Is Rhodiola Rosea Extract Anti-Aging?

In the traditional medical system, Rhodiola rosea is used to stimulate the nervous system, eliminate fatigue, reduce depression and prevent altitude sickness. In recent years, it has been found that Rhodiola rosea contains a variety of active ingredients, such as polysaccharides, glycosides, terpenoids, sterols, ellagic acid, organic acids, flavonoids, amino acids, coumarins, volatile oils, enzymes, organic acids, minerals, steroids and alkaloids, etc.[1,2] . It has the effects of anti-aging, anti-hypoxia, anti-tumor, anti-cold, anti-fatigue, anti-radiation, anti-virus, regulating the nervous system, cardiovascular and cerebral vascular system and immunity, etc. [3]. In this paper, the anti-aging mechanism of Rhodiola rosea is mainly reviewed from the aspects of free radical scavenging, antioxidant enzyme activity and signal transduction.

1 Scavenging free radicals

According to modern aging theory, the aging process of the organism is related to the damage of free radicals and induced lipid peroxidation on cells and the organism [4]. Free radicals and their derivatives are highly reactive groups of atoms containing unpaired electrons, which are important reaction components involved in redox reactions in the human body. Commonly found free radicals in organisms include oxygen radicals (OH-), hydroxyl radicals, lipid radicals, and hydrogen radicals. An appropriate amount of free radicals can promote cell proliferation, stimulate white blood cells and phagocytes to kill bacteria and eliminate inflammation. However, an excessive amount of free radicals can cause damage to proteins, lipids, nucleic acids, etc., thus leading to accelerated aging. Normally, the production and removal of free radicals are in dynamic balance in the body, but as we age, the body's ability to remove free radicals is weakened, resulting in a large accumulation of free radicals in the body, and excessive free radicals can oxidize and decompose the unsaturated fatty acids contained in phospholipids on the biofilm, resulting in metabolic products such as lipid peroxide (LPO) and malondialdehyde (MDA). At the same time, it is also a strong oxidizing agent, which can damage DNA molecules, cause cell death or mutation, and lead to a series of aging manifestations in the organism [5].

Studies have shown that Rhodiola rosea extracts Rhodiola rosea glycosides, Rhodiola rosea polysaccharides and Rhodiola rosea total flavonoids have strong scavenging effects on 1,1-diphenyl-2-trinitrobenzene swellings (DPPH), superoxide anion (O2 -), and OH - to reduce the generation of free radicals, which indicates that Rhodiola rosea has a very strong antioxidant activity in vitro [6-8]. Rhodiola rosea extract can not only effectively scavenge free radicals in vitro, but also has been proved to scavenge excessive free radicals in vivo [9]. In recent years, it has been found that the central link in the formation of Alzheimer's disease (AD) is the abnormal metabolism and deposition of β-amyloid protein (Aβ) [10 ], and some experiments have proved that rhodiola rosea glycosides can play a neuroprotective role by scavenging free radicals in hippocampal tissues induced by Aβ1-40 and inhibiting lipid peroxidation, thus playing a therapeutic role in the treatment of AD [11 ].

2 Enhancement of antioxidant enzymes

Antioxidant enzymes include superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Once peroxides are formed in the body, they use redox to convert the peroxides into less toxic or harmless substances. The body's metabolism generates its own antioxidants, and during the formative years, high levels of antioxidants such as GSH-Px and SOD balance the body's metabolism, but as we age, the synthesis of antioxidants in the body slows down, which affects the normal functioning of the organs in the body and leads to organ function decline. Therefore, increasing the activity of antioxidant enzymes can slow down the rate of oxidation and slow down the aging process.

When the activity of antioxidant enzymes (SOD, GSH-Px, CAT) decreases in the body, the oxidative damage caused by excess free radicals generated by external stimuli or cellular aging in the body cannot be effectively inhibited, resulting in cellular damage or death, leading to aging. Although the aging caused by accumulation of free radicals is a normal metabolic phenomenon, if exogenous antioxidants can be supplemented timely and adequately, the content of GSH-Px and SOD in the body can be enhanced, and the oxidative damage caused by free radicals can be effectively inhibited, thus realizing the effect of slowing down the aging process. A large number of experiments have proved that rhodiola rosea can promote protein synthesis, reduce acid phosphatase activity, inhibit the formation of LPO, and reduce the content of MDA, the final decomposition product of LPO, through the activities of SOD, GSH-Px and CAT, thus enhancing the body's ability to scavenge free radicals, reducing the degree of peroxidation of biofilm, and protecting the body's cells and tissues from the damage caused by free radicals, and thus playing the role of preventing and delaying aging of the organism. It can prevent and slow down the aging of the organism [12-14].

