Therapeutic potential of vasopressin in the treatment of neurological disorders.

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.

Formulation and evaluation of magnesium sulphate nanoparticles for improved CNS penetrability.

Magnesium (Mg2+) is the fourth most abundant cation in the human body and is involved in maintaining varieties of cellular and neurological functions. Magnesium deficiency has been associated with numerous diseases, particularly neurological disorders, and its supplementation has proven beneficial. However, magnesium therapy in neurological diseases is limited because of the inability of magnesium to cross the blood-brain barrier (BBB). The present study focuses on developing magnesium sulphate nanoparticles (MGSN) to improve blood-brain barrier permeability. MGSN was prepared by precipitation technique with probe sonication. The developed formulation was characterized by DLS, EDAX, FT-IR and quantitative and qualitative estimation of magnesium. According to the DLS report, the average size of the prepared MGSN is found to be 247 nm. The haemocompatibility assay studies revealed that the prepared MGSN are biocompatible at different concentrations. The in vitro BBB permeability assay conducted by Parallel Artificial Membrane Permeability Assay (PAMPA) using rat brain tissue revealed that the prepared MGSN exhibited enhanced BBB permeability as compared to the marketed i.v. MgSO4 injection. The reversal effect of MGSN to digoxin-induced Na+/K+ ATPase enzyme inhibition using brain microslices confirmed that MGSN could attenuate the altered levels of Na+ and K+ and is useful in treating neurological diseases with altered expression of Na+/K+ ATPase activity.

Small Molecules as Modulators of Voltage-Gated Calcium Channels in Neurological Disorders: State of the Art and Perspectives.

Voltage-gated calcium channels (VGCCs) are widely expressed in the brain, heart and vessels, smooth and skeletal muscle, as well as in endocrine cells. VGCCs mediate gene transcription, synaptic and neuronal structural plasticity, muscle contraction, the release of hormones and neurotransmitters, and membrane excitability. Therefore, it is not surprising that VGCC dysfunction results in severe pathologies, such as cardiovascular conditions, neurological and psychiatric disorders, altered glycemic levels, and abnormal smooth muscle tone. The latest research findings and clinical evidence increasingly show the critical role played by VGCCs in autism spectrum disorders, Parkinson's disease, drug addiction, pain, and epilepsy. These findings outline the importance of developing selective calcium channel inhibitors and modulators to treat such prevailing conditions of the central nervous system. Several small molecules inhibiting calcium channels are currently used in clinical practice to successfully treat pain and cardiovascular conditions. However, the limited palette of molecules available and the emerging extent of VGCC pathophysiology require the development of additional drugs targeting these channels. Here, we provide an overview of the role of calcium channels in neurological disorders and discuss possible strategies to generate novel therapeutics.

Chemical constituents and medicinal properties of Allium species.

Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as food. Garlic, onions, leeks and chives, which belong to this family, have been reported to have medicinal properties. The Allium species constituents have been shown to have antibacterial and antioxidant activities, and, in addition, other biological properties. These activities are related to their rich organosulfur compounds. These organosulfur compounds are believed to prevent the development of cancer, cardiovascular, neurological, diabetes, liver diseases as well as allergy and arthritis. There have also been reports on toxicities of these compounds. The major active compounds of Allium species includes, diallyl disulfide, diallyl trisulfide, diallyl sulfide, dipropyl disulfide, dipropyl trisulfide, 1-propenylpropyl disulfide, allyl methyl disulfide and dimethyl disulfide. The aim of this review is to focus on a variety of experimental and clinical reports on the effectiveness, toxicities and possible mechanisms of actions of the active compounds of garlic, onions, leek and chives.

Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury.

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

Metal-Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin.

Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the ß-diketone moiety to generate metal-curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal-curcumin complexes are discussed. Metal-curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal-curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer's disease. These biological activities of metal-curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal-curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal-curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases.

Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome.

