Search

Dioscorea bulbifera L., a commonly used medicinal plant in China, is reported to induce hepatotoxicity. The present study is undertaken to investigate the hepatotoxicity induced by diosbulbin B (DB), a diterpene lactone isolated from D. bulbifera L., and to further explore its underlying mechanism. DB was administered to mice at the doses of 0, 16, 32, and 64 mg/kg once daily for 12 consecutive days. Liver injury induced by DB was evidenced by the increased activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver histological evaluation showed that the mice treated with DB exhibited liver damage with the swelling of hepatocytes. Further results showed that the amount of malondialdehyde (MDA) in the liver was increased in mice treated with DB, while the glutathione amount and the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), copper/zinc–superoxide dismutase (CuZn-SOD), manganese-SOD (Mn-SOD), and catalase (CAT) were all decreased. DB also decreased the gene expression of CuZn-SOD and CAT. Taken together, our results indicate that oral administration of DB for 12 consecutive days can lead to the oxidative stress liver injury in mice. [ABSTRACT FROM AUTHOR]

Endotoxic shock exhibits a considerably high mortality risk. It is defined as a systemic inflammatory response syndrome caused by a microbial infection. Radix Isatidis has anti-inflammatory, antiviral, and antipyretic effects and is used worldwide. This study investigated the antiendotoxin sepsis effects of an aqueous R. Isatidis extract (RIE) and explored the possible pharmacological molecular mechanisms. Male C57BL/6J mice were intravenously injected with 15 mg/kg lipopolysaccharide (LPS) to induce endotoxic shock. The results demonstrated that the survival rate of mice pretreated with RIE increased, and LPS-induced liver and lung damage were reduced by inhibiting inflammation. For elucidating detailed molecular mechanisms, we focused on LPS-induced transcription factors: nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3). Our results demonstrated that the protective effects of RIE were strongly dependent on IRF3-induced interferon-β, not on NF-κB-induced tumor necrosis factor-α and interleukin-1β. In addition, RIE suppressed the phosphorylation of IRF3, not NF-κB. In conclusion, this study revealed the antiendotoxic properties of RIE on LPS-induced sepsis and provided mechanistic evidence for the beneficial effects of RIE. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. Aim of the study The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. Materials and methods The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues. Results The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8 mg/kg, EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90 mg/kg ( P <0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90 mg/kg ( P >0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650 mg/kg and ALK at dosages of 30, 90 mg/kg ( P <0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90 mg/kg ( P <0.05), compared with scopolamine-treated group. Conclusions EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Gentiopicroside (GPS), one of iridoid glucoside representatives, is the most potential active component in Gentiana rigescens Franch. ex Hemsl and Gentiana macrophylla Pall. These two herbs have been used to treat jaundice and other hepatic and billiary diseases in traditional Chinese medicine for thousands of years. Aim of the study This study aimed to investigate the protective effects and mechanisms of GPS on α-naphthylisothiocyanate (ANIT) induced cholestatic liver injury in mice. Materials and methods Mice were treated with GPS (130 mg/kg, ig) for 5 consecutive days. On the third day, mice were given a single dose of Alpha-naphthylisothiocyanate (75 mg/kg, ig). Serum biochemical markers and individual bile acids in serum, liver, urine and feces were measured at different time points after ANIT administration. The expression of hepatic bile acid synthesis, uptake and transporter genes as well as ileum bile acid transporter genes were assayed. Results In this study, ANIT exposure resulted in serious cholestasis with liver injury, which was demonstrated by dramatically increased serum levels of ALT, ALP, TBA and TBIL along with TCA CA, MCAs and TMCAs accumulation in both liver and serum. Furthermore, ANIT significantly decreased bile acid synthesis related gene expressions, and increased expression of bile acid transporters in liver. Continuous treatment with GPS attenuated ANIT-induced acute cholestasis as well as liver injury and correct the dyshomeostasis of bile acids induced by ANIT. Our data showed that GPS significantly upregulated the hepatic mRNA levels of synthesis enzymes ( Cyp8b1 and Cyp27a1) and transporters ( Mrp4 Mdr1 and Ost-β ) as well as ileal bile acid circulation mediators ( Asbt and Fgf15) , accompanied by serum and hepatic bile acid levels decrease and further urinary and fecal bile acid levels increase. Conclusion GPS can change bile acids metabolism which highlights its importance in mitigating cholestasis, resulting in the marked decrease of intracellular bile acid pool back toward basal levels. And the protective mechanism was associated with regulation of bile acids-related transporters, but the potential mechanism warrants further investigation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Diosbulbin B (DB) is the main hepatotoxic compound distributed in Dioscorea bulbifera L., which is widely used for the treatment of cancer and thyroid disorders in Asia. Scutellarin (SC) is