Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 21, Issue 7, 2021

This study summarized the benefits of oxytocin in the attenuation of coronavirus disease (COVID-19) pathogenesis. The recent outbreak of COVID-19 has become a pandemic with 7,323,761 infected patients and has created a health emergency worldwide. On the basis of the clinical study, COVID-19 shows homology with other coronavirus pathogenesis, i.e., inflammation, oxidative stress, and hyperactivation of the immune system, resulting in cytokine storm and causing acute lung infection (ALI), acute respiratory distress syndrome (ARDS), and kidney dysfunction. Oxytocin is a peptide of nine amino acids and a well-known anti-inflammatory, anti-oxidant, and immune-modulator, which is protective against ALI/ARDS, nephrotoxicity, sepsis, and ischemia- reperfusion medical condition. Oxytocin is a neuromodulator, effective for stress, anxiety, social behavior, and depression, which may be helpful for better outcomes in patients with COVID-19. Significant data show that oxytocin can be useful in the treatment of COVID-19 pathogenesis. A direct application of OT in COVID-19 is unclear; however, its use in an experimental model and humans has continuously demonstrated its safety, and its use in patients with COVID-19 is predicted to be highly beneficial.

Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients’ features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing trastuzumab (the most widely used anti-HER2 drug). In neoadjuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients. More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offer cancer patients a better quality of life.

Dietary habits strongly influence our health status, mostly in terms of maintenance of the inflammatory/anti-inflammatory homeostasis. High fat and high sugar diets account for the development of a low-grade inflammation, which is the pathogenic common denominator of various chronic diseases. Severe Acute Respiratory Syndrome Coronavirus (SARS)-CoV2 (COVID-19) infection affects all ages and especially frail elderly people and a nutritional intervention seems to be crucial in the course of this pandemic. The present review describes the properties of some vegetal products and their derivatives, such as Lupin sp., garlic, salvia and extra virgin olive oil (EVOO) that can be exploited for their beneficial effects, as preventive and/or nutritional treatment of coronavirus disease SARS-CoV2. Lupin, salvia, garlic and EVOO share overlapping properties, such as anti-oxidant, anti-inflammatory and anti-viral activities. Quite importantly, these products and their derivatives are able to recover the expression of angiotensin converting enzyme expression 2 on cell membrane, otherwise suppressed by COVID-19 binding and entry into cytoplasm. Dietary administration of the above nutraceuticals or their extracts may play a preventive or nutritional role in the course of SARS-CoV2 infection, even including the effects of the lockdown and the condition of inflamm-ageing.

Despite the evidence that plants do not possess sessile cells, they are able to mount a vigorous immune response against invaders or under stressful conditions. Plants are endowed with pattern recognition receptors (PPRs) which perceive damage-associated molecular patterns and microbe- associated molecular patterns or pathogen-associated molecular patterns (PAMPs), respectively. PPR activation leads to either the initiation of PAMP-triggered immunity (PTI) (early response) or the effector-triggered immunity (ETI). Both PTI and ETI contribute to plant systemic acquired resistance as an expression of immunological memory or trained immunity. PTI is initiated by activation of both receptor-like kinases and receptor-like proteins, while ETI depends on nucleotide- binding leucine-rich-repeat protein receptors for microbe recognition. Plant chloroplasts contribute to both PTI and ETI through the production of peptides, which act as hormones or phytocytokines. Salicylic acid, jasmonic acid and ethylene are the major compounds involved in plant defense. The interaction between plant receptors and/or their products and bacterial components will be discussed. Also, emphasis will be placed on plant microbiome for its contribution to plant immune response. Finally, the mutual interplay between insects and plants will also be illustrated. A better knowledge of plant immunity may pave the way for the exploitation of plant derivatives in the field of agriculture and medicine, as well.

Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in the haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. The participation of platelets in inflammatory processes will also be discussed in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

Hormonal contraceptives contain an Estrogen and/or a Progestin, which are the substrates of the CYP3A4 enzyme and the drugs inducing the CYP3A4 enzyme can decrease the plasma concentrations and thereby therapeutic efficacy of Hormonal contraceptives resulting in unintended pregnancy. Moreover, the hormonal contraceptives associated risk of thrombotic events are further exacerbated by the simultaneous administration of drugs like Tranexamic acid and tobacco smoke. Therefore, while prescribing hormonal contraception and other drugs to women, drug interactions should always be considered because there could be a possible contraceptive failure or other adverse drug effects. This article provides a summary of guidance to healthcare professionals such as prescribers and pharmacists on pharmacokinetic based interactions between hormonal contraception and other drugs.

Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases, including cardiovascular disease (CVD), inflammation, neurological diseases, cancer, and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation, as shown by the development of CVD, following the imbalance of its metabolites. This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. In silico literature searches were performed on PubMed and Scopus as main sources. Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI2), thromboxane (TXA), epoxyeicosatrienoic acids (EETs), and hydroxyeicosatetraenoic acids (HETEs). It is believed that by targeting Hcy in the AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for a dietician to manipulate diets to improve health.

Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of severity, from mild, self-limited infections to highly lethal forms as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Coronavirus Disease 2019 (COVID-19). Scanty data are reported for the involvement of endocrine glands in human coronaviruses, in particular SARS-CoV-2. In this review, we summarize endocrinological involvement in human coronaviruses, including data on animal coronaviruses. Avians, ferrets and bovine are affected by specific coronavirus syndromes, with variable involvement of endocrine glands. SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a target receptor, so ACE2 plays a central role in viral transmission and initial organ involvement. Autoptic studies on SARS patients revealed that thyroid, parathyroid, pituitary gland, endocrine pancreas and especially adrenals and testis could be impaired by different mechanisms (direct damage by SARS-CoV, inflammation, vascular derangement and autoimmune reactions) and few clinical studies have evidenced functional endocrine impairment. Only few data are available for COVID-19 and gonads and endocrine pancreas seem to be involved. International endocrinological societies have brought some recommendations for the COVID-19 pandemic, but further studies need to be performed, especially to detect long-term hormonal sequelae.

Background: Probiotics can improve immune function leading to the prevention and management of viral infections like SARS-CoV-2 infection (COVID-19 disease). Methods: We searched PubMed, EMBASE, Google Scholar, Science Direct, Scopus, and Web of Science up to May 2020 to identify interventional & observational studies documenting the effects of probiotics on incidence, severity, duration, and other clinical manifestations of viral infections, especially SARS-CoV-2-induced. Results: From a total of 91 records, 24 studies were obtained and classified into three domains based on the efficacy of probiotics on 1) shortening the period and severity of infections (n=9), 2) incidence (n=6), and 3) other clinical complications that may be followed by viral disorders (n=9). Identified probiotics have positive effects on the mentioned domains. Conclusion: Based on the evidence, some probiotic strains may be useful in SARS-CoV-2 infection; randomized trials are needed to show the facts.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that has turned out to be a pandemic all over the world. In China, some traditional Chinese herbal formulas have enjoyed a high reputation in T2DM treatment for centuries. Methods: In this study, ShenQi compound (SQC) is proposed, a formula that has been performed on T2DM clinical therapeutics in China for many years. The efficacy of SQC in a diabetic rat model by measuring food and water intake and examining islet microcirculatory index involves islets microvessel quantity and density, islets size, pancreatic microvascular wall thickness is evaluated. Meanwhile, gene microarray experiments were performed to explore the molecular mechanism of SQC treatment. In addition, a western medicine, metformin, was employed as a comparison. Results: The results indicated that SQC could effectively improve polydipsia, polyphagia and weight loss caused by diabetes as well as pancreatic tissue damage and vascular injury for T2DM. Meanwhile, the gene microarray experiments indicated that SQC may improve the T2DM by affecting the biological functions related to detection of chemical stimulus involved in sensory perception of smell, G-protein coupled receptor signaling pathway, cytoplasmic translation. In addition, SQC presented curative effect by the regulated function associated with translation, while metformin presented curative effect by the regulated function associated coagulation. Conclusion: SQC is an effective therapeutic drug on T2DM, and presents curative effect by regulated function associated with translation.

Objective: The aim of this study was to examine the effect of berberine on diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms. Methods: Rat models of type 2 diabetes mellitus (T2DM) were established and were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated. Results: Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation response of thoracic aorta to SNP in the model and berberine groups decreased after the IbTX treatment. Conclusion: Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting of the inflammation and intervening of the calcium- activated potassium (BKCa).

