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Monica Butnariu,1 Cristina Quispe,2 Niranjan Koirala,3,4 Sujan Khadka,5,6 Carla Marina Salgado-Castillo,7 Muhammad Akram,8 Rabia Anum,9 Balakyz Yeskaliyeva,10 Natália Cruz-Martins,11– 14 Miquel Martorell,15,16 Manoj Kumar,17 Radu Vasile Bagiu,18,19 Ahmad Faizal Abdull Razis,20,21 Usman Sunusi,21,22 Ramla Muhammad Kamal,21,23 Javad Sharifi-Rad7 1Chemistry & Biochemistry Discipline, University of Life Sciences “King Mihai I” from Timisoara, 300645, Calea Aradului 119, Timis, Romania; 2Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, 1110939, Chile; 3Department of Natural Products Research, Dr. Koirala Research Institute for Biotechnology and Biodiversity, Kathmandu, 44600, Nepal; 4Laboratory of Biotechnology, Faculty of Science and Technology, University of Macau, Macau SAR, 999078, People’s Republic of China; 5University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 6State Key Laboratory of Environmental Aquatic Chemistry” with “State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, People’s Republic of China; 7Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador; 8Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan; 9SINA Health, Education and Welfare Trust, Karachi, Pakistan; 10Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty, Kazakhstan; 11Faculty of Medicine, University of Porto, Porto, Portugal; 12Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal; 13Institute of Research and Advanced Training in Health Sciences and Technologies (CESPU), Gandra PRD, 4585-116, Portugal; 14TOXRUN-Oxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, Gandra, 4585-116, Portugal; 15Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, 4070386, Chile; 16Universidad de Concepción, Unidad de Desarrollo Tecnológico, UDT, Concepción, 4070386, Chile; 17Chemical and BioChemical Processing Division, ICAR – Central Institute for Research on Cotton Technology, Mumbai, 400019, India; 18Victor Babes University of Medicine and Pharmacy of Timisoara Department of Microbiology, Timisoara, Romania; 19Preventive Medicine Study Center, Timisoara, Romania; 20Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; 21Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; 22Department of Biochemistry, Bayero University Kano, Kano, Nigeria; 23Department of Pharmacology, Federal University Dutse, Dutse, Jigawa State, NigeriaCorrespondence: Natália Cruz-Martins; Ahmad Faizal Abdull Razis, Email ncmartins@med.up.pt; madfaizal@upm.edu.myAbstract: 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.Keywords: curcumin, bioactivities, HIV therapy, nanoparticles, nanoformulations

Allergic diseases (ADs) are a major concern when it comes to public well-being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4-( α -L-rhamnopyranosyloxy)-benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha-cyclodextrin-moringin ( α -CD/MG) complex on rat basophilic leukaemia (RBL-2H3) cell line at both the early and late stages of an allergic reaction. The α -CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α -CD/MG. The release of beta-hexosaminidase ( β -hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor-alpha (TNF- α ), and interleukin (IL-4) was considered in the late stage. Higher concentrations of α -CD/MG (5  μ M, p < 0.001) in mast cell degranulation significantly inhibited the expression of β -hexosaminidase, histamine, TNF- α , PGD2, and IL-4 in both the early and late stages. Thus, α -CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Ebtisam Yousef A. Alnakeeb et al.)

