Highly potent antioxidant Olea europaea L. leaf extract affects carotid and renal haemodynamics in experimental hypertension

Haemodynamic alterations in carotid and renal arteries are associated with the severity of target organ damage in patients with hypertension. Dietary habits, such as the Mediterranean diet, regulate blood pressure and oxidative stress, thus reduce the mortality rate due to cardiovascular diseases. In this study, our aim was to evaluate the reducing activity, antioxidant capacity and metal chelating ability of standardized Olea europaea L. leaf extract (OLE), and to test its (5, 25, 50 mg/kg) acute in vivo effects, as well as oleuropein’s (OP, 10 mg/kg) on oxidative stress, carotid, renal and systemic haemodynamic parameters (blood pressure, heart rate, cardiac output, peripheral resistance) in spontaneously hypertensive rats (SHR). OLE has a higher antioxidative capacity than BHT, higher reducing ability than vitamin C, and 23 times lower capacity for metal ion chelation than EDTA. All three doses of OLE, and OP, improved oxidative stress in SHR. OLE5 improved carotid and renal haemodynamics, without significant effects on systemic haemodynamics. Two different mechanisms of antihypertensive responses to OLE were observed, OLE25 was most effective in reducing cardiovascular risks by improving systemic and regional (carotid and renal) haemodynamics, peripheral and regional vascular resistance. OLE50 causes the improvement of blood pressure and cardiac performances, but tends to retain elevated vascular resistance, therefore, reducing the inflow of blood into the brain and kidneys of the SHR. The OP did not alter systemic or regional haemodynamics, suggesting others constituents responsible for changes of cardiac function, as well as carotid and renal haemodynamics in response to OLE50

An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer

Calotropin is a pharmacologically active compound isolated from milkweed plants like Calotropis procera, Calotropis gigantea, and Asclepias currasavica that belong to the Asclepiadaceae family. All of these plants are recognised as medical traditional plants used in Asian countries. Calotropin is identified as a highly potent cardenolide that has a similar chemical structure to cardiac glycosides (such as digoxin and digitoxin). During the last few years, cytotoxic and antitumor effects of cardenolides glycosides have been reported more frequently. Among cardenolides, calotropin is identified as the most promising agent. In this updated and comprehensive review, we aimed to analyze and discuss the specific mechanisms and molecular targets of calotropin in cancer treatment to open new perspectives for the adjuvant treatment of different types of cancer. The effects of calotropin on cancer have been extensively studied in preclinical pharmacological studies in vitro using cancer cell lines and in vivo in experimental animal models that have targeted antitumor mechanisms and anticancer signaling pathways. The analyzed information from the specialized literature was obtained from scientific databases until December 2022, mainly from PubMed/MedLine, Google Scholar, Scopus, Web of Science, and Science Direct databases using specific MeSH search terms. The results of our analysis demonstrate that calotropin can be a potential chemotherapeutic/chemopreventive adjunctive agent in cancer pharmacotherapeutic management

Effects of losartan, tempol, and their combination on renal nitric oxide synthases in the animal model of chronic kidney disease

Down-regulation of nitric oxide synthase (NOS) and NO defi ciency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T + L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were signifi cantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a signifi cant decline in the glomerular fi ltration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fi broblasts and myofi broblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD

Optimization of extraction of stinging nettle leaf phenolic compounds using response surface methodology

A full three level factorial design was implemented for optimization of extraction parameters in order to maximize total phenolic (TP) yield from stinging nettle leaf. Factors considered were percentage of methanol in solvent (X-1 : 50-100% methanol) and extraction time (X-2: 30-90 min), and maceration was used as extraction method. A second-order polynomial model was applied for fitting experimental data and predicting the response, and this mathematical model produced a satisfactory fit (R-2 = 0.993,p LT 0.01). The optimal extraction conditions were 54% aqueous methanol and 38 min extraction time, while maximal theoretical TP yield was 8.9 mg GAE/g DW. Solvent composition significantly affected extraction efficiency causing decrease of TP yield with increase of methanol percentage. On the other hand, extraction time did not influence significantly efficiency of extraction. Using LC/MS and HPLC analysis we detected and quantified three most abundant phenolic compounds: 2-O-caffeoyl malic acid, chlorogenic acid, and rutin. Comparison between maceration and ultrasound-assisted extraction (UAE) obtained extracts based on TP content as well as antiradical activity and HPLC results, showed that UAE have a better extraction capability affecting yield and time of extraction. Of all tested extracts, 54% aqueous methanolic extracts obtained with UAE and 38 min extraction time had the highest TP content

