Tetrachloride-induced Liver Injury In Mice Research Articles

Retraction: Preventive effect of lemon seed flavonoids on carbon tetrachloride-induced liver injury in mice.

[This retracts the article DOI: 10.1039/D0RA01415J.].

Extracts from sojae semen germinatum ameliorated carbon tetrachloride-induced liver injury in mice

Sojae semen germinatum (SSG) prepared from the germinating black soybean Glycine max L. Merr. is a traditional Chinese herbal medicine with heat-clearing, dampness-removing, and detoxifying properties. In the present study, we explored the effects and possible underlying mechanisms of petroleum ether extract (PEE), ethyl acetate extract (EAE), n-butanol extract (NBE) and aqueous fraction (AF) of SSG on the carbon tetrachloride (CCl4)-induced liver injury in mice, an animal model representing pathological features of “dampness-heat” syndrome from the perspective of Traditional Chinese Medicine. Results showed that the EAE and NBE of SSG significantly protected mice against the CCl4-induced increases of liver tissue index and serum transaminase levels, ameliorated the CCl4-induced liver morphological changes. Compared with CCl4 model controls, EAE and NBE of SSG decreased malondiadehyde (MDA) levels, enhanced glutathione (GSH) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues, as well as reduced the number of apoptotic hepatocytes. Moreover, the CCl4-induced increase of pro-inflammatory cytokine levels in livers was markedly suppressed by pre-treatment with EAE of SSG. Data suggested that SSG extracts showed protective effect on the CCl4-induced liver injury via multiple pharmacological mechanisms including anti-oxidation, anti-inflammation and anti-apoptosis. EAE and NBE appeared to be superior to other fractions.

The Combination of Epigallocatechin Gallate and Lactiplantibacillus plantarum P101 Alleviated Carbon Tetrachloride-Induced Liver Injury in Mice by Regulating Gut Microbiota

Epigallocatechin gallate (EGCG) is a main active ingredient in tea, but it is difficult for it to be absorbed and utilized by the body, resulting in limited bioactivity. Therefore, we explored the role of probiotics in enhancing the physiological activity of EGCG in a mice model of liver injury. Mice were methodically treated with either a single ingredient or a combination of EGCG and Lactiplantibacillus plantarum P101 (LP.P101) for 21 days, and then administrated with intraperitoneal injection of carbon tetrachloride (CCl4) on the last day. As a result, the antioxidative genes were activated and pro-inflammatory genes were suppressed, reducing the oxidative and inflammatory injury of mice, which indicated a better preventive effect of the combination of EGCG and LP.P101 than the single ingredient. Furthermore, 16S rRNA high-throughput sequencing revealed the role of gut microbiota played in liver injury mitigation. The combination of EGCG and LP.P101 increased the relative abundance of Lactobacillus, Akkermansia and other beneficial bacteria that negatively correlated with inflammation and positively correlated with antioxidation. In conclusion, the combination of EGCG and LP.P101 was more effective than the single ingredient in alleviating liver damage caused by CCl4. Altered gut microbiota may be an important cause.

Protective effect of UV-irradiated red perilla (Perilla frutescens (L.) Britton) on carbon tetrachloride-induced liver injury in mice.

UV-irradiated red perilla demonstrated promising protective effects against carbon tetrachloride-induced liver injury in mice. UV exposure significantly enhanced the accumulation of rosmarinic acid, malonylshisonin, and shisonin in red perilla, and increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity. The hepatoprotective effect of UV-irradiated red perilla may be attributed to the high level of its polyphenolic compounds, which exhibit antioxidant activity.

Specnuezhenide reduces carbon tetrachloride-induced liver injury in mice through inhibition of oxidative stress and hepatocyte apoptosis.

