Rosa Direito

@imed.ulisboa.pt

Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science
Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa

https://researchid.co/rdireito

Rosa Direito earned her PhD in Pharmacy (Food Science), having been awarded a fellowship by the Dean of the University of Lisbon. She has a background in experimental models of disease, mainly on animal models of acute and chronic inflammation (ulcerative colitis, rheumatoid arthritis) and in vitro model of colon cancer, and how certain fruits, vegetables and herbs can have an impact on inflammatory processes. Her research interests span the crossroads of the brain-gut axis and how diet and the microbiome can have an impact on health. Over the years she has also mentored and collaborated with students from different degrees, is certified in the handling of laboratory animals, and is an instructor of a postgraduate course on laboratory animal sciences. After finishing her PhD, she has sought to contribute to science internationally by becoming an active certified reviewer and has joined the board of reviewers and editorial board of several scientific journals.

EDUCATION

Post-doctoral Fellow (2021-2022), IHMT, Lisboa, Portugal
Post-doctoral Fellow (2020), Instituto Gulbenkian Ciência (IGC), Oeiras, Portugal
PhD (2019) in Pharmacy (Food Science), University of Lisbon, Lisbon, Portugal
MSc (2009) in Biochemistry, University of Coimbra, Coimbra, Portugal
BSc (2005) in Biochemistry, University of Coimbra, Coimbra, Portugal

RESEARCH INTERESTS

Her research interests span the crossroads of the brain-gut axis and how diet and the microbiome can have an impact on health.

Scopus Publications

1090

Scholar Citations

Scholar h-index

Scholar i10-index

Scopus Publications

Polyphenols, Alkaloids, and Terpenoids Against Neurodegeneration: Evaluating the Neuroprotective Effects of Phytocompounds Through a Comprehensive Review of the Current Evidence
Enzo Pereira de Lima, Lucas Fornari Laurindo, Vitor Cavallari Strozze Catharin, Rosa Direito, Masaru Tanaka, Iris Jasmin Santos German, Caroline Barbalho Lamas, Elen Landgraf Guiguer, Adriano Cressoni Araújo, Adriana Maria Ragassi Fiorini,et al.
MDPI AG
Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation of neuronal structure, or loss of neuronal function, leading to a substantially reduced quality of life. They remain a significant focus of scientific and clinical interest due to their increasing medical and social importance. Most neurodegenerative diseases present intracellular protein aggregation or their extracellular deposition (plaques), such as α-synuclein in Parkinson’s disease and amyloid beta (Aβ)/tau aggregates in Alzheimer’s. Conventional treatments for neurodegenerative conditions incur high costs and are related to the development of several adverse effects. In addition, many patients are irresponsive to them. For these reasons, there is a growing tendency to find new therapeutic approaches to help patients. This review intends to investigate some phytocompounds’ effects on neurodegenerative diseases. These conditions are generally related to increased oxidative stress and inflammation, so phytocompounds can help prevent or treat neurodegenerative diseases. To achieve our aim to provide a critical assessment of the current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, and COCHRANE, seeking clinical trials that utilized phytochemicals against neurodegenerative conditions. A few clinical trials investigated the effects of phytocompounds in humans, and after screening, 13 clinical trials were ultimately included following PRISMA guidelines. These compounds include polyphenols (flavonoids such as luteolin and quercetin, phenolic acids such as rosmarinic acid, ferulic acid, and caffeic acid, and other polyphenols like resveratrol), alkaloids (such as berberine, huperzine A, and caffeine), and terpenoids (such as ginkgolides and limonene). The gathered evidence underscores that quercetin, caffeine, ginkgolides, and other phytochemicals are primarily anti-inflammatory, antioxidant, and neuroprotective, counteracting neuroinflammation, neuronal oxidation, and synaptic dysfunctions, which are crucial aspects of neurodegenerative disease intervention in various included conditions, such as Alzheimer’s and other dementias, depression, and neuropsychiatric disorders. In summary, they show that the use of these compounds is related to significant improvements in cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, and mood disorders.

