Part Ⅱ：East To West: Research Progress in Traditional Chinese Medicine For Antiaging Strategies
Mar 03, 2022
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Pharmacological studies of TCMs
Heshouwu (Polygoni multiflora radix) (Polygoni multiflora radix). Heshouwu (Polygoni multiflora radix) is the dry root tuber of Polygonum multiflorum Thunb., and its primary functions involve reducing blood lipid levels and exerting antiaging properties such as improved immunity and increased intelligence. The emodin derivative, emodin-8-o-(6'-o-malonyl)-glucoside, was isolated from Heshouwu (Polygoni multiflora radix) by Lo et al.. This derivative was shown to stimulate growth hormone release in rat anterior pituitary cells by activating the auxin receptor, which serves to induce auxin release and has antiaging properties [70]. In addition, Chen et al. [71] found that the aqueous extract of Heshouwu (Polygoni multiflora radix) obviously inhibited the activity of monoamine oxidase in the brain and liver tissues of aged mice, suggesting that Heshouwu (Polygoni multiflora radix) prevents and treats senile diseases such as depression and Parkinson's disease-related to the disorder of monoamines in the brain. Tang et al. studied the effects of ethyl acetate extract of Heshouwu (Polygoni multiflora radix) on the lifespan of Caenorhabditis elegans and demonstrated that the average lifespan of the nematodes was significantly longer in the low, medium, and high concentration groups (25, 37.5, and 50 mg/L ethyl acetate, respectively, calculated based on the crude drug) than in the blank group, particularly of those in the medium concentration group. A further discussion regarding the ability of 37.5 mg/L ethyl acetate to delay senescence in the nematodes without damaging their reproductive ability was presented [72]
Cistanche phenylethanoid glycosides has a strong ability to scavenge free radicals. Its reducing ability is higher than that of vitamin C. Its ability to scavenge diphenyl and trinitrohydrazine free radicals and anti-lipid peroxidation activity is higher than that of vitamin E. Cistanche Polysaccharides can increase the activity of superoxide dismutase and glutathione photooxidative in red blood cells and lung tissues of aging patients, while reducing the content of malondialdehyde and collagen in lungs and plasma, and has a good effect on clearing DPPH. Cistanche cistanche polysaccharide has a good scavenging effect on superoxide anions, hydroxyl groups, DPPH free radicals and singlet oxygen, increases the content of tryptophan and kynurenine in the lens of rapidly aging patients, improves the vitality of serum SOD, and delays aging The patient's physiological degeneration and cell morphology degeneration.
Danggui (Angelicae Sinensis radix) (Angelicae Sinensis Radix). Danggui (Angelicae Sinensis Radix) is the dry root of Angelica Sinensis (Oliv.) Diels. Modern pharmacological experiments have demonstrated that Danggui (Angelicae Sinensis radix) has various antiaging roles via several mechanisms [73]. Qi et al. [74] used D-galactose-induced aging mice as research models to study the antiaging properties of Danggui (Angelicae Sinensis Radix). The water decoction of Danggui (Angelicae Sinensis radix) demonstrated good antiaging properties that were dose-dependent. In addition, the antiaging mechanisms of Danggui (Angelicae Sinensis radix) include increasing the activity of Ca2+–ATP enzyme and stabilizing the concentrations of nitric oxide synthase and Ca2+, thus balancing the content of NO. Furthermore, An et al. [75] found that Danggui (Angelicae Sinensis radix) could reduce the protein expression of p16 in brain tissues and decrease the activity of monoamine oxidase in the brain and kidney tissues while enhancing the activity of CAT in liver and kidney tissues. Thus, the antiaging mechanism of Danggui (Angelicae Sinensis radix) may be associated with enhancement of antioxidant capacity, downregulation of p16 expression, and inhibition of aging cell proliferation. In addition, Danggui (Angelicae Sinensis radix) can also increase SOD activity in blood and tissue and enhance free radical scavenging ability, which results in reduced MDA production, protein dissolution, and protein denaturation, thus ensuring the integrity of the cell membrane structure and function and subsequently delaying the occurrence of apoptosis [76].