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 (LC 50 ) 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 (LD 50 ) using adult zebrafish and (4) to screen the metabolites profile of adulterated honey from blood serum of adult zebrafish. The result indicated the LC 50 of 31.10 ± 1.63 (mg/ml) for pure A. mellifera honey, while acetic acid demonstrates the lowest LC 50 (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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The present research examined patulin's presence across the whole supply chain of selected fruits. A comprehensive analysis was conducted on 442 samples of fruits (oranges, apples, apricots, lemons, and guava) to determine the presence of patulin contamination. This analysis used Liquid Chromatography (HPLC) with a UV detector. The findings indicate that 17, 23, and 28 % of selected fruit samples tested positive for patulin levels in farm, transportation, and market samples. However, the sample collected during the transportation step showed that 56 % (percentage of positive samples) of fruits have patulin levels greater than 50 μg/kg, and 41 % (percentage of positive samples) have greater levels than 50 μg/kg in market samples. The findings of the one-way analysis of variance indicated that no statistically significant variation existed between the amounts of patulin across the various stages of the food supply chain system (p > 0.05). Nevertheless, the analysis of the correlation study, namely Kendall's tau&#95;b and Spearman's rho, denote a robust association between the levels of patulin and the food supply system. The apple samples exhibited the most significant average dietary intake of patulin, with an average value of 0.11 μg/kg bw/day. The maximum mean hazard quotient (HQ) of 0.28 was also recorded. The prevalence and incidence of patulin in specific fruits were found to be relatively high, and it was observed that market samples had elevated levels of patulin in the selected fruits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peña-Corona, Hernández-Parra, Bernal-Chávez, Mendoza-Muñoz, Romero-Montero, Del Prado-Audelo, Cortés, Ateşşahin, Habtemariam, Almarhoon, Abdull Razis, Modu, Sharifi-Rad and Leyva-Gómez.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chaudhary, Janmeda, Docea, Yeskaliyeva, Abdull Razis, Modu, Calina and Sharifi-Rad.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hafeez, Khan, Armaghan, Khan, Sönmez Gürer, Abdull Razis, Modu, Almarhoon, Setzer and Sharifi-Rad.)

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 1 H and 13 C 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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pires, Reis, Cardoso, Pezzani, Paredes-Osses, Seilkhan, Ydyrys, Martorell, Sönmez Gürer, Setzer, Abdull Razis, Modu, Calina and Sharifi-Rad.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Islam, Martorell, González-Contreras, Villagran, Mardones, Tynybekov, Docea, Abdull Razis, Modu, Calina and Sharifi-Rad.)

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 (LD 50 ) 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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).

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., Competing Interests: Author SC’N was employed by company CAIQTEST Malaysia Sdn. Bhd. The authors declare that this study received funding from MyPower Biotech Sdn. Bhd. (Malaysia). The funder was involved in the study, related to the development of value-added health products from tropical fruits., (Copyright © 2022 Mohd Israfi, Mohd Ali, Manickam, Sun, Goh, Tang, Ismail, Abdull Razis, Ch’ng and Chan.)

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., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

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.

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.

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.

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.

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.

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.

Chicken is known to be the most common meat type involved in food mislabeling and adulteration. Establishing a method to authenticate chicken content precisely and identifying chicken breeds as declared in processed food is crucial for protecting consumers' rights. Categorizing the authentication method into their respective omics disciplines, such as genomics, transcriptomics, proteomics, lipidomics, metabolomics, and glycomics, and the implementation of bioinformatics or chemometrics in data analysis can assist the researcher in improving the currently available techniques. Designing a vast range of instruments and analytical methods at the molecular level is vital for overcoming the technical drawback in discriminating chicken from other species and even within its breed. This review aims to provide insight and highlight previous and current approaches suitable for countering different circumstances in chicken authentication.

Microplastics (MPs) have become pollutants of concern due to their unknown human health effect and negative impact on terrestrial and aquatic ecosystems. There is increasing number of experimental research on MPs globally with its effects not fully understood; recent animal studies explore its effects on the intestines, yet on other vital organs. Javanese medaka fish was exposed to polystyrene microplastics (PS-MPs) beads for a period of 21 days. Histological alterations, intestinal oxidative stress, permeability and neurotoxicity were evaluated. Significant inflammatory changes and tissue damage were observed in the intestine, liver and kidney. Intestinal oxidative stress and permeability were found to be significantly increased. In the brain, neurotoxicity characterised by a significant induction of oxidative stress, lipid peroxidation and the inhibition of acetylcholinesterase enzyme were elucidated. This study provided an insight into the multiple organ effect of microplastics exposure, necessitating further exploration and identification of biomarkers to be utilised for biomonitoring population at risk in the future.

