Study on the Pharmacological Effects of Aucubin

Yue TENG, Chenghao JIN

College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing 163319, China

Abstract In this paper, the pharmacological effects of aucubin include anti-inflammatory effect, anti-tumor effect, neuroprotective effect, anti-cardiovascular disease effect, hepatoprotective effect, anti-oxidation effect and anti-aging effect, antibacterial effect, anti-diabetes effect and bone protection. The purpose of this study is to provide theoretical basis for the development and clinical application of aucubin.

Key words Aucubin, Pharmacological effects, Anti-inflammation, Anti-tumor, Neuroprotection

1 Introduction

Aucubin is a white needle-like solid compound with the molecular formula C8H10O3. Aucubin has many pharmacological effects, such as anti-inflammation, anti-cancer, anti-oxidation, bacteriostasis, neuron protection, bone protection and liver protection. This paper summarizes the pharmacological effects and mechanism of aucubin in recent years, in order to provide a theoretical basis for the clinical application of aucubin.

2 Pharmacological effects

2.1 Anti-inflammatory effectInflammation is mainly divided into two categories, infectious and non-infectious, and it is the body’s defense response to external attacks and a complex process with vascular reaction as the main link. Any tissue injury may cause inflammation. Common inflammatory reactions mainly occur locally, but local lesions are also easy to cause overall injury. If the circumstances are serious, there will be obvious systemic reactions, such as body scalding and organ damage.

Kupeli Esraetal.[1]found that aucubin can effectively inhibit mouse toe swelling caused by inflammation, and the anti-inflammatory effect of aucubin is more obvious than its derivatives. The results showed that aucubin exerted its anti-inflammatory effect through its own 6-O substituent and 7, 8 double bonds. It can be seen that aucubin can promote the entry of nuclear transcription factors into the nucleus and reduce the synthesis of inflammatory factors. Wang Boweietal.[2]found that aucubin can effectively protect the articular cartilage of mice and alleviate the degree of inflammation of bones and joints. In addition, aucubin can play an anti-inflammatory effect by inhibiting the apoptosis of chondrocytes and preventing the excessive production of reactive oxygen species. Inflammation is mainly caused by interleukin-6 (IL-6), interleukin-8 (IL-8) and other factors to promote systemic immune response. Dimitrovaetal.[3]found that aucubin can effectively reduce the secretion of IL-6, thus relieving fever caused by inflammation. Georgievetal.[4]found that aucubin can exert its anti-inflammatory effect by reducing the expression of IL-8 and monocyte chemoattractant protein-1 (MCP-1). And the higher the dosage of aucubin, the more obvious the anti-inflammatory effect. Recio MCetal.[5]found that aucubin can effectively inhibit local edema caused by inflammation. Han Wangetal.[6]found that aucubin can effectively reduce the protein expression of inflammatory factors and inhibit their release. In addition, aucubin can effectively prevent the enhancement of inflammatory response by inhibiting the activation of microglia and preventing them from secreting inflammatory cytokines. The above results show that aucubin has good anti-inflammatory effects.

2.2 Anti-tumor effectDue to the influence of carcinogenic factors, tumors lead to diseased massive processes formed by infinite clonal proliferation of local cells, which will cause serious damage and even death to human body. At present, the rapid development of molecular biology and pharmacology accelerates the development of antineoplastic drugs.

Hung Jenyuetal.[7]found that aucubin can inhibit the proliferation of A549 lung cancer cells. At the same time, it can also increase the expression of p21 and p53 protein and induce apoptosis in A549 cells. Kim Min Beometal.[8]found that1H-aucubin can induce apoptosis of K562 human bone marrow leukemia cells. In addition,1H-aucubin can also activate caspase-3 protein activity and inhibit BCR-ABL protein phosphorylation, induce cell apoptosis and inhibit cell proliferation by cleavage of part of polymerase. Mei Fanetal.[9]found that aucubin can effectively reduce theODvalue, survival rate and cholesterol regulatory primary binding protein-1 (SREBP-1) mRNA protein expression of NSCLC H460 cells, and increase the expression of tumor suppressor gene SOX7. It can be seen that aucubin can effectively inhibit the proliferation of NSCLC H460 cells. Feng Shujiongetal.[10]found that aucubin can effectively reduce the survival rate of human colon cancer HT-29 cells, significantly inhibit the expression of SREBP cleavage activating protein, SREBP-1 mRNA and protein, and promote cell apoptosis. It can be seen that aucubin can inhibit the proliferation of HT-29 human colon cancer cells and induce apoptosis by inhibiting SCAP/SREBP-1 pathway. The above results show that aucubin has a good anti-tumor effect.