This study aimed to investigate the hepatoprotective effects of specnuezhenide against carbon tetrachloride (CCl4)-induced liver injury in mice. Male C57BL/6 mice were intraperitoneally injected with 10 ml/kg body weight of CCl4 (0.5% diluted in arachis oil) for acute liver injury after oral administration of specnuezhenide for 7 days. Twenty-four hours after the final CCl4 injection, mice were euthanized and plasma and liver samples were collected. The results showed that specnuezhenide markedly and dose-dependently reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and relative liver weight, as well as ameliorated histopathological damage caused by CCl4 and decreased malondialdehyde (MDA) levels, and increased the activity of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, specnuezhenide promoted the expression and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the mRNA and protein expression of Nrf2 signalling-related genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Finally, TUNEL staining and immunohistochemistry indicated that specnuezhenide prevented CCl4-induced hepatocytic apoptosis by up-regulating B-cell lymphoma 2 (Bcl-2) expression and downregulating Bcl-2-associated X (Bax) expression. Specnuezhenide reduced CCl4-induced liver injury in mice by inhibiting oxidative stress via activation of Nrf2 signalling and decreasing hepatocyte apoptosis.

New phthalimide analog ameliorates CCl4 induced hepatic injury in mice via reducing ROS formation, inflammation, and apoptosis.

The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.

Protective Effect of Chemically Characterized Polyphenol-Rich Fraction from Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes on Carbon Tetrachloride-Induced Liver Injury in Mice

Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes (A. europaea) is a medicinal plant widely used in traditional medicines to treat various diseases including hepatic pathogenesis. This study was conducted to evaluate the protective effect of chemically characterized polyphenol-rich fraction from A. europaea on carbon tetrachloride-induced liver injury in mice. The chemical characterization of A. europaea polyphenol-rich fraction was carried out using HPLC-DAD (high-performance liquid chromatography (HPLC) with a diode-array detector (DAD)). Carbon tetrachloride (CCl4) was used to induce liver injuries in mice as described in previous works. A polyphenol-rich fraction from A. europaea was used at a dose of 50 mg/Kg to study its hepatoprotective effect. Next, histopathological and biochemical alterations were investigated. The HPLC analysis revealed the presence of several phenolic compounds: gallic acid, methyl gallate, rutin, ferulic acid, and resorcinol. Regarding the mice treated with a polyphenol-rich fraction from A. europaea up to 50 mg/Kg and carbon tetrachloride, no significant biochemical nor histological alterations occurred in their liver; meanwhile, serious biochemical and histopathological changes were noted for liver recovered from the mice treated with carbon tetrachloride only. In conclusion, A. europaea extract is a promising source of hepatoprotective agents against toxic liver injury.

Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis

Ethnopharmacological relevanceKadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases.Aim of the study: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. Materials and methodsThe acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. ResultsThe MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. ConclusionsThis research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

Structural characterization of phosphorylated Pleurotus ostreatus polysaccharide and its hepatoprotective effect on carbon tetrachloride-induced liver injury in mice

This study aimed to explore the basic structural features of phosphorylated Pleurotus ostreatus polysaccharide (PPOP) and study the protective effect of PPOP on liver injury induced by carbon tetrachloride in male Kunming mice. The phosphorylated polysaccharide was prepared from the natural polysaccharide extracted from Pleurotus ostreatus (POP). The structures of PPOP and POP were characterized by FT-IR, ESEM spectroscopy, and Congo red test. Chemical composition analysis revealed that PPOP was mainly composed of rhamnose, galacturonic acid, and xylose in a molar ratio of 0.10: 1.98: 1.00. Structural analysis indicated that PPOP had multi-strand structure and the absorption peaks of PO and P-O-C. Furthermore, animal experiments showed that the hepatoprotective effect of PPOP against liver injury was reflected by decreasing the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, trilaurin, and low-density lipoprotein cholesterol in the serum, increasing the content of high-density lipoprotein cholesterol and albumin in blood, reducing the content of malondialdehyde and promoting the activity of antioxidant enzymes in liver. PPOP exhibited stronger hepatoprotective effect and antioxidant activity in vivo than POP. The final results indicated that PPOP could be used in the treatment of chemical-induced hepatotoxicity based on the above biological research.

Hepatoprotection of pine nut polysaccharide via NRF2/ARE/MKP1/JNK signaling pathways against carbon tetrachloride-induced liver injury in mice

Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl4)-induced liver injury in vitro. The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection. PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl4. The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkp1, which inhibited the activation of JNK induced by CCl4, and suppressed hepatocytes apoptosis by regulating the protein expression of Bax, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkp1/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl4-induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.

