BioActives – General Background for Neurodegenerative Conditions

 

BioActives and Parkinson’s Disease

Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease.

Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson’s disease.

Van Kampen J, Robertson H, Hagg T, Drobitch R.

Source

Department of Anatomy & Neurobiology, Dalhousie University, Tupper Medical Building, Halifax, B3H 4H7, Nova Scotia, Canada.

Abstract

The herbal remedy, ginseng, has recently been demonstrated to possess neurotrophic and neuroprotective properties, which may be useful in preventing various forms of neuronal cell loss including the nigrostriatal degeneration seen in Parkinson’s disease (PD). In these studies, we examine the potential neuroprotective actions of the ginseng extract, G115, in two rodent models of PD. Animals received oral administration of G115 prior to and/or following exposure to the parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in mice, or its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP(+)), in rats. Such treatment significantly and dramatically blocked tyrosine hydroxylase-positive cell loss in the substantia nigra and reduced the appearance of locomotor dysfunction. Thus, oral administration ofginseng appears to provide protection against neurotoxicity in rodent models of PD. Further examination of the neuroprotective actions ofginseng and its various elements may provide a potential means of slowing the progress of PD.

http://www.ncbi.nlm.nih.gov/pubmed/14637121

Therapeutic efficacy of the neuroprotective plant adaptogen in neurodegenerative disease (Parkinson's disease as an example).

Therapeutic efficacy of the neuroprotective plant adaptogen in neurodegenerative disease (Parkinson’s disease as an example).

Bocharov EV, Ivanova-Smolenskaya IA, Poleshchuk VV, Kucheryanu VG, Il’enko VA, Bocharova OA.

Source

Laboratory for General Pathology of Nervous System, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences. ebocharov@rambler.ru

Abstract

Therapeutic efficacy of the plant neuroprotector Phytomix-40 in Parkinson’s disease was demonstrated. This preparation consists of the components from extracts of 40 plants, including some adaptogens (ginseng, eleutherococcus, Rhodiola rosea, etc.). The preparation normalized immune, antioxidant, and hormonal parameters in patients. The neuroprotective plant adaptogen can be used in complex therapy for Parkinson’sdisease for improving its efficacy.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Therapeutic+Efficacy+of+the+Neuroprotective+Plant+Adaptogen+in+Neurodegenerative+Disease

Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway.

Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson’s disease through the IGF-I receptor signalling pathway.

Xu L, Chen WF, Wong MS.

Source

Department of Physiology, Medical College of Qingdao University, Qingdao, China.

Abstract

BACKGROUND AND PURPOSE:

We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin-like growth factor-I receptor (IGF-IR) signalling pathway in human breast cancer MCF-7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF-IR signalling pathway in a rat model of Parkinson’s disease, induced by 6-hydroxydopamine (6-OHDA).

EXPERIMENTAL APPROACH:

Ovariectomized rats were infused unilaterally with 6-OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6-OHDA injections) in the absence or presence of the IGF-IR antagonist JB-1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl-2 in the substantia nigra were also determined.

KEY RESULTS:

Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB-1. 6-OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6-OHDA-lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl-2 protein and gene level in the substantia nigra. These effects were abolished by JB-1.

CONCLUSIONS AND IMPLICATIONS:

These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6-OHDA model of nigrostriatal injury and its actions might involve activation of the IGF-IR signalling pathway.

Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity.

Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity.

Leung KW, Yung KK, Mak NK, Chan YS, Fan TP, Wong RN.

Source

Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong. kwl_melody@yahoo.co.uk

Abstract

Ginsenoside-Rg1, the pharmacologically active component isolated from ginseng, demonstrated neuroprotective effects on primary cultured rat nigral neurons against rotenone toxicity. Rotenone, a common household pesticide known for its specific and irreversible mitochondria complex I inhibition, has been suggested to be the causal agent of Parkinson’s disease (PD) by inducing degeneration of cells in the substantial nigra. The present study demonstrated that co-treatment of rotenone and Rg1 could reduce rotenone-induced cell death by 58% (SEM=+/-5.60; N=3). Rotenone-induced mitochondria membrane potential (MMP, DeltaPsim) depletion was restored and elevated by at least 38% (SEM=+/-2.15; N=3) by Rg1. In addition, Rg1 prevented cytochrome c release from the mitochrondrial membrane and increased the phosphorylation inhibition of the pro-apoptotic protein Bad through activation of the PI3K/Akt pathway. The protective effects of Rg1 was blocked by glucocorticoid receptor antagonist RU486, indicating that the action of Rg1 is mediated through glucocorticoid receptor (GR). In conclusion, Rg1 inhibits the mitochondrial apoptotic pathway and increases the survival chance of the primary cultured nigral neurons against rotenone toxicity. Thus, Rg1 and its related compounds may be developed as protective agents against neurodegenerative diseases induced by mitochondrial toxins.

