Biomedical subjects

Liang Liu

Publications and source records attributed to Liang Liu.

At least 55 records · Page 3Linked to original sources

PubMed2005

Pharmacokinetic interaction of paeoniflorin and sinomenine: pharmacokinetic parameters and tissue distribution characteristics in rats and protein binding ability in vitro.

The root of Paeonia lactiflora and the stem of Sinomenium acutum are two herbs widely used in Chinese herbal medicine for the treatment of inflammatory and arthritic diseases. Studies on the interaction of the active constituents of these herbs, i.e., paeoniflorin and sinomenine, in pharmacokinetic parameters, tissues distribution, and protein binding ability could provide empirical data to support their clinical application. Following oral administration to rats, the pharmacokinetic alterations were compared. The results showed that the pharmacokinetic parameters (Cmax, Tmax, AUC, MRT, C(L), and Vd) of paeoniflorin were markedly enhanced when co-administrated with sinomenine. At 45 min after oral administration, the concentrations of paeoniflorin in the main internal organs were significantly increased when co-administrated with sinomenine. These phenomena were not ascribable to the alteration of the protein binding ability of paeoniflorin by sinomenine because obvious interactions of paeoniflorin and sinomenine in protein binding abilities in vitro to rat and rabbit plasma, human albumin, and alpha-1-acid-glycoprotein were not observed. However, with respect to the in vivo influence of paeoniflorin on sinomenine, the results showed that co-administration of paeoniflorin did not affect the pharmacokinetic parameters and tissue distribution of sinomenine.

Animals↗

PubMed2005

Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K.

We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

Administration, Oral↗

PubMed2005

Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta, JNK, and NF-kappaB transcription factor.

The effects of saikosaponin-d, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), on the signaling pathways of T cell activation were examined. The results showed that saikosaponin-d potently suppressed both early (CD69) and late (CD71) expressions of mouse T cells stimulated with Con A or PMA. It interfered with PKCtheta translocation from cytosol to membrane fraction and inhibited the phosphorylations of IkappaBalpha and JNK, but not ERK, in PMA-activated mouse T cells. Additionally, it inhibited PMA and ionomycin-stimulated IL-2 production in mouse T cells. In summary, these results indicate that the mechanism by which saikosaponin-d inhibits T cell activation would involve the suppression of CD69 and CD71 expressions and IL-2 production, and the modulation of PKC pathway through PKCtheta, JNK, and NF-kappaB transcription factor. This may herald a novel approach for further studies of saikosaponin-d as a candidate for use in the treatment of inflammatory and autoimmune diseases.

Animals↗

PubMed2005

Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography.

By optimizing the extraction, separation and analytical conditions, a reliable and accurate high-performance liquid chromatography (HPLC) method coupled with photodiode array detector (DAD) was developed for simultaneous quantitative determination of six Aconitum alkaloids, i.e., aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine, in Chinese medicinal herbs, aconite roots, and 12 proprietary Chinese medicines containing processed aconite roots. The separation of these Aconitum alkaloids was achieved on an ODS column with gradient elution using solvents of acetonitrile and ammonium bicarbonate buffer (pH 10.0+/-0.2). Intra-assay and inter-assay precision of the analytes were less than 2.97%, and the average recovery rates obtained were in the range of 90-103% for all with RSDs below 3.28%. Good linear relationships were showed with correlation coefficients for the analytes exceeded 0.999. Quantitative analysis of the six Aconitum alkaloids in the unprocessed and processed aconite roots and in twelve proprietary Chinese medicines containing processed aconite roots showed that the contents of the alkaloids varied significantly. This method and quantitation results can provide a scientific and technical platform to the products manufacturers for setting up a quality control standard as well as to the public for quality and safety assurance of the proprietary Chinese medicines and other herbal preparations containing aconite roots.

Aconitum↗

PubMed2005

Suppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-induced arthritis.

