[Exploring the therapeutic mechanism of Simiao pills for hyperuricemia based on network pharmacology and molecular docking].

OBJECTIVE: To explore the mechanism of Simiao pills for treatment of hyperuricemia based on network pharmacology and molecular docking. OBJECTIVE: The active ingredients of Simiao pills and their targets of action were predicted using TCMSP, SEA, Swiss and PharmMapper databases. GeneCards and TCD databases were searched for the disease targets related to hyperuricemia. Cytoscape 3.6.1 was used to construct a protein-protein interaction network. GO enrichment analysis and KEGG pathway analysis were carried out on the STRING platform. The binding between the main compounds and the key targets were predicted using the SwissDock platform for molecular docking. OBJECTIVE: We identified 28 active ingredients and 429 potential targets in Simiao pills, 494 disease targets related to hyperuricemia, and 118 common targets between Simiao pills and hyperuricemia. Several key targets including AKT1, IL- 6, JUN, TNF and CASP3 were screened for molecular docking, which had good binding activities with berberrubine, epiberberine, stigmasterol and sitosterol. AKT1, IL-6, JUN, TNF and CASP3 were predicted to be the key targets for Simiao pills for treating hyperuricemia. KEGG pathway enrichment analysis showed that Simiao pills produced therapeutic effects on hyperuricemia through multiple signaling pathways including the TNF signaling pathway, apoptosis signaling pathway and IL-17 signaling pathway. OBJECTIVE: Simiao pills produces therapeutic effects on hyperuricemia through multiple components and targets and the synergy of several pathways. Our finding provides a theoretical basis for further study of the active ingredients and therapeutic mechanism of Simiao pills for treating hyperuricemia.

[Advances in effect of unilateral auditory deprivation on sound localization].

In patients with single-sided deafness (SSD), the interaural time difference and the interaural level difference signals are insufficient or missing, which result in the lack of sound localization ability and the decrease of speech comprehension in the noise environments. SSD can also cause the morphological and functional changes of the central auditory system, resulting in auditory deprivation. In early stage of the development, the auditory center is more susceptible to ambient environment and auditory inputs. It is a critical period of auditory function and morphological refinement. It is also sensitive period of central adaptability after auditory deprivation. SSD in the sensitive period of development can cause significant laterality activities of bilateral sound localization pathway. Unilateral auditory deprivation can distort tonotopic maps, disrupt the binaural integration, reorganize the neural network and change the synaptic transmission in the primary auditory cortex or sub cortex. In order to compensate for the deficiency of the interaural time difference and interaural level difference cues, the auditory pathway is used to improve the ability of sound source localization by using the spectral-shape cues remaining unchanged. In order to improve the effectiveness of the functional areas of the cortex, auditory center is also reorganized by cross-modal. However, central compensation after SSD is a double-edged sword. If SSD onset in the sensitive period, the laterality of auditory pathway will be continued and difficult to reverse by even long term bilateral hearing in the post-sensitive period. Therefore, in order to improve the understanding of the characteristics of unilateral auditory deprivation, this paper reviewed the evidence for adaptive changes in spatial hearing following a developmental hearing loss in one ear.

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage.

The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

In vitro anthelmintic activity of Zanthoxylum simulans essential oil against Haemonchus contortus.

The need for new anthelmintic agents with low impact on the environment is becoming urgent. Phytotherapy is an alternative method to control gastrointestinal nematodes in small ruminants. This study aims to determine the composition of Zanthoxylum simulans essential oil (ZSEO) and evaluate the in vitro ovicidal and larvicidal effects of ZSEO on Haemonchus contortus using egg hatch assay, larval development assay (LDA), and larval migration inhibition assay (LMIA). The chemical composition of ZSEO was determined through gas chromatography and mass spectrometry and 94 compounds were identified from the ZSEO. The major constituents of ZSEO were borneol (18.61%), ß-elemene (10.87%). ZSEO and borneol both at 40 mg/mL inhibited larval hatching by 100%, with LC50 values of 3.98 and 1.50mg/mL, respectively. The LC50 value of ß-elemene was not determined because of its insufficient activity. The results of LDA showed that ZSEO, borneol, and ß-elemene all at 40 mg/mL inhibited larval development by 99.8%, 100%, and 55.4%, respectively, and exhibited dose-dependent responses with LC50 values of 4.02, 1.99, and 32.17 mg/mL, respectively. The results of LMIA showed that ZSEO, borneol, and ß-elemene all at 40 mg/mL inhibited larval migration by 74.3%, 97.0%, and 53.2%, respectively. ZSEO presented ovicidal and larvicidal activities in vitro. Therefore, Zanthoxylum may be an alternative source of anthelmintic agents to control gastrointestinal nematodes in sheep.

