Brain-targeted lycopene-loaded microemulsion modulates neuroinflammation, oxidative stress, apoptosis and synaptic plasticity in ß-amyloid-induced Alzheimer's disease mice.

OBJECTIVES: ß-Amyloid protein (Aß) plays pivotal roles in pathogenesis of Alzheimer's disease (AD) and triggers various pathophysiological events. Lycopene is a promising neuroprotector with multiple bioactivities, while its bioavailability is limited. Lycopene-loaded microemulsion (LME) possessing superior bioavailability and brain-targeting efficiency was developed in our previous study. In this investigation, we aimed to comprehensively evaluate its neuroprotective effects and underlying mechanisms using intracerebroventricular (ICV) Aß1-42 injection mice. METHODS: Mice were assigned to the Sham, Aß, Aß + LME and Aß + lycopene dissolved in olive oil (LOO) groups. ICV Aß1-42 administration was performed, followed by oral gavage of brain-targeted LME or conventional LOO formulation for 3 weeks. Brain samples were harvested for immunohistochemistry, biochemical assays and western blotting analyses. RESULTS: Our findings verified Aß-induced neurotoxicity on neuroinflammation, oxidative stress, apoptosis, Aß metabolisms and synaptic plasticity. LME supplementation dramatically attenuated astrocytosis and microgliosis, decreased malondialdehyde production and rescued antioxidant capacities, normalized apoptotic parameters and alleviated neuronal loss, inhibited amyloidogenic processing and activated non-amyloidogenic pathway, together with upregulating synaptic protein expressions and restoring synaptic plasticity. Nevertheless, most of these phenomena were not observed for mice treated with LOO, implying that LME showed significantly higher therapeutic efficacy against Aß injury. DISCUSSION: In summary, brain-targeted LME could exert neuroprotective function via suppressing a series of cascades triggered by Aß aggregates, thus ameliorating Aß neurotoxicity and associated abnormalities. Given this, LME may serve as an attractive candidate for AD prevention and treatment, and superiority of brain-targeting delivery is highlighted.

The possible effect of lycopene in ameliorating experimentally induced ulcerative colitis in adult male albino rats (A histological, immunohistochemical, and ultrastructural study).

Ulcerative colitis (UC) is considered a long-term inflammatory disorder worldwide. Its pathogenesis is associated with reduced antioxidant capacity. Lycopene (LYC) is a powerful antioxidant with strong free radical scavenging property. The present work has done to assess changes of colonic mucosa in induced UC and the possible ameliorative effects of LYC. Forty-five adult male albino rats were randomly divided into four groups: group I (control), group II was given 5 mg/kg/day (LYC) by oral gavage for 3 weeks. Group III (UC) was received single intra-rectal injection of acetic acid. Group IV (LYC+UC) received LYC in same dose and duration as before and acetic acid on 14th day of the experiment. UC group showed loss of surface epithelium with destructed crypts. Congested blood vessels with heavy cellular infiltration were observed. Significant decrease in goblet cell numbers and the mean area percentage of ZO-1 immunoexpression were noticed. Significant increase in the mean area percentage of collagen and the mean area percentage of COX-2 were also noticed. Ultrastructural changes were matched with light microscopic results that showed abnormal destructive columnar and goblet cells. Histological, immunohistochemical, and ultrastructural findings in group IV supported the ameliorative role of LYC against destructive changes induced by UC.

A phase II study of docetaxel plus lycopene in metastatic castrate resistant prostate cancer.

We carried out a phase II study to investigate the activity of docetaxel plus lycopene in advanced castrate resistant adenocarcinoma of the prostate. Patients were chemotherapy and biological therapy naive. Docetaxel 75 mg/m2 was given every 21 days with daily oral lycopene 30 mg. The primary endpoint was a ≥50% reduction in PSA. Secondary endpoints were median time to PSA progression, duration of response and overall survival. Thirteen patients were initiated on protocol therapy. Median age was 77 (range 55-90). Twelve patients (92%) had bone metastases. Four patients (30%) had both bone and visceral metastases. PSA response was seen in 10 patients (76.9% [95% confidence interval (CI), 46.2-94.9%]). Two patients had stable disease (SD), yielding a disease control rate of 92%. Median time to PSA progression was 8 months [95% CI, 3.5-8.7]. Median duration of response (DOR) was 7.3 months [95% CI, 4.8-13.2]. Median overall survival at 5 years was 35.1 months [95% CI 25.7-57.7]. No new safety signals were noted. No patients experienced grade 3 or above anemia. One patient (7%) experienced febrile neutropenia. A PSA response rate of 76.9% and median survival of 35.1 months compares favorably to the 45% PSA response rate and 17.4 months median survival reported for the TAX 237 trialists. While our study was limited due to small sample size, our results suggest that the combination of docetaxel and lycopene merits further study.

Potential inhibitory effect of lycopene on prostate cancer.

