Hesperetin's health potential: moving from preclinical to clinical evidence and bioavailability issues, to upcoming strategies to overcome current limitations.

Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.

Dietary supplements, vitamins and minerals as potential interventions against viruses: Perspectives for COVID-19.

The novel coronavirus (SARS-CoV-2) causing COVID-19 disease pandemic has infected millions of people and caused more than thousands of deaths in many countries across the world. The number of infected cases is increasing day by day. Unfortunately, we do not have a vaccine and specific treatment for it. Along with the protective measures, respiratory and/or circulatory supports and some antiviral and retroviral drugs have been used against SARS-CoV-2, but there are no more extensive studies proving their efficacy. In this study, the latest publications in the field have been reviewed, focusing on the modulatory effects on the immunity of some natural antiviral dietary supplements, vitamins and minerals. Findings suggest that several dietary supplements, including black seeds, garlic, ginger, cranberry, orange, omega-3 and -6 polyunsaturated fatty acids, vitamins (e.g., A, B vitamins, C, D, E), and minerals (e.g., Cu, Fe, Mg, Mn, Na, Se, Zn) have anti-viral effects. Many of them act against various species of respiratory viruses, including severe acute respiratory syndrome-related coronaviruses. Therefore, dietary supplements, including vitamins and minerals, probiotics as well as individual nutritional behaviour can be used as adjuvant therapy together with antiviral medicines in the management of COVID-19 disease.

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention.

Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.

Human microbiome and homeostasis: insights into the key role of prebiotics, probiotics, and symbiotics.

The interest in the study of the gut microbiome has grown exponentially. Indeed, its impact on health and disease has been increasingly reported, and the importance of keeping gut microbiome homeostasis clearly highlighted. However, and despite many advances, there are still some gaps, as well as the real discernment on the contribution of some species falls far short of what is needed. Anyway, it is already more than a solid fact of its importance in maintaining health and preventing disease, as well as in the treatment of some pathologies. In this sense, and given the existence of some ambiguous opinions, the present review aims to discuss the importance of gut microbiome in homeostasis maintenance, and even the role of probiotics, prebiotics, and symbiotics in both health promotion and disease prevention.

Phytochemical constituents, biological activities, and health-promoting effects of the genus Origanum.

Origanum species are mostly distributed around the Mediterranean, Euro-Siberian, and Iran-Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name "oregano" or "pizza-spice." Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p-cymen and -terpinene) or of terpinene-4-ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti-obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure-activity studies are needed to explore the potential use of Origanum-derived phytochemicals as promising drug candidates.

Vicia plants-A comprehensive review on chemical composition and phytopharmacology.

The plants belonging to the genus Vicia are of great interest as a source of many bioactive compounds and micronutrients. A snapshot of their cultivation, habitat, main components, from which essential oils can be obtained, is given. The traditional medicinal uses of Vicia plants are also reported, as well as the wide spectrum of the main biological activities attributed to Vicia plants is discussed regarding potential health beneficial properties, in particular anti-Parkinson, anticholinesterase, antidepressant, anticonvulsant, antimicrobial, cytotoxic, antioxidant, antiinflammatory and antinociceptive, antidiabetic, antihemolytic, anticoagulant, estrogenic, diuretic, antihypoxic activities.

Antioxidant potential of family Cucurbitaceae with special emphasis on Cucurbita genus: A key to alleviate oxidative stress-mediated disorders.

Oxidative stress is the imbalance between reactive oxygen species (ROS) production, and accumulation and the ability of a biological system to clear these reactive products. This imbalance leads to cell and tissue damage causing several disorders in human body, such as neurodegeneration, metabolic problems, cardiovascular diseases, and cancer. Cucurbitaceae family consists of about 100 genera and 1,000 species of plants including mostly tropical, annual or perennial, monoecious, and dioecious herbs. The plants from Cucurbita species are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacins, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant, antitumor, antidiabetic, hepatoprotective, antimicrobial, anti-obesity, diuretic, anti-ulcer activity, and antigenotoxic. A wide number of in vitro and in vivo studies have ascribed these health-promoting effects of Cucurbita genus. Results of clinical trials suggest that Cucurbita provides health benefits for diabetic patients, patients with benign prostate hyperplasia, infertile women, postmenopausal women, and stress urinary incontinence in women. The intend of the present review is to focus on the protective role of Cucurbita spp. phytochemicals on oxidative stress-related disorders on the basis of preclinical and human studies. The review will also give insights on the in vitro and in vivo antioxidant potential of the Cucurbitaceae family as a whole.

