<p><b>Oxidative Stress, Plant natural antioxidants, and Obesity :</b></p><p>Oxidative stress is important in the pathophysiology of obesity, altering regularity factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and also the size of adipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite.&nbsp; &nbsp; &nbsp;</p><p><b>What is Obesity:</b></p><ul><li>Obesity is a complex disease having an important public health impact worldwide, and its prevalence is increasing.</li><li>it is the result of an individual complex interaction of factors which includes genetic predisposition, diet, metabolism, and also physical activities&nbsp; </li><li>It is related to several severe complications like metabolic syndrome, type 2 diabetes mellitus, cardiovascular dysfunction(CVD), and also hypertension&nbsp; &nbsp; &nbsp; &nbsp;</li></ul><p><br></p><p><b>Balancing Redox in Obesity:</b></p><p><span style="color: rgb(33, 33, 33); font-family: Helvetica; font-size: 14px;">The most important site, where intracellular ROS are produced, is mitochondria, due to the leakage of electrons through the respiratory chain. According to research, ROS may also be produced by plasma membrane organelles and systems, such as the endoplasmic reticulum which is known as ER, lysosomes, peroxisomes, and by cytosolic enzymes. ROS/RNS both have many biological effects at low concentrations, including the defense against pathogenic microorganisms, they are mediated by the immune system and intracellular signaling.</span></p><p><span style="color: rgb(33, 33, 33); font-family: Helvetica; font-size: 14px;">At high levels, they damage DNA, lipids as well as proteins, resulting in injury to tissues and cell death.</span></p><p><span style="color: rgb(33, 33, 33); font-family: Helvetica; font-size: 14px;"><br></span></p><h3 id="sec2dot7-ijms-22-01786title" style="box-sizing: inherit; clear: initial; font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; line-height: 22.5pt; margin: 20pt 0px 10pt; font-size: 15.795pt; letter-spacing: -0.01em;"><b style=""><span style="font-family: Helvetica; font-size: 14px;"><font color="#000000">Oxidative Stress, Iron Metabolism, and Hepdicin in Obesity</font></span></b></h3><ul><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">Obesity is characterized by chronic low-grade inflammation that leads to the production of inflammatory cytokines, which is for increasing OS and elevating hepcidin secretion in hepatocytes and macrophages</span><span style="font-family: Helvetica; font-size: 14px;">. </span></li><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">Hepcidin is for peptidic hormone, which is mainly produced by the liver, which regulates iron metabolism </span><span style="font-family: Helvetica; font-size: 14px;">The increased OS is used to contribute to the development and progression of various diseases that influence obesity.</span></li><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">Serum hepcidin is significantly elevated in obese people mostly.</span><span style="font-family: Helvetica; font-size: 14px;">&nbsp;Iron induces OS since it is a metal with redox activity. </span></li><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">It is also used to enhance ER stress, inflammation, and endocrine dysfunction of adipose tissue. Mechanisms of toxicity mediated by iron modify aspects of the pathogenesis of obesity, resulting in its exacerbation. Free intracellular iron is cytotoxic, promoting the Fenton reaction, and exacerbating OS</span><span style="font-family: Helvetica; font-size: 14px;">. </span></li><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">Ferritin is of crucial importance in the protection of the liver against oxidative damage. When there is insufficient positive regulation of ferritin, free iron can exert its pro-oxidant and cytotoxic effects. These molecular events lead to positive feedback in ROS production and contribute to the pathophysiological alterations in obesity. Medicine also targets the intestinal absorption of iron and the function of ferroportin within the cell, thus playing a central role in iron homeostasis</span><span style="font-family: Helvetica; font-size: 14px;">.</span></li><li style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">Overproduction of hepcidin is a possible cause of obesity-related hypoferremia</span><span style="font-family: Helvetica; font-size: 14px;">. Excessive secretion of this protein leads to iron sequestration in cells of the reticuloendothelial system. The latter results in increased iron content in adipose tissue, which programs adverse effects and also an overload of local iron.</span></li></ul><h3 id="sec2dot3-ijms-22-01786title" style="box-sizing: inherit; clear: initial; font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; line-height: 22.5pt; margin: 20pt 0px 10pt; font-size: 15.795pt; letter-spacing: -0.01em;"><img src="/media/django-summernote/2022-10-26/acff1462-f47b-4c77-a8f5-841ecd9b7538.png" style="width: 698.013px;"><span style="font-family: Helvetica; font-size: 14px;"><font color="#000000"><b>ROS and ER Stress in obesity:</b></font></span></h3><p id="__p14" class="p p-first-last" style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><span style="font-family: Helvetica; font-size: 14px;">The ER controls many cellular processes, like inflammation and lipid metabolism, via the unfolded protein response (UPR) signaling pathway. It also participates in the storage of glucose, proteins, as well as calcium ions. High levels of Ca</span><span style="box-sizing: inherit; font-size: 14px; line-height: 0; position: relative; vertical-align: baseline; top: -0.5em; font-family: Helvetica;">2+</span><span style="font-family: Helvetica; font-size: 14px;">&nbsp;are released from the ER internal deposits which are used to lead to mitochondrial dysfunction and the generation of mitochondrial ROS. Reactions by ER chaperones and oxidoreductases also generate ROS. Elevated levels of free fatty acids, by including saturated fatty acids, result from the activation of the UPR in many tissues and cell types. Moreover, it makes changes in the lipid composition of the ER to activate the UPR, and these results in modifications of the activity of the Sarco-/endoplasmic reticulum calcium ATPase and the subsequent disequilibrium in homeostasis</span><span style="font-family: Helvetica; font-size: 14px;">. </span></p><p id="__p14" class="p p-first-last" style="box-sizing: inherit; line-height: inherit; margin-top: 20pt; margin-bottom: 20pt; hyphens: none; color: rgb(33, 33, 33); font-family: Cambria, &quot;Cambria Math&quot;, stixgeneral, &quot;Times New Roman&quot;, Times, serif; font-size: 20px;"><br></p>