A Comprehensive Review on Distribution, Pharmacological Properties, and Mechanisms of Action of Sesamin

Sesamin is a kind of fat-soluble lignan extracted from sesame seeds or other plants. It has attracted more and more attention because of its extensive pharmacological activities. In this study, we systematically summarized the pharmacological activities of sesamin including antioxidant, anti-inammatory, anticancer, protection of liver and kidney, prevention of diabetes, hypertension, and atherosclerosis. Studies focus on the abilities of sesamin to attenuate oxidative stress by reducing the levels of ROS and MDA, to inhibit the release of pro-inammatory cytokines (TNF-α, IL-1β, IL-6, etc.), and to induce apoptosis and autophagy in cancer cells through a variety of signaling pathways such as NF-κB, JNK, p38 MAPK, PI3K/AKT, caspase-3, and p53. By inhibiting the production of ROS, sesamin can also enhance the biological activities of NO in blood vessels, improve endothelial dysfunction and hypertension, and change the process of atherosclerotic lesion formation. In line with this, the various pharmacological properties of sesamin have been discussed in this review so that we can have a deeper understanding of the pharmacological activities of sesamin and clear the future development direction of sesamin.


Introduction
Sesamin, which was rst discovered in Sesamum indicum L, is a natural lignan component. Sesamum indicum is one of the most archaic crops, which is rich in nutrition and has been used as a nutritional product for a long history. It has been known to replenish liver and kidney, nourish blood, and moisten intestinal dryness. Previous studies found that sesamin is the most important ingredient to exert medicinal e ects in this plant [1]. Nowadays, sesamin has always been a research hotspot for scientists and more and more pharmacological activities of sesamin have been reported.
As we all know, oxidative damage and in ammation can cause many diseases. However, sesamin was reported to have antioxidant and anti-in ammatory e ects. It can increase the activities of antioxidant enzymes and reduce the production of reactive oxygen species and malondialdehyde. At the same time, it can also inhibit the release of pro-inammatory cytokines to ensure the normal functions of liver, kidney, heart, and other organs [2][3][4]. In addition, sesamin can also resist a variety of cancers such as liver cancer and lung cancer. It inhibits the growth of cancer cells by downregulating the expression of related proteins and inducing cell cycle arrest [5,6]. What is more, sesamin also has certain preventive and therapeutic e ects on some cardiovascular and cerebrovascular diseases such as diabetes, hypertension, and atherosclerosis [7]. Although there have been many reports on the activities of sesamin, no one has made a comprehensive and systematic summary. In this study, we systematically summarized the plant sources and pharmacological properties of sesamin ( Figure 1) to understand the current research status and de ciencies of sesamin and de ne the future development direction.

Physicochemical Properties and
Sources of Sesamin

Antioxidant Activity of Sesamin.
Under normal circumstances, the production and removal of free radicals in the organism are in a balanced state. However, when excessive free radicals are produced, this balance will be broken, showing oxidative stress damage and disruption to the normal function of cells and tissues. Studies have shown that sesamin can scavenge free radicals in the body and therefore exhibit antioxidant activity.
Oxidation is the most difficult problem in the process of oil preservation. e synthetic antioxidants have potential toxicity, so the antioxidant activity of sesamin can be used in oil preservation. e antioxidant activity of different dosages of sesamin in soybean oil has been reported and the results showed that sesamin shows significant antioxidant activity in soybean oil, with the activity increasing in a dose-dependent manner [18]. e peroxide value and conjugated diene value of soybean oil added with sesamin were both lower than those of the blank group, and within a certain range, the peroxide value and conjugated diene value decreased with the increase in sesamin addition, indicating that sesamin showed significant antioxidant activity [19]. Sesamin can also exert its antioxidant effect at high temperature. At a high temperature of 120°C, the peroxide value of lard and rapeseed oil added with sesamin was significantly lower than that of the control group, indicating that the antioxidant activity of sesamin has good thermal stability [20]. ese studies have shown that sesamin can be used as a natural antioxidant in the process of oil preservation.
