Moringa oleifera: A Tree of Life as a Promising Medicinal Plant for Neurodegenerative Diseases.

Moringa oleifera, popularly known as a miracle tree or tree of life, has been extensively used as a functional food and nutritional asset worldwide. Ethnomedicinal and traditional uses of M. oleifera indicate that this plant might have a pleiotropic therapeutic efficacy against most human ailments. In fact, M. oleifera is reported to have several pharmacological activities, including antioxidant, antibacterial, antifungal, antidiabetic, antipyretic, antiulcer, antispasmodic, antihypertensive, antitumor, hepatoprotective, and cardiac stimulant properties. Recently, a few experimental studies reported the neuroprotective effects of M. oleifera against Alzheimer's disease, dementia, Parkinson's disease, stroke, and neurotoxicity-related symptoms. In addition, several neuroprotective phytochemicals have been isolated from M. oleifera, which signifies that it can have promising neuroprotective effects. Therefore, this review aimed to explore the current updates and future prospective of neuroprotective efficacies of M. oleifera.

Tanshinone IIA: A phytochemical as a promising drug candidate for neurodegenerative diseases.

Tanshinones, lipophilic diterpenes isolated from the rhizome of Salvia miltiorrhiza, have diverse pharmacological activities against human ailments including neurological diseases. In fact, tanshinones have been used to treat heart diseases, stroke, and vascular diseases in traditional Chinese medicine. During the last decade, tanshinones have been the most widely studied phytochemicals for their neuroprotective effects against experimental models of cerebral ischemia and Alzheimer's diseases. Importantly, tanshinone IIA, mostly studied tanshinone for biological activities, is recently reported to attenuate blood-brain barrier permeability among stroke patients, suggesting tanshinone IIA as an appealing therapeutic candidate for neurological diseases. Tanshinone I and IIA are also effective in experimental models of Parkinson's disease, Multiple sclerosis, and other neuroinflammatory diseases. In addition, several experimental studies suggested the pleiotropic neuroprotective effects of tanshinones such as anti-inflammatory, antioxidant, anti-apoptotic, and BBB protectant further value aiding to tanshinone as an appealing therapeutic strategy in neurological diseases. Therefore, in this review, we aimed to compile the recent updates and cellular and molecular mechanisms of neuroprotection of tanshinone IIA in diverse neurological diseases.

Nitric Oxide as a Target for Phytochemicals in Anti-Neuroinflammatory Prevention Therapy.

Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS). Therefore, controlling excessive NO production is a desirable therapeutic strategy for managing various neuroinflammatory disorders. Recently, phytochemicals have attracted considerable attention because of their potential to counteract excessive NO production in CNS disorders. Moreover, phytochemicals and nutraceuticals are typically safe and effective. In this review, we discuss the mechanisms of NO production and its involvement in various neurological disorders, and we revisit a number of recently identified phytochemicals which may act as NO inhibitors. This review may help identify novel potent anti-inflammatory agents that can downregulate NO, specifically during neuroinflammation and neurodegeneration.

Adjunctive Nutraceutical Therapies for COVID-19.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.

Phytochemicals as regulators of microglia/macrophages activation in cerebral ischemia.

The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests from stroke scientists due to their strong brain protective effects in animal stroke models. The underlying mechanism of action is likely owing to their anti-inflammatory properties, even though other mechanisms such as anti-oxidation and vasculoprotection have also been proposed. It is generally held that the early proinflammatory responses after stroke can lead to a secondary brain injury, mainly due to the damaging effect exerted by over-activation of brain resident microglial cells and infiltration of circulating monocytes and macrophages. This review focuses on the anti-inflammatory properties of bioactive phytochemicals, including activation and polarization of microglia/macrophages in the post-ischemic brain. The latest studies in animal stroke models demonstrate that this group of bioactive phytochemicals exerts their anti-inflammatory effects via attenuation of brain proinflammatory microglia and macrophages M1 polarization while promoting anti-inflammatory microglial and macrophages M2 polarization. As a result, stroked animals treated with brain protective phytochemicals have significantly fewer brain active M1 microglia and macrophages, smaller brain infarct volume, better functional recovery, and better survival rate. Therefore, this review provides insights into a new category of drug candidates for stroke drug development by employing neuroprotective phytochemicals.

Sphingosine 1-Phosphate Receptors in Cerebral Ischemia.

