Anti-aging Functional Factors And Mechanism Of Cistanche Deserticola Ⅲ
May 22, 2024
4 Discussion
As my country's population ages, it is crucial to explore anti-aging mechanisms and develop health products that delay aging. Traditional Chinese medicine has the advantages of small adverse reactions and overall balanced regulation and plays a unique role in anti-aging research [15]. Aging belongs to the category of "deficiency" in traditional Chinese medicine and is closely related to internal injuries to the five internal organs. The root cause is a deficiency of kidney qi and lack of consolidation of kidney essence. The disease is mainly located in the kidneys and is closely related to spleen and stomach deficiency. The kidneys are the foundation of innateness, and the spleen is the foundation of acquired diseases. Therefore, traditional Chinese medicine believes that nourishing the spleen and kidneys can prolong life, prevent diseases, and resist aging [16].
With the development of modern medicine, relevant research on the mechanism of aging is increasing, and the free radical theory, telomere theory, DNA damage repair theory, immunosenescence theory, and endocrine theory, etc. have emerged, among which the free radical theory is widely recognized [17]. Traditional Chinese medicine points out that the nature of kidney deficiency involves multiple theories of aging. Patients with kidney deficiency have free radical damage and immune dysfunction, as well as neuroendocrine dysfunction. It can be seen that the essence of kidney deficiency involves the mechanisms of aging such as the theory of free radical damage, the theory of decreased immune function, and the theory of neuroendocrine dysfunction. Multiple studies have shown that anti-aging traditional Chinese medicine can inhibit oxidative stress reactions by increasing the activity of antioxidant enzymes in the body, clearing excess ROS, and protecting cells from oxidative damage, thereby delaying aging [18-19]
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CISTANCHE EXTRACT FOR ANTI-AGING
Cistanche deserticola belongs to the kidney meridian, and its effects are to nourish kidney yang and replenish essence and blood. "Shen Nong's Materia Medica" records: "Cistanche deserticola is an important medicine for nourishing the kidneys and nourishing essence and blood" [20]. Current research on Cistanche deserticola's anti-aging focus focuses on the protective effects of sugars and phenylethanol glycosides on D-galactose-induced aging rat models. Among them, Cistanche deserticola polysaccharides are mainly responsible for delaying aging through antioxidants, improving learning and memory, and enhancing immune function and telomerase activity; Cistanche deserticola total glycosides are mainly responsible for antioxidants, reducing
It plays a role in brain damage and regulating body immunity; echinaceaside among phenylethanoid glycosides can extend the lifespan of nematodes through ROS signaling pathway, dietary restriction signaling pathway and insulin/insulin-like growth factor signaling pathway [21]. The function of Cistanche deserticola in delaying aging has been confirmed, but its mechanism of action is not been fully studied.
The network pharmacology results in this study show that salidroside and 6-deoxycatalpol may jointly regulate mitochondrial function and reduce insulin resistance by acting on HRAS and HK2 on the IIS pathway and HRAS and ESR1 on the thyroid hormone pathway. And then play a role in delaying aging [22]; it has been reported that inhibiting the Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways can delay cell aging [23], verbascoside, cistanche glycoside F, isorbascoside, 2ʹ-acetyl mullein
Glycosides, forsythiarin glucoside, and salidroside may act on HSP90AA1 and ESR1 to jointly regulate PI3K/Akt/mTOR [24-25]. Salidroside may act on HRAS to regulate PI3K/Akt/mTOR, Ras/ Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/
mTOR[23], 2ʹ-acetyl mullein glycoside can act on F2 to regulate MMP-2[26]
, Echinaceaside, verbascoside, cistancheaside F, isolebascoside, 2ʹ-acetyl verbascoside, cistancheaside A, and salidroside bind to MMP2, thereby regulating c-af/MEK/ERK
and ERK/MAPK pathways [27]. The above compounds may delay aging by inhibiting cancer signaling pathways; downregulation of phospholipase D (PLD) can stimulate the accumulation of ROS in human cells and accelerate cellular aging, which is widely believed to play a role in aging. Importantly, salidroside and 2ʹ-acetyl verbascoside may act on HRAS and F2 respectively, jointly upregulating PLD by activating the RAS and cAMP pathways, thereby reducing the accumulation of ROS and delaying aging [28]. The above results show that the HRAS gene plays an important role in anti-aging-related signaling pathways, and KEGG pathway analysis shows that HRAS is a key gene in the human lifespan-related signaling pathway IGF-1/PI3K/Akt/FoxO, which provides a basis for subsequent research using C. elegans In vivo experimental verification provides a basis.