Anoectochilus roxburghii polysaccharide prevents carbon tetrachloride-induced liver injury in mice by metabolomic analysis

Anoectochilus roxburghii (Wall.) Lindl, a traditional Chinese medicine, is used for the effective treatment of liver disease in China. Anoectochilus roxburghii polysaccharide (ARPT) is an important constituent of Anoectochilus roxburghii. ARPT exerts a hepatoprotective effect and contributes directly to the therapeutic benefit of Anoectochilus roxburghii. However, the hepatoprotective mechanism of ARPT requires further elucidation. The present study was designed to assess the effects and underlying mechanism of ARPT when used to pretreat carbon tetrachloride (CCl4)-induced liver injury in mice. Mice were randomly divided into three groups: control group (no ARPT treatment or liver injury), model group (liver injury induced with CCl4), and the ARPT group (ARPT pretreatment followed by liver injury). A metabolomic method, based on liquid chromatography combined with mass spectrometry (LC-MS) and pattern recognition analysis, was applied. The data were analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), to determine differentiating metabolites in the serum and liver tissue between the experimental groups. The PCA and OPLS-DA scores plots of the serum and liver tissue samples based on the LC-MS data showed a clear separation between the control and liver injury model group, while the ARPT-treated group showed a trend of close with the control. There were eleven metabolites [PS(O-18:0/0:0), phosphocholine, phenylalanine, hippuric acid, α-ketoisovaleric acid, metyrosine, leucinic acid, ketoleucine, Cer(d18:1/19:0), α-kamlolenic acid, and 4-formyl indole] were identified as candidate biomarkers in the serum samples, eight such metabolites (valine, phosphohydroxypyruvic acid, phosphocholine, ornithine, indole, xanthine, uridine, and glucose 6-phosphate) were found in the liver tissue samples, and one metabolite (phosphocholine) was observed in both the serum and liver tissue samples. These endogenous metabolites are considered to be in response to the hepatoprotective effects of ARPT and are involved in amino acid metabolism, lipid metabolism, gut bacteria metabolism, energy metabolism, and the methylation pathway. These findings suggest that ARPT mitigates the metabolic effect of CCl4-induced hepatotoxicity in mice by affecting at least five different pathways. LC-MS-based metabolomics provides a powerful approach for identifying potential biomarkers and for elucidating the protective mechanisms of traditional Chinese medicines against disease.

Improvement Effect of Lotus Leaf Flavonoids on Carbon Tetrachloride-Induced Liver Injury in Mice.

In this study, the effect of lotus leaf flavonoids (LLF) on carbon tetrachloride (CCl4)-induced liver injury in mice was studied. CCl4 was injected intraperitoneally to induce liver injury in Kunming mice. Mice were treated with LLF by gavage, and the mRNA expression levels in serum and liver were detected. Compared with the model group, LLF significantly reduced the liver index and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) levels in mice with CCl4-induced liver injury. Pathological observation showed that LLF effectively reduced morphological incompleteness and hepatocyte necrosis in CCl4-treated liver tissue. The result of quantitative polymerase chain reaction (qPCR) indicated that LLF significantly up-regulated the mRNA expression levels of copper/zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), and catalase (CAT) and down- regulated the expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β) (p < 0.05). Thus, LLF is an active ingredient that ameliorates liver injury, and it has good application prospect.

Preventive effect of lemon seed flavonoids on carbon tetrachloride-induced liver injury in mice.

