Ginsenoside Rg2 Delays Brain Aging via Inhibiting α-Synuclein Expression and Promoting FoxO-Mediated Neurogenesis in Mice

 Will your competent? doctor ensure human testing occurs to recover your 5 lost years of brain cognition due to your stroke? Oh, your doctor doesn't consider that part of the job! Why hasn't that doctor been fired yet?

Ginsenoside Rg2 Delays Brain Aging via Inhibiting α-Synuclein Expression and Promoting FoxO-Mediated Neurogenesis in Mice

Ethnopharmacological relevance

Panax ginseng C.A. Meyer (ginseng) has been utilized in East Asian medicine for centuries to enhance cognitive function, improve memory, and mitigate age-related decline. Ginsenoside Rg2, a key bioactive saponin from red ginseng, is thought to contribute to its neuroprotective effects on brain health.

Aim of the study

This study aimed to investigate the role of α-synuclein (α-Syn) in brain aging and to elucidate whether ginsenoside Rg2 can delay brain aging by modulating α-Syn expression and promoting FoxO1-mediated neurogenesis in mice.

Materials and methods

Naturally aging mice and D-galactose-induced aging mouse models were utilized. α-Syn expression was bi-directionally manipulated in the dentate gyrus (DG) through stereotaxic injection of adeno-associated virus (AAV) for α-Syn overexpression or knockdown. Behavioral tests, immunofluorescence, Western blot, and ELISA were performed to evaluate cognitive function, neurogenesis markers (Ki67, Nestin), aging markers (p53, p21), oxidative stress indicators (MDA, LDH, CAT), and α-Syn expression. Ginsenoside Rg2 was administered to assess its effects.

Results

α-Syn expression was significantly elevated in the DG of both naturally aging and D-galactose-induced aging mice. Overexpression of α-Syn accelerated brain aging and cognitive decline, whereas knockdown alleviated these effects. Mechanistically, α-Syn overexpression inhibited neurogenesis in the DG via the FoxO1 signaling pathway. Treatment with ginsenoside Rg2 significantly reduced α-Syn expression, decreased oxidative stress and aging markers, enhanced neurogenesis, and improved cognitive function in aging mice.

Conclusions

This study demonstrates that α-Syn acts as an “accelerator” of brain aging by impairing FoxO1-mediated neurogenesis in the DG. Ginsenoside Rg2 mitigates brain aging and cognitive decline by inhibiting α-Syn expression and promoting neurogenesis, supporting the traditional use of ginseng for cognitive health and aging resilience.

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Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation

 Lots of words but NO ACTIONABLE INTERVENTIONS! So useless; you're fired!

Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation

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https://doi.org/10.1016/j.brainresbull.2024.111043

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Highlights

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  Ginsenoside Rg1 significantly improves cerebral hemorrhagic reperfusion injury.

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  Ginsenoside Rg1 attenuates microglial cell inflammatory response.

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  Ginsenoside Rg1 reduces mitochondrial autophagy in microglia and inhibits inflammatory vesicle activation.

Abstract

Objective

This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion.

Methods

In this study, we observed the apoptosis of RM cells (microglia) after oxygen-glucose deprivation/reoxygenation (OGD/R) modeling before and after Rg1 administration, changes in mitochondrial membrane potential, changes in the content of Reactive oxygen species (ROS) and inflammatory vesicles NLR Family Pyrin Domain Containing 3 (NLRP3), and the expression levels of autophagy-related proteins, inflammatory factors, and apoptosis proteins. We further examined the pathomorphological changes in brain tissue, neuronal damage, changes in mitochondrial morphology and mitochondrial structure, and the autophagy-related proteins, inflammatory factors, and apoptosis proteins expression levels in CI/RI rats before and after administration of Rg1 in vivo experiments.

