Vaccine adjuvant activity of emulsified oils from species of the Pinaceae family.

BACKGROUND: Next to aluminum salts, squalene nanoemulsions comprise the most widely employed class of adjuvants in approved vaccines. Despite their importance, the mechanisms of action of squalene nanoemulsions are not completely understood, nor are the structure/function requirements of the oil composition. PURPOSE: In this study, we build on previous work that compared the adjuvant properties of nanoemulsions made with different classes of oil structures to squalene nanoemulsion. Here, we introduce nanoemulsions made with polyprenols derived from species of the Pinaceae family as novel vaccine adjuvant compositions. In contrast with long-chain triglycerides that do not efficiently enhance an immune response, both polyprenols and squalene are comprised of multimeric isoprene units, which may represent an important structural property of oils in nanoemulsions with adjuvant properties. STUDY DESIGN: Oils derived from species of the Pinaceae family were formulated in nanoemulsions, with or without a synthetic Toll-like receptor 4 (TLR4) ligand, and characterized regarding physicochemical and biological activity properties in comparison to squalene nanoemulsions. METHODS: Oils were extracted from species of the Pinaceae family and used to prepare oil-in-water nanoemulsions by microfluidization. Emulsion droplet diameter stability was characterized by dynamic light scattering. Nanoemulsions were evaluated for in vitro biological activity using human whole blood, and in vivo biological activity in mouse, pig, and ferret models when combined with pandemic influenza vaccine antigens. RESULTS: Nanoemulsions comprised of Pinaceae-derived polyprenol oils demonstrated long-term physical stability, stimulated cytokine production from human cells in vitro, and promoted antigen-specific immune responses in various animal models, particularly when formulated with the TLR4 ligand glucopyranosyl lipid adjuvant (GLA). CONCLUSION: Pinaceae-derived nanoemulsions are compatible with inclusion of a synthetic TLR4 ligand and promote antigen-specific immune responses to pandemic influenza antigens in mouse, pig, and ferret models.

Antidepressant-Like Effect of Ropren® in ß-Amyloid-(25-35) Rat Model of Alzheimer's Disease with Altered Levels of Androgens.

This study elucidated the potential antidepressant-like effect of prolonged Ropren® administration (8.6 mg/kg, orally, once daily for 28 days) using a ß-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of ß-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5 mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren® was administered to the GDX rats and GDX rats treated with TP. Depression-like behavior was assessed in the forced swimming test, and the spontaneous locomotor activity was assessed using the open-field test. The corticosterone and testosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with Ropren® significantly decreased the immobility time of GDX rats with ß-amyloid (25-35) in the forced swimming test. Coadministration of Ropren® with TP exerted a markedly synergistic antidepressant-like effect in the GDX rats with ß-amyloid (25-35 on the same model of depression-like behavior testing. Ropren® administered alone or together with TP significantly enhanced crossing, frequency of rearing, and grooming of the GDX rats with ß-amyloid (25-35) in the open-field test. Moreover, Ropren® administered alone or together with TP significantly decreased the elevated corticosterone levels in the blood serum of GDX rats with ß-amyloid (25-35) following the forced swimming test. These results indicate that Ropren® has a marked antidepressant-like effect in the experimental model of Alzheimer's disease in male rats with altered levels of androgens.

Conifer Green Needle Complex in Patients with Precancerous Gastric Lesions: An Observational Pilot Study.

