Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

Cholecalciferol supplementation lowers leptin and TMAO but increases NO and VEGF-A levels in obese vitamin D deficient patients: Is it one of the potential cardioprotective mechanisms of vitamin D?

BACKGROUND: Vitamin D deficiency is one of the most common health issues in developed countries. Obese patients are most at risk of having serum 25-hydroxyvitamin D3 (25(OH)D3) levels that are too low due to the accumulation of vitamin D in adipose tissue. While the effects of a deficiency on the skeletal or immune system are known, the effects on the cardiovascular system are not yet clear. Our study investigates the effect of cholecalciferol supplementation in obese patients on selected biomarkers associated with cardiovascular diseases (CVDs). METHODS: The study enrolled 33 obese patients with insufficient 25(OH)D3 levels. For three months, the subjects supplemented with cholecalciferol at a dose of 2000 IU/day. Concentrations of nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), leptin, trimethylamine N-oxide (TMAO) and soluble suppression of tumorigenicity 2 (sST2) were measured in baseline samples using ELISA (BioTek EPOCH). 25(OH)D3 levels measured on Beckman Coulter DXI 800 by chemiluminescence method. RESULTS: After supplementation, 25(OH)D3 levels increased significantly. Normal levels were achieved in most patients. A statistically significant reduction leptin and TMAO levels was observed. At the same time, NO and VEGF-A levels increased statistically significantly. CONCLUSION: This study indicates that restoring normal 25(OH)D3 levels in obese people reduces the concentration of pro-inflammatory factors associated with cardiovascular diseases. Reducing inflammation and the potential impact on vascular reactivity leads to the conclusion that cholecalciferol supplementation in obese patients may benefit the cardiovascular system.

Vitamin D Supplementation and Its Impact on Different Types of Bone Fractures.

Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures that occur at specific ages and due to different circumstances, the influence of vitamin D on the frequency of a particular fracture may differ. Thus, the authors investigated the possible preventive effect of vitamin D on the risks of vertebral fractures, hip fractures, stress fractures and pediatric fractures. Additional aspects of vitamin D, especially on recuperation after injures and its impact on the severity of particular fractures, were also discussed. It was suggested that vitamin D supplementation may contribute to a reduction in hip fracture risk due to reduced bone turnover, decreased frequency of falls and improved muscle function. Furthermore, vitamin D appears to lower the risk of stress fractures in athletes and military recruits. Due to a nonunified protocol design, presented investigations show inconsistencies between vitamin D supplementation and a decreased risk of vertebral fractures. However, a vitamin D preventive effect on pediatric fractures seems to be implausible.

Beneficial Effects of Ursolic Acid and Its Derivatives-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.

Ursolic acid (UA) is a natural pentacyclic triterpenoid found in a number of plants such as apples, thyme, oregano, hawthorn and others. Several in vitro and in vivo studies have presented its anti-inflammatory and anti-apoptotic properties. The inhibition of NF-κB-mediated inflammatory pathways and the increased scavenging of reactive oxygen species (ROS) in numerous ways seem to be the most beneficial effects of UA. In mice and rats, administration of UA appears to slow down the development of cardiovascular diseases (CVDs), especially atherosclerosis and cardiac fibrosis. Upregulation of endothelial-type nitric oxide synthase (eNOS) and cystathionine-λ-lyase (CSE) by UA may suggest its vasorelaxant property. Inhibition of metalloproteinases activity by UA may contribute to better outcomes in aneurysms management. UA influence on lipid and glucose metabolism remains inconsistent, and additional studies are essential to verify its efficacy. Furthermore, UA derivatives appear to have a beneficial impact on the cardiovascular system. This review aims to summarize recent findings on beneficial effects of UA that may make it a promising candidate for clinical trials for the management of CVDs.

Impact of Vitamin D Supplementation on Inflammatory Markers' Levels in Obese Patients.

In view of research suggesting a possible beneficial impact of vitamin D on systemic inflammatory response, the authors decided to investigate an influence of vitamin D supplementation on serum levels of certain inflammatory markers in obese patients. The current study included such biomarkers as interleukin-6 (IL-6), pituitary adenylate cyclase-activating peptide (PACAP), advanced oxidation protein products (AOPP), C-X3-C Motif Chemokine Ligand 1 (CX3CL1), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO). The measurements were performed with the ELISA method before and after 3-month-long supplementation of 2000 IU of vitamin D orally. The results showed that the therapy did not induce any statistically significant changes in serum levels of MCP-1, IL-6, CX3CL1, and PACAP. The supplementation was related to a significant increase in measurements of NO and AOPP levels, although the correlation analysis between vitamin D concentration after its supplementation and the concentration of the molecular parameters did not show significant relation. In conclusion, our study seems to contradict certain aspects of findings available in the literature regarding the vitamin D's impact.

