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  1. Khodavandi A, Alizadeh F, Razis AFA
    Eur J Nutr, 2021 Jun;60(4):1707-1736.
    PMID: 32661683 DOI: 10.1007/s00394-020-02332-y
    PURPOSE: It is unclear how dietary intake influences the ovarian cancer. The present paper sets out to systematically review and meta-analyze research on dietary intake to identify cases having high- or low-risk ovarian cancer.

    METHODS: Scopus, PubMed, and Wiley Online Libraries were searched up to the date November 24, 2019. Two reviewers were requested to independently extract study characteristics and to assess the bias and applicability risks with reference to the study inclusion criteria. Meta-analyses were performed to specify the relationship between dietary intake and the risk of ovarian cancer identifying 97 cohort studies.

    RESULTS: No significant association was found between dietary intake and risk of ovarian cancer. The results of subgroup analyses indicated that green leafy vegetables (RR = 0.91, 95%, 0.85-0.98), allium vegetables (RR = 0.79, 95% CI 0.64-0.96), fiber (RR = 0.89, 95% CI 0.81-0.98), flavonoids (RR = 0.83, 95% CI 0.78-0.89) and green tea (RR = 0.61, 95% CI 0.49-0.76) intake could significantly reduce ovarian cancer risk. Total fat (RR = 1.10, 95% CI 1.02-1.18), saturated fat (RR = 1.11, 95% CI 1.01-1.22), saturated fatty acid (RR = 1.19, 95% CI 1.04-1.36), cholesterol (RR = 1.13, 95% CI 1.04-1.22) and retinol (RR = 1.14, 95% CI 1.00-1.30) intake could significantly increase ovarian cancer risk. In addition, acrylamide, nitrate, water disinfectants and polychlorinated biphenyls were significantly associated with an increased risk of ovarian cancer.

    CONCLUSION: These results could support recommendations to green leafy vegetables, allium vegetables, fiber, flavonoids and green tea intake for ovarian cancer prevention.

