Kinetin stimulates differentiation of C2C12 myoblasts

Kinetin or N6-furfuryladenine (K) belongs to a class of plant hormones called cytokinins, which are biologically active molecules modulating many aspects of plant growth and development. However, biological activities of cytokinins are not only limited to plants; their effects on animals have been widely reported in the literature. Here, we found that Kinetin is a potent small molecule that efficiently stimulates differentiation of C2C12 myoblasts into myotubes in vitro. The highest efficacy was achieved at 1μM and 10μM Kinetin concentrations, in both mitogen-poor and rich media. More importantly, Kinetin was able to strongly stimulate the MyoD-dependent conversion of fibroblasts into myotubes. Kinetin alone did not give rise to fibroblast conversion and required MyoD; this demonstrates that Kinetin augments the molecular repertoire of necessary key regulatory factors to facilitate MyoD-mediated myogenic differentiation. This novel Kinetin pro-myogenic function may be explained by its ability to alter intracellular calcium levels and by its potential to impact on Reactive Oxygen Species (ROS) signalling. Taken together, our findings unravel the effects of a new class of small molecules with potent pro-myogenic activities. This opens up new therapeutic avenues with potential for treating skeletal muscle diseases related to muscle aging and wasting.

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Metabolomics of Healthy Berry Fruits

Current Medicinal Chemistry ◽

10.2174/0929867323666161206100006 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4888-4902 ◽

Cited By ~ 3

Author(s):

Gilda D'Urso ◽

Sonia Piacente ◽

Cosimo Pizza ◽

Paola Montoro

Keyword(s):

Biological Activities ◽

Biologically Active ◽

In Vivo Studies ◽

Bioactive Metabolites ◽

Active Metabolites ◽

Positive Effects ◽

Cell Functions ◽

Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

Current Medicinal Chemistry ◽

10.2174/0929867325666180508090640 ◽

2019 ◽

Vol 26 (30) ◽

pp. 5609-5624

Author(s):

Dijana Saftić ◽

Željka Ban ◽

Josipa Matić ◽

Lidija-Marija Tumirv ◽

Ivo Piantanida

Keyword(s):

Molecular Weight ◽

Small Molecules ◽

Biomedical Applications ◽

Protein Targets ◽

New Class ◽

Rna Targets ◽

Covalently Linked ◽

Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

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Preservation of immunological and biological activities of insulin by insulinase inhibitor in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y70-048 ◽

1970 ◽

Vol 48 (5) ◽

pp. 291-298

Author(s):

J. Pierluissi ◽

J. Campbell ◽

K. S. Rastogi ◽

G. R. Green ◽

V. Lazdins

Keyword(s):

Biological Effect ◽

Biological Activities ◽

Biologically Active ◽

Immunoreactive Insulin ◽

Maximal Velocity ◽

Appreciable Change ◽

Glycogen Accumulation ◽

Fractional Rate ◽

Diaphragm In Vitro

The relation of insulinase activity to the biological effect of insulin on isolated tissue was studied. Rat diaphragm in vitro caused the rapid disappearance of immunoreactive insulin (IRI) in physiological concentrations. IRI loss at time intervals was exponential. The fractional rate of loss of IRI was therefore independent of IRI concentration and was also approximately constant per milligram of tissue, the value being 0.0216%/mg∙mm. The value of the Michaelis constant (Km), obtained from initial velocities at five initial concentrations of IRI, was 1.85 × 10−8M, and of the maximal velocity (Vmax) was 2.32 × 10−11 mole/g∙min, based on insulin dimer. The addition of an insulinase inhibitor (a partial hydrolysate of insulin) to hemidiaphragm in vitro reduced the fractional rate of IRI loss by 60%. The increase in Km, without appreciable change in Vmax, indicated that the inhibition was competitive. The IRI preserved by means of the inhibitor was biologically active, since it increased the glycogen accumulation and the incorporation of 14C-U-glucose into glycogen in a second, fresh hemidiaphragm. In single incubation of hemidiaphragm with insulin, the gain in glycogen was correlated with the amount of inhibitor. The biological effect of insulin on diaphragm in vitro was therefore limited by tissue insulinase activity, and insulinase inhibitor potentiated to some extent the action of insulin.

