Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays.

BACKGROUND: A previously unstudied medicinal plant, Leucophyllum frutescens (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer's disease. METHODS: Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including in vitro enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active n-butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC-MS/MS), and in silico molecular docking by Maestro® Schrödinger. RESULTS: The n-butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The in vivo study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC-MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6'-O-malonate, diosmetin-7-O-glucuronide-3'-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3'-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6'-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase. CONCLUSIONS: The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.

Prevention of Inflammation Initiation on Acetic Acid-Induced Ulcerative Colitis in Rats by Malva nicaeensis All.

BACKGROUND: Aerial parts of Malva nicaeensis All. are preferred in the prevention and treatment of intestinal infections and hemorrhoids in Turkish traditional medicine. This study is planned to evaluate the pharmacological activity of M. nicaeensis extracts on rats with acetic acid-induced colitis. METHODS: The plant material was subsequently extracted with n-hexane, ethanol, and water, respectively. All of these extracts were tested for efficacy in the acetic acid-induced rat colitis model. The aqueous and polysaccharide extracts regulated cytokine levels and antioxidant parameters. Furthermore, the aqueous extract in particular regulated myeloperoxidase and caspase-3 levels in this rat model. In addition, the polysaccharide-rich fraction was separated from the aqueous extract. RESULTS: The polysaccharide-rich fraction and aqueous extract regulated cytokine levels and antioxidant parameters. The aqueous extract also positively affected myeloperoxidase and caspase-3 levels. The phytochemical studies revealed that the aqueous extract had the highest phenolic content. In addition, the polysaccharide fraction was found to contain total sugars, sulfated groups, uronic acids, and total proteins in 78.4%, 0.9%, 1.5%, and 14.7%, respectively, and was rich in monosaccharide-type compounds, especially galactose (36.4%). CONCLUSIONS: M. nicaeensis was discovered to be a drug lead in the future treatment of irritable bowel diseases or as a complementary therapeutic agent that aided conventional treatments.

Terapia médico-nutricional en pacientes politraumatizados: una carrera contra el tiempo.

A polytraumatized patient is defined as one who has multiple lesions involving different organs and systems, which are usually serious and lead to life-threatening respiratory or circulatory dysfunction. Traumatic stress in the polytraumatized patient results in many metabolic changes that are evident from the first days, but usually persist for weeks, requiring adequate nutritional support as they influence outcomes. Nutritional treatment should be a priority in the comprehensive treatment of polytraumatized patients since it attenuates the metabolic response to trauma and prevents the deterioration of body reserves. It should be noted that some patients present previous nutritional risk. Nutritional intervention should be considered at the same level as any other therapy that supports organic functions, especially in patients in the intensive care unit. Nutritional intervention in polytraumatized patients is a pillar of treatment that has multiple benefits and can improve prognosis. All efforts must be aimed at the early detection of malnourished patients at nutritional risk and providing timely therapies that improve clinical outcomes.

El paciente politraumatizado se define como aquel que tiene múltiples lesiones que involucran diferentes órganos y sistemas, suelen ser graves y conllevan una disfunción respiratoria o circulatoria que pone en riesgo la vida. El estrés traumático en el paciente politraumatizado da lugar a muchos cambios metabólicos que son evidentes desde los primeros días, pero suelen persistir durante semanas y exigen un adecuado soporte nutricional, ya que influyen en los desenlaces. El tratamiento nutricional debe ser una prioridad en el tratamiento integral de los pacientes politraumatizados, porque atenúa la respuesta metabólica al trauma y evita el deterioro de las reservas corporales (cabe mencionar que algunos pacientes presentan riesgo nutricional previo). La intervención nutricional debe considerarse al mismo nivel que cualquier otra terapia que apoye las funciones orgánicas, sobre todo en pacientes en la unidad de terapia intensiva. La intervención nutricional en pacientes politraumatizados es un pilar en el tratamiento que tiene múltiples beneficios y puede mejorar el pronóstico. Todo esfuerzo debe ir encaminado a la detección temprana de pacientes desnutridos o en riesgo nutricional, y proporcionar de manera oportuna terapias que mejores los desenlaces clínicos.

Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites.

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.

Phytochemical Composition and Biological Activities of Arctium minus (Hill) Bernh.: A Potential Candidate as Antioxidant, Enzyme Inhibitor, and Cytotoxic Agent.

Arctium minus (Hill) Bernh. (Asteraceae), which has a wide distribution area in Turkey, is a medicinally important plant. Eighty percent methanol extracts of the leaf, flower head, and root parts of A. minus were prepared and their sub-fractions were obtained. Spectrophotometric and chromatographic (high-performance liquid chromatography) techniques were used to assess the phytochemical composition. The extracts were evaluated for antioxidant activity by diphenyl-2-picrylhydrazil radical (DPPH●), 2,2'-Azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS●+) radical scavenging, and ß-carotene linoleic acid bleaching assays. Furthermore, the extracts were subjected to α-amylase, α-glucosidase, lipoxygenase, and tyrosinase enzyme inhibition tests. The cytotoxic effects of extracts were investigated on MCF-7 and MDA-MB-231 breast cancer cell lines. The richest extract in terms of phenolic compounds was identified as the ethyl acetate sub-fraction of the root extract (364.37 ± 7.18 mgGAE/gextact). Furthermore, chlorogenic acid (8.855 ± 0.175%) and rutin (8.359 ± 0.125%) were identified as the primary components in the leaves' ethyl acetate sub-fraction. According to all methods, it was observed that the extracts with the highest antioxidant activity were the flower and leaf ethyl acetate fractions. Additionally, ABTS radical scavenging activity of roots' ethyl acetate sub-fraction (2.51 ± 0.09 mmol/L Trolox) was observed to be as effective as that of flower and leaf ethyl acetate fractions at 0.5 mg/mL. In the ß-carotene linoleic acid bleaching assay, leaves' methanol extract showed the highest antioxidant capacity (1422.47 ± 76.85) at 30 min. The enzyme activity data showed that α-glucosidase enzyme inhibition of leaf dichloromethane extract was moderately high, with an 87.12 ± 8.06% inhibition value. Lipoxygenase enzyme inhibition was weakly detected in all sub-fractions. Leaf methanol extract, leaf butanol, and root ethyl acetate sub-fractions showed 99% tyrosinase enzyme inhibition. Finally, it was discovered that dichloromethane extracts of leaves, roots, and flowers had high cytotoxic effects on the MDA-MB-231 cell line, with IC50 values of 21.39 ± 2.43, 13.41 ± 2.37, and 10.80 ± 1.26 µg/mL, respectively. The evaluation of the plant extracts in terms of several bioactivity tests revealed extremely positive outcomes. The data of this study, in which all parts of the plant were investigated in detail for the first time, offer promising results for future research.

In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.

Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations.

Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined.

Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke.

Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel in the brain, called ischemic stroke and hemorrhagic stroke, respectively. Stroke is more common in men than women. Atrial fibrillation, hypertension, kidney disease, high cholesterol and lipids, genetic predisposition, inactivity, poor nutrition, diabetes mellitus, family history and smoking are factors that increase the risk of stroke. Restoring blood flow by repositioning blocked arteries using thrombolytic agents or endovascular therapy are the most effective treatments for stroke. However, restoring circulation after thrombolysis can cause fatal edema or intracranial hemorrhage, and worsen brain damage in a process known as ischemia-reperfusion injury. Therefore, there is a pressing need to find and develop more effective treatments for stroke. In the past, the first choice of treatment was based on natural compounds. Natural compounds are able to reduce the symptoms and reduce various diseases including stroke that attract the attention of the pharmaceutical industry. Nowadays, as a result of the numerous studies carried out in the field of herbal medicine, many useful and valuable effects of plants have been identified. The death-associated protein kinase (DAPK) family is one of the vital families of serine/threonine kinases involved in the regulation of some biological functions in human cells. DAPK1 is the most studied kinase within the DAPKs family as it is involved in neuronal and recovery processes. Dysregulation of DAPK1 in the brain is involved in the developing neurological diseases such as stroke. Natural products can function in a variety of ways, including reducing cerebral edema, reducing brain endothelial cell death, and inhibiting TNFα and interleukin-1ß (IL-1ß) through regulating the DAPK1 signal against stroke. Due to the role of DAPK1 in neurological disorders, the aim of this article was to investigate the role of DAPK1 in stroke and its modulation by natural compounds.

