Neuropharmacological insights into Gardenia jasminoides Ellis: Harnessing therapeutic potential for central nervous system disorders.

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well documented in the literature, highlighting its significant medicinal potential.

Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is widely used in clinical practice to treat diseases related to central nervous system (CNS) damage. However, the blood-brain barrier (BBB) constitutes a significant impediment to the effective delivery of TCM, thus substantially diminishing its efficacy. Advances in nanotechnology and its applications in TCM (also known as nano-TCM) can deliver active ingredients or components of TCM across the BBB to the targeted brain region. This review provides an overview of the physiological and pathological mechanisms of the BBB and systematically classifies the common TCM used to treat CNS diseases and types of nanocarriers that effectively deliver TCM to the brain. Additionally, drug delivery strategies for nano-TCMs that utilize in vivo physiological properties or in vitro devices to bypass or cross the BBB are discussed. This review further focuses on the application of nano-TCMs in the treatment of various CNS diseases. Finally, this article anticipates a design strategy for nano-TCMs with higher delivery efficiency and probes their application potential in treating a wider range of CNS diseases.

Food-Derived Peptides: Beneficial CNS Effects and Cross-BBB Transmission Strategies.

Food-derived peptides, as dietary supplements, have significant effects on promoting brain health and relieving central nervous system (CNS) diseases. However, the blood-brain barrier (BBB) greatly limits their in-brain bioavailability. Thus, overcoming the BBB to target the CNS is a major challenge for bioactive peptides in the prevention and treatment of CNS diseases. This review discusses improvement in the neuroprotective function of food-derived active peptides in CNS diseases, as well as the source of BBB penetrating peptides (BBB-shuttles) and the mechanism of transmembrane transport. Notably, this review also discusses various peptide modification methods to overcome the low permeability and stability of the BBB. Lipification, glycosylation, introduction of disulfide bonds, and cyclization are effective strategies for improving the penetration efficiency of peptides through the BBB. This review provides a new prospective for improving their neuroprotective function and developing treatments to delay or even prevent CNS diseases.

Nanocarrier-mediated curcumin delivery: An adjuvant strategy for CNS disease treatment.

Neurological disorders are a major global challenge, which counts for a substantial slice of disease burden around the globe. In these, the challenging landscape of central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and neuro-AIDS, demands innovative and novel therapeutic approaches. Curcumin, a versatile natural compound with antioxidant and anti-inflammatory properties, shows great potential as a CNS adjuvant therapy. However, its limited bioavailability and suboptimal permeability to the blood-brain barrier (BBB) hamper the therapeutic efficacy of curcumin. This review explores how nanocarrier facilitates curcumin delivery, which has shown therapeutic efficacy for various non-CNS diseases, for example, cancers, and can also revolutionize the treatment outcomes in patients with CNS diseases. Toward this, intranasal administration of curcumin as a non-invasive CNS drug delivery route can also aid its therapeutic outcomes as an adjuvant therapy for CNS diseases. Intranasal delivery of nanocarriers with curcumin improves the bioavailability of curcumin and its BBB permeability, which is instrumental in promoting its therapeutic potential. Furthermore, curcumin's inhibitory effect on efflux transporters will help to enhance the BBB and cellular permeability of various CNS drugs. The therapeutic potential of curcumin as an adjuvant has the potential to yield synergistic effects with CNS drugs and will help to reduce CNS drug doses and improve their safety profile. Taken together, this approach holds a promise for reshaping CNS disease management by maximizing curcumin's and other drugs' therapeutic benefits.

Pterostilbene as a Therapeutic Alternative for Central Nervous System Disorders: A Review of the Current Status and Perspectives.