ere have been some detailed reports on the mechanism of sesamin's antioxidant effect. Waralee et al. found that sesamin can inhibit the production of ROS and enhance the activities of CAT, SOD, and other enzymes to protect the body from oxidative damage [21]. Likewise, after spinal cord injury in rats, the production of MDA increased and the activities of protective enzymes such as SOD and CAT decreased significantly. However, this trend was obviously reversed after treatment with sesamin, which indicated that sesamin can effectively inhibit the oxidative stress response that occurs in rats with spinal cord injury [22]. e  antioxidant effect of sesamin had also been confirmed in hypertensive rats. e SOD activity decreased in the hippocampus and cortex tissues of hypertensive rats and the levels of MDA and H 2 O 2 increased, showing a typical oxidative stress response. After treatment with sesamin, the levels of MDA and H 2 O 2 were significantly reduced while the SOD activity was obviously increased, revealing that sesamin can reduce the oxidative stress damage in hippocampus and cortex tissues in hypertensive rats and improve the antioxidant capacity [23]. Furthermore, studies have found that sesamin showed antioxidant effects by activating certain signal transcription. When adult drosophila with high levels of ROS was fed with sesamin-containing feed, Nrf2/Cnc was strongly activated in neurons, and the transcription factor Nrf2 (Cnc in drosophila) was critical in reducing oxidative stress. erefore, the antiaging effect of sesamin is to reduce the accumulation of oxidative stress in neurons by activating the Nrf2/Cnc pathway [24]. Sesamin can also reduce the oxidative stress damage in zebrafish head caused by fluoride stress and enhance the activities of immune enzymes such as ACP and AKP [25]. e above studies have shown that the antioxidant activity of sesamin is related to the regulation of the activity of protective enzymes and immune enzymes in the body and the inhibition of the production of ROS and MDA.
Other relevant reports about the antioxidant effects of sesamin in vivo and in vitro are shown in Table 1.

Anti-Inflammatory Activity of Sesamin.
Inflammation is a part of defense mechanism in the body and is typically characterized by pain, swelling, and fever. Pathogen infection, chemical stimulation, physical injury, connective tissue disease, allergic reaction, and so on can all cause the occurrence of inflammatory reaction. Some uncontrolled chronic inflammation often leads to many diseases. Natural or synthetic anti-inflammatory drugs are currently considered as a treatment for the disease. It has been reported that sesamin can play an anti-inflammatory role in vivo and resist a variety of inflammations [34]. Ulcerative colitis (UC) is the main form of inflammatory bowel disease. Patients show clinical symptoms such as abdominal pain, diarrhea, and physical weakness. Bai et al. used dextran sodium sulfate (DSS)-induced ulcerative colitis mice as a model and found that sesamin can enhance Nrf2mediated protection against H 2 O 2 -induced oxidative stress in vitro and alleviate colitis induced by DSS in vivo. e research also proved for the first time that sesamin can activate Nrf2-mediated oxidative stress protective signaling pathway in colitis via AKT and ERK activation [35]. Physical damage such as ultraviolet (UV) exposure can also cause skin inflammation. Studies have confirmed that sesamin treatment can reduce the production of reactive oxygen species in human dermal fibroblasts after UVB irradiation and prevent the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby resisting UVB-induced skin inflammation [36].
In addition, some neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are occurring more and more frequently in our country. One of the causes of this disease is the activation of microglia mediated by neuroinflammation. Toll-like receptor (TLR4) is a key innate immune receptor involved in microglia activation and neuroinflammation. It was reported that sesamin reduced the expression of TLR4 by inhibiting the pathway of JNK and NF-κB. It also led to the downregulation of neurotoxicity in BV2 microglia and reduced the release of NO, prostaglandin E2 (PGE2), and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in microglia [37]. As for airway inflammation, allergic asthma is a typical one, which is a chronic airway inflammatory disease. Lin et al. found that sesamin exerted a significant anti-inflammatory effect in ovalbumin (OVA)induced asthma mice. e expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE decreased in OVAstimulated mice treated with sesamin, as did the number of total inflammatory cells and eosinophils in bronchoalveolar lavage fluid (BALF).
ese results indicated that sesamin exhibited a good therapeutic effect on OVA-induced allergic asthma in mice [30]. Other experiments on the anti-inflammatory activity of sesamin in vivo and in vitro are shown in Table 2.

