NeuroFactor is a clinically formulated blend of incredible herbs which have been researched to exert antidepressant effects and increase brain-derived neurotrophic factor (BDNF) levels in the brain. This is a cognitive aid, has antioxidant-neuroprotective, mood balancing and anti-inflammatory effects.
Symptoms it is fabulous for include:
• Chronic stress
• Cognitive impairment due to stress
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor widely expressed in the central nervous system and it’s neuroprotective effect plays an important role in neuronal survival. Decreased levels of BDNF are associated with neurodegenerative diseases such as:
• Parkinson’s disease
• Alzheimer’s disease
• Multiple sclerosis and
• Huntington’s disease
Primary Actions of this amazing new nutritional supplement include:
• Reduces effects of stress
• Improves memory, cognition and attention
• Regulates heathy sleep cycle (people RAVE about the sleep effects)
• Increases BDNF
• Regulates stress hormone production
• Reduces serum levels of cortistatin, adrenocorticotropic hormone (ACTH), and corticotropin-releasing factor (CRF)
• Upregulates GABA receptors
• Reduces glutamic acid levels
• Increases serotonin
The primary indications include:
• Depression (Treatment-Resistant Depression TRD)
• Chronic Stress
• Stress related memory impairment
• Cognitive impairment
• Neurodegenerative conditions
It comes in veggiecaps, and doesn’t contain ANY wheat, gluten, soy, milk, eggs, fish, crustacean shellfish, tree nuts or peanuts.
DOSAGE: The suggested dose is just one a day – there are 120 capsules (potentially 4 months’ worth!) but more can be taken. Not to be taken in pregnancy.
NeuroFactor is a clinically formulated blend of Euphoria longana, Houttuynia cordata, Dioscorea japonica with Schisandra chinensis (Schisandrin B). The NeuroFactor combination of Euphoria longana, Houttuynia cordata and Dioscorea japonica has been researched to exert antidepressant effects and increase Brain-derived neurotrophic factor (BDNF) levels in the brain. Schisandra a well- known adaptogen and cognitive aid, has been included for its antioxidant-neuroprotective, mood balancing and anti-inflammatory effects.
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor widely expressed in the CNS. It has a neuroprotective effect playing an important role in neuronal survival. In the brain, BDNF is involved in plasticity, formation of new synapses, dendritic branching, and modulation of excitatory and inhibitory neurotransmitter profiles. BDNF is active at all stages of development and is essential for learning and memory. Low levels of serum BDNF have been associated with depression implying an inverse relationship between serum BDNF levels and the severity of depression. Decreased levels of BDNF are also associated with neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease.1-2
Schisandra Chinensis (Schisandrin B) (extract 35:1)
Other Ingredients: Vegetable cellulose (hypromellose); Vegetable Stearic Acid; Microcrystalline Cellulose and Vegetable Magnesium Stearate.
Dosage / Contents
• 1 capsule once or twice a day
Size & presentation: 120 x 500mg capsules
Packed in a white plastic bottle, aluminium sealed, with a childproof lid
Route of administration: Oral, absorption GIT
Store instructions: Store below 30 degrees C
As with all medicines, keep complementary or alternative medicines out of the sight and reach of children.
• Reduces effects of stress
• Improves memory, cognition and attention
• Regulates heathy sleep cycle
• Increases Brain-derived neurotrophic Factors (BDNF)
• Regulates stress hormone production
• Reduces serum levels of cortistatin, adrenocorticotropic hormone (ACTH), and corticotropin-releasing factor (CRF)
• Upregulates GABAA receptors
• Reduces glutamic acid levels
• Increases serotonin
Caution in pregnancy. Schisandra may affect medications metabolised by the liver enzymes CYP 2C9 and CYP 3A4.
NeuroFactor Formulation Research
The NeuroFactor formulation consisting of Euphoria longana, Houttuynia cordata and Dioscorea japonica has been researched for its effects on brain-derived neurotrophic factor (BDNF).