Melatonin from Plants: Going Beyond Traditional Central Nervous System Targeting—A Comprehensive Review of Its Unusual Health Benefits
Lucas Fornari Laurindo, Otávio Augusto Garcia Simili, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rosa Direito, Vitor Engrácia Valenti, Vitor de Oliveira, Juliana Santos de Oliveira, José Luiz Yanaguizawa Junior, Jefferson Aparecido Dias,et al.
MDPI AG
Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time.

Evaluating the effects of seed oils on lipid profile, inflammatory and oxidative markers, and glycemic control of diabetic and dyslipidemic patients: a systematic review of clinical studies
Lucas Fornari Laurindo, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Jéssica da Silva Camarinha Oliveira, Beatriz Leme Boaro, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Claudia Rucco Penteado Detregiachi, Virgínia Maria Cavallari Strozze Catharin, Eduardo Federighi Baisi Chagas,et al.
Frontiers Media SA
Diabetes mellitus and dyslipidemia are significant health concerns that elevate the risk of cardiovascular disease and other metabolic disorders, necessitating effective management strategies. Recent research has highlighted the potential role of dietary fats, particularly seed oils, in influencing health outcomes in these conditions. This systematic review evaluates the impact of seed oils on lipid profiles, inflammatory and oxidative markers, and glycemic control in patients with diabetes and dyslipidemia. A comprehensive search across databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, identified studies focusing on the effects of seed oils. The studies include randomized controlled, parallel-design, double-blind, placebo-controlled, and open-label studies published in English. The quality of the studies was assessed through a detailed review process, and data were extracted to evaluate the effects of seed oils on key metabolic markers. The review included 11 studies demonstrating that seed oils derived from canola, flaxseed, and sesame seeds can positively influence lipid profiles and glycemic control while potentially modulating oxidative stress markers. The findings suggest that seed oils may benefit in managing diabetes and dyslipidemia, although the results are sometimes inconsistent. This review provides valuable insights for dietary recommendations and therapeutic strategies, highlighting the need for further research to clarify the role of seed oils in metabolic health.

Isoorientin: Unveiling the hidden flavonoid's promise in combating cancer development and progression – A comprehensive review
Lucas Fornari Laurindo, Karina Torres Pomini, Enzo Pereira de Lima, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Jéssica da Silva Camarinha Oliveira, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rose Eli Grassi Rici, Durvanei Augusto Maria,et al.
Elsevier BV

Targeting AMPK with Irisin: Implications for metabolic disorders, cardiovascular health, and inflammatory conditions — A systematic review
Lucas Fornari Laurindo, Victória Dogani Rodrigues, Lívia Fornari Laurindo, Luana Maria Amaral Cherain, Enzo Pereira de Lima, Beatriz Leme Boaro, Jéssica da Silva Camarinha Oliveira, Eduardo Federighi Baisi Chagas, Vitor Cavallari Strozze Catharin, Jesselina Francisco dos Santos Haber,et al.
Elsevier BV

Health benefits of acerola (Malpighia spp) and its by-products: A comprehensive review of nutrient-rich composition, pharmacological potential, and industrial applications
Lucas Fornari Laurindo, Larissa Naomi Takeda, Nathalia Mendes Machado, Alda Maria Machado Bueno Otoboni, Ricardo de Alvares Goulart, Vitor Cavallari Strozze Catharin, Luís R. Silva, Sandra Maria Barbalho, and Rosa Direito
Elsevier BV

The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review
Lucas Fornari Laurindo, Enzo Pereira de Lima, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Eduardo Federighi Baisi Chagas, Ricardo de Alvares Goulart, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Karina Torres Pomini, Rose Eli Grassi Rici,et al.
Elsevier BV

Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols
Raissa Bulaty Tauil, Paula Takano Golono, Enzo Pereira de Lima, Ricardo de Alvares Goulart, Elen Landgraf Guiguer, Marcelo Dib Bechara, Claudia C. T. Nicolau, José Luiz Yanaguizawa Junior, Adriana M. R. Fiorini, Nahum Méndez-Sánchez,et al.
MDPI AG
Metabolic-Associated Fatty Liver Disease (MAFLD) is a clinical–pathological scenario that occurs due to the accumulation of triglycerides in hepatocytes which is considered a significant cause of liver conditions and contributes to an increased risk of death worldwide. Even though the possible causes of MAFLD can involve the interaction of genetics, hormones, and nutrition, lifestyle (diet and sedentary lifestyle) is the most influential factor in developing this condition. Polyphenols comprise many natural chemical compounds that can be helpful in managing metabolic diseases. Therefore, the aim of this review was to investigate the impact of oxidative stress, inflammation, mitochondrial dysfunction, and the role of polyphenols in managing MAFLD. Some polyphenols can reverse part of the liver damage related to inflammation, oxidative stress, or mitochondrial dysfunction, and among them are anthocyanin, baicalin, catechin, curcumin, chlorogenic acid, didymin, epigallocatechin-3-gallate, luteolin, mangiferin, puerarin, punicalagin, resveratrol, and silymarin. These compounds have actions in reducing plasma liver enzymes, body mass index, waist circumference, adipose visceral indices, lipids, glycated hemoglobin, insulin resistance, and the HOMA index. They also reduce nuclear factor-KB (NF-KB), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), blood pressure, liver fat content, steatosis index, and fibrosis. On the other hand, they can improve HDL-c, adiponectin levels, and fibrogenesis markers. These results show that polyphenols are promising in the prevention and treatment of MAFLD.

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions
Iris Jasmin Santos German, Sandra Maria Barbalho, Jesus Carlos Andreo, Tereza Lais Menegucci Zutin, Lucas Fornari Laurindo, Victória Dogani Rodrigues, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rosa Direito, Karina Torres Pomini,et al.
MDPI AG
Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

Exploring Lectin Bioactivity and Total Phenolic Compounds in Kiwifruit (Actinidia deliciosa var. Hayward)
Raquel Rodrigues, Maria Eduardo Figueira, Rosa Direito, Andreia Bento-Silva, Ricardo Boavida Ferreira, and Ana Cristina Ribeiro
MDPI AG
Background: The consumption of kiwifruit (Actinidia deliciosa var. Hayward) is recognized for its health benefits due to its high vitamin C content and bioactive secondary metabolites, such as phenolic compounds with antioxidant properties. These compounds may help prevent chronic noncommunicable diseases, currently the leading cause of death. Additionally, plants and fruits contain proteins like lectins, which contribute to plant defense and may also have health-promoting effects, including antitumor and hypoglycemic activities. Objectives: The objective of this work was to evaluate and identify the phenolic compounds in this variety of kiwifruit, as well as to investigate the lectin activity and the potential dietary benefits of this combination. Methods: This study quantified and identified total phenolic compounds and flavonoids in a kiwifruit extract using HPLC-DAD-MS/MS, and assessed their antioxidant activity through the DPPH method. Results: Novel lectin activity was also investigated, with polypeptide characterization and glycoprotein profiling performed. The affinity of lectins for glycans was evaluated using a hemagglutination inhibition assay. Results indicated that kiwifruit lectins bind to glycoreceptors on tumor cell membranes, with a specific affinity for sialic acid, an important glycan in tumor-associated glycomic aberrations. Conclusions: These findings suggest that the bioactive components of kiwifruit may offer multiple health benefits through a synergistic effect.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review
Guilherme Lopes de Oliveira Pagotto, Livia Maria Oliveira dos Santos, Najwa Osman, Caroline Barbalho Lamas, Lucas Fornari Laurindo, Karina Torres Pomini, Leila M. Guissoni, Enzo Pereira de Lima, Ricardo de Alvares Goulart, Virginia M. C. Strozze Catharin,et al.
MDPI AG
Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Plant-Derived Bioactive Compounds: Exploring Neuroprotective, Metabolic, and Hepatoprotective Effects for Health Promotion and Disease Prevention
Rosa Direito, Sandra Maria Barbalho, Bruno Sepodes, and Maria Eduardo Figueira
MDPI AG
There is a growing trend among consumers to seek out natural foods and products with natural ingredients. This shift in consumer preferences had a direct impact on both food and pharmaceutical industries, leading to a focus of scientific research and commercial efforts to meet these new demands. The aim of this work is to review recent available scientific data on foods of interest, such as the artichoke, gooseberry, and polygonoideae plants, as well as olive oil and red raspberries. Interestingly, the urgency of solutions to the climate change emergency has brought new attention to by-products of grapevine bunch stem and cane, which have been found to contain bioactive compounds with potential health benefits. There is a pressing need for a faster process of translating scientific knowledge from the laboratory to real-world applications, especially in the face of the increasing societal burden associated with non-communicable diseases (NCDs), environmental crises, the post-pandemic world, and ongoing violent conflicts around the world.

Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis
Luiz José Valotto Neto, Matheus Reverete de Araujo, Renato Cesar Moretti Junior, Nathalia Mendes Machado, Rakesh Kumar Joshi, Daiene dos Santos Buglio, Caroline Barbalho Lamas, Rosa Direito, Lucas Fornari Laurindo, Masaru Tanaka,et al.
MDPI AG
The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM’s beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Grape Processing Waste: Effects on Inflammatory Bowel Disease and Colorectal Cancer
Lucas Fornari Laurindo, Rosa Direito, Alda M. M. Bueno Otoboni, Ricardo Alvares Goulart, Karina Quesada, and Sandra Maria Barbalho
Informa UK Limited

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis
Frantisek Drafi, Katarina Bauerova, Martin Chrastina, Mohsen Taghdisiesfejír, João Rocha, Rosa Direito, Maria Eduardo Figueira, Bruno Sepodes, and Silvester Ponist
MDPI AG
Rhodiola rosea L. extract (RSE) is mostly known for its adaptogen properties, but not for its antiarthritic activities, therefore monotherapy and combination with low-dose methotrexate (MTX) was studied. The collagen-induced arthritis (CIA) model was used to measure the functional score, and the change in hind paw volume (HPV). Both parameters had significant antiarthritic effects. Based on these preliminary results, an adjuvant arthritis (AA) model was further applied to assess another parameters. The experiment included these animal groups: healthy controls, untreated AA, AA administered with RSE (150 mg/kg b.w. daily, p.o.), AA administered by MTX (0.3 mg/kg b.w. twice a week, p.o.), and AA treated with the combination of RSE+MTX. The combination of RSE+MTX significantly reduced the HPV and increased the body weight. The combination significantly decreased HPV when compared to MTX monotherapy. The plasmatic levels of inflammatory markers (IL-6, IL-17A, MMP-9 and CRP) were significantly decreased by MTX+RSE treatment. The RSE monotherapy didn’t influence any of the inflammatory parameters studied. In CIA, the RSE monotherapy significantly decreased the arthritic parameters studied. In summary, the combination of RSE and sub-therapeutic MTX was significantly effective in AA by improving inflammatory and arthritic parameters.

