Development of a zebrafish model for toxicity evaluation of adulterated Apis mellifera honey.

Since ancient times, honey has been used for medical purposes and the treatment of various disorders. As a high-quality food product, the honey industry is prone to fraud and adulteration. Moreover, limited experimental studies have investigated the impact of adulterated honey consumption using zebrafish as the animal model. The aims of this study were: (1) to calculate the lethal concentration (LC50) of acid-adulterated Apis mellifera honey on embryos, (2) to investigate the effect of pure and acid-adulterated A. mellifera honey on hatching rate (%) and heart rate of zebrafish (embryos and larvae), (3) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish and (4) to screen the metabolites profile of adulterated honey from blood serum of adult zebrafish. The result indicated the LC50 of 31.10 ± 1.63 (mg/ml) for pure A. mellifera honey, while acetic acid demonstrates the lowest LC50 (4.98 ± 0.06 mg/ml) among acid adulterants with the highest mortality rate at 96 hpf. The treatment of zebrafish embryos with adulterated A. mellifera honey significantly (p ≤ 0.05) increased the hatching rate (%) and decreased the heartbeat rate. Acute, prolong-acute, and sub-acute toxicology tests on adult zebrafish were conducted at a concentration of 7% w/w of acid adulterants. Furthermore, the blood serum metabolite profile of adulterated-honey-treated zebrafish was screened by LC-MS/MS analysis and three endogenous metabolites have been revealed: (1) Xanthotoxol or 8-Hydroxypsoralen, (2) 16-Oxoandrostenediol, and (3) 3,5-Dicaffeoyl-4-succinoylquinic acid. These results prove that employed honey adulterants cause mortality that contributes to higher toxicity. Moreover, this study introduces the zebrafish toxicity test as a new promising standard technique for the potential toxicity assessment of acid-adulterated honey in this study and hazardous food adulterants for future studies.

Neopeltolide and its synthetic derivatives: a promising new class of anticancer agents.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases.

Introduction: Free radicals are reactive oxygen species that constantly circulate through the body and occur as a side effect of many reactions that take place in the human body. Under normal conditions, they are removed from the body by antioxidant processes. If these natural mechanisms are disrupted, radicals accumulate in excess and contribute to the development of many diseases. Methodology: Relevant recent information on oxidative stress, free radicals, reactive oxidative species, and natural and synthetic antioxidants was collected by researching electronic databases such as PubMed / Medline, Web of Science, and Science Direct. Results: According to the analysed studies, this comprehensive review provided a recent update on oxidative stress, free radicals and antioxidants and their impact on the pathophysiology of human diseases. Discussion: To counteract the condition of oxidative stress, synthetic antioxidants must be provided from external sources to supplement the antioxidant defense mechanism internally. Because of their therapeutic potential and natural origin, medicinal plants have been reported as the main source of natural antioxidants phytocompounds. Some non-enzymatic phytocompounds such as flavonoids, polyphenols, and glutathione, along with some vitamins have been reported to possess strong antioxidant activities in vivo and in vitro studies. Thus, the present review describes, in brief, the overview of oxidative stress-directed cellular damage and the unction of dietary antioxidants in the management of different diseases. The therapeutic limitations in correlating the antioxidant activity of foods to human health were also discussed.

Exploring the therapeutic and anti-tumor properties of morusin: a review of recent advances.

Morusin is a natural product that has been isolated from the bark of Morus alba, a species of mulberry tree. It belongs to the flavonoid family of chemicals, which is abundantly present in the plant world and is recognized for its wide range of biological activities. Morusin has a number of biological characteristics, including anti-inflammatory, anti-microbial, neuro-protective, and antioxidant capabilities. Morusin has exhibited anti-tumor properties in many different forms of cancer, including breast, prostate, gastric, hepatocarcinoma, glioblastoma, and pancreatic cancer. Potential of morusin as an alternative treatment method for resistant malignancies needs to be explored in animal models in order to move toward clinical trials. In the recent years several novel findings regarding the therapeutic potential of morusin have been made. This aim of this review is to provide an overview of the present understanding of morusin's beneficial effects on human health as well as provide a comprehensive and up-to-date discussion of morusin's anti-cancer properties with a special focus on in vitro and in vivo studies. This review will aid future research on the creation of polyphenolic medicines in the prenylflavone family, for the management and treatment of cancers.

Phytates as a natural source for health promotion: A critical evaluation of clinical trials.

