[Xanthoceras sorbifolium Bunge flower extract inhibits benign prostatic hyperplasia in rats].

OBJECTIVE: To assess the inhibitory effect of the extract of Xanthoceras sorbifolium Bunge flower against benign prostatic hyperplasia (BPH) and explore its possible mechanism. METHODS: MTT assay was used to examine the effect of the extract of Xanthoceras sorbifolium Bunge flower on proliferation of benign prostatic hyperplasia cells (BPH-1), and cell apoptosis and cell cycle changes following the treatment were analyzed using annexin V/PI double staining and flow cytometry. The protein expression levels of Bcl-2, Bax, caspase-3, PI3K and AKT in the treated cells were detected using Western blotting. A rat model of BPH established by subcutaneous injection of testosterone propionate was treated with the flower extract for 28 days, and pathological changes in the prostate tissue were observed with HE staining. The protein expression levels of Bcl-2, Bax, caspase3 and PI3K/AKT in the prostate tissue were detected with Western blotting. RESULTS: Within the concentration range of 125-1000 µg/mL, the flower extract of Xanthoceras sorbifolium Bunge significantly inhibited the proliferation of BPH-1 cells and caused obvious cell cycle arrest at G0/G1 phase; the apoptotic rate of the cells was positively correlated with the concentration of the flower extract (P < 0.05). Bcl-2, p-PI3K and p-AKT expression levels were significantly down-regulated and Bax and caspase-3 expression levels were significantly increased in the cells after treatment with the flowers extract (P < 0.05). In the rat models of BPH, the rats treated with the flowers extract at moderate and high doses showed obviously decreased expressions of p-AKT and Bcl-2 and an increased expression of Bax in the prostate tissue; a significantly lowered p-AKT expression was observed in the prostate tissue of rats receiving the low-dose treatment (P < 0.05). CONCLUSION: The flower extract of Xanthoceras sorbifolium Bunge has a inhibitory effect on BPH both in vitro and in rats, suggesting its potential value in the development of medicinal plant preparations for treatment of BPH.

The mechanism of Epimedium in the treatment of coronary atherosclerotic heart disease based on network pharmacology, molecular docking, and in vitro studies.

OBJECTIVE: There are many challenges related to the treatment of coronary atherosclerotic heart disease (CAD). Studies have confirmed that Epimedium extract inhibits myocardial injury induced by myocardial ischaemia, but the mechanism of action remains unclear. This study aimed at analysed the effective components and mechanisms of Epimedium in treating CAD based on network pharmacology and molecular docking studies and to verify the mechanism in vitro. MATERIALS AND METHODS: The TCMSP and UniProt databases were used to filter for the active components and drug targets of Epimedium. The GeneCards database was used to screen disease targets associated with CAD. The intersection of the drug targets of Epimedium and the disease targets of coronary heart disease was studied to identify the targets of Epimedium in the treatment of CAD. Cytoscape software was used to establish and analyse an activity-target network. The STRING database was used to analyse a protein-protein interaction (PPI) network, and proteins in the PPI network were visualized in the R language. Bioconductor software was used for GO function and KEGG pathway enrichment analyses, and visualization analysis was performed in the R language. PyMOL software was used to verify the molecular docking between selected active components of Epimedium and the targets of CAD, and the potential key effective components of Epimedium in the treatment of coronary heart disease were identified. The involvement of the PI3K/Akt pathway was validated by Western blot analysis. RESULTS: (1) Twenty-three active compounds, including Epimedium glycoside, quercetin, luteolin, and olive resin, were screened out. There were 68 common targets of Epimedium and CAD, including IL-6, ESR1, RELA, FOS, NCOA1, CCND1, EGFR, MAPK8, VEGFA, and CASP8. The potential signaling pathways involved in the treatment of CAD by Epimedium included the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway, and the HIF-1 signaling pathway. (2) Luteolin, quercetin, sitosterol, and anhydroicaritin showed strong binding to targets of CAD based on molecular docking studies. (3) Epimedium extract increased the expression of PI3K, Akt and P-Akt but decreased the expression of IL-6  in vitro. CONCLUSIONS: (1) Icariin, quercetin and luteolin may act on target proteins, including IL-6, ESR1, EGFR, MAPK8, VEGFA and CASP8, to participate in the regulation of the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway and other signaling pathways in order to effectively treat CAD. (2) In vitro studies confirmed that Epimedium extract can treat CAD by upregulating PI3K, Akt and P-Akt protein expression and downregulating IL-6 protein expression in SD rat cardiomyocytes.