Neurological disorders are diverse, have complex causes, and often result in disability; yet, effective treatments remain scarce. The resveratrol derivative pterostilbene possesses numerous physiological activities that hold promise as a novel therapy for the central nervous system (CNS) disorders. This review aimed to summarize the protective mechanisms of pterostilbene in in vitro and in vivo models of CNS disorders and the pharmacokinetics and safety to assess its possible effects on CNS disorders. Available evidence supports the protective effects of pterostilbene in CNS disorders involving mechanisms such as antioxidant and anti-inflammatory activity, regulation of lipid metabolism and vascular smooth muscle cell proliferation, improvement of synaptic function and neurogenesis, induction of glioma cell cycle arrest, and inhibition of glioma cell migration and invasion. Studies have identified possible molecular targets and pathways for the protective actions of pterostilbene in CNS disorders including the AMPK/STAT3, Akt, NF-κB, MAPK, and ERK signaling pathways. The possible pharmacological effects and molecular pathways of pterostilbene in CNS disorders are critically discussed in this review. Future studies should aim to increase our understanding of pterostilbene in animal models and humans to further evaluate its role in CNS disorders and the detailed mechanisms.

Research progress of plant-derived natural alkaloids in central nervous system diseases.

Central nervous system (CNS) disease is one of the most important causes of human death. Because of their complex pathogenesis, more and more attention has been paid to them. At present, drug treatment of the CNS is the main means; however, most drugs only relieve symptoms, and some have certain toxicity and side effects. Natural compounds derived from plants can provide safer and more effective alternatives. Alkaloids are common nitrogenous basic organic compounds found in nature, which exist widely in many kinds of plants and have unique application value in modern medicine. For example, Galantamine and Huperzine A from medicinal plants are widely used drugs on the market to treat Alzheimer's disease. Therefore, the main purpose of this review is to provide the available information on natural alkaloids with the activity of treating central nervous system diseases in order to explore the trends and perspectives for the further study of central nervous system drugs. In this paper, 120 alkaloids with the potential effect of treating central nervous system diseases are summarized from the aspects of sources, structure types, mechanism of action and structure-activity relationship.

Stachydrine, a potential drug for the treatment of cardiovascular system and central nervous system diseases.

Cardiovascular disease (CVD) is the leading cause of death globally and poses at significant challenge in terms of effective medical treatment. Leonurus japonicus Houtt, a traditional Chinese herb, is widely used in China for the treatment of obstetrical and gynecological disorders, including menstrual disorders, dysmenorrhea, amenorrhea, blood stasis, postpartum bleeding, and blood-related diseases such as CVD. Stachydrine, the main alkaloid component of Leonurus, has been shown to exhibit a wide range of biological activities including anti-inflammatory, antioxidant, anti-coagulant, anti-apoptotic, vasodilator, angiogenic promoter. Additionally, it has been demonstrated to have unique advantages in the prevention and treatment of CVD through regulation of various disease-related signaling pathways and molecular targets. In this comprehensive review, we examine the latest pharmacological effects and molecular mechanisms of Stachydrine in treating cardiovascular and cerebrovascular diseases. Our aim is to solid scientific basis for the development of new CVD drug formulations.

Ameliorating potential of curcumin and its analogue in central nervous system disorders and related conditions: A review of molecular pathways.

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.

An Overview of the Neuropharmacological Potential of Thymoquinone and its Targeted Delivery Prospects for CNS Disorder.

At present, people and patients worldwide are relying on the medicinal plant as a therapeutic agent over pharmaceuticals because the medicinal plant is considered safer, especially for chronic disorders. Several medicinal plants and their components are being researched and explored for their possible therapeutic contribution to CNS disorders. Thymoquinone (TQ) is one such molecule. Thymoquinone, one of the constituents of Plant Nigella Sativa, is effective against several neurodegenerative diseases like, Alzheimer's, Depression, Encephalomyelitis, Epilepsy, Ischemia, Parkinson's, and Traumatic. This review article presents the neuropharmacological potential of TQ's, their challenges, and delivery prospects, explicitly focusing on neurological disorders along with their chemistry, pharmacokinetics, and toxicity. Since TQ has some pharmacokinetic challenges, scientists have focused on novel formulations and delivery systems to enhance bioavailability and ultimately increase its therapeutic value. In the present work, the role of nanotechnology in neurodegenerative disease and how it improves the bioavailability and delivery of a drug to the site of action has been discussed. There are a few limitations to developing novel drug formulations, including solubility, pH, and compatibility of nanomaterials. Since here we are targeting CNS disorders, the bloodbrain barrier (BBB) becomes an additional challenge. Hence, the review summarized the novel aspects of delivery and biocompatible nanoparticles-based approaches for targeted drug delivery into CNS, enhancing TQ bioavailability and its neurotherapeutic effects.

Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights.

Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.

Comparative Review of Effects of Pien Tze Huang and AnGong NiuHuang Pill and their Potential on Treatment of Central Nervous System Diseases.

The ancient composite formulae Angong Niuhuang pill and Pien Tze Huang, which were used a few hundred years ago to treat febrile disease and inflammation, respectively, are found to exert effects benefiting other neurological diseases and conditions. This short review introduces the main constituents of the two formulae, looking into both the cumulative synergetic and possible individual effects of each herb or animal apcoien. In essence, the main effects of Angong Niuhuang pill include anti-inflammation, antioxidation, anti-cell death, anticonvulsion, antiedema, antipyretic, antithrombotic, antimicrobial (bacteria, viruses, fungi), neuroprotective effects, and cardiovascular protection. The main effects of Pien Tze Huang include anti-inflammation, antioxidation, anti-cell death, antithrombotic, antimicrobial, neuroprotective effects, and cardiovascular protection. Comparing both composites, similarities in the effects and part of the components are found, showing some pharmacological evidence. This review casts light on research on the effects of neuroprotective and cardiovascular protective mechanisms as well as treatment mechanisms for cerebral accidents from the integrative medicine perspective.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics.

The nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root of Panax species, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti-inflammatory effects, anti-apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.

mTOR pathway: A potential therapeutic target for spinal cord injury.

Spinal cord injury (SCI) is the most common disabling spinal injury, and the complex pathological process can eventually lead to severe neurological dysfunction. Many studies have reported that the mammalian target of rapamycin (mTOR) signaling pathway plays an important role in synaptogenesis, neuron growth, differentiation, and survival after central nervous system injury. It is also involved in various traumatic and central nervous system diseases, including traumatic brain injury, neonatal hypoxic-ischemic brain injury, Alzheimer's disease, Parkinson's disease, and cerebral apoplexy. mTOR has also been reported to play an important regulatory role in various pathophysiological processes following SCI. Activation of mTOR signals after SCI can regulate physiological and pathological processes, such as proliferation and differentiation of neural stem cells, regeneration of nerve axons, neuroinflammation, and glial scar formation, through various pathways. Inhibition of mTOR activity has been confirmed to promote repair in SCI. At present, many studies have reported that Chinese herbal medicine can inhibit the SCI-activated mTOR pathway to improve the microenvironment and promote nerve repair after SCI. Due to the role of the mTOR pathway in SCI, it may be a potential therapeutic target for SCI. This review is focused on the pathophysiological process of SCI, characteristics of the mTOR pathway, role of the mTOR pathway in SCI, role of inhibition of mTOR on SCI, and role and significance of inhibition of mTOR by related Chinese herbal medicine inhibitors in SCI. In addition, the review discusses the deficiencies and solutions to mTOR and SCI research shortcomings. This study hopes to provide reference for mTOR and SCI research and a theoretical basis for SCI biotherapy.

Medicinal plants used in traditional Mayan medicine for the treatment of central nervous system disorders: An overview.