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Phytochemical Characterization and Evaluation of Biological Activities of Egyptian Carob Pods (Ceratonia siliqua L.) Aqueous Extract: In Vitro Study

Plants ◽

10.3390/plants10122626 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2626

Author(s):

Wael Sobhy Darwish ◽

Abada El Sayed Khadr ◽

Maher Abd El Naby Kamel ◽

Mabrouk A. Abd Eldaim ◽

Ibrahim El Tantawy El Sayed ◽

...

Keyword(s):

Aqueous Extract ◽

Biological Activities ◽

Radical Scavenging ◽

Antimicrobial Activities ◽

Biologically Active ◽

Phytochemical Analysis ◽

Type I ◽

Hypotonic Solution ◽

Ceratonia Siliqua

Ceratonia siliqua (Carob) is an evergreen Mediterranean tree, and carob pods are potentially nutritive and have medicinal value. The present study was carried out to estimate the possible biological activities of phytochemical-characterized carob pod aqueous extract (CPAE). The phytochemical contents of CPAE were determined by using colorimetric methods and HPLC. In addition, the free radical scavenging properties and anti-diabetic, anti-hemolytic, and antimicrobial activities were estimated by using standardized in vitro protocols. The phytochemical analysis revealed that CPAE was rich in polyphenols, flavonoids, and alkaloids, where it contained a significant amount of gallic acid, catechin, and protocatechuic acid. Furthermore, CPAE exhibited strong antioxidant activity where it prevented the formation of 2, 2-Diphenyl-1-picryl hydrazyl, hydroxyl, and nitric oxide free radicals. Additionally, it had a potent inhibitory effect against digestive enzymes (amylase, maltase, sucrase, and lactase). Moreover, CPAE exhibited anti-Staph aureus, anti-Escherichia coli, anti-Candida albicans, and anti-herpes simplex type I virus (HSV-I). Finally, CPAE protected the erythrocyte membrane from hypotonic solution-induced hemolysis. Altogether, CPAE could be regarded as an interesting source of biologically active antioxidant, anti-diabetic, and antimicrobial preparation for a potential application in pharmaceutical and food supplement fields.

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Cell-Permeable, Small-Molecule Activators of the Insulin-Degrading Enzyme

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057112451921 ◽

2012 ◽

Vol 17 (10) ◽

pp. 1348-1361 ◽

Cited By ~ 8

Author(s):

Sayali S. Kukday ◽

Surya P. Manandhar ◽

Marissa C. Ludley ◽

Mary E. Burriss ◽

Benjamin J. Alper ◽

...

Keyword(s):

Small Molecules ◽

Biologically Active ◽

Small Peptides ◽

Insulin Degrading Enzyme ◽

Potential Therapeutic Target ◽

Aβ Peptides ◽

Degrading Enzyme ◽

Enzyme Substrate ◽

A Cell

The insulin-degrading enzyme (IDE) cleaves numerous small peptides, including biologically active hormones and disease-related peptides. The propensity of IDE to degrade neurotoxic Aβ peptides marks IDE as a potential therapeutic target for Alzheimer disease. Using a synthetic reporter based on the yeast a-factor mating pheromone precursor, which is cleaved by multiple IDE orthologs, we identified seven small molecules that stimulate rat IDE activity in vitro. Half-maximal activation of IDE by the compounds is observed in vitro in the range of 43 to 198 µM. All compounds decrease the Km of IDE. Four compounds activate IDE in the presence of the competing substrate insulin, which disproportionately inhibits IDE activity. Two compounds stimulate rat IDE activity in a cell-based assay, indicating that they are cell permeable. The compounds demonstrate specificity for rat IDE since they do not enhance the activities of IDE orthologs, including human IDE, and they appear specific for a-factor–based reporters since they do not enhance rat IDE-mediated cleavage of Aβ-based reporters. Our results suggest that IDE activators function in the context of specific enzyme-substrate pairs, indicating that the choice of substrate must be considered in addition to target validation in IDE activator screens.

