Adaptogens

[mccoy]

Dear all,

I did a search in the 'Forums' but only found cursory hints to adaptogens. Do they have a place in CR/ longevity schemes/healthy regimens? Do you guys take any of'em and with which purpose?

 

definitions from wiki follows as well as a recognized list. In my youth, young boys used to extract licorice roots and chew them. Right now I learn licorice is classified into the adaptogens group

 

 

Adaptogenesis was later applied in the former Soviet Union to describe remedies that increase the resistance of organisms to biological stress in experimental and clinical studies.^[3] According to the original definition, adaptogens are:

non-specific remedies 

"that increase resistance to a broad spectrum of harmful factors (stressors) of different physical, chemical and biological natures"

.

[7]

This definition has been updated and today adaptogens are conceptualized as a:

"new class of metabolic regulators (of a natural origin) which increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors."

[7]

Another definition requires that, for an herb to be considered an adaptogen, it must be nontoxic, nonspecific and have a normalizing effect on physiology.^[8]

 

 

• American Ginseng (Panax quinquefolius), root
• Ashwagandha (Withania somnifera), root
• Asian Ginseng (Panax ginseng), root
• Cordyceps (Cordyceps sinensis), mushroom/mycelium
• Dang Shen (Codonopsis pilosula, C. tangshen), root
• Eleuthero (Eleutherococcus senticosus), root/stem bark
• Green Chirayta (Andrographis paniculata), leaves^[10]
• Guduchi (Tinospora cordifolia), root/stem
• Holy Basil (Ocimum sanctum, O. gratissimum), herb
• Jiaogulan (Gynostemma pentaphyllum), herb
• Licorice (Glycyrrhiza glabra, G. uralensis), root
• Reishi (Ganoderma ludicum), mushroom/mycelium
• Rhaponticum (Rhaponticum carthamoides), root
• Rhodiola (Rhodiola rosea), root
• Schisandra (Schisandra chinensis), fruit/seed
• Siberian Ginseng (Eleutherococcus Senticosus), root,
• Shilajit (Asphaltum bitumen), pitch ^[11]
• Shiitake (Lentinula edodes)

[Sibiriak]

Excellent topic!   I've been taking rhodiola regularly.

 

I posted in another thread:
 

Rhodiola (+ eleutherococcus senticosus, aka Siberian ginseng) and the general theory of adaptogens recently caught my interest.   According to Siberian folk wisdom, those who take rhodiola daily and live well will make it  to 100 years.  [baba Yaga agrees! ]

 

Rhodiola rosea, Siberia, Altai mountains, Katun ridge.

 

Cf. "Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity" 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

Edited June 4, 2017 by Sibiriak

[mccoy]

Siberiak, now I remember it, the thread came out of the search but I missed it evidently.

 

How would you rate the effects of rhodiola? I've started to watch this podcast of D. Asprey. Among the alleged properties are those related to longevity. Very interesting story about Nikolai Lazarov, Chinese Ginseng and Rhodiola. Also, I'd need some help with stress right now. Sligthly dubious about the effects, real or exaggerated? Some of these adaptogens are really costly. Anyway, that seems to be the next level beyond non-adaptogen phytochemicals. 

 

Edited June 4, 2017 by mccoy

[Sibiriak]

Mccoy,  I'll have to get back to you with more detail  on  my personal experience with rhodiola.   I just started watching your video.  The two gentlemen strike me as a bit supplement-salesmen-like, but I'm only a few minutes into it.    I'm quite close to the Altai rhodiola source, and standarized extracts are widely available and very cheap. Siberian ginseng is common as well.  I've taken some of that sporadically, but right now I'm using just rhodiola-- regular fairly low dose.

 

If you go to that article I linked, you easily find other scientific studies on adaptogens.  Alexander Panossian appears to be one of the major authorities.

Edited June 4, 2017 by Sibiriak

[mccoy]

Thanks Sibiriak, pls report at your ease, not an urgent issue.