Background: Cardiovascular-diseases (CVD) are caused by different metabolic-anomalies related to hypertension/sedentary lifestyle/drug-addiction/dyslipidemia and diabetes. The scanty report suggests that metabolic-rate regulating thyroid hormones are linked to CVD. Methods: A total of 59 individuals (male, >45 yrs) were involved in this study. Blood-samples from diagnosed cardiac-patients troponin (N=13, trop-T+), individuals with high-risk (N=15) (high glucose/cholesterol/triglycerides), and with age-matched controls (N=31) were tested for the evaluation of lipid-profiles/thyroid-hormones; Triiodothyronine, Thyroxine, and thyroid-stimulating hormone (T3/T4/TSH), blood-glucose/oxidative-stress indicators like malondialdehyde(MDA)/ non-protein-soluble-thiol(NPSH) and metabolic inflammatory-marker; human C-reactive protein hsCRP by biochemical-methods/ELISA. Results: Correlation-data suggest that in normal conditions, there is no significant correlation between thyroid-hormones and other parameters. On the contrary, blood-glucose/triglyceride/uric-acid/ proteins are correlated in cardiac and high-risk patients, suggesting hypermetabolic conversion of nutrients by biochemical connectors like the TCA cycle and gluconeogenesis pathways. Further, the hypermetabolic-state is favored by the rise in the thyroid hormones level. In the high-glucose group, there is a significant correlation between metabolic-parameter and oxidative-stress indices like uric-acid/NPSH/MDA. T3 and T4 have also been linked to the serum-protein. But in the trop t+ group, all thyroid hormones have been significantly associated with blood cholesterol/triglyceride and glucose, suggesting the increasing involvement of thyroid-hormone in risk-factors and disease groups. The hsCRP level was ~100% and ~5-fold higher in high cholesterol and trop t+ groups, respectively. T3 was also ~70%, ~4.5-fold, and ~3.5-fold higher in high-glucose/high-cholesterol/ trop-t+ groups, respectively. This suggests that T3/TSH is linked to pathogenesis and severity. Conclusion: Dyslipidemia, oxidant-stress in association with T3, augments cardiac-pathogenesis.

Aims The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in the Moroccon population. Methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats received MPAE (180 and 300 mg/kg) orally for six hours for acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. In the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca²⁺ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to the dilation of blood vessels via blockage of Ca²⁺ channels.

Background and Aims: This study aimed to assess the changes in platelet counts of patients with liver cirrhosis due to chronic HCV, who achieved sustained virological response (SVR) after taking direct acting antivirals (DAAs) in a large cohort study in Egypt. Methods: This multicenter observational retrospective study was carried out on 2500 chronic hepatitis C virus (HCV) infected patients who achieved (SVR) after treatment with direct acting antiviral drugs (DAA). HCV infection was confirmed by positive PCR for HCV RNA infection. SVR was defined as a negative PCR test for HCV-RNA 12 weeks after completion of DAA therapy. Platelets count was measured before therapy, during therapy, at the end of treatment, and 12 weeks after the end of the treatment. Results: There were 2186 patients enrolled in the study; 1866 (85.4%) were treatment naïve. There were 1006 (46%) males and 1180 (54%) females. Mean age was 50.82± 11.66 years, 2142 (98%.0) patients achieved SVR, 2118 (96.9%) patients had Child -Pugh class A cirrhosis, and 68 (3.1%) had Child -Pugh class B liver cirrhosis. A significant increase in the platelets count was detected at the end of treatment in comparison to the pretreatment levels (P<0.001), and after achieving SVR (P <0.001) when compared to the pretreatment values. Conclusion: Improvement of platelets count occurs after HCV therapy with DAAS in patients with liver cirrhosis. These results suggested that HCV eradication may have a role in the improvement of platelet count.