Sphingosine 1-phosphate (S1P) is an important lipid biomolecule that exerts pleiotropic cellular actions as it binds to and activates its five G-protein-coupled receptors, S1P1-5. Through these receptors, S1P can mediate diverse biological activities in both healthy and diseased conditions. S1P is produced by S1P-producing enzymes, sphingosine kinases (SphK1 and SphK2), and is abundantly present in different organs, including the brain. The medically important roles of receptor-mediated S1P signaling are well characterized in multiple sclerosis because FTY720 (Gilenya™, Novartis), a non-selective S1P receptor modulator, is currently used as a treatment for this disease. In cerebral ischemia, its role is also notable because of FTY720's efficacy in both rodent models and human patients with cerebral ischemia. In particular, some of the S1P receptors, including S1P1, S1P2, and S1P3, have been identified as pathogenic players in cerebral ischemia. Other than these receptors, S1P itself and S1P-producing enzymes have been shown to play certain roles in cerebral ischemia. This review aims to compile the current updates and overviews about the roles of S1P signaling, along with a focus on S1P receptors in cerebral ischemia, based on recent studies that used in vivo rodent models of cerebral ischemia.

Herbal Medicine in Ischemic Stroke: Challenges and Prospective.

Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.

Anti-neuroinflammatory and neuroprotective effects of the Lindera neesiana fruit in vitro.

BACKGROUND: Lindera neesiana Kurz (Lauraceae), popularly known as Siltimur in Nepal, is an aromatic and spicy plant with edible fruits. It is a traditional herbal medicine widely used for the treatment of diarrhea, tooth pain, headache, and gastric disorders and is also used as a stimulant. PURPOSE: The aim of the present study was to examine in vitro cytoprotective, anti-neuroinflammatory and neuroprotective potential of an aqueous extract of L. neesiana (LNE) fruit using different central nervous system (CNS) cell lines. METHODS: In order to study the neuroprotective potential of LNE, we used three different types of CNS cell lines: murine microglia (BV2), rat glioma (C6), and mouse neuroblastoma (N2a). Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent, and prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and nerve growth factor (NGF) release in the culture media was determined using enzyme linked immunosorbent assay (ELISA) kits. Western blot analysis was performed to determine the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), mitogen activated protein kinase (MAPK) family proteins, Bax, B cell lymphoma (BCL)-2, and cleaved caspase 3. Neurite outgrowth was determined using the IncuCyte imaging system. RESULTS: LNE treatment not only reduced nitric oxide (NO) production in a dose-dependent manner, but also significantly reduced proinflammatory cytokines, iNOS and COX-2 production by lipopolysaccharide (LPS) stimulated BV-2 cells. LNE increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), whereas p-p38 and p- janus kinase (JNK) expression was significantly decreased in activated microglia. Furthermore, LNE increased cell viability of N2a cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl2 protein expression as well as increased NGF and neurite outgrowth, suggesting its neuroprotective potential against LPS-induced effects. Additionally, LNE substantially increased nuclear factor erythroid 2-related factor 2 (Nrf2) secretion in N2a cells and inhibited lipid dehydrogenase (LDH) release in H2O2-stimulated BV2 cells demonstrating the strong anti-inflammatory and antioxidant effects of LNE in CNS cell lines. CONCLUSION: Here we found that water the soluble extract of LNE has promising anti-neuroinflammation and anti-apoptotic properties and identify LNE as a potential natural candidate for neuroprotection.

Phytochemistry, pharmacology and medicinal properties of Phyllanthus emblica Linn.

Phyllanthus emblica L. (syn. Emblica officinalis) is commonly known as Indian gooseberry. In Ayurveda, P. emblica has been extensively used, both as edible (tonic) plants and for its therapeutic potentials. P. emblica is highly nutritious and is reported as an important dietary source of vitamin C, minerals and amino acids. All parts of the plant are used for medicinal purposes, especially the fruit, which has been used in Ayurveda as a potent Rasayana (rejuvenator). P. emblica contains phytochemicals including fixed oils, phosphatides, essential oils, tannins, minerals, vitamins, amino acids, fatty acids, glycosides, etc. Various pharmaceutical potential of P. emblica has been reported previously including antimicrobial, antioxidant, anti-inflammatory, analgesic and antipyretic, adaptogenic, hepatoprotective, antitumor and antiulcerogenic activities either in combined formulation or P. emblica alone. The various other Ayurvedic potentials of P. emblica are yet to be proven scientifically in order to explore its broad spectrum of therapeutic effects. On this regards we, in this review, tried to explore the complete information of P. emblica including its pharmacognosy, phytochemistry and pharmacology.

Neuroprotective effects of Fructus Chebulae extracts on experimental models of cerebral ischemia.