Results

In vitro experiments showed that Rg1 induced mitochondrial autophagy, decreased mitochondrial membrane potential, and reduced ROS content thereby inhibiting NLRP3 activation, decreasing secretion of inflammatory factors and RM cell apoptosis by regulating the PTEN induced putative kinase 1(Pink1) /Parkin signaling pathway. In vivo experiments showed that Rg1 induced mitochondrial autophagy, inhibited NLRP3 activation, improved inflammatory response, and reduced apoptosis by regulating the Pink1/Parkin signaling pathway, and Rg1 significantly reduced the area of cerebral infarcts, improved the pathological state of brain tissue, and attenuated the neuronal damage, thus improving cerebral ischemia/reperfusion injury in rats.

Conclusion

Our results suggest that ginsenoside Rg1 can ameliorate cerebral ischemia-reperfusion injury by modulating Pink1/ Parkin-mediated mitochondrial autophagy in microglia and inhibiting microglial NLRP3 activation.

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Keywords

Cerebral ischemia/reperfusion injury

Ginsenoside Rg1

Pink1/Parkin

Mitochondrial autophagy

Microglia

1. Introduction

Cerebral ischemia-reperfusion injury (CI/RI) refers to cerebral ischemia that triggers cellular dysfunction and cell death after a specific period, and ischemic tissues are rescued by restoration of blood flow and perfusion. However, reperfusion itself causes tissue damage, which in turn aggravates the degree of cerebral tissue damage (Lim et al., 2021). The complex pathogenesis of CIRI involves multiple components. The early decline in cerebral blood flow causes energy loss and impairs energy synthesis, leading to depolarization of neuronal cell membranes and imbalance of intra- and extracellular ion homeostasis. This can lead to a series of cascade reactions after cerebral ischemia inducing mitochondrial damage, oxidative stress, inflammatory response, Ca²⁺ overload, accelerating neuronal apoptosis, and thus hindering the recovery of neurological function (Zhang et al., 2022). In recent years, research on treating cerebral ischemia-reperfusion injury by regulating mitochondrial autophagy-related molecules has made some progress, which is of positive significance for protecting neurons from ischemia-reperfusion injury and improving patient healing.

As one of the organism's most critical and sensitive organelles, mitochondria plays a crucial role in cell survival (Koch et al., 2017). Among the multiple pathogenesis of cerebral ischemia-reperfusion injury, the mechanism of mitochondrial autophagy plays an important role. Moderate enhancement of mitochondrial autophagy attenuates cerebral ischemia/reperfusion injury, whereas dysfunctional mitochondrial autophagy activates various pathological mechanisms to exacerbate cellular damage (Wu et al., 2021). The Pink1/Parkin pathway is a classical pathway mediating mitochondrial autophagy. Pink1 (PTEN-induced kinase1) senses mitochondrial damage and activates Parkin through phosphorylation and ubiquitination. Activated Parkin constructs a ubiquitin chain on damaged mitochondria and labels them as mitochondria with ubiquitin. Activated Parkin builds ubiquitin chains on damaged mitochondria, tagging them for degradation of damaged mitochondria (Eiyama and Okamoto, 2015, Bingol and Sheng, 2016). Damaged mitochondria releases large amounts of reactive oxygen species, which are involved in the activation of NLRP3 (NLR Family Pyrin Domain Containing 3) inflammatory vesicles, the activation of which further triggers apoptosis and tissue damage. Studies have shown that inhibiting mitochondrial reactive oxygen species production can suppress NLRP3 inflammasome activation (Lin et al., 2019).

