Protective effect of triterpenes of Ganoderma lucidum on lipopolysaccharide-induced inflammatory responses and acute liver injury.

Ganoderma lucidum is a popular medicinal mushroom, which has been used as therapeutic for centuries in traditional Chinese medicine. Although G. lucidum showed strong protective effects in prevention or treatment of a variety of inflammatory diseases, the mechanisms underlying the anti-inflammatory properties of triterpenes of G. lucidum remain undefined. In the current study, we demonstrated that ethanol extract and triterpenes of G. lucidum specifically suppressed LPS-mediated inflammatory responses. Notably, ganodermanontriol inhibited the expressions and interactions of TLR4 and MyD88, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of p38, ErK1/2 and JNK. In vivo, we showed that ganodermanontriol effectively prevented LPS/D-Galactosamine-induced liver injury by reducing TNF-α and IL-6 production, and decrease of ALT/AST release. Collectively, our results revealed a novel role in inhibition of inflammatory diseases for triterpenes that may act through potential inhibition of TLR4-MyD88-mediated NF-κB and MAPK signaling pathways.

Anti-inflammatory and antioxidant activities of naringin isolated from Carissa carandas L.: In vitro and in vivo evidence.

BACKGROUND: Carissa carandas L. is known in folk medicine for its anti-inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub that constitutes a continuous source of leaves throughout the year. HYPOTHESIS/PURPOSE: The leaves of Carissa carandas L. may be rich in compounds that can be used as safe anti-inflammatory and antioxidant remedies. The combined antioxidant and anti-inflammatory activities provoked the study of the hepatoprotective effects. STUDY DESIGN: To isolate major constituents from the leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant activities in-vivo and in-vitro. METHODS: The leaves of Carissa carandas L. were extracted with 80% MeOH and then defatted with CHCl3 to yield Carissa carandas defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, then subjected to different chromatographic separation steps and naringin (NG) was isolated in a high yield. The anti-inflammatory activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was also evaluated in-vitro by measuring its inhibitory effect on LPS induced release of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by superoxide and DPPH radical scavenging ability. The safety of NG was tested against primary rat hepatocytes. The hepatoprotective effect of CCDE was evaluated by detecting its effects on serum liver function markers and liver cell oxidative stress markers. RESULTS: NG exhibited potent inhibition of inflammation as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO from macrophages (IC50, 6.4 µM). NG showed significant antioxidant activity as it scavenged the superoxide radical (EC90, 10.95 µM) and DPPH radical (EC50, 11.2 µM). CCDE inhibited the elevation of the serum liver marker enzymes and increased GSH and decreased MDA contents in the liver homogenate. Liver histopathology supported the biochemical findings. CONCLUSION: C. carandas has potent anti-inflammatory, antioxidant and hepatoprotective activities.

Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells.

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells.

Simultaneous determination of paeonilactone A and paeonilactone B in rat plasma after oral administration of albiflorin by UPLC/TOF/MS following picolinoyl derivatization.

A new highly sensitive analytical method was developed to investigate the in vivo metabolism of albiflorin, one of the most principal components in traditional Chinese medicine. After hydrolyzation with sulfatase, the main metabolites paeonilactone A and paeonilactone B of paeoniflorin in rat plasma were successfully detected for the first time by liquid chromatography mass spectrometry following picolinoyl derivatization. Borneol was used as the internal standard compound to quantify paeonilactone A and paeonilactone B in rat plasma. Paeonilactone A and paeonilactone B show different pharmacokinetic behaviors. The maximum plasma concentration of paeonilactone A reached 36.4±5.6ng/mL at about 8h after oral administration of albiflorin at a dose of 5mg/kg, while the maximum plasma concentration of paeonilactone B reached 12.4±3.4ng/mL at about 2h. The total metabolic pathway of albiflorin in rats was proposed. Albiflorin was found to be metabolized to the sulfate of paeonilactone A and paeonilactone B which may be responsible for the biological effect of albiflorin. The new analytical method may help to elucidate the clinical efficacy of traditional Chinese formula containing albiflorin.

New analytical method for determination of epimer metabolites in rat plasma after oral administration of Paeoniflorin by UPLC-TOF-MS following picolinoyl derivatization.