Several clinical reports have shown depression-induced deregulation of serum BDNF concentration. Depressed patients were characterized by low serum BDNF levels, implying an inverse relationship between serum BDNF levels and the severity of depression.3 4 5 Support for this comes from a number of studies demonstrating that treatment with antidepressants has been shown to increase BDNF levels in serum and plasma. 6 7 8 9
It is speculated that lower BDNF levels may be caused by dysregulation of BDNF expression. This was evidenced with decreased BDNF mRNA and protein levels in post- mortem hippocampus and frontal cortex of suicide victims.10 Recent reports further support the speculation that antidepressant treatment increased BDNF protein levels in serum and in both prefrontal cortex and hippocampus.11 12 In the current study, herbal mixture administration with low and high dose increased the BDNF protein levels in hippocampus and cortex com- pared to the stress group. Herbal mixture might have significantly increased the BDNF transcript levels as well although they were not evaluated in our study.
Several types of stressors have been known to disrupt BDNF expression. For example, single (one day) or repeated (7 days) immobilization for 2 hours per day markedly reduced BDNF mRNA levels in the dentate gyrus and hippocampus.13 This was later confirmed by other investigators who used the same stress paradigm.14
In this study using immobilization as a stressor, no significant changes in BDNF protein level were observed in hippocampus and cortex. It can be proposed that stress induced changes in BDNF protein level may be involved in other brain regions. The other hypothesis is that immobilization stress duration was too long enough to neutralize the downregulation of BDNF expression. Interestingly, brief immobilization stress can induce BDNF expression as part of a compensatory response to preserve hippocampal homeostasis to cope with new stress.15
This study provides further data that herbal mixture is able to modulate serum corticosterone level in mice under stress conditions. This effect could be either of peripheral origin through a direct action of herbal mixture on adrenal glands, or of central origin via the hypothalamic-pituitary- adrenal axis. The inverse relationship between memory performance and corticosterone level in stress conditions from the study confirms the past report that chronic stress in has mostly impairing effects on memory .16 Moreover, a long-term immobilization stress has been shown to affect spatial memory, which is in accordance with the data of short-term immobilization paradigm.17
In conclusion, the study showed that herbal mixture administration has antidepressant effects. Each herb induced the expression of BDNF, pCREB and pAkt. The administration of herbal mixture significantly increased BDNF protein expression in mouse hippocampus and cortex.
Euphoria longan research
Euphoria longan has memory enhancing effects and that these effects are mediated by increased BDNF expression via the phosphorylated extracellular signal-regulated kinase (pERK) 1/2,
phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF) pathway and by increased immature neuronal survival.18
Cerebral Ischemia/Reperfusion Injury
Compared with the I/R group, polysaccharides of the Euphoria longan (Lour.) Steud could obviously reduce the neurological score, the infract volume, the brain water content, MDA content, MPO activity, TNF- and IL-1 level, expression of Bax, and increase SOD, GSH, GSH-Px activity and expression of Bcl-2. The present experiments demonstrated that polysaccharides of the Euphoria longan (Lour.) Steud significantly reduce the MDA content and increase SOD, GSH and GSH-Px activities.
This study demonstrated that polysaccharides of the Euphoria longan (Lour.) Steud significantly reduced MPO activity (final product of lipid peroxidate) and concentrations of TNF- and IL-1 in the brain tissue, the mechanism may be related to polysaccharides of the Euphoria longan (Lour.) Steud which can scavenge free radicals effectively in vivo.19
Houttuynia cordata research
Huh E, Kim HG, Park H, Kang MS, Lee B, OH MS. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models. Biomol Ther 22(3), 176-183, 2014. http://dx.doi.org/10.4062/biomolther.2014.040
The aerial part of Houttuynia cordata Thunb. (Hottuyniae herba, Saururaceae) is a traditional herbal medicine for furunculus, disorders of urines and fever in East Asia and, recently, it has been shown to have effective anti-inflammatory, antioxidant, anti-virus, and anti-leukemic effects.20 21 22 23 24 Additionally, there is a report that H. cordata enhances memory and learning in a mouse model via an antioxidant effect.25
H. cordata had a protective effect against Ab-toxicity in regulating intracellular calcium levels, preventing reactive oxygen species overproduction, and inhibiting mitochondria- mediated apoptosis in rat primary neuronal cells.26 Taken together, the results reported here indicate that HCW has neuroprotective effects against memory impairment by inhibiting tau hyper- phosphorylation and cholinergic dysfunction.