Traumatic brain injury (TBI) alters microbial populations present in the gut, which may impact healing and tissue recovery. However, the duration and impact of these changes on outcome from TBI are unknown. Short-chain fatty acids (SCFAs), produced by bacterial fermentation of dietary fiber, are important signaling molecules in the microbiota gut-brain axis. We hypothesized that TBI would lead to a sustained reduction in SCFA producing bacteria, fecal SCFAs concentration, and administration of soluble SCFAs would improve functional outcome after TBI. Adult mice (n = 10) had the controlled cortical impact (CCI) model of TBI performed (6 m/sec, 2-mm depth, 50-msec dwell). Stool samples were collected serially until 28 days after CCI and analyzed for SCFA concentration by high-performance liquid chromatography-mass spectrometry/mass spectrometry and microbiome analyzed by 16S gene sequencing. In a separate experiment, mice (n = 10/group) were randomized 2 weeks before CCI to standard drinking water or water supplemented with the SCFAs acetate (67.5 mM), propionate (25.9 mM), and butyrate (40 mM). Morris water maze performance was assessed on post-injury Days 14-19. Alpha diversity remained stable until 72 h, at which point a decline in diversity was observed without recovery out to 28 days. The taxonomic composition of post-TBI fecal samples demonstrated depletion of bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families, and enrichment of bacteria from the Verrucomicrobiaceae family. Analysis from paired fecal samples revealed a reduction in total SCFAs at 24 h and 28 days after TBI. Acetate, the most abundant SCFA detected in the fecal samples, was reduced at 7 days and 28 days after TBI. SCFA administration improved spatial learning after TBI versus standard drinking water. In conclusion, TBI is associated with reduced richness and diversity of commensal microbiota in the gut and a reduction in SCFAs detected in stool. Supplementation of soluble SCFAs improves spatial learning after TBI.

Potential benefits of phytochemicals from Azadirachta indica against neurological disorders.

Azadirachta indica or Neem has been extensively used in the Indian traditional medical system because of its broad range of medicinal properties. Neem contains many chemically diverse and structurally complex phytochemicals such as limonoids, flavonoids, phenols, catechins, gallic acid, polyphenols, nimbins. These phytochemicals possess vast array of therapeutic activities that include anti-feedant, anti-viral, anti-malarial, anti-bacterial, anti-cancer properties. In recent years, many phytochemicals from Neem have been shown to be beneficial against various neurological disorders like Alzheimer's and Parkinson's disease, mood disorders, ischemic-reperfusion injury. The neuroprotective effects of the phytochemicals from Neem are primarily mediated by their anti-oxidant, anti-inflammatory and anti-apoptotic activities along with their ability to modulate signaling pathways. However, extensive studies are still required to fully understand the molecular mechanisms involved in neuropotective effects of phytochemicals from Neem. This review is an attempt to cover the neuroprotective properties of various phytochemicals from Neem along with their mechanism of action so that the potential of the compounds could be realized to reduce the burden of neurodegenerative diseases.

Salvianolate lyophilized injection regulates the autophagy-lysosomal pathway in cerebral ischaemia/reperfusion rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Activation of autophagy has been implicated in cerebral ischiemia/reperfusion (I/R) injury. Salvianolate lyophilized injection (SLI) has been widely used in the clinical treatment of cerebrovascular disease in China. Whether SLI has any influence on the activation of autophagy in cerebral I/R injury remains elusive. AIM OF THE STUDY: The aim of this study were to assess whether SLI attenuates I/R-induced brain injury and evaluate its associated mechanisms. MATERIALS AND METHODS: Focal cerebral ischaemia was induced by middle cerebral artery occlusion (MCAO). SLI (21 mg/kg) was injected intravenously at the beginning of the reperfusion period and 24 and 48 h after ischaemia. The effects of SLI on brain injury were detected according to infarct volume, neurological score, brain oedema, and HE and TUNEL staining at 72 h post-MCAO. Western blotting was used to detect alterations in the autophagy-relevant proteins LC3, Beclin-1, mTOR, p62, Lamp-1, and CTSD in the ipsilateral cortex at 24 or 72 h post-MCAO. RESULTS: We first demonstrated that SLI significantly alleviated the infarct volume, neurological deficits, and brain oedema, and reduced the number of TUNEL-positive cells in rats with cerebral I/R injury. Next, we found that SLI has a bidirectional regulatory effect on autophagy: early-stage (24 h) cerebral ischaemia promotes the activation of autophagy and developmental-stage (72 h) cerebral ischaemia has an inhibitory effect. SLI enhanced I/R-induced autophagy as evidenced by the increased expression level of the autophagy marker protein LC3Ⅱ, as well as the decreased expression of mTOR and the autophagy substrate protein p62, but there was no change in lysosomal activity at 24 h after I/R-induced injury. Moreover, SLI also inhibited excessive activation of autophagy at 72 h after I/R-induced injury, which manifested as downregulating LC3Ⅱ expression, upregulating mTOR and p62 expression, and inhibiting lysosomal activity. CONCLUSION: SLI has a protective effect on cerebral ischaemia/reperfusion injury, which may be mediated by the autophagy-lysosome pathway.

Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress.

BACKGROUND: Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. METHODS: Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. RESULTS: GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. CONCLUSIONS: GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Coenzyme Q10 effects in neurological diseases.

Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).

TCD, a triterpenoid isolated from wild bitter gourd, reduces synaptosomal release of glutamate and protects against kainic acid-induced neuronal death.

3ß,7ß,25-Trihydroxycucurbita-5,23(E)-dien-19-al (TCD) is a triterpenoid isolated from wild bitter gourd that is a common tropical vegetable with neuroprotective effects. Because excessive glutamate release is a major cause of neuronal damage in various neurological disorders, the aims of this study were to examine the effect of TCD on glutamate release in vitro and to examine the effect of TCD in vivo. In rat cerebrocortical synaptosomes, TCD reduced 4-aminopyridine (4-AP)-stimulated glutamate release and Ca2+ concentration elevation, but had no effect on plasma membrane potential. TCD-mediated inhibition of 4-AP-induced glutamate release was dependent on the presence of extracellular calcium; persisted in the presence of the glutamate transporter inhibitor dl-TBOA, P/Q-type Ca2+ channel blocker ω-agatoxin IVA, and intracellular Ca2+-releasing inhibitors dantrolene and CGP37157; and was blocked by the vesicular transporter inhibitor bafilomycin A1 and the N-type Ca2+ channel blocker ω-conotoxin GVIA. Molecular docking studies have demonstrated that TCD binds to N-type Ca2+ channels. TCD-mediated inhibition of 4-AP-induced glutamate release was abolished by the Ca2+-dependent protein kinase C (PKC) inhibitor Go6976, but was unaffected by the Ca2+-independent PKC inhibitor rottlerin. Furthermore, TCD considerably reduced the phosphorylation of PKC, PKCα, and myristoylated alanine-rich C kinase substrate, a major presynaptic substrate for PKC. In a rat model of kainic acid (KA)-induced excitotoxicity, TCD pretreatment substantially attenuated KA-induced neuronal death in the CA3 hippocampal region. These results suggest that TCD inhibits synaptosomal glutamate release by suppressing N-type Ca2+ channels and PKC activity and exerts protective effects against KA-induced excitotoxicity in vivo.

Optimizing Nitrogen Balance Is Associated with Better Outcomes in Neurocritically Ill Patients.

Marked protein catabolism is common in critically ill patients. We hypothesized that optimal protein supplementation using nitrogen balance might be associated with better outcomes in the neurointensive care unit (NICU) patients. A total of 175 patients admitted to the NICU between July 2017 and December 2018 were included. Nitrogen balance was measured after NICU admission and measurements were repeated in 77 patients. The outcomes were compared according to initial nitrogen balance results and improvement of nitrogen balance on follow-up measurements. A total of 140 (80.0%) patients had a negative nitrogen balance on initial assessments. The negative balance group had more events of in-hospital mortality and poor functional outcome at three months. In follow-up measurement patients, 39 (50.6%) showed an improvement in nitrogen balance. The improvement group had fewer events of in-hospital mortality (p = 0.047) and poor functional outcomes (p = 0.046). Moreover, improvement of nitrogen balance was associated with a lower risk of poor functional outcomes (Odds ratio, 0.247; 95% confidence interval, 0.066-0.925, p = 0.038). This study demonstrated that a significant proportion of patients in the NICU were under protein hypercatabolism. Moreover, an improvement in protein balance was related to improved outcomes in neurocritically ill patients. Further studies are needed to confirm the relationship between protein balance and outcomes.