Potential of herbal products in prevention and treatment of COVID-19. Literature review.

The COVID-19 epidemic is the greatest pandemic that human kind experienced for decades, with high morbidity and mortality. Despite recent development of vaccines there is still many severe cases of COVID-19. Unfortunately there is still no standardized therapies and treatment of severe cases is very challenging. The aim of this study is to indicate if herbs administered alone or as a complementary therapy could be used as prophylaxis or treatment of SARS-CoV-2 infection. Over 85% of patients with COVID-19 in China used Traditional Chinese Medicine (TCM), and a most common herb is Glycyrrhiza glabra, which in vitro inhibits replication of different enveloped viruses, including coronaviruses. Glycyrrhizin in vitro connects and changes conformation of ACE2 receptors, which are vital for SARS-CoV-2 penetration into host cells. Pelargonium sidoides show immunomodulatory and antiviral properties in clinical and in vitro studies, and it inhibits replication of HCo-229E coronavirus. Glycyrrhiza glabra in combination with standard therapies significantly reduces the hospitalization rate and occurrence of COVID-19 symptoms. As complementary therapies lianhuaqingwen capsules and jinhua qinggan granules reduces hospitalization rates, time to symptoms recovery and improve patient psychological comfort. In view of SARS-CoV-2 other herbs are not effective, e.g. maxingshigan-yinqiaosan, or therapeutic concentration would be impossible to achieve, e.g. ephedra herb, or there is simply no proper data. Therefore, Liquorice and Pelargonium sidoides are effective against coronaviruses and could be possibly used as prophylaxis and treatment of COVID-19, while lianhuaqingwen capsules and jinhua qinggan granules can be useful as a complementary therapy to conventional treatment.

Curcumin May Prevent Basement Membrane Disassembly by Matrix Metalloproteinases and Progression of the Bladder Cancer.

Authors present a review of crucial mechanisms contributing to the invasion of the basement membrane (BM) of the urothelium by cancer cells and to the progression of bladder cancer (BC). The breeching of the urothelial BM, facilitated by an aberrant activation of matrix metalloproteinases (MMP) is particularly perilous. Inhibition of activation of these proteinases constitutes a logic opportunity to restrain progression. Because of limited efficacy of current therapeutic methods, the search for the development of alternative approaches constitutes "the hot spot" of modern oncology. Recent studies revealed significant anticancer potential of natural phytochemicals. Especially, curcumin has emerged as a one of the most promising phytochemicals and showed its efficacy in several human malignancies. Therefore, this article addresses experimental and clinical data indicating multi-directional inhibitory effect of curcumin on the growth of bladder cancer. We particularly concentrate on the mechanisms, by which curcumin inhibits the MMP's activities, thereby securing BM integrity and alleviating the eventual cancer invasion into the bladder muscles. Authors review the recently accumulating data, that curcumin constitutes a potent factor contributing to the more effective treatment of the bladder cancer.

Anemia of Chronic Diseases: Wider Diagnostics-Better Treatment?

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is the second most common type of anemia after iron deficiency anemia in the world. Its severity generally correlates with the severity of the underlying disease. This disease most often coexists with chronic inflammation, autoimmune diseases, cancer, and kidney failure. Before starting treatment, one should undertake in-depth diagnostics, which includes not only assessment of complete blood count and biochemical parameters, but also severity of the underlying disease. The differential diagnosis of anemia of chronic diseases is primarily based on the exclusion of other types of anemia, in particular iron deficiency. The main features of anemia of chronic diseases include mild to moderate lowering of hemoglobin level, decreased percentage of reticulocyte count, low iron and transferrin concentration, but increased ferritin. Due to the increasingly better knowledge of the pathomechanism of chronic diseases and cancer biology, the diagnosis of this anemia is constantly expanding with new biochemical indicators. These include: the concentration of other hematopoietic factors (folic acid, vitamin B12), hepcidin, creatinine and erythropoietin. The basic form of treatment of anemia of chronic diseases remains supplementation with iron, folic acid and vitamin B12 as well as a diet rich in the above-mentioned hematopoietic factors. The route of administration (oral, intramuscular or intravenous) requires careful consideration of the benefits and possible side effects, and assessment of the patient's clinical status. New methods of treating both the underlying disease and anemia are raising hopes. The novel methods are associated not only with supplementing deficiencies, but also with the administration of drugs molecularly targeted to specific proteins or receptors involved in the development of anemia of chronic diseases.

