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.

Revisiting the Nutritional, Chemical and Biological Potential of Cajanus cajan (L.) Millsp.

The genus Cajanus (Family: Fabaceae) consists of approximately 37 species, and Cajanus cajan (C. cajan) is a significant member of the genus. It is a commercial legume crop widely grown in sub-tropical and semi-arid tropical areas of the world. C. cajan is well known for its folk medicinal uses to treat various disorders, such as toothache, dizziness, diabetes, stomachache, female ailments and chronic infections. These properties have been linked to the presence of several value-added nutritional and bioactive components. Different solvent extracts from C.cajan (leaves, root, stem and seeds) have been evaluated for their phytochemical and biological activities, namely antioxidant, antimicrobial, antidiabetic, neuroprotective, and anti-inflammatory effects. Taken together, and considering the prominent nutraceutical and therapeutic properties of C. cajan, this review article focuses on the important details including ethnomedicinal uses, chemical composition, biological applications and some other medicinal aspects related to C.cajan nutraceutical and pharmacological applications.

Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases.

Neuroinflammation, a protective response of the central nervous system (CNS), is associated with the pathogenesis of neurodegenerative diseases. The CNS is composed of neurons and glial cells consisting of microglia, oligodendrocytes, and astrocytes. Entry of any foreign pathogen activates the glial cells (astrocytes and microglia) and overactivation of these cells triggers the release of various neuroinflammatory markers (NMs), such as the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-1ß (IL-10), nitric oxide (NO), and cyclooxygenase-2 (COX-2), among others. Various studies have shown the role of neuroinflammatory markers in the occurrence, diagnosis, and treatment of neurodegenerative diseases. These markers also trigger the formation of various other factors responsible for causing several neuronal diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), ischemia, and several others. This comprehensive review aims to reveal the mechanism of neuroinflammatory markers (NMs), which could cause different neurodegenerative disorders. Important NMs may represent pathophysiologic processes leading to the generation of neurodegenerative diseases. In addition, various molecular alterations related to neurodegenerative diseases are discussed. Identifying these NMs may assist in the early diagnosis and detection of therapeutic targets for treating various neurodegenerative diseases.

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.

Global status, recent trends, and knowledge mapping of olive oil research and cardiovascular disease: 50 years of investigations through bibliometric analysis.

In the Mediterranean diet, olive oil serves as the predominant fat source and has been linked to a decreased risk of mortality related to cardiovascular diseases (CVD). Still, there is no conclusive evidence correlating olive oil consumption to CVD. The aim of this study is to assess the global research, current research trends, and knowledge mapping related to the correlation between the consumption of olive oil and CVD using bibliometric analysis. On August 19, 2023, a title-specific literature search was conducted on the Scopus database using the search terms "olive oil" and "cardiovascular disease" with a date range of the past 50 years. Subsequently, bibliometric tools such as VOSviewer and Bibliometrix were employed to analyze and evaluate the obtained documents. The search yielded (n = 429) publications and showed an upward trend in the annual publication count over the last five decades. The publication number exhibited a gradual increase with a rate of 5.55%. The results also indicated that 2530 authors, 759 institutions, 47 countries, and 223 journals have publications in this research domain. The present bibliometric study will be a valuable research reference for describing the worldwide research patterns concerning the relationship between olive oil and CVD during the past 50 years. In the future, the application of olive oil for the treatment of CVDs may be an emerging research trend. Apart from this, collaborations among authors, countries, and organizations are expected.

Emergence of monkeypox: a worldwide public health crisis.

The human monkeypox virus (MPV), a zoonotic illness that was hitherto solely prevalent in Central and West Africa, has lately been discovered to infect people all over the world and has become a major threat to global health. Humans unintentionally contract this zoonotic orthopoxvirus, which resembles smallpox, when they come into contact with infected animals. Studies show that the illness can also be transferred through frequent proximity, respiratory droplets, and household linens such as towels and bedding. However, MPV infection does not presently have a specified therapy. Smallpox vaccinations provide cross-protection against MPV because of antigenic similarities. Despite scant knowledge of the genesis, epidemiology, and ecology of the illness, the incidence and geographic distribution of monkeypox outbreaks have grown recently. Polymerase chain reaction technique on lesion specimens can be used to detect MPV. Vaccines like ACAM2000, vaccinia immune globulin intravenous (VIG-IV), and JYNNEOS (brand name: Imvamune or Imvanex) as well as FDA-approved antiviral medications such as brincidofovir (brand name: Tembexa), tecovirimat (brand name: TPOXX or ST-246), and cidofovir (brand name: Vistide) are used as therapeutic medications against MPV. In this overview, we provide an outline of the MPV's morphology, evolution, mechanism, transmission, diagnosis, preventative measures, and therapeutic approaches. This study offers the fundamental information required to prevent and manage any further spread of this emerging virus.