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review
Rosa Direito, Sandra Maria Barbalho, Maria Eduardo Figueira, Giulia Minniti, Gabriel Magno de Carvalho, Bárbara de Oliveira Zanuso, Ana Rita de Oliveira dos Santos, Natália de Góes Corrêa, Victória Dogani Rodrigues, Ricardo de Alvares Goulart,et al.
MDPI AG
Ongoing research explores the underlying causes of ulcerative colitis and Crohn’s disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term “microbiota” pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1β. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1β, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Anthocyanins: Metabolic Digestion, Bioavailability, Therapeutic Effects, Current Pharmaceutical/Industrial Use, and Innovation Potential
Huseyin Ayvaz, Turgut Cabaroglu, Asiye Akyildiz, Cigdem Uysal Pala, Riza Temizkan, Erdal Ağçam, Zayde Ayvaz, Alessandra Durazzo, Massimo Lucarini, Rosa Direito,et al.
MDPI AG
In this work, various concepts and features of anthocyanins have been comprehensively reviewed, taking the benefits of the scientific publications released mainly within the last five years. Within the paper, common topics such as anthocyanin chemistry and occurrence, including the biosynthesis of anthocyanins emphasizing the anthocyanin formation pathway, anthocyanin chemistry, and factors influencing the anthocyanins’ stability, are covered in detail. By evaluating the recent in vitro and human experimental studies on the absorption and bioavailability of anthocyanins present in typical food and beverages, this review elucidates the significant variations in biokinetic parameters based on the model, anthocyanin source, and dose, allowing us to make basic assumptions about their bioavailability. Additionally, special attention is paid to other topics, such as the therapeutic effects of anthocyanins. Reviewing the recent in vitro, in vivo, and epidemiological studies on the therapeutic potential of anthocyanins against various diseases permits a demonstration of the promising efficacy of different anthocyanin sources at various levels, including the neuroprotective, cardioprotective, antidiabetic, antiobesity, and anticancer effects. Additionally, the studies on using plant-based anthocyanins as coloring food mediums are extensively investigated in this paper, revealing the successful use of anthocyanins in coloring various products, such as dietary and bakery products, mixes, juices, candies, beverages, ice cream, and jams. Lastly, the successful application of anthocyanins as prebiotic ingredients, the innovation potential of anthocyanins in industry, and sustainable sources of anthocyanins, including a quantitative research literature and database analysis, is performed.

Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review
Lucas Fornari Laurindo, Gabriel Magno de Carvalho, Bárbara de Oliveira Zanuso, Maria Eduardo Figueira, Rosa Direito, Ricardo de Alvares Goulart, Daiene Santos Buglio, and Sandra Maria Barbalho
MDPI AG
Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR’s numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR’s solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), Huntington’s disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

Anti-Inflammatory, Antioxidant, and Other Health Effects of Dragon Fruit and Potential Delivery Systems for Its Bioactive Compounds
Daniela Franceschi Nishikito, Ana Claudia Abdalla Borges, LUCAS FORNARI LAURINDO, Alda M. M. Bueno Otoboni, R. Direito, R. Goulart, C. C. T. Nicolau, A. Fiorini, Renata Vargas Sinatora and S. Barbalho

Dragon fruit (Hylocereus genus) has the potential for the prevention of diseases associated with inflammatory and oxidative processes. We aimed to comprehensively review dragon fruit health effects, economic importance, and possible use in delivery systems. Pubmed, Embase, and Google Scholar were searched, and PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis) guidelines were followed. Studies have shown that pitaya can exert several benefits in conditions such as diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer due to the presence of bioactive compounds that may include vitamins, potassium, betacyanin, p-coumaric acid, vanillic acid, and gallic acid. Moreover, pitaya has the potential to be used in food and nutraceutical products as functional ingredients, natural colorants, ecologically correct and active packaging, edible films, preparation of photoprotective products, and additives. Besides the importance of dragon fruit as a source of bioactive compounds, the bioavailability is low. The development of delivery systems such as gold nanoparticles with these compounds can be an alternative to reach target tissues.