Anticancer Activity of Sesamin.
Cancer has always been a major problem that humans need to overcome. Chemotherapy is still the main method of treating cancer at present. However, chemotherapy also has the disadvantages of low efficiency and large side effects. erefore, the development of natural anticancer drugs should be a new research direction. Studies have shown that sesamin can effectively inhibit a variety of tumors, which provides a new idea for the development of anticancer drugs.
Liver cancer is a high-incidence and extremely harmful malignant tumor. According to the data released by the National Cancer Center in 2019, the incidence of liver cancer is the fourth highest in China and the mortality rate is as  Reduction in blood sugar, TNF-α, and ICAM-1; inhibition of microglia activation [40] CUMS-induced mouse model 50 mg/kg/d Orally 6 weeks Sesamin inhibits the excessive activation of cortical microglia and the expression of iNOS, COX-2, TNF-α, and other inflammatory factors [41] high as the second [48]. Studies have reported the antitumor effect of sesamin on H22 hepatocellular carcinoma-bearing mice. Experiments have found that low-dose sesamin had a certain inhibitory effect on H22 liver cancer cells, while highdose sesamin had less inhibitory effect. Although the inhibiting effect was not as good as traditional anticancer drugs, sesamin was far less harmful to human body than traditional anticancer drugs. is suggests that there are more medicinal ingredients in natural plants to be developed. In the experiment of mice treated with sesamin and given diethylnitrosamine (DEN) intragastric administration, all mice in the model groups suffered from liver cancer, and  Figure 3: Scheme of sesamin metabolism in the liver.
Sesamin P450 S1 Ca 2+ S1 ANX A1 Phosphorylation S1 ANX A1  Figure 4: Schematic of the anti-inflammatory effect of S1 mediated by ANX A1 activation. S1 directly binds to the repeat 3 domain of ANX A1 in monocytes. Under stimulation, S1 promotes the phosphorylation of ANX A1 Ser27 and the subsequent extracellular release of ANX A1 and inhibits the production of TNF-α or MCP-1 to exert anti-inflammatory effect. liver index, ALT, AST, and other liver function indexes were higher than those of the control groups. However, the liver index and various indicators of the sesamin treatment groups were normal, which indicated that sesamin had a protective effect on DEN-induced liver cancer in mice [49][50][51]. HepG2 cells are also a type of hepatocarcinoma cells that are currently studied. e study found that after treating human hepatoma HepG2 cells with sesamin for 48 hours, the inhibition rate can reach 41.8%, and the cell growth is obviously inhibited. However, the inhibition effect on normal liver cells L02 was significantly lower than that of HepG2 cells under the same conditions, indicating that sesamin had no significant toxicity to normal human cells [52]; at the same time, it was found that sesamin can induce early apoptosis of HepG2 cells, which indicated that sesamin can inhibit the proliferation of HepG2 cells by inducing apoptosis [53]. In addition, studies have found that the inhibiting effect of sesamin on the proliferation of HepG2 was related to the expression of related proteins. Sesamin could inhibit the proliferation of HepG2 cells to varying degrees at the concentration of 0-96 ug/mL, and the inhibiting effect became more obvious with the increase in concentration and the extension of time. e optimal treatment time was 48 h. HepG2 cells were reduced in G1 phase and increased in G2 phase after 48 hours of sesamin treatment, which was found to be related to the decrease in the expression of cyclin A and cyclin B1 proteins. It indicated that sesamin inhibited the proliferation of HepG2 cells by downregulating the expression of these two proteins [54].