Phytates are a type of organophosphorus compound produced in terrestrial ecosystems by plants. In plant feeds, phytic acid and its salt form, phytate, account for 60%-80% of total phosphorus. Because phytate is a polyanionic molecule, it can chelate positively charged cations such as calcium, iron, and zinc. Due to its prevalence in vegetal tissues and the fact that people consume plants, phytate was first considered a potential health benefit. This updated review aims to summarize the current data on the results of clinical trials of phytates on human health, highlighting both beneficial and undesirable effects. To obtain these updated data, published papers in electronic databases such as PubMed/MedLine, TRIP database, Wiley, Google Scholar, Baidu, and Scopus were searched. Study results have shown that phytate can have beneficial health effects such as antioxidant, anticancer potential and reduction of pathological calcifications in blood vessels and organs; but also, negative effects by reducing the absorption of minerals important for maintaining the homeostasis of the human body. According to these recent results derived from recent clinical studies, phytates may be a potential natural source for health benefits. To improve clinical efficacy and human health benefits, further dose-response studies are needed to determine effective therapeutic doses and potential interactions with conventional drugs.

An updated overview of anticancer effects of alternariol and its derivatives: underlying molecular mechanisms.

Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti-inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms.

Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.

Apoptotic Potential of Glucomoringin Isothiocyanate (GMG-ITC) Isolated from Moringa oleifera Lam Seeds on Human Prostate Cancer Cells (PC-3).

Inhibition of several protein pathways involved in cancer cell regulation is a necessary key in the discovery of cancer chemotherapy. Moringa oleifera Lam is often used in traditional medicine for the treatment of various illnesses. The plant contains glucomoringin isothiocyanate (GMG-ITC) with therapeutic potential against various cancer cells. Therefore, GMG-ITC was evaluated for its cytotoxicity against the PC-3 prostate cancer cell line and its potential to induce apoptosis. GMG-ITC inhibited cell proliferation in the PC-3 cell line with IC50 value 3.5 µg/mL. Morphological changes as a result of GMG-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GMG-ITC in a time-dependent manner. Moreover, GMG-ITC induced a time-dependent G2/M phase arrest, with reduction of 39.1% in the PC-3 cell line. GMG-ITC also activates apoptotic genes including caspase, tumor suppressor gene (p53), Akt/MAPK, and Bax of the proapoptotic Bcl family. Early apoptosis proteins (JNK, Bad, Bcl2, and p53) were significantly upregulated upon GMG-ITC treatment. It is concluded that apoptosis induction was observed in PC-3 cells treated with GMG-ITC. These phenomena suggest that GMG-ITC from M. oleifera seeds could be useful as a future cytotoxic agent against prostate cancer.

7-Geranyloxycinnamic Acid Isolated from Melicope lunu-ankenda Leaves Perturbs Colon Cancer and Breast Cancer Cell Lines' Growth via Induction of Apoptotic Pathway.

Globally, breast cancer is the most prevalent form of cancer in women and there is a need for alternative therapies such as plant-derived compounds with low systemic toxicity and selective toxicity to cancer cells. The aim of this study is to assess the cytotoxicity effects of 7-geranyloxycinnamic acid isolated from leaves of Melicope lunu-ankenda, a traditional medicinal plant, on the human breast cancer cell lines. Dried leaf powder was used for the preparation of different crude extracts using different solvents of increasing order of polarity. The structure of the isolated compound from the petroleum ether extract was elucidated by 1H and 13C NMR, LC-MS, and DIP-MS spectroscopy. The cytotoxic activity of the crude extract and 7-geranyloxycinnamic acid analyzed using MTT assay. Apoptotic analysis was evaluated using Annexin V-PI staining, AO/PI staining, intracellular ROS measurement, and measurement of activities of caspases 3/7, 8, and 9. Crude extracts and the isolated pure compound showed significant cytotoxicity against tested cancer cell lines. 7-geranyloxycinnamic acid was found to exert significant cytotoxic effects against breast cancer cell lines such as the MCF-7 and MDA-MB-231 cell lines. The cytotoxic effects are attributed to its ability to induce apoptosis via accumulation of ROS and activation of caspases in both breast cancer cell lines. The pure compound, 7-geranyloxycinnamic acid isolated from the leaves of M. lunu-ankenda, can exert significant cytotoxic effects against breast cancer cell lines without affecting the normal cells.

