Integrated metabolomics and network pharmacology to reveal the lipid-lowering mechanisms of Qizha Shuangye granules in hyperlipidemic rats.

BACKGROUND: Qizha Shuangye granules (QSG) comprise six traditional Chinese herbal medicines (TCHMs), which have a long history of treating hyperlipidemia (HLP) in China. This study aimed to evaluate the potential lipid-lowering effects of QSG in an HLP rat model and investigate possible mechanisms. The HLP rat model was induced by a high-fat diet. Lipid-related indicators in serum were detected. Serum and liver metabolites were investigated using a liquid chromatography-mass spectrometry-based metabolomics approach. A herb-compound-target-metabolite (H-C-T-M) network was further constructed to reveal the possible molecular mechanism of QSG to alleviate HLP. RESULTS: The administration of QSG inhibited the HLP-induced changes in total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) levels. Additionally, QSG significantly attenuated the liver histopathological changes induced by HLP. Metabolomic analysis showed the serum and liver metabolic disorders presented in HLP rats. QSG can reverse the abnormal metabolism caused by HLP. Through network pharmacology analysis, key proteins such as androgen receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and peroxisome proliferator-activated receptor-α were screened out, and they were speculated to be possible therapeutic targets for QSG to treat HLP. CONCLUSION: The present study integrated metabolomics and network pharmacology analysis to reveal the efficacy and possible mechanism of QSG in treating HLP, which provides a new reference for the research and development of QSG as a functional food. © 2023 Society of Chemical Industry.

Anti-lipid accumulation effects and mechanism of the extract and isolated compounds from Potentilla longifolia.

Potentilla longifolia is effective in the treatment of hepatitis as a Chinese herb. We firstly evaluated the effect of water extract of P. longifolia (WEPL) on mice with nonalcoholic fatty liver disease (NAFLD) induced by high-fat (HF) diet. The results showed that WEPL reduced HF-induced increases of the serum ALT, AST, TG and TC, and reduced lipid drops of liver tissues to a different extent compared with HF group; WEPL dose-dependently promoted the phosphorylation degrees of AMPK and ACC; WEPL decreased significantly genes expressions of SREBP1α, FAS and SCD1 and increased PPARα and CD36. Then three new (1-3) and 13 known compounds (4-16) were firstly-isolated from the 95% ethanol extract of this plant. Further experiments showed that a new compound (ganyearmcaooside C) showed the best inhibitory effect on lipid accumulation in 3 T3-L1 cells such as reducing the accumulation of oil droplets and triglyceride level, showing new drug potential for related diseases.

Pharmacological Properties of Ginsenoside Re.

Ginsenoside Re is a protopanaxatriol-type saponin extracted from the berry, leaf, stem, flower bud, and root of Panax ginseng. In recent years, ginsenoside Re (Re) has been attracting attention as a dietary phytochemical. In this review, studies on Re were compiled by searching a combination of keywords, namely "pharmacology," "pharmacokinetics," and "toxicology," in the Google Scholar, NCBI, PubMed, and Web of Science databases. The aim of this review was to provide an exhaustive overview of the pharmacological activities, pharmacokinetics, and toxicity of Re, focusing on clinical evidence that has shown effectiveness in specific diseases, such as diabetes mellitus, nervous system diseases, inflammation, cardiovascular disease, and cancer. Re is also known to eliminate virus, enhance the immune response, improve osteoporosis, improve skin barrier function, enhance intracellular anti-oxidant actions, regulate cholesterol metabolism, alleviate allergic responses, increase sperm motility, reduce erectile dysfunction, promote cyclic growth of hair follicles, and reduce gastrointestinal motility dysfunction. Furthermore, this review provides data on pharmacokinetic parameters and toxicological factors to examine the safety profile of Re. Such data will provide a theoretical basis and reference for Re-related studies and future applications.

Corosolic acid ameliorates non-alcoholic steatohepatitis induced by high-fat diet and carbon tetrachloride by regulating TGF-ß1/Smad2, NF-κB, and AMPK signaling pathways.