The aim of this study was to determine the preventive effect of lemon seed flavonoids (LSF) on carbon tetrachloride-induced liver injury in mice. Liver injury was induced by injection with 2 mL kg−1 of carbon tetrachloride after administration of LSF by gavage. Liver index, serological parameters, and expression intensities of related mRNA and protein in the liver tissue were observed. The results indicated that LSF reduced liver weight and liver index, downregulated serum levels of AST, ALT, ALP, TG, TC, BUN, NO, and MDA, and upregulated levels of ALB, SOD, CAT, and GSH-Px in the mice with liver injury. It also downregulated serum cytokines, such as IL-6, IL-12, TNF-α, and IFN-γ in these mice. qPCR and western blot confirmed that LSF upregulated mRNA and protein expression of Mn-SOD, Cu/Zn-SOD, CAT, GSH-Px, and IκB-α, and downregulated expression of NF-κB-p65, iNOS, COX-2, TNF-α, IL-1β, and IL-6 in the liver tissue of mice with liver injury. The preventive effect on carbon tetrachloride-induced liver injury was attributed to (−)-epigallocatechin, caffeic acid, (−)-epicatechin, vitexin, quercetin, and hesperidin, which were active substances that were detected in LSF by HPLC. Moreover, the effect of LSF is similar to that of silymarin, but the synergistic effect of the five active substances working in concert acted to produce a more robust liver-protecting effect.

Genipin Ameliorates Carbon Tetrachloride-Induced Liver Injury in Mice via the Concomitant Inhibition of Inflammation and Induction of Autophagy.

Genipin, as the most effective ingredient of various traditional medications, encompasses antioxidative, anti-inflammatory, and antibacterial capacities. More recently, it is suggested that genipin protects against septic liver damage by restoring autophagy. The purpose of the current study was to explore the protective effect of genipin against carbon tetrachloride- (CCl4-) induced acute liver injury (ALI) and its underlying molecular machinery. Our results indicated that treatment with genipin significantly reduced CCl4-induced hepatotoxicity by ameliorating histological liver changes, decreasing the aspartate aminotransferase and alanine transaminase levels, alleviating the secretion of inflammatory cytokines, and promoting autophagic flux. Moreover, genipin effectively induced the conversion of LC3 and inhibition of p62 accumulation. The liver expressions of ATG5, ATG7, and ATG12 were significantly increased by genipin pretreatment in the ALI mice model. This protective effect may be mediated by the inhibition of mTOR and the activation of p38 MAPK signaling pathways. Meanwhile, genipin attenuated CCl4-induced inflammatory response by inhibiting the NF-κB and STAT3 signaling pathway. In addition, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or inhibition of p38 MAPK by SB203580 abolished the hepatoprotective effect of genipin. Taken together, our study implicates that genipin has a protective potential against CCl4-induced hepatotoxicity, which might be strongly associated with the induction of autophagy and the attenuation of inflammatory response.

Hepatoprotective effect of crude polysaccharides extracted from Ganoderma lucidum against carbon tetrachloride-induced liver injury in mice.

Background and Aim:Natural products are currently widely used as alternative treatments for liver disease. The study aimed to determine the hepatoprotective effect of crude polysaccharides extracted from Ganoderma lucidum against liver injury induced by carbon tetrachloride (CCl4).Materials and Methods:Twenty-four male BALB/C mice were randomly divided into six groups. Serum and liver samples were taken on day 10 after G. lucidum administration. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were measured using enzyme-linked immunosorbent assays, and the histology of the liver was evaluated using light microscopy.Results:G. lucidum extract significantly decreased the levels of ALT, AST, and MDA and significantly increased the levels of SOD and CAT. In the histological evaluation, the liver tissue of CCl4-treated mice exhibited hydropic degeneration, necrosis, and sinusoidal dilatation. G. lucidum extract administration improved this liver tissue histopathology.Conclusion:Crude polysaccharides extracted from G. lucidum showed a hepatoprotective effect, regenerating damaged liver tissue.

Protective Effect of Selenium-Enriched Red Radish Sprouts on Carbon Tetrachloride-Induced Liver Injury in Mice.