A pilot study of toxicological safety evaluation in acute and subacute (28-day) oral assessments of kenaf seed beverage in rats.

Kenaf (Hibiscus cannabinus L.) seed is a non-conventional edible oilseed that can be valorized into various food products. There is a recent discovery of kenaf seed beverage (KSB) potential as a novel plant-based beverage. KSB had less crude protein than soybean (SB)but more carbohydrate, magnesium, and phosphorus contents.Levels of crude fat, phytates, oxalates, total saponins, and lipid peroxidability in KSB were lower than SB. Sugar content between KSB and SB were comparable, while antioxidant properties of KSB were superior. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis detected gluconic acid, citric acid, palmitic acid, oleic acid, and 13-hydroxyoctadecadienoic acid in both KSB and SB. Considering its novelty, acute and subacute oral toxicity assessments in male Sprague Dawley rats were conducted. The acute toxicity assessment was performed at a single dose of 9.2 ml/kg body weight of KSB. In the following subacute toxicity assessment, different groups of rats consumed different doses of KSB (3.1, 6.1, and 9.2 ml/kg body weight) daily for 28 days. Rats presented normal behavioral and physiological states in both toxicity studies. Growth, food and water intakes, organ weight, and hematological parameters were unaffected. No mortality was reported. Several alterations in serum biochemical parameters were within the normal range, and unassociated with histopathological changes. The oral lethal dose (LD50) and the no-observed-adverse-effect-level (NOAEL) of KSB in rats was greater than 9.2 ml/kg (=1533 mg/kg) body weight. Interestingly, KSB exhibited comparable effects with soybean beverage (SB) on high-density lipoprotein cholesterol and triglycerides which worth further research Follow-up toxicity assessments in animals and human trials are also recommended to ascertain its long term safety.

Utilizing Nutritional and Polyphenolic Compounds in Underutilized Plant Seeds for Health Application.

Plants represent a significant part of the human diet. Humans have utilized every part of plants for survival, and seeds are no exception. Seeds offer high protein, unsaturated fats, fibre, essential vitamins, and minerals for various food applications. They are also a promising reservoir of bioactive compounds, where various phytochemicals, such as polyphenolic compounds, capable of maintaining and improving well-being, are present in abundant quantities. Plants from Malvaceae and Cannabaceae families are known for their fibre-rich stems that benefit humankind by serving numerous purposes. For many centuries they have been exploited extensively for various commercial and industrial uses. Their seeds, which are often regarded as a by-product of fibre processing, have been scientifically discovered to have an essential role in combating hypercholesterolemia, diabetes, cancer, and oxidative stress. Maximizing the use of these agricultural wastes can be a promising approach to creating a more sustainable world, in accordance with the concept of Sustainable Development Goals (SDGs).

Essential oils and plant extracts for tropical fruits protection: From farm to table.

The tropical fruit industry in Malaysia makes up a large proportion of the agriculture sector, contributing to the local economy. Due to their high sugar and water content, tropical fruits are prone to pathogenic infections, providing optimal microorganism growth conditions. As one of the largest exporters of these fruits globally, following other Southeast Asian countries such as Thailand, Indonesia and the Philippines, the quality control of exported goods is of great interest to farmers and entrepreneurs. Traditional methods of managing diseases in fruits depend on chemical pesticides, which have attracted much negative perception due to their questionable safety. Therefore, the use of natural products as organic pesticides has been considered a generally safer alternative. The extracts of aromatic plants, known as essential oils or plant extracts, have garnered much interest, especially in Asian regions, due to their historical use in traditional medicine. In addition, the presence of antimicrobial compounds further advocates the assessment of these extracts for use in crop disease prevention and control. Herein, we reviewed the current developments and understanding of the use of essential oils and plant extracts in crop disease management, mainly focusing on tropical fruits. Studies reviewed suggest that essential oils and plant extracts can be effective at preventing fungal and bacterial infections, as well as controlling crop disease progression at the pre and postharvest stages of the tropical fruit supply chain. Positive results from edible coatings and as juice preservatives formulated with essential oils and plant extracts also point towards the potential for commercial use in the industry as more chemically safe and environmentally friendly biopesticides.

Bioactive Effects of Curcumin in Human Immunodeficiency Virus Infection Along with the Most Effective Isolation Techniques and Type of Nanoformulations.