Combined seawater toilet flushing and urine separation for economic phosphorus recovery and nitrogen removal: a laboratory-scale trial.

Freshwater toilet flushing consumes 20-35% of typical household water demand. Seawater toilet flushing, as practised by Hong Kong since 1958, provides an alternative water source. To maximise the benefits of this unique dual water supply, urine separation could be combined to allow low-cost struvite production and subsequent urine nitrification - in-sewer denitrification. This paper reports on a laboratory-scale study of seawater urine phosphate recovery (SUPR) and seawater-urine nitrification. A laboratory-scale SUPR reactor was run under three phases with hydraulic retention time between 1.5 and 6 h, achieving 91-96% phosphorus recovery. A urine nitrification sequencing batch reactor (UNSBR) was also run for a period of over 650 days, averaging 90% ammonia removal and loading of up to 750 mg-N/L.d. Careful control of the SUPR phosphate removal was found necessary for operation of the downstream UNSBR, and system integration considerations are discussed.

Effects of Omega-3 fatty acid on major cardiovascular events and mortality in patients with coronary heart disease: a meta-analysis of randomized controlled trials.

AIM: There is considerable discrepancy regarding the protective effects of Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) in patients with coronary heart disease (CHD) from the early-phase clinical randomized controlled trials (RCTs). We conducted a meta-analysis of RCTs to address this issue. DATA SYNTHESIS: Pubmed, the Cochrane Central Register of Controlled Trials, and EMBASE databases (∼ May 2013) were systematically searched. Odds ratios (OR) and associated 95% CI were retrieved by using random-effect model according to heterogeneity. A total of 14 RCTs involving 16,338 individuals in the Omega-3 PUFAs group and 16,318 in the control group were identified. Patients assigned to Omega-3 PUFAs did not demonstrate satisfactory improvements on major cardiovascular events (OR, 0.93; 95% CI, 0.86 to 1.01; P = 0.08; I(2) = 46%). By contrast, the reduced risks of death from cardiac causes, sudden cardiac death and death from all causes (OR, 0.88; 95% CI, 0.80 to 0.96; P = 0.003; I(2) = 0%; OR, 0.86; 95% CI, 0.76 to 0.98; P = 0.03; I(2) = 29%; and OR, 0.92; 95% CI, 0.85 to 0.99; P = 0.02; I(2) = 6%; respectively) were shown. CONCLUSIONS: Supplement of Omega-3 PUFAs in patients with CHD is not associated with a protective effect on major cardiovascular events, while it does exert beneficial effects in reducing death from cardiac causes, sudden cardiac death and death from all causes. However, with currently available cardio-protective therapies, whether dietary supplementation with Omega-3 PUFAs should be still considered in patients with CHD is currently debated.

In vitro ovicidal and larvicidal activity of the essential oil of Artemisia lancea against Haemonchus contortus (Strongylida).

Prolonged use of chemical anthelmintics has been found to result in anthelmintic resistance and environmental issues, thereby limiting the application of these drugs in domestic animals and prompting interest in the study of plant extracts as alternative sources thereof. The aim of this study was to evaluate the in vitro effect of the essential oil (EO) of Artemisia lancea against the parasitic nematode Haemonchus contortus using egg hatch assay, larval development assay, and larval migration inhibition assay. The EO yield of extraction was 0.63% (w/w), and the major constituents were 1,8-cineole (34.56%) and camphor (16.65%). In the egg hatch assay, an inhibition greater than 99% was observed with the EO at 10 mg mL(-1) and the LC50 was 1.82 mg mL(-1). 1,8-Cineole demonstrated moderate ovicidal activity with a LC50 of 4.64 mg mL(-1), whereas camphor did not show enough activity to have its LC50 determined. In the larval development assay, the EO, 1,8-cineole, and camphor inhibited 93.6%, 65.2%, and 57% of larval development at 10 mg mL(-1) and exhibited dose-dependent responses with LC50 values of 1.66, 5.07, and 7.80 mg mL(-1), respectively. In the migration inhibition assay, the EO and 1,8-cineole at best inhibited 77% and 60.3% of larval migration at 10 mg mL(-1), respectively. Camphor showed low inhibition capacity, and its efficacy was not dose dependent. The results indicate that the in vitro anthelmintic activity of the EO of A. lancea may be associated with the additive action of the two major constituents, as well as other more minor terpenoid components.

Antibacterial effects of blackberry extract target periodontopathogens.

