Periplogenin Activates ROS-ER Stress Pathway to Trigger Apoptosis via BIP-eIF2α- CHOP and IRE1α-ASK1-JNK Signaling Routes.

BACKGROUND: Periplogenin (PPG), a natural compound isolated from traditional Chinese herb Cortex Periplocae, has been reported to possess anti-inflammatory and anti-cancer properties. OBJECTIVE: The present study aims to investigate the antitumor effects of PPG and the underlying mechanism in human colorectal cancer cells. METHODS: The inhibition of cell growth in vitro was assessed by MTT assay. The induction of apoptosis and the ROS production induced by PPG was investigated by flow cytometry analysis. Western blotting was applied to measure the protein expression. Small interference RNA (siRNA) and a specific pharmacological inhibitor were used to knock down or inhibit the expression of related genes. RESULTS: PPG was able to cause the production of ROS, inhibit the cancer cell growth and induce apoptosis. Nacetylcysteine was able to inhibit ROS production and apoptosis. PPG up-regulated the protein levels of BIP, peIF2α and CHOP as well as IRE1α and p-JNK, and down-regulated the protein level of p-ASK1, all of which were reversed by N-acetylcysteine. Importantly, knockdown of CHOP or JNK protein level attenuated the PPGelicited apoptosis. CONCLUSION: PPG-induced apoptosis was regulated by ROS-mediated BIP/eIF2α/CHOP and BIP/ASK1/JNK signaling pathways in colon cancer cells, suggesting that PPG is a promising therapeutic agent for the treatment of human colon cancer.

Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats.

OBJECTIVE: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on liver regeneration of rats with liver cirrhosis after hepatectomy and antifibrosis. MATERIALS AND METHODS: Omega-3 polyunsaturated fatty acids were intravenously injected in n-3 PUFA group 3 days before the operation to 1 day after partial hepatectomy. 70% hepatectomy was performed in rats, which were subsequently divided into 4 groups, namely normal and hepatectomy group (PH); liver cirrhosis and hepatectomy group (LC+PH); liver cirrhosis, n-3 PUFA (1 mL/kg), and hepatectomy group (LC+n-3 PUFA+PH); liver cirrhosis, n-3 PUFA (2 mL/kg) and hepatectomy group (LC+n-3PUFA*+PH). Body/liver weight ratios, serum parameters, histopathological examination, immunostaining, inflammatory cytokine and quantification of mRNA expression were also investigated. RESULTS: Liver regeneration was significantly delayed compared with PH group 7 days after hepatectomy (PH) in LC+PH group. Besides, liver regeneration of LC+n-3 PUFA*+PH group increased significantly compared with LC+PH group 7 days after PH. In LC+PH group, liver cirrhotic was significantly higher compared with LC+n-3 PUFA+PH group 7 days after PH. In the meantime, liver cirrhosis of LC+n-3 PUFA*+PH group was significantly reduced compared with LC+n-3 PUFA+PH group 7 days after PH. Anti-inflammatory cytokine IL-10 was increased and pro-inflammatory cytokine IL-6 was decreased in LC+n-3 PUFA*+PH group compared with LC+PH group. N-3 PUFA also suppressed increments in mRNA expression for transforming growth factor-ß and up-regulated the expression of matrix metalloproteinase-9 and matrix metalloproteinase-1 in the liver. CONCLUSIONS: The mentioned results clearly show that n-3 PUFA reduces liver fibrosis and promotes liver regeneration, even under cirrhotic conditions. This could be a potentially useful treatment for liver cirrhosis.

RN1, a novel galectin-3 inhibitor, inhibits pancreatic cancer cell growth in vitro and in vivo via blocking galectin-3 associated signaling pathways.

Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 binds to epidermal growth factor receptor (EGFR) and Gal-3, thereby disrupting the interaction between Gal-3 and EGFR and downregulating extracellular-related kinase (ERK) phosphorylation and the transcription factor of Gal-3, Runx1 expression. Inhibiting the expression of Runx1 by RN1, suppresses Gal-3 expression and inactivates Gal-3-associated signaling pathways, including the EGFR/ERK/Runx1, BMP/smad/Id-3 and integrin/FAK/JNK signaling pathways. In addition, RN1 can also bind to bone morphogenetic protein receptors (BMPR1A and BMPR2) and block the interaction between Gal-3 and the BMPRs. Thus, our results suggest that a novel Gal-3 inhibitor RN1 may be a potential candidate for human PDAC treatment via multiple targets and multiple signaling pathways.

Drug-use pattern of Chinese herbal medicines in insomnia: a 4-year survey in Taiwan.

BACKGROUND AND OBJECTIVE: Insomnia is a common complaint in the general population. Interest in the use of alternative treatments for insomnia is increasing exponentially and is fairly common in Taiwan. We undertook a survey to define the drug utilization patterns of Chinese herbal medicines (CM) for insomnia in Taiwan. METHODS: The survey was conducted over a period of 4 years, from January 2003 to December 2006. Outpatients with primary insomnia and being treated with CM were studied. Core drug-use indicators were the number of CM items per prescription, the dosing frequency and duration of CM prescriptions, the most common prescribed CM herbs and CM formulae used. RESULTS: Six thousand eight hundred and sixty patients, using 37,046 CM herb items, were screened during the study period. The average CM items per prescription was 5.40. Most of prescriptions (95.23%) were prescribed for administration three times a day. The most often prescribed Chinese herbal products were Hong-Hwa (Carthamus tinctorius) and Jia-Wey-Shiau-Yau-San, which includes Angelica sinensis, Atractylodes macrocephala, Paeonia lactiflora, Bupleurum chinense, and Poria coco. CONCLUSION: This is the first extensive survey examining the drug utilization patterns of Chinese herbal medicines in the treatment of insomnia. Although the data were generated in Taiwan, the herbs and practices identified are likely to be widely generalizable wherever Chinese herbal remedies are used for insomnia. Multiple herbs and complex formulae were commonly used. The baseline data generated should be of use in informing subsequent studies, including those aimed at a thorough evaluation of the herbs' effectiveness.

Effects of feeding tuna oil on the lipid composition of pig spermatozoa and in vitro characteristics of semen.

The aim of the present study was to characterize the effects of feeding tuna oil on the lipid and fatty acid composition of boar spermatozoa and to relate changes in composition to boar semen characteristics. Ten boars were paired by age and allocated to one of two diets (five boars per diet). The diets, which were offered for 6 weeks, consisted of a basal diet that was either unsupplemented or supplemented with 30 g tuna oil kg(-1) diet. Adding tuna oil to the diet increased the ether extract concentration of the diets fed from 65 to 92 g kg(-1) dry matter and supplied 10.5 g long chain polyunsaturated (n-3) fatty acids per 100 g total fatty acids. There were no changes in semen fatty acid composition after 3 weeks of feeding tuna oil. However, after 5 and 6 weeks, the proportions (g per 100 g total fatty acids) of 22:6(n-3) in sperm phospholipid fatty acids were increased from 34.5 to 42.9 g by feeding tuna oil and 22:5(n-6) decreased from 29.8 to 17.9 g. No changes were observed in other sperm lipids or seminal plasma phospholipids as a result of the diets fed. Feeding tuna oil increased the proportion of spermatozoa with progressive motility and with a normal acrosome score and reduced the proportion of spermatozoa with abnormal morphologies.

Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis.