Hawthorn (Crataegus pinnatifida Bunge. var. major) is an edible and medicinal fruit that is very common in food and traditional Chinese medicine. Corosolic acid (CA), a pentacyclic triterpenoid, which is an active component of hawthorn (Crataegus pinnatifida Bunge. var. major), has been exhibiting various pharmacological activities such as antidiabetic, antibacterial, anticancer, antiinflammatory, and antioxidant effects. The study aimed to evaluate the effect of CA on non-alcoholic steatohepatitis (NASH) in mice induced by 60 kcal% high-fat diet (HFD) and carbon tetrachloride (CCl4 ). CA lowered liver index and serum AST, ALT, TG, and TC levels compared to those in the model group. Histological analyses of the liver tissues of mice treated with CA revealed significantly decreased number of lipid droplets and alleviated inflammation and fibrosis. CA inhibited the transcripts of pro-fibrogenic markers (including α-SMA, collagen I, and TIMP-1) and the levels of pro-inflammatory cytokines (including TNF-α, IL-1ß, caspase-1, and IL-6) associated with hepatic fibrosis, and NF-κB translocation and TGF-ß1/Smad2 and AMPK pathways. In addition, CA reduced lipid accumulation via the regulation of AMPK and NF-κB activation in FFA-induced steatotic HepG2 cells. CA also decreased α-SMA, collagen I expressions, and Smad2 phosphorylation, which were reduced by TGF-ß1 treatment in LX2 cells. Our results suggested that CA ameliorated NASH through regulating TGF-ß1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.

Inhibitory Effects of Twenty-Nine Compounds From Potentilla longifolia on Lipid Accumulation and Their Mechanisms in 3T3-L1 Cells.

Potentilla longifolia Willd. ex D.F.K.Schltdl., which is a kind of traditional Chinese herb, is often referred to as "Ganyancao" in China, which means "the herb is effective in the treatment of liver inflammation". Three new (ganyearmcaoosides A and B and ganyearmcaoic acid A; 1-3) and 26 known compounds (4-29) were isolated from the 95% ethanol extract of the dried aerial parts of this plant, of which 21 were isolated for the first time from this plant. The chemical structures of these compounds were elucidated using NMR and HR-ESI-MS analysis. The inhibitory effects of the 29 compounds with safe concentrations on the lipid accumulation in 3T3-L1 cells were evaluated using photographic and quantitative assessments of lipid contents by Oil Red O staining, and measurement of the triglyceride levels. Comprehensive analysis showed that compound 12 (3,8-dimethoxy-5,7,4'- trihydroxyflavone) showed the best inhibitory effect on lipid accumulation such as reducing the accumulation of oil droplets and triglyceride level, and was superior to the reference in positive control. Western blot analysis and RT-PCR results showed that compound 12 enhanced the phosphorylations of AMPK and ACC, and inhibited the expressions of adipogenesis-related proteins or genes including SREBP1c, FAS, SCD1, GPAT, PPARγ and C/EBPα, and thereby significantly inhibited lipid accumulation in a concentration-dependent manner. P. longifolia and its bioactive compounds could be promising as potential therapeutic agents for diseases related to lipid accumulation in the future.

Inhibitory effects of compounds from the roots of Potentilla longifolia on lipid accumulation.

Potentilla longifolia is a kind of Chaoyao medicine, which is a branch of traditional Chinese medicine. The plant is often referred to as ganyancao or ganyearmcao, which means that it has a significant therapeutic effect on liver inflammation. In previous experiments, we found that a water extract of ganyearmcao inhibited lipid accumulation. In the present study, we isolated one new (ganyearmcaoone A, 1) and eight known compounds (2-9) from a water extract of the dried roots of ganyearmcao; all of the compounds were isolated for the first time from this medicinal plant. We elucidated the chemical structures of these compounds using comprehensive analyses of HR-ESI-MS and 1D, 2D NMR. We evaluated the inhibitory effects of the nine compounds on lipid accumulation in 3T3-L1 cells; we did so using photographic and quantitative assessments of the lipid content with oil red O staining and by measuring triglyceride levels. Compared with the control, compounds 6 and 9 significantly inhibited differentiation of 3T3-L1 cells and lipid accumulation. Compound 1 showed potential inhibitory effects on lipid accumulation. Molecular docking results indicated that compounds 6 and 9 may efficiently bind to AMPK and its downstream kinase (SCD1), thereby inhibiting lipid accumulation. Our results demonstrate that ganyearmcao and its components may play an important role in treating diseases related to lipid accumulation in the future.