Astragalus species: Insights on its chemical composition toward pharmacological applications.

Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties.

Ficus plants: State of the art from a phytochemical, pharmacological, and toxicological perspective.

Ficus genus is typically tropical plants and is among the earliest fruit trees cultivated by humans. Ficus carica L. is the common fig, Ficus benjamina L. is the weeping fig, and Ficus pumila L. is the creeping fig. These species are commonly used in traditional medicine for a wide range of diseases and contain rich secondary metabolites that have shown diverse applications. This comprehensive review describes for Ficus genus the phytochemical compounds, traditional uses and contemporary pharmacological activities such as antioxidant, cytotoxic, antimicrobial, anti-inflammatory, antidiabetic, antiulcer, and anticonvulsant. An extended survey of the current literature (Science Direct, Scopus, PubMed) has been carried out as part of the current work. The trends in the phytochemistry, pharmacological mechanisms and activities of Ficus genus are overviewed in this manuscript: antimicrobial, antidiabetic, anti-inflammatory and analgesic activity, antiseizure and anti-Parkinson's diseases, cytotoxic and antioxidant. Health-promoting effects, recent human clinical studies, safety and adverse effects of Ficus plants also are covered. The medical potential and long-term pharmacotherapeutic use of the genus Ficus along with no serious reported adverse events, suggests that it can be considered as being safe.

Phytotherapy and food applications from Brassica genus.

Plants of the genus Brassica occupy the top place among vegetables in the world. This genus, which contains a group of six related species of a global economic significance, three of which are diploid: Brassica nigra (L.) K. Koch, Brassica oleracea L., and Brassica rapa L. and three are amphidiploid species: Brassica carinata A. Braun, Brassica juncea (L.) Czern., and Brassica napus L. These varieties are divided into oily, fodder, spice, and vegetable based on their morphological structure, chemical composition, and usefulness of plant organs. The present review provides information about habitat, phytochemical composition, and the bioactive potential of Brassica plants, mainly antioxidant, antimicrobial, anticancer activities, and clinical studies in human. Brassica vegetables are of great economic importance around the world. At present, Brassica plants are grown together with cereals and form the basis of global food supplies. They are distinguished by high nutritional properties from other vegetable plants, such as low fat and protein content and high value of vitamins, fibers along with minerals. In addition, they possess several phenolic compounds and have a unique type of compounds namely glucosinolates that differentiate these crops from other vegetables. These compounds are also responsible for numerous biological activities to the genus Brassica as described in this review.

Curcumin nanoformulations for antimicrobial and wound healing purposes.

The development and spread of resistance to antimicrobial drugs is hampering the management of microbial infectious and wound healing processes. Curcumin is the most active and effective constituent of Curcuma longa L., also known as turmeric, and has a very long and strong history of medicinal value for human health and skincare. Curcumin has been proposed as strong antimicrobial potentialities and many attempts have been made to determine its ability to conjointly control bacterial growth and promote wound healing. However, low aqueous solubility, poor tissue absorption and short plasma half-life due its rapid metabolism needs to be solved for made curcumin formulations as suitable treatment for wound healing. New curcumin nanoformulations have been designed to solve the low bioavailability problem of curcumin. Thus, in the present review, the therapeutic applications of curcumin nanoformulations for antimicrobial and wound healing purposes is described.

Organochlorine pesticide residues in raw milk samples collected from dairy farms and urban areas of Lahore district, Pakistan.