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Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study

Molecules ◽

10.3390/molecules23123266 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3266 ◽

Cited By ~ 38

Author(s):

Gokhan Zengin ◽

Luigi Menghini ◽

Antonella Di Sotto ◽

Romina Mancinelli ◽

Francesca Sisto ◽

...

Keyword(s):

Essential Oil ◽

Galleria Mellonella ◽

Cannabis Sativa ◽

Biological Activities ◽

Methodological Approach ◽

Volatile Component ◽

Biologically Active ◽

Antioxidant Compounds

Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.

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Phytochemicals and cancer

Proceedings of The Nutrition Society ◽

10.1017/s0029665107005459 ◽

2007 ◽

Vol 66 (2) ◽

pp. 207-215 ◽

Cited By ~ 108

Author(s):

Ian T. Johnson

Keyword(s):

Fruits And Vegetables ◽

Biological Activities ◽

Human Subjects ◽

Biological Effects ◽

Plant Secondary Metabolites ◽

Biologically Active ◽

Carcinogenic Activity ◽

Plant Foods ◽

Carcinogenic Effects

Epidemiological studies showing a protective effect of diets rich in fruits and vegetables against cancer have focused attention on the possibility that biologically-active plant secondary metabolites exert anti-carcinogenic activity. This huge group of compounds, now collectively termed ‘phytochemicals’, provides much of the flavour and colour of edible plants and the beverages derived from them. Many of these compounds also exert anti-carcinogenic effects in animal models of cancer, and much progress has been made in defining their many biological activities at the molecular level. Such mechanisms include the detoxification and enhanced excretion of carcinogens, the suppression of inflammatory processes such as cyclooxygenase-2 expression, inhibition of mitosis and the induction of apoptosis at various stages in the progression and promotion of cancer. However, much of the research on phytochemicals has been conducted in vitro, with little regard to the bioavailability and metabolism of the compounds studied. Many phytochemicals present in plant foods are poorly absorbed by human subjects, and this fraction usually undergoes metabolism and rapid excretion. Some compounds that do exert anti-carcinogenic effects at realistic doses may contribute to the putative benefits of plant foods such as berries, brassica vegetables and tea, but further research with human subjects is required to fully confirm and quantify such benefits. Chemoprevention using pharmacological doses of isolated compounds, or the development of ‘customised’ vegetables, may prove valuable but such strategies require a full risk–benefit analysis based on a thorough understanding of the long-term biological effects of what are often surprisingly active compounds.

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Sapogenol is a Major Microbial Metabolite in Human Plasma Associated with High Protein Soy-Based Diets: The Relevance for Functional Food Formulations

Foods ◽

10.3390/foods9040422 ◽

2020 ◽

Vol 9 (4) ◽

pp. 422

Author(s):

Madalina Neacsu ◽

Vassilios Raikos ◽

Yara Benavides-Paz ◽

Sylvia H. Duncan ◽

Gary J. Duncan ◽

...

Keyword(s):

Functional Foods ◽

Biological Activities ◽

Epidemiological Studies ◽

High Protein ◽

Biologically Active ◽

Soya Meal ◽

Human Volunteers ◽

Faecal Samples ◽

Health Promoting

Legumes are a source of health-promoting macro- and micronutrients, but also contain numerous phytochemicals with useful biological activities, an example of which are saponins. Epidemiological studies suggest that saponins may play a role in protection from cancer and benefit human health by lowering cholesterol. Therefore, they could represent good candidates for specialised functional foods. Following the consumption of a soya-rich high-protein weight-loss diet (SOYA HP WL), the concentrations of Soyasaponin I (SSI) and soyasapogenol B (SSB) were determined in faecal samples from human volunteers (n = 10) and found to be between 1.4 and 17.5 mg per 100 g fresh faecal sample. SSB was the major metabolite identified in volunteers’ plasma (n = 10) after consumption of the soya test meal (SOYA MEAL); the postprandial (3 h after meal) plasma concentration for SSB varied between 48.5 ng/mL to 103.2 ng/mL. The metabolism of SSI by the gut microbiota (in vitro) was also confirmed. This study shows that the main systemic metabolites of soyasaponin are absorbed from the gut and that they are bioavailable in plasma predominantly as conjugates of sapogenol. The metabolism and bioavailability of biologically active molecules represent key information necessary for the efficient development of functional foods.

