Cytotoxic Effect of Andrographis paniculata Associated with 2-Aminoethyl Dihydrogen Phosphate in Triple-Negative Breast Cells.

Cancer stands out as a major global public health concern and a significant impediment to increasing life expectancy worldwide. Natural bioactives derived from plants are renowned for their efficacy in treating various types of cancer. Andrographis paniculata (Burm.f.) is a well-known plant traditionally employed in diverse medical systems across the globe. The 2-AEH2P monophosphoester, a molecule intricately involved in phospholipid turnover, demonstrates antiproliferative effects across a broad spectrum of cancer types. This study aims to assess the antitumor, antiproliferative, and pharmacological effects of andrographolide at different concentrations, both individually and in conjunction with 2-aminoethyl dihydrogen phosphate. The cytotoxicity of the treatments was evaluated using the colorimetric MTT method, cell cycle phases, mitochondrial electrical potential, and markers expression via flow cytometry, while the pharmacological effects were assessed using SynergyFinder software 3.0. Treatments with A. paniculata, isolated at concentrations of 10%, 30%, and 50% of andrographolide, induced cell death in tumor cells, resulting in a reduction in mitochondrial electrical potential and alterations in cell cycle phases, particularly a decrease in the population of MDA MB-231 cells in the G0/G1 phase. The combination treatments exhibited significant cytotoxicity toward tumor cells, with minimal toxicity observed in normal fibroblast cells FN1. This led to a reduction in mitochondrial electrical potential and cell cycle arrest in the S phase for MDA MB-231 cells. Across all concentrations, the combined treatments demonstrated a synergistic pharmacological effect, underscoring the efficacy of the association. There was a change in the markers involved in cell death, such as p53, caspase 3, Bcl-2, and cytochrome c, suggesting the induction of regulated cell death. Markers associated with progression and proliferation, such as cyclin D1 and p21, corroborate the findings for cytotoxicity and cell cycle arrest.

Contemporary Techniques and Potential Transungual Drug Delivery Nanosystems for The Treatment of Onychomycosis.

The humanoid nail is considered an exceptional protective barrier that is formed mainly from keratin. Onychomycosis is the cause of 50% of nail infections that is generally caused by dermatophytes. Firstly, the infection was regarded as a cosmetic problem but because of the tenacious nature of onychomycosis and its relapses, these infections have attracted medical attention. The first line of therapy was the oral antifungal agents which were proven to be effective; nevertheless, they exhibited hepato-toxic side effects, alongside drug interactions. Following, the opportunity was shifted to the topical remedies, as onychomycosis is rather superficial, yet this route is hindered by the keratinized layers in the nail plate. A potential alternative to overcome the obstacle was applying different mechanical, physical, and chemical methods to boost the penetration of drugs through the nail plate. Unfortunately, these methods might be expensive, require an expert to be completed, or even be followed by pain or more serious side effects. Furthermore, topical formulations such as nail lacquers and patches do not provide enough sustaining effects. Recently, newer therapies such as nanovesicles, nanoparticles, and nanoemulsions have emerged for the treatment of onychomycosis that provided effective treatment with possibly no side effects. This review states the treatment strategies such as mechanical, physical, and chemical methods, and highlights various innovative dosage forms and nanosystems developed in the last 10 years with a focus on advanced findings regarding formulation systems. Furthermore, it demonstrates the natural bioactives and their formulation as nanosystems, and the most relevant clinical outcomes.

Nanovesicles from Organic Agriculture-Derived Fruits and Vegetables: Characterization and Functional Antioxidant Content.

Dietary consumption of fruits and vegetables is related to a risk reduction in a series of leading human diseases, probably due to the plants' antioxidant content. Plant-derived nanovesicles (PDNVs) have been recently receiving great attention regarding their natural ability to deliver several active biomolecules and antioxidants. To investigate the presence of active antioxidants in fruits, we preliminarily analyzed the differences between nanovesicles from either organic or conventional agriculture-derived fruits, at equal volumes, showing a higher yield of nanovesicles with a smaller size from organic agriculture-derived fruits as compared to conventional ones. PDNVs from organic agriculture also showed a higher antioxidant level compared to nanovesicles from conventional agriculture. Using the PDNVs from fruit mixes, we found comparable levels of Total Antioxidant Capacity, Ascorbic Acid, Catalase, Glutathione and Superoxide Dismutase 1. Finally, we exposed the nanovesicle mixes to either chemical or physical lytic treatments, with no evidence of effects on the number, size and antioxidant capacity of the treated nanovesicles, thus showing a marked resistance of PDNVs to external stimuli and a high capability to preserve their content. Our study provides for the first time a series of data supporting the use of plant-derived nanovesicles in human beings' daily supplementation, for both prevention and treatment of human diseases.