[Biography of Moody Meng].

Moody Meng(1897-1983) was a pioneer of pharmacy in China. He was the main editor of the first Chinese Pharmacopoeia, the first president of the National College of Pharmacy (now China Pharmaceutical University), the first director of Chongqing Union Pharmaceutical Factory during the Anti-Japanese War and the first director of the China National Institute for the Control of Pharmaceutical and Biological Products. He made important contributions in many fields of pharmacy in China.

An update on acupuncture point injection.

This overview reports the global research advances in acupuncture point injection in the last 5 years. Acupuncture point injection can be applied to a wide range of curable diseases, predominantly those involving pain, but it has poor clinical evidence. Progress has been attained in the mechanism research on acupuncture point injection, but further studies remain necessary. With the reported adverse effects of acupuncture point injection, the need to standardize its clinical procedure has become urgent.

Prospective randomised evaluation of traditional Chinese medicine combined with chemotherapy: a randomised phase II study of wild toad extract plus gemcitabine in patients with advanced pancreatic adenocarcinomas.

BACKGROUND: An intravenous formulated extract of the venom of the wild toad Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, huachansu, is currently used in China for the treatment of lung, liver, pancreatic, and colorectal cancers. We performed a randomised, single-blinded, phase II clinical study of huachansu plus gemcitabine versus placebo plus gemcitabine in patients with locally advanced and/or metastatic pancreatic adenocarcinomas. METHODS: Patients with tissue-proven locally advanced and/or metastatic pancreatic adenocarinoma were randomly assigned to receive either gemcitabine 1000 mg m(-2) on days 1, 8, and 15 with huachansu 20 ml m(-2) daily for 21 days (arm A) or placebo (arm B); treatment cycles were 28 days in length. Primary end point was 4-month progression-free overall survival (PFS); secondary end points were objective radiographical response rate (ORR), time to progression (TTP), and toxicity. RESULTS: A total of 80 subjects were enrolled; 76 patients were evaluable (received at least 1 week therapy). Median overall survival was 160 days for arm A and 156 days for arm B (P=0.339); ORR was 9 and 3% in arms A and B, respectively (P=0.332), median TTP was 98 and 115 days, respectively (P=0.825); the median 4-month PFS was 99 and 98 days, respectively (P=0.679). CONCLUSION: Huachansu when combined with gemcitabine did not improve the outcome of patients with locally advanced and/or metastatic pancreatic cancer.

[The development of clinical application of the rejuvenator and a study of its mechanism for the treatment of functional erectile dysfunction].

In this paper, we describe the development and clinical application of the Rejuvenator and report the result of our study on its mechanism for the treatment of functional erectile dysfunction (FED). The Rejuvenator, which can be used both at home and in hospitals to treat patients with FED, was developed on the basis of our clinical practice in the light of the modern theory of traditional Chinese medicine and by integrating multiple techniques of engineering science. It works by means of the paraoral use of the special herbal medicine, electro-magnetic effects, thermal moxibustion and drug-ingression. 2250 patients with FED received the treatment. Using combined electro-neurophysiological techniques, pulsed ultrasound Doppler and microcomputer image-scanning, we further studied the mechanism of the Rejuvenator for the treatment of FED. The total effective rate was 92%. The clinical data and result of study indicate that the Rejuvenator for the patients with functional erectile dysfunction is a safe, effective and scientific new method.

Effect of six steroidal saponins isolated from anemarrhenae rhizoma on platelet aggregation and hemolysis in human blood.

Six steroidal saponins were isolated from Anemarrhena asphodeloides Bunge (Liliaceae), a traditional chinese medicine, and named anemarrhenasaponin I (An-I), anemarrhenasaponin Ia (An-Ia), timosaponin B-I (TB-I), timosaponin B-II (TB-II), timosaponin B-III (TB-III), and timosaponin A-III (TA-III). The effects of these six compounds on platelet aggregation and hemolysis in human blood were studied. All these compounds provoked remarkable inhibiting effect on platelet aggregation, and activated partial thromboplastin times (APTT) are sensitive to the presence of these six compounds. Using an in vitro system, APTT was delayed with the increment of the concentrations of these six compounds. In these six compounds, only timosaponin A-III appeared a strong effect on hemolysis, and anemarrhenasaponin Ia had a slight effect on hemolysis, other had no effect on hemolysis. These results suggested that these steroidal saponins isolated from Anemarrhena asphodeloides Bunge (Liliaceae) might be used as a novel antithrombotic therapeutic agents in post-myocardial infarction.

