The biologically active compound of Withania somnifera (L.) Dunal, docosanyl ferulate, is endowed with potent anxiolytic properties but devoid of typical benzodiazepine-like side effects

2021 ◽  
pp. 026988112110085
Author(s):  
Riccardo Maccioni ◽  
Filippo Cottiglia ◽  
Elias Maccioni ◽  
Giuseppe Talani ◽  
Enrico Sanna ◽  
...  

Background: Clinical and experimental studies support the therapeutic potential of Withania somnifera ( WS) (L.) Dunal on anxiety disorders. This potential is attributable to components present in different plant extracts; however, the individual compound(s) endowed with specific anxiolytic effects and potential modulatory activity of the GABAA receptor complex (GABAAR) have remained unidentified until the recent isolation from a WS methanolic root extract of some GABAAR-active compounds, including the long alkyl-chain ferulic acid ester, docosanyl ferulate (DF). Aims: This study was designed to assess whether DF (0.05, 0.25 and 2 mg/kg), similarly to diazepam (2 mg/kg), may exert anxiolytic effects, whether these effects may be significantly blocked by the benzodiazepine antagonist flumazenil (10 mg/kg) and whether DF may lack some of the benzodiazepines’ typical motor, cognitive and motivational side effects. Methods: The behavioural paradigms Elevated Plus Maze, Static Rods, Novel Object Recognition, Place Conditioning and potentiation of ethanol-induced Loss of Righting Reflex were applied on male CD-1 mice. Results: Similarly to diazepam, DF exerts anxiolytic effects that are blocked by flumazenil. Moreover, at the full anxiolytic dose of 2 mg/kg, DF lacks typical benzodiazepine-like side effects on motor and cognitive performances and on place conditioning. Moreover, DF fails to potentiate ethanol’s (3 g/kg) depressant activity at the ethanol-induced Loss of Righting Reflex paradigm. Conclusions: These data point to DF as an effective benzodiazepine-like anxiolytic compound that, in light of its lack of motor, mnemonic and motivational side effects, could be a suitable candidate for the treatment of anxiety disorders.

Author(s):  
A. Farkhutdinova

The expediency of using the probiotic drug Biolax-U in the rations of lactating and dry cows of Black-and-White breed has been studied and scientifically proved. The influence of this drug on the morphological and biochemical parameters of animal blood has been determined. The composition of the probiotic drug Biolax-U consists of eight strains of a balanced complex of living lactic acid bacteria, yeast and actinomycetes, as well as biologically active substances. For experimental studies conducted on 2 groups of cows have been selected by the method of pairs-analogs, the influence of feeding of feed have been prepared with the use of the microbiological drug with probiotic action Biolax-U on feed consumption, morphological and biochemical changes in blood has been studied. Analysis of the rations of cows indicates that the content of calcium, phosphorus, magnesium, sulfur and trace elements such as manganese, copper, zinc and cobalt in the feed has been reduced. It has been found by studies that the use of probiotic drug Biolax-U had the positive influence on the feed intake, digestibility and better assimilation of feed nutrients and contributed to the improvement of blood morphological and biochemical parameters. For example, in animals of the experimental group hemoglobin has increased by 3,6 % (Р < 0,05), red blood cells by 10,1 (P ≤ 0,05), the content of leukocytes by 4,43, carotene by 9,6, glucose by 3,4; reserve alkalinity by 15,6, calcium by 19,4 (P ≤ 0,01), and phosphorus by 18,4 % compared with the control group of animals. During the lactation significantly improved hematological parameters including alkalinity reserve by 5,11 %, calcium level by 11,1, phosphorus by 8,6, hemoglobin by 14,2 %, the content of erythrocytes by 12,3, leukocyte by 3,86, and carotene 11,1 % against the parameters of animals of control group. The improvement of morphological and biochemical parameters of blood of cows indicates about stimulating effect on hematopoiesis and the general clinical condition of animals that contributes to the improvement of metabolic processes when using feed prepared with the use of microbiological drug with probiotic action Biolax-U.


Separations ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 8
Author(s):  
Kollur Shiva Prasad ◽  
Shashanka K Prasad ◽  
Ravindra Veerapur ◽  
Ghada Lamraoui ◽  
Ashwini Prasad ◽  
...  