A natural solution for obesity: bioactives for the prevention and treatment of weight gain. A review.

OBJECTIVES: Obesity and obesity-related disorders are reaching epidemic proportions worldwide. In this review, we summarize the accumulating studies that have emerged in the last few decades demonstrating that bioactives from different natural sources could potentially have anti-obesity effects. METHODS: We carried out an extensive search of relevant literature from Pubmed, Web of Knowledge, and other online databases for studies where anti-obesity effects were shown by compounds from natural sources. RESULTS: Appetite suppression, lipid metabolism regulation, and increase of energy expenditure are the main mechanisms by which anti-obesity effects are exerted. Plants represent the most studied natural source of anti-obesity bioactives. Camellia sinensis is the most representative species exerting several anti-obesity effects. Moreover, probiotics (bacteria which bestow health benefit), such as strains of Bifidobacteria and Lactobacillus families, and certain prebiotics (non-viable food components that confers a health benefit on the host associated with modulation of the microbiota effects), such as insulin-type fructans, have also shown capability to combat obesity. Finally, compounds from animal sources, in particular bioactive peptides derived from milk-derived whey and casein protein digestion, high dietary calcium, and omega-3s polyunsaturated fatty acids (n-3 PUFA) present in fish oils, have also shown potential anti-obesity effects. DISCUSSION: Several anti-obesity effects have been observed in different natural bioactives providing an interesting and potentially safer and more desirable treatment strategy for the development of anti-obesity functional or medical foods.

Phytochemical profile, in vitro antioxidant and antibacterial activities of different extracts of an Algerian endemic: Teucrium atratum.

Teucrium atratum Pomel. is a species belonging to the Lamiaceae family used in Algerian folk medicine. The present work essentially aimed to assess the phenolic composition and to evaluate some of the biological effects of different extracts, never previously studied, of T. atratum growing in Algeria. High levels of total phenolic and flavonoids were recorded in the hydromethanolic extract. Chlorogenic acid, isoquercetin, coumarin, cinnamic acid, quercetin dihydrate, and catechin were identified in the methanolic extract by mean of HPLC. The antioxidant activity assessed showed that the methanolic extract was the most active, while, the hydromethanolic extract showed a great power to reduce iron. In addition, all extracts had a significant antibacterial effect against the four tested bacterial strains, with Staphylococcus aureus as the most sensitive one. These findings can be a starting point to evaluate the plant as a source of natural bioactive compounds with antioxidant and antibacterial effects.

Lycopene in Combination with Insulin Triggers Antioxidant Defenses and Increases the Expression of Components That Detoxify Advanced Glycation Products in Kidneys of Diabetic Rats.

BACKGROUND: Biochemical events provoked by oxidative stress and advanced glycation may be inhibited by combining natural bioactives with classic therapeutic agents, which arise as strategies to mitigate diabetic complications. The aim of this study was to investigate whether lycopene combined with a reduced insulin dose is able to control glycemia and to oppose glycoxidative stress in kidneys of diabetic rats. METHODS: Streptozotocin-induced diabetic rats were treated with 45 mg/kg lycopene + 1 U/day insulin for 30 days. The study assessed glycemia, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma. Superoxide dismutase (SOD) and catalase (CAT) activities and the protein levels of advanced glycation end-product receptor 1 (AGE-R1) and glyoxalase-1 (GLO-1) in the kidneys were also investigated. RESULTS: An effective glycemic control was achieved with lycopene plus insulin, which may be attributed to improvements in insulin sensitivity. The combined therapy decreased the dyslipidemia and increased the PON-1 activity. In the kidneys, lycopene plus insulin increased the activities of SOD and CAT and the levels of AGE-R1 and GLO-1, which may be contributing to the antialbuminuric effect. CONCLUSIONS: These findings demonstrate that lycopene may aggregate favorable effects to insulin against diabetic complications resulting from glycoxidative stress.

Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Oral Treatment with Plant-Derived Exosomes Restores Redox Balance in H2O2-Treated Mice.

Plant-derived exosomes (PDEs) are receiving much attention as a natural source of antioxidants. Previous research has shown that PDEs contain a series of bioactives and that their content varies depending on the fruit or vegetable source. It has also been shown that fruits and vegetables derived from organic agriculture produce more exosomes, are safer, free of toxic substances, and contain more bioactives. The aim of this study was to investigate the ability of orally administered mixes of PDE (Exocomplex®) to restore the physiological conditions of mice treated for two weeks with hydrogen peroxide (H2O2), compared with mice left untreated after the period of H2O2 administration and mice that received only water during the experimental period. The results showed that Exocomplex® had a high antioxidant capacity and contained a series of bioactives, including Catalase, Glutathione (GSH), Superoxide Dismutase (SOD), Ascorbic Acid, Melatonin, Phenolic compounds, and ATP. The oral administration of Exocomplex® to the H2O2-treated mice re-established redox balance with reduced serum levels of both reactive oxygen species (ROS) and malondialdehyde (MDA), but also a general recovery of the homeostatic condition at the organ level, supporting the future use of PDE for health care.