Gouqizi (Lycii fructus) (Lycii fructus). Gouqizi (Lycii Fructus), a common medicine food homologous drug, is the dry ripe fruit of Lycium barbarum L. A previous study used human fetal lung diploid fibroblasts (2BS cells) as aging models to study the antiaging properties of Gouqizi (Lycii Fructus) and demonstrated that the aqueous extract of Gouqizi (Lycii Fructus) could accelerate the rate of DNA synthesis in the fusion cells of 2BS and thus prolong their lifespan [77]. Medlar polysaccharide (MP) is a type of water-soluble polysaccharide comprising six monosaccharide components; it is the main active component of Gouqizi (Lycii Fructus) and is believed to be the primary ingredient responsible for the antiaging properties of Gouqizi (Lycii Fructus), indicating its important role in the pharmacological significance of Gouqizi (Lycii Fructus). In addition, it has been found that MP can increase SOD activity and decrease MDA content in aging mice [78]. MP can also significantly increase glutathione peroxidase and SOD activities and reduce MDA content in the plasma of MP-treated aging rats with cavernous nerve injury [79]. Furthermore, it has been demonstrated that MP plays an antiaging role by increasing the activity of endogenous antioxidant enzymes to slow down the processes associated with oxidative damage, and this mechanism may be associated with the activation of the Nrf2/ARE pathway by MP [80].
Study on the prescription of antiaging TCM
The unique understanding of cell senescence and antiaging as related to TCM prescriptions has great advantages, gaining considerable attention from Chinese scholars in particular.
Pharmacological studies of prescription of antiaging TCMs
More than 100 prescriptions of antiaging TCMs are available. Some of the main prescriptions are summarized below:
Classic ancient prescription of Liuwei Dihuang pill. In a study on Liuwei Dihuang pill (LWDH), naturally aging ICR mice were intragastrically treated with LWDH for 30 days, and the antiaging properties of LWDH were investigated using metabonomics. In this previous study, 10 biomarkers related to the antiaging properties of LWDH were obtained and various antiaging mechanisms were identified, including those related to linoleic acid metabolism, pantothenate, and CoA biosynthesis, glycerophospholipid metabolism, and amino sugar and nucleotide sugar metabolism [81]. In addition, Zhou et al. have reported that LWDH can significantly inhibit the distortion and rate of sister chromatid exchange in mouse bone marrow cells exposed to cyclophosphamide, which has good DNA damaging properties. These results suggest that LWDH plays a role in delaying aging by improving the ability of the body to resist DNA damage [82]. In addition, LWDH can increase SOD activity and decrease MDA and lipid peroxide contents in the serum of mice; it also exhibits a good scavenging ability against free radicals in the body [83].
Classic ancient prescription of Jingui Shenqi pill. Yan et al. studied the pharmacological effects of Jingui Shenqi pill (JGSQ) on autoimmune encephalomyelitis mouse models and demonstrated that JGSQ significantly decreased neurological function scores, shortened the course of the disease, and regulated the ratio of CD4/CD8 cells and the number of NK cells in the autoimmune encephalomyelitis mouse models [84]. In another study, the effects of JGSQ on telomerase in the liver and brain of aging mouse models were studied using enzyme-linked immunosorbent assay and qRT–PCR at the protein and transcription levels, respectively. The results showed that the expression of telomerase in the tissues of aging mice was enhanced after JGSQ administration. It is believed that the therapeutic effects of JGSQ on aging mice are related to the upregulation of telomerase expression in some tissues [85]. Moreover, JGSQ can restrain apoptosis of renal tissue cells by inhibiting the expression of tumor necrosis factor receptor superfamily member 6, promoting the expression of Bcl-2, and increasing the levels of testosterone and testicular SOD in the serum of rats, indicating that it has good antioxidant properties [86].
Classic ancient prescription of Erzhi pill. Zhang et al. [87] treated aged rats induced with D-galactose with Erzhi pill (EZ) and demonstrated that the activity of serum peroxides and the content of lipid peroxides were significantly higher in the EZ-treated rats than in the control rats, suggesting that EZ improves the antioxidant capacity and delays the aging processes. Furthermore, Yao et al. [88] found that EZ could significantly increase the proliferation of spleen lymphocytes; the phagocytosis of abdominal macrophages; and the levels of IL-1, IL-2, and IL-12 in the serum after EZ administration, indicating that EZ has immunomodulatory properties related to enhanced mRNA expression of T-lymphocyte factor. Zhao et al. used EZ-containing serum to culture the liver cancer cell line BEL-7402 and the lung cancer cell line A549 and found that the inhibition rates of the two cancer cell lines were significantly higher than that of the serum culture, suggesting that EZ has inhibitory effects on tumor growth [89]. In addition, it has also been reported that EZ has many pharmacological properties such as reducing blood lipid levels [90], improving iron deficiency anemia [91], and preventing osteoporosis [92].