 

Alexander Panossian is also cited in the links provided in the podcast comments

 

Sunhorse sells some proprietary adaptogens blends. Dan Moriarty seems to be a man in the know and cites Jiaogulan as a longevity adaptogen. Of course he and Dave Asprey are businessemen (Asprey's expensive bulletproof coffe is known worldwide). It remains to be seen if Sunhorse products can keep their promise-

Edited June 4, 2017 by mccoy

[Gordo]

I had been planning to research more and do a write up on Jiaogulan (Gynostemma pentaphyllum). I think it's quite promising, and is actually called "The Immortality herb" by the locals that first cultivated and drank its green tea (a population that supposedly has a high proportion of centenarians). There are quite a lot of published studies about it, and I believe it is a BAT activator, and is noted for glucose lowering effect. I do take it occasionally and might increase my frequency. I ordered seeds to grow it myself, but they would not germinate unfortunately. I'll probably try again some time.

[Sibiriak]

McCoy: Sunhorse sells some proprietary adaptogens blends

 

Their "Ultimate Energy Adaptogenic Formula" Contains:

 

Jiaogulan, Himalayan Goji, Acai, Peruvian Maca, American Ginseng, Schisandra Fruit, Asian Licorice Root, Rhodiola Rosea, Astragalus Root, Reishi Mushroom, Catuaba, Guarana, Ashwagandha, pure organic grade B maple syrup

http://www.potentiatethycells.com/product/ultimate-energy-adaptogenic-formula-2/

 

 

I wouldn't doubt that Sunhorse uses high quality ingredients, but it's quite expensive ($60 bottle -30 doses,  $51 monthly),  and I'm not sure of the value using so many herbs in a blend,  however impressive the long list of names appears (with possible potent placebo effect!)

 

I prefer using rhodiola alone (or possibly with Siberian ginseng) because-- besides being a local product/cheap-- it's the same standardized product used in the many Russian etc. studies, so I can be sure of the dose/potency I'm using in relation to the studies and experiment accordingly.

Edited June 5, 2017 by Sibiriak

[mccoy]

@ gordo: just by hunch, jiaogulan, the immortality herb, by its definition gives me the impression to be an mTOR downregulator, something like rapamycin but far milder (and without side effects).

 

Actually, it turns out there is some research which points out that jiaoguloan upregulates AMPK by a cascade involving sestrin upregulation. And we know that AMPK downregulates mTOR.

 

So In a sense, jiaogulan really appears to act on the masterswitch itself, mTOR, although indirectly.

 

 

 

 

[mccoy]

Some scientific references drawn by a commercial article

 

https://www.nutraceuticalbusinessreview.com/technical/article_page/A_new_way_to_turn_on_the_master_metabolic_switch/100048

 

8. S.H Park, et al., “Antiobesity Effect of Gynostemma pentaphyllum Extract (Actiponin): A Randomized, Double-Blind, Placebo-Controlled Trial,” Obesity (Silver Spring) 22(1), 63–71 (2014).

9. J.H. Lee, A.V. Budanov and M. Karin, “Sestrins Orchestrate Cellular Metabolism to Attenuate Aging,” Cell Metab. 18(6), 792–801 (2013).

 

10. J.H. Lee, et al., “Maintenance of Metabolic Homeostasis by Sestrin2 and Sestrin3,” Cell Metab. 16(3), 311–321 (2012). 

11. P.H. Nguyen, et al., “New Dammarane-Type Glucosides as Potential Activators of AMP-Activated Protein Kinase (AMPK) from Gynostemma pentaphyllum,” Bioorg. Med. Chem. 19, 6254–6260 (2011).

12. V. Razmovski-Naumovski, et al., “Chemistry and Pharmacology of Gynostemma pentaphyllum,” Phytochem Rev. 4, 197–219 (2005).

13. R. Gauhar, et al., “Heat-Processed Gynostemma pentaphyllum Extract Improves Obesity in ob/ob Mice by Activating AMP-Activated Protein Kinase,” Biotechnol. Lett. 34(9), 1607–16 (2012).

 

[mccoy]

 

 

I prefer using rhodiola alone (or possibly with Siberian ginseng) because-- besides being a local product/cheap-- it's the same standardized product used in the many Russian etc. studies, so I can be sure of the dose/potency I'm using in relation to the studies and experiment accordingly.

 

 

Local shopping is undoubtedly the best. Too bad there are not many adaptogens around here in Italy, unless licorice can be defined so by its effects on blood pressure

[Sibiriak]

McCoy,   you could always rely on the the great altruist Dr. Mercola for an authentic rhodiola product that comes from plants adapted to the kind of extraordinarily stressful cold temperatures not to be found in milder Italian climes.

