Endogenous Active Substances Research Articles

Effects of calcium chloride and licorice flavonoids on Tan sheep myofibrillar protein oxidation and gelation: Synergistic impact of endogenous characteristic active substances

Effects of calcium chloride and licorice flavonoids on Tan sheep myofibrillar protein oxidation and gelation: Synergistic impact of endogenous characteristic active substances

Mesoporous carbon hollow spheres based sensitive SPME probes for in vivo sampling analysis of selected plant hormones in Chinese aloes

Phytohormones are a class of endogenous substances that separately or synergistically regulate the growth, development, and differentiation of plants. Accurately and efficiently detecting and monitoring the concentration of plant hormones in living plants is of significant importance. Herein, a novel mesoporous carbon hollow spheres (MCHS)-based in vivo solid phase microextraction (SPME) probe was designed for in vivo sampling of plant hormones. The designed MCHS features the advantages of high surface area, porous shells, and large hollow spaces, facilitating the dynamic adsorption and enrichment of target phytohormone. In addition, a cationic polyelectrolyte, (poly (diallyl dimethyl ammonium chloride) (PDDA), was further modified onto the MCHS to expedite the extraction process by electrostatic interaction. Utilizing the MCHS@PDDA probe in combination with HPLC-MS/MS facilitated the continuous monitoring of three plant hormones (abscisic acid (ABA), indole-3-acetic acid (IAA), and gibberellin (GA3)) in Chinese aloe. The detection limit of this method was 0.016–0.090 μg/L, the linear range was 10–1000 μg/L, and both the RSD of the single probe (n = 6) and probe-to-probe test (n = 6) were less than 7.2 %. This method had excellent accuracy and good reproducibility comparable to the traditional sample pretreatment method. Ultimately, this established in-vivo SPME method was successfully adopted to quantify three selected plant hormones in living Chinese Aloes, providing a new method for the long-term monitoring of endogenous active substances in living system.

Effects of extraction solvents on antarctic krill oil quality characteristics and some insights into the oxidation stability of antarctic krill oil

The effects of 6 solvent combinations (Folch, acetone/ethanol [1:1, v/v], ethanol [95%, v/v], n-hexane/ethyl acetate [7:3, v/v], n-hexane/ethanol [10:1, v/v], and isopropanol alcohol [95%, v/v] with different polarities on the quality characteristics of Antarctic krill oil (AKO) extracted from Antarctic krill were investigated in this study. The relationship between endogenous active substances and oxidative stability was also explored. There was a significant positive correlation between solvent polarity and AKO yield (r = 0.91, p < 0.05), a significant positive correlation with total tocopherols (r = 0.84, p < 0.05) and a weak correlation with astaxanthin (r = 0.53). In addition, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in AKO were mostly located in phosphatidylcholines, lysophosphatidylcholine, phosphatidylethanolamine and lysophosphatidylethanolamine. ethanol (95%, v/v) had the highest efficiency of glycerophospholipids (34.39%), EPA (20.83%) and DHA (9.61%). For liposolubility trace substances, astaxanthin were extracted most efficiently with Folch (283.49 μg/g) and acetone/ethanol (1:1, v/v, 264.58 μg/g), whereas tocopherols were extracted most efficiently with ethanol (95%, v/v, 114.29 μg/g). Astaxanthin, tocopherol and phosphatidylcholines were closely related to the oxidative stability of AKO. Astaxanthin in AKO showed a significant (p < 0.05) positive correlation with ABTS· scavenging capacity, whereas tocopherol and phosphatidylcholines showed a significant (p < 0.05) dose-effect relationship with total reducing power.

Betaine alleviates spermatogenic cells apoptosis of oligoasthenozoospermia rat model by up-regulating methyltransferases and affecting DNA methylation

BackgroundOligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on improving semen quality. BET also belongs to endogenous physiological active substances in the testis. However, the physiological function of BET in rat testis and its pharmacological mechanism against oligoasthenozoospermia remain unclear. PurposeThis research aims to prove the therapeutic effect and potential mechanism of BET on oligoasthenozoospermia rat model induced by Tripterygium wilfordii glycosides (TWGs). MethodsThe oligoasthenozoospermia rat model was established by a continuous gavage of TWGs (60 mg/kg) for 28 days. Negative control group, oligoasthenozoospermia group, positive drug group (levocarnitine, 300 mg/kg), and 200 mg/kg, 400 mg/kg, and 800 mg/kg BET groups were created for exploring the therapeutic effect of BET on the oligoasthenozoospermia rat model. The therapeutic effect was evaluated by HE and TUNEL staining. Immunofluorescence assay of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3, methylation capture sequencing, Pi-RNA sequencing, and molecular docking were used to elucidate potential pharmacological mechanisms. ResultsIt is proved that BET can significantly restore testicular pathological damage induced by TWGs, which also can significantly reverse the apoptosis of spermatogenic cells. The spermatogenic cell protein expression levels of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3 significantly decreased in oligoasthenozoospermia group. 400 mg/kg and 800 mg/kg BET groups can significantly increase expression level of the above-mentioned proteins. Methylation capture sequencing showed that BET can significantly increase the 5mC methylation level of Spata, Spag, and Specc spermatogenesis-related genes. Pi-RNA sequencing proved that the above-mentioned genes produce a large number of Pi-RNA under BET intervention. Pi-RNA can form complexes with PIWI proteins to participate in DNA methylation of target genes. Molecular docking indicated that BET may not directly act as substrate for methyltransferase and instead participates in DNA methylation by promoting the methionine cycle and increasing S-adenosylmethionine synthesis. ConclusionBET has a significant therapeutic effect on oligoasthenozoospermia rat model induced by TWPs. The mechanism mainly involves that BET can increase the methylation level of Spata, Specc, and Spag target genes through the PIWI/Pi-RNA pathway and up-regulation of methyltransferases (including DNA methyltransferases and histone methyltransferases).

Neuropeptides as Potential Biomarkers in Vascular Dementia.

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions.

Effective degradation of anthraquinones in Folium Sennae with Monascus fermentation for toxicity reduce and efficacy enhancement

Folium Sennae are widely used around the world, mainly in purging and removal of endogenous active substances, such as anthraquinone and its derivatives. However, the potential toxicity of anthraquinones to the liver, kidney, and intestinal limits the application of Folium Sennae. In this study, we aimed at safe regulation of Folium Sennae to degrade anthraquinones, boosting medicinal properties and reducing toxicity and potency with Monascus fermentation. Monascus strains H1102 for Folium Sennae fermentation were selected as the initial strain which was capable of producing high yields of functional pigment and low yields of hazardous citrinin. The anthraquinone degradation rate reached 41.2%, with 212.2 U mL−1 of the pigment and approximately 0.038 mg L−1 of the citrinin under optimal fermentation conditions followed by response surface streamlining, which met the requirements of reducing toxicity, increasing efficiency of Monascus fermented Folium Sennae. Furthermore, the Monascus/Folium Sennae culture had no observable toxic effect on HK-2 and L-02 cells in vitro and further inhibited cell apoptosis and necrosis. Overall, our results showed that Monascus fermentation could provide an alternative strategy for toxicity reduction of herbal medicines as well as efficacy enhancement.

A Review of Pedal Peptide/Orcokinin-type Neuropeptides.

Neuropeptides are endogenous active substances that play important roles in a number of physiological processes and are ubiquitous in the nervous tissue in vivo. The gene encoding pedal peptide/orcokinin-type (PP/OK-type) neuropeptide is an important member of the neuropeptide gene family and is ubiquitous in invertebrates of Bilateria; orcokinin (OK) is mainly found in Arthropoda, while pedal peptide (PP) is mainly found in Mollusca. OK and PP are also present in other animals. PP/OK-type neuropeptides are a kind of multifunctional neuropeptides predominantly expressed in the nervous tissue and play important roles in the nerve regulation of movement. Moreover, OK has a number of other physiological functions. This review describes the distribution, expression, function and maturation of PP/OK-type neuropeptides to facilitate investigations of new functions and receptors of PP/OK-type neuropeptides, providing the theoretical foundation for the potential use of PP/OK-type neuropeptides in the prevention and control of agricultural and forestry pests, as an additive for skin care products and in the screening of drugs for the treatment of diabetes.

The Effect of Pedal Peptide-Type Neuropeptide on Locomotor Behavior and Muscle Physiology in the Sea Cucumber Apostichopus japonicus.

Neuropeptides are endogenous active substances that are present in nervous tissues and participate in behavioral and physiological processes of the animal system. Locomotor behavior is basic to predation, escape, reproduction in animals, and neuropeptides play an important role in locomotion. In this study, the function of pedal peptide-type neuropeptide (PDP) in the process of locomotor behavior of the sea cucumber Apostichopus japonicus was evaluated. The locomotor behavior of A. japonicus was recorded by infrared camera before and after PDP administration, and muscle physiology was studied by ultra performance liquid chromatography and quadrupole time-off-light mass spectrometry (UPLC-Q-TOF-MS) to clarify the potential physiological mechanisms. The results showed that PDP enhanced the cumulative duration of moving significantly at the 7th h after injection, and reduced the mean and maximum velocity by 16.90 and 14.22% in A. japonicus. The data of muscle metabolomics suggested that some significantly changed metabolites were related to locomotor behavior of sea cucumbers. The decreases of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) might result in the increases of lysophosphatidylcholines (lysoPC) and lysophosphatidylethanolamine (lysoPE), and suggested the change of fluidity and permeability in the muscle cell membrane, which would affect the physiology and function of muscle cells, and finally alter the locomotor behavior. In addition, the increased level of arachidonic acid (ARA) might activate K+ ion channels and then affect the signaling of muscle cells, or promote the sensitivity of muscle cells to Ca2+ and then result in the contractility of longitudinal muscles in sea cucumbers. ARA was also involved in the linoleic acid metabolism which was the only pathway that disturbed significantly after PDP administration. In conclusion, PDP participated in the regulation of locomotor behavior in the sea cucumber, and the decreased PE and PC, increased lysoPC, lysoPE and ARA might be the potential physiological mechanisms that responsible for behavioral effects of PDP in A. japonicus.

Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae).

Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.

Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities.

Once considered to be mere by-products of metabolism, reactive oxygen, nitrogen and sulfur species are now recognized to play important roles in diverse cellular processes such as response to pathogens and regulation of cellular differentiation. It is becoming increasingly evident that redox imbalance can impact several signaling pathways. For instance, disturbances of redox regulation in the brain mediate neurodegeneration and alter normal cytoprotective responses to stress. Very often small disturbances in redox signaling processes, which are reversible, precede damage in neurodegeneration. Recent Advances: The identification of redox-regulated processes, such as regulation of biochemical pathways involved in the maintenance of redox homeostasis in the brain has provided deeper insights into mechanisms of neuroprotection and neurodegeneration. Recent studies have also identified several post-translational modifications involving reactive cysteine residues, such as nitrosylation and sulfhydration, which fine-tune redox regulation. Thus, the study of mechanisms via which cell death occurs in several neurodegenerative disorders, reveal several similarities and dissimilarities. Here, we review redox regulated events that are disrupted in neurodegenerative disorders and whose modulation affords therapeutic opportunities. Although accumulating evidence suggests that redox imbalance plays a significant role in progression of several neurodegenerative diseases, precise understanding of redox regulated events is lacking. Probes and methodologies that can precisely detect and quantify in vivo levels of reactive oxygen, nitrogen and sulfur species are not available. Due to the importance of redox control in physiologic processes, organisms have evolved multiple pathways to counteract redox imbalance and maintain homeostasis. Cells and tissues address stress by harnessing an array of both endogenous and exogenous redox active substances. Targeting these pathways can help mitigate symptoms associated with neurodegeneration and may provide avenues for novel therapeutics. Antioxid. Redox Signal. 30, 1450-1499.

Overview of Experimental and Clinical Findings regarding the Neuroprotective Effects of Cerebral Ischemic Postconditioning.

Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and inhibition of calcium overload, as well as the release of endogenous active substances, alterations in membrane channel function, and activation of protein kinases. Here we review the novel discovery, mechanism, key factors, and clinical application of ischemic postconditioning and discuss its implications for future research and problem of clinical practice.

ChemInform Abstract: Evaluation of Time Course and Inter-Relationship of Inflammatory Mediators in Experimental Inflammatory Reaction

Inflammatory signs, such as heat, redness, swelling and pain, have been described from the Greek era. In these phenomena various endogenous active substances, i.e., inflammatory mediators, could cause and manifest vascular dilatation, a vascular permeability increase and sensitization of pain receptors, etc. In order to evaluate the roles of inflammatory mediators, we have studied the time courses of inflammatory reaction along with detection of various active substances directly or indirectly in the experimental animal model of pleurisy, such as rat carrageenin-induced, and zymosan-induced pleurisy. These pleurisies showed almost similar time courses of pleural exudate accumulation and neutrophil migration. However, mediators detected in the exudates of such pleurisies were different; in carrageenin-induced pleurisy bradykinin and prostacyclin (PGI2) caused exudate formation, while zymosan-induced pleurisy showed early degradation of mast cells and activation of complements, followed by an increase in platelet activating factor (PAF). In both pleurisies TNF alpha, IL-1, IL-6 and CINC (cytokine-induced neutrophil chemoattractant) appeared similarly in the exudates to cause chemoattractant for neutrophils. TNF alpha and IL-1 could stimulate to produce IL-6 and IL-8. While prostaglandins may regulate cytokine production via a cellular cAMP-dependent mechanism. Thus one should consider the time for application of anti-inflammatory drugs, such as cyclooxygenase inhibitor, indomethacin, since it causes increases in TNF alpha and IL-1 production by reducing PGI2 and prostaglandin E2 (PGE2) levels. In conclusion, inflammatory reaction has its own automatic regulation mechanism through complex cross talks between inflammatory mediators.