Resveratrol is a polyphenolic stilbene derivative widely present in grapes and red wine. Broadly known for its antioxidant effects, numerous studies have also indicated that it exerts anti-inflammatory and antiaging abilities and a great potential in cancer therapy. Regrettably, the oral administration of resveratrol has pharmacokinetic and physicochemical limitations such as hampering its effects so that effective administration methods are demanding to ensure its efficiency. Thus, the present review explores the published data on the application of resveratrol nanoformulations in cancer therapy, with the use of different types of nanodelivery systems. Mechanisms of action with a potential use in cancer therapy, negative effects, and the influence of resveratrol nanoformulations in different types of cancer are also highlighted. Finally, the toxicological features of nanoresveratrol are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sharifi-Rad, Quispe, Mukazhanova, Knut, Turgumbayeva, Kipchakbayeva, Seitimova, Mahomoodally, Lobine, Koay, Wang, Sheridan, Leyva-Gómez, Prado-Audelo, Cortes, Rescigno, Zucca, Sytar, Imran, Rodrigues, Cruz-Martins, Ekiert, Kumar, Abdull Razis, Sunusi, Kamal and Szopa.)

The recent COVID-19, a viral outbreak calls for a high demand for non-conventional antiviral agents that can reduce the risk of infections and promote fast recovery. Fermented foods and their probiotics bacteria have recently received increasing interest due to the reported potential of high antiviral activity. Several probiotics strains demonstrated broad range of antiviral activities and different mechanisms of action. This article will review the diversity, health benefits, interaction with immune system and antiviral activity of fermented foods and their probiotics bacteria. In addition, the mechanisms of action will be reviewed to determine the broad range potential antiviral activity against the respiratory and alimentary tracts viruses. The probiotics bacteria and bioactive compounds in fermented foods demonstrated antiviral activities against respiratory and alimentary tracts viruses. The mechanism of action was reported to be due to the stimulation of the immune system function via enhancing natural killers cell toxicity, enhance the production of pro-inflammatory cytokines, and increasing the cytotoxic of T lymphocytes (CD3 + , CD16 + , CD56 + ). However, further studies are highly recommended to determine the potential antiviral activity for traditional fermented foods., (© 2021 Elsevier Ltd. All rights reserved.)

Aflatoxins (AFs) are secondary metabolites toxic to humans as well as animals. The environmental conditions, conventional agricultural practices, and illiteracy are the main factors which favor the production of AFs in food and feed. In the current study 744 samples of vegetable seeds and oils (soybean, sunflower, canola, olive, corn, and mustard) were collected and tested for the presence of aflatoxin B 1 (AFB 1 ) and total AFs. Liquid-liquid extraction was employed for the extraction of AFs from seeds and oil samples. Reverse phase high performance liquid chromatography equipped with fluorescence detection was used for the analysis. The results have shown that 92 (56.7%) samples of imported and 108 (57.0%) samples of local edible seeds were observed to be contaminated with AFs. All samples of edible seeds have AFB 1 levels greater than the proposed limit set by the European Union (EU, 2 µg/kg) and 12 (7.40%) samples of imported seeds and 14 (7.40%) samples of local seeds were found in the range ≥ 50 µg/kg. About 78 (43.3%) samples of imported edible oil and 103 (48.3%) sample of local edible oil were observed to be positive for AFs. Furthermore, 16 (8.88%) and six (3.33%) samples of imported vegetable oil have levels of total AFs in a range (21-50 µg/kg) and greater than 50 µg/kg, respectively. The findings indicate significant differences in AFs levels between imported and local vegetable oil samples (t = 22.27 and p = 0.009) at α = 0.05 and a significant difference in AFs levels were found between vegetable seeds and oil samples (t = -17.75, p = 0.009) at α = 0.05. The highest dietary intake was found for a local sunflower oil sample (0.90 µg/kg/day) in female individuals (16-22 age group). The results have shown considerably high levels of AFB1 and total AFs in seeds and oil samples and emphasise the need to monitor carefully the levels of these toxic substances in food and feed on regular basis.