Herein we report the synthesis of zinc oxide nanoparticles (ZnONPs) using Withania somnifera root extract (WSE) as an effective chelating agent. The microscopic techniques viz., X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED) were employed to analyze the as-obtained ZnONPs. The crystalline planes observed from the XRD pattern agrees with the hexagonal wurtzite structure of the as-prepared ZnONPs. The aggregations and agglomerations observed in the SEM images indicated that the size of the as-prepared ZnONPs was between 30 and 43 nm. The interplanar distance between the lattice fringes observed in the HRTEM image was found to be 0.253 nm, which is in good agreement with the (100) plane obtained in the XRD pattern. Furthermore, the anti-breast cancer cytotoxic evaluation was carried out using the MCF-7 cell line, and the results showed significant cytotoxic effects in a dose-dependent manner.


Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 145
Author(s):  
Su-In Hwang ◽  
Young-Jin Yoon ◽  
Soo-Hyun Sung ◽  
Ki-Tae Ha ◽  
Jang-Kyung Park

Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.


Author(s):  
Kai Kisielinski ◽  
Paul Giboni ◽  
Andreas Prescher ◽  
Bernd Klosterhalfen ◽  
David Graessel ◽  
...  

Many countries introduced the requirement to wear masks in public spaces for containing SARS-CoV-2 making it commonplace in 2020. Up until now, there has been no comprehensive investigation as to the adverse health effects masks can cause. The aim was to find, test, evaluate and compile scientifically proven related side effects of wearing masks. For a quantitative evaluation, 44 mostly experimental studies were referenced, and for a substantive evaluation, 65 publications were found. The literature revealed relevant adverse effects of masks in numerous disciplines. In this paper, we refer to the psychological and physical deterioration as well as multiple symptoms described because of their consistent, recurrent and uniform presentation from different disciplines as a Mask-Induced Exhaustion Syndrome (MIES). We objectified evaluation evidenced changes in respiratory physiology of mask wearers with significant correlation of O2 drop and fatigue (p < 0.05), a clustered co-occurrence of respiratory impairment and O2 drop (67%), N95 mask and CO2 rise (82%), N95 mask and O2 drop (72%), N95 mask and headache (60%), respiratory impairment and temperature rise (88%), but also temperature rise and moisture (100%) under the masks. Extended mask-wearing by the general population could lead to relevant effects and consequences in many medical fields.


2021 ◽  
Vol 43 (1) ◽  
pp. 127-141
Author(s):  
Matúš Čoma ◽  
Veronika Lachová ◽  
Petra Mitrengová ◽  
Peter Gál

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.


2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.


Author(s):  
Meghan M. Louis ◽  
Gregory Scott ◽  
Dustin Smith ◽  
Brigid V. Troan ◽  
Larry J. Minter ◽  
...  

Euthanasia techniques in amphibians are poorly described and sparsely validated. This study investigated potassium chloride (KCl) for euthanasia of anesthetized marine toads ( Rhinella marina ). Twenty three toads were immersed in buffered MS-222 (2 g/L) for five minutes (min) beyond loss of righting reflex, manually removed, and randomly administered KCl (n = 6/group) via one of three routes: intracardiac at 10 mEq/kg (IC), intracoelomic at 100 mEq/kg (ICe), or immersion at 4500 mEq/L (IMS) or no treatment (C) (n = 5/group). Doppler sounds were assessed continuously from prior to treatment until two min post-treatment and every five min thereafter until sound cessation or resumption of spontaneous movement. Plasma potassium concentration (K+) was measured at the time of Doppler sound cessation in ICe and IMS. In IC, ICe, IMS, and C, Doppler sound cessation occurred in 4/6, 6/6, 6/6, and 1/5 toads with median (range) or mean + SD times of 0.23 (0-4.65), 17.5 + 9.0, 40.6 + 10.9, and &gt;420 min, respectively. Nonsuccess in 2/6 toads in IC was suspected due to technique failure. Plasma K+ exceeded the limits of detection (&gt;9 mmol/L) in 12/12 toads in ICe and IMS. Five of six toads in C resumed spontaneous movement at median (range) times of 327 (300-367) min. KCl delivered via an intracardiac, intracoelomic, or immersion routes resulted in Doppler sound cessation in 16 of 18 toads and may be appropriate for euthanasia of anesthetized marine toads.


2021 ◽  
Vol 66 (4) ◽  
pp. 273-283
Author(s):  
Zhousheng Jin ◽  
Fangfang Xia ◽  
Jiaojiao Dong ◽  
Tingting Lin ◽  
Yaoyao Cai ◽  
...  