Lung cancer is one of the most harmful malignant tumors with the fastest increasing morbidity and mortality. Numerous studies have found that sesamin also had good inhibitory activities on lung cancer. According to statistics, non-small cell lung cancer (NSCLC) accounts for about 85% of the total incidence of lung cancer. At present, there are many studies on the human non-small cell lung cancer cell line A549. A549 cells were treated with sesamin. e cell viability, migration ability, and cell cycle were detected by the CCK8 method, scratch method, and flow cytometer. e results showed that sesamin could inhibit the viability and migration ability of A549 cells and induce G0/G1 phase arrest. It can produce lethal effects on lung cancer cells by inducing autophagy and mitochondrial apoptosis [55]. In addition, the experiments in vivo and in vitro had shown that sesamin inhibited Akt activity and upregulated the expression of p53, indicating that sesamin induced the arrest of cell cycle in G1 phase through Akt/p53 signaling pathway and inhibited the proliferation of NSCLC cells [56]. Watanabe et al. used the MTT to determine the antiproliferative effect in human lung adenocarcinoma cell line A549 by sesamin, vinorelbine, and sesamin collaborative vinorelbine. When A549 cells were treated with sesamin in the range of 10-100 ug/mL for 48 hours, it is found that low concentrations of sesamin had an antiproliferative effect on A549 cells. e combination of sesamin and vinorelbine had a higher inhibitory rate on the growth of A549 cells than the two drugs used alone [57]. Studies have also found that the proliferation of A549 and H1792 cancer cells could be significantly inhibited by the treatment of sesamin within the concentration gradient of 10-40 μM for 24 or 48 hours. e apoptosis of A549 and H1792 cells was significantly induced at 10-30 μM for 24 hours in a dose-effect relationship. An indepth study of its mechanism has found that sesamin upregulated the expression of p53 and downregulated the expression of cyclin D1 and CDK2, so that G1 phase was arrested and the proliferation of NSCLC cells was inhibited [58]. In addition to the study on A549 cells, Binaifer et al. explored the resistance of sesamin combined with cisplatin to lung cancer cell H460 through proliferation inhibition experiments and Western blot experiments. e results showed that sesamin combined with cisplatin synergistically suppressed the proliferation of H460 cells and this may be achieved by inhibiting the expression of p-Akt [59].
In addition, sesamin also has a certain inhibitory effect on other malignant tumors. Dou et al. studied the effect of sesamin on cervical cancer (HeLa) cells, and the results showed that in the sesamin treatment groups, the expressions of Bax, caspase-12, GRP78, GADD153, p-IRE1α, p-JNK, LC3I/II, and beclin-1 increased and the expression of Bcl-2 decreased. Further studies have confirmed that sesamin can also induce autophagy in HeLa cells and inhibit their proliferation and migration [60]. Sun et al. discussed the effect of sesamin on human colon cancer SW480 cells. After 48 hours of treatment with sesamin at 100 μM, the inhibition rate reached 49.95%, and the maximum inhibition rate reached 79.21%. Compared with the control group, the sesamin group's early apoptosis rate is statistically significant and the expression of caspase-3 and caspase-8 was more significant (P < 0.01), indicating that sesamin could inhibit the proliferation of SW480 through the activation of caspase family members [61].
rough the above studies, it is found that sesamin plays an anticancer effect mainly by regulating the expressions of related proteins, promoting cell cycle arrest in G1 phase, inhibiting the proliferation of cancer cells, and inducing apoptosis. ere are many other reports on the effects of sesamin on other cancer cells in Table 3.

e Protection of Liver and Kidney.
With the changes in modern lifestyles, the incidence of various diseases such as fatty liver disease caused by dietary imbalance is getting higher and higher. e pathological changes in liver cells are often caused by lipid metabolism disorders and lipid peroxidation. Studies at home and abroad have found that sesamin has a good regulatory effect on lipid metabolism disorders and can effectively prevent the formation of fatty liver and protect the liver.