炎症反応に関与する炎症性メディエーターの消長と意義

Inflammatory signs, such as heat, redness, swelling and pain, have been described from the Greek era. In these phenomena various endogenous active substances, i.e., inflammatory mediators, could cause and manifest vascular dilatation, a vascular permeability increase and sensitization of pain receptors, etc. In order to evaluate the roles of inflammatory mediators, we have studied the time courses of inflammatory reaction along with detection of various active substances directly or indirectly in the experimental animal model of pleurisy, such as rat carrageenin-induced, and zymosan-induced pleurisy. These pleurisies showed almost similar time courses of pleural exudate accumulation and neutrophil migration. However, mediators detected in the exudates of such pleurisies were different; in carrageenin-induced pleurisy bradykinin and prostacyclin (PGI2) caused exudate formation, while zymosan-induced pleurisy showed early degradation of mast cells and activation of complements, followed by an increase in platelet activating factor (PAF). In both pleurisies TNF alpha, IL-1, IL-6 and CINC (cytokine-induced neutrophil chemoattractant) appeared similarly in the exudates to cause chemoattractant for neutrophils. TNF alpha and IL-1 could stimulate to produce IL-6 and IL-8. While prostaglandins may regulate cytokine production via a cellular cAMP-dependent mechanism. Thus one should consider the time for application of anti-inflammatory drugs, such as cyclooxygenase inhibitor, indomethacin, since it causes increases in TNF alpha and IL-1 production by reducing PGI2 and prostaglandin E2 (PGE2) levels. In conclusion, inflammatory reaction has its own automatic regulation mechanism through complex cross talks between inflammatory mediators.

Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors.

Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS.

代謝物をいかに微量で迅速に定量するか ハイファネイテッドＭＳ法による生体試料中の生理活性物質の高感度微量定量法 そのノウハウ

Mass spectrometry (MS) has been recognized as an integral method in biological research and our ability to analyze a wide variety of biologically relevant molecules has been greatly advanced by MS. Highly sensitive, highly selective, and reproducible hyphenated MS (GC/MS, LC/MS) or MS/MS method is necessary to get high quality information. We show that the optimization of MS interface is very important for high sensitivity. Chromatography techniques are also indispensable to distinguish identical mass substances. In addition to avoiding adsorption and contaminants problem, our optimized conditions have resulted in a suitable quantitative analysis method for endogenous biological active substances in biological materials.

The fate of circulating biologically active peptides in the lungs.

The factors which regulate the disappearance of endogenous active substances during pulmonary transit are discussed. The presence of hydrolytic enzymes in the cytosol is not the only factor regulating pulmonary metabolism. An uptake-transport process is required to permit access to intracellular enzymes. No endothelial cell transport mechanism has yet been described for peptides. However, bradykinin and angiotensin I are metabolized by the pulmonary circulation because the enzyme is localized on the luminal surface of the endothelial cells. The pulmonary and extrapulmonary conversion of angiotensin in rat is still a matter of debate. Evidence is presented which supports the idea that when low doses of angiotensin I (greater than 10 ng) are given intravenously, most of the conversion is pulmonary. With higher doses, extrapulmonary conversion also contributes to the final pressor effect of angiotensin I.

Aspects of the spasmogenic effects of acetate esters on ileal smooth muscle

Acetate esters, sush as aspirin methylester, aspirin and resorcinol monoacetate, induced contractions of guinea-pig ileum. Their actions were selectively antagonized by atropine, but were not affected by ganglion blocking agents, conduction blockers, aging with cooling, anoxia or antihistaminics. On the other hand, N-acetates, such as acetanilide and p-acetaminophenol, had no contractile action on the ileum. The acetate esters thus seemed to have a cholinergic action, and not a direct action on muscle or other known specific receptors for endogenous active substances. The contractions induced by the acetate esters were selectively potentiated by low concentrations of choline, whereas those induced by acetylcholine, nicotine, 5-hydroxytryptamine and histamine were not. However, N-acetates did not induce the contractions even in the presence of choline. Organophosphorus cholinesterase inhibitors, such as diisopropyl fluorophosphate and paraoxon, selectively and irreversibly inhibited the actions of aspirin and N,O-diacetyl-p-aminophenol with or without choline. From these results, it is concluded that the acetate esters with or without choline act through the cholinergic system. However, their actions cannot be explained in terms of known mechanisms, such as acetylcholine release, cholinesterase inhibition or a direct muscarinic action. Therefore, the acetate esters, including phenyl acetate which was supposed to be a releaser of acetylcholine, seem to have a hitherto underscribed type of cholinergic actions whose mechanism is unknown. It seems that organophosphate-sensitive esterase(s) in the preparation may be essential for initiation of the actions of the acetate esters with or without choline, but the mechanism of the effect of choline is unknown.