2.1.4. Diabetic Eye Disease

Diabetic retinopathy is a microvascular complication that affects the neurovascular of the retina as a result of neurodegeneration, neuro-inflammation, eventual fibrosis and other diabetic-related damage [84]. In general theory, pathological conditions related to inflammatory activates microglia in the retina and further initiate neuro-inflammation [85]. This eventually led to tissue ischemia, vascular occlusion and cell death causing blindness [86].

In streptozotocin (STZ)-induced diabetic retinopathy mice model, administered 30 ppm of sesamin alleviates the retinal inflammation. The treatment decreases the mRNA levels of *TNF-*α and *ICAM-1* I unlike in the diabetic group. This further elaborates the possibility of reducing the production of inflammatory cytokines in diabetic retina. Sesamin suppresses the induced diabetic retinal injury by inhibition of TNF-α and microglia Iba-1 [87].

#### 2.1.5. Inflammatory Bowel Disease

Ulcerative colitis is an inflammatory bowel disease (IBD) that involves damaging of mucosal tissue via dysregulation of the inflammatory system. In the dinitrochlorobenzene (DNCB)-induced IBD albino rat model [88], sesamol decreases the activity of myeloperoxidase (MPO), which is considered to manifest the anti-inflammatory activities. Although sesamol has incapability to decrease the IL-6 and TNF-α cytokine levels induced by DNCB, sesamol can undergo through ROS pathway.

Aspirin, when ingested, can kill different inflammatory diseases however this can possibly cause acute gastroduodenal injury, which considers the bleeding of ulcers [89]. This happens when there is lipid peroxidation in gastric mucosal caused by ROS, which then regulates the inflammatory cytokines [90,91]. In an aspirin-induced gastric mucosal rat model [92], sesamol has been reported to have suppression effect on neutrophil activation and infiltration when aspirin induces gastric inflammation. The activation of neutrophil initiates the expression of proinflammatory mediators and eventually upregulates the production of nitric oxide, which causes cell damage and lipid peroxidation. The inhibition of sesamol on the neutrophil activation, moreover, is reported to have no effect on the physiological aspect of the aspirin-treated system.

In one study [93], sesaminol triglucoside can be metabolized to enterolignans through the walls of the large intestines such as ST-1, ST-2 and ST-3. Correspondingly, these sesaminol triglucoside metabolites are transformed further into hydroxylate metabolites when absorbed to the intestines and is excreted in urine. ST-1 and ST-2 possess catechol moiety, which considers its antioxidant activity. ST-2 has showed a remarkable inhibitory effect against the LPS stimulated TNF-α and IL-6 production in RAW 264.7 cells. STG blocks the generation of NO, which is induced by LPS and inhibits cytosolic phospholipase A2 (cPLA2), *COX-2* and *iNOS* expression [94].

In one small study of adhesive small bowel obstruction (SBO) [95], a clinical trial wherein sixty-four patients (control: 33 patients; intervention: 31 patients) were administered, is conducted in a span of three hours with 150 mL sesame oil. The results show more effectivity of sesame oil in SBO as compared to the control group. Only a few patients were required to undergo surgery in the intervention group as compared to the control group and the observed duration of stay in the hospital was shorter than the control group.

#### 2.1.6. Cardiovascular Disease

Endothelial dysfunction ignites the start of the chronic inflammatory process called atherosclerosis. This pathogen pathway is enhanced by transforming low-density lipoprotein (LDL) to oxidized low-density lipoprotein (oxLDL) as a consequence of ROS and oxidative stress. Exposure of endothelial cells to oxLDL promotes the expression of proinflammatory cytokines [96].

In the human umbilical vein endothelial cells (HUVECs) model [97], sesamin at a dose of 100 μM has nearly 100% inhibitory effect on the activation of NF-кB induced by oxLDL. Similarly, sesamin also suppresses the discharge of interleukin IL-8, and endothelin ET-1, prompted by oxLDL. The expression of adhesion molecules on the surface has been attenuated by sesamin by half of the initial dose.

Cardiac hypertrophy is the unusual enlargement of heart muscles that leads to the changes in the extracellular matrix of the heart. Renin-angiotensin system (RAS) is crucial in the development of cardiac hypertrophy especially in the left ventricle. MAPK stimulates the hypertrophic response of Angiotensin II (Ang II), the bioactive peptide component of RAS [98–101]. In the study of DOCA/salt-induced left ventricular hypertrophy (LVH) rat model, sesame oil exhibited a down-regulation of p-p38 and p-JNK levels. However, sesame oil had no observed effect on the ERK activation in the LVH rat [102].