In conclusion, we evaluated HCW, in vitro and in vivo, and conclude that it has effects on cognitive development in two ways, improving cholinergic dysfunction induced by tau hyperphosphorylation and blocking cholinergic receptors. In addition, HCW has a neuroprotective effect via inhibiting Ca2+- induced apoptosis. Phenolic compounds are well known to have antioxidant, anti-inflammatory, and anti-apoptotic effects, then they have been reported to inhibit neurotoxin-induced damages, resulting neuroprotection.27 28 Chlorogenic acid and caffeic acid have a neuro- protective effect against methylglyoxal or cryo-injury via anti- apoptotic and anti-inflammatory activities.29 30 Also, chlorogenic acid has anti-amnesic effect via inhibition of AChE activity.31 In addition, quercetin and rutin were also showed protective effect from neuronal damage induced by Ab and ischemia.32 33 Thus, we assumed that phenolic compounds in HCW could partially contribute the effects in the present study. From these results, HCW may be an effective treatment for improving the cholinergic system and protecting neurons from toxicity. We suggest that HCW may be an interesting candidate to investigate for the treatment of AD.
Anti-Neuroinflammatory Effects of Houttuynia cordata Extract on LPS-Stimulated BV-2 Microglia
Park TK, Koppula S, Kim MS, Jung SH, Kang H. Tropical Journal of Pharmaceutical Research August 2013; 12 (4): 523-528. http://dx.doi.org/10.4314/tjpr.v12i4.12
Purpose: To evaluate the anti-neuroinflammatory effects of Houttuynia cordata extract (H. cordata) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells, and its anti-oxidant properties.
Methods: Anti-oxidant properties were evaluated by 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. Cell viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyl- tetrazolium bromide (MTT) assay. LPS was used to stimulate BV-2 cells. Nitric oxide (NO) levels were measured using Griess assay. Inducible NO synthase (iNOS) expression, interleukin (IL)-6
expressional level were determined by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis.
Results: Ethyl actetae (HC-EA) extract of H. cordata significantly scavenged DPPH free radicals in a concentration-dependent fashion. The increased levels of NO, iNOS and IL-6 in LPS-stimulated BV-2 microglial cells were also suppressed by HC-EA extract in a concentration-dependent manner.
Conclusion: The result indicate that the HC-EA extract exhibited strong anti-oxidant properties and inhibited the excessive production of pro-inflammatory mediators, including NO, iNOS and IL-6, in LPS-stimulated BV-2 cells. The anti-oxidant phenolic compounds present in HC-EA extract might play an important role in ameliorating neuroinflammatory processes in LPS-stimulated BV-2 microglial cells.
Antioxidant and Neuronal Cell Protective Effects of an Extract of Houttuynia cordata Thunb (a Culinary Herb)
Hee Rok Jeong, Ji Hyun Kwak, Ji Hye Kim, Gwi Nam Choi, Chang-Ho Jeong and Ho Jin Heo. Korean J. Food Preserv. Vol. 17, No. 5. pp. 720-726, October 2010
The in vitro antioxidant activities and neuronal cell protective effects of 60% (w/v) methanolic extract from Houttuynia cordata were investigated. The contents of total phenolics and quercitrin in the extract were 17.71 mg/g and 75.80 μg/g, respectively. DPPH and ABTS radical-scavenging activities were 87.79% and 99.27%, respectively, when the extract was tested at 5 mg/ml. The FRAP (ferric reducing/antioxidant power) assay showed a dose-dependent increase in activity. In a cell viability assay using MTT, the extract protected against H2O2-induced neurotoxicity. Lactate dehydrogenase (LDH) leakage was also inhibited by the extract, as was lipid peroxidation as shown using the mouse brain homogenate test. These data indicate that a 60% (w/v) methanolic extract of Houttuynia cordata has in vitro antioxidant activities, and ingestion thereof may reduce the risk of developing neurodegenerative disorders.
Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease
Houttuynia cordata (HC) has an effect on cognitive development in two ways, by improving cholinergic dysfunction induced by tau hyperphosphorylation and blocking cholinergic receptors. In addition, HC has a neuroprotective effect via inhibiting Ca2+-induced apoptosis. Phenolic compounds in HC could partially contribute the effects as they are well known to have antioxidant, anti- inflammatory, and anti-apoptotic effects, then they have been reported to inhibit neurotoxin-induced damages, resulting neuroprotection.