DataSheet1_An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer.docx

Calotropin is a pharmacologically active compound isolated from milkweed plants like Calotropis procera, Calotropis gigantea, and Asclepias currasavica that belong to the Asclepiadaceae family. All of these plants are recognised as medical traditional plants used in Asian countries. Calotropin is identified as a highly potent cardenolide that has a similar chemical structure to cardiac glycosides (such as digoxin and digitoxin). During the last few years, cytotoxic and antitumor effects of cardenolides glycosides have been reported more frequently. Among cardenolides, calotropin is identified as the most promising agent. In this updated and comprehensive review, we aimed to analyze and discuss the specific mechanisms and molecular targets of calotropin in cancer treatment to open new perspectives for the adjuvant treatment of different types of cancer. The effects of calotropin on cancer have been extensively studied in preclinical pharmacological studies in vitro using cancer cell lines and in vivo in experimental animal models that have targeted antitumor mechanisms and anticancer signaling pathways. The analyzed information from the specialized literature was obtained from scientific databases until December 2022, mainly from PubMed/MedLine, Google Scholar, Scopus, Web of Science, and Science Direct databases using specific MeSH search terms. The results of our analysis demonstrate that calotropin can be a potential chemotherapeutic/chemopreventive adjunctive agent in cancer pharmacotherapeutic management.</p

Antioxidant enzymes activities in kidney among the experimental groups.

<p>SOD—superoxide dismutase, CAT—catalase, and GSH-Px—glutathione peroxidase. *<i>p<0</i>.<i>05</i>, **<i>p<0</i>.<i>01</i>, ***<i>p<0</i>.<i>001</i> vs. SHC; ^#<i>p<0</i>.<i>05</i>, ^###<i>p<0</i>.<i>001</i> vs. SHADR; ^$<i>p<0</i>.<i>05</i>, ^$ $<i>p<0</i>.<i>01</i>, ^$ $$<i>p<0</i>.<i>001</i> vs. SHADR+L; ^&&<i>p<0</i>.<i>01</i> vs. SHADR+T; n = 8 animals per group. Data represent mean ± SEM. SHC—control group, SHADR–SHR treated with adriamycin, L—losartan, T—tempol.</p

Systolic arterial pressure (SAP), urine protein-to-creatinine ratio (Up/cr), urine protein (Up), and plasma creatinine (Pcr) in experimental groups.

<p><i>*p<0</i>.<i>05</i>, <i>**p<0</i>.<i>01</i>, <i>***p<0</i>.<i>001</i> vs. SHC; <i>#p<0</i>.<i>05</i>, <i>###p<0</i>.<i>001</i> vs. SHADR; <i>$p<0</i>.<i>05</i>, <i>$ $p<0</i>.<i>01</i>, <i>$ $$p<0</i>.<i>001</i> vs. SHADR+L; n = 6–7 animals per group. Data represent mean ± SEM. SHC—control group, SHADR–SHR treated with adriamycin, L—losartan, T–tempol.</p

Morphological changes of glomeruli and tubules in experimental groups (PAS, x20 magnification, bar = 100μm).

<p>(<b>A</b>) Normal shape of glomeruli and (<b>B</b>) tubulointerstitium in SHC group. (<b>C</b>) Glomerulus (upper right) with advanced glomerular sclerosis involving almost entire glomerular tuft, periglomerular interstitial fibrosis and mononuclear inflammatory infiltrate; (<b>D</b>) tubular atrophy and dilatation with PAS positive casts, interstitial fibrosis with mononuclear inflammatory infiltrate in SHADR group. (<b>E</b>) Moderate capsular adhesion and segmental glomerular sclerosis involving almost one third of the glomerular tuft; (<b>F</b>) well-preserved tubules and interstitium in SHADR+L group. (<b>G</b>) Glomerulus with mild capsular adhesions and incipient sclerosis; (<b>H</b>) slightly prominent tubular dilatation with infrequent PAS positive casts in SHADR+T group. (<b>I</b>) Left glomerulus with capsular adhesion and advanced segmental glomerular sclerosis, right glomerulus with capsular adhesion, incipient segmental sclerosis, and collapse of the glomerular capillary loops; (<b>J</b>) tubular dilatations with PAS positive casts, interstitial mononuclear inflammatory infiltrate, and slight interstitial fibrosis in SHADR+T+L group.</p

Glomerular nestin expression in experimental groups.

<p>(<b>A</b>) Negative control (×200). (<b>B</b>) SHC group: Nestin was observed focally in some of glomeruli, whereby expression was usually limited on single podocyte per glomerulus. (<b>C</b>) SHADR group: Diffuse glomerular nestin expression was detected involving almost all podocytes within glomerulus. After losartan and tempol treatment, either single or in combination, kidneys restored nestin expression similar to controls (SHC group). Thus, SHADR+L group (<b>D</b>), SHADR+T group (<b>E</b>) and SHADR+T+L group (<b>F</b>) exhibited similar glomerular nestin immunomorphological profile as observed in control animals. However, in addition to rare expression in podocytes, nestin was also detected in some interstitial cells, mainly within periglomerular area, as it is shown in images (E) and (F). Arrows indicate nestin expressing cells (podocytes and interstitiual cells). Magnification for images B-F ×400.</p