NMDA Inhibitors: A Potential Contrivance to Assist in Management of Alzheimer's Disease.

Alzheimer's disease (AD) is an increasingly common neurodegenerative disease that attracts the attention of researchers and medical community in order to develop new, safe and more effective drugs. Currently available drugs could only slow the AD progression and relieve the symptoms, in addition to being linked to moderate-to-severe side effects. N-methyl D-aspartate (NMDA) receptors antagonists were reported to have the ability to block the glutamate-mediated excitotoxic activity being good therapeutic targets for several neurodegenerative diseases, including AD. Based on data obtained so far, this review provides an overview over the use of NMDA antagonists for AD treatment, starting with a key emphasis on present features and future aspects regarding the use of NMDA antagonists for AD, and lastly a key focus is also given on its use in precision medicine.

The medicinal chemistry of Urtica dioica L.: from preliminary evidence to clinical studies supporting its neuroprotective activity.

Urtica dioica is a perennial herb from the family of Urticaceae that is commonly known as stinging nettle. This plant is widespread in Europe, Africa, America, and a part of Asia, as it adapts to different environments and climatic conditions. The leaves, stalk, and bark of U. dioica found applications in the field of nutrition, cosmetics, textile, pest control and pharmacology. In this connection, bioactive chemical constituents such as flavonoids, phenolic acids, amino acids, carotenoids, and fatty acids have been isolated from the plant. With this review, we aim at providing an updated and comprehensive overview of the contributions in literature reporting computational, in vitro, pre-clinical and clinical data supporting the therapeutic applications of U. dioica. Experimental evidence shows that U. dioica constituents and extracts can provide neuroprotective effects by acting through a combination of different molecular mechanisms, that are discussed in the review. These findings could lay the basis for the identification and design of more effective tools against neurodegenerative diseases.

Exploring the nutritional and health benefits of pulses from the Indian Himalayan region: A glimpse into the region's rich agricultural heritage.

Pulses have been consumed worldwide for over 10 centuries and are currently among the most widely used foods. They are not economically important, but also nutritionally beneficial as they constitute a good source of protein, fibre, vitamins and minerals such as iron, zinc, folate and magnesium. Pulses, but particularly species such as Macrotyloma uniflorum, Phaseolus vulgaris L., Glycine max L. and Vigna umbellate, are essential ingredients of the local diet in the Indian Himalayan Region (IHR). Consuming pulses can have a favourable effect on cardiovascular health as they improve serum lipid profiles, reduce blood pressure, decrease platelet activity, regulate blood glucose and insulin levels, and reduce inflammation. Although pulses also contain anti-nutritional compounds such as phytates, lectins or enzyme inhibitors, their deleterious effects can be lessened by using effective processing and cooking methods. Despite their great potential, however, the use of some pulses is confined to IHR regions. This comprehensive review discusses the state of the art in available knowledge about various types of pulses grown in IHR in terms of chemical and nutritional properties, health effects, accessibility, and agricultural productivity.

Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach.

Background: Helicobacter pylori (H. pylori) is a persistent bacterial inhabitant in the stomachs of approximately half the global populace. This bacterium is directly linked to chronic gastritis, leading to a heightened risk of duodenal and gastric ulcer diseases, and is the predominant risk factor for gastric cancer - the second most common cause of cancer-related deaths globally. The increasing prevalence of antibiotic resistance necessitates the exploration of innovative treatment alternatives to mitigate the H. pylori menace. Methods: Initiating our study, we curated a list of thirty phytochemicals based on previous literature and subjected them to molecular docking studies. Subsequently, eight phytocompounds-Glabridin, Isoliquiritin, Sanguinarine, Liquiritin, Glycyrrhetic acid, Beta-carotin, Diosgenin, and Sarsasapogenin-were meticulously chosen based on superior binding scores. These were further subjected to an extensive computational analysis encompassing ADMET profiling, drug-likeness evaluation, principal component analysis (PCA), and molecular dynamic simulations (MDs) in comparison with the conventional drug, Mitomycin. Results: The natural compounds investigated demonstrated superior docking affinities to H. pylori targets compared to the standard Mitomycin. Notably, the phytocompounds Diosgenin and Sarsasapogenin stood out due to their exceptional binding affinities and pharmacokinetic properties, including favorable ADMET profiles. Conclusion: Our comprehensive and technologically-advanced approach showcases the potential of identified phytocompounds as pioneering therapeutic agents against H. pylori-induced gastric malignancies. In light of our promising in silico results, we recommend these natural compounds as potential candidates for advancing H. pylori-targeted drug development. Given their potential, we strongly advocate for subsequent in vitro and in vivo studies to validate their therapeutic efficacy against this formidable gastrointestinal bacterium.