The free radical theory of aging shows that the oxidative stress mechanism is an important mechanism leading to human aging and is also the focus of current research on delaying aging with traditional Chinese medicine [29-30]. Under normal circumstances, free radicals in the body are in a state of balance. Once the antioxidant defense system is destroyed, the excess ROS produced will put the redox reaction in a progressive oxidation state, leading to lipid peroxidation, attacking cell membranes, DNA and proteins, leading to their denaturation. , damage, and accelerate the occurrence of aging and related diseases [31].
The results of this study show that Cistanche deserticola can significantly increase the activity of antioxidant enzymes SOD, CAT, and GSH-Px in nematodes and reduce the level of ROS and the accumulation of MDA, thus improving the oxidative stress caused by hydrogen peroxide. In addition, it can effectively relieve nematodes Heat stress significantly inhibits the accumulation of lipofuscin and enhances the body bending ability of nematodes, extending their lifespan. The IIS signaling pathway of C. elegans is closely related to its growth, development, lifespan and metabolism. It is the first signal related to aging that has been studied.
pathway [32], and is homologous to the human lifespan IGF-1/PI3K/Akt/FOXO pathway [33]. The insulin signaling receptor in C. elegans is DAF-2, which is located on the cell membrane. When the active substance activates the DAF-2 receptor, it can activate the PI3K homologue AGE-1. The second messenger produced by AGE-1 can promote the activation of downstream Akt, thereby phosphorylating the transcription factor DAF-16. Phosphorylated DAF-16 cannot enter the nucleus to exert transcriptional regulatory functions. Therefore inhibiting DAF-2, which negatively affects DAF-16
After the regulatory effect is released, DAF-16 enters the nucleus to exert its transcriptional regulatory function and interacts with other factors in the nucleus, including SIR-2. 1, HSF-1 and SKN-1, extending the lifespan of nematodes [34]. The nematode Nrf family transcription factor SKN-1 is an important component of the body's response to oxidative stress. The IIS signal transduction pathway can directly inhibit SKN-1. This process is similar to DAF-16. Akt-1, Akt-2 and SGK-1 on the IIS pathway can all inhibit SKN-1 by phosphorylating SKN-1. activity[35]. In vivo experimental research results in nematodes show that Cistanche deserticola can reduce the phosphorylation levels of DAF-16 and SKN-1 by down-regulating the IIS pathway, that is, reducing the expression levels of daf-2, age-1 and akt-1 genes, and promote their nuclear translocation, thereby upregulating the downstream antioxidant phase
The expression levels of offrin genes and heat shock-related genes ultimately extend the lifespan of nematodes and slow down aging.In summary, this study takes the potential functional factors in Cistanche deserticola as the research object, uses network pharmacology to analyze the complex network relationship of medicinal materials-components-targets-pathways, and analyzes its possible targets and pathways for delaying aging. Based on the prediction results, further In vivo experiments on nematodes were used to verify the mechanism of action of Cistanche deserticola in delaying aging. The results showed that Cistanche deserticola can significantly extend the life span of nematodes, inhibit the accumulation of aging pigments and improve the decline in exercise capacity of nematodes due to aging. It can effectively resist heat stress and oxidative stress by enhancing the antioxidant system of nematodes. Free radical damage caused by stimulation. The mechanism of life extension mediated by Cistanche deserticola may be through the IIS signaling pathway down-regulation of daf-2, age-1, up-regulation of daf-16 and its downstream target genes (sod-3, mtl-1, gst-4, ctl-1 and ctl- 2), achieved by simultaneously activating the expression of skn-1 and heat shock-related genes (hsf-1, hsp-16. 1 and hsp-16. 2).