2.3 Neuroprotective effectAt present, nerve injury mainly includes two kinds of treatment, one is surgical treatment, the other is drug treatment. Because of the high risk of surgery, people usually use conservative drug treatment. Neuroprotective drugs can repair damaged nerves and prevent normal nerve damage. Hong Yuxueetal.[11]found that aucubin can significantly improve the survival rate of neurons to avoid the decrease of its number. Hong Yuxueetal.[12]further found that aucubin can effectively inhibit cell damage induced by hydrogen peroxide by inhibiting the activation of caspase.

Alzheimer’s disease (AD) is a common memory and behavioral disorder in human beings. The typical symptom is amnesia. There are many pathogenic factors, among which β-amyloid protein is the most common. Through the establishment of the model of SH-SY5Y cells acting on primary cortical neurons, Ma Zhihuietal.[13]found that aucubin can not only repair damaged neurons and treat atrophic neuronal processes, but also protect normal neurons, extend normal neuronal processes, and repair damaged memory through the prevention and treatment of neuronal necrosis. Wang Han[14]studied the neural function of mice with traumatic brain injury, and found that aucubin can gradually restore the neurological function of mice, indicating that aucubin can improve short-term neurological function. Liu Qiutingetal.[15]found that aucubin can repair damaged neurons by regulating the expression of NF-κB protein complex and interleukin-1β (IL-1β) protein. The above results show that aucubin has a good neuroprotective effect.

2.4 Anti-cardiovascular effectCardiovascular disease can cause large quantities of lipids and other substances to accumulate on the inner wall of blood vessels, resulting in vascular blockage, reducing blood flux per unit time, leading to heart disease and arteriosclerosis. By the beginning of 2022, the global fatality rate of cardiovascular disease was as high as 41%, seriously affecting social development. According to the World Health Organization (WHO), the early symptoms of cardiovascular disease are elevated blood pressure, which can lead to heart failure.

Li Chunxiaoetal.[16]found that aucubin can prevent cardiomyocyte apoptosis, combat myocardial injury and improve cardiac function. Wang Boetal.[17]found that aucubin can inhibit cardiomyocyte apoptosis and a series of inflammatory reactions induced by lipopolysaccharide by regulating the expression of acetaldehyde dehydrogenase (ALDH2). Cai Zhulanetal.[18]found that aucubin can increase the secretion of adhesion molecules, make platelets in heart tissue firmly adhere to endothelial cells, and effectively reduce the number of interstitial cell markers. The results showed that aucubin can effectively prevent the transformation of endothelial stroma and inhibit the excessive polymerization of collagen fibers in myocardial tissue, thus reducing the incidence of myocardial fibrosis. The above results show that aucubin has a good anti-cardiovascular effect.

2.5 Hepatoprotective effectThe liver is an important digestive and detoxification organ for human beings, and a large number of people suffer from liver injury. Liver injury can lead to liver disease and its incubation period is short. Excessive drinking, often staying up late, overeating and other behaviors will make the liver under great pressure, resulting in a large amount of hepatocyte necrosis. In serious cases, it can lead to liver cirrhosis or liver cancer.

Geum-Hwa Leeetal.[19]found that aucubin can protect hepatocytes from necrotizing apoptosis by reducing the release of cathepsin B, weakening the activation of cathepsin and reducing the permeability of lysosomal membrane in human hepatocyte line. Geum-Hwa Leeetal.established a mouse model of non-alcoholic fatty liver and treated it with aucubin. They found that aucubin can significantly inhibit the production of reactive oxygen species and the activation of protease in non-alcoholic fatty liver mice, regulate the transfer of rabbit anti-human monoclonal antibody Bax, and lead to apoptosis. This fully shows that aucubin can effectively treat non-alcoholic fatty liver. Hwa-Young Leeetal.[20]found that aucubin can inhibit lipid genes, regulate endoplasmic reticulum and reduce carrier proteins, thus inhibiting hepatocyte injury. Lu Peiyu[21]found that aucubin can reduce the degree of liver fibrosis by regulating p38-MAPK signal pathway, so as to play its hepatoprotective effect. In addition, aucubin can also effectively treat rats with liver injury caused by α-ampelopsin[22], carbon tetrachloride[23]and poisonous mushroom[24]. The above results show that aucubin has a good hepatoprotective effect.

2.6 Antioxidant and anti-aging effectsOxidation occurs in our bodies all the time, promoting the production of free radicals in the body, a large number of free radicals lead to aging, and in severe cases can lead to cancer. On the other hand, antioxidants can scavenge free radicals, or indirectly eliminate substances that are easy to produce free radicals, effectively inhibit oxidation and prevent the further occurrence of oxidation.

