Components study on gastroprotective effect and holistic mechanism of the herbal pair Alpinia officinarum - Cyperus rotundus based on spectrum-effect relationship and integrated transcriptome and metabolome analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal pair Alpinia officinarum-Cyperus rotundus (HPAC) has an extended history of use in the treatment of gastric ulcers, and its curative effect is definite. AIM OF THE STUDY: To explore the material basis and holistic mechanism of HPAC on ethanol-induced gastric ulcers. MATERIALS AND METHODS: Three chemometrics, GRA, OPLS, and BCA, were used to construct the spectrum-effect relationship between the HPLC fingerprints of HPAC extracts and the bioactivity indices (cell viability; the levels of TNF-α, IL-6, COX-2, and PGE2; and wound healing rate) against GES-1 cell damage to screen the bioactive ingredients. The bioactive components were isolated and validated in vitro. Simultaneously, the effects of HPAC with concentrated bioactive ingredients was tested on ethanol-induced gastric ulcers in vivo, and the mechanism was investigated using transcriptomics and metabolomics. The mechanism was further validated by Western blotting. Finally, the contents of the main components of HPAC were determined before and after compatibility. RESULTS: Twelve bioactive components were screened, and the structures of nine compounds were confirmed. An in vitro verification test showed that DPHA and galangin could protect GES-1 cells from injury, and that their content increased after compatibility. The CH2Cl2 fraction of HPAC (HP-CH2Cl2) can protect mice from ethanol-induced gastric mucosal injury by reducing hemorrhage and decreasing inflammatory cell infiltration. Western blot analysis indicated that this fraction may up-regulate TRPV1 protein and down-regulate PI3K and AKT proteins. CONCLUSIONS: DPHA and galangin may be the bioactive components against ethanol-induced GES-1 cell injury. HP-CH2Cl2 may exert gastroprotective effects by regulating PI3K, AKT and TRPV1 proteins.

Dichapetalin-type triterpenoids from Dichapetalum longipetalum and their anti-inflammatory activity.

A phytochemical research on the twigs of Dichapetalum longipetalum (Turcz.) Engl. Resulted in five undescribed dichapetalin-type triterpenoids 1-5. Their chemical structures were determined by spectroscopic analysis of HR-ESIMS and NMR spectra and the absolute configuration of compound 1 was completely elucidated by single crystal X-ray crystallography. Through preliminary anti-inflammatory activity assessment, compound 1 exhibited inhibitory effect on LPS-induced NO production in RAW264.7 murine macrophages with an IC50 value of 2.09 µM.

Longipetalol A: A Highly Modified Triterpenoid from Dichapetalum longipetalum.

Longipetalol A (1) is an unprecedented highly modified triterpenoid with a unique 1,2-seco-3-(2-oxo-phenylethyl)-17α-13,30-cyclodammarane skeleton, featuring an acetal-lactone fragment. It was isolated from Dichapetalum longipetalum along with two additional derivatives, namely, longipetalols B (2) and C (3). Their structures were elucidated using spectroscopic analyses combined with single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages.

Anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from barks of Litsea glutinosa in ob/ob mice.

The present study investigated the anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from Litsea glutinosa barks (CG) in ob/ob mice. CG was orally administrated (50, 100 and 200 mg/kg) to ob/ob mice for 4 weeks. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and inflammation were measured. CG was chemically characterized using UPLC-QTOF-MS. CG dose-dependently decreased body and fat weights without reducing average food intake. CG (100-200 mg/kg) significantly reduced the serum levels of fasting glucose, glycosylated hemoglobin (HbAlc) and glycosylated serum protein (GSP). CG increased insulin sensitivity as manifested by decreased fasting serum insulin, reduced homeostasis model assessment-estimated insulin resistance (HOMA-IR) and improved oral glucose tolerance. CG also alleviated dyslipidemia, ameliorated liver steatosis, increased the activity of serum lipase and alleviated inflammation. The activities of liver pyruvate kinase and glucokinase as well as liver content of glycogen were increased after CG treatment. CG was rich in alkaloids and eight main alkaloids were identified, many of which had been demonstrated to possess adequate anti-diabetic activities. These results suggest that the alkaloid-rich extract of CG possesses potential anti-hyperglycemic and anti-hyperlipidemic effects and can be utilized as an effective agent for the treatment of type 2 diabetes.

Two new eunicellin diterpenoids from the East China Sea gorgonian Muricella sp.