ETHNOPHARMACOLOGICAL RELEVANCE: For thousands of years, different cultural groups have used and transformed natural resources for medicinal purposes focused on psychological or neurological conditions. Some of these are recognized as central nervous system (CNS) disorders and diseases, whereas other ethnopsychiatric interpretations are explained in culture-specific terms. In traditional Mayan medicine, several herbs have been part of treatments and rituals focused on cultural and ethnomedical concepts. AIM OF REVIEW: This study aims to provide a comprehensive overview of the medicinal plants used in Mesoamerica by traditional healers and Mayan groups to CNS disorders and associate the traditional use with demonstrated pharmacological evidence to establish a solid foundation for directing future research. METHODS: A systematic search for primary sources of plant use reports for traditional CNS-related remedies of Mesoamerica were obtained from library catalogs, thesis and scientific databases (PubMed, Scopus, Google Scholar; and Science Direct), and entered in a database with data analyzed in terms of the usage frequency, use by ethnic groups, plant endemism, and pharmacological investigation. RESULTS: A total of 155 plants used for ethnopsychiatric conditions in Mesoamerica by Mayan groups were found, encompassing 127 native species. Of these, only 49 native species have reported in vitro or in vivo pharmacological analyses. The most commonly reported ethnopsychiatric conditions are related to anxiety, depression, memory loss, epilepsy, and insomnia. The extent of the scientific evidence available to understand the pharmacological application for their use against CNS disorders varied between different plant species, with the most prominent evidence shown by Annona cherimola, Justicia pectoralis, J. spicigera, Mimosa pudica, Persea americana, Petiveria alliacea, Piper amalago, Psidium guajava, Tagetes erecta and T. lucida. CONCLUSION: Available pharmacological data suggest that different plant species used in traditional Mayan medicine may target the CNS, mainly related to GABA, serotonin, acetylcholine, or neuroprotective pathways. However, more research is required, given the limited data regarding mechanism of action at the preclinical in vivo level, identification of active compounds, scarce number of clinical studies, and the dearth of peer-reviewed studies.

Application and advantages of zebrafish model in the study of neurovascular unit.

The concept of "Neurovascular Unit" (NVU) was put forward, so that the research goal of Central Nervous System (CNS) diseases gradually transitioned from a single neuron to the structural and functional integrity of the NVU. Zebrafish has the advantages of high homology with human genes, strong reproductive capacity and visualization of neural circuits, so it has become an emerging model organism for NVU research and has been applied to a variety of CNS diseases. Based on CNKI (https://www.cnki.net/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/about/) databases, the author of this article sorted out the relevant literature, analyzed the construction of a zebrafish model of various CNS diseases，and the use of diagrams showed the application of zebrafish in the NVU, revealed its relationship, which would provide new methods and references for the treatment and research of CNS diseases.

[Hypothalamic-pituitary dysfunction in a patient with neurosarcoidosis].

This is a case report of a 64-year-old man with pulmonary sarcoidosis also affecting the joints. He was admitted to an emergency department following 21 days of fatigue, visual disturbances and headache. Initial blood tests revealed hypothalamic-pituitary dysfunction including acute adrenal insufficiency, and an MRI scan of the cerebrum showed a neurosarcoidosis tumour involving the hypothalamus-pituitary gland. Neurosarcoidosis is a condition with widespread clinical variation and early, and correct diagnosis is important.

Suggesting 7,8-dihydroxyflavone as a promising nutraceutical against CNS disorders.

7,8-dihydroxyflavone (DHF), a naturally-occurring plant-based flavone, is a high-affinity tyrosine kinase receptor B (TrkB) agonist and a bioactive molecule of therapeutic interest for neuronal survival, differentiation, synaptic plasticity and neurogenesis. In the family of neurotrophic factors, this small BDNF-mimetic molecule has attracted considerable attention due to its oral bioavailability and ability to cross the blood-brain barrier. Recent evidences have shed light on the neuroprotective role of this pleiotropic flavone against several neurological disorders, including Alzheimer's disease, Parkinson's disease, cerebral ischemia, Huntington's disease, and other CNS disorders. DHF also elicits potent protective actions against toxins-induced insults to brain and neuronal cells. DHF shows promising anti-oxidant and anti-inflammatory properties in ameliorating the neurodegenerative processes affecting the CNS. This review provides an overview of the significant neuroprotective potentials of DHF and discusses how it exerts its multitudinous beneficial effects by modulating different pathways linked with the pathophysiology of CNS disorders, and thus proposes it to be a nutraceutical against a broad spectrum of neurological disorders.

Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery.

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients' CNS and serve as a platform for therapeutic development and personalized precision medicine.