The Role of Natural Products in Treatment of Depressive Disorder.

Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's life. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic- pituitary-adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.

A Critical Analysis of Quercetin as the Attractive Target for the Treatment of Parkinson's Disease.

Parkinson's Disease (PD) is a multifaceted disorder with various factors suggested to play a synergistic pathophysiological role, such as oxidative stress, autophagy, pro-inflammatory events, and neurotransmitter abnormalities. While it is crucial to discover new treatments in addition to preventing PD, recent studies have focused on determining whether nutraceuticals will exert neuroprotective actions and pharmacological functions in PD. Quercetin, a flavonol-type flavonoid, is found in many fruits and vegetables and is recognised as a complementary therapy for PD. The neuroprotective effect of quercetin is directly associated with its antioxidant activity, in addition to stimulating cellular defence against oxidative stress. Other related mechanisms are activating Sirtuins (SIRT1) and inducing autophagy, in addition to induction of Nrf2-ARE and Paraoxonase 2 (PON2). Quercetin, whose neuroprotective activity has been demonstrated in many studies, unfortunately, has a disadvantage because of its poor water solubility, chemical instability, and low oral bioavailability. It has been reported that the disadvantages of quercetin have been eliminated with nanocarriers loaded with quercetin. The role of nanotechnology and nanodelivery systems in reducing oxidative stress during PD provides an indisputable advantage. Accordingly, the present review aims to shed light on quercetin's beneficial effects and underlying mechanisms in neuroprotection. In addition, the contribution of nanodelivery systems to the neuroprotective effect of quercetin is also discussed.

Impact of Probiotics on the Performance of Endurance Athletes: A Systematic Review.

BACKGROUND: Probiotic supplements contain different strains of living microorganisms that promote the health of the host. These dietary supplements are increasingly being used by athletes to improve different aspects such as athletic performance, upper respiratory tract infections (URTIs), the immune system, oxidative stress, gastrointestinal (GI) problems, etc. This study aimed to identify the current evidence on the management of probiotics in endurance athletes and their relationship with sports performance. METHODS: A systematic review of the last five years was carried out in PubMed, Scopus, Web of science, Sportdiscus and Embase databases. RESULTS: Nine articles met the quality criteria. Of these, three reported direct benefits on sports performance. The remaining six articles found improvements in the reduction of oxidative stress, increased immune response and decreased incidence of URTIs. There is little scientific evidence on the direct relationship between the administration of probiotics in endurance athletes and sports performance. CONCLUSIONS: Benefits were found that probiotics could indirectly influence sports performance by improving other parameters such as the immune system, response to URTIs and decreased oxidative stress, as well as the monitoring of scheduled workouts.

Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson's Disease.

Parkinson's disease (PD) is one of the most prevalent and debilitating neurodegenerative conditions, and is currently on the rise. Several dysregulated pathways are behind the pathogenesis of PD; however, the critical targets remain unclear. Accordingly, there is an urgent need to reveal the key dysregulated pathways in PD. Prevailing reports have highlighted the importance of mitochondrial and cross-talked mediators in neurological disorders, genetic changes, and related complications of PD. Multiple pathophysiological mechanisms of PD, as well as the low efficacy and side effects of conventional neuroprotective therapies, drive the need for finding novel alternative agents. Recently, much attention has been paid to using plant secondary metabolites (e.g., flavonoids/phenolic compounds, alkaloids, and terpenoids) in the modulation of PD-associated manifestations by targeting mitochondria. In this line, plant secondary metabolites have shown promising potential for the simultaneous modulation of mitochondrial apoptosis and reactive oxygen species. This review aimed to address mitochondria and multiple dysregulated pathways in PD by plant-derived secondary metabolites.

