scholarly journals Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook

2021 ◽  
Vol 12 ◽  
Author(s):  
Hirotaka Kushida ◽  
Takashi Matsumoto ◽  
Yasushi Ikarashi
Keyword(s):  
Pharmacological Activity ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Drug Products ◽  
Crude Drug ◽  
Future Challenges ◽  
Central Nervous Systems ◽  
Anti Oxidant ◽  
The Brain ◽  
Oxindole Alkaloids

Uncaria Hook (UH) is a dry stem with hook of Ucaria plant and is contained in Traditional Japanese and Chinese medicine such as yokukansan, yokukansankachimpihange, chotosan, Gouteng-Baitouweng, and Tianma-Gouteng Yin. UH contains active indole and oxindole alkaloids and has the therapeutic effects on ailments of the cardiovascular and central nervous systems. The recent advances of analytical technology led to reports of detailed pharmacokinetics of UH alkaloids. These observations of pharmacokinetics are extremely important for understanding the treatment’s pharmacological activity, efficacy, and safety. This review describes properties, pharmacology, and the recently accumulated pharmacokinetic findings of UH alkaloids, and discusses challenges and future prospects. UH contains major indole and oxindole alkaloids such as corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether (GM). These alkaloids exert neuroprotective effects against Alzheimer’s disease, Parkinson’s disease, and depression, and the mechanisms of these effects include anti-oxidant, anti-inflammatory, and neuromodulatory activities. Among the UH alkaloids, GM exhibits comparatively potent pharmacological activity (e.g., agonist activity at 5-HT1A receptors). UH alkaloids are absorbed into the blood circulation and rapidly eliminated when orally administered. UH alkaloids are predominantly metabolized by Cytochrome P450 (CYP) and converted into various metabolites, including oxidized and demethylated forms. Regarding GM metabolism by CYPs, a gender-dependent difference is observed in rats but not in humans. Several alkaloids are detected in the brain after passing through the blood–brain barrier in rats upon orally administered. GM is uniformly distributed in the brain and binds to various channels and receptors such as the 5-HT receptor. By reviewing the pharmacokinetics of UH alkaloids, challenges were found, such as differences in pharmacokinetics between pure drug and crude drug products administration, food-influenced absorption, metabolite excretion profile, and intestinal tissue metabolism of UH alkaloids. This review will provide readers with a better understanding of the pharmacokinetics of UH alkaloids and their future challenges, and will be helpful for further research on UH alkaloids and crude drug products containing UH.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

scholarly journals A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3168
Author(s):  
Serena Silvestro ◽  
Cinzia Sindona ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Phosphorylation ◽  
Neurodegenerative Diseases ◽  
Neuronal Cells ◽  
Antioxidant Properties ◽  
Neuroprotective Effects ◽  
Energy Needs ◽  
Anti Oxidant ◽  
Therapeutic Properties ◽  
The Brain ◽  
Lateral Sclerosis

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.

scholarly journals L-Serine, an Endogenous Amino Acid, Is a Potential Neuroprotective Agent for Neurological Disease and Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Lisha Ye ◽  
Yechao Sun ◽  
Zhenglin Jiang ◽  
Guohua Wang
Keyword(s):  
Amino Acid ◽  
Neuronal Development ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Neurological Injury ◽  
Therapeutic Effects ◽  
Cns Injury ◽  
Neuroprotective Effects ◽  
Neuroprotective Agent ◽  
The Brain

Central nervous system (CNS) lesions are major causes of human death and disability worldwide, and they cause different extents of motor and sensory dysfunction in patients. Thus, it is crucial to develop new effective neuroprotective drugs and approaches targeted to the heterogeneous nature of CNS injury and disease. L-serine is an indispensable neurotrophic factor and a precursor for neurotransmitters. Although L-serine is a native amino acid supplement, its metabolic products have been shown to be essential not only for cell proliferation but also for neuronal development and specific functions in the brain. Growing evidence has suggested that L-serine regulates the release of several cytokines in the brain under some neuropathological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination and exert other neuroprotective effects on neurological injury. L-serine has also been used to treat epilepsy, schizophrenia, psychosis, and Alzheimer’s Disease as well as other neurological diseases. Furthermore, the dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine generally support the safety of L-serine. The high significance of this review lies in its emphasis on the therapeutic potential of using L-serine as a general treatment for numerous CNS diseases and injuries. Because L-serine performs a broad spectrum of functions, it may be clinically used as an effective neuroprotective agent.