A phytochemical investigation on gorgonian Muricella sp. from East China Sea resulted in the isolation of eight eunicellin diterpenoids including two new ones, muricellins A-B (1, 2). Chemical structures of these compounds were elucidated by spectroscopic techniques (1D and 2D NMR and MS) and by comparison with data reported in the literature. Anti-rheumatoid arthritis activities of 1, 3, 4, and 6 have been evaluated.

Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

BACKGROUND: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis. RESULTS: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively. CONCLUSIONS: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.

Three new polyunsaturated lipids from a Guangxi marine sponge Haliclona sp.

Three new polyunsaturated lipids, (6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraen-3-one (1), (6Z,9Z,12Z,15Z)-1-bromooctadeca-6,9,12,15-tetraen-3-one (2), and (Z)-ethyl docos-5-enoate (3), together with two known polyunsaturated lipids, 4(Z),7(Z),10(Z)-tridecatrienoic acid (4) and (6Z,9Z,12Z,15Z)-octadeca-1,6,9,12,15-pentaen-3-one (5), were isolated from the marine sponge Haliclona sp., which was collected from Guangxi, using HSCCC and HPLC methods. Chemical structures of the five compounds were elucidated by spectroscopic techniques.

Jaspiferins C-F, four new isomalabaricane-type triterpenoids from the South China Sea sponge Jaspisstellifera.

A chemical investigation of marine sponge Jaspis stellifera, collected from the South China Sea, led to the isolation of four new isomalabaricane-type triterpenoids, jaspiferins C-F (1-4). The structures of those compounds were elucidated by extensive spectroscopic methods. Jaspiferin C (1), which has the six-membered carbon ring at the side chain, was discovered for the first time from the isomalabaricane-type triterpenoids. The hypothesis of a biogenetic pathway to generate jaspiferin C (1) was depicted.

KAI1/CD82 and MRP1/CD9 serve as markers of infiltration, metastasis, and prognosis in laryngeal squamous cell carcinomas.

OBJECTIVE: The current study explored the expression of KAI1/CD82 and MRP1/CD9 and its significance in laryngeal squamous cell carcinoma (LSCC). METHODS: The expression levels of KAI1/CD82 and MRP1/CD9 in 100 LSCC tissue specimens, as well as in 30 para-LSCC non-carcinomatous tissue specimens randomly taken from the patients, were assessed using the quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry and correlations with pathological parameters of LSCC and their influence on survival function were analyzed. RESULTS: KAI1/CD82 and MRP1/CD9 showed basically consistent changes in both mRNA and protein expression. Their expression in the 30 LSCC specimens was significantly lower compared with that in the corresponding non-carcinous tissues (P < 0.01 or 0.05), notably correlating with TNM stage, differentiation degree, clinical stage, and lymphatic metastasis (P < 0.01 or 0.05), but not gender, age, and LSCC growth sites (P > 0.05). The median survival of patients with positive KAI1/CD82 and MRP1/CD9 protein expression was longer than that of patients with negative protein expression (P < 0.01 or 0.05). KAI1/CD82 protein expression negatively correlated with MRP1/CD9 protein expression in LSCC (χ(2) = 31.25, P < 0.01). CONCLUSION: KAI1/CD82 and MRP1/CD9 may jointly participate in the development of LSCC. They may serve as the markers for judging the infiltration, metastasis, and prognosis of LSCC.