Chlorogenic acid and caffeic acid have a neuro-protective effect against methylglyoxal or cryo-injury via anti-apoptotic and anti-inflammatory activities. Also, chlorogenic acid has anti-amnesic effect via inhibition of AChE activity. In addition, quercetin and rutin were also showed protective effect from neuronal damage induced by Aβ and ischemia.34
Dioscorea japonica research
Nerve growth factor (NGF)
Nerve growth factor (NGF) was first discovered by Levi-Montalcini in 1966. NGF has neurotrophic actions that protect cholinergic neurons of the basal forebrain against axotomy-induced neurodegeneration and aged-related atrophy. Exogenous NGF improves impaired function of the cholinergic neuron system, such as neuronal degeneration, and has therapeutic potential for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and diabetic polyneuropathy. However, NGF cannot pass through the blood–brain barrier (BBB) and therefore requires neurosurgical approaches for administration. The development of small molecules that induce NGF secretion or mimic NGF activity is therefore desirable.
In this study two new furostanol saponins (1–2), along with ten known compounds (3–12) isolated from the rhizomes of D. japonica were identified. With regard to bioactivity, compounds 2, 6, 8, 9, and 11 induced NGF secretion in C6 cells at 20 lM. The most potent stimulant of NGF release, coreajaponin B (2), may have a potential for neuroprotection via inducing NGF secretion and may deserve further investigation as a candidate for regulation of neurodegenerative diseases and diabetic polyneuropathy.35
Schisandra (Sch B) Research
Glycogen synthase kinase-3β (GSK-3β) is a key enzyme in hyper-phosphorylation of tau proteins and is a promising therapeutic target in Alzheimer’s disease (AD). Here, we reported, for the first time, that the stereoisomers of Schisandrin B (Sch B), (+)–1, (–)–1, (+)–2, and (–)–2, were potent GSK-3β inhibitors. They were demonstrated to selectively target GSK-3β in an orthosteric binding mode, with IC50 values of 340, 290, 80, and 70 nM, respectively. Further study showed that these stereoisomers can significantly increase the expression of p-GSK-3β (Ser9), and decrease the expressions of p- GSK-3β (Tyr216) and p-GSK-3β (Tyr279). Finally, these compounds can alleviate the cell injury induced by Aβ, and the cognitive disorders in AD mice, especially (+)-2 and (-)-2. Collectively, the stereoisomers of Sch B, especially (+)–2 and (–)–2, were found to be potential selective ATP- competitive GSK-3β inhibitors, which further affected their anti-AD effects. These promising findings explained the biological target of Sch B in AD, and bring a new understanding in the stereochemistry and bioactivities of Sch B.36
Schisandrin B was found to restore cell morphological appearance and viability following Aβ1-42 induced SH- SY5Y cells in a concentration-dependent manner. The inhibitory effect mediated by Schisandrin B on AD model cells involved DNA methylation via regulation of DNMT3A and DNMT 1 mRNA expression, sequentially increasing DNMT 3A and DNMT 1 protein expression levels.37
Memory impairment in Alzheimer’s disease
Sch B attenuated learning and memory impairment of AD mice induced by Aβ1-42. The restoration of glutamate transporter type 1 (GLT-1) and the capacity of glycogen synthase kinase3β (GSK3β) were maintained by Sch B treatment.