Multifunctional Therapeutic Potential of Phytocomplexes and Natural Extracts for Antimicrobial Properties.

Natural products have been known for their antimicrobial factors since time immemorial. Infectious diseases are a worldwide burden that have been deteriorating because of the improvement of species impervious to various anti-infection agents. Hence, the distinguishing proof of antimicrobial specialists with high-power dynamic against MDR microorganisms is central to conquer this issue. Successful treatment of infection involves the improvement of new drugs or some common source of novel medications. Numerous naturally occurring antimicrobial agents can be of plant origin, animal origin, microbial origin, etc. Many plant and animal products have antimicrobial activities due to various active principles, secondary metabolites, or phytochemicals like alkaloids, tannins, terpenoids, essential oils, flavonoids, lectins, phagocytic cells, and many other organic constituents. Phytocomplexes' antimicrobial movement frequently results from a few particles acting in cooperative energy, and the clinical impacts might be because of the direct effects against microorganisms. The restorative plants that may furnish novel medication lead the antimicrobial movement. The purpose of this study is to investigate the antimicrobial properties of the phytocomplexes and natural extracts of the plants that are ordinarily being utilized as conventional medications and then recommended the chance of utilizing them in drugs for the treatment of multiple drug-resistant disease.

Promising Perspective to Facioscapulohumeral Muscular Dystrophy Treatment: Nutraceuticals and Phytochemicals.

Facioscapulohumeral Muscular Dystrophy (FSHD) is in the top three list of all dystrophies with an approximate 1:8000 incidence. It is not a life-threatening disease; however, the progression of the disease extends over being wheelchair bound. Despite some drug trials continuing, including DUX4 inhibition, TGF-ß inhibition and resokine which promote healthier muscle, there is not an applicable treatment option for FSHD today. Still, there is a need for new agents to heal, stop or at least slow down muscle wasting. Current FSHD studies involving nutraceuticals as vitamin C, vitamin E, coenzyme Q10, zinc, selenium, and phytochemicals as curcumin or genistein, daidzein flavonoids provide promising treatment strategies. In this review, we present the clinical and molecular nature of FSHD and focus on nutraceuticals and phytochemicals that may alleviate FSHD. In the light of the association of impaired pathophysiological FSHD pathways with nutraceuticals and phytochemicals according to the literature, we present both studied and novel approaches that can contribute to FSHD treatment.

Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens.

Ageratum conyzoides L. (Family-Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant's dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.

Natural Compounds as Medical Strategies in the Prevention and Treatment of Psychiatric Disorders Seen in Neurological Diseases.

Psychiatric disorders are frequently encountered in many neurological disorders, such as Alzheimer's and Parkinson diseases along with epilepsy, migraine, essential tremors, and stroke. The most common comorbid diagnoses in neurological diseases are depression and anxiety disorders along with cognitive impairment. Whether the underlying reason is due to common neurochemical mechanisms or loss of previous functioning level, comorbidities are often overlooked. Various treatment options are available, such as pharmacological treatments, cognitive-behavioral therapy, somatic interventions, or electroconvulsive therapy. However oral antidepressant therapy may have some disadvantages, such as interaction with other medications, low tolerability due to side effects, and low efficiency. Natural compounds of plant origin are extensively researched to find a better and safer alternative treatment. Experimental studies have shown that phytochemicals such as alkaloids, terpenes, flavonoids, phenolic acids as well as lipids have significant potential in in vitro and in vivo models of psychiatric disorders. In this review, various efficacy of natural products in in vitro and in vivo studies on neuroprotective and their roles in psychiatric disorders are examined and their neuro-therapeutic potentials are shed light.

Role of natural products for the treatment of Alzheimer's disease.