  2. Fakhlaei R, Selamat J, Razis AFA, Sukor R, Ahmad S, Amani Babadi A, et al.
    Molecules, 2021 Oct 15;26(20).
    PMID: 34684803 DOI: 10.3390/molecules26206222
    Honey is prone to be adulterated through mixing with sugars, cheap and low-quality honey, and other adulterants. Consumption of adulterated honey may cause several health issues such as weight gain, diabetes, and liver and kidney dysfunction. Therefore, studying the impact of consumption of adulterated honey on consumers is critical since there is a lack of study in this field. Hence, the aims of this paper were: (1) to determine the lethal concentration (LC50) of adulterated honey using zebrafish embryo, (2) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish, (3) to determine the effects of adulterated honey on histological changes of zebrafish, and (4) to screen the metabolites profile of adulterated honey by using zebrafish blood serum. The LC50 of Heterotrigona itama honey (acacia honey) and its sugar adulterants (light corn sugar, cane sugar, inverted sugar, and palm sugar in the proportion of 1-3% (w/w) from the total volume) was determined by the toxicological assessment of honey samples on zebrafish embryos (different exposure concentrations in 24, 48, 72, and 96 h postfertilization (hpf)). Pure H. itama honey represents the LC50 of 34.40 ± 1.84 (mg/mL) at 96 hpf, while the inverted sugar represents the lowest LC50 (5.03 ± 0.92 mg/mL) among sugar adulterants. The highest concentration (3%) of sugar adulterants were used to study the toxicology of adulterated honey using adult zebrafish in terms of acute, prolong-acute, and sub-acute tests. The results of the LD50 from the sub-acute toxicity test of pure H. itama honey was 2.33 ± 0.24 (mg/mL). The histological studies of internal organs showed a lesion in the liver, kidney, and spleen of adulterated treated-honey groups compared to the control group. Furthermore, the LC-MS/MS results revealed three endogenous metabolites in both the pure and adulterated honey treated groups, as follows: (1) S-Cysteinosuccinic acid, (2) 2,3-Diphosphoglyceric acid, and (3) Cysteinyl-Tyrosine. The results of this study demonstrated that adulterated honey caused mortality, which contributes to higher toxicity, and also suggested that the zebrafish toxicity test could be a standard method for assessing the potential toxicity of other hazardous food additives. The information gained from this research will permit an evaluation of the potential risk associated with the consumption of adulterated compared to pure honey.
  3. Usman S, Razis AFA, Shaari K, Azmai MNA, Saad MZ, Isa NM, et al.
    Toxicol Rep, 2022;9:1369-1379.
    PMID: 36518379 DOI: 10.1016/j.toxrep.2022.05.001
    Microplastics (MPs) have become emerging pollutants of public health concern, due to their impact on aqua-terrestrial ecosystems and integration into the food web, with evidence of human exposure and unrevealed health implications. There is a paucity of information regarding the effects of MPs exposure on the gut system using metagenomic and metabolomic approaches. In this study, Javanese medaka fish was exposed to 5 µm beads of polystyrene microplastics (PS-MPs) suspensions, at concentrations of 100 μg/L (MP-LOW), 500 μg/L (MP-MED), and 1000 μg/L (MP-HIGH), for a duration of 21 days, and evaluated for gut microbiome and metabolome responses. The results revealed a significant reduction (p < 0.05) in richness and diversity of the gut microbiome in the MP-HIGH group, and identification of 7 bacterial genera as differential features by the Linear discriminant analysis Effect Size (LEfSe). The gut metabolic profile revealed upregulation of 9 metabolites related to energy metabolism, via tricarboxylic acid cycle (TCA), creatine pathway, and urea cycle, as determined by the pathway analysis. Furthermore, positive correlation was found between the genus Aeromonas and glucose, lactate, and creatine metabolites. The study revealed that PS-MPs exposure resulted in altered bacterial microbiome and metabolic disorder related to energy metabolism. It further provided additional data on gut bacterial genera and metabolites associated with MPs toxicity in aquatic organism, which will inevitably enable its future health risks assessment in animals and possibly humans.
  4. Eliaser EM, Ho JH, Hashim NM, Rukayadi Y, Ee GCL, Razis AFA
    Molecules, 2018 Oct 20;23(10).
    PMID: 30347850 DOI: 10.3390/molecules23102708
    Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world's population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicopelunu-ankenda, also known as Euodialunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M.lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M.lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M.lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future.
  5. Al-Zuaidy MH, Mumtaz MW, Hamid AA, Ismail A, Mohamed S, Razis AFA
    BMC Complement Altern Med, 2017 Jul 10;17(1):359.
    PMID: 28693595 DOI: 10.1186/s12906-017-1849-2
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract.

    METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.

    RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.

    CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.