Ginsenoside Rg1 (Rg1) is the main active ingredient of ginseng, which can produce significant neuroprotective effects against cerebral ischemic injury through the interaction of different signaling pathways (Xie et al., 2018). Studies have shown that Rg1 can improve ischemic conditions by repairing inflammation associated with dendrites, axons, microglia, and astrocytes, which can significantly reduce apoptosis (Yang et al., 2023, Han et al., 2022a). However, little is known about the mechanism of action of Rg1 in regulating mitochondrial function to inhibit microglia NLRP3 activation to ameliorate cerebral ischemia-reperfusion injury. We utilized aspirin as a positive drug to eliminate the interference of negative results, and set up the FCCP group as a PINK1 activator, and set up the Rg1+CsA group to test whether Rg1 could reverse mitochondrial autophagy caused by CsA. In this study, we observed the changes in mitochondrial morphology and structure as well as the effects on the expression levels of mitochondrial autophagy-related proteins before and after administration of Rg1 in rats with cerebral ischemia-reperfusion model. The possible mechanism of action of Rg1 for the treatment of cerebral ischemia-reperfusion injury was further elucidated by in vivo and in vitro experiments. This will further promote the development of drug candidates to improve cerebral ischemia-reperfusion injury and provide more information and data support for clinical application.

More at link.

Ginseng as a therapeutic target to alleviate gut and brain diseases via microbiome regulation

 What in here will give your doctor information to have a diet protocol created for ginseng? Or doesn't your competent? doctor have the ability to create stroke rehab protocols?

Ginseng as a therapeutic target to alleviate gut and brain diseases via microbiome regulation

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Abstract

The human gut, which contains a diverse microbiome, plays an important role in maintaining physiological balance and preserving the immune system. The complex interplay between the central nervous system (CNS) and the gut microbiome has gained significant attention due to its profound implications for overall health, particularly for gut and brain disorders. There is emerging evidence that the gut-brain axis (GBA) represents a bidirectional communication system between the CNS and the gastrointestinal tract and plays a pivotal role in regulating many aspects of human health. Ginseng has shown potential to ameliorate conditions associated with dysbiosis, such as gut and CNS disorders by restoring microbial balance and enhancing gut barrier function. This comprehensive review provides valuable insights into the potential of ginseng as a herbal modulator of GBA as a therapeutic intervention for preventing and treating gut and neurological diseases via microbiota regulation to ultimately enhance overall health. Furthermore, we emphasize the therapeutic benefits of ginseng, its ability to enhance beneficial probiotics, such as Firmicutes, Bacteroides, Lactobacillus, Bifidobacterium, and Akkermansia while reducing pathogenic bacteria prevalence, such as Helicobacter, Clostridium, and Proteobacteria. Although the connection between ginseng regulation of microbial communities in response to the gut and neuropsychiatric disorders is lacking, additional investigations are warranted to elucidate the underlying mechanisms, optimize dosages, and explore the clinical relevance of ginseng in promoting GBA balance and ultimately overall health.

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Brain plasticity and ginseng

 Oh hell, just ask your competent? doctor how much ginseng to consume, supplement or real item!  Will your doctor guarantee that neuroplasticity will work and you'll recover?

Brain plasticity and ginseng

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https://doi.org/10.1016/j.jgr.2024.03.007Get rights and content

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Abstract

Brain plasticity refers to the brain's ability to modify its structure, accompanied by its functional changes. It is influenced by learning, experiences, and dietary factors, even in later life. Accumulated researches have indicated that ginseng may protect the brain and enhance its function in pathological conditions. There is a compelling need for a more comprehensive understanding of ginseng's role in the physiological condition because many individuals without specific diseases seek to improve their health by incorporating ginseng into their routines. This review aims to deepen our understanding of how ginseng affects brain plasticity of people undergoing normal aging process. We provided a summary of studies that reported the impact of ginseng on brain plasticity and related factors in human clinical studies. Furthermore, we explored researches focused on the molecular mechanisms underpinning the influence of ginseng on brain plasticity and factors contributing to brain plasticity. Evidences indicate that ginseng has the potential to enhance brain plasticity in the context of normal aging by mediating both central and peripheral systems, thereby expecting to improve age-related declines in brain function. Moreover, given modern western diet can damage neuroplasticity in the long term, ginseng can be a beneficial supplement for better brain health.

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Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

This from Feb. 2015 completely proves the incompetence of everyone in stroke, no followup, no nothing, so more research writeups are done because that database of stroke research and protocols doesn't exist.