Classic ancient prescription of Sijunzi decoction. The antiaging mechanism of SJZ was studied in D-galactose-induced aging rats, and the results showed that Sijunzi decoction (SJZ) could increase glutathione peroxidase levels and MDA content in the tissues (e.g., the brain and liver tissues) and serum of aging rats, thus enhancing the antioxidative properties of SJZ and delaying the aging process [93]. Pang [94] also studied the antiaging mechanisms of SJZ and found that SJZ could improve the functioning of the mitochondrial respiratory chain enzyme complex, reduce damage to mtDNA, and increase the synthesis of ATP in brain mitochondria in aged rats. These results suggest that SJZ exhibits anti-aging properties by protecting mtDNA. In addition, Yang [95] studied the effects of SJZ on telomerase activity in the heart, brain, and liver of aging mice. The results showed that SJZ could increase the telomerase activity in the thymus of D-galactose-induced aging mice and that this effect was related to the activation of T lymphocytes in the thymus. Moreover, Liu et al. [96] studied the effects of SJZ on intestinal dysbacteriosis in aging mice and found that intestinal Enterobacter, Enterococcus, Bifidobacterium, and Lactobacillus returned to normal levels and the lifespan of the aging mice was prolonged after administration of SJZ. In addition, SJZ could inhibit the mammalian target of the rapamycin signaling pathway and decrease the expression of p70 ribosomal protein S6 kinase by reducing the activation of phosphoinositide-3-kinase to reduce the damage caused by oxidative stress, thus delaying aging [97].
Clinical study of antiaging prescriptions LWDH. Qing et al. investigated the effects of LWDH on Alzheimer's disease; 50 patients in the treatment group were administered LWDH and 52 in the control group were administered piracetam tablets (a medicine for Alzheimer's disease), and the experiment lasted for 6 months. The results of this clinical study showed that LWDH had better effects in terms of improving intelligence, living ability, and memory of patients with Alzheimer's disease than the piracetam tablets [98]. In another study, Zhong et al. studied the effects of LWDH on Parkinson's disease in 53 patients who were treated with both a conventional Parkinson's disease drug and LWDH (treatment group) and 36 patients who were treated with the conventional Parkinson's disease drug alone (control group). The duration of administration was 6 months, and the results demonstrated that the total clinical efficacy rates of the treatment and control groups were 81% and 61.5%, respectively, suggesting that LWDH had better effects in improving Parkinson's disease than the conventional drug [99]. In addition, Zhang et al. studied LWDH for the treatment of type 2 diabetes. In the clinical experiment, 150 patients were treated with LWDH (6 pills a day) for 6 months. The results showed that fasting blood glucose, postprandial blood glucose, and glycosylated hemoglobin levels decreased, whereas C-peptide levels increased after LWDH administration. In addition, there were no adverse reactions such as heart, liver, or kidney function damage after taking the medicine [100].
JGSQ. The clinical effects of JGSQ were studied in 76 patients with Alzheimer's disease who were randomly divided into a treatment group and a control group, with 38 patients in each group. This study was conducted to evaluate the clinical effects of JGSQ on Alzheimer's disease. To this end, the treatment group was administered JGSQ, and the control group was administered piracetam tablets. Activities of daily living and functionality questionnaire scores were determined 3 months after treatment. The experimental results showed that the total clinical efficacy rate was 82.05% in the treatment group and 39.74% in the control group, indicating that JGSQ exhibits good effects in terms of improving Alzheimer's disease [101]. Cao treated 24 elderly patients with secondary fungal infection with JGSQ and fluconazole. The results showed that all the patients were cured except 1 patient with lung cancer who died of multiple organ failure, suggesting that JGSQ not only treats several basic diseases found in elderly patients but also prevents the side effects of fluconazole [102]. Zhao studied 30 elderly patients with hypertension who were to be treated with JGSQ. Among them, 12 developed hyperlipidemia, 6 developed coronary heart disease, and 2 developed diabetes. The treatment results showed that the systolic blood pressure of some patients decreased to normal, and the blood lipid levels also improved significantly after treatment [103].