In a study by Chen et al. Sch B showed a protective effect in rats with cerebral ischemia/reperfusion (I/R) injury by strengthening the cerebral mitochondrial antioxidant effect. With the Sch B treatment, the GSH, α-TOC, and Mn-SOD expressions were increased, whereas the MDA-level and Ca2+- induced permeability transition was decreased. In addition, Sch B relieved microglial-mediated inflammatory injury by inhibiting ROS and NADPH oxidase activity. Sch B also modulated acetylcholine (ACh) activity in mice with dementia induced by scopolamine. The ACh level was maintained as normal, while the acetylcholinesterase (AChE) activity was inhibited by Sch B.38
Sch B has been effective at inhibiting neural inflammation during in vivo and in vitro studies. Giridharan reported that Sch B modulated receptors for advanced glycation end products (RAGE), NF-κB, and the mitogen-activated protein kinases (MAPK) signaling pathway. Moreover, an overexpression of the proteins prompting inflammation were inhibited by Sch B. As Lee reported, Sch B attenuated cerebral ischemia injury in rats by suppressing the overexpression of inflammatory markers in ischemic hemispheres, and relieved microglial-mediated inflammatory injury by inhibiting the TLR4-dependent MyD88/IKK/NF-κB signaling pathway. Moreover, Sch B showed an inhibitory effect on the LPS-induced inflammatory response by suppressing NF-κB activation, while activating PP AR-γ.39
Microglial-mediated neuroinflammation is now considered to be central to the pathogenesis of various neurodegenerative processes, including Alzheimer’s disease and Parkinson’s disease. Sch B exerted significant neuroprotective effects against microglial-mediated inflammatory injury in microglia–neuron co-cultures. In addition, Sch B significantly downregulated pro-inflammatory cytokines, including nitrite oxide (NO), tumor necrosis factor (TNF)-α, prostaglandin E2 (PGE2), interleukin (IL)-1β and IL-6. Additionally, Sch B inhibited the interaction of Toll-like receptor 4 with the Toll adapter proteins MyD88, IRAK-1 and TRAF-6 resulting in an inhibition of the IKK/nuclear transcription factor (NF)-κB inflammatory signaling pathway. Furthermore, Sch B inhibited the production of reactive oxygen species (ROS) and NADPH oxidase activity in microglia. In summary, Sch B may exert neuroprotective activity by attenuating the microglial-mediated neuroinflammatory response by inhibiting the TLR4-dependent MyD88/IKK/NF-κB signaling pathway.40
Sch B can promote the depolymerization of Aβ oligomers, increase the cell proliferation rates of SH- SY5 Y induced by Aβ, inhibit apoptosis of SH-SY5 Y after injured by Aβ, it can increase expression of Bcl-XL and reduce expression of Caspase-3, inhibit expression of Aβ1-42 and p-Tau, down-regulated expression of NF-κB/TNF-α signaling pathway.41
Schisandrin B alleviates acute oxidative stress via modulation of the Nrf2/Keap1-mediated antioxidant pathway.
Ying Wu, Zheng-cai Li, Li-qing Yao, Mai Li, Mei Tanga. Applied Physiology, Nutrition, and Metabolism, 2019, 44(1): 1-6, https://doi.org/10.1139/apnm-2018-0251
Using the elevated plus maze and open field test, we found that forced swimming, an acute stressor, significantly induced anxiety-like behavior that was alleviated by oral Sch B treatment. In addition, the Sch B treatment reduced toxicity, malondialdehyde levels, and production of reactive oxygen species, an important factor for neuron damage. Antioxidants under the control of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, such as superoxide dismutase and glutathione, were significantly increased by Sch B treatment.
Moreover, a higher percentage of intact cells in the amygdala of treated mice, revealed by Nissl staining, further verified the neuroprotective effect of Sch B. Several proteins, such as Nrf2 and its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1), were abnormally expressed in mice subjected to forced swimming, but this abnormal expression was significantly reversed by Sch B treatment. The results suggest that Sch B may be a potential therapeutic agent against anxiety associated with oxidative stress. The possible mechanism is neuroprotection through enhanced antioxidant activity.
Schisandrin B alleviates acute oxidative stress via modulation of the Nrf2/Keap1-mediated antioxidant pathway
Wu Y, Li Z, Yao L, Li M, Tang M. Applied Physiology, Nutrition, and Metabolism, 2019, 44(1): 1-6, https://doi.org/10.1139/apnm-2018-0251
Schisandrin B (Sch B), one of the main effective components of the dried fruit of Schisandra chinensis, protects neurons from oxidative stress in the central nervous system. Here we investigated the neuroprotective effect of Sch B against damage caused by acute oxidative stress and attempted to define the possible mechanisms. Using the elevated plus maze and open field test, we found that forced swimming, an acute stressor, significantly induced anxiety-like behavior that was alleviated by oral Sch B treatment.
In addition, the Sch B treatment reduced toxicity, malondialdehyde levels, and production of reactive oxygen species, an important factor for neuron damage. Antioxidants under the control of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, such as superoxide dismutase and glutathione, were significantly increased by Sch B treatment.
Moreover, a higher percentage of intact cells in the amygdala of treated mice, revealed by Nissl staining, further verified the neuroprotective effect of Sch B. Several proteins, such as Nrf2 and its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1), were abnormally expressed in mice subjected to forced swimming, but this abnormal expression was significantly reversed by Sch B treatment. Our results suggest that Sch B may be a potential therapeutic agent against anxiety associated with oxidative stress. The possible mechanism is neuroprotection through enhanced antioxidant activity.