Ginseng: a promising neuroprotective strategy in stroke

February 2015

But lets do more repeated research here:

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

Lei Liu¹, Gigi A. Anderson¹, Tyler G. Fernandez¹ and Sylvain Doré^1,2*

• ¹Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease and McKnight Brain Institute, University of Florida, Gainesville, FL, United States
• ²Departments of Neurology, Psychiatry, Pharmaceutics, and Neuroscience, University of Florida, Gainesville, FL, United States

Stroke is one of the leading causes of death and long-term disability worldwide. However, effective therapeutic approaches are still limited. The disruption of blood supply triggers complicated temporal and spatial events involving hemodynamic, biochemical, and neurophysiologic changes, eventually leading to pathological disturbance and diverse clinical symptoms. Ginseng (Panax ginseng), a popular herb distributed in East Asia, has been extensively used as medicinal and nutritional supplements for a variety of disorders worldwide. In recent years, ginseng has displayed attractive beneficial effects in distinct neurological disorders including stroke, involving multiple protective mechanisms. In this article, we reviewed the literature on ginseng studies in the experimental stroke field, particularly focusing on the in vivo evidence on the preventive or therapeutic efficacy and mechanisms of ginseng and ginsenosides in various stroke models of mice and rats. We also summarized the efficacy and underlying mechanisms of ginseng and ginsenosides on short- and long-term stroke outcomes.

Introduction

Ginseng (Panax ginseng C. A. Meyer) has been extensively used as medicinal and nutritional supplements for a variety of disorders worldwide (Rastogi et al., 2014; Colzani et al., 2016). Asian ginseng has a history of herbal use over thousands of years, first described in the ancient Chinese pharmacopeia, Shen Nong Ben Cao Jing (300 BC−200 AD, also Divine Farmer's Classic of Materia Medica) (Unschuld, 1985; Yang and Wu, 2016). It is one of the most highly regarded herbs in the Orient used to promote health, general body vigor, and to prolong life span. The Greek word “Panax” originates from the word “panacea,” which means “cure all diseases,” and true to its name, ginseng has been proven to have a wide variety of medicinal uses, including benefits in cardiovascular disorders (Karmazyn et al., 2011; Sun et al., 2016; Kim, 2018), aging-related disorders (Bjorklund et al., 2018), and others (Sotaniemi et al., 1995; An et al., 2011; Shergis et al., 2014; Zhang et al., 2017; Arring et al., 2018). In recent years, preclinical and clinical studies revealed that ginseng displayed attractive beneficial effects in multiple neurological disorders like stroke, hypertension, cancer, and maintenance of hemostasis in the immune system, involving multiple protective mechanisms (Lee et al., 2009; Im and Nah, 2013; Rastogi et al., 2014; Gonzalez-Burgos et al., 2015; Ong et al., 2015; Oh and Kim, 2016; Wang et al., 2016b; Kim et al., 2018).

Stroke is a leading cause of death and long-term disability worldwide (Feigin et al., 2017; Benjamin et al., 2018); however, effective therapies are limited (Feigin et al., 2016). The disruption of blood supply triggers complicated temporal and spatial events involving hemodynamic, biochemical, and neurophysiologic changes, eventually leading to pathological disturbance and diverse clinical symptoms (Lo et al., 2003; Iadecola and Anrather, 2011; Annunziato et al., 2013; Bernhardt et al., 2018). The severity and dynamic progression of brain injury depend on the degree of cerebral blood flow (CBF) interruption, lesion volume and site, duration of stroke, and the coexisting complications (Shen and Duong, 2008; Sun et al., 2014b; Fu et al., 2015; Ward, 2017). Accumulated evidence shows that oxidative stress and inflammation play key roles in the pathophysiology of stroke (Iadecola and Anrather, 2011; Li et al., 2011a; Carbone et al., 2015; Fu et al., 2015). Although the ginseng remedy has been widely applied to improve cardiac health and circulation, their studies in the stroke field are still limited (Gan and Karmazyn, 2018; Kim, 2018). Over the last decade, much promising advancements were made in the therapeutic effects of ginseng or ginsenosides on experimental stroke brain injury.