Poisonous Plants of the Indian Himalaya: An Overview.

Indian Himalayan region (IHR) supports a wide diversity of plants and most of them are known for their medicinal value. Humankind has been using medicinal plants since the inception of civilization. Various types of bioactive compounds are found in plants, which are directly and indirectly beneficial for plants as well as humans. These bioactive compounds are highly useful and being used as a strong source of medicines, pharmaceuticals, agrochemicals, food additives, fragrances, and flavoring agents. Apart from this, several plant species contain some toxic compounds that affect the health of many forms of life as well as cause their death. These plants are known as poisonous plants, because of their toxicity to both humans and animals. Therefore, it is necessary to know in what quantity they should be taken so that it does not have a negative impact on health. Recent studies on poisonous plants have raised awareness among people who are at risk of plant toxicity in different parts of the world. The main aim of this review article is to explore the current knowledge about the poisonous plants of the Indian Himalayas along with the importance of these poisonous plants to treat different ailments. The findings of the present review will be helpful to different pharmaceutical industries, the scientific community and researchers around the world.

Therapeutic applications of curcumin nanomedicine formulations in cystic fibrosis.

Medicinal applications of turmeric-derived curcumin have been known to mankind for long ages. Its potential in managing "cystic fibrosis" has also been evaluated. This autosomal recessive genetic disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) which involves an impaired secretion of chloride ions and leads to hypersecretion of thick and sticky mucus and serious complications including airway obstruction, chronic lung infection, and inflammatory reactions. This narrative review aims to highlight the available evidence for the efficacy of curcumin nanoformulations in its potential treatment of cystic fibrosis. Recent research has shown that curcumin acts on the localized mutant CFTR ion channel at the plasma membrane. Preclinical studies have also shown that curcumin nanoformulations have promising effects in the treatment of cystic fibrosis. In this context, the purpose of this narrative review is to highlight the general bioactivity of curcumin, the types of formulations and related studies, thus opening new therapeutic perspectives for CF.

Diosgenin: An Updated Pharmacological Review and Therapeutic Perspectives.

Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin's pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin's nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin's safety profile.

Nutraceutical Profiling, Bioactive Composition, and Biological Applications of Lepidium sativum L.

The roots, leaves, and seeds of Lepidium sativum L., popularly known as Garden cress in different regions, have high economic importance; although, the crop is particularly cultivated for the seeds. In traditional medicine, this plant has been reported to possess various biological activities. This review is aimed at providing updated and critical scientific information about the traditional, nutritional, phytochemical, and biological activities of L. sativum. In addition, the geographic distribution is also reviewed. The comprehensive literature search was carried out with the help of different search engines PubMed, Web of Science, and Science Direct. This review highlighted the importance of L. sativum as an edible herb that possesses a wide range of therapeutic properties along with high nutritional values. Preclinical studies (in vitro and in vivo) displayed anticancer, hepatoprotective, antidiabetic, hypoglycemic, antioxidant, antimicrobial, gastrointestinal, and fracture/bone healing activities of L. sativum and support the clinical importance of plant-derived bioactive compounds for the treatment of different diseases. Screening of literature revealed that L. sativum species and their bioactive compounds may be a significant source for new drug compounds and also could be used against malnutrition. Further clinical trials are needed to effectively assess the actual potential of the species and its bioactive compounds.

Exploring the journey of emodin as a potential neuroprotective agent: Novel therapeutic insights with molecular mechanism of action.

Emodin is an anthraquinone derivative found in the roots and bark of a variety of plants, molds, and lichens. Emodin has been used as a traditional medication for more than 2000 years and is still common in numerous herbal drugs. Emodin is plentiful in the three plant families, including Polygonaceae (Rheum, Rumex, and Polygonum spp.), Fabaceae (Cassia spp.), and Rhamnaceae (Rhamnus, Frangula, and Ventilago spp.). Emerging experimental evidences indicate that emodin confers a wide range of pharmacological activities; special focus was implemented toward neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, anxiety and depression, schizophrenia, chronic hyperglycemic peripheral neuropathy, etc. Numerous preclinical evidences were established in support of the neuroprotection of emodin. However, this review highlighted the role of emodin as a potent neurotherapeutic agent; therefore, its evidence-based functionality on neurological disorders (NDs).

The Neuroprotective Potential of Endophytic Fungi and Proposed Molecular Mechanism: A Current Update.