  6. Iqbal SZ, Usman S, Razis AFA, Basheir Ali N, Saif T, Asi MR
    Int J Environ Res Public Health, 2020 Aug 03;17(15).
    PMID: 32756472 DOI: 10.3390/ijerph17155602
    The main goal of the present research was to explore the seasonal variation of deoxynivalenol (DON) in wheat, corn, and their products, collected during 2018-2019. Samples of 449 of wheat and products and 270 samples of corn and their products were examined using reverse-phase liquid chromatography with a UV detector. The findings of the present work showed that 104 (44.8%) samples of wheat and products from the summer season, and 91 (41.9%) samples from winter season were contaminated with DON (concentration limit of detections (LOD) to 2145 µg/kg and LOD to 2050 µg/kg), from summer and winter seasons, respectively. In corn and products, 87 (61.2%) samples from summer and 57 (44.5%) samples from winter season were polluted with DON with levels ranging from LOD to 2967 µg/kg and LOD to 2490 µg/kg, from the summer and winter season, respectively. The highest dietary intake of DON was determined in wheat flour 8.84 µg/kg body weight/day from the summer season, and 7.21 µg/kg body weight/day from the winter season. The findings of the work argued the need to implement stringent guidelines and create awareness among farmers, stakeholders, and traders of the harmful effect of DON. It is mostly observed that cereal crops are transported and stockpiled in jute bags, which may absorb moisture from the environment and produce favorable conditions for fungal growth. Therefore, these crops must store in polyethylene bags during transportation and storage, and moisture should be controlled. It is highly desirable to use those varieties that are more resistant to fungi attack. Humidity and moisture levels need to be controlled during storage and transportation.
  7. Aslam K, Iqbal SZ, Razis AFA, Usman S, Ali NB
    PMID: 33668973 DOI: 10.3390/ijerph18052270
    This research aims to assess the natural occurrence of patulin (PAT) in selected citrus fruits from central cities of Punjab and Pakistan's northern cities. A total of 2970 fruit samples from 12 citrus cultivars were examined using liquid chromatography fitted with a UV detector. The detection limit (LOD) and quantification limit were 0.04 and 0.12 µg/kg, respectively. About 56% of samples of citrus fruits from Punjab's central cities, Pakistan, were found to be contaminated with PAT, with values ranging from 0.12 to 1150 µg/kg in samples from central Punjab cities. Furthermore, 31.7% of samples of citrus fruits from northern cities of Pakistan were contaminated with PAT, with values ranging from 0.12 to 320 µg/kg. About 22.1% of citrus fruit samples had PAT levels greater than the suggested limits established by the European Union (EU). The dietary intake levels of PAT ranged from 0.10 to 1.11 µg/kg bw/day in the central cities of Punjab, Pakistan, and 0.13 to 1.93 µg/kg bw/day in the northern cities of Pakistan.
  8. Razis AFA, Shehzad MM, Usman S, Ali NB, Iqbal SZ, Naheed N, et al.
    PMID: 33276517 DOI: 10.3390/ijerph17238964
    A total of 779 samples of edible nuts (melon seeds, watermelon seeds, pumpkin seeds, and cantaloupe seeds) from Southern Punjab (Pakistan), were collected during the summer and the winter seasons. The natural occurrence of aflatoxins (AFs) and vitamin E (tocopherols) levels were investigated using HPLC. The results have shown that 180 (43.4%) of samples from the winter season and 122 (33.4%) samples from the summer season were found positive for AFs. Elevated average levels of total AFs (20.9 ± 3.10 μg/kg, dry weight) were observed in watermelon seeds without shell, and the lowest average amount (15.9 ± 3.60 μg/kg) were documented in melon seeds without shell samples from the winter season. An elevated average amount of total AFs 17.3 ± 1.50 μg/kg was found in pumpkin seeds available without a shell. The results have documented a significant difference in total AFs levels in edible seeds available with shells versus without shells (α = 0.05 & 0.01). The highest dietary intake of 6.30 μg/kg/day was found in female individuals from consuming pumpkin seeds (without shell) in the winter season. A value of 3.00 μg/kg/day was found in pumpkin seed without shell in the summer season in female individuals. The highest total tocopherol levels were 22.2 ± 7.70 ng/100 g in pumpkin seeds samples from the winter season and 14.5 ± 5.50 mg/100 g in melon seed samples from the summer season. The variation of total tocopherol levels in edible seeds among the winter and summer seasons showed a significant difference (p ≤ 0.0054), except watermelon seeds samples with non-significant differences (p ≥ 0.183).
  9. Asif Ali M, Khan N, Kaleem N, Ahmad W, Alharethi SH, Alharbi B, et al.
    Front Oncol, 2023;13:1168321.
    PMID: 37397365 DOI: 10.3389/fonc.2023.1168321