A highly sensitive analytical method was developed to study the in vivo metabolism of paeoniflorin, one of the most principal components in traditional Chinese medicine. After hydrolyzation with sulfatase, the epimer metabolites 7S-paeonimetabolin I and 7R-paeonimetabolin I of paeoniflorin in rat plasma were successfully detected and well separated by LC-MS following picolinoyl derivatization for the first time. Borneol was used as the internal standard to quantify 7S-paeonimetabolin I and 7R-paeonimetabolin I in rat plasma. 7S-paeonimetabolin I and 7R-paeonimetabolin I show similar but different pharmacokinetic behavior. 7S-paeonimetabolin I reached the maximum mean plasma concentration of 45.7±4.6ng/mL at about 1.5h after oral administration of paeoniflorin at a dose of 5mg/kg, while 7R-paeonimetabolin I reached the maximum mean plasma concentration of 39.2±3.5ng/mL at about 1.5h. The full metabolic pathway of paeoniflorin in rats was proposed. The monoterpene compound paeoniflorin was found to be metabolized to the sulfate of 7S-paeonimetabolin I and 7R-paeonimetabolin I in vivo which maybe responsible for the pharmacological effect of paeoniflorin.

Analysis of aristolochic acids, aristololactams and their analogues using liquid chromatography tandem mass spectrometry.

More than 80 aristolochic acids (AAs) and aristololactams (ALs) have been found in plants of the Aristolochiaceae family, but relatively few have been fully studied. The present study aimed at developing and validating a liquid chromatography tandem mass spectrometry (LC/MS(n)) for the analysis of these compounds. We characterized the fragmentation behaviors of 31 AAs, ALs, and their analogues via high performance liquid chromatography coupled with electrospray ionization mass spectrometry. We summarized their fragmentation rules and used these rules to identify the constituents contained in Aristolochia contorta, Ar. debilis, Ar. manshurensis, Ar. fangchi, Ar. cinnabarina, and Ar. mollissima. The AAs and ALs showed very different MS behaviors. In MS(1) of AAs, the characteristic pseudomolecular ions were [M + NH4](+), [M + H](+), and [M + H - H2O](+). However, only [M + H](+) was found in the MS(1) of ALs, which was simpler than that of AAs. Distinct MS(n)fragmentation patterns were found for AAs and ALs, showing the same skeleton among the different substituent groups. The distribution of the 31 constituents in the 6 species of Aristolochia genus was reported for the first time. 25 Analogues of AAs and ALs were detected in this genus. A hierarchical schemes and a calculating formula of the molecular formula of these nitrophenanthrene carboxylic acids and their lactams were proposed. In conclusion, this method could be applied to identification of similar unknown constituents in other plants.

Determination of the metabolic profile of gentianine after oral administration to rats by high performance liquid chromatography/electrospray ionization-trap mass spectrometry.

We investigated the metabolic fate of gentianine after oral administration to Wistar rats for the first time. Liquid chromatography/ion trap mass spectrometry detected four metabolites secogentianoxide, gentiandiol, gentianepoxide and gentianoxide in rat plasma together with the original compound gentianine. The structures of the metabolites were identified by comparing the retention times, as well as MS (mass) and MS/MS (tandem mass) spectra with those of authentic compounds, which were synthesized from gentianine or isolated from the urine. Three of the metabolites, secogentianoxide, gentianepoxide and gentianoxide, are novel compounds. The major in vivo metabolic processes associated with gentianine include N-oxide, epoxidation, dihydroxylation of double bond and hydrolysis of lactone. Gentianine together with the metabolites in plasma were quantified using gentianone as the internal standard. The mean C(max) of G0, G1, G2 and G3 are 425.76, 287.56, 188.45 and 85.05 ng/mL, respectively. The mean T(max) of G0, G1, G2 and G3 are 1.16, 3.87, 6.23 and 4.28 h, respectively. The mean T(1/2) of G0, G1, G2 and G3 are 5.23, 12.34, 7.78 and 5.64 h, respectively. A comprehensive metabolic pathway was proposed. The new metabolites may shed light on clinical efficacy of gentianine.

Metabolites of isocorynoxeine in rats after its oral administration.

This work presents the metabolites of isocorynoxeine (ICOR), which is one of four bioactive tetracyclic oxindole alkaloids isolated from Uncaria hooks used commonly in the traditional Chinese medicines and Kampo medicines. After oral administration of 40 mg kg(-1) ICOR to rats, bile was drained and analyzed by LC-MS. Two phase I metabolites, namely 11-hydroxyisocorynoxeine (M1) and 10-hydroxyisocorynoxeine (M2), and two phase II metabolites, namely 11-hydroxyisocorynoxeine 11-O-ß-D-glucuronide (M3) and 10-hydroxyisocorynoxeine 10-O-ß-D-glucuronide (M4), were isolated from rat excreta and bile, respectively, whose structures were elucidated on the basis of CD, NMR, and MS.