Rg1 protects the MPP+-treated MES23.5 cells via attenuating DMT1 up-regulation and cellular iron uptake.

Rg1 protects the MPP+-treated MES23.5 cells via attenuating DMT1 up-regulation and cellular iron uptake.

Xu H, Jiang H, Wang J, Xie J.

Source

State Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao 266071, China.

Abstract

Ginsenoside-Rg1 is one of the pharmacologically active component isolated from ginseng. Our previous study observed the protective effect of Rg1 on iron accumulation in the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated Parkinson’s disease (PD) mice. However, the mechanisms of this neuroprotective effect of Rg1 are unknown. In this study, we elucidated possible mechanisms for this effect using 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells. Previous study showed MPP+ treatment induced up-regulation of divalent metal transporter 1 without iron responsive element (DMT1-IRE) in MES23.5 cells. In the present study, we observed that pretreatment with Rg1 could inhibit MPP+-induced up-regulation of DMT1-IRE in MES23.5 cells. Up-regulation of DMT1-IRE by MPP+ treatment was associated with ROS production and translocation of nuclear factor-kappaB (NF-kappaB) to nuclei, both of which were significantly inhibited by Rg1 pretreatment. The role of ROS and NF-kappaB in the up-regulation of DMT1-IRE was supported by application of an antioxidant NAC and BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation. Furthermore, we also showed Rg1 could decrease DMT1-mediated ferrous iron uptake and iron-induced cell damage by inhibiting the up-regulation of DMT1-IRE. These results indicate that Rg1 protected the MPP+-treated MES23.5 cells via attenuating DMT1-IRE up-regulation likely through inhibition of ROS-NF-kappaB pathway; Attenuation of DMT1-IRE expression decreased the iron influx and iron-induced oxidative stress.

http://www.ncbi.nlm.nih.gov/pubmed/19744503

BioActives and Alzheimer’s Disease

Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease.

Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer’s disease.

Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M.

Abstract

OBJECTIVES:

Ginseng has been reported to improve cognitive function in animals and in healthy and cognitively impaired individuals. In this study, we investigated the efficacy of a heat-processed form ofginseng that contains more potent ginsenosides than raw ginseng in the treatment of cognitive impairment in patients with moderately severe Alzheimer’s disease (AD).

METHODS:

Forty patients with AD were randomized into one of three different dose groups or the control group as follows: 1.5 g/day (n = 10), 3 g/day (n = 10), and 4.5 g/day (n = 10) groups, or control (n = 10). The Alzheimer’s Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE) were used to assess cognitive function for 24 weeks.

RESULTS:

The treatment groups showed significant improvement on the MMSE and ADAS. Patients with higher dose group (4.5 g/day) showed improvements in ADAS cognitive, ADAS non-cognitive, and MMSE score as early as at 12 weeks, which sustained for 24-week follow-up.

DISCUSSION:

These results demonstrate the potential efficacy of a heat-processed form of ginseng on cognitive function and behavioral symptoms in patients with moderately severe AD.

http://www.ncbi.nlm.nih.gov/pubmed/22780999

An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease.

An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer’s disease.

Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M.

Source

Department of Neurology, Seoul Medical Center, Seoul, Korea.

Abstract

BACKGROUND AND PURPOSE:

Ginseng is one of the most popular herbs worldwide. Ginseng has various medical applications, and it seems to have significant effects as a cognition-enhancing drug. In this study, we examined the efficacy of Korean red ginseng (KRG) as an adjuvant therapy to conventional anti-dementia medications in patients with Alzheimer’s disease.

METHODS:

The trial was designed as a 12-week randomized study. Sixty-one patients (24 males and 37 females) with Alzheimer’s disease were randomly assigned to one of the following treatment groups: low-dose KRG (4.5 g/day, n = 15), high-dose KRG (9 g/day, n = 15) or control (n = 31). The Alzheimer’s DiseaseAssessment Scale (ADAS), Korean version of the Mini-Mental Status Examination (K-MMSE) and Clinical Dementia Rating (CDR) scale were used to assess the change in cognitive and functional performance at the end of the 12-week study period.