    Sulforaphane (SFN) is an isothiocyanate with multiple biomedical applications. Sulforaphane can be extracted from the plants of the genus Brassica. However, broccoli sprouts are the chief source of sulforaphane and are 20 to 50 times richer than mature broccoli as they contain 1,153 mg/100 g. SFN is a secondary metabolite that is produced as a result of the hydrolysis of glucoraphanin (a glucosinolate) by the enzyme myrosinase. This review paper aims to summarize and understand the mechanisms behind the anticancer potential of sulforaphane. The data was collected by searching PubMed/MedLine, Scopus, Web of Science, and Google Scholar. This paper concludes that sulforaphane provides cancer protection through the alteration of various epigenetic and non-epigenetic pathways. It is a potent anticancer phytochemical that is safe to consume with minimal side effects. However, there is still a need for further research regarding SFN and the development of a standard dose.
  10. Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, et al.
    Biomed Pharmacother, 2021 Aug;140:111732.
    PMID: 34130201 DOI: 10.1016/j.biopha.2021.111732
    Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.
  11. Posadino AM, Giordo R, Ramli I, Zayed H, Nasrallah GK, Wehbe Z, et al.
    Biomed Pharmacother, 2023 Jul;163:114783.
    PMID: 37121149 DOI: 10.1016/j.biopha.2023.114783
    Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-β-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.
  12. Posadino AM, Giordo R, Pintus G, Mohammed SA, Orhan IE, Fokou PVT, et al.
    Biomed Pharmacother, 2023 Jul;163:114866.
    PMID: 37182516 DOI: 10.1016/j.biopha.2023.114866
    Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.
  13. Tan H, Mong GR, Wong SL, Wong KY, Sheng DDCV, Nyakuma BB, et al.
    Environ Sci Pollut Res Int, 2024 Jan;31(1):109-126.
    PMID: 38040882 DOI: 10.1007/s11356-023-31228-7
    This paper presents the landscape of research on airborne microplastics and nanoplastics (MPs/NPs) according to the bibliometric analysis of 147 documents issued between 2015 and 2021, extracted from the Web of Science database. The publications on airborne MPs/NPs have increased rapidly from 2015 onwards, which is largely due to the existence of funding support. Science of the Total Environment is one of the prominent journals in publishing related papers. China, England, the USA, and European Countries have produced a significant output of airborne MP/NP research works, which is associated with the availability of funding agencies regionally or nationally. The research hotspot on the topic ranges from the transport of airborne MPs/NPs to their deposition in the terrestrial or aquatic environments, along with the contamination of samples by indoor MPs/NPs. Most of the publications are either research or review papers related to MPs/NPs. It is crucial to share the understanding of global plastic pollution and its unfavorable effects on humankind by promoting awareness of the existence and impact of MPs/NPs. Funding agencies are vital in boosting the research development of airborne MPs/NPs. Some countries that are lacking funding support were able to publish research findings related to the field of interest, however, with lesser research output. Without sufficient fundings, some impactful publications may not be able to carry a substantial impact in sharing the findings and discoveries with the mass public.
  14. Sharifi-Rad J, Quispe C, Herrera-Bravo J, Belén LH, Kaur R, Kregiel D, et al.
    Oxid Med Cell Longev, 2021;2021:7571132.
    PMID: 34349875 DOI: 10.1155/2021/7571132
    The Glycyrrhiza genus, generally well-known as licorice, is broadly used for food and medicinal purposes around the globe. The genus encompasses a rich pool of bioactive molecules including triterpene saponins (e.g., glycyrrhizin) and flavonoids (e.g., liquiritigenin, liquiritin). This genus is being increasingly exploited for its biological effects such as antioxidant, antibacterial, antifungal, anti-inflammatory, antiproliferative, and cytotoxic activities. The species Glycyrrhiza glabra L. and the compound glycyrrhizin (glycyrrhizic acid) have been studied immensely for their effect on humans. The efficacy of the compound has been reported to be significantly higher on viral hepatitis and immune deficiency syndrome. This review provides up-to-date data on the most widely investigated Glycyrrhiza species for food and medicinal purposes, with special emphasis on secondary metabolites' composition and bioactive effects.
  15. Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, et al.
    Oxid Med Cell Longev, 2021;2021:3268136.
    PMID: 34336089 DOI: 10.1155/2021/3268136
    Genistein is an isoflavone first isolated from the brooming plant Dyer's Genista tinctoria L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.
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