Dr. Mercola:  As with any supplement you’re considering, it’s important to do your homework and highly scrutinize the label and find out about the manufacturer’s quality processes. I put together a selection checklist that includes what I consider to be the most important factors in finding a high-quality Rhodiola rosea supplement. Hopefully, this will help save you time in the long run.  Now, here’s the list I created, in which I recommend that a Rhodiola rosea formula...

• Originates from the dry, hostile environment of Siberia – I believe this is the best area of the world to source the raw materials.
• Contains active ingredients: Rosavin, Rosaridin, Rosarin, Rosin, Salidroside, and Tyrosol
• Avoids unnecessary fillers and excipients – Certain unnecessary fillers and excipients can be harmful to your health.
• Utilizes a first-rate effective extraction process integrated by a high-quality producer – Look for evidence of a skilled Rhodiola processor with experience in environmental-sensitive growing, harvesting, extracting, and production.

One of the best areas in the world to get Rhodiola rosea is from Siberia.

 

How My Team Helped Save You Time by Sourcing This Outstanding Solution

Using the above selection checklist to choose a Rhodiola rosea supplement could be a bit challenging. For example, it’s not always evident from the bottle label what constituents of the source ingredients are in the formula. And, finding details on the manufacturer could take some digging time.  Well, I decided to help you save time and take most of the guesswork out of your search. I think you’ll be pleased with what my research team discovered in Rhodiola Extract, a truly extraordinary formula.

[...]The Rhodiola rosea herb for this formula is harvested from the Atlai region of Siberia in Russia.

http://products.mercola.com/rhodiola-extract/

Edited June 5, 2017 by Sibiriak

[Sibiriak]

McCoy:   jiaogulan, the immortality herb, by its definition gives me the impression to be an mTOR downregulator...

 

It could be that some adaptogens increase longevity via "hormesis B"  rather than/as well as "hormesis A",  to use Blagosklonny's scheme.

 

Longevity: (a) slow aging and (b) aging-tolerance 

 

Life span can be extended by either (a) slowing down aging and (b) by increasing aging tolerance, defined as the ability to survive complications (catastrophes) of aging [36].

 

a. Obviously, inhibition of aging should extend life span and delay age-related diseases. For example, calorie restriction (CR) slows aging. CR delays age-related diseases such as cancer and atherosclerosis, thus extending life span. In other words, inhibition of mTOR-driven aging delays catastrophic complications of aging: namely, complications of age-related diseases such as stroke, myocardial infarction (Figure 2). These non-random catastrophes actually cause death.

 

b. But inhibition of aging (and delaying diseases) is not the only way to extend life span. The second way is to increase aging tolerance, which allows an organism to survive catastrophes caused by age-related diseases.

 

* * * * *

 

Two types of hormesis: (a) slowing down aging and  (b) increasing aging-tolerance

 

Hormetic stresses include two groups of agents that (a) slow down aging by inhibiting the TOR pathway and (b) increase aging tolerance, without affecting the aging process (Figure 2). We will call them hormesis A and hormesis B.

 

Examples of hormesis A are calorie restriction, rapamycin, resveratrol and p53-inducing agents.

 

Examples of hormesis B are adaptive preconditioning to ischemia and coronary bypass. Heat shock, hypoxia and physical exercise belong to both groups.

 

https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/2wBkpNoQjfF[hautuL.pdf

[emphasis added]

 

 

Cf.  Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones     PMID: 19188053

https://www.ncbi.nlm.nih.gov/pubmed/19188053

http://sunhorseenergy.com/wp-content/uploads/2015/11/Adaptogens-Stress-Protective-Panossian.pdf

 

 

Abstract

Adaptogens are medicinal plants that augment resistance to stress, and increase concentration, performance and endurance during fatigue. Experiments were curried out with BALB/c mice taking ADAPT-232 forte, a fixed combination of three genuine (native) extracts of Eleutherococcus senticocus, Schisandra chinensis and Rhodiola rosea, characterised for the content of active markers eleutherosides, schisandrins, salidroside, tyrosol and rosavin and in doses of about 30, 90 and 180 mg/kg for seven consecutive days followed by forced swimming test to exhaustion. ADAPT-232 forte strongly augments endurance of mice, increasing the time taken to exhaustion (TTE) in a dose dependent manner from 3.070.5 to 21.171.7 min, approximately seven fold. Serum Hsp72 was measured by EIA both in normal and stressful conditions before and after swimming test.