A systematic review and meta-analysis: The effects of probiotic supplementation on metabolic profile in patients with neurological disorders.

BACKGROUND AND OBJECTIVE: The objective of meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of probiotic supplementation on metabolic status in patients with neurological disorders. METHODS: The following databases were search up to April 2019: Pubmed, Scopus, Google scholar, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 % Confidence Intervals (95 % CI). RESULTS: Nine studies were included in this meta-analysis. The findings suggested that probiotic supplementation resulted in a significant reduction in C-reactive protein (CRP) [Weighted Mean Difference (WMD): -1.06; 95 % CI: -1.80, -0.32] and malondialdehyde (MDA) levels (WMD: -0.32; 95 % CI: -0.46, -0.18). Supplementation with probiotics also significantly reduced insulin (WMD: -3.02; 95 % CI: -3.88, -2.15) and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.71; 95 % CI: -0.89, -0.52). Probiotics significantly reduced triglycerides (WMD: -18.38; 95 % CI: -25.50, -11.26) and VLDL-cholesterol (WMD: -3.16; 95 % CI: -4.53, -1.79), while they increased HDL-cholesterol levels (WMD: 1.52; 95 % CI: 0.29, 2.75). CONCLUSION: This meta-analysis demonstrated that taking probiotic by patients with neurological disorders had beneficial effects on CRP, MDA, insulin, HOMA-IR, triglycerides, VLDL-cholesterol and HDL-cholesterol levels, but did not affect other metabolic parameters.

A natural product solution to aging and aging-associated diseases.

Aging is a natural biological progress accompanied by the gradual decline in physiological functions, manifested by its close association with an increased incidence of human diseases and higher vulnerability to death. Those diseases include neurological disorders, cardiovascular diseases, diabetes, and cancer, many of which are currently without effective cures. Even though aging is inevitable, there are still interventions that can be developed to prevent/delay the onset and progression of those aging-associated diseases and extend healthspan and/or lifespan. Here, we review decades of research that reveals the molecular pathways underlying aging and forms the biochemical basis for anti-aging drug development. Importantly, due to the vast chemical space of natural products and the rich history of herb medicines in treating human diseases documented in different cultures, natural products have played essential roles in aging research. Using several of the most promising natural products and their derivatives as examples, we discuss how natural products serve as an inspiration resource that helped the identification of key components/pathways underlying aging, their mechanisms of action inside the cell, and the functional scaffolds or targeting mechanisms that can be learned from natural products for drug engineering and optimization. We argue that natural products might eventually provide a solution to aging and aging-associated diseases.

Lycopene - A pleiotropic neuroprotective nutraceutical: Deciphering its therapeutic potentials in broad spectrum neurological disorders.

Lycopene is a naturally occurring carotenoid found abundantly in red fruits and vegetables. Myriads of literature documented potential health benefits of lycopene, owing to its sublime capacity of suppressing oxidative stress, inflammation, and modulation of various cell survival pathways. Due to its lipophilic nature, lycopene can reach brain adequately by traversing the blood-brain barrier thereby extending it's promising therapeutic benefits in neurological disorders. Lycopene efficiently assists in restoring the characteristic behavioural and pathophysiological changes associated with neurodegenerative disorders, epileptic conditions, aging, subarachnoid hemorrhage, spinal cord injury, and neuropathy. The detrimental impacts of environmental neurotoxins on brain and neuropathological consequences of consumption of high-lipid diet can also be mitigated by lycopene. Apart from its high antioxidant potency, lycopene confers neuroprotection by preventing proteinopathies, neuroinflammation, apoptosis, cerebral edema, and synaptic dysfunction. This review provides a lucid idea on the potential multi-faceted benefits of lycopene in disorders of the central nervous system and elucidates the molecular mechanisms and pathways of its action.

Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review.

Acupuncture is clinically used to treat various diseases and exerts positive local and systemic effects in several nervous system diseases. Advanced molecular and clinical studies have continually attempted to decipher the mechanisms underlying these effects of acupuncture. While a growing understanding of the pathophysiology underlying several nervous system diseases shows it to be related to inflammation and impair cell regeneration after ischemic events, the relationship between the therapeutic mechanism of acupuncture and the p38 MAPK signal pathway has yet to be elucidated. This review discusses the latest advancements in the identification of the effect of acupuncture on the p38 signaling pathway in several nervous system diseases. We electronically searched databases including PubMed, Embase, and the Cochrane Library from their inception to April 2020, using the following keywords alone or in various combinations: "acupuncture", "p38 MAPK pathway", "signaling", "stress response", "inflammation", "immune", "pain", "analgesic", "cerebral ischemic injury", "epilepsy", "Alzheimer's disease", "Parkinson's disease", "dementia", "degenerative", and "homeostasis". Manual acupuncture and electroacupuncture confer positive therapeutic effects by regulating proinflammatory cytokines, ion channels, scaffold proteins, and transcription factors including TRPV1/4, Nav, BDNF, and NADMR1; consequently, p38 regulates various phenomena including cell communication, remodeling, regeneration, and gene expression. In this review article, we found the most common acupoints for the relief of nervous system disorders including GV20, GV14, ST36, ST37, and LI4. Acupuncture exhibits dual regulatory functions of activating or inhibiting different p38 MAPK pathways, contributing to an overall improvement of clinical symptoms and function in several nervous system diseases.

Effects of rosmarinic acid on nervous system disorders: an updated review.

Nowadays, the worldwide interest is growing to use medicinal plants and their active constituents to develop new potent medicines with fewer side effects. Precise dietary compounds have prospective beneficial applications for various neurodegenerative ailments. Rosmarinic acid is a polyphenol and is detectable most primarily in many Lamiaceae families, for instance, Rosmarinus officinalis also called rosemary. This review prepared a broad and updated literature review on rosmarinic acid elucidating its biological activities on some nervous system disorders. Rosmarinic acid has significant antinociceptive, neuroprotective, and neuroregenerative effects. In this regard, we classified and discussed our findings in different nervous system disorders including Alzheimer's disease, epilepsy, depression, Huntington's disease, familial amyotrophic lateral sclerosis, Parkinson's disease, cerebral ischemia/reperfusion injury, spinal cord injury, stress, anxiety, and pain.

Dl-3-n-Butylphthalide promotes neovascularization and neurological recovery in a rat model of intracerebral hemorrhage.

BACKGROUND: Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke. RESULTS: In the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa's motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region. CONCLUSION: These results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.

Coenzyme Q10 and neuropsychiatric and neurological disorders: relevance for schizophrenia.

Objective: Mitochondrial dysfunction has been implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. Though the exact mechanisms and clinical implications for this dysfunction are not fully determined, there is a hypothesis that deficiency in coenzyme Q10 (CoQ10) may contribute to mitochondrial impairments and be reflected in cognitive, affective, and energy disturbances in the disorders. CoQ10 is a critical component of the mitochondrial respiratory chain and an essential free radical scavenger, necessary for mitochondrial function. Here, we review the results of CoQ10 supplementation interventions for adults with various neurological and neuropsychiatric disorders and consider the therapeutic potential of CoQ10 supplementation for schizophrenia in light of these studies. Methods: A literature review of randomised controlled trials and open-label studies investigating the effect of CoQ10 as a single intervention in adults with neurological and neuropsychiatric disorders was conducted. Results: CoQ10 supplementation has some positive effects on fatigue, cognitive impairment and affective difficulties in several neurological and neuropsychiatric conditions with associated mitochondrial dysfunction. Discussion: CoQ10 may be of therapeutic value to schizophrenia given evidence of mitochondrial dysfunction in the disorder.