This study aimed to investigate the effect of Se (Selenium) treatment on nutritional quality in radish sprouts. The results showed that 15 µM sodium selenite significantly increased phenolics compounds, flavonoids compounds, anthocyanins, and some essential amino acid content, while improving the total antioxidant capacity of radish sprouts. Besides, the Se-enriched radish sprouts significantly alleviated the liver damage caused by carbon tetrachloride (CCl4 ) in mice and improved the antioxidant capacity of the liver in mice, whereas the Se-enriched radish sprouts alleviated the inflammatory reaction and apoptosis caused by CCl4 . These results imply that Se-enriched radish sprouts have a positive impact on mice with CCl4 -induced liver injury, and that in future Se-enriched radish sprouts could be developed into an effective food and health care product for the liver injury prevention. PRACTICAL APPLICATION: Because selenium is an essential trace element in the human body, selenium-enriched sprouts can help eliminate free radicals in the body, relieve aging, and selenium-deficient diseases. They are easy to grow and have low costs. Hence, selenium-enriched sprouts have a great potential of being widely consumed.

Antioxidant and hepatoprotective activity of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside against carbon tetrachloride-induced liver injury in mice.

This study aims to investigate the antioxidant and hepatoprotective effects of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside (KG) isolated from unripe soybean leaves. Carbon tetrachloride (CCl4)-induced hepatotoxic ddY mice were used in the study. The mice were divided into three groups, namely the control group, the CCl4 group (CCl4, CCl4 injected), and the KG group (KG, CCl4 injected with KG administration). Hepatic injury markers of serum and liver were analyzed. The results show that serum ALT, AST activities, hepatic glutathione, superoxide dismutase, catalase, and glutathione peroxidase activities were normalized in mice pretreated with KG. Furthermore, the liver thiobarbituric acid reactive substances levels were found to be improved by pretreatment with KG, indicating that KG is available to alleviate liver injury, this may be due to its antioxidant properties. This study suggests that unripe soy leaves could be used as functional food materials.

4-O′-methylhonokiol protects from alcohol/carbon tetrachloride-induced liver injury in mice

Methylhonokiol improves liver damage and survival. Methylhonokiol reduces hepatic fibrosis and necroinflammation. Methylhonokiol prevents myofibroblast activation and induces apoptosis. Methylhonokiol upregulates endocannabinoids and related N-acylethanolamines. Methylhonokiol contributes to lipid hydrolysis via PPARα/γ.

Hepatoprotective effect against CCl4-induced acute liver damage in mice and High-performance liquid chromatography mass spectrometric method for analysis of the constituents of extract of Rubus crataegifolius

This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl4. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts. According to the data of HPLC-EIS-MS/MS, the chemical structures of the largely 14 constituents of R. crataegifolius were identified online without time-consuming isolation. Ethyl acetate extracts of R. crataegifolius showed strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4. According to the data of HPLC-EIS-MS/MS, Oleanic acid, Phlorizin dehydrate and Quercetin-3-rhamnoside are considered as the main hepatoprotective factor in ethyl acetate extract.

Schisandra Lignan Extract Protects against Carbon Tetrachloride-Induced Liver Injury in Mice by Inhibiting Oxidative Stress and Regulating the NF-κB and JNK Signaling Pathways.

Schisandra chinensis (S. chinensis) is a traditional Chinese herbal medicine widely used for the treatment of liver disease, whose main active components are lignans. However, the action mechanisms of the lignans in S. chinensis remain unclear. This study aimed to investigate the protective effect and related molecular mechanism of Schisandra lignan extract (SLE) against carbon tetrachloride- (CCl4-) induced acute liver injury in mice. Different doses of SLE at 50, 100, and 200 mg/kg were administered daily by gavage for 5 days before CCl4 treatment. The results showed that SLE significantly decreased the activities of serum ALT/AST and reduced liver pathologic changes induced by CCl4. Pretreatment with SLE not only decreased the content of MDA but increased SOD, GSH, and GSH-Px activities in the liver, suggesting that SLE attenuated CCl4-induced oxidative stress. The expression levels of inflammatory cytokines TNF-a, IL-1β, and IL-6 were decreased after oral administration of SLE, probably because lignans inhibited the NF-κB activity. Additionally, SLE also inhibited hepatocyte apoptosis by suppressing JNK activation and regulating Bcl-2/Bax signaling pathways. In conclusion, these results suggested that SLE prevented CCl4-induced liver injury through a combination of antioxidative stress, anti-inflammation, and antihepatocyte apoptosis and alleviated inflammation and apoptosis by regulating the NF-κB, JNK, and Bcl-2/Bax signaling pathways.