Hongetal.[11]found that aucubin can reduce reactive oxygen species in the body, and they explored its regulatory mechanism. It was found that aucubin can enhance the activity of enzymes such as glutathione peroxidase and regulate the release of lactate dehydrogenase in cells, thus reducing reactive oxygen species in cells and preventing serious oxidative damage in cells. Ruan Degongetal.[25]found that aucubin had the effect of antioxidation and can remove common free radicals in cells, and the scavenging ability of hydrogen peroxide free radical was the strongest. Ultraviolet UVA and UVB can cause photoaging damage of cells. Chen Qiaoyunetal.[26]found that aucubin can exert its anti-photoaging effect by increasing the activity of fibroblasts and reducing the expression of MMP-1. In addition, Chen Qiaoyunetal.[27]also found that aucubin can protect damaged cells caused by UVB irradiation by inhibiting the release of inflammatory factors. The above results show that aucubin has a good antioxidant effect.

2.7 Antibacterial activityPathogenic microorganisms can cause infection and lead to a variety of serious infectious diseases. A certain concentration of antibiotics can effectively inhibit the growth and reproduction of pathogenic microorganisms. Excessive use of antibiotics can lead to drug resistance and adverse reactions. Therefore, there is an urgent need for a new type of antimicrobial agents with low adverse reactions.

Zheng Jieetal.[28]found that aucubin had a good inhibitory effect on the growth of common bacteria such asEscherichiacoliand Gram-positive bacteriaStaphylococcusaureus, but there were too few strains, and its antibacterial research still needed to be further studied. Li Yetal.[29]found that aucubin can not only inhibit the growth ofSalmonellaandPseudomonasaeruginosa, but also inhibit the growth of Staphylococcus aureus. Shirley KPetal.[30]found that aucubin can effectively inhibit the formation of biofilm of Candida albicans, thus inhibiting its metabolic activity. Zajdel SMetal.[31]found that aucubin had obvious inhibitory effect on Gram-like bacteria. The above results show that aucubin has good antibacterial activity.

2.8 Antidiabetic effectDiabetes is a chronic disease related to metabolism. Too little insulin secretion will lead to diabetes. Diabetes often occurs in the elderly, long-term hyperglycemia will lead to an increase in advanced glycation end products (AGEs) levels, and then induce a variety of serious diabetic complications, causing a heavy burden on the body.

Jin Leietal.[32]found that aucubin can also regulate the number of rat islet B cells to a certain extent, improve the immune ability of insulin in rats, thus inhibiting lipid peroxidation and reducing their blood glucose value. Xue Hongyuetal.[33]found that aucubin inhibited rat brain disease caused by diabetes by down-regulating the expression of Bcl-2 on the mitochondrial membrane and up-regulating the expression of Bax protein. Through in vivo andinvitroexperiments, Jung Eetal.[34]found that aucubin can significantly reduce the level of AGEs in rats, and at the same time, the formation of AGEs bovine serum albumin and its conjugates with collagen decreased significantly. Aucubin can also resist a variety of diseases caused by AGEs. The above results show that aucubin has a good antidiabetic effect.

2.9 Bone protection effectOsteoporosis is a primary or secondary disease caused by the decrease of bone mineral density, which ranks fourth among chronic diseases in China. With the increasing number of people over 60 years old in China, osteoporosis has become the most serious problem in China.

Ha Hetal.[35]found that aucubin can promote the secretion of growth hormone by thalamic cells of mice. At the same time, it can regulate the activity of alkaline phosphatase, promote the proliferation of osteoblasts and inhibit the activity of osteoclasts, so as to play the role of bone protection. Zhu Zetal.[36]found that aucubin can increase the activity of mouse osteoblast line and reduce its oxidative stress response, which can effectively inhibit apoptosis. In addition, aucubin can increase the protein expression level of osteogenic factor and inhibit the expression level of Bax, thus reducing the rate of apoptosis and promoting the proliferation of osteoblasts.

3 Conclusion

In addition to the above-mentioned effects, aucubin also has a variety of pharmacological effects, such as resisting virus and promoting wound healing, and it has very low side effects. Although it has been found that aucubin can assist β-glucosidase to act on the body and produce stronger therapeutic effect, the understanding of aucubin used alone is not deep enough. It is necessary to make use of the knowledge of cytology and pharmacology and adopt simple and effective methods to conduct in-depth study on its own therapeutic effect. In addition, because the aglycone of aucubin has poor thermal stability and is easy to decompose under neutral and alkaline conditions, the preparation and preservation of its pure products are particularly difficult compared with general drugs, which is also an urgent problem to be solved in the future. In order to solve this problem, a large number of experimental analyses need to be carried out to find out the most suitable preparation and preservation methods, so as to provide a theoretical basis for drug development.