Zhao et al. used AlCl 3 gavage combined with D-galactose intraperitoneal injection to establish the rat model of liver injury to study the protective effect of sesamin on the liver. e results of the study showed that the rats in the liver injury model groups not only lost weight and eat less but also decreased the activities of SOD and other enzymes in the body indicating that the liver of rat had oxidative damage. After treatment with sesamin, the above symptoms were relieved to varying degrees, the activities of SOD and other protective enzymes increased, and the content of MDA decreased. It is suggested that sesamin can improve the ability of antioxidative damage in rats with liver injury, which may be one of the mechanisms of sesamin to protect against liver injury [75]. Some studies have also shown that sesamin plays an antioxidant role by downregulating the expression of iNOS protein and has a protective effect on rat liver disease induced by AlCl 3 and D-galactose [76]. Fluoride exposure can also cause liver histological changes in animals. When determining the effect of sesamin on oxidative stress and immune damage in zebrafish liver under fluorine exposure, it was found that sesamin can regulate the activities of immune-related enzymes and the expressions of related gene. For example, it can increase the expression of LZM, ACP, AKP, and IL-10 and reduce the expression of TNF-α, INF, IL-11, M17, IL-1β, IL-6, and IL-12P40 mRNAs [77]. Some related experiments have been carried out in rabbits. Rabbits were fed with hyperlipidemic feed for 10 weeks to establish hyperlipidemia rabbit models. From the fifth week, they were fed with sesamin (25, 225 mg/kg) once a day. After 6 weeks of continuous feeding of sesamin, the levels of TC, LDL-C, and TG in the rabbits were significantly reduced and the expression of HDL-C increased, indicating that sesamin had the effect of lowering blood lipids. At the same time, the AST, ALT, and other liver indexes were significantly reduced, which proved that sesamin also had a certain hepatoprotective effect [78]. e significant increase in blood pressure can also cause abnormal blood flow in the kidneys and cause damage to kidney function. Acute kidney injury (AKI) is a common comorbidity in critically ill patients, with an incidence of up to 30-60%. AKI not only affects the acute phase but can also develop into chronic kidney disease (CKD) in the later stage, affecting the prognosis of the disease and increasing the mortality rate. Researchers usually expose mouse to lipopolysaccharide (LPS) to make AKI mouse models. In the study of the protective effect of sesamin on LPS-induced acute renal injury, 25, 50, and 100 mg/kg of sesamin were injected one hour before the injection of LPS (10 mg/kg). Compared with the control groups, the level of blood urea nitrogen (BUN) in LPS groups increased significantly and the level of creatinine also increased one day later. In contrast, the levels of BUN and creatinine in 100 mg/kg sesamin groups decreased significantly. e measurement results of oxidative stress parameters showed that the levels Sesamin inhibits the activities of mushroom tyrosinase and cell tyrosinase; absorbs ultraviolet [74] of MDA and nitrate increased and the levels of SOD, CAT, and GSH decreased significantly in LPS groups, while the 100 mg/kg sesamin could significantly reverse this trend. It indicated that sesamin can protect the kidneys from the damage of LPS by reducing oxidative stress and inflammation [79]. Xuan found that sesamin can reduce the levels of serum creatinine, urea nitrogen, and urinary microalbumin in spontaneously hypertensive rats and reduce the damage of renal fibrosis [80]. It can be seen that the protective effect of sesamin on liver and kidney is mainly achieved by reducing oxidative stress damage and regulating lipid metabolism. Sesamin can reduce the content of MDA, increase the activities of antioxidant enzymes, and therefore reduce the damage caused by oxidative stress. At the same time, it can reduce the levels of TC, LDL-C, and TG in the body, promote the expression of HDL-C, and improve lipid metabolism disorders and lipid peroxidation, to play a role in liver and kidney protection. Other related reports are shown in Table 4.

e Effect of Sesamin on Hypertension.