Millions of people are affected by neuronal disorders that are emerging as a principal cause of death after cancer. Alzheimer's disease, ataxia, Parkinson's disease, multiple system atrophy, and autism comprise the most common ones, being accompanied by loss of cognitive power, impaired balance, and movement. In past decades, natural polyphenols obtained from different sources including bacteria, fungi, and plants have been utilized in the traditional system of medicine for the treatment of several ailments. Endophytes are one such natural producer of secondary metabolites, namely, polyphenols, which exhibit strong abilities to assist in the management of such affections, through modifying multiple therapeutic targets and weaken their complex physiology. Limited research has been conducted in detail on bioactive compounds present in the endophytic fungi and their neuroprotective effects. Therefore, this review aims to provide an update on scientific evidences related to the pharmacological and clinical potential along with proposed molecular mechanism of action of endophytes for neuronal protection.

Anticancer effects of acteoside: Mechanistic insights and therapeutic status.

Cancer, the uncontrolled proliferation and metastasis of abnormal cells, is a major public health issue worldwide. To date, several natural compounds have been reported with their efficacy in the treatment of different types of cancer. Chemotherapeutic agents are used in cancer treatment and prevention, among other aspects. Acteoside is a phenylethanoid glycoside, first isolated from Verbascum sinuatum, which has demonstrated multiple effects, including antioxidant, anti-epileptic, neuroprotective, anti-inflammatory, antifungal, antihypertensive, and anti-leishmanial properties. This review gathered, analyzed, and summarized the literature on acteoside and its anticancer properties. All the available information about this compound and its role in different types of cancer was collected using different scientific search engines, including PubMed, Scopus, Springer Link, Wiley Online, Web of Science, Scifinder, ScienceDirect, and Google Scholar. Acteoside is found in a variety of plants and has been shown to have anticancer activity in many experimental models through oxidative stress, apoptosis, anti-angiogenesis, anti-invasion, anti-metastasis, synergism with other agents, and anti-proliferative effects through modulation of several pathways. In conclusion, acteoside exhibited potent anticancer activity against different cancer cell lines through modulating several cancer signaling pathways in different non- and pre-clinical experimental models and thus could be a strong candidate for further clinical studies.

Nanoparticles in clinical trials of COVID-19: An update.

Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.

Xanthones: A Class of Heterocyclic Compounds with Anticancer Potential.

Xanthones (9H xanthen-9-one) are an important class of heterocyclic compounds containing oxygen and a moiety of gamma-pirone, dense with a two-benzene ring structure, distributed widely in nature. Naturally occurring xanthones are found in micro-organisms and higher plants as secondary metabolites in fungi and lichens. Compounds of the family Caryophyllaceae, Guttiferae and Gentianaceae, are the most common natural source of xanthones. The structure of the xanthones nucleus, coupled with its biogenetic source, imposes that the carbons are numbered according to the biosynthetic pact. The characteristics oxygenation pattern of xanthones earlier is mixed shikimateacetate biogenesis. The major class of xanthones includes simple oxygenated, non-oxygenated, xanthonolignoids, bisxanthones, prenylated and related xanthones, miscellaneous xanthones. Their great pharmacological importance and interesting scaffolds were highly encouraged by scientists to investigate either the synthesis design or natural products for cancer treatment. Because currently used antitumor drugs possess high toxicity and low selectivity, efficacious treatment may be compromised. This review is limited to the antitumor activity of xanthones and the chemistry of xanthone core, which may help provide fundamental knowledge to the medicinal chemist for new and advanced research in drug development.

Artemisia spp.: An Update on Its Chemical Composition, Pharmacological and Toxicological Profiles.

Artemisia plants are traditional and ethnopharmacologically used to treat several diseases and in addition in food, spices, and beverages. The genus is widely distributed in all continents except the Antarctica, and traditional medicine has been used as antimalarial, antioxidant, anticancer, antinociceptive, anti-inflammatory, and antiviral agents. This review is aimed at systematizing scientific data on the geographical distribution, chemical composition, and pharmacological and toxicological profiles of the Artemisia genus. Data from the literature on Artemisia plants were taken using electronic databases such as PubMed/MEDLINE, Scopus, and Web of Science. Selected papers for this updated study included data about phytochemicals, preclinical pharmacological experimental studies with molecular mechanisms included, clinical studies, and toxicological and safety data. In addition, ancient texts and books were consulted. The essential oils and phytochemicals of the Artemisia genus have reported important biological activities, among them the artemisinin, a sesquiterpene lactone, with antimalarial activity. Artemisia absinthium L. is one of the most famous Artemisia spp. due to its use in the production of the absinthe drink which is restricted in most countries because of neurotoxicity. The analyzed studies confirmed that Artemisia plants have many traditional and pharmacological applications. However, scientific data are limited to clinical and toxicological research. Therefore, further research is needed on these aspects to understand the full therapeutic potential and molecular pharmacological mechanisms of this medicinal species.