Protective effect of Aframomum melegueta phenolics against CCl4-induced rat hepatocytes damage; role of apoptosis and pro-inflammatory cytokines inhibition.

Aframomum melegueta is a commonly used African spice. Through a hepatoprotective bioassay-guided isolation, the chloroform fraction of A.melegueta seeds yielded one new diarylheptanoid named 3-(S)-acetyl-1-(4'-hydroxy-3', 5'-di methoxyphenyl)-7-(3″,4″, 5″-trihydroxyphenyl)heptane (1), and two new hydroxyphenylalkanones, [8]-dehydrogingerdione (2) and [6]-dehydroparadol (3), in addition to six known compounds (4-9). The hepatoprotective effect of A. melegueta methanol extract, sub-fractions and isolated compounds was investigated using carbon tetrachloride (CCl4)-induced liver injury in a rat hepatocytes model. The methanol, chloroform extracts and compounds 1, 5, 8 and 9 of A. melegueta significantly inhibited the elevated serum alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNFα), interleukin-1beta (Il-1ß), caspase3 and 9 and enhanced the reduced liver glutathione (GSH) level caused by CCl4 intoxication. These results indicate that A.melegueta extracts, and isolated compounds play a protective role in CCl4 induced acute liver injury which might be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue.

Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this.

OBJECTIVES: To investigate the influence of co-administrated Da-Chaihu-Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions. METHODS: A single dose of DCT was administered with nifedipine simultaneously, 2 h before, 30 min before or 30 min after nifedipine administration. Pharmacokinetics of nifedipine with or without DCT were compared. The influences of DCT on nifedipine intestinal mucosal and hepatic metabolism were studied by using rat in-vitro everted jejunal sac model and hepatic microsomes. KEY FINDINGS: A simultaneous co-administration of DCT significantly increased the area under concentration-time curve from time zero to infinity (AUC0-inf ) of nifedipine. In-vitro mechanism investigations revealed that DCT inhibited both the intestinal and the hepatic metabolism of nifedipine. Further study on the optimal dosing interval for nifedipine and DCT revealed that administration of DCT 30 min before or after nifedipine did not significantly change the AUC of nifedipine. CONCLUSIONS: The bioavailability of nifedipine is significantly increased by a simultaneous oral co-administration of DCT. This increase is caused by the inhibitory effect of DCT on both the intestinal mucosal and the hepatic metabolism of nifedipine. The dose interval between DCT and nifedipine needs to be set for over 30 min to avoid such drug-drug interactions.

Phylogenetic examination of crude drugs derived from Yunnanese Swertia plants.

Aiming to examine whether the genetic background of the crude drugs derived from four Yunnanese Swertia plants and their chemical constituent profiles correlate, we analyzed the nucleotide sequences of their nuclear ribosomal DNA regions including ITS1, 5.8S ribosomal RNA gene, and ITS2, together with those of Japanese S. japonica and S. pseudochinensis from Hebei Province. The result that two of the Yunnanese Swertia plants, S. binchuanensis and S. punicea, were genetically similar may explain their similarity in chemical constituent profiles. On the other hand, in spite of differences in chemical profile, S. decora and S. pseudochinensis were genetically close. The other Yunnanese Swertia plants, S. delavayi, and S. japonica, stood at intermediate positions between these two genetically similar pairs. The result suggests that although genetic background would have an influence, environmental factors, e.g., soil and weather conditions, might be critical for their production of secondary metabolites.

[Toxic effects of aqueous extract of crotalariae assamicae semen in rats and possible mechanism in association with liver damage].

