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.

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.

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.

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.

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.

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.

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).

A Review of Recent Studies on the Antioxidant and Anti-Infectious Properties of Senna Plants.

The use of phytochemicals is gaining interest for the treatment of metabolic syndromes over the synthetic formulation of drugs. Senna is evolving as one of the important plants which have been vastly studied for its beneficial effects. Various parts of Senna species including the root, stem, leaves, and flower are found rich in numerous phytochemicals. In vitro, in vivo, and clinical experiments established that extracts from Senna plants have diverse beneficial effects by acting as a strong antioxidant and antimicrobial agent. In this review, Senna genus is comprehensively discussed in terms of its botanical characteristics, traditional use, geographic presence, and phytochemical profile. The bioactive compound richness contributes to the biological activity of Senna plant extracts. The review emphasizes on the in vivo and in vitro antioxidant and anti-infectious properties of the Senna plant. Preclinical studies confirmed the beneficial effects of the Senna plant extracts and its bioactive components in regard to the health-promoting activities. The safety, side effects, and therapeutic limitations of the Senna plant are also discussed in this review. Additional research is necessary to utilize the phenolic compounds towards its use as an alternative to pharmacological treatments and even as an ingredient in functional foods.

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.

Papaver Plants: Current Insights on Phytochemical and Nutritional Composition Along with Biotechnological Applications.

The genus Papaver is highly esteemed in the pharmacy industry, in the culinary field, and as ornamental plants. These plants are also valued in traditional medicine. Among all Papaver species, Papaver somniferum L. (opium poppy) is the most important species in supplying phytochemicals for the formulation of drugs, mainly alkaloids like morphine, codeine, rhoeadine, thebaine, and papaverine. In addition, Papaver plants present other types of phytochemicals, which altogether are responsible for its biological activities. Therefore, this review covers the phytochemical composition of Papaver plants, including alkaloids, phenolic compounds, and essential oils. The traditional uses are reviewed along with their pharmacological activities. Moreover, safety aspects are reported to provide a deep overview of the pharmacology potential of this genus. An updated search was carried out in databases such as Google Scholar, ScienceDirect, and PubMed to retrieve the information. Overall, this genus is a rich source of alkaloids of different types and also contains interesting phenolic compounds, such as anthocyanins, flavonols, and the characteristic indole derivatives nudicaulins. Among other pharmacological properties, numerous preclinical studies have been published about the analgesic, anticancer, antimicrobial, antioxidant, and antidiabetic activities of Papaver plants. Although it highlights the significant impact of this genus for the treatment of a variety of diseases and conditions, as a future prospect, characterization works accompanying preclinical studies are required along with clinical and toxicology studies to establish a correlation between the scientific and traditional knowledge.

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.

Antispasmodic Potential of Medicinal Plants: A Comprehensive Review.

Numerous medicinal plants have been utilized for the treatment of different types of diseases and disorders including gastrointestinal (GI) diseases. GI diseases are the most common complaints that normally affects the largest proportion of children and adolescents with overlapping clinical manifestation in diagnosis and medical needs. Drugs with antispasmodic effects are normally applied for the symptomatic treatment of contraction and cramping of smooth muscles in gastrointestinal diseases as well as in other critical clinical situations. In alternative system of medicines, the antispasmodic herbs played a significant role in the cure of GI diseases. These medicinal plants and their herbal products are used from generation to generation because of multiple nutritional and therapeutic benefits. The multiple uses might be attributed to the presence on biologically active chemical constitutes. The main aim of this review is to focus on the medicinal potential of plants possessing antispasmodic activities with their proposed mechanism of action. Several databases such as Google Scholar, Cochrane database, Scopus, and PubMed were used to search the relevant literature regarding "plants with antispasmodic activities." This present study highlights the updated and quantified information on several medicinal plants with antispasmodic activity like Zanthoxylum armatum, Matricaria chamomilla, Foeniculum vulgare, Pycnocycla spinosa, Atropa belladonna, Lavandula angustifolia, Mentha pulegium, Glycyrrhiza ularensis, Anethum graveolens, and Origanum majorana. Moreover, recent studies on other medicinal plant species also have been included in this review article. Additionally, the study also revealed that the active compounds of all these plants possess significant spasmolytic effect which is safest, efficacious, and cost effective as compared to the available synthetic drugs.

Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, Phytochemical, and Pharmacological Overview of the Himalayan Ferns.

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes. Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum. The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum, but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as "Diplazium esculentum, bioactive compounds, biological activities and health benefits" from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo, and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species.

Paving Plant-Food-Derived Bioactives as Effective Therapeutic Agents in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, where social and communication deficits and repetitive behaviors are present. Plant-derived bioactives have shown promising results in the treatment of autism. In this sense, this review is aimed at providing a careful view on the use of plant-derived bioactive molecules for the treatment of autism. Among the plethora of bioactives, curcumin, luteolin, and resveratrol have revealed excellent neuroprotective effects and can be effectively used in the treatment of neuropsychological disorders. However, the number of clinical trials is limited, and none of them have been approved for the treatment of autism or autism-related disorder. Further clinical studies are needed to effectively assess the real potential of such bioactive molecules.

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy.

Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.

Peganum spp.: A Comprehensive Review on Bioactivities and Health-Enhancing Effects and Their Potential for the Formulation of Functional Foods and Pharmaceutical Drugs.

The genus Peganum includes four species widely distributed in warm temperate to subtropical regions from the Mediterranean to Mongolia as well as certain regions in America. Among these species, Peganum harmala L., distributed from the Mediterranean region to Central Asia, has been studied and its phytochemical profile, traditional folk use, and application in pharmacological and clinical trials are well known. The review is aimed at presenting an insight into the botanical features and geographical distribution of Peganum spp. along with traditional folk uses. This manuscript also reviews the phytochemical profile of Peganum spp. and its correlation with biological activities evidenced by the in vitro and in vivo investigations. Moreover, this review gives us an understanding of the bioactive compounds from Peganum as health promoters followed by the safety and adverse effects on human health. In relation to their multipurpose therapeutic properties, various parts of this plant such as seeds, bark, and roots present bioactive compounds promoting health benefits. An updated search (until December 2020) was carried out in databases such as PubMed and ScienceDirect. Chemical studies have presented beta-carboline alkaloids as the most active constituents, with harmalol, harmaline, and harmine being the latest and most studied among these naturally occurring alkaloids. The Peganum spp. extracts have shown neuroprotective, anticancer, antimicrobial, and antiviral effects. The extracts are also found effective in improving respiratory disorders (asthma and cough conditions), dermatoses, and knee osteoarthritis. Bioactivities and health-enhancing effects of Peganum spp. make it a potential candidate for the formulation of functional foods and pharmaceutical drugs. Nevertheless, adverse effects of this plant have also been described, and therefore new bioproducts need to be studied in depth. In fact, the design of new formulations and nanoformulations to control the release of active compounds will be necessary to achieve successful pharmacological and therapeutic treatments.

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.

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications.

Several flavonoids have been recognized as nutraceuticals, and myricetin is a good example. Myricetin is commonly found in plants and their antimicrobial and antioxidant activities is well demonstrated. One of its beneficial biological effects is the neuroprotective activity, showing preclinical activities on Alzheimer, Parkinson, and Huntington diseases, and even in amyotrophic lateral sclerosis. Also, myricetin has revealed other biological activities, among them as antidiabetic, anticancer, immunomodulatory, cardiovascular, analgesic and antihypertensive. However, few clinical trials have been performed using myricetin as nutraceutical. Thus, this review provides new insights on myricetin preclinical pharmacological activities, and role in selected clinical trials.