Nowadays, the high demand for village chickens in Malaysia leads to the fraudulent substitution of indigenous chickens with other cheaper counterparts. Discriminating different chicken breeds based on their phenotypic characteristics is one strategy to avoid chicken adulteration. The main objective of this study was to authenticate and group dominant chicken breeds in Malaysia, including commercial chickens (Cobb, Hubbard, DeKalb) and cross-bred village chickens (Ayam Kampung, Akar Putra). The further discrimination of village chickens from underaged colored broilers (UCBs) (Hubbard, Sasso) was performed based on phenotype traits. The results showed that the breed had a significant effect ( p < 0.05) on phenotypic characteristics, while the sex effect was not significant for some characteristics. In the first phase, the most remarkable discriminating factors were abdominal fat weight, breast muscle weight, chest circumference, shank length, and wingspan. However, in the second phase, notable variations in phenotypic characteristics between village chickens and UCBs were not detected. Principal component analysis (PCA) showed the successful separation of village chickens from high-performance breeds (broiler and colored broiler). Nevertheless, there was overlap among observations for Sasso and village chickens, which approved the possible similarities in their phenotypic characteristics. This study showed clear breed clustering, which leads to the chicken authentication based on their phenotypic characteristics.

Rice is a worldwide staple food and heavy metal contamination is often reported in rice production. Heavy metal can originate from natural sources or be present through anthropogenic contamination. Therefore, this review summarizes the current status of heavy metal contamination in paddy soil and plants, highlighting the mechanism of uptake, bioaccumulation, and health risk assessment. A scoping search employing Google Scholar, Science Direct, Research Gate, Scopus, and Wiley Online was carried out to build up the review using the following keywords: heavy metals, absorption, translocation, accumulation, uptake, biotransformation, rice, and human risk with no restrictions being placed on the year of study. Cadmium (Cd), arsenic (As), and lead (Pb) have been identified as the most prevalent metals in rice cultivation. Mining and irrigation activities are primary sources, but chemical fertilizer and pesticide usage also contribute to heavy metal contamination of paddy soil worldwide. Further to their adverse effect on the paddy ecosystem by reducing the soil fertility and grain yield, heavy metal contamination represents a risk to human health. An in-depth discussion is further offered on health risk assessments by quantitative measurement to identify potential risk towards heavy metal exposure via rice consumption, which consisted of in vitro digestion models through a vital ingestion portion of rice.

Momordica species (Family Cucurbitaceae) are cultivated throughout the world for their edible fruits, leaves, shoots and seeds. Among the species of the genus Momordica, there are three selected species that are used as vegetable, and for medicinal purposes, Momordica charantia L (Bitter melon), Momordica foetida Schumach (Bitter cucumber) and Momordica balsamina L (African pumpkin). The fruits and leaves of these Momordica species are rich in primary and secondary metabolites such as proteins, fibers, minerals (calcium, iron, magnesium, zinc), β -carotene, foliate, ascorbic acid, among others. The extracts from Momordica species are used for the treatment of a variety of diseases and ailments in traditional medicine. Momordica species extracts are reputed to possess anti-diabetic, anti-microbial, anthelmintic bioactivity, abortifacient, anti-bacterial, anti-viral, and play chemo-preventive functions. In this review we summarize the biochemical, nutritional, and medicinal values of three Momordica species ( M. charantia , M. foetida and M. balsamina ) as promising and innovative sources of natural bioactive compounds for future pharmaceutical usage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muronga, Quispe, Tshikhudo, Msagati, Mudau, Martorell, Salehi, Abdull Razis, Sunusi, Kamal and Sharifi-Rad.)

Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa . The pharmacological studies reported in vitro , in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N . sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Salehi, Quispe, Imran, Ul-Haq, Živković, Abu-Reidah, Sen, Taheri, Acharya, Azadi, del Mar Contreras, Segura-Carretero, Mnayer, Sethi, Martorell, Abdull Razis, Sunusi, Kamal, Rasul Suleria and Sharifi-Rad.)

This study investigated the natural incidence of deoxynivalenol (DON) in corn and corn products from corn-producing districts of Punjab, Pakistan. The analysis was carried out using high performance liquid chromatography (HPLC) with UV detector and immunoaffinity cleanup columns. The detection limit (LOD) and limit of quantification were 25 and 50 µg/kg, respectively. A total of 1220 samples of corn and corn products were analyzed to detect DON, and 539 (44.2%) samples were observed to be contaminated with DON ( n ≥ LOD). Furthermore, 92 (7.5%) samples of corn and corn products had DON levels that were higher than the proposed limits of the EU. The data are significantly different from a normal distribution of DON in samples of corn and corn products from different locations ( p < 0.05) for Shapiro-Wilk and Kolmogorov-Smirnov values. However, a significant difference in DON levels was found between corn and corn-derived products ( p ≤ 0.05). The lowest and highest exposures, and hazard quotient (HQ) values of 0.92 and 9.68 µg/kg bw/day, were documented in corn flour samples.