Glucocorticoid excess often causes a variety of cardiovascular complications, including hypertension, atherosclerosis, and cardiac hypertrophy. To abrogate its cardiac side effects, it is necessary to fully disclose the pathophysiological role of glucocorticoid in cardiac remodelling. Previous clinical and experimental studies have found that omentin-1, one of the adipokines, has beneficial effects in cardiovascular diseases, and is closely associated with metabolic disorders. However, there is no evidence to address the potential role of omentin-1 in glucocorticoid excess-induced cardiac injuries. To uncover the links, the present study utilized rat model with glucocorticoid-induced cardiac injuries and clinical patients with abnormal cardiac function. Chronic administration of glucocorticoid excess reduced rat serum omentin-1 concentration, which closely correlated with cardiac functional parameters. Intravenous administration of adeno-associated virus encoding omentin-1 upregulated the circulating omentin-1 level and attenuated glucocorticoid excess-induced cardiac hypertrophy and functional disorders. Overexpression of omentin-1 also improved cardiac mitochondrial function, including the reduction of lipid deposits, induction of mitochondrial biogenesis, and enhanced mitochondrial activities. Mechanistically, omentin-1 phosphorylated and activated the GSK3β pathway in the heart. From a study of 28 patients with Cushing’s syndrome and 23 healthy subjects, the plasma level of glucocorticoid was negatively correlated with omentin-1, and was positively associated with cardiac ejection fraction and fractional shortening. Collectively, the present study provided a novel role of omentin-1 in glucocorticoid excess-induced cardiac injuries and found that the omentin-1/GSK3β pathway was a potential therapeutic target in combating the side effects of glucocorticoid.


Author(s):  
SHAPOVALOVA Nataliia ◽  
VEZHLIVTSEVA Svitlana ◽  
ANTIUSHKO Dmytro

Background. The deficiency of essential nutrients in the human body is the root cause of reduced efficiency, general resistance of the body to various diseases. That is an urgent problem in the context of the spread of coronavirus infection. In this regard, the search for opportunities to meet the needs of the population in food products that contain biologically active substances (BAS) through the use of high-value and at the same time available plant raw materials is extremely important. Marigolds attract special attention among such raw materials. The aim of the work is to study the chemical composition and evaluate the consumer properties of Tagetes L. varieties, zoned in the Kiev region, to prove the possibility of increasing the biological value of pasta by adding to their recipe powder from marigold inflorescences. Materials and methods. The object of research is pasta of B group (noodles). Inflorescences of marigolds of different varieties gathered during the flowering period in July-September 2019–2020 in the territory of Vasylkiv and Obukhiv districts of Kyiv region, Ukraine were used as enriching plant raw materials. The quality of finished pasta was assessed by organoleptic and physicochemical indexes (moisture content and titratable acidity). The content of mineral elements in the fine powder of marigold inflorescences was determined on the EXHERT-3L device, the quantitative composition and BAS identification – by spectrophotometric analysis on the device Specord-200 Analytic Jena UV-vis. The integrated quality index of pasta products was calculated taking into account the importance factors of individual indexes. Results. Comparing the obtained results, we can state that all the studied varieties – Gold Kopfen, Orange Flame, Hawaii, Equinox are characterized by high biological value, regardless of the area of collection. As a result of calculated and experimental studies it was determined that the addition of 7 % of the supplement does not provide the required supply of vitamins and minerals. Replacing the flour in the recipe by 20 % significantly improves the mineral composition, but deteriorates the taste and aromatic properties of pasta. The most optimal and rational amount of added additive is 15 %, as it improves the organoleptic properties of pasta and enriches their BAS. Conclusion. The usage of non-traditional vegetable raw materials, in particular powder from marigold inflorescences, which is rich in biologically active substances, allows not only to expand the range, improve the quality of finished products, but also increase the biological value of the product. The optimal amount of additive –powder from marigold inflorescences, was defined. It is 15 % by weight of flour in the production of noodles. This concentration allows not only to improve the organoleptic properties, but also to increase the content of biologically active substances – vitamins, micro- and macronutrients. The usage of non-traditional natural raw materials (powder from marigold inflorescences) allows to abandon artificial colorsand give the finished pasta a pleasant colorand aroma.


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