MiR-34 family members have been previously shown to play potential functional role in Parkinson’s disease (PD) pathogenesis. This study aims to clarify the potential neuroprotective effect of Schisandrin B (Sch B) involving miR-34a function in 6-OHDA-induced PD model.
Sch B pretreatment ameliorated 6-OHDA-induced changes in vitro, like upregulated miR-34a expression, inhibited Nrf2 pathways and decreased cell survival, and PD feathers in vivo. Moreover,
Nrf2 was negatively regulated by miR-34a, while miR-34a overexpression inhibited the neuroprotection of Sch B in both dopaminergic SH-SY5Y cells and PD mice.
Sch B showed neuroprotective effect in 6-OHDA-induced PD pathogenesis, which could be inhibited by miR-34a, involving the negative regulatory mechanism of miR-34a on Nrf2 pathways.42
Spinal cord injury
Notably, schisandrin B reduced the activation of traumatic injury-associated pathways, including SOD, MDA, NF-κB p65 and TNF-α, in TSCI rats. In addition, schisandrin B suppressed the TSCI-induced expression of caspase-3 and p-p53 in TSCI rats. These results indicated that schisandrin B may attenuate the inflammatory response, oxidative stress and apoptosis in TSCI rats by inhibiting the p53 signaling pathway in adult rats.43
Reactive oxygen species (ROS)‐mediated activation of inflammasome is involved in the development of a wide spectrum of diseases. Results showed that Sch B can induce an nuclear factor erythroid 2‐ related factor 2‐driven thioredoxin expression in primary peritoneal macrophages and cultured RAW264.7 macrophages.
A 4‐h priming of peritoneal macrophages with LPS followed by a 30‐min incubation with ATP caused the activation of caspase 1 and the release of IL‐1β, indicative of inflammasome activation. Although LPS/ATP did not activate inflammasome in RAW264.7 macrophages, it caused the ROS‐dependent c‐Jun N‐terminal kinase1/2 (JNK1/2) activation and an associated lactate dehydrogenase (LDH) release in RAW264.7 macrophages, an indication of cytotoxicity.
Sch B suppressed the LPS/ATP‐induced activation of caspase 1 and release of IL‐1β in peritoneal macrophages. Sch B also attenuated the LPS/ATP‐induced ROS production, JNK1/2 activation and LDH release in RAW264.7 macrophages.
The ability of Sch B to suppress LPS/ATP‐mediated inflammation in vitro was further confirmed by an animal study, in which schisandrin B treatment (2 mmol/kg p.o.) ameliorated the Inject Alum‐induced peritonitis, as indicated by suppressions of caspase1 activation and plasma IL‐1β level. The ensemble of results suggests that Sch B may offer a promising prospect for preventing the inflammasome‐mediated disorders.44
The pharmacological data of Sch B and its active ingredients in protecting against NDs by anti-inflammation effect 45
Aβ-induced neuronal dysfunction in rats 46 Inhibits iNOS, COX-2, IL-1β, IL-6, TNF-α levels and DNA damage
Inhibites RAGE, NF-κB, MAPKs
Protecting against NDs by suppressing apoptosis: Inhibites Caspase-3, TUNEL positive cells Up-regulates HSP70, beclin-1
LPS-induced inflammation in microglia (BV2 cells) 47 Down-regulates TNF-α, IL-6, IL-1β, and PGE2 levels Inhibites NF-κB activation
Up-regulates the expression of PPAR-γ
Microglial-mediated inflammatory injury 48 Down-regulates NO, TNF-α, PGE2, IL-1β, IL-6 levels Inhibits TLR 4, MyD88, IRAK-1, TRAF-6 interaction Inhibits IKK, NF-κB levels
Intraluminal thread induced focal cerebral ischemia in rats 49 Inhibits TNF-α, IL-1β, matrix metalloproteinase (MMP)-2, MMP-9, OX-42 levels
Compared with blank control group, the GABA levels in the peripheral blood and brain tissue of the mice in 10.0 mg · kg-1 SchB group, were significantly increased (P<0.01),the Glu levels in the peripheral blood and brain tissue were significantly reduced (P<0.01),the ratios of GABA/Glu were significantly increased (P<0.01),and the expression levels of GABAARα1and GABAARγ2 in the brain tissue were significantly increased (P<0.01).Conclusion: SchB has an antianxiety effect in the mice, and the effect may be related to its regulating the levels of GABA and Glu in the peripheral blood and brain tissue and the expression levels of GABAA Rα1 and GABAA Rγ2 in the brain tissue.50
GABA / glutamic acid
Results showed that SchB can significantly decrease mouse locomotor activities and improved sleeping quality index, including increased number of sleeping mice treated with the subthreshold dose of pentobarbital sodium, increased sleep time, shortened sleep latency and prolonged sleep duration. SchB could significantly elevate the level of γ-aminobutyric acid (GABA) and reduce the level of glutamic acid(Glu)in the peripheral blood of mice as well as in the cerebral cortex, hippocampus, hypothalamus of rats, resulting in the increased ratio of GABA/Glu.51
Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism.