Corosolic Acid Attenuates Hepatic Lipid Accumulation and Inflammatory Response via AMPK/SREBPs and NF-κB/MAPK Signaling Pathways.

Corosolic acid (CA) is the main active component of Lagetstroemia speciosa and has been known to serve as several different pharmacological effects, such as antidiabetic, anti-oxidant, and anticancer effects. In this study, effects of CA on the hepatic lipid accumulation were examined using HepG2 cells and tyloxapol (TY)-induced hyperlipidemia ICR mice. CA significantly inhibited hepatic lipid accumulation via inhibition of SREBPs, and its target genes FAS, SCD1, and HMGCR transcription in HepG2 cells. These effects were mediated through activation of AMPK, and these effects were all abolished in the presence of compound C (CC, an AMPK inhibitor). In addition, CA clearly alleviated serum ALT, AST, TG, TC, low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) levels, and obviously attenuated TY-induced liver steatosis and inflammation. Moreover, CA significantly upregulated AMPK, ACC, LKB1 phosphorylation, and significantly inhibited lipin1, SREBPs, TNF-α, F4/80, caspase-1 expression, NF-κB translocation, and MAPK activation in TY-induced hyperlipidemia mice. Our results suggest that CA is a potent antihyperlipidemia and antihepatic steatosis agent and the mechanism involved both lipogenesis and cholesterol synthesis and inflammation response inhibition via AMPK/SREBPs and NF-κB/MAPK signaling pathways.

Synergistic Inhibitory Effects of Acacetin and 11 Other Flavonoids Isolated from Artemisia sacrorum on Lipid Accumulation in 3T3-L1 Cells.

Artemisia sacrorum Ledeb., a Compositae forage plant in China, has been found to have an inhibitory effect on lipid accumulation. We selected 12 flavonoids, which we had isolated from A. sacrorum and had the potential to inhibit lipid accumulation in the literature or in our preliminary experiments, and grouped them into 11 compound combinations; we investigated their synergistic inhibitory effects on lipid accumulation in 3T3-L1 cells. In screening experiments, Oil-Red O staining, triglyceride levels, and lipid accumulation levels all indicated that combined acacetin and apigenin displayed a significant synergistic inhibitory effect and the best repeatability. Subsequent research showed that this combination could synergistically promote the phosphorylations of AMPK and ACC. Furthermore, to a different extent, that combination had significant synergistic inhibitory effects on various genes or proteins related to adipogenesis and lipogenesis. Thus, that combination could significantly reduce triglyceride levels and lipid accumulation compared with acacetin or apigenin acting alone.

How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.

Tetrahydropalmatine inhibits lipid accumulation through AMPK signaling pathway in 3T3­L1 adipocytes.

Tetrahydropalmatine (THP), one of the active components of Rhizoma corydalis, has been reported to exert several pharmacological effects, including anti­inflammatory, anti­tumor and analgesic activities. However, its effect on obesity and the underlying molecular mechanisms that may be involved have not yet been elucidated. In the present study, the inhibitory effects of THP on the adipogenesis in 3T3­L1 adipocytes was examined using hstology, western blotting and RT­qPCR. THP was identified to significantly suppress lipid accumulation in 3T3­L1 cells and it inhibited pre­adipocyte differentiation in a concentration­dependent manner, as evidenced by the reduced formation of lipid droplets and decreased triglyceride levels and glycerol­3­phosphate dehydrogenase activity. THP downregulated the adipogenesis­associated protein and gene expressions of sterol regulatory element­binding protein 1, fatty acid synthase, stearoyl­CoA desaturase 1, peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein­α in a concentration­dependent manner. In addition, it reduced adipocyte fatty acid binding protein and glycerol­3­phosphate acyltransferase gene expression in a concentration­dependent manner. Conversely, THP increased the mRNA expression of carnitine palmitoyltransferase 1 in a concentration­dependent manner. Furthermore, THP increased AMP­activated protein kinase (AMPK) and acetyl­CoA carboxylase phosphorylation in a concentration­dependent manner. These results suggested that anti­adipogenic activity of TPH may be mediated via the AMPK pathway in 3T3­L1 cells.