In this article, we reviewed the literature on ginseng and ginsenosides studies in the experimental stroke field, particularly focusing on the in vivo evidence in diverse stroke models of mice and rats. We summarized the efficacy of ginseng and ginsenosides on short- and long-term stroke outcomes, as well as the underlying molecular and cellular mechanisms. This review provides current understanding of the pharmacological benefits of ginseng that contribute to stroke prevention and recovery.

 

 

9 Natural Supplements for Cognitive Impairment from Neurology Times

Your doctor can vet all these and give you protocols for amounts and timings. 
http://www.neurologytimes.com/slideshows/9-natural-supplements-cognitive-impairment?elq_cid=1818492&elq_mid=1580&rememberme=1
Slide show at link. 
Ginko biloba: Some research shows it does not improve cognition without cognitive impairment does not prevent dementia; may improve cognitive function with Alzheimer disease (AD) or vascular dementia (VaD).
The data on ginkgo biloba for improving cognition in patients with dementia are more extensive than the data on prevention of cognitive impairment.
Omega 3 fatty acids: Some research shows eating fish reduces incidence of AD; omega 3 supplementation does not prevent AD; improved attention & processing speed with mild dementia (MD); does not improve cognition in AD.
Ginseng: Some improvement in cognition in AD. For more on this topic, see Ginkgo, ginseng, and royal jelly combination improves memory in patients with mild cognitive impairment.
Vitamin B12, B9: Some improvement in cognition in cognitively intact individuals but not those with dementia.  Note that supplementation does not improve dementia in those with normal levels of Vitamin B, but if Vitamin B12 deficiency exists, supplementation can improve memory. For related content, see: Mild Cognitive Impairment: Impact of Exercise.
Huperzine: Modest improvement in cognition in AD. For more on this topic, see Vitamin Supplements for Neurological Disorders.
Vitamin D: Increased dementia with deficiency. For more on this topic, see Study Confirms Vitamin D, Dementia Risk Link. 
Curcumin: No impact on cognition, but data are limited. For more on curcumin, see Curcumin: New Use for an Old Spice? 
Coconut oil/caprylidene: Improved cognition in persons with AD who are not APOE-4 allele carriers.
Resveratrol: No changes in cognition in persons with AD but reduced biomarker AB levels.
For more on this topic, see Natural Supplements and Vitamins for Treatment and Prevention of Dementia and Cognitive Decline, on which this slideshow is based.   

Coconut oil/caprylidene: Improved cognition in persons with AD who are not APOE-4 allele carriers.

    

Ginseng: a promising neuroprotective strategy in stroke

Is anyone ever going to write up a stroke protocol for this kind of stuff?  My god, neurons are dying by the trillions every day because our stroke medical people will not get off their asses and put this together.  This is not somebody else's problem to solve, it's yours. So buckle down and put some f*cking neuroprotective stroke protocols together.  My ideas here:
these 31 hyperacute possibilities I'm going to insist my doctor give me the first week. 

http://journal.frontiersin.org/article/10.3389/fncel.2014.00457/full? 

Vaibhav Rastogi^1,2, Juan Santiago-Moreno¹ and Sylvain Doré^1,2,3,4*

• ¹Departments of Anesthesiology, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, USA
• ²Departments of Neurology, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, USA
• ³Departments of Psychiatry, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, USA
• ⁴Departments of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida College of Medicine, Gainesville, FL, USA