Yan T, He B, Wan S, et al. Sci Rep. 2017;7(1):6903. Published 2017 Jul 31. doi:10.1038/s41598-017- 07407-1
The aim of this study was to evaluate whether Schisandra chinensis extract (SCE) administration influences chronic unpredictable mild stress (CUMS)-induced depression and cognitive impairment, and explores underlying mechanisms. Sucrose preference test (SPT) and forced swimming test (FST) were used for assessing depressive symptoms, and Y-maze, Morris water maze were used for evaluating cognition processes. The results showed that CUMS (4 weeks) was effective in producing both depression and memory deficits in mice. Additionally, CUMS exposure significantly decreased brain derived neurotrophic factor (BDNF) levels in hippocampus as indicated by ELISA, immunohistochemistry and immunofluorescence assays, accompanied by down-regulated tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB)/extracellular signal- regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3β (GSK-3β) signaling pathways. Chronic administration of SCE (600 or 1200 mg/kg, i.g.) significantly prevented all these CUMS-induced behavioral and biochemical alterations. It suggested that SCE could improve the depression-like emotional status and associated cognitive deficits in CUMS mice, which might be mediated by regulation of BDNF levels in hippocampus, as well as up-regulating of TrkB/CREB/ERK and PI3K/AKT/GSK-3β pathways.
The effect of Schisandra chinensis extracts on depression by noradrenergic, dopaminergic, GABAergic and glutamatergic systems in the forced swim test in mice.
Yan T, Xu M, Wu B, Liao Z, Liu Z, Zhao X, Bi K, Jia Y. Food Funct. 2016 Jun 15;7(6):2811-9. doi: 10.1039/c6fo00328a.
Schisandra chinensis (Turcz.) Baill., as a Chinese functional food, has been widely used in neurological disorders including insomnia and Alzheimer’s disease. The treatment of classical neuropsychiatric disorder depression is to be developed from Schisandra chinensis. The antidepressant-like effects of the Schisandra chinensis extracts (SCE), and their probable involvement in the serotonergic, noradrenergic, dopaminergic, GABAergic and glutamatergic systems were investigated by the forced swim test (FST). Acute administration of SCE (600 mg kg(-1), i.g.), a combination of SCE (300 mg kg(-1), i.g.) and reboxetine (a noradrenalin reuptake inhibitor, 2.5 mg kg(-1), i.p.) or imipramine (a TCA, 2 mg kg(-1), i.p.) reduced the immobility time in the FST. Pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, a selective noradrenergic neurotoxin, 50 mg kg(-1), i.p., 4 days), haloperidol (a non-selective D2 receptor antagonist, 0.2 mg kg(-1), i.p.), SCH 23390 (a selective D1 receptor antagonist, 0.03 mg kg(-1), i.p.), bicuculline (a competitive GABA antagonist, 4 mg kg(-1), i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg kg(-1), i.p.) effectively reversed the antidepressant-like effect of SCE (600 mg kg(-1), i.g.). However, p-chlorophenylalanine (pCPA, an inhibitor of 5-HT synthesis,
100 mg kg(-1), i.p., 4 days,) did not eliminate the reduced immobility time induced by SCE (600 mg kg(-1), i.g.). Moreover, the treatments did not change the locomotor activity. Altogether, these results indicated that SCE produced antidepressant-like activity, which might be mediated by the modification of noradrenergic, dopaminergic, GABAergic and glutamatergic systems.