BACKGROUND AND OBJECTIVE: Antimicrobial agents provide valuable adjunctive therapy for the prevention and the control of oral diseases. Limitations in their prolonged use have stimulated the search for new, naturally occurring agents with more specific activity and fewer adverse effects. Here we sought to determine the antibacterial properties of blackberry extract (BBE) in vitro against oral bacterial commensals and periodontopathogens. MATERIAL AND METHODS: The effects of whole and fractionated BBE on the metabolism of 10 different oral bacteria were evaluated using the colorimetric water-soluble tetrazolium-1 assay. The bactericidal effects of whole BBE against Fusobacterium nucleatum were determined by quantitating the numbers of colony-forming units (CFUs). Cytotoxicity was determined in oral epithelial (OKF6) cells. RESULTS: BBE at 350-1400 µg/mL reduced the metabolic activity of Porphyromonas gingivalis, F. nucleatum and Streptococcus mutans. The reduced metabolic activity observed for F. nucleatum corresponded to a reduction in the numbers of CFUs following exposure to BBE for as little as 1 h, indicative of its bactericidal properties. An anthocyanin-enriched fraction of BBE reduced the metabolic activity of F. nucleatum, but not of P. gingivalis or S. mutans, suggesting the contribution of species-specific agents in the whole BBE. Oral epithelial cell viability was not reduced following exposure to whole BBE (2.24-1400 µg/mL) for ≤ 6 h. CONCLUSION: BBE alters the metabolic activity of oral periodontopathogens while demonstrating a minimal effect on commensals. The specific antibacterial properties of BBE shown in this study, along with its previously demonstrated anti-inflammatory and antiviral properties, make this natural extract a promising target as an adjunct for prevention and/or complementary therapy of periodontal infections.

Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis.

BACKGROUND: Oxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity. METHODS: Two independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects. RESULTS: This meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR=0.26; 95% confidence interval (CI), 0.11 to 0.62; P=0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR=0.42; 95% CI 0.26-0.65; P=0.0001; OR=0.60; 95% CI 0.39-0.92; P=0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD=246.73 mg/m2; 95% CI 3.01-490.45; P=0.05; MD=1.55; 95% CI 0.46-2.63; P=0.005, respectively). No significant differences were found in median PFS (MD=0.71 month; 95% CI -0.59-2.01; P=0.29), median OS (MD=0.10 month; 95% CI -0.41-0.61; P=0.70) or RRs (OR=0.82; 95% CI 0.61-1.10; P=0.18). CONCLUSION: Ca/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.

Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells.

BACKGROUND AND PURPOSE: Microglial activation plays an important role in neurodegenerative diseases by producing an array of proinflammatory enzymes and cytokines. Ginsenoside Rg1 (Rg1), a well-known Chinese herbal medicine, has been well recognized for its anti-inflammatory effect. This study sought to determine the anti-inflammatory effects of Rg1 and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells. EXPERIMENTAL APPROACH: Murine BV-2 microglial cells were treated with Rg1 (10, 20, and 40 µM) and/or LPS (1 µg·ml(-1)). The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR assay and double immunofluorescence labeling, respectively. Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP- responsive element (CRE)-binding protein (CREB) were measured by western blot. U73122 (5 µM), a specific phospholipase C (PLC) inhibitor, was used to determine if PLC signaling pathway might be involved in Rg1's action on activated BV-2 cells. KEY RESULTS: Pretreatment with Rg1 significantly attenuated the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and nuclear factor-κB (NF-κB) in BV-2 cells. U73122 blocked the effects of Rg1 on LPS-induced microglial activation. In addition, PLC-γ1 inhibition partially abolished the inhibitory effect of Rg1 on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). CONCLUSION AND IMPLICATIONS: This investigation demonstrates that Rg1 significantly attenuates overactivation of microglial cells by repressing expression levels of neurotoxic proinflammatory mediators and cytokines via activation of PLC-γ1 signaling pathway.

A comprehensive study of anthocyanin-containing extracts from selected blackberry cultivars: extraction methods, stability, anticancer properties and mechanisms.

The purpose of these studies was to investigate and compare the composition, stability, antioxidant and anticancer properties and mechanisms of anthocyanin-containing blackberry extracts (ACEs) from selected cultivars and using different extraction methods. ACEs were analyzed for total anthocyanin and phenolics content, polymeric color, and total antioxidant capacity (TAC). The influence of water content in the extraction system was evaluated. A 90-day stability study of the extract and a 48-h stability study of the extract in biologically relevant buffers were completed. The cytotoxic effects of ACEs on HT-29, MCF-7, and HL-60 cells were determined. H2O2 production in culture medium was measured and intracellular ROS levels were quantified. As compared to powder-derived ACEs, puree-derived ACEs contained similar amounts of anthocyanins, but greater levels of phenolics, increased TAC, significantly enhanced production of H2O2, and significantly enhanced cytotoxicity in all cell lines. Catalase could not protect cells from ACE-induced cell death. Cyanidin 3-glucoside exerted anticancer effect by acting synergistically or additively with other active components in the extracts. These data suggest that anthocyanins and non-anthocyanin phenolics in ACEs act synergistically or additively in producing anticancer effects. These studies also provide essential information for the development of fruit-derived ACEs as potential Botanical Drug Products.