Background: Multiple sclerosis (MS), a disease of the central nervous system (CNS), is associated with damage to the myelin sheath of neurons. It is demonstrated that vitamin D deficiency plays an important role in the development of the disease. Binding of vitamin D to its specific nuclear receptors is a way to exert its function. Objective: Possible correlation between the vitamin D receptor (VDR) gene and MS was evaluated in the Azeri population of Iran. Methods: Different genotypes of the Bsml site were determined by using the PCR-RFLP method in 148 MS patients and 220 non-relative healthy controls. Results: In MS patients, genotype bb was significantly higher than the healthy controls (p<0.05). Additionally, most subjects of the MS group had been insufficiently exposed to sunlight before the age of 15 (p<0.001). Our findings indicated that the red meat intake in MS patients was significantly higher than the healthy controls (p<0.001). In addition, the healthy controls had appropriate dieting behaviors in comparison to MS patients (excessive intake of some foods) (p=0.0001). Conclusion: In conclusion, genotype BB and sufficient exposure to sunlight before the age of 15 were the protective factors against MS. Although, excessive consumption of red meat and inappropriate dieting behaviors were predisposing factors to MS disease.

Background: Osteosarcoma (OS) is the basic bone neoplasm with lower survival and poor prognosis. It is distinguished by its offensive nature and metastatic potential. The fundamental death source in OS patients is lung metastasis. In addition, the proliferation and cell migration are thus essential for cancer progression, especially for intrusion and transformation. Several studies have illustrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D) has a critical role in the growth and differentiation of bone. However, knowledge of the outcome of 1,25(OH)2D on the progression and incursion of osteosarcoma cells is minimal. Objective: The present study aimed to analyze the effect of different concentrations of 1,25(OH)2D on the multiplication, progression, and intrusion of OS cells and verify the effective doses of 1,25(OH)2D that can decrease the intensity of the disease and improving the prognosis in OS patients. Methods: Saos-2 cells were treated with 1,25(OH)2D (0, 50, 100, and 200 nM) for 48, 72, and 96 hours. Proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and Scratch test, respectively. The levels of c-Myc and FOXO1 proteins were determined by Western blotting. Results: The proliferation, invasiveness, and migration of Saos-2 cells that were treated with 1,25(OH)2D were significantly decreased compared with untreated cells. Although 1,25(OH)2D notably decreased c-Myc protein levels (after 48 and 72 hours), FOXO1 protein levels have been significantly increased after 48 and 72 hours. 1,25(OH)2D and the vitamin D receptor (VDR) suppress c-Myc function through regulating the c-Myc/MXD1 network and thus, providing a molecular basis of 1,25(OH)2D related to the cancer-preventive actions. Conclusion: Based on the present results, 1,25(OH)2D by targeting c-Myc and FOXO1 expression displays anti-invasive, anti-migration and anti-proliferative effects on OS cells in vitro. Our findings suggest that effective doses of the 1,25(OH)2D may reduce the aggressive potential of the OS cell line. However, further investigation and clinical trials are needed.

Aim: We evaluated cardiovascular (CV) risk stratification for nonfunctioning adrenal incidentalomas (NFAIs) via the coronary-artery-calcium (CAC) score. Materials and Methods: The participants were patients with NFAI (n = 55). They were compared to patients with chest pain, a low-intermediate Framingham-risk score, and a non-diagnostic treadmill- exercise test, which served as the control group (n = 49). Subsequently, the NFAI group was subdivided according to a CAC score of <100 Agatston units – mild coronary-artery calcification (n = 40) – and ≥100 Agatston units – moderate-to-severe calcification (n = 15). Results: Similar rates of traditional risk factors were observed between the NFAI and control groups, and lower low-density lipoprotein cholesterol rates were observed in the NFAI group. The CAC score was significantly higher for the NFAI group than the control group. Glucose, potassium, adrenocorticotropic-hormone, and basal-cortisol levels were higher in those with a CAC score of ≥100. High-density-lipoprotein cholesterol estimated glomerular filtration rate and ejection fraction (EF) were higher in those with a CAC score of <100. Adenoma size and location were similar between the groups. Age, EF, and glucose were the most significant variables related to CAC score in patients with NFAI, at ≥100 Agatston units. Discussion: Patients with a low-intermediate CV risk profile and NFAI have a higher risk of atherosclerosis when compared to patients with a low-intermediate CV risk profile, but no NFAI. Conclusion: In patients with NFAI, CAC score evaluation may be used to predict increased atherosclerosis, especially in patients of an older age with higher glucose and decreased EF.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain. It is more common in women than in men, and sex hormones may play a role in this predominance. Therefore, this research investigated the clinical findings among Turkish females and whether Estrogen-α (ESR1) gene variants are associated with FMS. Methods: A total of 219 individuals were enrolled in this study. ESR1 variants (PvuII/XbaI) were genotyped using PCR-RFLP methods. The results of the analyses were evaluated for statistical significance. Results: There was a significant association between the ESR1 PvuII and FMS risk among Turkish women. The ESR1 PvuII CC genotype and C allele were higher in the patients than those in the controls (p=0.021, p=0.007, respectively). A more statistically significant association was observed between the patients and the controls in terms of TT genotype vs. TC+CC genotypes (p=0.022). Also, there was a statistically significant association between the patients and the controls in terms of TT+TC genotype vs. CC genotypes (p =0.028). There was no significant association between patients and the control group concerning the genotype distribution and allele frequencies of ESR1 XbaI (p>0.05). Headache was seen more frequently in the XbaI GA genotype (p=0.025), while XbaI AA genotype was associated with dysmenorrhea in patients with FMS (p=0.041). Conclusion: Our results indicate that ESR1 PvuII/XbaI variants are possibly effective in the development of FMS and some clinical features.