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Oxytocin analogues with amide groups substituted by tetrazole groups in position 4, 5 or 9.

Acta Biochimica Polonica ◽

10.18388/abp.2007_3169 ◽

2007 ◽

Vol 54 (4) ◽

pp. 805-811 ◽

Cited By ~ 4

Author(s):

Michał Manturewicz ◽

Zbigniew Grzonka ◽

Lenka Borovicková ◽

Jirina Slaninová

Keyword(s):

Amino Acids ◽

Solid Phase ◽

Biological Activities ◽

Synthesis Method ◽

Oxytocin Receptor ◽

Amide Group ◽

Biologically Active ◽

Side Chain ◽

Electronic Effects

Eleven oxytocin analogues substituted in position 4, 5 or 9 by tetrazole analogues of amino acids were prepared using solid-phase peptide synthesis method and tested for rat uterotonic in vitro and pressor activities, as well as for their affinity to human oxytocin receptor. The tetrazolic group has been used as a bioisosteric substitution of carboxylic, ester or amide groups in structure-activity relationship studies of biologically active compounds. Replacement of the amide groups of Gln(4) and Asn(5) in oxytocin by tetrazole analogues of aspartic, glutamic and alpha-aminoadipic acids containing the tetrazole moiety in the side chains leads to analogues with decreased biological activities. Oxytocin analogues in which the glycine amide residue in position 9 was substituted by tetrazole analogues of glycine had diminished activities as well. The analysis of differences in rat uterotonic activity and in the affinity to human oxytocin receptors of analogues containing either an acidic 5-substituted tetrazolic group or a neutral 1,5- or 2,5-tetrazole nucleus makes it possible to draw some new conclusions concerning the role of the amide group of amino acids in positions 4, 5 and 9 of oxytocin for its activity. The data suggest that the interaction of the side chain of Gln(4) with the oxytocin receptor is influenced mainly by electronic effects and the hydrogen bonding capacity of the amide group. Steric effects of the side chain are minor. Substitution of Asn(5) by its tetrazole derivative gave an analogue of very low activity. The result suggests that in the interaction between the amide group of Asn(5) and the binding sites of oxytocic receptor hydrogen bonds are of less importance than the spatial requirements for this group.

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Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation

PLoS ONE ◽

10.1371/journal.pone.0244791 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244791

Author(s):

Wan-Huai Teo ◽

Jeng-Fan Lo ◽

Yu-Ning Fan ◽

Chih-Yang Huang ◽

Tung-Fu Huang

Keyword(s):

Myogenic Differentiation ◽

Atp Synthesis ◽

C2c12 Cells ◽

Myoblast Differentiation ◽

C2c12 Myoblast ◽

Muscle Loss ◽

C2c12 Myoblasts ◽

Immunomodulatory Protein ◽

Pre Treatment

Ageing and chronic diseases lead to muscle loss and impair the regeneration of skeletal muscle. Thus, it’s crucial to seek for effective intervention to improve the muscle regeneration. Tid1, a mitochondrial co-chaperone, is important to maintain mitochondrial membrane potential and ATP synthesis. Previously, we demonstrated that mice with skeletal muscular specific Tid1 deficiency displayed muscular dystrophy and postnatal lethality. Tid1 can interact with STAT3 protein, which also plays an important role during myogenesis. In this study, we used GMI, immunomodulatory protein of Ganoderma microsporum, as an inducer in C2C12 myoblast differentiation. We observed that GMI pretreatment promoted the myogenic differentiation of C2C12 myoblasts. We also showed that the upregulation of mitochondria protein Tid1 with the GMI pre-treatment promoted myogenic differentiation ability of C2C12 cells. Strikingly, we observed the concomitant elevation of STAT3 acetylation (Ac-STAT3) during C2C12 myogenesis. Our study suggests that GMI promotes the myogenic differentiation through the activation of Tid1 and Ac-STAT3.

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