Deciphering the interaction mechanism of natural actives against larval proteins of Aedes aegypti to identify potential larvicides: a computational biology analysis.

Aedes aegypti is the target for repellents to curb incidences of vector-borne diseases. Stopping breeding of this mosquito species at its larval stages helps in controlling spread of insect-borne diseases. Therefore, the present study focused on deciphering the mechanism of interaction of selected natural actives against larval proteins of A. aegypti to identify potential natural alternative larvicides. 65 larval proteins were identified from literature, whose structures were modelled and validated using RaptorX and ProCheck. 11 natural actives were selected for predicting their ligand properties and toxicities via Toxicity Estimation Software Tool and ProTox-II. Molecular docking studies were carried out using POAP followed by 100 ns molecular dynamic simulation studies for top three best docked complexes to better understand the robustness of docking, complex stabilities and molecular mechanisms of interactions. Toxicity predictions revealed that 6 molecules belonged to toxicity class 4, and five to toxicity class 5, implying that they were all safe to use. Complexes goniothalamin-translation elongation factor (-10 kcal/mol), andrographolide-acetyl-CoA C-myristoyltransferase (-9.2 kcal/mol) and capillin-translation elongation factor (-8.4 kcal/mol) showed best binding energies. When simulated, capillin-translation elongation factor showed most stability, while the remaining two also evidenced robust docking. Evolutionary studies for top two larval proteins disclosed 100 other insect species in which these proteins can be targeted using various larvicides. Protein-protein interaction network analysis revealed several protein pathways that might be affected due to aforesaid naturals. Therefore, this study provides computational insights into the molecular interaction of naturals against larval proteins, acting as potential natural larvicides.Communicated by Ramaswamy H. Sarma.

Biopolymeric nanoparticles based effective delivery of bioactive compounds toward the sustainable development of anticancerous therapeutics.

Nowadays, effective cancer therapy is a global concern, and recent advances in nanomedicine are crucial. Cancer is one of the major fatal diseases and a leading cause of death globally. Nanotechnology provides rapidly evolving delivery systems in science for treating diseases in a site-specific manner using natural bioactive compounds, which are gaining widespread attention. Nanotechnology combined with bioactives is a very appealing and relatively new area in cancer treatment. Natural bioactive compounds have the potential to be employed as a chemotherapeutic agent in the treatment of cancer, in addition to their nutritional benefits. Alginate, pullulan, cellulose, polylactic acid, chitosan, and other biopolymers have been effectively used in the delivery of therapeutics to a specific site. Because of their biodegradability, biopolymeric nanoparticles (BNPs) have received a lot of attention in the development of new anticancer drug delivery systems. Biopolymer-based nanoparticle systems can be made in a variety of ways. These systems have developed as a cost-effective and environmentally friendly solution to boost treatment efficacy. Effective drug delivery systems with improved availability, increased selectivity, and lower toxicity are needed. Recent research findings and current knowledge on the use of BNPs in the administration of bioactive chemicals in cancer therapy are summarized in this review.

Recent development in nanoencapsulation and delivery of natural bioactives through chitosan scaffolds for various biological applications.

Nowadays, nano/micro-encapsulation as a pioneering technique may significantly improve the bioavailability and durability of Natural bioactives. For this purpose, chitosan as a bioactive cationic natural polysaccharide has been frequently used as a carrier because of its distinct chemical and biological properties, including polycationic nature, biocompatibility, and biodegradability. Moreover, polysaccharide-based nano/micro-formulations are a new and extensive trend in scientific research and development in the disciplines of biomedicine, bioorganic/ medicinal chemistry, pharmaceutics, agrochemistry, and the food industry. It promises a new paradigm in drug delivery systems and nanocarrier formulations. This review aims to summarize current developments in approaches for designing innovative chitosan micro/nano-matrix, with an emphasis on the encapsulation of natural bioactives. The special emphasis led to a detailed integrative scientific achievement of the functionalities and abilities for encapsulating natural bioactives and mechanisms regulated in vitro/in vivo release in various biological/physiological environments.

Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae.

Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.

Role of Natural Bioactives and their Nanocarriers for Overcoming Oxidative Stress Induced Cancer.