Hypertension is the most common chronic disease and the most dangerous factor in inducing cardiovascular and cerebrovascular diseases. Long-term hypertension can lead to impaired heart function, cause hypertrophy and apoptosis of cardiomyocytes, and ultimately lead to heart failure. Maintaining good living habits, reducing the intake of salt and alcohol, and maintaining a healthy weight can effectively prevent the occurrence of high blood pressure. In addition to lifestyle changes, medical treatment is also an important way to prevent and treat hypertension. Natural compounds such as sesamin have been found to have good antihypertensive effects. Li et al. found that right ventricular systolic pressure and mean pulmonary artery pressure significantly decreased after sesamin was applied to hypertensive rats induced by monocrotaline. e mechanism may be related to sesamin's inhibition of the production of NADPH and MDA [85]. Studies had also confirmed that the antihypertensive mechanism of sesamin was related to the increase in NO activities in the organism. Kong et al. confirmed that sesamin treatment reduced the systolic blood pressure, improved vascular relaxation induced by acetylcholine, and enhanced aortic NO bioactivities. e increase in NO biosynthesis was due to the upregulation of P-eNOS and the inhibition of eNOS uncoupling. In addition, sesamin also reduced the inactivation of NO and the production of superoxide anions by downregulating p47phox. A series of experiments have proved that sesamin can reduce hypertension and improve endothelial dysfunction by enhancing the biological activities of NO in the aorta of hypertensive rats [86]. e antihypertensive effect of sesamin is also attributed to the ability of its metabolites to scavenge free radicals. e systolic blood pressure is positively correlated with the production of superoxide in the aorta. erefore, the antioxidant activities of sesamin may contribute to its antihypertensive effect [87]. Taking DOCA salt hypertensive rats as models, studies have confirmed that the ability of sesamin to inhibit superoxide production and improve vasodilation contributes to its antihypertensive effect [88][89][90]. Sesamin is also considered to be an inhibitor of 20hydroxyeicosatetraenoic acid (20-HETE), which is the metabolite of arachidonic acid. 20-HETE can act on the renin-angiotensin system and change the regulation of blood pressure, leading to hypertension [91]. e experiments in vitro have shown that sesamin can prevent the synthesis of 20-HETE in human liver and kidney microsomes with IC 50 < 20 μmol/L. In a randomized controlled crossover trial, overweight men and women (n � 33) were given 25 g sesame (approximately 50 mg sesame lignan) daily for 5 weeks. e content of 20-HETE in plasma and urine decreased by 28% and 32%, respectively [92]. e above studies have shown that sesamin may reduce systolic blood pressure and mean arterial pressure, enhance aortic NO activities, and improve vascular endothelial function, thereby lowering blood pressure. Other reports on the antihypertensive effects of sesamin in vivo and in vitro are shown in Table 5.

e Effect of Sesamin on Atherosclerosis. Atherosclerosis (As) is a chronic inflammatory disease.
Under the influence of risk factors such as hyperlipidemia and high blood pressure, it is easy to cause lipid metabolism disorders in the body and result in a large amount of lipid accumulation under the intima of blood vessels, leading to chronic inflammation [97][98][99]. e proliferation of SMCs, lipid accumulation in blood vessels, the necrosis, apoptosis, and fibrosis of cells are the characteristics of atherosclerosis [100]. According to reports, there are 8 to 10 million people die every year from cardiovascular disease and stroke caused by atherosclerosis. Studies have confirmed that feeding lowdensity lipoprotein receptor defect mouse with feed containing sesame oil for 3 months can significantly inhibit the formation of atherosclerotic lesions in mouse and reduce the levels of plasma cholesterol, triglycerides, and low-density lipoprotein cholesterol [101]. To explore the mechanism by which sesame oil may regulate atherosclerosis, Narasimhulu et al. did relate research and found that there were at least three mechanisms by which sesame oil inhibited atherosclerosis: (a) lowering plasma cholesterol by accelerated catabolism through the oxidation of