Lux vs. wavelength in light treatment of Seasonal Affective Disorder.

OBJECTIVE: Published dosing guidelines for treatment of Seasonal Affective Disorder (SAD) refer to photopic lux, which is not appropriate for short-wavelength light. Short wavelengths are most potent for many non-visual responses to light. If SAD therapy were similarly mediated, standards utilizing lux risk overestimating necessary dose. We investigated antidepressant responses to light using two light-emitting diode (LED) sources, each emitting substantial short-wavelength light, but <2500 lux. METHOD: A randomized, double-blind trial investigated 3-week 45 min/day out-patient treatment with blue-appearing (goLITE) or blue-enriched white-appearing light in 18 moderately-depressed adults (12F, 49.1 +/- 9.5 years). Equivalent numbers of photons within the short-wavelength range were emitted, but the white source emitted twice as many photons overall and seven-fold more lux. RESULTS: Depression ratings (SIGH-ADS; http://www.cet.org) decrease averaged 82% (SD = 17%) from baseline (P < 0.0001) in both white- and blue-light groups. Both sources were well tolerated. CONCLUSION: Short-wavelength LED light sources may be effective in SAD treatment at fewer lux than traditional fluorescent sources.

Leptin is involved in the effects of cysteamine on egg laying of hens, characteristics of eggs, and posthatch growth of broiler offspring.

Cysteamine has been reported to modulate energy homeostasis and exert significant growth-promoting effects in broiler chickens. However, little is known concerning its effects on egg production of hens and the growth rate of their offspring. In the present study, 67-wk-old broiler breeders were allotted at random to control and cysteamine-supplemented (400 mg/kg) groups for 8 wk. The hatchlings were fed under the same condition until 6 wk of age. Cysteamine significantly increased the average laying rate by 2.24% (P < 0.01), decreased dramatically the percentage of the broken eggs by 40.55% (P < 0.01), and increased that of the abnormal eggs by 20.15% (P < 0.05). Cysteamine did not alter the egg weight, egg quality, fertility, or hatch-ability but significantly increased eggshell weight (P < 0.05) and decreased albumin weight (P < 0.05). Serum concentrations of total thyroxine (P < 0.01) and leptin (P < 0.01) were significantly lower in cysteamine-treated hens, whereas total triiodothyronine (T(3)), free T(3), and glucagon were not affected. Western blot analysis with leptin-specific antibody detected a band of approximately 15 to 16 kDa in egg yolk and albumin extracts as well as in liver homogenates of hens. Cysteamine did not affect the yolk content of T(3), thyroxine, estradiol, or glucagon, but significantly increased leptin content in liver of hens (P < 0.05), as well as in yolk (P < 0.05) and albumin (P < 0.05) of eggs. These changes were accompanied by a significant downregulation of leptin receptor mRNA expression (P < 0.05) in the yolk sac of d-12 embryos. Female offspring hatched from cysteamine-treated eggs demonstrated significantly lower body weight at hatching (P < 0.01) and 42 d of age (P < 0.01). The results indicate that cysteamine improves laying performance of hens and affects the early posthatch growth of broiler offspring, in a sex-specific fashion. The modified leptin secretion and egg deposition, together with altered yolk sac leptin receptor expression, may be involved in such an effect.

Effects of Chinese herbal polysaccharides on the immunity and growth performance of young broilers.