Flavonoids from Artemisia sacrorum Ledeb. and their cytotoxic activities against human cancer cell lines.

Flavonoids have been demonstrated to have cytotoxic activities toward numerous human cancer cells, whereas they have little or no effect on normal cells. The numerous flavonoids in traditional Chinese herbs may be promising candidates for the development of novel anti-cancer drugs. Our previous study demonstrated that CH2Cl2 and 95% ethanol eluate (EE) fractions have the strongest cytotoxic activities against human cancer cell lines of the 9 fractions separated from Artemisia sacrorum Ledeb., which is widely used to prevent and treat diverse diseases in Northeast China. In the present study, 8 flavonoids were isolated from the 95% EE fraction of Artemisia sacrorum Ledeb. The chemical structures of the compounds were elucidated by extensive spectroscopic analyses. The following 5 flavonoids were isolated for the first time from this plant: Jaceosidin, kaempferol, quercetin, luteolin and quercitrin. A total of 2 flavonoids from the CH2Cl2 fraction and 8 flavonoids from the 95% EE fraction were examined to evaluate their cytotoxic activities against human SK-HEP-1 hepatoma cancer cells and human HeLa cervical cancer cells, respectively. The results revealed that 2 flavonoids had marked cytotoxic activities against HeLa cells.

The Traditional Medicine and Modern Medicine from Natural Products.

Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

Combination of deep sea water and Sesamum indicum leaf extract prevents high-fat diet-induced obesity through AMPK activation in visceral adipose tissue.

The aim of the present study was to evaluate the protective effects of a combination of deep sea water (DSW) and Sesamum indicum leaf extract (SIE) against high-fat diet (HFD)-induced obesity and investigate its molecular mechanisms in adipose tissue. ICR mice were randomly divided into three groups: HFD control (HFC), DSW and DSW + 125 mg/kg SIE (DSS) groups. The mice in the HFC group had free access to drinking water while those in the DSW and DSS groups had free access to DSW. The mice in the DSS group were treated with SIE once per day for 8 weeks. The mice in all three groups were allowed to freely access a HFD. Compared with the HFC group, the DSS group showed lower body weight gain and serum levels of glucose, triglycerides and leptin. Histological analyses of the epididymal white, retroperitoneal white and scapular brown adipose tissue of mice in the DSS group revealed that the adipocytes were markedly decreased in size compared with those in the HFC group. Moreover, DSS significantly increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC) in mice epididymal adipose tissues. Furthermore, DSS upregulated the expression levels of lipolysis-associated mRNA, specifically peroxisome proliferator-activated receptor-α (PPAR-α) and cluster of differentiation 36 (CD36), and energy expenditure-associated mRNA, namely uncoupling protein 2 (UCP2) and carnitine palmitoyltransferase-1 (CPT1) in the epididymal adipose tissues. By contrast, DSS suppressed the expression of the lipogenesis-related gene sterol regulatory element-binding protein-1 (SREBP1) at the mRNA level. These results suggest that DSS is effective for suppressing body weight gain and enhancing the lipid profile.

Synthesis of 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives and evaluation of their anticonvulsant activities.

