute hepatitis by down-regulating the ACE-AngII-AT1 R axis, broadening the research approach to prevent acute hepatitis, and providing experimental data for the development and utilization of cashews. © 2019 Society of Chemical Industry.

Brain Trauma Disrupts Hepatic Lipid Metabolism: Blame It on Fructose?

SCOPE: The action of brain disorders on peripheral metabolism is poorly understood. The impact of traumatic brain injury (TBI) on peripheral organ function and how TBI effects can be influenced by the metabolic perturbation elicited by fructose ingestion are studied. METHODS AND RESULTS: It is found that TBI affects glucose metabolism and signaling proteins for insulin and growth hormone in the liver; these effects are exacerbated by fructose ingestion. Fructose, principally metabolized in the liver, potentiates the action of TBI on hepatic lipid droplet accumulation. Studies in isolated cultured hepatocytes identify GH and fructose as factors for the synthesis of lipids. The liver has a major role in the synthesis of lipids used for brain function and repair. TBI results in differentially expressed genes in the hypothalamus, primarily associated with lipid metabolism, providing cues to understand central control of peripheral alterations. Fructose-fed TBI animals have elevated levels of markers of inflammation, lipid peroxidation, and cell energy metabolism, suggesting the pro-inflammatory impact of TBI and fructose in the liver. CONCLUSION: Results reveal the impact of TBI on systemic metabolism and the aggravating action of fructose. The hypothalamic-pituitary-growth axis seems to play a major role in the regulation of the peripheral TBI pathology.

Protective effect of herbal medicine Huangqi decoction against chronic cholestatic liver injury by inhibiting bile acid-stimulated inflammation in DDC-induced mice.

BACKGROUND: Huangqi decoction (HQD), a classic traditional herbal medicine, has been used for liver fibrosis, but its effect on intrahepatic chronic cholestatic liver injury remains unknown. PURPOSE: In the present study, we investigated the hepatoprotective effect of HQD and the underlying molecular mechanisms in 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine (DDC)-induced chronic cholestatic mice. METHODS: The DDC-induced cholestatic mice were administrated HQD for 4 or 8 weeks. Serum biochemistry and morphology were investigated. The serum and liver bile acid (BA) levels were detected by ultra performance liquid chromatography-tandem mass spectrometry. The liver expression of BA metabolizing enzymes and transporters, and inflammatory and fibrotic markers was measured by real-time polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: HQD treatment for 4 or 8 weeks ameliorated DDC-induced liver injury by improving impaired hepatic function and tissue damage. HQD treatment for 8 weeks further decreased the liver expression of cytokeratin 19, tumor growth factor (TGF)-ß, collagen I, and α-smooth muscle actin, and ameliorated ductular reaction and liver fibrosis. HQD markedly decreased the accumulation of serum and liver BA. The expression of BA-metabolizing enzymes, cytochrome P450 2b10 and UDP glucuronosyltransferase 1 A1, and multidrug resistance-associated protein 2, Mrp3, and Mrp4 involved in BA homeostasis was increased by 4 weeks of HQD treatment. The expression of BA uptake transporter Na+-taurocholate cotransporting polypeptide was decreased and that of Mrp4 was increased after 8 weeks of HQD treatment. Nuclear factor-E2-related factor-2 (Nrf2) was remarkably induced by HQD treatment. Additionally, HQD treatment for 8 weeks decreased the liver expression of inflammatory factors, interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and intracellular adhesion molecule-1. HQD suppressed the nuclear factor (NF)-κB pathway. CONCLUSION: HQD protected mice against chronic cholestatic liver injury and biliary fibrosis, which may be associated with the induction of the Nrf2 pathway and inhibition of the NF-κB pathway, ameliorating BA-stimulated inflammation.