The current study was employed to investigate the organochlorine pesticides (OCP) concentrations in milk, as the milk we consume, has residues of these notorious pesticides. The residual concentrations of OCP in milk have numerous harmful effects on health especially the children. Therefore, milk was analyzed using gas chromatography equipped with µECD for seven OCP residues, namely α-endosulfan, ß-endosulfan, Endosulfan-sulphate, DDE, γ-HCH, Dieldrin, and DDT. Three hundred and sixty raw milk samples were collected from urban areas (10 areas of Lahore N = 300) and Dairy Farms (10 farms in Lahore N = 60) from September 2012 to September 2013. Samples were collected after an interval of 2 months, for 12 months. Mean values of OCPs in milk samples from urban areas were reported as α-endosulfan, ß-endosulfan, Endosulfan-sulphate, DDE, γ-HCH, and Dieldrin with concentration of 17.44 ± 3.99, 35.74 ± 7.50, 20.28 ± 3.95, 2.51 ± 0.55, 0.93 ± 0.16 and 1.12 ± 0.18 µg kg-1, respectively, while the milk samples from dairy farms with concentration of 26.94 ± 4.63, 59.88 ± 6.76, 32.07 ± 4.51, 4.64 ± 0.48, 1.20 ± 0.17 and 1.93 ± 0.18 µg kg-1, respectively. None of the samples analyzed were found positive for the presence of DDT, just as none of the samples from area milk shops exceeded the Maximum Residual Limits (MRLs). γ-HCH and ß-endosulfan were found higher in dairy farm milk samples than the MRLs. Conclusively, these pesticide residues are present in milk available in Lahore in enough quantity (some exceeding the MRLs) to threaten human health, particularly the infant and children.

LncRNA & Wnt signaling in colorectal cancer.

The outlook for new therapeutic approaches is pivotal to ameliorate the deterioration caused by the abrogated Wnt signaling. Long non-coding RNAs (lncRNAs) are tiny molecules that have begun emerging as vital molecular manager for the regulation of various cellular processes at transcription and translation levels in the colorectal cancer (CRC). Targeting Wnt pathway with lncRNA seems a promising approach to eradicate CRC. However, little is known of their active role in commencing both apoptosis and proliferation in CRC. This article  reviews the importance of these molecules in the pathogenesis of CRC and also emphasizes on the development of new therapeutic strategies to cope with the Wnt mediated CRC.

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer.

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.

Phytochemical screening of Moringa oleifera leaf extracts and their antimicrobial activities.

Moringa oleifera is a tree native to tropical and subtropical regions of South India and used in traditional medicine. The aim of this study was characterize the phytochemicals present in M. oleifera leaf extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical analysis, and the antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides, amino acids, oils and fats were found in the different crude extracts analyzed. Water and methanol extracts showed antibacterial activity against all selected bacteria, hexane and benzene extracts showed antifungal activity against all fungi tested, and hexane, benzene and isopropanol extracts showed activity against Hepatitis B virus. In conclusion, the leaves of M. oleifera have antimicrobial phytochemicals.

Anxiolytic-like effects of Moringa oleifera in Swiss mice.

Moringa oleifera is evident to act against many neurological diseases, including muscle spasm, epilepsy, nervousness, fatigue, memory impairment, convulsion, and epilepsy. Anxiety represents the most common and disabling psychiatric condition, being often associated with depressive symptoms. This study investigated the anxiolytic-like effects of crude organic fractions of M. oleifera leaves in different behavioral paradigms that evaluate anxiety in mice. To this end, mice were administered with crude extracts (500 mg/kg, p.o.) and/or diazepam (2 mg/kg, p.o.), and submitted to behavioral tests. In the open-field test, the number of square field cross, grooming and rearing were calculated, while in light-dark and swing test were, respectively, the time spent in dark portion and number of swings. Each test was performed for 3 min. M. oleifera leaf methanol and n-hexane extracts elicited an anxiolytic-like effect observed by increased total time in the center and decreased number of rearings and groomings responses in the open field and swing tests, and residence in the dark portion in the light-dark box, similar to the diazepam group. A moderate anxiolytic effect was observed in the aqueous fraction group, while insignificant effects were recorded in the ethyl acetate fraction group in all test paradigms. In addition, both extracts potentiate the calming effects of diazepam in experimental animals. Preliminary phytochemical reports suggest that M. oleifera contains alkaloids, flavonoids, phenols, steroids, glycosides, saponins, tannin, terpenes, and gums. Of note, the results expand the understanding of M. oleifera effects in central nervous system and suggest that plant metabolites may be helpful for anxiety-related disorders management.

p-Cymene metallo-derivatives: An overview on anticancer activity.