RESULTS:

The patients in the high-dose KRG group showed significant improvement on the ADAS and CDR after 12 weeks of KRG therapy when compared with those in the control group (P = 0.032 and 0.006 respectively). The KRG treatment groups showed improvement from baseline MMSE when compared with the control group (1.42 vs. -0.48), but this improvement was not statistically significant.

CONCLUSIONS:

KRG showed good efficacy for the treatment of Alzheimer’s disease; however, further studies with larger samples of patients and a longer efficacy trial should be conducted to confirm the efficacy of KRG.

http://www.ncbi.nlm.nih.gov/pubmed/18684311

Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model.

Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model.

Fang F, Chen X, Huang T, Lue LF, Luddy JS, Yan SS.

Source

Department of Surgery, Physicians & Surgeons College of Columbia University, New York, NY 10032, USA.

Abstract

There has been no extensive characterization of the effects of Ginsenoside Rg1, a pharmacological active component purified from the nature product ginseng, in an Alzheimer’s disease mouse model. The well-characterized transgenic Alzheimer disease (AD) mice over expressing amyloid precursor protein (APP)/Aβ (Tg mAPP) and nontransgenic (nonTg) littermates at age of 6 and 9 months were treated with Rg 1 for three months via intraperitoneal injection. Mice were then evaluated for changes in amyloid pathology, neuropathology and behavior. Tg mAPP treated with Rg1 showed a significant reduction of cerebral Aβ levels, reversal of certain neuropathological changes, and preservation of spatial learning and memory, as compared to vehicle-treated mice. Rg1 treatment inhibited activity of γ-secretase in both Tg mAPP mice and B103-APP cells, indicating the involvement of Rg1 in APP regulation pathway. Furthermore, administration of Rg1 enhanced PKA/CREB pathway activation in mAPP mice and in cultured cortical neurons exposed to Aβ or glutamate-mediated synaptic stress. Most importantly, the beneficial effects on attenuation of cerebral Aβ accumulation, improvement in neuropathological and behavioral changes can be extended to the aged mAPP mice, even to 12-13 months old mice that had extensive amyloid pathology and severe neuropathological and cognitive malfunction. These studies indicate that Rg1 has profound multi-faced and neuroprotective effects in an AD mouse model. Rg1 induces neuroprotection through ameliorating amyloid pathology, modulating APP process, improving cognition, and activating PKA/CREB signaling. These findings provide a new perspective for the treatment of AD and demonstrate potential for a new class of drugs for AD treatment.

http://www.ncbi.nlm.nih.gov/pubmed/22015470

BioActives: Other Research

Ginsenosides and their CNS targets.

Ginsenosides and their CNS targets.

Radad K, Moldzio R, Rausch WD.

Source

Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt. khaledradad@hotmail.com

Abstract

Ginsenosides are a special group of triterpenoid saponins attributed to medical effects of ginseng. Therefore, they have been research targets over the last three decades to explain ginseng actions and a wealth of literature has been presented reporting on ginsenosides’ effects on the human body. Recently, there is increasing evidence on beneficial effects of ginsenosides to the central nervous system (CNS). Using a wide range of in vitro and in vivo models, researchers have attributed these effects to specific pharmacological actions of ginsenosides on cerebral metabolism, oxidative stress and radical formation, neurotransmitter imbalance and membrane stabilizing effects, and even antiapoptotic effects. Modulating these particular mechanisms by ginsenosides has thus been reported to exert either general stimulatory effects on the brain functions or protecting the CNS against various disease conditions. In this review, we try to address the recently reported ginsenosides’ actions on different CNS targets particularly those supporting possible therapeutic efficacies in CNS disorders and neurodegenerative diseases.

http://www.ncbi.nlm.nih.gov/pubmed/21143430

Use of ginseng in medicine with emphasis on neurodegenerative disorders.

Use of ginseng in medicine with emphasis on neurodegenerative disorders.

Radad K, Gille G, Liu L, Rausch WD.

Source

Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Egypt. khaledradad@hotmail.com

Abstract

Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as a traditionalmedicine in China, Korea, and Japan for thousands of years and is now a popular and worldwide used naturalmedicine. The active ingredients of ginseng are ginsenosides which are also called ginseng saponins. Recently, there is increasing evidence in the literature on the pharmacological and physiological actions ofginseng. However, ginseng has been used primarily as a tonic to invigorate weak bodies and help the restoration of homeostasis. Current in vivo and in vitro studies have shown its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency, and hepatotoxicity. Moreover, recent research has suggested that some of ginseng’s active ingredients also exert beneficial effects on aging, central nervous system (CNS) disorders, and neurodegenerative diseases. In general, antioxidant, anti-inflammatory, anti-apoptotic, and immune-stimulatory activities are mostly underlying the possible ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms that involve decreasing nitric oxide (NO), scavenging of free radicals, and counteracting excitotoxicity. In this review, we focus on recently reported medicinal effects of ginseng and summarize the current knowledge of its effects on CNS disorders and neurodegenerativediseases.

http://www.ncbi.nlm.nih.gov/pubmed/16518078

Biological Activities of Ginseng and Its Application to Human Health.