KAI1/CD82 and cyclin D1 as biomarkers of invasion, metastasis and prognosis of laryngeal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the expressions and significance of KAI1/CD82 and cyclin D1 in laryngeal squamous cell carcinoma (LSCC). METHODS: Real-time quantitative PCR (Q-PCR) and Western blot assay were employed to detect the expressions of KAI1/CD82 and cyclin D1 in the laryngeal tissues of 86 LSCC patients, 32 patients with laryngeal polyp and 38 patients with laryngeal leukoplakia, and the influence of both proteins on the clinicopathological features and survival of LSCC patients. RESULTS: The changes in mRNA and protein expressions of KAI1/CD82 and cyclin D1 were consistent in three groups, and the expressions of KAI1/CD82 and cyclin D1 were significantly different among three groups (P<0.01 or <0.05). The KAI1/CD82 expression in patients with TNM stage III-IV LSCC, poorly differentiated LSCC, clinical stage III-IV LSCC or lymph node metastasis was markedly lower than that in those with TNM stage I-II LSCC, well differentiated LSCC, clinical stage I-II LSCC or no lymph node metastasis (P<0.01 or <0.05). However, there was no marked difference in KAI1/CD82 expression between males and females and among patients in different age groups (P>0.05). In LSCC patients positive for KAI1/CD82 protein expression, the median survival time was 76 months, which was significantly longer than that in LSCC patients negative for KAI1/CD82 protein expression (48 months; X(2)=16.293, P=0.000). The Cyclin D1 expression in patients with TNM stage III-IV LSCC, poorly differentiated LSCC, or clinical stage III-IV LSCC was dramatically higher than that in patients with TNM stage I-II LSCC, well differentiated LSCC, or clinical stage I-II LSCC (P<0.01 or <0.05). However, no marked difference was noted in cyclin D1 expression between males and females, among patients in different age groups and between patients with and without lymph node metastasis (P>0.05). In LSCC patients positive for cyclin D1 protein expression, the median survival time was 40 months, which was markedly shorter than that in LSCC patients negative for cyclin D1 protein expression (X(2)=9.517, P=0.02). In LSCC patients, there was a negative correlation between KAI1/CD82 expression and cyclin D1 expression (X(2)=7.86, P<0.01). CONCLUSION: KAI1/CD82 affects cell cycle. Both KAI1/CD82 and cyclin D1 are involved in the occurrence and development of LSCC, and may provide clinical information for evaluation of invasiveness, metastasis and prognosis of LSCC. Thus, KAI1/CD82 and cyclin D1 may serve as markers for determination of invasiveness, metastasis and prognosis of LSCC.

Inhibitory action of chamaejasmin A against human HEP-2 epithelial cells: effect on tubulin protein.

In this work, the anticancer activity of chamaejasmin A was studied by evaluating its in vitro cytotoxicity against several cell lines (CAL-27, UMSCC-1, UMSCCG19, HEP-2 and Vero cells) using the 3-(4,5)-dimethylthiazoly1)-3,5-diphenytetrazolium bromide assay. Results indicated chamaejasmin A shows more notable anticancer activity against HEP-2 cells, with IC(50) values of 3.48 µM. Furthermore, western blot analysis showed that chamaejasmin A is able to increase the expression of ß-tubulin (TB), but not α-TB. In vivo, chamaejasmin A intake through gavage resulted in ß-TB depolymerization inhibition in HEP-2 tumors. In silico simulations indicated that chamaejasmin A specifically interacts with the binding site which is located at the top of ß-TB, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB protein active site, associated with two strong H-bonds. The binding energy (E (inter)) was calculated to be -129.40 kcal mol(-1). Results above suggest that chamaejasmin A possesses anti-cancer properties relating to ß-TB depolymerization inhibition.

[Anti-tumor peptide of tumstatin in the treatment of the transplantable model of human laryngeal squamous carcinoma in nude mice].

OBJECTIVE: To study the effect of anti-tumor peptide of tumstatin on tumor growth of human laryngeal squamous carcinoma in nude mice and the underlying mechanism. METHOD: Nude mice model bearing laryngocarcinoma were established by using human laryngeal squamous carcinoma cell line (Hep-II). The animals were given tumstatin or PBS for 10 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immunohistochemical examination was adopted and ultra-micro-structural changes of carcinoma after administration of tumstatin were observed under light and electron microscopes for pathology examination. RESULT: The differences was statistically significant in the net mice weight, tumor weight, tumor volume and tumor weight/net mice weight between the treatment group and the control group (P<0.01). The restrained percentage of tumor was 51.58%. The necrosis and apoptosis of the tumor cells and the angiogenesis reduction were found under light and electron microscope in the treatment group. MVD of the treatment group was lower than that of the control group (P<0.01). CONCLUSION: Tumstatin can significantly restrain the development of laryngocarcinoma.

A new feruloyl amide derivative from the fruits of Tribulus terrestris.

A new feruloyl amide derivative, named tribulusamide C, was isolated from the fruits of Tribulus terrestris. Its structure was determined on the basis of spectroscopic analysis including IR, 1-D-, 2-D-NMR and HR-ESI-MS. The structure of tribulusamide C was characterised by a unit of pyrrolidine-2,5-dione, which distinguished it from other lignanamides previously isolated from the fruits of T. terrestris.

Down-regulation of MiR-206 promotes proliferation and invasion of laryngeal cancer by regulating VEGF expression.