cholesterol; (b) enhancing reverse cholesterol transport mediated by SR-B1 and ABC transporters; and (c) controlling mediators of inflammation [102]. To clarify the role of lignans in this antiinflammatory response, a more in-depth study was carried out on the mechanism of sesame oil against atherosclerosis, and it was found that sesamin can reduce the formation of atherosclerotic lesions in ApoE-deficient mice with the reduction of nearly 40%, although this was not statistically significant [103]. Related studies have found that in ApoE gene-deficient mice, whether fed with food or atherosclerotic food, the mice showed hypercholesterolemia and 8 Journal of Chemistry atherosclerotic lesions [104], while in LDL receptor-deficient mice, hypercholesterolemia and atherosclerotic lesions will only appear after feeding foods that cause atherosclerosis [105]. e anti-atherosclerotic effect of sesamin is expected to be more pronounced in LDL-deficient mice than in ApoE gene-deficient mice. erefore, it is recommended that LDLdeficient mice be used as a model to evaluate the antiatherosclerotic effect of sesamin. Studies have found that sesamin inhibited the growth and proliferation of vascular smooth muscle cells (VSMCs) in humans, mouse, and rat induced by PDGF-BB by inhibiting the activation of MAPK and PI3K pathways and reducing oxidative stress by inducing the expression of heme oxygenase-1 [106]. In fact, other studies have shown that sesamin (25-100 μM) upregulated the expression and transcriptional activities of PPARc1 and LXRα in macrophages through MAPK signals and enhanced cholesterol efflux from macrophages. PPARc1 and LXRα are important nuclear receptors involved in macrophage cholesterol homeostasis and inflammation. erefore, another mechanism of sesamin's anti-atherosclerosis may be to promote the outflow of macrophage cholesterol and prevent the formation of foam cells [107].
Studying the effect of sesamin on the adhesion molecules of endothelial leukocytes can provide a more in-depth understanding of the anti-atherosclerotic mechanism of DOCA salt-sensitive hypertensive rats 10 g/kg Orally 5 weeks e systolic blood pressure and the expression of p22phox, gp91phox, and Nox1 decreased [89] Two-kidney one-clip hypertensive rats 60, 120 mg/kg Orally 8 weeks e systolic blood pressure decreased by 11% (60 mg/kg) and 17% (120 mg/kg) [95] Streptozotocininduced diabetic rat model  Decreases the diastolic blood pressure in SHR rats; inhibits over-activated PI3K/AKT/ mTOR signaling pathway [84] Journal of Chemistry 9 sesamin. Studies have shown that treatment of human aortic endothelial cells (HAECs) treated with tumor necrosis factor-alpha with sesamin (10 μM, 100 μM) reduced the expression of intercellular adhesion molecule-1 by 35% and 70%, respectively [108]. e inhibitory effect of sesamin on ICAM-1 was also mediated by the downregulation of ERK1/ 2 and p38. In addition to ICAM-1, sesamin can also inhibit the expression of VCAM-1 in the rat aorta with an inhibition rate of 27.59% [109]. ICAM-1 and VCAM-1 play a role in the adhesion of monocytes to endothelial cells, and both participate in the formation of atherosclerotic lesions [110].
Other reports on the anti-atherosclerosis effect of sesamin are shown in Table 6.

e Effect of Sesamin on Diabetes.
Diabetes is one of the leading causes of death in the world. ere are approximately 2.2 million people die of diabetes worldwide each year. In fact, diabetes is a manifestation of metabolic disorders. High blood lipids and high blood sugar cause inflammation and oxidative stress damage. When the body cannot control blood sugar levels, it shows that insulin secretion or insulin response is blocked, leading to the occurrence of diabetes [118].
Studies have reported the effect of sesamin on diabetes and its complications. Sesamin treatment of spontaneous diabetic mice (KK-Ay) can significantly reduce the levels of fasting blood glucose, cholesterol, and triglycerides and improve the insulin-binding capacity to liver crude plasma membranes [119]. Some researchers have done experiments in humans. Patients with type 2 diabetes took 200 mg of sesamin daily for 8 weeks. e examination found that fasting blood glucose (FBS), glycosylated hemoglobin (HbA1c), TNF-α, body adiposity index (BAI), and other indicators were significantly reduced [120]. All these indicate that sesamin can regulate blood sugar levels and reduce inflammation.