OBJECTIVE: To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and in vitro models of cerebral ischemia. METHODS: As an in vitro model, oxygen glucose deprivation followed by reoxygenation (OGD-R) and hydrogen peroxide (H2O2) induced cellular damage in rat pheochromocytoma (PC12) cells was used to investigate the neuroprotective effects of extract of Fructus Chebulae. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to calculate cell survival. For in vivo, occlusion of left middle cerebral artery on rats was carried out as a focal cerebral ischemic model. RESULTS: Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2 by 68% and 91.4% respectively. Fructus Chebulae also decreases the cerebral infarct volume by 39% and extent of hemisphere swelling from 17% in control group to 10% in Fructus Chebulae treated group. CONCLUSION: Fructus Chebulae, as a traditional medicine, can rescue the neuronal cell death against ischemia related damage. The possible mechanism for the neuroprotection might be the inhibition of oxidative damages occurring after acute phase of cerebral ischemia.

Scutellaria baicalensis in stroke management: nature's blessing in traditional Eastern medicine.

Scutellaria baicalensis Georgi is the most widely used medicinal plant in traditional Eastern medicine, especially in Chinese medicine. The major phytochemicals isolated from S. baicalensis are flavonoids, glycosides and their glucoronides such as baicalin, baicalein, wogonin etc. More than 30 different kinds of flavonoids are isolated from this plant. S. baicalensis and its flavonoids are reported to have several pharmacological activities, which includes anti-allergic, antioxidant, anti apoptic, anti-inflammatory effects and many more. Recently, S. baicalensis and its isolated flavonoids have been studied for their neuroprotective effects, through a variety of in vitro and in vivo models of neurodegenerative diseases, plausibly suggesting that S. baicalensis has salutary effect as a nature's blessing for neuroprotection. In this review, we are focousing on the neuroprotective effects of S. baicalensis and its flavonoids in ischemia or stroke-induced neuronal cell death. We aimed at compiling all the information regarding the neuroprotective effect of S. baicalensis in various experimental models of cerebral ischemia or stroke.

Terminalia chebula extract protects OGD-R induced PC12 cell death and inhibits lps induced microglia activation.

Terminalia chebula, native to Southeast Asia, is a popular medicinal plant in Ayurveda. It has been previously reported to have strong antioxidant and anti-inflammatory efficacy. In this study, we aimed to investigate if fruit extract from T. chebula might protect neuronal cells against ischemia and related diseases by reduction of oxidative damage and inflammation in rat pheochromocytoma cells (PC12) using in vitro oxygen-glucose deprivation followed by reoxygenation (OGD-R) ischemia and hydrogen peroxide (H2O2) induced cell death. Cell survival was evaluated by a 2-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Free radical scavenging, lipid peroxidation and nitric oxide inhibition were measured by diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid (TBA) and Griess reagent, respectively. We found that T. chebula extract: (1) increases the survival of cells subjected to OGD-R by 68%, and H2O2 by 91.4%; (2) scavenges the DPPH free radical by 96% and decreases malondialdehyde (MDA) levels from 237.0 ± 15.2% to 93.7 ± 2.2%; (3) reduces NO production and death rate of microglia cells stimulated by lipopolysaccharide (LPS). These results suggest that T. chebula extract has the potential as a natural herbal medicine, to protect the cells from ischemic damage and the possible mechanism might be the inhibition of oxidative and inflammatory processes.

A review on the pharmacological and toxicological aspects of Datura stramonium L.

Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.

A review on the pharmacological and toxicological aspects of Datura stramonium L / 中西医结合学报

Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.

Anti-obesity effect of HT048, a herbal combination, in high fat diet-induced obese rats.

This study evaluated the anti-obesity effects of HT048, a combination of C. pinnatifida fruit and C. unshiu peel extracts, in high-fat diet (HFD)-induced obese rats. 4-Week-old male Sprague Dawley (SD) rats were divided into normal and high fat diet (HFD) groups. The HFD groups were further divided into five groups treated with distilled water, orlistat (40 mg/kg, twice daily, p.o) and HT048 (30, 100 and 300 mg/kg, twice daily, p.o.) for 12 weeks. Orlistat, an anti-obesity drug, was used as positive control in the HFD-induced obese rats. We measured the food intake, body weight, epididymal adipose tissue and liver weights, and serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) levels. The body weight and epididymal adipose tissue and liver weights of the HT048 100 and 300 mg/kg treated groups were significantly lower than that of the HFD control group. Also, serum TC, TG, ALT, and AST levels in the HT048 100 and 300 mg/kg treated groups were significantly decreased. Moreover, the orlistat treated group showed significantly reduced body weight and improved serum lipoprotein, compared with the HFD control group. These results show that HT048 supplements improved obesity-related body weight and serum lipoprotein parameters in a HFD-induced obese rat model.