Background: Metabolic syndrome has been associated with an increased risk of cardiovascular disease, diabetes mellitus, and neurodegenerative disorders. Known side-effects of currently- available drugs necessitate the search for possibly better treatment options. Objective: This study examined the effects of dietary lepidium meyenii (MACA) supplementation on neurobehaviour, metabolic profile, levels of inflammatory markers, and oxidative stress parameters in a mouse model of metabolic syndrome. Methods: Mice were randomly assigned into 8 groups of ten animals each. Groups consist of standard diet (SD) control, high fat/high sugar (HFHS) control and three groups each of lepidium meyenii incorporated into either SD or HFHS diet at 0.1, 0.2 and 0.4%. Mice were fed for seven weeks, and body weight was measured weekly. Open-field behaviors and radial-arm/Y-maze spatial memory were scored at the end of the study. Twenty-four hours after the last behavioral test, fasting blood glucose levels were estimated. Animals were then euthanized, and blood was drawn for estimation of serum lipid profile. Whole brains were excised, weighed and homogenized to estimate the levels of lipid peroxidation, inflammatory markers, antioxidant status, and acetylcholinesterase activity. Results: MACA-supplemented diet was associated with a decrease in body weight gain, an increase in food intake (at lower concentrations), suppression of grooming behavior, and decrease in acetylcholinesterase activity. MACA-supplement also reversed HFHS-induced memory impairment, anxiety, hyperglycaemia, lipid derangement, oxidative stress, and derangement of inflammatory markers. Conclusion: Dietary supplementation with MACA shows beneficial effects in mitigating the effects of metabolic syndrome on the brain in mice.

Background: Benfotiamine is a synthetic liposoluble derivative of vitamin B1 that has been shown to have anti-inflammatory properties. Objective: To study the effects of benfotiamine on dendritic cells. Methods: Dendritic cells were obtained from murine bone marrow precursor cells in the presence of GM-CSF. Benfotiamine was applied to the cell culture during the process of bone marrow cell differentiation into dendritic cells. Dendritic cells were stimulated with lipopolysaccharide (LPS) and expression of MHC class II molecules and CD86 was determined by flow cytometry, while levels of tumor necrosis factor (TNF) and interleukin (IL)-1β in cell culture supernatants were measured by ELISA. F-Actin, NF-ΚB and Nrf2 were visualized by immunofluorescent staining and microscopy. Results: Benfotiamine potently reduced LPS-induced expression of MHC class II molecules and CD86, in addition to suppressing the release of pro-inflammatory cytokines TNF and IL-1β. It also prevented LPS-imposed morphological changes of dendritic cells, i.e. enlargement and intensified protrusions. The effects were paralleled with the reduction of NF-ΚB translocation to the nucleus, but not of Nrf2 activation inhibition. Conclusion: Having in mind the importance of dendritic cells for the configuration of the immune response, our results imply that benfotiamine has the ability to regulate the immune response through inhibition of inflammatory properties of dendritic cells.