Negative psychological and physiological consequences of neurodegenerative disorders represent a high social and health cost. Among the neurodegenerative disorders Alzheimer's disease (AD) is recognized as a leading neurodegenerative condition and a primary cause of dementia in the elderlys. AD is considered as neurodegenerative disorder that progressively impairs cognitive function and memory. According to current epidemiological data, about 50 milLion people worldwide are suffering from AD. The primary symptoms of AD are almost inappreciable and usually comprise forgetfulness of recent events. Numerous processes are involved in the development of AD, for example oxidative stress (OS) mainly due to mitochondrial dysfunction, intracellular the accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, excessive the accumulation of extracellular plaques of beta-amyloid (Aß), genetic and environmental factors. Running treatments only attenuate symptoms and temporarily reduce the rate of cognitive progression associated with AD. This means that most treatments focus only on controlLing symptoms, particularly in the initial stages of the disease. In the past, the first choice of treatment was based on natural ingredients. In this sense, diverse natural products (NPs) are capable to decrease the symptoms and alleviate the development of several diseases including AD attracting the attention of the scientific community and the pharmaceutical industry. Specifically, numerous NPs including flavonoids, gingerols, tannins, anthocyanins, triterpenes and alkaloids have been shown anti-inflammatory, antioxidant, anti-amyloidogenic, and anti-choLinesterase properties. This review provide a summary of the pathogenesis and the therapeutic goals of AD. It also discusses the available data on various plants and isolated natural compounds used to prevent and diminish the symptoms of AD.

Attenuation of Nrf2/Keap1/ARE in Alzheimer's Disease by Plant Secondary Metabolites: A Mechanistic Review.

Alzheimer's disease (AD) is a progressive neuronal/cognitional dysfunction, leading to disability and death. Despite advances in revealing the pathophysiological mechanisms behind AD, no effective treatment has yet been provided. It urges the need for finding novel multi-target agents in combating the complex dysregulated mechanisms in AD. Amongst the dysregulated pathophysiological pathways in AD, oxidative stress seems to play a critical role in the pathogenesis progression of AD, with a dominant role of nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1)/antioxidant responsive elements (ARE) pathway. In the present study, a comprehensive review was conducted using the existing electronic databases, including PubMed, Medline, Web of Science, and Scopus, as well as related articles in the field. Nrf2/Keap1/ARE has shown to be the upstream orchestrate of oxidative pathways, which also ameliorates various inflammatory and apoptotic pathways. So, developing multi-target agents with higher efficacy and lower side effects could pave the road in the prevention/management of AD. The plant kingdom is now a great source of natural secondary metabolites in targeting Nrf2/Keap1/ARE. Among natural entities, phenolic compounds, alkaloids, terpene/terpenoids, carotenoids, sulfur-compounds, as well as some other miscellaneous plant-derived compounds have shown promising future accordingly. Prevailing evidence has shown that activating Nrf2/ARE and downstream antioxidant enzymes, as well as inhibiting Keap1 could play hopeful roles in overcoming AD. The current review highlights the neuroprotective effects of plant secondary metabolites through targeting Nrf2/Keap1/ARE and downstream interconnected mediators in combating AD.

A phytopharmacological overview of medicinal plants used for prophylactic and treatment of colitis.

Inflammatory bowel diseases are chronic diseases that develop on the genetic background. They are characterized by an idiopathic, chronic course and periods of activation and remission. However, genetic and environmental factors are thought to play a role in its pathogenesis. Significant improvements in treatment strategies have been witnessed. Depending on the severity of the disease, mesalamine, immunosuppressants, anti-TNF, anti-integrin, Janus kinase inhibitors, and thiopurines can be used for treatment. However, these treatments have side effects such as headache, dizziness, nausea, loss of appetite, hair loss, gas, vomiting, rash, fever, and decreased white blood cell count. The search for treatment that may be a safer alternative, immunomodulatory, and immunosuppressive therapy has gained importance nowadays. Herbal medicine is preferred to treat a wide range of acute and chronic gastrointestinal diseases, including ulcerative colitis. Preclinical and clinical studies show that plants are promising in terms of their use in treating pathological conditions. The effectiveness of plants in treating ulcerative colitis has been determined. However, more studies are needed to explore the long-term effects of these herbal medicines. The present review presents information on medicinal plants and phytochemicals reported for use or potential of application in ulcerative colitis, a type of inflammatory bowel diseases.