In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer's health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic selection, feeding strategies, housing, and environmental strategies, as well as hormone supplementation. Recent investigations at the molecular level have revealed the significant role of the transcriptional and post-transcriptional regulatory networks and their interaction on modulating fat metabolism in chickens. At the transcriptional level, different transcription factors are known to regulate the expression of lipogenic and adipogenic genes through various signaling pathways, affecting chicken fat metabolism. Alternatively, at the post-transcriptional level, the regulatory mechanism of microRNAs (miRNAs) on lipid metabolism and deposition has added a promising dimension to understand the structural and functional regulatory mechanism of lipid metabolism in chicken. Therefore, this review focuses on the progress made in unraveling the molecular function of genes, transcription factors, and more notably significant miRNAs responsible for regulating adipogenesis, lipogenesis, and fat deposition in chicken. Moreover, a better understanding of the molecular regulation of lipid metabolism will give researchers novel insights to use functional molecular markers, such as miRNAs, for selection against excessive fat deposition to improve chicken production efficiency and meat quality.

Cancer is a multifactorial disease characterized by complex molecular landscape and altered cell pathways that results in an abnormal cell growth. Natural compounds are target-specific and pose a limited cytotoxicity; therefore, can aid in the development of new therapeutic interventions for the treatment of this versatile disease. Berberine is a member of the protoberberine alkaloids family, mainly present in the root, stem, and bark of various trees, and has a reputed anticancer activity. Nonetheless, the limited bioavailability and low absorption rate are the two major hindrances following berberine administration as only 0.5% of ingested berberine absorbed in small intestine while this percentage is further decreased to 0.35%, when enter in systemic circulation. Nano-based formulation is believed to be an ideal candidate to increase absorption percentage as at nano scale level, compounds can absorb rapidly in gut. Nanotechnology-based therapeutic approaches have been implemented to overcome such problems, ultimately promoting a higher efficacy in the treatment of a plethora of diseases. This review present and critically discusses the anti-proliferative role of berberine and the nanotechnology-based therapeutic strategies used for the nano-scale delivery of berberine. Finally, the current approaches and promising perspectives of latest delivery of this alkaloid are also critically analyzed and discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Javed Iqbal, Quispe, Javed, Sadia, Qadri, Raza, Salehi, Cruz-Martins, Abdulwanis Mohamed, Sani Jaafaru, Abdull Razis and Sharifi-Rad.)

Technological advances, coupled with increasing demands by consumers, have led to a drastic increase in plastic production. After serving their purposes, these plastics reach our water bodies as their destination and become ingested by aquatic organisms. This ubiquitous phenomenon has exposed humans to microplastics mostly through the consumption of sea food. This has led the World Health Organization (WHO) to make an urgent call for the assessment of environmental pollution due to microplastics and its effect on human health. This review summarizes studies between 1999 and 2020 in relation to microplastics in aquatic ecosystems and human food products, their potential toxic effects as elicited in animal studies, and policies on their use and disposal. There is a paucity of information on the toxicity mechanisms of microplastics in animal studies, and despite their documented presence in food products, no policy has been in place so far, to monitor and regulates microplastics in commercial foods meant for human consumption. Although there are policies and regulations with respect to plastics, these are only in a few countries and in most instances are not fully implemented due to socioeconomic reasons, so they do not address the problem across the entire life cycle of plastics from production to disposal. More animal research to elucidate pathways and early biomarkers of microplastic toxicity that can easily be detected in humans is needed. This is to create awareness and influence policies that will address this neglected threat to food safety and security.

Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H 2 O 2 -induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H 2 O 2 -induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.

Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p &lt; 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.