 

Repeated administration of adaptogen dose dependently increases basal level of Hsp72 in serum of mice from 0.8–1.5 to 5.5–6.3 pg/ml. This effect is even stronger than the effect of stress, including both physical (swimming) and emotional impacts: 3.271.2 pg/ml. Cumulative effect of stress and adaptogen was clearly observed in groups of animals treated with adaptogen after swimming to exhaustion, when serum Hsp72 increased to 15.171 pg/ml and remained at almost the same level during the 7 days. It can be concluded that adaptogens induce increase of serum Hsp72, regarded as a defense response to stress, and increase tolerance to stress (in our model combination of physical and emotional stresses).

 

It can be suggested that increased tolerance to stress induced by adaptogen is associated with its stimulation of expression of Hsp70 and particularly with Hsp72 production and release into systemic circulation, which is known as a mediator of stress response involved in reparation of proteins during physical load. Our studies suggest that this could be one of the mechanisms of action of plant adaptogens.

[emphasis added]

 

Molecular chaperones are a group of proteins that promote correct three-dimensional folding of other proteins, prevent their aggregation and assist in refolding of misfolded proteins, which are the main contributors to many devastating human diseases. The 70-kDa heat shock protein Hsp72 plays a central role in the mechanism that rids the cell of stress-induced misfolding or incompletely synthesized polypeptides that otherwise would interfere with normal cellular function, thereby playing critical roles in maintaining cellular homeostasis and in protecting the cell from stressful conditions and increase cell survival in the face of otherwise lethal cellular stress.

 

In addition, Hsp72 may function as an endogenous ‘‘danger signal’’ for the immune system. The danger theory postulates that immune activation involves danger/non-danger molecular recognition schemas and suggests that innate immune cells are activated by danger signals that are derived from stressed or damaged self-proteins (Matzinger 1998; Gallucci and Matzinger 2001). It is now widely accepted that circulating serum Hsp72 fits this criteria (Asea 2007, 2008). Exposure to physical or psychological acute stressors stimulates the release of endogenous Hsp72 into the blood and this elevated Hsp72 functions to facilitate innate immunity in the presence of bacterial challenge (Asea 2005; Febbraio and Koukoulas 2000; Fleshner and Johnson 2005; Gonza´lez and Manso 2004; Johnson and Fleshner 2005; Lancaster and Febbraio 2005; Whitham and Fortes 2008).  [emphasis added]

 

Our hypothetical model proposes that ADAPT-232 forte exerts its beneficial effects via the stimulation of the stress response (Fig. 2). In the absence or presence of harmful stressful stimuli, ADAPT-232 induces the up-regulation of intracellular Hsp70 expression, which is transported to the extracellular milieu and exerts immunostimulatory effects on the hosts’ immune system. Inside the cell, increased Hsp72 expression inhibits detrimental signal transduction cascades activated by stress, e.g., JNK-induced apoptosis activated by JKK. This allows some of the more favorable functions of JNK to be initiated, including Jun-dependent transcription and the phosphorylation cytoplasmic DAF-16/forkhead transcription factor, which then translocates to the nucleus and synthesizes additional proteins to confer stress resistance and increased longevity (Fig. 2).

 

Our hypothesis is that adaptogens adapt (make less sensitive) the organism to stress, acting somewhat like low molecular weight ‘‘vaccines’’ or stress mimetics, inducing mild activation of stress system in order to cope more severe stress. It should be mentioned that principally, Hsp 72 inducers could have a therapeutic application in the treatment of neurodegenerative diseases (Westerheide and Morimoto 2005),  [emphasis added]

Edited June 5, 2017 by Sibiriak

[mccoy]

Thanks sibiriak for the altruistic suggestions of Dr Mercola, his prices are lower than sunhorse, although his ingredients are not 13, rather one. A good one though.

 

The examine.com site has some review on adaptogens based on literature, it's interesting that they cite the 3 allegedly most important ones: Ashwagandha, rhodiola, Panax gingseng. Maybe just rotating with these might be a good scheme, for those who have not the good luck to reside in Krasnoyarsk Krai and be able to pick up rhodiolas in their home gardens.

 

https://examine.com/nutrition/updated-adaptogen-ashwagandha/

[Sibiriak]

The mildly Panglossian  Mr. Panossian likes a combination of  eleutherococcus senticosus, schisandra chinensis  and rhodiola, which made up the core of the  Swedish "ADAPT 232" formula he's studied/promoted (no longer available, I believe).