Steroidal saponins from Anemarrhena asphodeloides and their effects on superoxide generation.

A new steroidal saponin, timosaponin F, along with six known compounds was isolated from the rhizomes of Anemarrhena asphodeloides Bge. On the basis of chemical and spectroscopic evidence, the structure of timosaponin F was elucidated as (5beta, 25 S):-spirostan-3beta,15alpha,23alpha-triol-3-O-beta- glucopyranosyl-(1--->2)-beta-galactopyranoside. The six known compounds were anemarrhenasaponin I, anemarrhenasaponin Ia, timosaponin BI, timosaponin BII, timosaponin B, timosaponin AIII; their effects on superoxide generation are also reported.

[Treatment of chronic prostatitis with computerized herbal drug penetrator].

A computerized herbal drug penetrator for chronic prostatitis was designed and developed on the basis of a combination of the authors' clinical practice with modern Traditional Chinese Medicinal theories. The device has integrated many hi-techs of current engineering science. It works by applying special herbal medicine, electro-magnetic effects, thermal moxibustion, perfusion and pulsated massage with water-capsule. The result of using this technique in the treatment of 100 cases has demonstrated its satisfying effectiveness.

Coral as a carrier for recombinant human bone morphogenetic protein-2.

By combining coral with recombinant human bone morphogenetic protein-2 (rhBMP-2), rhBMP-2/coral composite was obtained in this study. Following implantation of the composite into the muscle pouches of mice, cartilage growth was induced in the pores or on the surface of the implants at one week, woven bone at three week and lamellar bone with bone marrow at six week, and coral was absorbed partially. The induced formation of endochondral bone was time-related and rhBMP-2 dose-related. The results of this study indicate that the composite possesses a superior ability of osteogenesis, and coral acts as one of the most suitable rhBMP-2 slowrelease carriers currently available. The composite will be a new type of bone substitute to be used in orthopaedics and maxillofacial surgery.

Pulmonary responses to oil fly ash particles in the rat differ by virtue of their specific soluble metals.

Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.

Production and characterization of monoclonal antibodies against fumitremorgin B.

This paper reports the preparation and identification of two monoclonal antibodies against FTB, and the establishment of an indirect competitive ELISA methods for FTB determination in buckwheat, rice, and corn. Two of the hybridoma cell lines (1C9 and 2D10), which could produce specific antibodies against fumitremorgin B(FTB), were selected and developed. The affinity Kaff constants of the monoclonal antibodies with the coating antigen, FTBS-IgG, were found to be 6 x 10(8) M-1 and 9.8 x 10 M-1, respectively. The isotypes of the monoclonal antibodies are of two isotypes, IgG1 and IgM, respectively. The antibody titers were found around 1 x 10(6) and 1.5 x 10(6). The standard curves showed that as little as 5 pg of FTB in 50 mL could be detected, and the linear range of standard curve was from 10 pg to 1000 pg of standard FTB. There were no cross-reaction for McAbs in the assay system with some mycotoxins tested. The mean recovery rate from buckwheat spiked with 10-60 ng/g of FTB was 78-88.7%.

[Timosaponins E1 and E2].

By means of silica gel chromatography and HPLC, two compounds were isolated from Anemarrhena asphodeloides Bge.. On the basis of chemical and spectral (MS, 1H, 13CNMR, IR) analyses, their structures were elucidated as (25S)-26-O-beta-D-glucopyranosyl-22-hydroxy-5 beta-furost-3 beta, 15 alpha, 26-triol-3-O-beta-D-glucopyranosyl (1-->2)-beta-D-galactopyranoside (1), and (25S)-26-O-beta-D-glucopyranosyl-22-methoxy-5 beta-furost-3 beta, 15 alpha, 26-triol-3-O-beta-D-glucopyranosyl (1-->2)-beta-D-galactopyranoside (2). They are named as timosaponin E1 (1) and timosaponin E2 (2) respectively. The structure of anemarrhenasaponin-I (A) is briefly discussed. Timosaponins are the main active constituents of Anemarrhena asphodeloides, most of them were shown to can inhibit platelet aggregation.

Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand.