scholarly journals A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Cao ◽  
MiMi Tang ◽  
Pei Jiang ◽  
BiKui Zhang ◽  
XiangXin Wu ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Quantitative Polymerase Chain Reaction ◽  
Growth Factor Receptor ◽  
Akt Pathway ◽  
Spatial Learning And Memory ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Liquid Chromatography Tandem Mass ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Ketamine exposure can model cognitive deficits associated with schizophrenia. Progesterone (PROG) and its active metabolite allopregnanolone (ALLO) have neuroprotective effects and the pathway involving progesterone receptor membrane component 1 (PGRMC1), epidermal growth factor receptor (EGFR), glucagon-like peptide-1 receptor (GLP-1R), phosphatidylinositol 3 kinase (PI3K), and protein kinase B (Akt) appears to play a key role in their neuroprotection. The present study aimed to investigate the effects of PROG (8,16 mg kg−1) and ALLO (8,16 mg kg−1) on the reversal of cognitive deficits induced by ketamine (30 mg kg−1) via the PGRMC1 pathway in rat brains, including hippocampus and prefrontal cortex (PFC). Cognitive performance was evaluated by Morris water maze (MWM) test. Western blot and real-time quantitative polymerase chain reaction were utilized to assess the expression changes of protein and mRNA. Additionally, concentrations of PROG and ALLO in plasma, hippocampus and PFC were measured by a liquid chromatography-tandem mass spectrometry method. We demonstrated that PROG or ALLO could reverse the impaired spatial learning and memory abilities induced by ketamine, accompanied with the upregulation of PGRMC1/EGFR/GLP-1R/PI3K/Akt pathway. Additionally, the coadministration of AG205 abolished their neuroprotective effects and induced cognitive deficits similar with ketamine. More importantly, PROG concentrations were markedly elevated in PROG-treated groups in hippocampus, PFC and plasma, so as for ALLO concentrations in ALLO-treated groups. Interestingly, ALLO (16 mg kg−1) significantly increased the levels of PROG. These findings suggest that PROG can exert its neuroprotective effects via activating the PGRMC1/EGFR/GLP-1R/PI3K/Akt pathway in the brain, whereas ALLO also restores cognitive deficits partially via increasing the level of PROG in the brain to activate the PGRMC1 pathway.

scholarly journals Exploiting the neuroprotective effects of ɑ-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction

2021 ◽  
Author(s):  
Kelsey Hanson ◽  
Kate Fisher ◽  
Nigel M Hooper
Keyword(s):  
Cognitive Dysfunction ◽  
Significant Proportion ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Ageing Population ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Klotho Protein ◽  
The Brain

Cognitive dysfunction is a key symptom of aging and neurodegenerative disorders, such as Alzheimer’s disease. Strategies to enhance cognition would impact the quality of life for a significant proportion of the ageing population. The ɑ-klotho protein may protect against cognitive decline through multiple mechanisms: such as promoting optimal synaptic function via activation of N-methyl-D-aspartate receptor signalling; stimulating the anti-oxidant defence system; reducing inflammation; promoting autophagy; and enhancing clearance of amyloid-β. However, the molecular and cellular pathways by which ɑ-klotho mediates these neuroprotective functions have yet to be fully elucidated. Key questions remain unanswered: which form of ɑ-klotho (transmembrane, soluble or secreted) mediates its cognitive enhancing properties; what is the neuronal receptor for ɑ-klotho and which signalling pathways are activated by ɑ-klotho in the brain to enhance cognition; how does peripherally administered ɑ-klotho mediate neuroprotection; and what is the molecular basis for the beneficial effect of the VS variant of ɑ-klotho? In this review we summarise the recent research on neuronal ɑ-klotho and discuss how the neuroprotective properties of ɑ-klotho could be exploited to tackle age- and neurodegeneration-associated cognitive dysfunction.