NoveLin I and NoveLin II are palm-based oils. NoveLin I has an equal distribution of saturated, monounsaturated and polyunsaturated fatty acids, whereas NoveLin II has a moderate level of monounsaturated fatty acids, and a lower content of saturated and polyunsaturated fatty acids. However, their hypocholesterolaemic and anti-atherogenic effects have not been studied. Therefore, this study aimed to assess the hypocholesterolaemic and anti-atherogenic effects of these oils. Forty male New Zealand White rabbits were divided into four groups and fed with diets containing 35% energy fat with added 0.15% (w/w) dietary cholesterol. Group 1, as the control group (CNO) was fed with a diet containing coconut oil, group 2 and 3 were fed with diets containing either NoveLin I or NoveLin II, and group 4, was fed with diet containing olive oil (OLV) for 100 days. Our results demonstrated that both NoveLin groups have significantly lower total cholesterol and low-density lipoprotein-cholesterol (LDL-C) compared to CNO group and are comparable to the OLV group. Low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL/HDL-C) ratio was significantly lower after the NoveLin II diet but attained significance only in comparison to NoveLin I and CNO groups. Aortic fibrous plaque score was significantly lower in both NoveLin groups compared to CNO group. Our findings suggest that despite the high-fat cholesterol diet, NoveLin II oil resulted in atherogenic effects comparable to olive oil.

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC 50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-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 GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G 2 /M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.

Neurodegenerative diseases (NDDs) are pathological conditions characterised by progressive damage of neuronal cells leading to eventual loss of structure and function of the cells. Due to implication of multi-systemic complexities of signalling pathways in NDDs, the causes and preventive mechanisms are not clearly delineated. The study was designed to investigate the potential signalling pathways involved in neuroprotective activities of purely isolated glucomoringin isothiocyanate (GMG-ITC) against H 2 O 2 -induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. GMG-ITC was isolated from Moringa oleifera seeds, and confirmed with NMR and LC-MS based methods. Gene expression analysis of phase II detoxifying markers revealed significant increase in the expression of all the genes involved, due to GMG-ITC pre-treatment. GMG-ITC also caused significant decreased in the expression of NF-kB, BACE1, APP and increased the expressions of IkB and MAPT tau genes in the differentiated cells as confirmed by multiplex genetic system analysis. The effect was reflected on the expressed proteins in the differentiated cells, where GMG-ITC caused increased in expression level of Nrf2, SOD-1, NQO1, p52 and c-Rel of nuclear factor erythroid factor 2 (Nrf2) and nuclear factor kappa-B (NF-kB) pathways respectively. The findings revealed the potential of GMG-ITC to abrogate oxidative stress-induced neurodegeneration through Nrf2 and NF-kB signalling pathways., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rice ingestion is one of the major pathways for heavy metal bioaccumulation in human. This study aimed to measure the heavy metal content of paddy soils and its bioavailability in paddy grain in order to assess the health risk. In total, 10 rice samples (50 g each) of paddy plants were harvested from the Selangor and Terengganu areas of Malaysia to assess the bioavailability of heavy metal (As, Cd, Cu, Cr, and Pb) using the in vitro digestion model of Rijksinstituut voor Volksgezondheid en Milieu. The bioavailability of heavy metal concentrations in rice samples were analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The findings showed the bioavailability of heavy metal concentrations was decreased in the order Cr > Cu > Pb > As > Cd. Chromium was found to be the most abundant bioavailable heavy metal in cooked rice, which was the result of its high content in paddy soil. Hazard Quotient values for the bioavailability of the heavy metal studied were less than one indicating no non-carcinogenic health risks for adults and children. Meanwhile, the total Lifetime Cancer Risk exceeded the acceptable value showing a potential of carcinogenic health risk for both adults and children. The application of in vitro digestion model in assessing bioavailability of heavy metal produces a more realistic estimation of human health risks exposure. However, a regular monitoring of pollution in Selangor and Terengganu areas is crucial since the exposure of heavy metals through rice consumption poses the potential non-carcinogenic and carcinogenic health risk to the local residents.