The Rundown of Dietary Supplements and Their Effects on Inflammatory Bowel Disease-A Review.

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are a life-long, chronic, and relapsing problem affecting 11.2 million people worldwide. To date, there is pharmacological therapy to treat symptoms such as diarrhea, constipation, and abdominal cramping/pain. These medications also help to alleviate everyday discomfort; however, there are no curative therapies. Recent studies have investigated the combination of pharmacological treatment along with nutritional interventions to improve quality of life and risk of disease relapse. Dietary supplements, specifically probiotics, polyphenols, fibers, fatty acids and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diets (FODMAP diets), have been closely looked at to determine their effect, if any, on the development of inflammatory bowel disease and its course of progression. Approximately 30 studies were carefully reviewed and analyzed to appreciate the value of these above-mentioned supplements and their influence on this gastrointestinal disease. After analysis, it has been demonstrated that by implementing fibers, polyphenols, and fatty acids, as well as keeping a low-saccharide diet for those patients with Crohn's disease and ulcerative colitis can improve quality of life and invoke clinical remission. Some polyphenols, specifically curcumin and resveratrol, have proved to decrease disease activity in studies reviewed. Although these studies have become a topic of recent interest, it would be of great value to doctors and patients alike, to continue in this direction of research and to improve the findings for best treatment substances and dosages. This would lead to increased quality of life and disease control leading to fewer complications in the future.

The Role of Vitamin D in Primary Headache-from Potential Mechanism to Treatment.

Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. All articles concerning the association between primary headache and vitamin D published up to October 2019 were retrieved by searching clinical databases, including: EMBASE, MEDLINE, PubMed, Google scholar, and the Cochrane library. All types of studies (i.e., observational, cross-sectional, case-control, and clinical trials) were included. We identified 22 studies investigating serum vitamin D levels in association with headaches. Eight studies also evaluated the effect of vitamin D supplementation on the various headache parameters. Among them, 18 studies showed a link between serum vitamin D levels and headaches, with the strongest connection reported between serum vitamin D levels and migraine. Overall, there is not enough evidence to recommend vitamin D supplementation to all headache patients, but the current literature indicates that it may be beneficial in some patients suffering headaches, mainly migraineurs, to reduce the frequency of headaches, especially in those with vitamin D deficiency.

The influence of low level laser irradiation on vascular reactivity.

PURPOSE: The mechanism of action of low level laser irradiation on tissues is unclear. Authors of publications present the positive clinical impact of low and medium power laser irradiation on vascular reactivity. The purpose of this study was to analyze the role of vascular endothelium in laser-induced constricted by endothelin-1 and phenylephrine. MATERIALS AND METHODS: Experiments were performed on isolated and perfused rat tail arteries of weighing 250-350g male Wistar rats. Contractility of arteries as a response to endothelin-1 and phenylephrine was measured after exposure to laser stimulation (10, 30 and 110mW). RESULTS: Laser irradiation inhibits vascular smooth muscle contraction induced by endothelin-1 and an alpha-adrenergic receptor agonist, phenylephrine proportionally to the laser power. Concentration-response curves were shifted to the right with significant reduction in maximal response. Laser irradiation at the power of 10mW, 30mW, and 110mW reduced the maximum response of arteries stimulated with phenylephrine sequentially to 88%, 72%, and 52%. Similar findings were observed during stimulation of endothelin-1. Laser irradiation at the power of 10mW, 30mW and 110mW resulted in maximal response respectively reduced to 94%, 62% and 38%. CONCLUSION: Our results strongly suggest that during low level laser irradiation vascular smooth muscle cells reactivity is reduced, this effect is present in arteries with normal endothelium. The mechanism of action of laser biosimulation on tissues is unclear. Authors of publications present the positive clinical impact of low level laser irradiation on vascular reactivity.

High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells.

OBJECTIVE: To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular smooth muscle cells (VSMCs). METHODS: Wistar rats were orally administered ticagrelor (10 mg/kg) and/or aspirin (2 or 10 mg/kg) (n = 7 per each of 4 groups) or placebo (n = 9) 12 and 2 hours before experiments. Anticontractile effects of ticagrelor were assessed in perfusion solution containing ticagrelor (1 µM/L). Changes in perfusion pressure proportional to the degree of adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated. RESULTS: Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels. Suppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was maintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose aspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response curve for phenylephrine. With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect. CONCLUSION: High-dose, but not low-dose, aspirin impairs the anticontractile effect of ticagrelor on ADP-induced VSMC contraction in the rat model. Both the clinical significance and detailed underlying mechanism of our findings require further investigation.