Ginkgo biloba in the Aging Process: A Narrative Review
Sandra Maria Barbalho, Rosa Direito, Lucas Fornari Laurindo, Ledyane Taynara Marton, Elen Landgraf Guiguer, Ricardo de Alvares Goulart, Ricardo José Tofano, Antonely C. A. Carvalho, Uri Adrian Prync Flato, Viviane Alessandra Capelluppi Tofano,et al.
MDPI AG
Neurodegenerative diseases, cardiovascular disease (CVD), hypertension, insulin resistance, cancer, and other degenerative processes commonly appear with aging. Ginkgo biloba (GB) is associated with several health benefits, including memory and cognitive improvement, in Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancer. Its antiapoptotic, antioxidant, and anti-inflammatory actions have effects on cognition and other conditions associated with aging-related processes, such as insulin resistance, hypertension, and cardiovascular conditions. The aim of this study was to perform a narrative review of the effects of GB in some age-related conditions, such as neurodegenerative diseases, CVD, and cancer. PubMed, Cochrane, and Embase databases were searched, and the PRISMA guidelines were applied. Fourteen clinical trials were selected; the studies showed that GB can improve memory, cognition, memory scores, psychopathology, and the quality of life of patients. Moreover, it can improve cerebral blood flow supply, executive function, attention/concentration, non-verbal memory, and mood, and decrease stress, fasting serum glucose, glycated hemoglobin, insulin levels, body mass index, waist circumference, biomarkers of oxidative stress, the stability and progression of atherosclerotic plaques, and inflammation. Therefore, it is possible to conclude that the use of GB can provide benefits in the prevention and treatment of aging-related conditions.

Lupinus albus protein components inhibit MMP-2 and MMP-9 gelatinolytic activity in vitro and in vivo
Joana Mota, Rosa Direito, João Rocha, João Fernandes, Bruno Sepodes, Maria Eduardo Figueira, Anabela Raymundo, Ana Lima, and Ricardo Boavida Ferreira
MDPI AG
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg·kg−1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from δ-conglutin and, to a lower extent, small fragments of β-conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 µg·mL−1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system.

From diospyros kaki L. (persimmon) phytochemical profile and health impact to new product perspectives and waste valorization
Rosa Direito, João Rocha, Bruno Sepodes, and Maria Eduardo-Figueira
MDPI AG
Persimmon (Diospyros kaki L.) fruit’s phytochemical profile includes carotenoids, proanthocyanidins, and gallic acid among other phenolic compounds and vitamins. A huge antioxidant potential is present given this richness in antioxidant compounds. These bioactive compounds impact on health benefits. The intersection of nutrition and sustainability, the key idea behind the EAT-Lancet Commission, which could improve human health and decrease the global impact of food-related health conditions such as cancer, heart disease, diabetes, and obesity, bring the discussion regarding persimmon beyond the health effects from its consumption, but also on the valorization of a very perishable food that spoils quickly. A broad option of edible products with better storage stability or solutions that apply persimmon and its byproducts in the reinvention of old products or even creating new products, or with new and better packaging for the preservation of food products with postharvest technologies to preserve and extend the shelf-life of persimmon food products. Facing a global food crisis and the climate emergency, new and better day-to-day solutions are needed right now. Therefore, the use of persimmon waste has also been discussed as a good solution to produce biofuel, eco-friendly alternative reductants for fabric dyes, green plant growth regulator, biodegradable and edible films for vegetable packaging, antimicrobial activity against foodborne methicillin-resistant Staphylococcus aureus found in retail pork, anti-Helicobacter pylori agents from pedicel extracts, and persimmon pectin-based emulsifiers to prevent lipid peroxidation, among other solutions presented in the revised literature. It has become clear that the uses for persimmon go far beyond the kitchen table and the health impact consumption demonstrated over the years. The desired sustainable transition is already in progress, however, mechanistic studies and clinical trials are essential and scaling-up is fundamental to the future.