OBJECTIVE: To study the toxic effects of aqueous extract of Crotalariae Assamicae Semen (CAS), one of the pyrrolizidine alkaloid-containing Chinese herbal medicines, in rats and the possible mechanism in association with liver damage. METHOD: The aqueous extract of CAS (CASE) was prepared by the conventional water extracting-alcohol precipitating method. The LD50 value of CASE in rats was determined by Kärber method. Rats were randomly divided into four groups in which three groups were orally administered with different doses of the CASE and one group with distilled water as control. Toxic effects were assessed by morphological, biochemical and histopathological changes. Moreover, in vitro metabolism using rat liver microsomes was also conducted and applied for the exploration of the underlying mechanism of liver damage. RESULT: The LD50 value of CASE in Wistar rats was (2.36 +/- 0.26) g x kg(-1). The toxic effects were found in all groups of rats dosed with CASE, in which serum levels of ALT and AST were significantly elevated, and the obvious and dose-dependent damages in liver and lung were observed by histopathological examination. Moreover, the liver tissue-bound pyrroles were detected and generated in a dose-dependent manner, and the pyrrole metabolites observed in the in vitro microsomal metabolism. All the evidences suggested a strong correlation between metabolism and toxicity of CASE in rats. CONCLUSION: CASE could induce the acute toxicity in rats, of which liver and lung were the major targets. Toxic effects were strongly correlated with pyrrolizidine alkaloids in CAS. The possible mechanism for its liver toxicity may be related to the formation of pyrrole metabolites as well as the corresponding tissue-binding products.

Ligand binding affinities of arctigenin and its demethylated metabolites to estrogen receptor alpha.

Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (-)-arctigenin, the aglycone of arctiin, was demethylated to (-)-dihydroxyenterolactone (DHENL) by Eubacterium (E.) sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (-)-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (-)-arctigenin using a ligand binding screen assay method. The IC(50) value of (2R,3R)-2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dihydroxybenzyl)-butyrolactone was 7.9 × 10⁻4 M.

Further evidence on the intramolecular lactonization in rat liver microsomal metabolism of 12-O-acetylated retronecine-type pyrrolizidine alkaloids.

We have previously found evidence of intramolecular lactonization in rat liver microsomal metabolism of isoline, a 12-O-acetylated pyrrolizidine alkaloid. In this study, the metabolism of another 12-O-acetylated pyrrolizidine alkaloid, acetylduciformine, by the proposed transformation pathway was investigated under the same incubation conditions. Two deacetylated metabolites from acetylduciformine were isolated and purified by chromatographic methods, and further characterized based on their physical properties and spectral data. One metabolite (lankongensisine A) was the lactone of another one (duciformine). Both compounds were first obtained as hydrolyzed metabolites from acetylduciformine by rat liver microsomes. More importantly, the present study provided further evidence for the intramolecular lactonization in the microsomal metabolism of 12-O-acetylated retronecine-type PAs.

The simultaneous quantification of Ganoderma acids and alcohols using ultra high-performance liquid chromatography-mass spectrometry in dynamic selected reaction monitoring mode.

Ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry with dynamic selected reaction monitoring mode was developed to simultaneously quantify Ganoderma acids and alcohols. Cholic acid and hydrocortisone, whose physiochemical properties are similar to triterpene acids and alcohols, respectively, were added as internal standards before sample treatment. The method could be applied to the quantification of triterpenes in single fungus and traditional Chinese medicine preparations. This method also detected 5 triterpenes in the Coriolus genus for the first time.

Chemical components and antioxidant activity of the peels of commercial apple-shaped pear (fruit of Pyrus pyrifolia cv. pingguoli).

UNLABELLED: The apple-shaped pear, the fruit of the Pyrus pyrifolia cv. pingguoli (Rosaceae) tree, is one of the most popular fruits in the northern part of China. The current study is the 1st report of its bioactive components. We identified 10 metabolites from the peels (exocarp) of apple-shaped pear and assessed their toxicity. We then compared the anti-oxidant activity, amount of total phenolic compounds, and total condensed tannin content of the peels and flesh (mesocarp) of apple-shaped pear. The 6 major components in the peels and flesh of this fruit were quantified with Ultra Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry. Results revealed that the peels possessed stronger anti-oxidant activity and contained larger amounts of phenolic compounds than the flesh. These results provide insights into the potential health benefits of this fruit and support the use of the fruit peels and products containing peels or peel components. PRACTICAL APPLICATION: The present research provided evidences that the pulp and peel waste from the juice industry of apple-shaped pear may be a source of useful compounds.

Microemulsion-based oxyresveratrol for topical treatment of herpes simplex virus (HSV) infection: physicochemical properties and efficacy in cutaneous HSV-1 infection in mice.

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20-30% w/w was suitable for cutaneous HSV-1 mouse infection.

[Estrogen-like effects of Menoprogen on female ovariectomized rats].