Pharmacognostical and pharmacological activity of Justicia gendarussa burm.f.: a comprehensive review

2020 ◽  
Vol 11 (3) ◽  
pp. 3384-3390
Author(s):  
Ashish ◽  
Anjali ◽  
Dixit Praveen K ◽  
Nagarajan K ◽  
Sahoo Jagannath
Keyword(s):  
Pharmacological Activity ◽  
Chemical Constituents ◽  
Biological Action ◽  
Andaman Islands ◽  
Comprehensive Review ◽  
Medicinal Value ◽  
Anti Oxidant ◽  
Phytochemical Constituents ◽  
Pharmacologically Active ◽  
Different Parts

Justicia gendarussa Burm .f. (family Acanthaceae) which is also known as willow-leaves and commonly known as Nili-Nirgundi, it is very commonly found nearby to China and its availability is very common in larger parts of India and Andaman islands. Traditionally it is used to treat various sorts of disorders such as wound healing, anti-inflammatory, anti-oxidant, antiproliferative, anti-arthritic etc. Justicia gendarussa is one of the crucial herbs which has been used in the Ayurveda. Majorly leaves parts of the plant shows the pharmacological activity but the root of the plant Justicia gendarussa is also have the important medicinal values. A large variety of pharmacologically active constituents i.e., alkaloids, flavonoids, saponin, carbohydrates, steroids, triterpenoids, carotenoids, aminoacids, tannins, phenolics, coumarines and anthaquinones are also present in this plant and they makes the plant pharmacologically important. The activity of the plant is also dependent on the solvent which is used for the extraction the various vital chemical constituents. The different- different parts of the plants having the different medicinal values also differ in the chemical values. This review is not only focused on the essential phytochemical constituents which is available in the plant but it also explains their necessary medicinal value to shows the essential biological action and phytopharmacological actions of various parts of the plant.

In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson`s Disease using the C. elegans Model

2020 ◽  
Vol 23 (8) ◽  
pp. 814-826
Author(s):  
Pradeep Hanumanthappa ◽  
Arpitha Ashok ◽  
Inderjit Prakash ◽  
Carmel I. Priya ◽  
Julie Zinzala ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neurodegenerative Disorder ◽  
In Vivo Evaluation ◽  
Neuroprotective Effects ◽  
Ample Evidence ◽  
C Elegans ◽  
Rational Drug ◽  
Cullin 3 ◽  
Anti Oxidant

Background: Parkinson’s disease ranks second, after Alzheimer’s as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of “off-target” toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.

1,4-Dihydropyridine: A Dependable Heterocyclic Ring with the Promising and the Most Anticipable Therapeutic Effects

2019 ◽  
Vol 19 (15) ◽  
pp. 1219-1254 ◽  
Author(s):  
Abhinav Prasoon Mishra ◽  
Ankit Bajpai ◽  
Awani Kumar Rai
Keyword(s):  
Calcium Ion ◽  
Heterocyclic Compounds ◽  
Channel Blocker ◽  
Heterocyclic Ring ◽  
Therapeutic Effects ◽  
Voltage Gated ◽  
Therapeutic Benefits ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Synthetic Medicinal

: Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.

scholarly journals The Potential Effects of Phytoestrogens: The Role in Neuroprotection

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2954
Author(s):  
Justyna Gorzkiewicz ◽  
Grzegorz Bartosz ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Estrogen Therapy ◽  
Neuroprotective Effects ◽  
Potential Health ◽  
Naturally Occurring ◽  
Epigenetic Effects ◽  
Estrogen Synthesis ◽  
Health Promoting ◽  
The Brain

Phytoestrogens are naturally occurring non-steroidal phenolic plant compounds. Their structure is similar to 17-β-estradiol, the main female sex hormone. This review offers a concise summary of the current literature on several potential health benefits of phytoestrogens, mainly their neuroprotective effect. Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease. They also reduce the risk of brain disease. The effects of phytoestrogens and their derivatives on cancer are mainly due to the inhibition of estrogen synthesis and metabolism, leading to antiangiogenic, antimetastatic, and epigenetic effects. The brain controls the secretion of estrogen (hypothalamus-pituitary-gonads axis). However, it has not been unequivocally established whether estrogen therapy has a neuroprotective effect on brain function. The neuroprotective effects of phytoestrogens seem to be related to both their antioxidant properties and interaction with the estrogen receptor. The possible effects of phytoestrogens on the thyroid cause some concern; nevertheless, generally, no serious side effects have been reported, and these compounds can be recommended as health-promoting food components or supplements.

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