Andrzej Przemysław Herman

Caffeine’s Mechanisms of Action and Its Cosmetic Use

Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-α-reductase activity.

Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review

In this paper, we focused on essential oils and their constituents as skin penetration enhancers for transdermal drug delivery, mechanism of their action as well as their possible toxicity.

Central injection of exogenous IL-1β in the control activities of hypothalamic-pituitary-gonadal axis in anestrous ewes.

This study was performed to determine the effect of intracerebroventricular (icv) injection of interleukin (IL)-1β on the gene expression, translation and release of gonadotropin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) gene expression in the hypothalamus of anestrous ewes. In the anterior pituitary gland (AP), the expression of genes encoding: GnRHR, β subunits of luteinizing hormone (LH) and folliculotropic hormone (FSH) was determined as well as the effect of IL-1β on pituitary gonadotropins release. The relative mRNA level was determined by real-time PCR, GnRH concentration in the cerebrospinal fluid (CSF) was assayed by ELISA and the plasma concentration of LH and FSH were determined by radioimmunoassay. Our results showed that icv injection of IL-1β (10 or 50 μg/animal) decreased the GnRH mRNA level in the pre-optic area (POA) (35% and 40% respectively; p ≤ 0.01) and median eminence (ME) (75% and 70% respectively; p ≤ 0.01) and GnRHR gene expression in ME (55% and 50% respectively; p ≤ 0.01). A significant decrease in GnRHR mRNA level in the AP in the group treated with the 50 μg (60%; p ≤ 0.01) but not with the 10 μg dose was observed. The centrally administrated IL-1β lowered also GnRH concentration in the CSF (60%; p ≤ 0.01) and reduced the intensity of GnRH translation in the POA (p ≤ 0.01). It was not found any effect of icv IL-1β injection upon the release of LH and FSH. However, the central injection of IL-1β strongly decreased the LHβ mRNA level (41% and 50%; p ≤ 0.01; respectively) and FSHβ mRNA in the case of the 50 μg dose (49%; p ≤ 0.01) in the pituitary of anestrous ewes. These results demonstrate that the central IL-1β is an important modulator of the GnRH biosynthesis and release during immune/inflammatory challenge.

The role of immunological system in the regulation of gonadoliberin and gonadotropin secretion

This article reviews data concerning the interactions between immune and neuroendocrine systems in the regulation of reproduction processes at the hypothalamic and pituitary level during immunological stress. Hypothalamus seems to play the most important role in the inhibitory action of immune challenge on the gonadoliberin (GnRH) and gonadotropin secretion as well in the inhibition of the reproductive functions. The administration of endotoxin as a model of immunological stress could alter circulating concentrations of luteinizing hormone (LH) via actions at the hypothalamus through altered GnRH secretion, or at the level of the pituitary via inhibition of LH production and release in response to GnRH. At the central level, interleukin (IL)-1beta seems to play the most important role in the suppression of GnRH secretion during immune challenge. The inhibitory action of this cytokine on GnRH may involve different neural mechanisms: direct action on the GnRH neurons through the IL-1 receptors or indirect action involving other mediators such as opioids, catecholamines, gamma-aminobutyric acid, prostaglandins or nitric oxide.

Linalool Affects the Antimicrobial Efficacy of Essential Oils

Abstract The high concentrations of essential oils are generally required to receive microbial purity of the products (cosmetics, medicine). On the other hand, their application due to the high concentration of essential oils may be limited by changes in organoleptic and textural quality of the products, as well as they cause irritation and allergies in users. Addition of linalool to essential oil may significantly enhance its antimicrobial effectiveness and reduce their concentrations in products, taking advantage of their synergistic and additive effects. The aim of the study was to compare antimicrobial activity of essential oil alone and in combination with linalool. The antimicrobial activity of the essential oil of Thymusvulgaris, Juniperus communis, Pelargonium graveolens, Citrus bergamia, Citrus grandis, Lavandula angustifolia, Cinnamomum zeylanicum, Melaleuca alternifolia, Syzygium aromaticum, linalool and their combination was investigated against bacteria and fungi using the disc diffusion method. The addition of linalool to S. aromaticum oil in a synergistic manner enhanced its antimicrobial efficacy against P. aeruginosa and A. brasiliensis. Moreover, the additive interaction between this oil and linalool was observed against S. aureus, E. coli and C. albicans. It was also found that linalool in an additive manner increased the antimicrobial effectiveness of T. vulgaris oil against P. aeruginosa. The antimicrobial properties of mixture of essential oils with their active constituents may be used for creating new strategies to maintain microbiological purity of products.

LPS-induced inflammation potentiates the IL-1β-mediated reduction of LH secretion from the anterior pituitary explants.

Acting at the level of the brain, interleukin- (IL-)1β is considered to be one of the most potent downregulators of reproduction processes during immune/inflammatory challenge. IL-1β suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the luteinizing hormone (LH) release from the anterior pituitary (AP). However, the presence of IL-1β receptors in the AP suggests the possible direct action of this cytokine on LH secretion. The study was designed to determine the effect of IL-1β on the LH secretion from the AP explants collected from saline and LPS-treated ewes in the follicular phase. It was found that IL-1β suppressed (P ≤ 0.01) GnRH-stimulated LH release and LHβ gene expression in AP explants in both groups. However, IL-1β action was more potent in the explants collected from LPS-treated animals. Pituitaries from LPS-treated animals were characterized by increased (P ≤ 0.01) IL-1 type I receptor and decreased (P ≤ 0.01) GnRH receptor gene expression level compared to the saline-treated group. IL-1β also affected the GnRH-R gene expression in explants collected from LPS-treated animals. Our results show that direct action of IL-1β on the pituitary gonadotropes could be one of the reasons of the reproductive processes disorders accompanying an inflammatory state.