 

He discusses the synergistic effects of that adapto-combo in this article (which makes markedly soporific nighttime reading):
 

Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells

 

https://www.ncbi.nlm.nih.gov/pubmed/23430930

Edited June 5, 2017 by Sibiriak

[Sibiriak]

Mccoy:  The examine.com site has some review on adaptogens based on literature,

 

 

Thanks. I took a glance at what they had to say about Rhodiola.   Tidbit:

 

Adaptogens in general, but particularly rhodiola, appear to be involved with promoting longevity. A bell curve has been noted in nematodes, and the mechanism is thought to be from inducing nuclear translocation of DAF-16 (a response to stress)

https://examine.com/supplements/rhodiola-rosea/

Edited June 5, 2017 by Sibiriak

[mccoy]

The mildly Panglossian  Mr. Panossian likes a combination of  eleutherococcus senticosus, schisandra chinensis  and rhodiola, which made up the core of the  Swedish "ADAPT 232" formula he's studied/promoted (no longer available, I believe).

 

He discusses the synergistic effects of that adapto-combo in this article (which makes markedly soporific nighttime reading):

 

Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells

 

https://www.ncbi.nlm.nih.gov/pubmed/23430930

 

Excellent reading for those who like to geek it out in an obsessive-compulsive fashion (like myself). 

 

Anyway, he apparently was able to take the adaptogens from the rough world of herbal lore into the lofty realm of cell metabolism.

Edited June 5, 2017 by mccoy

[Sibiriak]

Mccoy,

 

1) Mercola is overpriced, imo. The quality may be good, but I wouldn't be surprised if, despite all the rhetoric about his  incredible Siberian rhodiola source,  other brands use the exact same source.   Or maybe they don't.    I use  iHerb.com if I  need something I can't get locally.

 

2)

Excellent reading for those who like to geek it out in an obsessive-compulsive fashion (like myself).

 

There's some interesting details in that article, for sure.  (Imagine doing that kind of synergy/antagonism study on Sunhorse's thirteen herb formula!).

 

It would be quite easy to make one's own version of the three-herb  "ADAPT- 232" formula,  something I may do  in the future.

 

Panossian et al.'s 2010 review (mentioned earlier)  provides a more generalized comparison of the three herbs' potential pharmocological effects.   Of course, the  evidence for all these wonderful effects in humans  is surely not up to CR Society standards.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

See tables 1 and 2.

Edited June 6, 2017 by Sibiriak

[Sibiriak]

Mccoy,  probably of little practical import, but perhaps of interest to aficionados of Drosophila melanogaster studies  such as yourself:

 

Lifespan extension and delay of age-related functional decline caused by Rhodiola rosea depends on dietary macronutrient balance.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922952/

PMID:24472572

 

Conclusions

Our current data indicate that R. rosea from the Carpathian Mountains increases lifespan and improves healthspan in a fruit fly line caught in the same region. However, the lifespan-prolonging effect of R. rosea on the fruit fly depends on the protein-to-carbohydrate ratio fed to it. Diets with high protein-to-carbohydrate ratios or high caloricity do not support the beneficial action of R. rosea on longevity. We also demonstrated that lifespan extension by R. rosea might depend on the physiological state of organism, being beneficial for individuals with moderate robustness. The maximum anti-stress effect of R. rosea is also observed for individuals with ages close to the half-life of the cohort. In addition to lifespan extension, R. rosea retards age-dependent decline in ‘life-quality’ indices of aged D. melanogaster individuals, such as climbing activity. The preparation from Carpathian R. rosea used in our study also has a positive effect on fruit fly egg-laying ability.

Edited June 13, 2017 by Sibiriak

[mccoy]

Those are really interesting and unexpected results!

[Gordo]

Those are really interesting and unexpected results!

Why unexpected?  Its well established that high calories, and high protein, are bad for longevity.

[mccoy]

Gordo, maybe I sort of expected we can binge and commit dietary abuse if we take adaptogens, LOL. Well, that may come true of rapamycin, but probably not even that.

 

Dietary regimen rulez!! 

[AlPater]

Nootrobox is now HVMN and will sell biohacking products beyond nootropics

Sarah Buhr

https://techcrunch.com/2017/06/27/hvmnafterall/?ncid=mobilenavtrend

 

"...Silicon Valley is brimming with tech execs trying to become faster, stronger and smarter by “hacking” their genetic code through various experimental methods called biohacks.