BACKGROUND: We have developed a knockout mouse model for adenine phosphoribosyltransferase (APRT) deficiency, a condition that often leads to 2,8-dihydroxyadenine (DHA) nephrolithiasis in humans. Aprt knockout male mice develop severe renal damage by three months of age, but this is strain specific. Renal damage in female mice is less pronounced than in males. The gene level changes that promote renal injury in APRT-deficient mice are not known. METHODS: We used mRNA differential display polymerase chain reaction (DD-PCR) to analyze renal gene expression changes in APRT-deficient male and female mice (strain C3H) compared with age- and sex-matched Aprt heterozygote controls. The differentially amplified bands were reamplified, cloned, sequenced, and queried against the National Center for Biotechnology Information nonredundant databases using the Basic Alignment Search Tool. Relative quantitative reverse transcription-polymerase chain reaction was used to confirm the results of DD-PCR for a selected number of genes in one-, three-, and six-month-old male and female mice. RESULTS: Sixty-three differentially amplified bands were identified, including 21 for known genes, and 8 of these were examined further. In three-month-old APRT-deficient male mice, the expression of C10 was increased tenfold, and there was a fourfold to sevenfold increase in the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), MGP (matrix Gla protein), and lysyl oxidase (LOX). The expression of cholecystokinin-A receptor (CCKAR), imprinted multimembrane-spanning polyspecific transporter-like gene 1 (IMPT-1), and kidney androgen-regulated protein (KAP) was diminished twofold to fourfold, but there was little or no change in the expression of organic anion transporter (OATP). Except for a more than tenfold increase in C10 expression and up to tenfold decrease in KAP expression, APRT-deficient female mice did not show significant changes in gene expression compared with controls. CONCLUSIONS: These findings suggest that (1) there are sex-related differences in gene expression in DHA lithiasis, possibly caused by increased deposition of DHA crystals in male compared with female kidneys; and (2) the expression of certain genes (for example, C10) may simply be an indication of nonspecific cellular stimulation and may not be related to renal injury.

[Clinical and experimental study on Ligusticum wallichii mixture in preventing and treating bronchial asthma].

UNLABELLED: To investigate the significance of Ligusticum wallichii Mixture (LWM) and its possible therapeutical mechanism in bronchial asthma, clinical and experimental studies were carried out. RESULTS: LWM inhibited bronchospasm induced by histamine and acetylcholine in guinea pigs; the plasma level of TXB2 was decreased remarkably and the incubation period from antigen inhalation to asthma attack could be delayed by LWM; the incidence of asthma and its mortality were reduced in guinea pigs, compared with control, P < 0.01. In addition, the prolonged period of induced asthma attack was negatively correlated to the plasma level of TXB2 in guinea pigs (P < 0.01). It was observed that the plasma level of TXB2 was decreased, the forced expiratory volume in 1 sec (FEV1%) was elevated significantly in asthmatic patients after they were treated by LWM. Moreover, the total effective rate was significantly better than that in the control (92% : 62%). It indicated that: (1) The effects of airway allergic inflammation (AAI) might be the important pathological basis for the bronchial asthma, (2) TXA2 might be an important inflammatory mediator in asthma which could be taken as an useful biochemical parameter for evaluating clinical effects, (3) LWM could relax tracheal smooth muscle, improve pulmonary function, inhibit the synthesis and release of TXA2 with no side effects.

[Ca2+ channel blocking effect of panaxadiol saponins and panaxatriol saponins of cultured cardiac cells].

It was found that PDS and PTS decreased the action potential parameters of the cultured myocardiocytes in a dosage-dependent way. The effects of PDS 1000 micrograms/ml, PTS 200 micrograms/ml were in correspondence with the known Ca2+ channel blocker Mn2+ 0.05 micrograms/ml. Washing out, administration of epinephrine 10 micrograms/ml or Ca2+ 80 micrograms/ml were able to reverse the action potential from inhibition. The above results indicate that both PDS and PTS have Ca2+ channel blockade action.

[Studies on the chemical constituents of the roots of Aralia continentalis Kitag].

Seven compounds were isolated from the roots of Aralia continentalis. Four of these compounds were identified as ent-kaur-16-en-19-oic acid, beta-sitosterol glucoside (daucosterol), beta-sitosterol and 16 alpha-hydroxy-(-)-kauran-19-oic acid. It is the first time that 16 alpha-hydroxy-(-)-karan-19-oic acid and beta-sitosterol glucoside were isolated from this plant.