Human immunodeficiency virus (HIV) is one of the leading causes of death worldwide, with African countries being the worst affected by this deadly virus. Curcumin (CUR) is a Curcuma longa-derived polyphenol that has attracted the attention of researchers due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory and antiviral effects. CUR also demonstrates anti-HIV effects by acting as a possible inhibitor of gp120 binding, integrase, protease, and topoisomerase II activities, besides also exerting a protective action against HIV-associated diseases. However, its effectiveness is limited due to its poor water solubility, rapid metabolism, and systemic elimination. Nanoformulations have been shown to be useful to enhance curcumin's bioavailability and its effectiveness as an anti-HIV agent. In this sense, bioactive effects of CUR in HIV infection are carefully reviewed, along with the most effective isolation techniques and type of nanoformulations available.

Theragnostic Applications of Mammal and Plant-Derived Extracellular Vesicles: Latest Findings, Current Technologies, and Prospects.

The way cells communicate is not fully understood. However, it is well-known that extracellular vesicles (EVs) are involved. Researchers initially thought that EVs were used by cells to remove cellular waste. It is now clear that EVs function as signaling molecules released by cells to communicate with one another, carrying a cargo representing the mother cell. Furthermore, these EVs can be found in all biological fluids, making them the perfect non-invasive diagnostic tool, as their cargo causes functional changes in the cells upon receiving, unlike synthetic drug carriers. EVs last longer in circulation and instigate minor immune responses, making them the perfect drug carrier. This review sheds light on the latest development in EVs isolation, characterization and, application as therapeutic cargo, novel drug loading techniques, and diagnostic tools. We also address the advancement in plant-derived EVs, their characteristics, and applications; since plant-derived EVs only recently gained focus, we listed the latest findings. Although there is much more to learn about, EV is a wide field of research; what scientists have discovered so far is fascinating. This paper is suitable for those new to the field seeking to understand EVs and those already familiar with it but wanting to review the latest findings.

A Review on Tradescantia: Phytochemical Constituents, Biological Activities and Health-Promoting Effects.

Tradescantia is a genus of herbaceous and perennial plants belonging to the Commelinaceae family and organized into three infrageneric classifications and 12 sections. More than 80 species within the genus have been used for centuries for medicinal purposes. Phytochemical compounds (from various species of the genus) such as coumarins, alkaloids, saponins, flavonoids, phenolics, tannins, steroids and terpenoids have recently been characterized and described with antioxidant, cytotoxic, anti-inflammatory, anticancer or antimicrobial properties. The objective of this review is to describe the different aspects of the genus Tradescantia, including its botanical characteristics, traditional uses, phytochemical composition, biological activities, and safety aspects.

The Burden of Microplastics Pollution and Contending Policies and Regulations.

The relationship between humans and plastics has become intricate due to their versatile nature and low production cost. Plastics generation has surpassed that of other manufactured products, which, coupled with the prevailing poor waste management systems, makes it a serious problem for the terrestrial and aquatic environments as its final destination. Their extensive presence has continued to pose a significant threat, not only to the aquatic ecosystem but also to the approximately 3 billion people relying on it for their livelihood. Even more disturbing were the recent findings of these plastics in food and drinking water and the evidence of human exposure, the long-term health effects of which are largely unknown. This ubiquitous phenomenon has over time put plastics under critical observation, leading to the development of many local and international policies, resolutions, and directives aimed at addressing and reversing the menace. This review provided the first snapshot of the global and local governance strategies currently aimed at mitigating plastic pollution, their limitations, and future directions. The findings of the review revealed several aspects of microplastics (MPs) pollution to be overlooked in policy formulation, a laxity in policy implementation, and an apparent lack of indices to ascertain the impact of the regulations. Furthermore, there is currently no regulation on MPs contamination of food and drinking water and an apparent lack of funding for research into the health effects of plastics and their alternatives. This, therefore, necessitates the need for a well-coordinated approach at international and national levels to scale up these policies in all countries and translate them from paper to measurable, holistic, and realizable actions that will address all forms of plastic pollution.

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases.