Biological Activities of Ginseng and Its Application to Human Health.

Wee JJ, Mee Park K, Chung AS.

Editors

In: Benzie IFF, Wachtel-Galor S, editors.

Source

Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press; 2011. Chapter 8.

Excerpt

The major bioactive components of P. ginseng are the ginsenosides, a group of saponins with dammarane triterpenoid structure (Huang 1999). Almost 50 ginsenosides have been isolated from P. ginseng root (white and red ginsengs), and novel structures continue to be identified, particularly fromPanax quinquefolius (American ginseng) and Panax japonica (Japanese ginseng) as well as their berries (Gillis 1997; Yoshikawa et al. 1998; Attele et al. 2002; Christensen 2009). In this chapter, we review the structural and pharmacological properties of ginseng, and its active constituents, including ginsenosides, polysaccharides, and polyacetylenic alcohols. The pharmacological and clinical usages of ginseng, particularly ginsenosides, are discussed in relation to its anticancer, antidiabetes, immunomodulatory functions, and improving CNS functions including learning, memory, and neurodegenerative diseases.

http://www.ncbi.nlm.nih.gov/pubmed/22593942

Effects of red ginseng extract on sleeping behaviors in human volunteers.

Effects of red ginseng extract on sleeping behaviors in human volunteers.

Han HJ, Kim HY, Choi JJ, Ahn SY, Lee SH, Oh KW, Kim SY.

Source

J Ethnopharmacol. 2013 Sep 16;149(2):597-9. doi: 10.1016/j.jep.2013.07.005. Epub 2013 Jul 16.

Abstract

ETHNOPHARMACOLOGICAL RELEVENCE:

The ginseng root has been traditionally used as a sedative in oriental countries. However, the condition “ginseng abuse syndrome” (GAS), defined as hypertension, nervousness, sleeplessness, skin eruption, and morning diarrhea, was coined as a result of a study of people who had been using a variety of ginseng preparations. However, we reported that administration of RGE increased rapid eye movement (REM) and non rapid eye movement (NREM) sleep via GABAergic systems in animals. Therefore, this study was performed to investigate how red ginseng extract (RGE) affects sleeping behaviors in human volunteers.

MATERIALS AND METHODS:

RGE (1500 mg) was orally administered to young male healthy volunteers (from 15 to 37 years old ages, n=15) three times a day for 7 days. Overnight polysomnographic (PSG) studies were performed two times, 1 day before and 7 days after RGE administration. We investigated differences in sleep architecture parameters such as total sleep time (TST), sleep efficacy (SE: total sleep time/time in bed), proportion of each sleep stage, and wakefulness after sleep onset (WASO) between baseline PSG and PSG after RGE administration.

RESULTS:

Total wake time (TWT) was significantly reduced (P<0.05) and SE was increased (P<0.05), although slow wave sleep stage 1 (N1) was reduced (P<0.01) and non-rapid eye movement (REM) sleep was increased (P<0.03) after administration.

CONCLUSION:From these results, it is presumed that RGE intake would improve the quality of sleep, thus having beneficial effects on sleep disturbed subjects.

http://www.ncbi.nlm.nih.gov/pubmed/22593942

Therapeutic & pharmacological effects of ginseng and ginsenosides in central nervous system

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

Hee Jin Kim, Pitna Kim, and Chan Young Shin

Source

Journal of Ginseng Research. March 2013; 37(1):8-29.

Abstract

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659622/

Ginsenoside rg1 prevents cognitive impairment and hippocampus senescence in a rat model of d-galactose-induced aging

Ginsenoside rg1 prevents cognitive impairment and hippocampus senescence in a rat model of d-galactose-induced aging

Zhu, J., Mu, X., Zeng, J., Xu, C., Liu, J., Zhang, M., Li, C., Chen, J., Li, T., Wang, Y.

Source

PLoS One. 2014 Jun 30;9(6):e101291. doi: 10.1371/journal.pone.0101291. eCollection 2014.

Abstract

Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus.

http://www.ncbi.nlm.nih.gov/pubmed/24979747#