The Possible Involvement of Salsolinol and Hypothalamic Prolactin in the Central Regulatory Processes in Ewes During Lactation

Salsolinol, a dopamine-related compound and prolactin-producing cells were found in the ovine hypothalamus. This study was designed to test the hypothesis that salsolinol, acting from the CNS level, is able to stimulate pituitary prolactin release as well as prolactin mRNA expression in the anterior pituitary cells (AP) and in the mediobasal hypothalamus (MBH) in lactating ewes. The intracerebroventricular infusions of salsolinol in two doses, total of 50 ng or 5 μg, were performed in a series of five 10-min infusions at 20-min intervals. All infusions were made from 12:30 to 15:00 and the pre-infusion period was from 10:00 to 12.30 h. The prolactin concentration in plasma samples, collected every 10 min, was determined by radioimmunoassay; prolactin mRNA expression in AP and MBH tissues was determined by real-time PCR. The obtained results showed that salsolinol infused at the higher dose significantly (p < 0.001) increased plasma prolactin concentration in lactating ewes, when compared with the concentration noted before the infusion and with that in lactating controls. In lactating ewes, the relative levels of prolactin mRNA expression in the AP and MBH were up to twofold and fivefold higher respectively than in non-lactating ewes (p < 0.05). In our experimental design, salsolinol did not significantly affect the ongoing process of prolactin gene expression in these tissues. We conclude that in ewes, salsolinol may be involved, at least, in the process of stimulation of prolactin release during lactation and that hypothalamic prolactin plays an important role in the central mechanisms of adaptation to lactation.

Expression of interleukin (IL)-1β and IL-1 receptors genes in the hypothalamus of anoestrous ewes after lipopolysaccharide treatment.

This study was designed to determine the effect of intravenous lipopolysaccharide (LPS) administration on the secretion of interleukin (IL)-1β and IL-1 receptors (IL-1Rs) gene expression in the hypothalamus of anoestrous ewes. Gene expression of IL-1β and its receptors was assayed by the real-time polymerase chain reaction. The expression of IL-1β in the hypothalamus was detected using Western blot. Our results showed that IL-1β mRNA is transcribed in the ovine hypothalamus. Lipopolysaccharide increased (p ≤ 0.01) the IL-1β gene expression in the pre-optic area 2.4-fold, the anterior hypothalamus (AHA) 3.4-fold, the medial basal hypothalamus 3.7-fold and the medial eminence 3.9-fold. The pro-form and mature form of IL-1β protein were found in the hypothalamus after endotoxin injection. In general, the endotoxin also increased more than two times (p ≤ 0.01) the expression of IL-1 receptor type I (IL-1R1) and type II (IL-1R2) genes in the hypothalamus, except the AHA, where the number of IL-1R2 mRNA was extremely low and not sufficient to the quantitative analysis. These results demonstrate that the peripheral immune/inflammatory challenge increases the IL-1β expression in the hypothalamus. This endogenous IL-1β seems to be involved in the modulation of processes which are regulated at the hypothalamic level. One of these processes could be a reproduction.

Peripheral Injection of SB203580 Inhibits the Inflammatory-Dependent Synthesis of Proinflammatory Cytokines in the Hypothalamus

The study was designed to determine the effects of peripheral injection of SB203580 on the synthesis of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor (TNF) α in the hypothalamus of ewes during prolonged inflammation. Inflammation was induced by the administration of lipopolysaccharide (LPS) (400 ng/kg) over 7 days. SB203580 is a selective ATP-competitive inhibitor of the p38 mitogen-activated protein kinase (MAPK), which is involved in the regulation of proinflammatory cytokines IL-1β, IL-6 and TNFα synthesis. Intravenous injection of SB203580 successfully inhibited (P < 0.01) synthesis of IL-1β and reduced (P < 0.01) the production of IL-6 in the hypothalamus. The p38 MAPK inhibitor decreased (P < 0.01) gene expression of TNFα but its effect was not observed at the level of TNFα protein synthesis. SB203580 also reduced (P < 0.01) LPS-stimulated IL-1 receptor type 1 gene expression. The conclusion that inhibition of p38 MAPK blocks LPS-induced proinflammatory cytokine synthesis seems to initiate new perspectives in the treatment of chronic inflammatory diseases also within the central nervous system. However, potential proinflammatory effects of SB203580 treatment suggest that all therapies using p38 MAPK inhibitors should be introduced very carefully with analysis of all expected and unexpected consequences of treatment.

The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes

This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from -2 to -0.5h before and +1 to +3h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9±9.5 to 99.3±15.1μmol/min/ml. Endotoxin suppressed LH (5.4±0.6ng/ml) and GnRH (4.6±0.4pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8±0.8ng/ml) to the control value (7.8±0.7ng/ml) and stimulated GnRH release (7.6±0.8pg/ml) compared to the control (5.9±0.4pg/ml). Immune stress decreased expression of the GnRH gene and its receptor (GnRH-R) in the median eminence as well as LHβ and GnRH-R in the pituitary. In the case of the GnRH and LHβ genes, the suppressive effect of inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin release (71.1±14.7 and 217.1±8.0ng/ml) compared to the control group (9.0±5.4 and 21.3±3.5ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1±13.1 and 169.7±29.5ng/ml). The present study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE inhibitor. This action of the AChE inhibitor could result from the suppression of pro-inflammatory cytokine release and the attenuation of the stress response. However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be considered.