BACKGROUND: Oxidative stress and free radicals are harmful to human health. Reactive oxygen species are the major source of oxidative stress and are one of the major causes of cancer development. Cancer is one of the leading causes of death worldwide. Prolonged use of synthetic chemotherapeutic due to their low bioavailability leads to systemic toxic side effects. To surmount this problem, the use of antioxidants is recommended as they have the ability to counteract oxidative stress and mitigate its effects on human health. They inhibit various pathways that are involved with the initiation and progression of cancer. Various nanoformulations have been used to deliver these antioxidants (curcumin, mangiferin, quercetin) in the treatment of various cancer for overcoming oxidative stress. OBJECTIVE: The main focus of this review article is to illustrate various studies performed using nanocarriers of natural bioactives to overcome oxidative stress and cancer associated with it. It also describes pathways associated with the induction, initiation and progression of cancer due to reactive oxidative species. METHODS: Research articles that focused on the use of natural bioactives and their nanoformulations for the treatment of various cancers induced due to oxidative stress, were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like oxidative stress, antioxidants, cancers, ROS, etc. Conclusion: Natural bioactives have shown great potential in overcoming oxidative stress for the treatment of various cancers. However, extensive research is required so that these antioxidants and their nanocarriers can be used for the welfare of mankind, in the treatment of various cancers, in the near future.

Anthocyanin-Related Pigments: Natural Allies for Skin Health Maintenance and Protection.

Human skin is commonly described as a particularly dynamic and complex environment, with a physiological balance continuously orchestrated by numerous internal and external factors. Intrinsic aging, exposure to UV radiation and skin pathogens are some of the key players that account for dermatological alterations and ailments. In this regard, this study intended to explore the potential skin-health beneficial properties of a group of molecules belonging to the anthocyanin family: cyanidin- and malvidin-3-O-glucosides and some of their structurally related pigments, resulting in a library of compounds with different structural properties and color hues. The inclusion of both purified compounds and crude extracts provided some insights into their distinctive effects when tested as individual agents or as part of multicomponent mixtures. Overall, most of the compounds were found to reduce biofilm production by S. aureus and P. aeruginosa reference strains, exhibit UV-filter capacity, attenuate the production of reactive oxygen species in human skin keratinocytes and fibroblasts and also showed inhibitory activity of skin-degrading enzymes, in the absence of cytotoxic effects. Carboxypyranocyanidin-3-O-glucoside stood out for its global performance which, combined with its greater structural stability, makes this a particular interesting compound for potential incorporation in topical formulations. Results provide strong evidence of the skin protective effects of these pigments, supporting their further application for cosmeceutical purposes.

Exploring safe and potent bioactives for the treatment of non-small cell lung cancer.

Activating and suppressing mutations in the MAPK pathway receptors are the primary causes of NSCLC. Of note, MEK inhibition is considered a promising strategy because of the diverse structures and harmful effects of upstream receptors in MAPK pathway. Thus, we explore a total of 1574 plant-based bioactive compounds activity against MEK using an energy-based virtual screening strategy. Molecular docking, binding free energy, and drug-likeness analysis were performed through GLIDE, Prime MM-GBSA, and QikProp module, respectively. The findings indicate that 5-O-caffeoylshikimic acid has an increased binding affinity to MEK protein. Further, molecular dynamic simulations and MM-PBSA analysis were performed to explore the ligand activity in real-life situations. In essence, compounds inhibitory activity was validated across 77 lung cancer cell lines using multimodal attention-based neural network algorithm. Eventually, our analysis highlight that 5-O-caffeoylshikimic acid obtained from the bark of Rhizoma smilacis glabrae would be developed as a potential compound for treating NSCLC.

The inhibitory effect of natural bioactives on the growth of pathogenic bacteria.

The objective of this study was to evaluate the inhibitory activity of natural products, against growth of Escherichia coli (ATCC 25922) and Salmonella typhimurium (KCCM 11862). Chitosan, epigallocatechin gallate (EGCG), and garlic were used as natural bioactives for antibacterial activity. The testing method was carried out according to the disk diffusion method. All of chitosan, EGCG, and garlic showed inhibitory effect against the growth of E. coli and Salmonella typhi. To evaluate the antibacterial activity of natural products during storage, chicken skins were inoculated with 10(6) of E. coli or Salmonella typhi. The inoculated chicken skins, treated with 0.5, 1, or 2% natural bioactives, were stored during 8 day at 4. The numbers of microorganisms were measured at 8 day. Both chitosan and EGCG showed significant decrease in the number of E. coli and Salmonella typhi in dose dependent manner (P < 0.05). These results suggest that natural bioactives such as chitosan, EGCG may be possible to be used as antimicrobial agents for the improvement of food safety.