One of the causes of diabetes is the long-term excessive consumption of fat-rich foods. However, taking sesamin together with high-fat foods can reduce the occurrence of this adverse reaction. For example, after taking sesamin in high-fat diet rats, it can significantly improve the fasting blood glucose and white adipose tissue concentration in the body, and it can also reduce the level of glucose-6-phosphatase (G6Pase) [121]. e reduction of G6Pase reduced the conversion of glucose-6-phosphate to glucose, thereby reducing blood glucose concentration. In addition to regulating blood sugar concentration, sesamin can also prevent the damage of skeletal muscle mitochondria in diabetic patients and effectively improve the decline of their exercise capacity. Sesamin mainly achieved this goal by inhibiting the increase of NADPH oxidase activities and the production of superoxide anions [122]. What is more, sesamin has also been found to have a cardioprotective function. Taking sesamin (100, 200 mg/kg) for 4 weeks in STZ-induced type 1 diabetic rats can significantly reduce blood sugar levels and improve heart rate and blood pressure [100]. Other reports on the antidiabetic effect of sesamin are shown in Table 7.
At present, there are few studies on the effects of sesamin on type 1 and type 2 diabetes, and the existing studies are only at the stage of model experiments, which needs to be further strengthened in clinical trial research. Furthermore, in addition to the effect of sesamin on fasting blood glucose, whether it has an effect on postprandial blood glucose and the secretion of insulin and C peptide needs to be further studied. 10 Journal of Chemistry

Conclusion
Sesamin is a natural lignan compound mainly found in sesame seeds. At present, many studies have reported that it has rich medicinal value.
is article systematically summarized its pharmacological activities and found that sesamin has obvious antioxidant and anti-inflammatory effects and multiorgan protection. e antioxidant effect of sesamin is achieved by reducing lipid peroxidation, reducing the levels of superoxide and nitric oxide, and improving the activities of antioxidase such as SOD, CAT, and GSH. Oxidative stress damage can also cause inflammation, sesamin can reduce COX and PEG2, and inhibit the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, etc.) to alleviate the inflammatory response, which also has a certain protective and therapeutic effect on the damage of liver, kidney, lung, and other organs caused by oxidative stress and inflammation. However, research shows that the antioxidant and anti-inflammatory effects of sesamin depend on its metabolites containing the catechol moieties. Inflammation can also cause a variety of complications including various cancers. Studies have found that sesamin can inhibit the occurrence of liver cancer, lung cancer, colon cancer, breast cancer, and other cancers to varying degrees. Research studies in vivo and in vitro have shown that sesamin inhibits the growth of cancer cells by downregulating protein expression, inhibiting the production of gene products, and inducing cell cycle arrest. In addition, by inhibiting the production of ROS, sesamin enhances the biological activities of NO in blood vessels, improves endothelial dysfunction and hypertension, and changes the process of atherosclerotic lesion formation. Continuously taking sesamin can reduce the levels of fasting blood glucose concentration, glycosylated hemoglobin (HbA1c), and body adiposity index (BAI), regulate blood sugar levels, and reduce the occurrence of diabetes. e various pharmacological properties of sesamin and its mechanism of action can be seen in Figure 5.
rough the above research reports, we can find that the current research reports on the pharmacological effects of sesamin are relatively extensive, but few studies can clearly point out the link between the mechanism of sesamin and the disease. In particular, the influence of inflammation and oxidative damage on the existence of disease is worthy of in-depth study. In addition, the research on the structure-activity relationship of sesamin is rarely reported. e structure-activity relationship study can infer the relationship between the chemical structure and physiological activities of the biologically active substance and then infer the structure of the target active site and design a new active substance structure. Surprisingly, studies have found that the catechol groups in sesamin metabolites play an important role in antioxidant and anti-inflammatory effects. is provides a new direction for further research on the structure-activity relationship of sesamin, and it has certain reference significance for its better application in clinical and new drug design.

Conflicts of Interest
e authors declare that they have no conflicts of interest.