Studying prostate cancer is important due to its high annual incidences and mortality rates in the world. Although prostate cancer mortality rates are reduced using new therapy, complicated routes and side effects of these current drugs require a daily available treatment for prevention. Lycopene is a natural, prominent, and effective product which has a high value in diet. The anti-cancer effect, non-toxicity, safety and preventive or therapeutic roles of lycopene have been investigated in several studies. In the current review, we have collected information about the anti-cancer, anti-progressive and apoptotic effects of lycopene on prostate cancer. This article is a summary of the most important original and review articles on lycopene and its anticancer effects that are systematically categorized and presents information about the molecular structure, different sources, biological functions, and its in-vivo and in-vitro effects of lycopene on variety of cancerous and normal cells. The clinical studies provide a clear image for continuous use of this adjunctive dietary for different type of cancers, especially prostate cancer in men. In addition, this article discusses the various molecular pathways activated by lycopene that eventually prevent or suppress cancer. Lycopene has been found to effectively suppress the progression and proliferation, arrest in-cell cycle, and induce apoptosis of prostate cancer cells in both in-vivo and in-vitro conditions. Additionally, lycopene showed that it could modulate the signaling pathways and their protein for the treatment or prevention of prostate cancer.

PEGylated Nanoliposomes Potentiated Oral Combination Therapy for Effective Cancer Treatment.

The conventional treatment regimen for cancer with a single chemotherapeutic agent is far behind the clinical expectations due to the complexity of cancer biology and is also associated with poor Quality of Life (QOL) due to off-site toxicity and multidrug resistance. In recent years, nanopotentiated combination therapy has shown significant improvement in cancer treatment via a synergistic approach. However, being synthetic in nature, nanocarriers have been associated with the activation of the Complement (C) activation system resulting in serious hypersensitivity reactions known as CActivation Related Pseudoallergy (CARPA) effect once given via intravenous injection. On the other hand, nanopotentiated oral drug delivery offers several advantages for the effective and safe delivery of the drug to the target site. This hypothesis aims to put forward wherein Exemestane (chemotherapeutic agent) and lycopene (herbal bioactive) co-laden into PEGylated liposomes and delivered to the breast cancer via the oral route. PEGylation of the liposomes would prevent both molecules from the harsh microenvironment of the Gastrointestinal Tract (GIT) and would eventually promote their intestinal absorption via the lymphatic pathway to the systemic circulation. Lycopene being a potent antioxidant and anti-cancer herbal bioactive would promote the therapeutic efficacy of the Exemestane via a synergistic approach. This nanopotentiated oral combination therapy would pave the path for the safe and effective treatment of cancer.

Enhanced antitumor efficacy and attenuated cardiotoxicity of doxorubicin in combination with lycopene liposomes.

The aim of this study was to evaluate whether lycopene-loaded liposomes (L-LYC) could interfere with the antitumor efficacy and cardiotoxicity of doxorubicin (DOX). L-LYC were prepared by a thin-film hydration method to overcome the instability, insolubility, and low bioavailability of lycopene. The mean diameter and morphology of the liposomes were determined by dynamic light scattering and transmission electron microscopy, respectively, and then, in vitro cytotoxicity and in vivo antitumor activity were determined to evaluate the effects of L-LYC and their combination with DOX. Finally, we evaluated whether L-LYC could decrease the DOX-induced cardiotoxicity in vivo. The results showed that the particle size of L-LYC appeared uniform, and the average diameter was approximately 160.4 nm. Compared with DOX treatment alone, the combination of L-LYC and DOX showed significantly increased cytotoxicity in vitro and decreased the tumor size in B16 melanoma-bearing mice in vivo. Furthermore, the DOX-induced cardiotoxicity was clearly relieved in combination with L-LYC. The overall findings indicated that L-LYC have a great potential for improving the therapeutic efficacy and attenuating the cardiotoxicity of the chemotherapy drug DOX.

Ginkgo biloba and Lycopene are Effective on Cisplatin Induced Ototoxicity?

OBJECTIVE: The purpose of this study was to examine the anti-ototoxic impact of Ginkgo biloba extract and lycopene on the model of cisplatin-induced ototoxicity in rats. MATERIALS AND METHODS: Thirty-two Wistar albino rats were examined with the distortion product otoacoustic emission (DPOAE) test (MADSEN Capella2 ; GN Otometrics, ICS Medical, Chicago USA), and they were randomly divided into four groups. Group 1 (n=8) was defined as the healthy control group. Cisplatin was given intraperitoneally as single dose of 12 mg/kg to group 2 (n=8), group 3 (n=8), and group 4 (n=8). Group 2 was determined as ototoxic control group. G. biloba extract (100 mg/kg) was given to group 3, and 20 mg/kg lycopene was given to group 4 with orogastric feeding tube daily for 10 days. DPOAE test was repeated on day 10 on all the groups. Finally, histopathological examination was performed. The study has been lead in agreement with the principles by the Institutional Animal Care and Use Committee Review Board at Kocaeli University Medical Center (KOÜ HADYEK- 1/9-14). The animals were treated in accordance with protocols approved by this committee. RESULTS: When DPOAE tests were compared, there was no significant difference in the four groups before the application (p > 0.05). At the end of day 10, in groups 2 to 4, statistically significant changes were observed (p < 0.05). According to the cisplatin group, a significant increase in the DP-grams on G. biloba and lycopene groups was observed (p < 00.5). Corti organ and spiral ganglion neurons of groups 1, 3, and 4 were observed to have weak expression. Strong reactions were determined in organum spirale and some spiral ganglions of the cisplatin group. The striae vascularis damage on group 2 was found to be more significant more compared with groups 3 and 4. CONCLUSION: There is a protective effect of G. biloba and lycopene on cisplatin-dependent ototoxic rat model.