3 Signal transduction

3.1 Mitogen-activated protein kinase (MARK) signaling

The MARK pathway is mainly composed of extracellular signal-regulated protein kinase (ERK), P38MARK and c-Jun N-terminal kinase (JNK), and the ERK signaling pathway is related to cell proliferation, while the P38MARK and JNK pathways are related to apoptosis [15 ]. Wang et al.[16] found that rhodiola rosea glycosides could increase SOD activity, decrease serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), MDA content, increase p-ERK protein expression, decrease p-P38 protein expression, and prevent and treat cardiovascular diseases at the level of enzymology and signal transduction. This suggests that rhodiola rosea glycosides can directly or indirectly block the MARK signaling pathway by reducing the production of free radicals and the lipid peroxidation caused by them, and attenuating the apoptosis induced by oxidative stress, thus protecting the heart damaged by the exercise of acute exhaustion.

3.2 Phosphatidylinositol kinase/serine kinase (PI3K/Akt) signaling  

Rhodiola rosea glycosides can inhibit hypoxia-induced cardiomyocyte apoptosis by activating hypoxia-inducible factor (HIF)-1α expression via PI3K/Akt. The PI3K inhibitor LY294002 is a protein kinase inhibitor that can block the signaling pathway of PI3K cells, and it can block the phosphorylation of Akt (p-Akt), the downstream target protein of PI3K, and rhodiola rosea can significantly inhibit the apoptosis of cardiomyocytes induced by hypoxia through the activation of HIF-1α expression by PI3K/Akt. Rhodiola rosea could significantly increase the expression of p-Akt protein in hypoxic cells, but after pretreatment with LY294002, the effect of rhodiola rosea in increasing p-Akt was blocked, and the expression level of p-Akt protein decreased significantly.

In addition, LY294002 can significantly reduce the protein expression of HIF-1α, and the rate of apoptosis increased significantly after pretreatment with rhodiola rosea, which suggests that rhodiola rosea may inhibit hypoxia-induced apoptosis of cardiomyocytes and delay tissue failure by activating the stabilized expression of p-Akt and then inducing the stable expression pathway of HIF-1α [17 ]. Some experiments have also shown that rhodiola rosea glycosides may prevent the generation of reactive oxygen species (ROS) by increasing the expression of the gene regulating the developmental and DNA damage response (REDD1), regulate the expression of HIF-1α, and regulate the activation of the PI3K/Akt pathway by activating the downstream molecules of the mammalian target of rapamycin (mTOR) and specificity protein 6 (SP), which can counteract the oxidative damage induced by hydrogen peroxide (H2 O2) [17 ]. induced oxidative damage [18].

3.3 Nuclear factor (NF)-κB-inducible nitric oxide (iNOS)-NO signaling  

It has been shown that oxidative stress and inflammatory responses interact with each other, and NF-κB may be a common nexus between the two to damage cells [19 ]. Zhang Jia et al.[11] showed that rhodiola rosea glycosides may inhibit NF-κB-iNOS-NO signaling by inhibiting the expression of NF-κB, thereby reducing the expression of iNOS and the production of NO, and thus alleviating oxidative stress-induced neuronal damage. On the other hand, rhodiola rosea may also reduce the expression of receptor for advanced glycosylation end products (RAGE) by inhibiting NF-κB expression through the inhibition of oxidative stress. However, by inhibiting RAGE, rhodiola rosea glycosides may in turn inhibit NF-κB expression, thereby reducing the inflammatory damage induced by oxidative stress. Therefore, rhodiola rosea may inhibit the vicious cycle of oxidative stress by inhibiting the two-way pathway of NF-κB-RAGE, reduce the damage of nerve cells, improve the structure and function of nerve centers, and slow down aging.

3. 4 Others  

Studies have shown that Rhodiola rosea extract can also affect the expression of apoptosis-related proteins, thereby inhibiting apoptosis and slowing down the aging process. Rhodiola rosea glycosides can reduce the expression of cysteinyl-containing aspartate protein hydrolase (Caspase)-3, increase the B-cell lymphocyte/(Bcl)-2-associated X-protein (Bax)/Bcl ratio, and reduce apoptosis to prevent cognitive dysfunctions induced by chronic ischemia in rats [20 ]. prevent cognitive dysfunction induced by chronic cerebral ischemia in rats [20 ]. Li Ting et al.[21] found that rhodiola rosea glycosides can up-regulate the expression of anti-apoptotic protein Bcl-2, increase the protein expression level of mitochondrial cytochrome C, and inhibit cell apoptosis. In addition, rhodiola rosea polysaccharide can also reduce apoptosis in bone marrow cells through Fas/FasL-Caspase-3 apoptosis signaling [22]. In conclusion, rhodiola rosea can reduce lipid metabolism, promote cell growth and reduce apoptosis by scavenging free radicals, increasing the activity of antioxidant enzymes, acting on signaling pathways and affecting apoptosis-related proteins, thus exerting its anti-aging effects.

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