SJZ. Yang et al. used SJZ to treat 62 elderly patients with functional constipation and studied the clinical effects of SJZ; these patients were randomly divided into a treatment group (31 patients) and a control group (31 patients). The treatment group was administered SJZ, whereas the control group was administered phenolphthalein tablets (a medicine for treating functional constipation). The results of this study showed that the total clinical efficacy rates in the treatment and control groups were 87.09% and 54.83%, respectively. The efficacy of SJZ combined with saxagliptin (a medicine for regulating blood glucose) in treating elderly patients with type 2 diabetes mellitus was also studied, and this combination was found to be effective in reducing blood glucose levels and improving insulin-related indicators. Besides, this treatment also regulated nesfatin-1 and sex hormone-binding globulin levels, thus effectively improving insulin resistance and reducing the risk of diabetic complications [104].
Prospects and summary
Effective methods to delay aging have been extensively studied with promising results. Indeed, with development in modern medicine and molecular biology, great achievements have been made in the study of aging mechanisms. However, a complete understanding of aging mechanisms has not been achieved because aging is a complex biological process caused by multiple factors. Accordingly, because of the complexity and uncertainty surrounding the aging process, aging cannot be explained by a single mechanism but must be explored in many aspects and at deeper levels. Based on the common point of aging, it is considered that there must be some internal connection in the research of aging mechanisms. Further research on this connection should help to expand our understanding of aging mechanisms. In view of the importance of interdisciplinary research, the combination of antiaging research with cell biology, molecular biology, genomics, metabolomics, and other disciplines should broaden the research findings related to the study of aging mechanisms in the future.
Care movements are widely used in antiaging strategies because they are natural, simple, and not limited by any equipment or site. Although care movements have unique advantages in antiaging strategies, they may also have negative impacts if they are not suitable for a particular patient. Therefore, it is considered that the best results related to the antiaging properties of care movements are achieved by choosing the appropriate care movement method for individual patients. This requires individuals to comprehensively improve the efficiency and quality of healthcare and promote the development of their physical and mental health according to their physical conditions and doctors' suggestions. Indeed, this strategy considers different perspectives, including those related to diet, health care, mental health, and sports and exercise.
With the development of modern research technologies associated with TCMs, more and more antiaging TCMs are being discovered. Indeed, the research and development of new antiaging drugs based on TCMs are expected to usher in a new chapter. However, there are some shortcomings in TCM-related antiaging research. First, most of the studies on the antiaging mechanisms of TCMs have focused on antioxidation and immune regulation. Therefore, studies must explore additional antiaging mechanisms in the future. In addition, combining strategies from the perspective of various antiaging mechanisms along with the concept of integrity and systematization should contribute to the research and development of healthy foods and antiaging drugs. Second, only a small part of the active antiaging ingredients of TCMs have been identified at present, with many active antiaging ingredients still requiring additional pharmacological studies. Third, further studies on the pharmacokinetics of TCMs will help in promoting the internationalization and recognition of TCMs. However, for a large number of TCMs, particularly those related to compound prescriptions, the ingredients are quite complex, thus affecting the feasibility of in-depth analyses and pharmacodynamic evaluations. Therefore, it is necessary to explore additional scientific research methods of pharmacology involving the combination of TCM theory and modern science and technology.
In the body, aging and regeneration occur simultaneously, and the process of aging occurs when the ability of regeneration cannot match that of aging. If the cells are immortalized, the process of tissue aging would be expected to be delayed or even blocked. Autologous stem cells are a class of multipotent cells with self-renewal and self-replication abilities. Under certain conditions, these cells can differentiate into a variety of adult pluripotent stem cells. Pluripotent cells supplement and regulate diseased cells, activate the functions of aging cells, increase the number of normal cells, improve the quality of cells, prevent and delay the lesion of cells, and restore the normal physiological functions of cells. At present, autologous stem cells have provided good results in the treatment of some diseases such as myeloma [105], heart disease [106], and thyroid dysfunction [107]. In addition, these cells have advantages of safety and reliability, with minimal immune rejection, thus presenting a promising strategy for future antiaging research.
Conclusion
In this study, the progress in research on antiaging strategies from east to west was reviewed, with a particular focus on the antiaging properties of various TCMs. Western medicine has made great achievements in research on aging mechanisms, and TCM has played an important role in the study of antiaging methods. With recent advancements in molecular biology techniques, an increasing number of studies on antiaging TCMs are being conducted using modern technology, which provides an opportunity for the in-depth study of antiaging. However, despite these advances, limitations such as unclear and unidentified active compounds and single mechanism research on antiaging TCMs require investigators across disciplines to work together. In recent years, methods aimed at delaying aging using autologous stem cell transplantation have been reported, which may represent a new direction in antiaging research.
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