This work concerns the design and synthesis of novel, substituted 5-alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives 5a-p prepared from 3-amino-2-thiophenecarboxylic acid methyl ester. The final compounds were screened for their in vivo anticonvulsant activity using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Neurotoxicity (NT) was tested using a rotarod test. The structure-anticonvulsant activity relationship analysis revealed that the most effective structural motif involves a substituted phenol, especially when substituted with a single chlorine, fluorine or trifluoromethyl group (at the meta-position), or two chlorine atoms. These molecules possessed high activity according to the MES and scPTZ models. Quantitative assessment of the compounds after intraperitoneal administration in mice showed that the most active compound was 5-[3-(trifluoromethyl)phenoxy]thieno[2,3-e] [1,2,4]triazolo[4,3-c]pyrimidine (5o) with ED50 values of 11.5 mg/kg (MES) and 58.9 mg/kg (scPTZ). Furthermore, compound 5o was more effective in the MES and scPTZ tests than the well-known anticonvulsant drugs carbamazepine and ethosuximide.

Cytotoxic fraction from Artemisia sacrorum Ledeb. against three human cancer cell lines and separation and identification of its compounds.

Artemisia sacrorum Ledeb. was extracted by 95% ethanol and water, respectively. By partitioning the 95% ethanol extract successively with different solvents and separating the water extract by macroporous resin, nine separate parts were obtained. According to the results of in vitro experiments, the CH2Cl2 (dichloromethane) fraction showed the most pronounced cytotoxic activity against HepG2, HT-29 and MCF-7 cells, with EC50 values 122.35, 49.76 and 28.51 µg mL⁻¹, respectively, at 48 h. Following this, the compounds of the CH2Cl2 fraction were separated and identified. Ten compounds were isolated from A. sacrorum Ledeb. and identified by spectral analysis. Four compounds, including acacetin, were isolated for the first time from A. sacrorum Ledeb.

An active part of Artemisia sacrorum Ledeb. suppresses gluconeogenesis through AMPK mediated GSK3ß and CREB phosphorylation in human HepG2 cells.

In this study, we investigated the effects of a petroleum ether fraction of Artemisia sacrorum Ledeb. (Compositae) (PEASL) on glucose production through AMP-activated protein kinase (AMPK) activation in human HepG2 cells. PEASL significantly inhibited glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. PEASL markedly induced the phosphorylation of AMPK and downstream acetyl-CoA carboxylase (ACC) in a time- and concentration-dependent manner. In addition, it markedly increased the phosphorylations of glycogen synthase kinase 3ß (GSK3ß) in a concentration-dependent manner. In contrast, cAMP response element binding protein (CREB), a key transcription factor for gluconeogenic enzyme phosphorylation, decreased in a concentration-dependent manner. PEASL downregulated the gluconeogenesis gene expression of peroxisome proliferation activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) in a concentration-dependent manner. In addition, the gene expression of orphan nuclear receptor small heterodimer partner (SHP) increased, also in a concentration-dependent manner. These effects were also abolished by pretreatment with compound C, an AMPK inhibitor. This indicates that PEASL inhibited glucose production via the AMPK-GSK-CREB pathway in HepG2 cells, and these effects appeared to be capable of revealing anti-diabetic mechanism of PEASL in HepG2 cells.

An active part of Artemisia sacrorum Ledeb. inhibits adipogenesis via the AMPK signaling pathway in 3T3-L1 adipocytes.

Artemisia sacrorum Ledeb. (Compositae) (ASL) has long been used in Oriental folk medicine to treat diverse hepatic diseases. In this study, we investigated the effect of ASL on adipocyte differentiation in 3T3-L1 cells. ASL significantly suppressed 3T3-L1 differentiation in a concentration-dependent manner. A significant increase of AMP-activated protein kinase (AMPK) was observed when the cells were treated with ASL. Activation of AMPK was also demonstrated by measuring the phosphorylation of acetyl-CoA carboxylase, a substrate of AMPK. These effects were abolished by pre-treatment with the AMPK inhibitor, compound C. In addition, ASL down-regulated the adipogenesis-related gene expression of the sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in a concentration-dependent manner. These effects were abolished by pre-treatment with compound C. ASL significantly reduced the gene expression of the peroxisome proliferator-activated receptor γ (PPARγ) and of the CCAAT/enhancer binding protein-α (C/EBPα), two key transcription factors in adipogenesis. Meanwhile, adipocyte fatty acid binding protein (aP2) gene expression was also reduced in a concentration-dependent manner. These findings indicated that ASL exerts anti-adipogenic activity via AMPK activation and may act to prevent obesity.