Metallo-drugs have gained a huge attention among scientific community in the couple years. These drugs types have become important compounds in cancer therapy, where, for instance, platinum complexes are being used against many tumors worldwide. Nonetheless, to p-cymene metallo-derivatives a promising anticancer potential has also been increasingly proposed. In this sense, the present review aims to provide an in-depth revision of p-cymene metallo-drugs possible mechanisms of anticancer action for upcoming pharmaceutical and biotechnological prospects. p-cymene metallo-derivatives have revealed very interesting anticancer activities in various test systems, including cancer cells, being thus worth of note to deepen knowledge through clinical trials on their upcoming use for cancer chemotherapy combination.

Biological activities of sinularin: A literature-based review.

Sinularin ((9E)-13-hydroxy-4,9,13-trimethyl-17-methylidene-5,15-dioxatricyclo[12.3.1.0(4,6)] octadec-9-en-16-one) is the soft coral-derived hopeful biologically active lead compound. In this review sinularin biological activities are summarized. For that, an up-to-date (from 1980 to Mar 2020) search was made in the PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society, Clinicaltrials.gov, and Google Scholar databases. Data available suggest that sinularin has interesting anti-inflammatory, anticancer, anti-fouling and analgesic potential. The inducible nitric oxide synthase (iNOS), cyclooxigenase (COX)-2, tumor growth factor beta 1 (TGF-ß1) are the most efficient enzymes for interacting with sinularin due to its anti-inflammatory activity, while phosphoinositol 3-kinase (PI3K), Akt and mechanistic target of rapamycin (mTOR) for its anticancer effect. In conclusion, sinularin seems to be a promissory lead compound in the treatment of inflammation, cancer and neurological disorders.

Herbal remedies as alternative to conventional therapies for the treatment of pediatric infectious diseases.

Pediatric infections still represent a leading cause of mortality in many developing countries. Since ancient times, traditional healing systems provided some herbal remedies to treat pediatric diseases, only in some cases validated by an evidence-based approach. Therefore, this review covers the herbal remedies in Iranian traditional medicine and aims to assess the potential of phytotherapeutics as safe and effective alternatives to conventional therapies for the treatment of pediatric infectious diseases. Notably, pediatric patients may also benefit from adjuvant therapy, i.e., combined treatment with herbal remedies and conventional therapies, to improve the efficacy of conventional drugs, decrease their adverse effects at the cell-tissue-organ-organism level and reduce the occurrence of microbial strains resistant to antibiotics. Therefore, traditional healing systems still represent an unlimited source of active ingredients to be tested in preclinical assays as well as in humans in terms of efficacy and safety.

Phenolic compounds, saponins and alkaloids on cancer progression: emphasis on p53 expression and telomere length.

Telomere length is correlated with cell proliferation, and cancer cells are characterized by an uncontrolled cell cycle. Being apoptosis one of the checks and balances incorporated into cells cycle, due to its characteristics, cancer cells are able to overcome this process. In particular, the tumour suppressor protein p53 loss or inactivation can lead to activation of telomerase enzyme, which can make cells unable to detect DNA damages that spurs apoptosis. Some bioactive compounds, in particular phenolic compounds, saponins and alkaloids have revealed good abilities to affect p53 expression and indirectly control the telomere length. In this sense, this review gives a key emphasis to the ability of these compounds in blocking cancer progression by acting on p53 expression and controlling telomere length. As main findings, phenolic compounds, saponins and alkaloids interfere with cancer progression by stimulating p53 expression, which can cause pro-apoptotic onset and restrict the anti-apoptotic activity, in addition to preventing telomerase enzyme activity.