Phenolic compounds impact on rheumatoid arthritis, inflammatory bowel disease and microbiota modulation
Rosa Direito, João Rocha, Bruno Sepodes, and Maria Eduardo-Figueira
MDPI AG
Non-communicable chronic diseases (NCDs) are nowadays the principal cause of death, especially in most industrialized nations. These illnesses have increased exponentially with the consumption of diets very high in fat and sugar, not to mention stress and physical inactivity among other factors. The potential impact of suboptimal diets on NCDs’ morbidity and mortality rates brings to the forefront the necessity for a new way of improving dietary habits. The literature provides extensive scientific work that presents evidence that phenolic compounds from diets have antioxidant, anti-inflammatory and antiproliferative activities that impact human health. Gut microbiota modulation by some phenolic compounds leads to favorable changes in abundance, diversity, and in the immune system. However, polyphenol’s limited bioavailability needs to be overcome, highlighting their application in new delivery systems and providing their health benefits in well-established ways such as health maintenance, treatment or adjuvant to conventional pharmacological treatments. In this context, novel dietary approaches, including new food supplements, have emerged to prevent diseases and preserve health.

Attenuation of colonic injury and inflammation by administration of a phenolic extract of summer savory (Satureja hortensis l.) in experimental inflammatory bowel disease in mice
João Rocha, Raquel Leandro, Rosa Direito, Margarida Gonçalves, Maria Paula Duarte, Adelaide Fernandes, Bruno Sepodes, and Maria-Eduardo Figueira
MDPI AG
Summer Savory (Satureja hortensis L.) is a plant traditionally used as a food spice in the Mediterranean region. Surprisingly, not much is known about the health beneficial effects of its phenolic-rich extracts. The majority of publications have always focused on the properties of their essential oil. One of the main phenolic compounds of Summer Savory is rosmarinic acid, which has demonstrated anti-inflammatory outcomes in several animal models of inflammatory-mediated diseases. Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease, in addition to Ulcerative Colitis and Crohn’s Disease, frequently related with increased morbidity and even mortality due to the complications associated, including colorectal cancer. Our work has shown, to our knowledge, for the first time, that administration of a phenolic extract of Summer Savory in a mouse model of Ulcerative Colitis led to the reduction of several markers for intestinal injury, including reduction of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2 or prostaglandin-endoperoxide synthase) expression, two well-known mediators of tissue inflammation and progression to cancer and led also to a reduction of the mortality. Given the chemical constitution found in the extract and the preclinical evidence of a beneficial effect of polyphenols in inflammatory processes, an opportunity arises for pharmacological modulation of pathways relevant for IBD and progression to cancer with phenolic-rich extracts.

Anti-inflammatory Effects of Persimmon (Diospyros kaki L.) in Experimental Rodent Rheumatoid Arthritis
Rosa Direito, João Rocha, Ana-Teresa Serra, Adelaide Fernandes, Marisa Freitas, Eduarda Fernandes, Rui Pinto, Rosário Bronze, Bruno Sepodes, and Maria-Eduardo Figueira
Informa UK Limited
Abstract Persimmon (Diospyros kaki L.) fruits are used in traditional medicine largely due to their claimed beneficial effects on human health. The aim of this work was to evaluate the anti-inflammatory activity of a persimmon extract in rats with collagen-induced arthritis (CIA). CIA was induced in Wistar rats through an intradermal injection of an emulsion of bovine type II collagen (CII) in complete Freund’s adjuvant (FCA). Macroscopic evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged rats, and the severity of CIA progressed for 35 days. Radiographs revealed focal resorption of bone, with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathologic features included erosion of the cartilage at the joint margins. The persimmon extract showed an anti-inflammatory effect given the significant reduction in both the edema volume and radiological alterations attributed to CIA in the bone. We demonstrate that the administration of persimmon extract attenuates the degree of chronic inflammation and tissue damage characteristic of CIA in rats, most probably by the potent antioxidant characteristics of the extract.