The antioxidant and neuroprotective activity of Glucomoringin isothiocyanate (GMG-ITC) have been reported in in vivo and in vitro models of neurodegenerative diseases. However, its neuroprotective role via mitochondrial-dependent pathway in a noxious environment remains unknown. The main objective of the present study was to unveil the mitochondrial apoptotic genes' profile and prospectively link with neuroprotective activity of GMG-ITC through its ROS scavenging. The results showed that pre-treatment of differentiated SH-SY5Y cells with 1.25 μg/mL purified isolated GMG-ITC, significantly reduced reactive oxygen species (ROS) production level, compared to H 2 O 2 control group, as evidenced by flow cytometry-based evaluation of ROS generation. Presence of GMG-ITC prior to development of oxidative stress condition, downregulated the expression of cyt-c, p53, Apaf-1, Bax, CASP3, CASP8 and CASP9 genes with concurrent upregulation of Bcl-2 gene in mitochondrial apoptotic signalling pathway. Protein Multiplex revealed significant decreased in cyt-c, p53, Apaf-1, Bax, CASP8 and CASP9 due to GMG-ITC pre-treatment in oxidative stress condition. The present findings speculated that pre-treatment with GMG-ITC may alleviate oxidative stress condition in neuronal cells by reducing ROS production level and protect the cells against apoptosis via neurodegenerative disease potential pathways., (Copyright © 2019. Published by Elsevier Masson SAS.)

Plant natural compounds have great potential as alternative medicines for preventing and treating diseases. Melicope lunu-ankenda is one Melicope species (family Rutaceae ), which is widely used in traditional medicine, consumed as a salad and a food seasoning. Consumption of different parts of this plant has been reported to exert different biological activities such as antioxidant and anti-inflammatory qualities, resulting in a protective effect against several health disorders including neurodegenerative diseases. Various secondary metabolites such as phenolic acid derivatives, flavonoids, coumarins and alkaloids, isolated from the M. lunu-ankenda plant, were demonstrated to have neuroprotective activities and also exert many other beneficial biological effects. A number of studies have revealed different neuroprotective mechanisms for these secondary metabolites. This review summarizes the most significant and recent studies for neuroprotective activity of M. lunu-ankenda major secondary metabolites in neurodegenerative diseases.

Glucoraphasatin (GRH), a glucosinolate present abundantly in the plants of the Brassicaceae family, is hydrolyzed by myrosinase to raphasatin, which is considered responsible for its cancer chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aims of this study are to determine the cytotoxicity of raphasatin, and to evaluate its potential to cause apoptosis and modulate cell cycle arrest in human breast adenocarcinoma MCF-7 cells. The cytotoxicity was determined following incubation of the cells with glucoraphasatin or raphasatin (0⁻100 µM), for 24, 48, and 72 h. GRH displayed no cytotoxicity as exemplified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. When myrosinase was added to the incubation system to convert GRH to raphasatin, cytotoxicity was evident. Exposure of the cells to raphasatin stimulated apoptosis, as was exemplified by cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Moreover, using Annexin V-FITC assay, raphasatin induced apoptosis, as witnessed by changes in cellular distribution of cells, at different stages of apoptosis; in addition, raphasatin caused the arrest of the MCF-7 cells at the G₂ + M phase. In conclusion, raphasatin demonstrated cancer chemopreventive potential against human breast adenocarcinoma (MCF-7) cells, through induction of apoptosis and cell cycle arrest.

Natural antioxidants in spices and herbs have attracted considerable attention as potential inhibitors against the formation of mutagenic heterocyclic amines (HCAs) in heat-processed meat. In this study, the inhibitory activity of four spices/herbs and their mixtures on HCAs formation in grilled beef were examined. A simplex centroid mixture design with four components comprising turmeric, curry leaf, torch ginger and lemon grass in 19 different proportions were applied on beef samples before grilling at 240 ºC for 10 min. The HCAs were extracted from the samples using solid phase extraction (SPE) method and analysed using Liquid chromatography mass spectrometry LC-MS/MS. All spices/herbs in single or mixture forms were found to reduce total HCA concentrations in marinated grilled beef ranging from 21.2% for beef marinated with curry leaf to 94.7% for the combination of turmeric and lemon grass (50:50 w/w). At the optimum marinade formula (turmeric: lemon grass 52.4%: 47.6%), concentration of 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), Harman, Norharman and AαC were 2.2, 1.4, 0.5, 2.8 and 1.2 ng/g, respectively. The results of the mutagenic activity demonstrated that this optimised marinade formula significantly (p < 0.05) diminished mutagenicity of marinated grilled beef in bacterial Ames test.

The potential of isothiocyanates to antagonize the carcinogenicity of structurally diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S-transferase, epoxide hydrolase, and UDP-glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increases the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to upregulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)