# Garlic Extract: Inhibition of Biochemical and Biophysical Changes in Glycated HSA
## 1 Introduction  
Non-enzymatic glycation reaction involves the binding of sugars (glucose, fructose,ribose, etc.) to free \(\epsilon\)-amino groups of proteins in the absence of enzymes. The reaction is classically covalent, in which a sugar protein complex is formed through N-glycoside bonding, via a cascade of chemical responses described by the chemist [PERSON] [1]. AGEs are endogenous compound groups formed by non-enzymatic reactions [2, 3]. Glycation exerts structural alteration of proteins, adversely affecting their physiological functions. Normal physiologic conditions lead to progressive increase in AGE formation with aging [4]. However, the process is accelerated under hyperglycemia conditions and in other inflammatory diseases [5, 6, 7, 8]. AGEs can even be ingested through food [9]. With aging, protein glycation products tend to get deposited and subsequently build up in the tissues of living organisms [10]. Many age-related degenerative alterations occurdue to protein degradation, deterioration of protein functionality, and development of toxic molecules leading to the activation of inflammatory pathways. Collectively, these changes often remain undetected by the individual, until clinical manifestation [11]. Glyceraldehyde derived AGEs are toxic and are referred to as toxic AGEs (TAGE) due to induction of cellular dysfunction and association with lifestyle related diseases such as cardiovascular diseases, hypertension, insulin resistance, diabetic complications, Alzheimer's disease, and cancer [11; 12; 13; 14; 15; 16; 17; 18; 19]. Glycation is one of the main sources in the generation of reactive oxygen species (ROS) by oxidative pathways. The close links between glycation and oxidation are supported by various studies, wherein autoxidation of glucose is essential to the non-enzymatic glycation of protein [9; 20]. Increasing concentrations of sugars proportionately lead to ROS levels, causing oxidative and carbonyl stress, resulting in increased rates of AGEs formation. Expression of receptor for AGEs (RAGE) is increased in some cells under conditions of inflammation and in patients with diabetes. The binding of AGEs to their respective receptors located on macrophages activates nuclear factor-\(\kappa\)B through p21 ras and mitogen-activated protein kinase pathway of signaling and induces oxidative stress [21; 22]. The effect of AGEs induced toxicities are difficult to reduce by simple lifestyle changes. Hence, adoption of preventive medicine is an ideal preventative strategy to combat damage caused by glycation. The side effects of long-term intake of synthetic medicinal compounds are usually greater as compared to natural products. Due to their therapeutic qualities, several plants and their products have been employed in the treatment of diseases [23]. Natural products, such as marine organisms, plants, microbes, animals, and have been utilized in traditional medicine to cure and relieve various ailments since ancient times [24]. The potential inhibition of AGEs through the use of natural products is both advisable and recommended. Synthetic inhibitors of glycation have been already discussed by many previous researchers. Various synthetic antiglycating compounds have been reported with the ability to inhibit the attachment of sugars with protein (e.g., inositol), inhibiting the last stage of glycation (e.g., aminoguanidine), cross-link breakers (e.g., N-henacylthiazolium bromide), inhibiting Amadori product (e.g., ethanol), and radical scavenging properties like amlodipine [2]. Antioxidants have also been identified as a way to protect cell organelles, organs, and tissues from oxidative stress and to avoid oxidative damage pathogenesis. Garlic and its various active components have been shown to play a vital role in illness management due to various health benefits (anti-inflammatory, antioxidant, anti-cancer, etc.) associated with regular consumption [25]. Some of garlic's anti-diabetic health-promoting properties include hyperinsulinemia, promotion of antioxidant levels, and catalase activity [26].