MicroRNAs (miRNA) are a class of small noncoding RNAs that regulate the expression of their target genes. The aim of the present study was to explore the effects of miR-206 on laryngeal suamous cell carcinoma (LSCC) cells. The expression level of miR-206 was quantified by qRT-PCR in primary LSCC tissues and corresponding adjacent non-neoplastic tissues. MTT, Matrigel invasion assays and flow cytometry methods were used to test the proliferation, invasion and apoptosis of MiR-206 transfection LSCC cells and a mouse model was used to investigate tumorigenesis. MiR-206 was significantly down regulated in the LSCC tissues. Inverse correlation of miR-206 expression was found with the T grade, nodal metastasis and clinical stage of LSCC. Cell proliferation, migration, invasion and tumorigenesis in the LSCC cells were significantly inhibited and apoptotic cells were also increased after miR-206 tansfection. Furthermore, miR-206 transfection down-regulated the expression of vascular endothelial growth factor (VEGF) in the LSCC cells. The loss of miR-206 may play an important role in the progress of LSCC and miR-206 may function as a novel tumor suppressed miRNA.

Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells.

In the present study, we investigated the mechanisms of chamaejasmine action on human HEp-2 larynx carcinoma cells, which possess constitutively active Akt. Results indicated that chamaejasmine showed more notable anticancer activity than apigenin against HEp-2, PC-3, NCI-H1975, HT-29 and SKOV-3. Moreover, chamaejasmine presented most significantly inhibition towards HEp-2, with IC50 values of 1.92 µM. Treatment of HEp-2 cells with chamaejasmine (1-4 µM) resulted in significant dose-dependent decrease in Akt phosphorylation at Serine473. Chamaejasmine-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was confirmed by reduced phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3, essential downstream targets of Akt. Inactivation of Akt seems to be associated with downregulation of insulin-like growth factor receptor 1 protein level and inhibition of its autophosphorylation upon chamaejasmine treatment. Exposure to chamaejasmine significantly induced caspase-9 and caspase-3 activity. In vivo, chamaejasmine intake through gavage resulted in inactivation of Akt and induction of apoptosis in HEp-2 tumors. These results suggest that Akt inactivation and dephosphorylation of BAD is a critical event, at least in part, in chamaejasmine-induced HEp-2 cells apoptosis.

Microarray gene analysis of Toll-like receptor signaling elements in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: To identify the regulatory mechanisms of Toll-like receptor (TLR)-associated genes in chronic rhinosinusitis (CRS) with nasal polyps (NP) using gene microarray analyses. METHODS: We pooled: (1) NP biopsy specimens from 10 nonatopic CRS patients and (2) healthy mucosal tissue from 10 additional nonatopic healthy patients (controls). These pooled samples were evaluated by gene microarrays that included 125 genes for TLRs and associated signaling elements. To validate gene product expressions, 20 NP and 15 normal nasal turbinate tissues were evaluated for TLR-9 expression by immunohistochemical staining and Western blots using samples from gland cells, epithelial cells, and mononuclear cells cytologically identified by HE staining. RESULTS: In pooled NP samples compared to pooled controls, 4 genes were upregulated (≥ 2-fold higher expression) and 19 were downregulated (≤ 0.5-fold lower expression). TLR-9 was an upregulated gene in NP tissue. Compared to control tissue, there were significantly higher percentages of TLR-9 positively stained NP gland cells, epithelial cells, and mononuclear cells (p < 0.001). On Western blots, while both normal and NP tissues expressed TLR-9 protein, the expression was significantly more pronounced for NP tissue (p < 0.001). CONCLUSIONS: Inflammation associated with CRS may be due to dysregulated innate immune elements, particularly TLR-9 and its associated signal transduction elements, which may impact upon prolonged activation of adaptive immune responses in the sinonasal mucosa.

[Apoptosis inducing effect by TRAIL on human laryngeal squamous carcinoma Hep-2 cells].

OBJECTIVE: To study the apoptosis inducing effect of tumor necrosis factor related apoptosis-ligand (TRAIL) on human laryngeal squamous carcinoma Hep-2 cells and its effect mechanism. METHOD: The human laryngeal squamous carcinoma Hep-2 cell line was treated with different concentration of TRAIL in vitro. The inhibition ratio of tumor cells was determined by MTT colorimetric assay, the incidence of cell apoptosis was determined by flow cytometry method. The morphologic changes of laryngeal squamous carcinoma Hep-2 cell were observed with transmission electron microscope. RESULT: In vitro, all the different concentrations of TRAIL inhibited laryngeal squamous carcinoma cell's growth. The inhibited growth ratio showed significant concentration-dependence. The concentrations for inducing apoptosis-ratio(TRAIL 1, 10, 100 microg/L) determined by flow cytometry was (11.49 +/- 0.36)%, (22.31 +/- 0. 82)%, (59.64 +/- 1.10)% respectively in the study group, and (3.13 +/- 0.12)% in the control group, which was significantly different between these two groups (P < 0. 01). CONCLUSION: In vitro, TRAIL inhibited the growth of human laryngeal squamous carcinoma Hep-2 cells. The induced apoptosis of TRAIL shows significant concentration- independence. TRAIL inhibits the growth of human laryngeal squamous carcinoma Hep-2 cells trough inducing apoptosis.