To analyze the anti-arthritic effects of QFGJS (a pharmaceutical preparation from herbs) on rheumatoid arthritis, adjuvant-induced arthritis (AIA) was established in male SD rats, and two administration protocols, i.e., oral treatment with different doses of QFGJS on the day of arthritis induction or on the day when visible clinical signs of arthritis occurred, were initiated and continued until day 30. Treatments with QFGJS using both administration protocols significantly suppressed the incidence and severity of arthritis in a dose-dependent manner, showing dramatic reduction of paw swelling and ESR throughout the disease progression of AIA. Radiological and histopathological examinations showed markedly decreased tissue and bone destruction of ankle joints in the QFGJS-treated rats. The serum levels of TNF-alpha, IL-1beta, and IL-6 were significantly decreased in the QFGJS-treated rats. QFGJS demonstrates pronounced anti-arthritic effects on AIA, indicating that this herbal preparation would be a potent candidate as a novel botanical drug for further investigation.

Animals↗

PubMed2005

The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.

Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro.

Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of sinomenine. Examination of the protein binding ability showed that sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.

Administration, Oral↗

PubMed2005

Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats.

Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected] g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced (P<0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.

Animals↗

PubMed2005

Epigenetic control of telomerase and modes of telomere maintenance in aging and abnormal systems.

Epigenetic control provides a mechanism for the reversible silencing of telomerase expression that occurs as a natural consequence of differentiation. Significant overlap between indirect telomerase regulation pathways and cell cycle checkpoint pathways exist, suggesting that these discrete genetic elements (namely, p21, p53, and hTERT) synergistically cooperate to inhibit tumorigenesis. Mutations in these pathways have been known to contribute to cancer formation. However, the incorporation of epigenetic regulatory mechanisms provides another line of defense against these negative occurrences. These proteins are also implicated in the process of senescence, caused in eukaryotic cell lines by telomere shortening. Although the debate continues, there is significant evidence to classify the process of cellular senescence as an in vitro model for human aging. In addition, the study of stem cells gives information about the down-regulation of hTERT in the aging process. Diseases such as Werner S syndrome, ATM (ataxia telangiectasia mutated kinase), DKC (dyskeratosis congenita), and atherosclerosis have been linked to aberrant telomerase expression and other aging-related tissue malfunctions could be related to the presence of senescent cells changing the cellular microenvironment. Therefore, restoring telomerase activity as a putative therapeutic strategy necessitates further study to elucidate the intricacies linking genetic and epigenetic modulations of hTERT.

Aging↗

PubMed2005

The impact of metabolism on DNA methylation.

Methylation of genomic cytosines is one of the best characterized epigenetic mechanisms, and investigation of its relationship with other biochemical pathways represents a critical stage in the elucidation of biological information processing. The field also has immense potential for the development of medical treatments for any number of conditions ranging from aging to neurological disorders. The DNA methylation status of genes is responsible for many heritable traits and varies more or less independently of the genetic code. This variation is often a result of cellular environmental factors including metabolism. A key metabolite in this regard is homocysteine. Knowledge of homocysteine metabolism continues to be amassed, yet the part played by aberrant DNA methylation in homocysteine-related pathologies is often, at best, conjectural. In this analysis, we will review recent insights and attempt to speculate meaningfully concerning the dynamics of the methionine cycle in relation to DNA methylation and disease.

Alzheimer Disease↗

PubMed2005

Investigation of sudden infant deaths in the State of Maryland (1990-2000).

The Office of the Chief Medical Examiner (OCME) has recorded a significant decline in the deaths of sudden infant death syndrome (SIDS) in the state of Maryland since 1994. However, infants who died of accidental or non-accidental injuries remained consistent during the same time period. This report focuses on the epidemiological characteristics and scene investigation findings of infant victims who died suddenly and unexpectedly in Maryland between 1990 and 2000. A retrospective study of OCME cases between 1990 and 2000 yielded a total of 1619 infant fatalities. 802 infant deaths were determined to be SIDS, which represented 50% of the total infant deaths in our study population. Five hundred and twenty-three (31.8%) deaths were due to natural diseases, 128 (7.9%) deaths were accidents, and 74 (4.6%) were homicides. The manner of death could not be determined after a thorough scene investigation, review of history and a complete postmortem examination in 92 (5.7%) infants. SIDS deaths most often involved infants who were male and black. The peak incidence of SIDS was between 2 and 4 months of age. The majority of SIDS infants (60%) were found unresponsive on their stomach. Among SIDS infants, 269 (33.4%) were found in bed with another person or persons (bed sharing). Of the bed-sharing SIDS cases, 182 (68%) were African-American. In the past 11 years, 52 infants died of asphyxia due to unsafe sleeping environment, such as defective cribs, ill-fitting mattresses, inappropriate bedding materials. Of the 74 homicide victims, 53 (70%) involved infants less than 6 months of age. Twenty (27%) exhibited the classical abuse syndrome characterized by repeated acts of trauma to the infants.