Neurodegenerative diseases (NDDs) and cardiovascular diseases (CVDs) are illnesses that affect the nervous system and heart, all of which are vital to the human body. To maintain health of the human body, vegetable diets serve as a preventive approach and particularly Brassica vegetables have been associated with lower risks of chronic diseases, especially NDDs and CVDs. Interestingly, glucosinolates (GLs) and isothiocyanates (ITCs) are phytochemicals that are mostly found in the Cruciferae family and they have been largely documented as antioxidants contributing to both cardio- and neuroprotective effects. The hydrolytic breakdown of GLs into ITCs such as sulforaphane (SFN), phenylethyl ITC (PEITC), moringin (MG), erucin (ER), and allyl ITC (AITC) has been recognized to exert significant effects with regards to cardio- and neuroprotection. From past in vivo and/or in vitro studies, those phytochemicals have displayed the ability to mitigate the adverse effects of reactive oxidation species (ROS), inflammation, and apoptosis, which are the primary causes of CVDs and NDDs. This review focuses on the protective effects of those GL-derived ITCs, featuring their beneficial effects and the mechanisms behind those effects in CVDs and NDDs.

Quantitative Analysis and Human Health Risk Assessment of Heavy Metals in Paddy Plants Collected from Perak, Malaysia.

Rice is one of the major crops as well as the staple food in Malaysia. However, historical mining activity has raised a concern regarding heavy metal contamination in paddy plants, especially in Perak, a state with major tin mining during the late nineteenth century. Therefore, the objective of this study is to investigate the heavy metals (As, Cd, Pb, Cu, Cr) contamination in paddy soils and paddy plants in three districts in Perak. The content of heavy metals was determined using ICP-MS, while the absorption and transferability of heavy metals in the paddy plants were investigated through enrichment (EF) and translocation (TF) factors. Principal component analysis (PCA) was employed to recognize the pattern of heavy metal contaminations in different sampling areas. Health risk assessment was performed through calculation of various indices. The quantification results showed that root contained highest concentration of the studied heavy metals, with As exhibiting the highest concentration. The EF results revealed the accumulation of As, Cu, and Cr in the rice grains while PCA showed the different compositional pattern in the different sampling areas. The health risk assessment disclosed both noncarcinogenic and carcinogenic risks in the local adults and children. Overall, findings from this study show that heavy metal contamination poses potential health risks to the residents and control measure is required.

Bioaccessibility of Polycyclic Aromatic Hydrocarbons (PAHs) in Grilled Meat: The Effects of Meat Doneness and Fat Content.

Exposure to polycyclic aromatic hydrocarbons (PAHs) through diet is gaining concern due to the risk it poses to human health. This study evaluated the bioaccessibility of PAHs contained in charcoal-grilled beef and chicken in different segments of the gastrointestinal tract (GIT) with regard to the degree of doneness and fat content of the meats. The levels of 15 PAHs in the grilled meat samples and bioaccessible fractions were determined using high-performance liquid chromatography (HPLC) equipped with PAH column, and UV and fluorescence detectors. Total PAHs were found in beef (30.73 ng/g) and chicken (70.93 ng/g) before its digestion, and different PAHs' bioaccessibility were observed in the different segments of GIT, with the highest in the stomach followed by the small intestine, despite the relatively higher bioaccessibility of individual PAHs in grilled beef as compared to those in grilled chicken. Additionally, the PAHs' bioaccessibility increased with the increase in the degree of doneness. Positive linear correlation was observed for the PAHs' bioaccessibility and the fat contents of grilled meat. Overall, this study highlights the influence of meat doneness (cooking time) and fat contents on the bioaccessibility and bioaccumulation of PAHs.

Heavy Metal Contamination in Oryza sativa L. at the Eastern Region of Malaysia and Its Risk Assessment.

Paddy plants tend to accumulate heavy metals from both natural and anthropogenic sources, and this poses adverse risks to human health. The objective of this study was to investigate heavy metal contamination in paddy plants in Kelantan, Malaysia, and its health risk assessment. The bioaccumulation of heavy metals was studied by means of enrichment (EF) and translocation factors (TF). The health risk assessment was performed based on USEPA guidelines. The EF for heavy metals in the studied areas was in the descending order of Cu > As > Cr > Cd > Pb. Meanwhile, Cr and Pb exhibited higher TF values from stem to grain compared with the others. The combined hazard index (HI) resulting from five heavy metals exceeded the acceptable limit (HI >1). The lifetime cancer risk, in both adult and children, was beyond the acceptable limit (10-4) and mainly resulted from exposure. The total cancer risk (CRt) due to simultaneous exposures to multiple carcinogenic elements also exceeded 10-4. In conclusion, intake of heavy metal through rice ingestion is likely to cause both non-carcinogenic and carcinogenic health risks. Further research is required to investigate the extent of heavy metal contamination in agricultural soils and, moreover, to establish human exposure as a result of rice consumption.