Two trials were conducted to study the effects of two Chinese herbal polysaccharides [achyranthan (ACH), a low-molecular-weight polysaccharide, and astragalan (APS), a high-molecular-weight polysaccaride] on the immunity and growth performance of young broilers. Trial 1 was a 28-d growth assay, in which 7-d-old broilers (n = 240) were randomly allotted to one of three dietary treatments, with eight replicate pens per treatment and ten chickens per pen. Dietary treatments included a control corn-soy-fishmeal (Treatment 1), a diet with 200 mg/kg APS (Treatment 2), and a diet with 200 mg/kg ACH (Treatment 3). Blood samples were collected by cardiac puncture on Days 7, 14, 21, and 28 for determination of serum parameters, and chickens were killed on Day 28 to measure immune organ indexes. Trial 2 was an in vitro trial to study the effects of different concentrations of polysaccharides on broiler splenocyte functions. In Trial 1, feeding either APS or ACH had no significant effects on growth performance of broilers relative to the control. However, compared to the control, feeding ACH significantly increased microhemagglutination inhibition (HI) antibody titers, bursa of Fabricius index, serum albumin, serum calcium, and nitric oxide (NO) concentrations at Day 28 (P < or = 0.05). In Trial 2, both polysaccharides showed significant immunostimulating effects. They increased NO and interleukin-2 (IL-2) production of splenocytes and enhanced splenocyte proliferation in a dose-dependent manner (P < 0.05). Those results indicate that the immunostimulating effects of APS are not as pronounced as those of ACH. Achyranthan showed immunostimulating effects in both the growth assay and in vitro studies. Therefore, ACH may be a Chinese herbal polysaccharide that has the potential to be used as a feed additive to improve broilers' immunity.

Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of mammary carcinogenesis is potentiated by the pineal hormone melatonin.

Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with melatonin (Mlt) followed 24h later with physiological concentrations of all-trans retinoic acid (atRA) results in apoptosis. These studies were extended into trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model. Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the chow) and administering melatonin by subcutaneous injection in the late afternoon demonstrated that the combination of Mlt and 9cRA was able to significantly prevent tumor development, and that the combination was more efficacious that either Mlt or 9cRA alone. In this report, we conducted studies to determine if lower doses of 9cRA could be used in combination with Mlt while still maintaining anti-tumor activity and if the route of administration of 9cRA (bolus (gavage) v.s. chronic (chow) routes) affected its interaction with Mlt. The studies presented here demonstrate that significantly reduced doses of 9cRA can be used in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our studies demonstrate that 9cRA is equally effective when it is administered chronically (chow) or as a bolus (gavage). These data demonstrate that the combined use of Mlt and 9cRA produces additive or synergistic effects, which are more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a potentially useful clinical treatment regimen for breast cancer since it allows the use of lower doses of retinoic acid, thus, avoiding the toxic side effects associated with the use of high dose retinoids.

Taraxastane-type triterpenoids from Saussurea petrovii.

Two taraxastane triterpenoids, i.e. taraxast-20-ene-3beta,30-diol (1) and 20alpha,21alpha-epoxy-taraxastane-3beta,22alpha-diol (2), as well as four known triterpenes taraxast-20(30)ene-3beta,21alpha-diol (3), taraxast-20(30)-ene-3beta-ol (4), taraxast-20-ene-3beta-ol (5) and taraxastane-3beta,20alpha-diol (6) were isolated from the Chinese medicinal plant Saussurea petrovii. Their structures were elucidated by spectroscopic methods. These compounds, especially 1 and 2, exhibit significant antitumor and antibacterial activity.

A pilot study on anticancer activities of Chinese leek.

OBJECTIVES: To investigate the anticancer activities of Chinese leek (Allium tuberosum Rottler; [CL]). DESIGN: Fresh CL was extracted and reconstituted in phosphate-buffered saline. The in vitro antiproliferation activities of the extract were tested with two murine cancer cell lines and four human cancer cell lines. The in vivo anticancer effects were tested in C57BL mice with lung metastases of B16-F10 melanoma. The mice were inoculated with B16-F10 melanoma cells by intravenous (IV) injection on day 1. CL extract was given on days 6-8 by either IV injection or oral gavage. The lung metastases were examined on day 16. RESULTS: The extract inhibited the in vitro growth of all six cancer cell lines studied. The dose-response curves were sigmoidal with IC50 (50% inhibition concentrations) in the range of 2.5-13.0 mg of raw material per milliliter for the six cancer cell lines. At the CL concentration of 8-100 mg of raw material per milliliter, all the cells underwent apoptosis, and no live cells were left after being exposed to CL for 4-6 hours. Typical apoptosis-specific cell morphology changes were observed under a microscope. The induction of cancer cell apoptosis by CL extract was further verified by the DNA ladder assay. Treatment with a daily oral dose of the extract (equivalent to 2.5 or 12.5 mg of raw material per gram of body weight) reduced the B16-F10 melanoma lung metastatic colonies in mice by 40% (p < 0.03). IV injection of the extract (equivalent to 1.25 or 6.25 mg of raw material per gram of body weight) did not show any effect. CONCLUSIONS: CL extract inhibited cancer cell growth and induced apoptosis in vitro. Oral administration of CL extract significantly reduced lung metastases in the present animal model.