Accidents, Home↗

PubMed2005

Correlative analysis on the relationship between PMI and DNA degradation of cell nucleus in human different tissues.

To determining the postmortem interval (PMI) through quantitative analysis of the DNA degradation of cell nucleus in human brain and spleen by using image analysis technique (IAT). The brain and spleen tissues from 32 cadavers with known PMI were collected, subjected to cell smear every 1 h within the first 5-36 h after death, stained by Feulgen-Van's staining, Three indices reflecting DNA in brain cells (astrocytes) and splenic lymphocytes, including integral optical density (IOD), average optical density (AOD), average gray (AG) were measured by employing the mage analysis instrument. The results showed that IOD and AOD declined and AG increased with the prolongation of dead time within 5-36 h. A correlation between the PMI and gray parameters (IOD, AOD and AG) was identified and the corresponding regression equation was obtained. The parameters (IOD, AOD and AG) were proved to be effective quantitative indicators for accurate estimation of PMI within 5-36 h after death.

Cell Nucleus↗

PubMed2005

Hemiterpene glucosides with anti-platelet aggregation activities from Ilex pubescens.

Two new hemiterpene glucosides named pubescenosides A and B were isolated from the root of Ilex pubescens. Their structures were elucidated on the basis of spectroscopic and chemical evidence as 2-(trans-caffeoyloxy)methyl-3-hydroxy-1-butene-4-O-beta-D-glucopyranoside and 2-hydroxymethyl-3-caffeoyloxy-1-butene-4-O-beta-D-glucopyranoside, respectively. Pharmacological investigation on pubescenosides A and B indicated that both possess potent anti-platelet aggregation activities.

Animals↗

PubMed2005

Quantification of sinomenine in caulis sinomenii collected from different growing regions and wholesale herbal markets by a modified HPLC method.

Caulis Sinomenii is the dried plant stems of Sinomenium acutum and Sinomenium acutum var. cinereum and has been used in Chinese medicine for treating rheumatic diseases for over a thousand years. Previous studies have demonstrated that sinomenine is a major active constituent in both plants and can be utilized as an indicator of quality of the medicinal herb Caulis Sinomenii. Currently, S. acutum and S. acutum var. cinereum are growing over a wide geographical range in China, with equally wide variations in growing conditions. The objectives of this research were to determine whether there were difference between the species and varieties, and whether the different growing conditions could result in different quality by determining the content of sinomenine in different samples. A modified HPLC method using a diode array detector (DAD) has been developed for efficiently quantifying sinomenine in the plants. Using this method, fourteen samples of S. acutum var. cinereum and eleven samples of S. acutum from growing regions as well as eighteen herbal samples of Caulis Sinomenii from wholesale herbal markets were evaluated. The results showed that there was no marked difference in the content of sinomenine between the species and varieties collected from growing regions; however, a very large variation was found among the samples collected from different regions. Moreover, the content of sinomenine in the plants of large size (stem diameter>3 cm) was much higher than those of small size (stem diameter<1 cm). This implies that the growing region has greater impact on the quality of Caulis Sinomenii in terms of the content of sinomenine than the species and varieties. The results also showed that the content of sinomenine in commercial Caulis Sinomenii was markedly lower than that in the plants collected directly from growing regions. This suggests that to obtain the herb with higher content of sinomenine and thus ensure greater efficacy, both in clinical applications and in pharmacological investigations, the plant of Caulis Sinomenii with controlled stem size collected directly from growing regions is preferable.

China↗

PubMed2005

Analgesic and anti-inflammatory activities of total extract and individual fractions of Chinese medicinal ants Polyrhachis lamellidens.