Several analogs of an endogenous cannabimimetic, arachidonylethanolamide (anandamide), were synthesized to study the structural requirements of the ethanolamide head group. CB1 receptor affinities of the analogs were evaluated by a standard receptor binding assay using tritiated CP-55,940 as the radioligand and compared to anandamide which was shown to have a Ki of 78 nM. Replacement of the amide carbonyl oxygen by a sulfur atom had a detrimental effect on the CB1 affinity. The thio analogs of both anandamide and (R)-methanandamide showed very weak affinity for CB1. The secondary nature of the amidic nitrogen was also shown to be important for affinity, indicating a possible hydrogen-bonding interaction between the amide NH and the receptor. Introduction of a phenolic moiety in the head group resulted in the loss of receptor affinity except when a methylene spacer was introduced between the amidic nitrogen and the phenol. A select group of analogs were also tested for their affinity for the CB2 receptor using a mouse spleen preparation and were found to possess low affinities for the CB2 sites. Notably, anandamide and (R)-methanandamide demonstrated high selectivity for the CB1 receptor. Overall, the data presented here show that structural requirements of the head group of anandamide are rather stringent.

[The progress of morphological research on the parabrachial nucleus].

In this paper, the progress of morphological research on the PBN, the cytoarchitecture of the PBN, and the fiber connections between the PBN and the spinal, the brainstem, the forebrain and the other nucleus were summarized. Its function in the relationship between the meridian and the internal organ was also assumed.

[The functional connection among the "zusanli"-spinal dorsal horn neurons-trigeminal sensory nucleus of rats].

Electrical stimulation of Zusanli (ST36) point and Trigeminal Sensory Nucleus (TSN) as well as microelectrode recording from the laminae II - VI of the lumbar spinal dorsal horn have been used on the pentobarbital anesthetized rats, finding and identifying 142 spinal neurons responding to the stimulation of both ST36 and TSN. Among them, 29 responded antidromically to TSN; the others, responded orthodromically to TSN; These neurons distributed in the L2-S1 segments, the most in the L3-L6 segments, and in the laminae III-V, occasionally in the laminae II and VI in the spinal dorsal horn, the LTM and WDR neurons were 50% respectively of them. The results indicate that (i) single spinal dorsal horn neurons receives ST36 afferent input and then conveys it to the TSN; (ii) some spinal dorsal horn neurons receive, in turn, innervation from TSN; (iii) The convergence and integration between ST36 and TSN inputs might occur in the spinal dorsal horn neurons.

The functional linkage among the "ZSL"-spinal dorsal horn-SN.

Electrical stimulation of the Zusanli point (ZSL) and solitary tract nucleus (SN) as well as microelectrode recording from the laminae III-V of the lumbar spinal dorsal horn have been used on the pentobarbital anesthetized rats, finding and identifying 57 spinal neurons responding to the stimulations of both ZSL and SN. Among them, 34 responded antidromically to SN; the others responded orthodromically to SN. Among them, the low-threshold mechano-receptive (LTM) neurons and wide-dynamic-range (WDR) neurons were 50 percent respectively. The results indicate that (i) a single spinal dorsal horn neuron receives somatic afferent input and then conveys it to the visceral sensory nucleus-SN; (ii) some spinal dorsal horn neurons receive, in turn, innervation from the SN; (iii) the convergence and integration between somatic and visceral sensory inputs might occur in the spinal dorsal horn neurons and/or SN.

Differential inhibitory effects of various herb extracts on the activities of reverse transcriptase and various deoxyribonucleic acid (DNA) polymerases.

Forty preparations of the extracts from 28 kinds of Asian herbs were tested for ability to inhibit the activities of murine retroviral reverse transcriptase and human deoxyribonucleic acid (DNA) polymerases. Among the 40 extracts, 35 inhibited reverse transcriptase activity and 29 inhibited DNA polymerase alpha activity. The inhibitory potencies of these extracts were expressed as the 50% inhibition concentrations (IC50), at which the enzyme activities were inhibited by 50%. Very strong inhibitions were observed with the extracts from Millettia pachycarpa (Leguminosae) and Mallotus apelta (Euphorbiaceae) as shown by their low IC50 values for reverse transcriptase (0.4-0.5 micrograms/ml) and DNA polymerase alpha (0.9-1.4 micrograms/ml). Enzyme kinetic analysis revealed that the mode of inhibition of reverse transcriptase by these two extracts was competitive with respect to the template.primer [poly(rA).oligo(dT)] and noncompetitive with respect to deoxythymidine triphosphate (dTTP) substrate. Besides reverse transcriptase and DNA polymerase alpha, DNA polymerase I and ribonucleic acid (RNA) polymerase from E. coli were inhibited by these two extracts. These results indicate that the herb extracts contain as yet unidentified substance(s) which inhibit the activities of reverse transcriptase and cellular DNA polymerases.