OBJECTIVE: To study the estrogen-like action mechanism of Menoprogen on ovariectomized female rats. METHOD: Ovariectomized rat model (OVX) was established and estradiol (17beta-estradiol, E2) was used as positive control. The uterine coefficient and serum E2 level were determined after administration of Menoprogen for 2 weeks. The uterine vascular endothelial growth factor (VEGF), water channel protein (aquaporin, AQP), estrogen receptor (ER), progesterone receptor (PR) and the expression of proto-oncogenes (c-jun, c-fos) were observed by immunohistochemical method. Yeast two-hybrid assay was applied to detect the existence of components combining with ERalpha or ERbeta in Menoprogen. RESULT: Both Menoprogen and E2 could significantly elevate the uterine coefficient of OVX rats, increase the level of serum E2 and up-regulate the expressions of VEGF, AQP2 as well as AQP5 in uterus. E2, not as E2 Menoprogen couldn't promote the expressions of ERalpha, PR, c-jun and c-fos in OVX rat uterus. And yeast two-hybrid assay showed no components combining with ERalpha or ERbeta in Menoprogen. CONCLUSION: Menoprogen has estrogen-like effect, and can be used to treat menopause syndrome. The risk of estrogen-mediated endometrial cancer is low for this treatment because its mechanism is different from estrogen-like substances.

Hepatoprotective effects of phloridzin on hepatic fibrosis induced by carbon tetrachloride against oxidative stress-triggered damage and fibrosis in rats.

The present study was to study the hepatoprotective effects of phloridzin (PHL) on hepatic fibrosis induced by carbon tetrachloride (CCl4) in rats, on the basis of this investigation, the possible mechanism of PHL was elucidated. Male Sprague Dawley (SD) rats were randomly divided into six groups: control, model, PHL-L, PHL-M, PHL-H and colchine. All rats except control group were intraperitoneally injected with CCl4, and control rats were injected with olive oil, twice a week for eight weeks. At the same time, the rats were orally given homologue drugs once a day, respectively. Hepatoprotective effects of PHL were evaluated by liver weight indexes, biochemical values, total antioxidant capacity and total-superoxide dismutase, histopathological observations, hepatic fibrosis, and the hepatic fibrosis relative gene and protein expressions. PHL significantly improved hepatic function; remarkably decreased serum hyaluronic acid (HA), transforming growth factor-ß1 (TGF-ß1), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and liver tissues hydroxyproline, malondialdehyde (MDA) levels, increased glutathione peroxidase (GSH-Px), total-antioxygen capacity (T-AOC) and total-superoxide dismutase (T-SOD) contents of liver tissues; Real-time polymerase chain reaction (PCR) and immunohisto-chemical results showed PHL might markedly reverse the up-regulated mRNA and protein expressions of the α-smooth muscle actin (SMA), TGF-ß1 and tissue inhibitor of metalloproteinase-1 (TIMP1), up-regulate the matrix metalloproteinase-1 (MMP1) mRNA and protein expressions. Histopathological observations provided supportive evidence for biochemical analyses and the hepatic fibrosis relative gene and protein expressions, and with the dose of PHL increasing, the aforesaid improvement became more and more strong. The studies demonstrated that PHL exerted beneficially hepatoprotective effects on hepatic fibrosis induced by CCl4, mainly enhancing antioxidant capacity of liver organizations, reduce the level of lipid peroxidation induced by CCl4, and protect hepatocyte membranes from damage, and alleviate hepatic fibrosis.

Chemical constituents from rhizome of Daphne papyracea var. crassiuscula / 中国中药杂志

<p><b>OBJECTIVE</b>To study chemical constituents from rhizome of Daphne papyracea var. crassiuscula.</p><p><b>METHOD</b>Ethyl acetate fraction of 75% ethanol extracts from rhizome of D. papyracea var. crassiuscula, and its strucutre was identified by spectral method.</p><p><b>RESULT</b>Nine compounds were separated and identified as daphneticin (1), daphnetin (2), hydrangetin (3), daphnoretin (4), 1-4'-hydroxyphenyl-5-phenyl-2 (E)-en-1-pentanone (5), daphneolon (6), 3beta-O-acetyl-olean-12-en (7), and (+)-usnic acid (8).</p><p><b>CONCLUSION</b>Compounds 1-8 were separated from D. papyracea var. crassiuscula for the first time. Compound 8 was separated from the genus for first time.</p>