the main compound in medicinal herb Scutellaria barbata D. Don, which is usually combined with Dioscorea bulbifera used for cancer therapy in clinic. Aim of the study This study aims to investigate the protection of SC against the liver injury induced by DB and its engaged mechanism. In addition, the anti-tumor effect of DB and SC is further observed in vivo . Materials and methods The protection of SC against DB-induced liver injury was evaluated by detecting serum alanine/aspartate aminotransferases (ALT/AST) and alkaline phosphatase (ALP) activities, and further liver histological observation. The inflammatory response was assessed by detecting liver myeloperoxidase (MPO) activity, and serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon-γ (IFN-γ). Western-blot analysis was used to detect the protein expression. The oxidative liver injury was evaluated by detecting liver malondialdehyde (MDA) and glutathione (GSH) contents, and glutathione peroxidase (GPx) enzymatic activity. In vivo anti-tumor activity was analyzed in S180 tumor-bearing mice. Results SC significantly decreased the increased serum ALT/AST, and ALP activities induced by DB. Liver histological observation evidenced the protection of SC against DB-induced liver injury. SC obviously reduced the increased liver MPO activity and the number of MPO-positive staining cells induced by DB. SC also reversed the decreased expression of inhibitor of κB (IκB) and the translocation of nuclear factor κB (NF-κB) p65 from cytoplasm to nucleus induced by DB. In addition, SC significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by DB. SC decreased the increased liver MDA content induced by DB significantly, and it also increased liver GSH level. The decreased GPx protein expression and its enzymatic activity induced by DB were both obviously reversed after SC treatment. The results in S180 tumor-bearing mice showed that SC combined with DB significantly inhibited tumor growth in vivo . Conclusions Our results demonstrate that SC prevents DB-induced liver injury by attenuating NF-κB-mediated hepatic inflammation and ameliorating liver oxidative stress injury. Meanwhile, DB plus SC has significant anti-tumor activity in vivo . This study indicates the potential combination of DB with SC for the treatment of cancer in clinic. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb in Uighur medicine in China, and it is traditionally used for treatment of cough and asthma.The aim of the present study is to evaluate the antitussive, expectorant and bronchodilating effects of extract and fractions (alkaloids and flavonoids) from APP, and to support its folk use with scientific evidence, and lay a foundation for its further researches. Materials and methods APP was extracted with 50% ethanol by reflux, extracts were concentrated in vacuum to afford total extract of APP (EXT). EXT was separated to provide alkaloid fraction (ALK) and flavonoid fraction (FLA) by macroporous resin. Antitussive evaluations were carried out with cough models in mice and guinea pigs induced by ammonia liquor, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity. Bronchodilating activities were evaluated with a bronchoconstrictive challenge induced by acetylcholine chloride and histamine in guinea pigs. Results In all the three antitussive tests, the EXT and ALK could significantly inhibit the frequency of cough, and prolong the cough latent period in animals. High dose of EXT (1650 mg/kg) and ALK (90 mg/kg) in mice and in guinea pigs created therapeutic activities as good as that of codeine phosphate (30 mg/kg). EXT could significantly increase phenol red secretion in mice for 0.64, 1.08 and 1.29 fold averagely at dosages of 183, 550, and 1650 mg/kg, ALK for 0.63, 0.96, 1.06 fold averagely at dosages of 10, 30, and 90 mg/kg, and ammonium chloride (1500 mg/kg, standard expectorant drug) for 0.97 fold, comparing with control group. Aminophylline could dramatically prolong the preconvulsive time for 162.28% in guinea pigs, EXT for 67.34%, 101.96% and 138.00% at dosages of 183, 550, and 1650 mg/kg, ALK for 55.47%, 97.74% and 126.77% at dosages of 10, 30, and 90 mg/kg, and FLA for 84.69%, 95.94% and 154.52% at dosages of 10, 30, and 90 mg/kg, comparing with pretreatment. Conclusions APP is an effective traditional folk medicine for the treatment of cough with potent antitussive, expectorant and bronchodilating activities. The alkaloid fraction is proved to be the most effective components of APP. The alkaloids from APP may be valuable lead compounds for drug development of respiratory diseases. [ABSTRACT FROM AUTHOR]

Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. Aim of the study: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α. Image 1 • Sweroside ameliorates the HFD-induce body weight gain, hepatic steatosis and serum lipid levels in DIO mice. • Sweroside improves glucose homeostasis and insulin sensitivity in DIO mice. • Sweroside attenuates HFD-induced hepatic inflammation in DIO mice. • Sweroside improves obesity with fatty liver by regulating the lipid metabolism and inflammatory responses. • The effect of sweroside in regulating inflammatory response and lipid metabolism is closely related with PPAR-α. [ABSTRACT FROM AUTHOR]

Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear. The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR. The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1 , Cyp3a11 , Fxr , and Shp were up-regulated in DNLA treatment group. DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption. Image 1 [ABSTRACT FROM AUTHOR]