 

These would be the people drinking buttered coffee, taking cold showers and not eating every other day — not because of some psychological disorder but because they believe caloric restriction will turn on certain genes to help them live longer."

Edited June 27, 2017 by AlPater

[mccoy]

It's interesting that they want to sell last generation nootropics but are experimenting with supplements-free practices like IF, CE and so on

[Sibiriak]

they want to sell last generation nootropics

 

I took a look- not even a hint of cutting-edge ideas.  I expected more.

Edited June 28, 2017 by Sibiriak

[Sibiriak]

 

Rhodiola rosea L.:  an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention (2018)

 

Quote

Recent findings

In addition to its multiplex stress-protective activity, Rhodiola rosea extracts have recently demonstrated its anti-aging, anti-inflammation, immunostimulating, DNA repair and anti-cancer effects in different model systems. Molecular mechanisms of Rhodiola rosea extracts’s action have been studied mainly along with one of its bioactive compounds, salidroside. Both Rhodiola rosea extracts and salidroside have contrast molecular mechanisms on cancer and normal physiological functions.

For cancer, Rhodiola rosea extracts and salidroside inhibit the mTOR pathway and reduce angiogenesis through down-regulation of the expression of HIF-1α/HIF-2α.

For normal physiological functions, Rhodiola rosea extracts and salidroside activate the mTOR pathway, stimulate paracrine function and promote neovascularization by inhibiting PHD3 and stabilizing HIF-1α proteins in skeletal muscles.

In contrast to many natural compounds, salidroside is water-soluble and highly bioavailable via oral administration and concentrated in urine by kidney excretion.

 

Quote

6.1. The mTOR pathway

There have been numerous reports of the mTOR pathway promoting aging in different model organisms [98, 99]. In addition, components of the mTOR pathway are major targets for developing new agents for cancer prevention and treatment [100, 101]. We have shown that Rhodiola rosea extracts SHR-5 and its active compound salidroside inhibited the mTOR pathway in bladder cancer cell lines via activation of AMP-activated protein kinase (AMPK)-α [86]. The growth inhibitory effects of Rhodiola rosea extract and salidroside on human bladder cancer cells were, partly, dependent on TSC2 expression [86]. Our results suggested that the Rhodiola rosea extract and salidroside may play an important role in regulation of TCS2 expression for the anti-proliferative effect in bladder cancer cell lines. More importantly, we have shown that 93% of homozygous mutant Ha-ras male transgenic mice which drank 0.625% Rhodiola rosea extract SHR-5 in the drinking water survived up to 6 months, whereas 42% of which drank normal water died due to mutant H-ras transgene driven bladder specific tumor development [102]. In addition, the mean bladder weights (as a surrogate for tumor burden) in male mice drinking Rhodiola rosea extract SHR-5 decreased by 69% compared to those who drank normal water [102]. This result indicates a potent in vivo antitumor activity of the Rhodiola rosea extract SHR-5 in a transgenic model of urinary bladder cancer. Fan et al [89] also reported that salidroside induced autophagy and apoptosis and inhibited the phosphorylation of PI3K, Akt and mTOR in human colorectal cancer cells.

On the contrary, salidroside can activate the mTOR pathway to promote bone marrow mesenchymal stem cells differentiation into neural cells [103] and to attenuate cobalt chloride-induced ultrastructural damage of the mitochondria and ROS production in PC12 differentiated cells [104], suggesting that salidroside may protect brain neurons from ischemic injury through activation of the mTOR pathway. In addition, salidroside was shown to promote angiogenic differentiation of human bone marrow-derived endothelial progenitor cells [105] and to protect against oxidative endothelial injury by activation of the mTOR pathway [105–107]. Salidroside also inhibited CT-26 and Lewis lung carcinoma tumor-induced cachexia and the loss of tumor-free body weight, adipose and gastrocnemius muscles, as well as extended the survival of the treated mice by increasing the expression of phosphorylated mTOR both in C2C12 myotubes and in gastrocnemius muscle of the mice [108].

These results suggested that salidroside has a text-dependent effect on the mTOR pathway.

It is likely that in normal cells, salidroside activate the mTOR pathway to protect and repair neurons, vasculatures and muscles, whereas in cancer cells it inhibited the mTOR pathway for reducing their growth.

 

 

 

Edited June 14, 2020 by Sibiriak