scholarly journals Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

2020 ◽  
Vol 21 (6) ◽  
pp. 2192 ◽  
Author(s):  
Forough Jahandideh ◽  
Jianping Wu
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Bioactive Peptides ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Physiological Models ◽  
Beneficial Effects ◽  
Potential Benefits ◽  
Antihypertensive Peptides

In addition to the regulation of blood pressure, the renin-angiotensin system (RAS) also plays a key role in the onset and development of insulin resistance, which is central to metabolic syndrome (MetS). Due to the interplay between RAS and insulin resistance, antihypertensive compounds may exert beneficial effects in the management of MetS. Food-derived bioactive peptides with RAS blocking properties can potentially improve adipose tissue dysfunction, glucose intolerance, and insulin resistance involved in the pathogenesis of MetS. This review discusses the pathophysiology of hypertension and the association between RAS and pathogenesis of the MetS. The effects of bioactive peptides with RAS modulating effects on other components of the MetS are discussed. While the in vivo reports on the effectiveness of antihypertensive peptides against MetS are encouraging, the exact mechanism by which these peptides infer their effects on glucose and lipid handling is mostly unknown. Therefore, careful design of experiments along with standardized physiological models to study the effect of antihypertensive peptides on insulin resistance and obesity could help to clarify this relationship.

scholarly journals The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

2012 ◽  
Vol 302 (6) ◽  
pp. H1219-H1230 ◽  
Author(s):  
Kelly Putnam ◽  
Robin Shoemaker ◽  
Frederique Yiannikouris ◽  
Lisa A. Cassis
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
The United States ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Metabolic Syndrome ◽  
Altered Glucose

The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.

scholarly journals Potential target for mitigation of COVID-19 by food-derived bioactive peptides

2021 ◽  
Vol 16 ◽  
Author(s):  
Kenji Sato
Keyword(s):  
Bioactive Peptides ◽  
Protein Hydrolysate ◽  
Renin Angiotensin System ◽  
The Body ◽  
Food Protein ◽  
Beneficial Effects ◽  
Target Organs ◽  
Acid Metabolites ◽  
Therapeutic Activities

Oral administration of food protein hydrolysate and naturally occurring peptides exert beneficial effects beyond conventional nutritional functions by supplying amino acids for protein synthesis. These peptides are referred to as food-derived bioactive peptides. The coronavirus disease 2019 (COVID-19) is caused by sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some host and viral proteins are involved in the entry of SARS-CoV-2 into cells and their replication. Peptides with specific sequences can interact with these proteins and have potential prophylactic and therapeutic activities against COVID-19. However, it is difficult to deliver food-derived peptides to target organs without degradation by exopeptidases in the body. Alternatively, food-derived peptides and amino acid metabolites have been suggested to decrease risk factors of COVID-19 by modulating the renin-angiotensin system, the innate immune system, and the antioxidant system. This mini-review is based on in vivo responses to food-derived peptides and aims to introduce potential targets for these peptides in decreasing the risk and severity of COVID-19. 

scholarly journals 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 492
Author(s):  
Laurence Dinan ◽  
Waly Dioh ◽  
Stanislas Veillet ◽  
Rene Lafont
Keyword(s):  
Respiratory Diseases ◽  
Therapeutic Potential ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Beneficial Effects ◽  
Invertebrate Predators ◽  
Polyhydroxylated Steroid

There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin–angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

scholarly journals Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1912
Author(s):  
Kaushik Chakravarty ◽  
Victor G. Antontsev ◽  
Maksim Khotimchenko ◽  
Nilesh Gupta ◽  
Aditya Jagarapu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Renin Angiotensin System ◽  
Mechanistic Modeling ◽  
Channel Blockers ◽  
Angiotensin System ◽  
In Silico Modeling ◽  
Site Of Action ◽  
Line Of Therapy

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.

Brain angiotensin system: a new promise in the management of epilepsy?

2021 ◽  
Vol 135 (6) ◽  
pp. 725-730
Author(s):  
Alberto Javier Ramos
Keyword(s):  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
B Cell Lymphoma ◽  
Ang Ii ◽  
Angiotensin System ◽  
Beneficial Effects ◽  
System A ◽  
Pilocarpine Model ◽  
Animal Models Of Epilepsy ◽  
Future Work

Abstract Epilepsy is a highly prevalent neurological disease and anti-epileptic drugs (AED) are almost the unique clinical treatment option. A disbalanced brain renin–angiotensin system (RAS) has been proposed in epilepsy and several reports have shown that angiotensin II (Ang II) receptor-1 (ATR1) activation is pro-inflammatory and pro-epileptogenic. In agreement, ATR1 blockage with the repurposed drug losartan has shown benefits in animal models of epilepsy. Processing of Ang II by ACE2 enzyme renders Ang-(1-7), a metabolite that activates the mitochondrial assembly (Mas) receptor (MasR) pathway. MasR activation presents beneficial effects, facilitating vasodilatation, increasing anti-inflammatory and antioxidative responses. In a recent paper published in Clinical Science, Gomes and colleagues (Clin. Sci. (Lond.) (2020) 134, 2263–2277) performed intracerebroventricular (icv) infusion of Ang-(1-7) in animals subjected to the pilocarpine model of epilepsy, starting after the first spontaneous motor seizure (SMS). They showed that this approach reduced the frequency of SMS, restored animal anxiety, increased exploration, and augmented the hippocampal expression of protective catalase enzyme and antiapoptotic protein B-cell lymphoma 2 (Bcl-2). Interestingly, but surprisingly, Gomes and colleagues showed that MasR expression and mTor activity were reduced in the hippocampus of the epileptic Ang-(1-7) treated animals. These results show that Ang-(1-7) administration could represent a new avenue for developing strategies for the management of epilepsy in clinical settings. However, future work is necessary to evaluate the levels of RAS metabolites and the activity of key enzymes in these experimental interventions to completely understand the therapeutic potential of the brain RAS manipulation in epilepsy.

Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Life Expectancy ◽  
Significant Risk ◽  
Low Grade ◽  
Aging Effects ◽  
Protective Function ◽  
Beneficial Effects ◽  
Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

Effects of Tokishakuyakusan, Keishibukuryogan, Shakuyakukanzoto and Unkeito on Ovarian Endothelin, Renin and Angiotensin II in Pregnant Mare's Serum Gonadotropin-treated Immature Rats

1992 ◽  
Vol 20 (02) ◽  
pp. 175-179 ◽  
Author(s):  
Satoshi Usuki ◽  
Yoshie Usuki ◽  
Junko Tanaka ◽  
Yuko Kawakura
Keyword(s):  
Angiotensin Ii ◽  
Herbal Medicines ◽  
Renin Angiotensin System ◽  
Concomitant Treatment ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Immature Rats ◽  
Serum Gonadotropin ◽  
Peptide System

We have previously proposed the ovarian ERAANPS (endothelin-renin-angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-l (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.

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