Pharmacological effects and biological analysis of Schisandra – Sch B 52 53 54
Anti-oxidant ACh activity
GSH antioxidant response GLT-1 and GSK3β activities ROS, NADPH oxidase activity
Anti- inflammatory RAGE, NF-κB, MAPKs signaling PPAR-γ activity
MyD88/IKK/NF-κB signaling pathway TNF-α, IL-1β activities
Cognitive function Passive avoidance-response Scopolamine-induced memory impairment Stress-induced depression-like model Pentobarbital-induced sleep behaviors
Immune Schisandrin B (Sch-B) altered cytokine secretion in Con A-treated mouse splenocytes.
Sch-B suppressed Th1/Th17 induction and T-bet/RORγt expression in mouse naïve Th cells.
Sch-B promoted Treg induction and FoxP3 expression in mouse naïve Th cells.
Sch-B inhibited IL-6/STAT3 pathway in mouse naïve Th cells.
The effect of Sch-B on Th subset differentiation was eliminated by heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin.
Mood Increases Brain-derived neurotrophic Factors (BDNF)
Regulates stress hormone production
Reduces serum levels of cortistatin, adrenocorticotropic hormone (ACTH), and corticotropin-releasing factor (CRF)
Upregulates GABAA receptors
Reduces glutamic acid levels
Neuroprotective Glutamate-induced toxicity tert-Butylhydroperoxide induced toxicity Cerebral ischemia/reperfusion injury
Paraquat-induced oxidative stress in PC12 cells
Amyloid-β and homocysteine toxicity in PC12 cells 3-Nitropropionic acid-induced cell injury in PC12 cells Focal cerebral ischemia
Amyloid-β-induced toxicity in SH-SY5Y cells Cisplatin-induced neurotoxicity
LPS − induced microglia cells
6-Hydroxy-dopamine-induced Parkinson’s disease in SH-SY5Y cells Serum and glucose deprivation injury in SH-SY5Y cells
Amyloid- β-stimulated microglia activation
Subventricular zone- rostral migratory stream-olfactory bulb neurogenesis system
Effects of BDNF on several neuropsychiatric and neurodegenerative conditions 55
Condition Peripheral BDNF Brain BDNF
Major depressive disorder (MDD) Decreased serum and plasma levels of BDNF protein; some literature findings showing no change or increased levels in MDD patients; euthymic patients have normalized BDNF levels in serum or plasma; increased methylation of the Bdnf gene is associated with a decrease in mRNA expression; treatment-resistant patients show lower BDNF levels in serum compared to treatment- responsive patients Decreased BDNF and TrkB mRNA expression in hippocampal slices of MDD patients; use of antidepressant medication was associated with increased Bdnf mRNA expression
Bipolar disorder (BD) Decreased serum and plasma levels of BDNF in both manic and depressive stages of BD; euthymic patients show no difference from controls Decreased BDNF mRNA expression in hippocampus of suicidal BD patients; no difference in Bdnf expression between different disease stages (euthymic, depressive or manic)
Schizophrenia (SCZ) Decreased BDNF protein levels in serum of SCZ patients; no changes in BDNF levels after treatment Decreased expression of Bdnf and Trkb genes in hippocampus and dorsolateral prefrontal cortex of SCZ patients; increased methylation of Bdnf gene in prefrontal cortex of SCZ patients
Alzheimer disease (AD) Low serum BDNF levels correlate with development of dementia—especially AD; decreased levels of BDNF in serum of AD patients; BDNF levels are not related to severity of disease; successful treatment transiently increases BDNF in AD BDNF genotype is related with reduced Hippocampal activity and cognitive function in subjects with high levels of A-β and AD patients; decreased BDNF mRNA levels in the hippocampus of AD patients; increase in methylation pattern of the Bdnf gene in the frontal cortex of AD patients
Parkinson disease (PD) Serum BDNF levels are directly correlated with degeneration of striatum in PD; low serum levels of BDNF is correlated with decreased cognitive function in early PD patients; BDNF decrease in serum is associated with the progression of motor symptoms Low BDNF mRNA expression in the striatum of PD patients; association between BDNF polymorphism and disease progression
Epilepsy BDNF val66met single nucleotide polymorphism is associated with higher BDNF protein expression and an increased risk of developing epilepsy; increased serum BDNF protein levels after epileptic seizures are associated with increased glutamate signaling Increased mRNA expression of Bdnf exons in the hippocampus and cortex of temporal lobe epilepsy patients; increased BDNF protein expression in the hippocampus of temporal lobe epilepsy patients