Ginseng is one of the most widely used herbal medicines in the world. It has been used in the treatment of various ailments and to boost immunity for centuries; especially in Asian countries. The most common ginseng variant in traditional herbal medicine is ginseng, which is made from the peeled and dried root of Panax Ginseng. Ginseng has been suggested as an effective treatment for a vast array of neurological disorders, including stroke and other acute and chronic neurodegenerative disorders. Ginseng’s neuroprotective effects are focused on the maintenance of homeostasis. This review involves a comprehensive literature search that highlights aspects of ginseng’s putative neuroprotective effectiveness, focusing on stroke. Attenuation of inflammation through inhibition of various proinflammatory mediators, along with suppression of oxidative stress by various mechanisms, including activation of the cytoprotective transcriptional factor Nrf2, which results in decrease in reactive oxygen species, could account for its neuroprotective efficacy. It can also prevent neuronal death as a result of stroke, thus decreasing anatomical and functional stroke damage. Although there are diverse studies that have investigated the mechanisms involved in the efficacy of ginseng in treating disorders, there is still much that needs to be clarified. Both in vitro and in vivo studies including randomized controlled clinical trials are necessary to develop in-depth knowledge of ginseng and its practical applications.

Introduction

Ginseng is a broad term that refers to a group of 11 species of perennial plants belonging to the Panax genus under the family Araliaceae. The commercially available herbal formulations of ginseng are extracted from the root of these plants. It has been used for more than 2000 years mainly in China, Korea and Japan. The most commonly used herbal derivative of ginseng is Korean ginseng which is derived from the peeled, steamed, and dried root of Panax ginseng also commonly known as Korean ginseng. Although there are other variants of ginseng that contain many of the same compounds and medicinal properties, we will mainly focus on Panax ginseng and its constituents. The chemical constituents of ginseng include triterpene saponins, polysaccharides, peptidoglycans, nitrogen-containing compounds, fatty acids, carbohydrates and phenolic compounds (Sticher, 1998). It also contains essential oil-containing polyacetylenes and sesquiterpenes (Sticher, 1998). Ginsenosides are the major active components in ginseng; they are a form of triterpene glycosides (saponins). Of the 150 ginsenosides that have been isolated from ginseng, 40 have been found in Panax ginseng alone (Christensen, 2009). These mainly include Rb1, Rb2, Rc, Rd, Rg1, Rg2, Rh1, and Re (Attele et al., 1999).

The Greek word “panax” means “cure-all” and true to its name, ginseng has proven to have a wide variety of medicinal uses. Ginseng can improve pulmonary lung function in stable chronic obstructive pulmonary disorder patients (An et al., 2011). Korean ginseng has been shown to provide symptomatic relief in the patients with complaints of erectile dysfunction (Hong et al., 2002). A large number of carcinomas, including those associated with smoking, could potentially be prevented by the regular use of ginseng (Yun and Choi, 1995). Ginseng’s efficacy in type-2 diabetics has been illustrated by the fact that the patients had a decrease in the fasting blood glucose, weight loss and HbA1c (glycated hemoglobin) along with improvement in mood and psychophysical performance (Sotaniemi et al., 1995). Ginseng also possesses numerous cardiovascular benefits that are mainly due to its cardioprotective and anti-hypertensive effects; it can also attenuate myocardial hypertrophy and heart failure (Karmazyn et al., 2011).

Ginseng is also known to affect various aspects of neurodevelopmental, neurodegenerative and neuropsychiatric disorders (Kim et al., 2013). Stroke is the 4th leading cause of death in United States with an estimated 1 death every 4 min. Stroke recurs in 1 out of every 4 stroke patients. Approximately 87% of strokes are a result of ischemic insult and 13% are hemorrhagic strokes. Subarachnoid hemorrhage (SAH) accounts for approximately 3% of all strokes, has an incidence rate of 30,000 cases per year (King, 1997) and is mostly seen after brain aneurysm rupture or in traumatic brain injury (TBI) patients. Stroke is also one of the leading causes of long term disability (Go et al., 2013). These are reasons for stroke’s high magnitude of mortality and morbidity. From this information, one can see that present preventive and treatment strategies are not sufficient to curb this health menace. Because of this, there is a need to look for other treatment modalities and ginseng has shown promising evidence in this regard.