The ethanol extract of Chinese medicinal ants Polyrhachis lamelliden was evaluated for its analgesic and anti-inflammatory activities in mice. It was shown that the extract significantly inhibited acetic acid-induced writhing response and increased hot-plate pain threshold of mice at doses of 1.5 and 3.0 g crude drug/kg. Meanwhile, the extract significantly inhibited the increase in vascular permeability induced by acetic acid and in ear edema induced by xylene in mice. However, it had no obvious effect on leukocyte migration induced by carboxymethylcellulose sodium (CMC-Na). The ethanol extract suspended in water was partitioned with diethyl ether, ethyl acetate and n-butanol successively to yield four fractions including water fraction. Among these fractions, diethyl ether and ethyl acetate fractions were found to increase hot-plate pain threshold and to inhibit acetic acid-induced writhing response in mice. Water fractions markedly inhibited acetic acid-induced writhing response and reduced the dye leakage to the peritoneal cavity induced by acetic acid and ear edema induced by xylene. These results suggest that P. lamellidens presents remarkable analgesic and anti-inflammatory activity, which supported the traditional use of the medicinal ants in the treatment of various diseases associated with inflammation. The diethyl ether fraction has greater contribution to the overall analgesic activity, whereas the water fraction showed the greatest anti-inflammatory and peripheral analgesic activities.

Analgesics↗

PubMed2005

[Effects of macrophages on the biological behaviors and VEGF receptor mRNA, Hoxb2 mRNA, and integrin alphavbeta3 expressions of vascular endothelial cells].

OBJECTIVE: To explore the mechanism by which macrophages regulate angiogenesis by co-culturing human umbilical vein endothelial cells (ECV-304) with human macrophage cells (U937) stimulated by concanavalin A (ConA). METHODS: Monolayer ECV-304 cells growing to 60% confluence were co-cultured with 1 x 10(5)/ml U937 cells in the presence or absence of ConA (ConA+U937+ECV-304 and U937+ECV-304 groups, respectively), with non-treated and ConA-treated ECV-304 cells serving as the control groups (ECV-304 and ConA+ECV-304 groups, respectively). Forty-eight h later, U937 cells were removed from the cell co-culture for examining changes in DNA synthesis of ECV-304 cells with (3)H-TdR incorporation assay and for cell cycle analysis with flow cytometry. RT-PCR was employed to assess the influence of macrophages stimulated by ConA on the expression of the target genes. With immunofluorescent method, the changes in the expression of integrin receptor alphavbeta3 of ECV-304 were determined. RESULTS: A significant increase in S-phase ECV-304 cells with enhanced DNA synthesis was observed after co-culture of the cells with ConA-stimulated U937 cells (P<0.01), which also resulted in significant up-regulation of the expressions of KDR mRNA (0.879+/-0.003), Hoxb2 mRNA (0.947+/-0.003) and integrin receptor alphavbeta3 (10.26+/-1.73). CONCLUSION: Macrophages can accelerate the proliferation, migration and adhesion of the vascular endothelial cells to the basilar membrane matrix by affecting their cell cycle, DNA synthesis, expression of KDR mRNA, Hoxb2 mRNA and integrin alphavbeta3, so as to modulate the angiogenetic process of the latter cells.

Cell Proliferation↗

PubMed2005

[The research progress in Marfan syndrome].

Marfan syndrome (MFS) is a potentially fatal connective disorder that is inherited as an autosomal dominant trait with a prevalence of around 2-3 in 10000 live births. It is characterized by defects in the cardiovascular, skeletal and ocular systems. Evidence from genetic indicates that mutations in FBN1, the gene that encodes fibrillin-1 are responsible for MFS. In addition to skeletal, ocular, and cardiovascular feathers, patients with MFS have also involvement of skin, integument, lungs, and muscle tissue, and the condition in sudden death is also very common due to severe abnormalities of cardiovascular system.

Cardiovascular Diseases↗

PubMed2005

[Study on ultra-structural pathological changes of rats poisoned by tetramine].

OBJECTIVE: To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. METHODS: Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. RESULTS: The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. CONCLUSION: The toxic target organs of tetramine are the heart, brain and liver.

Animals↗