Objectives. Helicobacter pylori infection is common and can lead to precancerous gastric lesions. Standard antibiotic therapy has a failure rate of more than 25% from antibiotic resistance. The primary aim of this observational pilot study was to test the feasibility of a large-scale clinical trial of Conifer Green Needle Complex (CGNC) to treat precancerous gastric lesions. Secondary aims were to investigate H. pylori infection, stomach function, and histopathology of the gastric mucosa. Methods. A tablet form of CGNC (extracted from Pinus sylvestris and Picea abies (L) Karst) was prescribed to 26 patients with precancerous gastric lesions (two tablets, 100 mg CGNC/tablet, three times per day for six months). Another 24 patients received no treatment. Results. Compared with control patients, CGNC-treated patients showed total or partial regression (using the quantitative Rome III diagnostic criteria) of dyspeptic symptoms (92.3%, p < 0.0001), eradication of H. pylori infection (57.1%, p < 0.03), a reduction in endoscopic signs of gastritis (92.3%, p < 0.001), an increase of pepsinogen-pepsin in the gastric juice (57.7%, p < 0.05), and total regression or reduction in the degree of intestinal metaplasia (46.2%, p < 0.05) and lymphoplasmacytic infiltration (53.8%, p < 0.05). Conclusions. This study justifies a randomised-controlled trial with CGNC in patients with atrophic gastritis.

Ropren® treatment reverses anxiety-like behavior and monoamines levels in gonadectomized rat model of Alzheimer's disease.

Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimer's disease. New drug candidates for Alzheimer's disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimer's disease. Ropren® is one such candidate for the treatment of Alzheimer's disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren® administration (8.6mg/kg, orally, once daily, for 28 days) on the anxiety-like behavior and monoamines levels in the rat hippocampus using a ß-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. Ropren® was administered to the gonadectomized (GDX) rats and GDX rats treated with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, for 28 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark test (LDT), locomotor and grooming activities were assessed in the open field test (OFT). Ropren® alone or in combination with TP-induced anxiolytic effects as evidenced in the EPM and in the LDT and increased locomotor activity in the OFT. Additionally, it was observed that dopamine (DA) and serotonin (5-HT) levels increased while 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in the hippocampus decreased. Our results indicate that Ropren® has a marked anxiolytic-like action due to an increase in the monoamines levels in the experimental rat model of Alzheimer's disease with altered levels of androgens.

Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized ß-amyloid (25-35) rat model of Alzheimer's disease.

The present preclinical study was designed to examine the effects of prolonged Ropren® administration (8.6 mg/kg, orally, once daily, 28 days) in a ß-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of ß-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren® was administered to the GDX rats and GDX rats treated with TP. Memory performance was assessed using the passive avoidance and the Morris water maze tests and the spontaneous locomotor activity was assessed using the open field test. Treatment with Ropren® significantly improved and restored the cognitive ability of GDX rats with ß-amyloid (25-35)-induced amnesia in the passive avoidance test and Morris water maze. Co-administration of Ropren® with TP exerted a markedly synergistic memory-enhancing effect in the GDX rats with ß-amyloid (25-35)-induced amnesia on the same models of memory testing. Ropren® administered alone or together with TP significantly enhanced crossing, frequency of rearing and grooming of the GDX rats with ß-amyloid (25-35)-induced amnesia in the open field test. These results indicate that Ropren® has a marked memory-enhancing action in the experimental model of Alzheimer's disease in male rats with altered levels of androgens.

Ropren(®) is a polyprenol preparation from coniferous plants that ameliorates cognitive deficiency in a rat model of beta-amyloid peptide-(25-35)-induced amnesia.

This study assesses the efficacy of a fixed dose of Ropren(®) (a plant preparation isolated from the neutral fraction of an extract of spruce needles) on cognitive impairment in rats with ß-amyloid peptide-(25-35)-induced amnesia. Ropren(®) was administered at a dose of 8.6mg/kg for 28 days, per os, to rats with ß-amyloid peptide-(25-35)-induced amnesia. Cognitive performance was assessed using the passive avoidance paradigm and the Morris water maze and behavior was assessed using the open field test. After four weeks, Ropren(®) treatment significantly improved non-spatial and spatial learning in rats with ß-amyloid peptide-(25-35)-induced amnesia. The results of the present study suggest that Ropren(®), a novel plant preparation, ameliorates cognitive deficiencies in an animal model relevant to Alzheimer's disease.