RECENT SCHOLAR PUBLICATIONS

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Investigating the neuroprotective and cognitive-enhancing effects of Bacopa monnieri: a systematic review focused on inflammation, oxidative stress, mitochondrial dysfunction
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Grape processing waste: Effects on inflammatory bowel disease and colorectal cancer
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Food Reviews International 40 (1), 336-369 2024

Rhodiola rosea L. Extract, A Known Adaptogen, Evaluated in Experimental Arthritis
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Molecules 28 (13), 5053 2023

Medicinal plants, phytochemicals and regulation of the NLRP3 inflammasome in inflammatory bowel diseases: a comprehensive review
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Curcumin-based nanomedicines in the treatment of inflammatory and immunomodulated diseases: an evidence-based comprehensive review
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MOST CITED SCHOLAR PUBLICATIONS

Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis
S Silva, B Sepodes, J Rocha, R Direito, A Fernandes, D Brites, M Freitas, ...
The Journal of nutritional biochemistry 26 (4), 360-368 2015
Citations: 99

Ginkgo biloba in the Aging Process: A Narrative Review
SM Barbalho, R Direito, LF Laurindo, LT Marton, EL Guiguer, RA Goulart, ...
Antioxidants 11 (3), 525 2022
Citations: 85

Anthocyanins: Metabolic digestion, bioavailability, therapeutic effects, current pharmaceutical/industrial use, and innovation potential
H Ayvaz, T Cabaroglu, A Akyildiz, CU Pala, R Temizkan, E Ağam, ...
Antioxidants 12 (1), 48 2022
Citations: 81

Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability
R Direito, C Reis, L Roque, M Gonalves, A Sanches-Silva, MM Gaspar, ...
Pharmaceutics 11 (6), 296 2019
Citations: 60

Chemical characterization of a red raspberry fruit extract and evaluation of its pharmacological effects in experimental models of acute inflammation and collagen-induced arthritis
ME Figueira, MB Cmara, R Direito, J Rocha, AT Serra, CMM Duarte, ...
Food & function 5 (12), 3241-3251 2014
Citations: 60

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities
R Direito, A Lima, J Rocha, RB Ferreira, J Mota, P Rebelo, A Fernandes, ...
The Journal of Nutritional Biochemistry 46, 100-108 2017
Citations: 55

Phenolic compounds impact on rheumatoid arthritis, inflammatory bowel disease and microbiota modulation
R Direito, J Rocha, B Sepodes, M Eduardo-Figueira
Pharmaceutics 13 (2), 145 2021
Citations: 54

Protective effects of a blueberry extract in acute inflammation and collagen-induced arthritis in the rat
ME Figueira, M Oliveira, R Direito, J Rocha, P Alves, AT Serra, C Duarte, ...
Biomedicine & Pharmacotherapy 83, 1191-1202 2016
Citations: 53

From Diospyros kaki L. (Persimmon) Phytochemical Profile and Health Impact to New Product Perspectives and Waste Valorization
R Direito, J Rocha, B Sepodes, M Eduardo-Figueira
Nutrients 13 (9), 3283 2021
Citations: 44

Combination of hyaluronic acid and PLGA particles as hybrid systems for viscosupplementation in osteoarthritis
AH Mota, R Direito, MP Carrasco, P Rijo, L Ascenso, AS Viana, J Rocha, ...
International journal of pharmaceutics 559, 13-22 2019
Citations: 34

Anti-inflammatory Effects of Persimmon (Diospyros kaki L.) in Experimental Rodent Rheumatoid Arthritis
R Direito, J Rocha, AT Serra, A Fernandes, M Freitas, E Fernandes, ...
Journal of Dietary Supplements 17 (6), 663-683 2020
Citations: 28

Reduction of inflammation and colon injury by a spearmint phenolic extract in experimental bowel disease in mice
R Direito, J Rocha, A Lima, MM Gonalves, MP Duarte, V Mateus, ...
Medicines 6 (2), 65 2019
Citations: 25

Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice
J Rocha, R Direito, A Lima, J Mota, M Gonalves, MP Duarte, J Solas, ...
Biomedicine & Pharmacotherapy 118, 109351 2019
Citations: 24