Down-regulation of cyclin D1 by small interfering RNA inhibits cell growth and induces apoptosis of laryngeal squamous cell carcinoma.

OBJECTIVE: The objective of the study was to explore the inhibitive role of cyclin D1 gene silence in laryngeal squamous cell carcinoma by lentivirus-mediated RNA interference. MATERIALS AND METHODS: Cd1-RNAi-Lentivirus and the control lentivirus (GFP-Lentivirus) were transfected into Hep-2 cells. Reverse transcriptase polymerase chain reaction was performed to explore the cyclin D1 expression level in Cd1-RNAi-Lentivirus-transfected Hep 2 cells. The apoptosis and viability of Cd1-RNAi-Lentivirus-treated Hep-2 cells were measured with flow cytometry and methyl thiazolyl tetrazoliym assay. In an animal experiment, 10 mice bearing Hep-2 cell tumor were intratumorally injected with Cd1-RNAi-Lentivirus; and the other 10 mice were injected with GFP-Lentivirus. Terminal deoxytransferase-mediated dUTP nick end labeling stains and transmission electron microscope were used to observe the apoptosis in the xenografts. RESULTS: Cyclin D1 was knocked down after Cd1-RNAi-Lentivirus was transfected into Hep-2 cells. The proliferative ability of Hep-2 cells was significantly inhibited by Cd1-RNAi-Lentivirus, and a significant apoptosis of Hep-2 cells was also observed after Cd1-RNAi-Lentivirus transfection. The average weight and volume of tumors in the Cd1-RNAi-Lentivirus-treated group were significantly lower than those in the control group (P < .01). The significant apoptosis was detected with terminal deoxytransferase-mediated dUTP nick end labeling stain and transmission electron microscope. CONCLUSIONS: The present findings suggest that cyclin D1 gene silence by lentivirus-mediated RNA interference can inhibit growth and promote apoptosis of laryngeal squamous cell carcinoma.

A role for the parafascicular thalamic nucleus in the development of morphine dependence and withdrawal.

The parafascicular thalamic nucleus (nPf) is a critical relay in the ascending system that mediates motor control in the central nervous system (CNS). Yet, little is known about whether or not the nPf is involved in the development of morphine dependence and withdrawal. In the present study, kainic acid was used to chemically destroy the nPf in Wistar rats, and morphine dependence and withdrawal models were established. Morphine withdrawal symptoms score was evaluated in each group. An electrophysiological method was used to measure the changes in spontaneous discharge of nPf neurons. mu-Opioid receptor (MOR) mRNA level in nPf was detected using semi-quantitative RT-PCR. The ultrastructural alterations were examined by transmission electron microscopy. Results showed that the bilateral lesion of nPf had a marked influence on the development of morphine dependence and withdrawal. In order to address the mechanisms underlying, we found: (1) the average frequency and sum of nPf neurons that exhibited spontaneous discharge were increased in the morphine withdrawal group in comparison with the sham model group (P<0.05); (2) MOR mRNA level in the nPf of the morphine dependence group was decreased in comparison with that of the sham model group (1.45+/-0.38 vs. 5.37+/-0.94, P<0.01). In the morphine withdrawal group, which underwent 40 h withdrawal, the MOR mRNA level was higher than that in the morphine dependence group (2.97+/-0.73 vs. 1.45+/-0.38, P<0.05) but still lower than that in the sham model group (P<0.05); (3) the ultrastructural injuries of nPf neurons, which were in the nucleus, organelles and neuropil, were marked in the morphine dependent and withdrawal groups. Our study indicated that nPf played an important role in the development of morphine dependence and withdrawal. The results suggest that nPf may become a therapeutic target for treating morphine withdrawal syndrome.

A new phenolic glucoside from the leaves of Heliciopsis lobata.

A new phenolic glucoside ester, 6'-E-(2''-methyl-2''-butenoyl) arbutin (1), was isolated from the leaves of Heliciopsis lobata. Its structure was elucidated by spectral analysis.