An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells.

Artemisia sacrorum Ledeb. (Compositae) (ASL) is a traditional Chinese medicine used to treat different hepatic diseases. However, a hypolipidemic effect of ASL on fatty liver disease has not been reported. Therefore, we investigated whether 95% ethanol eluate (EE), an active part of ASL, would attenuate hepatic lipid accumulation in human HepG2 cells by activating AMP-activated protein kinase (AMPK). Significant decreases in triglyceride levels and increases in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation were observed when the cells were treated with 95% EE. EE down-regulated the lipogenesis gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), in a time- and dose-dependent manner. In contrast, the lipolytic gene expression of peroxisome proliferator-activated receptor alpha (PPAR-alpha) and CD36 increased in a time- and dose-dependent manner. These effects were abolished by pretreatment with compound C, an AMPK inhibitor. However, there were no differences in the gene expression of SREBP2, low density lipoprotein receptor (LDLR), hydroxymethyl glutaryl CoA reductase (HMG-CoA), or glucose transporter 2 (GLUT2). At the same time, 95% EE significantly increased the gene expression of acyl CoA oxidase (ACOX) in a time- and dose-dependent manner. Thus, AMPK mediated 95% EE induced suppression of SREBP1c and activation of PPAR-alpha respectively. These finding indicate that 95% EE attenuates hepatic lipid accumulation through AMPK activation and may be active in the prevention of serious diseases such as fatty liver, obesity, and type-2 diabetic mellitus.

Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice.

AIMS OF STUDY: Although Artemisia sacrorum Ledeb. (Compositae) has long been used as one kind of oriental folk medicine to treat some liver diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. This study was designed to investigate the hepatoprotective effects of 50% ethanol eluate precipitation of Artemisia sacrorum Ledeb. (EEP) on acetaminophen (APAP)-induced toxicity in mice. MATERIALS AND METHODS: The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in mouse sera, and glutathione (GSH), malondialdehyde (MDA) in mouse liver tissues were measured. In addition, apoptosis and necrosis were evaluated by liver histopathological analysis and DNA laddering. Moreover, caspase-3 and -8 protein expressions in mouse livers were observed by Western blot analysis. RESULTS: Pretreated with EEP prior to the administration of APAP significantly prevented the increases of AST, ALT, and TNF-alpha levels in sera, and suppressed the GSH depletion, MDA accumulation in liver tissues markedly. In addition, EEP prevented APAP-induced apoptosis and necrosis, as indicated by liver histopathological analysis, immunohistochemical analysis, and DNA laddering. Furthermore, according to the results from Western blot analysis, EEP decreased APAP-induced caspase-3 and caspase-8 protein expressions in mouse livers markedly. CONCLUSION: All these results suggest that the protective effects of EEP against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-alpha mediated apoptosis. In a word, EEP could be a valuable candidate for further development for prevention and treatment of hepatic injury.

Protective Effects of the Supernatant of Ethanol Eluate from Artemisia sacrorum Ledeb. against Acetaminophen-Induced Liver Injury in Mice [corrected].

This study was designed to investigate the protective effects of the active part of Artemisia sacrorum Ledeb. Extract (ASE) against acetaminophen (APAP)-induced hepatotoxicity in mice. As a result, pretreated with ASE prior to the administration of APAP significantly prevented the increases of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-alpha) levels in serum, and glutathione (GSH) depletion, malondialdehyde (MDA) accumulation in liver tissue. In addition, ASE prevented APAP-induced apoptosis and necrosis, as indicated by a liver histopathological analysis and DNA laddering. Furthermore, according to the results from Western blot analysis, ASE markedly decreased APAP-induced caspase-3 and -8 protein expressions in mouse livers. All these results suggest that the protective effects of ASE against APAP-induced liver injury may involve mechanisms associated with its inhibitive effects of lipid peroxidation and the down-regulation of TNF-alpha mediated apoptosis.