42 Available Online at www.ijscia.com | Volume 3 | Issue 1 | Jan-Feb 2022 In Silico Analysis of Potential Nicotine Addiction Treatment by Cinnamomum verum Phytochemicals against nAChRα3 and nAChRα7 Zefo Kiyosi Wibowo 1 , Athaya Syahira Ramadhani 1 , Muhammad Auliya Rachman 1 , Siti Khaerunnisa 2* 1 Faculty of Medicine (60132), Universitas Airlangga, Surabaya, Indonesia 2 Department of Physiology and Medical Biochemistry, Faculty of Medicine (60132), Universitas Airlangga, Surabaya, Indonesia E-mail: zefo.kiyosi.wibowo-2018@fk.unair.ac.id; athaya.syahira.ramadhani-2018@fk.unair.ac.id; muhammad.auliya.rachman-2018@fk.unair.ac.id; st.khaerunnisa@fk.unair.ac.id *Corresponding author details: Siti Khaerunnisa; st.khaerunnisa@fk.unair.ac.id ABSTRACT Nicotine addiction has a direct effect on the occurrence of smoking-related diseases. The receptor that can increase absorption is the neuronal acetylcholine receptor alpha-3 (nAChRα3) and alpha-7 (nAChRα7). This in silico study was conducted to determine the effect of Cinnamomum verum to overcome nicotine addiction by inhibiting the target protein nAChRα3 and nAChRα7. Two hundred and eighty-one phytochemicals Cinnamomum verum were screened into nine ligands by Swiss Adme and PyRx. Molecular visualization and docking analyzes were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. The docking results showed that 2 of 9 ligands in 4zk4 and 6 of 9 ligands in 3sq9 had hydrogen bonds. Sesquiterpenes is the compound with the highest binding affinity in two proteins. However, in 4zk4, the highest affinity with H-bond is linalool. Phenols is the second ligand that effectively binds amino acids. Phytochemicals in Cinnamomum verum potentially reduce addiction to nicotine by inhibiting the receptor and improving the neuroinflammation due to nicotine. The sesquiterpenes is the primary ligand that binds to the 4zk4 and 3sq9. Keywords: in silico; Cinnamomum verum; nicotine addiction; nAChRα; sesquiterpenes INTRODUCTION Tobacco use has caused as many as 7 million deaths worldwide.[1] Indonesia is a country in Southeast Asia with the highest prevalence of smokers based on data from the Southeast Asia Tobacco Control Alliance (SEATCA) in 2018.[2] Based on data from the WHO, as many as 225,700 people died from smoking or other diseases related to smoking.[3] Smoking can cause several diseases such as heart disease, stroke, diabetes, and COPD and increase the risk of developing tuberculosis, eye diseases, and some diseases that attack the immune system.[4] Diseases related to smoking result from exposure to toxins in cigarettes; nicotine addiction directly influences smoking- related diseases.[5] The mechanism of action of nicotine is through three pathways, including ganglion transmission, nicotinic acetylcholine receptors (nAChRs) on chromaffin cells through catecholamines, the central nervous system nAChRs by stimulation.[6] The direct effects of nicotine use include irritation, burning sensation in the mouth and throat, increased saliva secretion, nausea and vomiting, stomach pain, and diarrhea.[7] Another effect of nicotine is driving cancer cell growth because it can trigger tumorigenesis by increasing cell proliferation, angiogenesis, and apoptotic pathways.[8] Nicotine is the primary substance that causes addiction in smokers. [6] Nicotine interacts with nicotinic acetylcholine receptors, which causes dopaminergic transmission, and causes an increase in mood and cognitive function. [6] One of the receptors that can increase absorption is the neuronal acetylcholine receptor alpha-3 (nAChRα3). The binding of nicotine initiates nicotine addiction to nAChRs. This interaction increases dopamine (DA) release in the mesolimbic and mesocortical dopaminergic circuits.[9] The nicotinic acetylcholine receptor is a ligand ion channel activated by acetylcholine and nicotine, which mediates synaptic transmission in the brain and various functions in the periphery. [10] Subtype 3 is well expressed in the habenula-interpeduncular midbrain pathway (aversion pathway). In the brain basal ganglia, a different regulatory variant characterized by rs1948 increases the expression of nAChRα3 mRNA (nAChRα3 enhancer), suggesting additional regulation in brain regions associated with nicotine dependence.[11] In addition, nAChRα3 is also expressed in the brainstem, cerebellum, spinal cord, substantia nigra, medial habenula, pineal gland, hippocampus, cortex, thalamus, ventral tegmental area, and interpeduncular nucleus.[9] Association of variants of the nAChRαx3 gene cluster usually with nAChRα5 and nAChRB4 due to various nicotine-related behaviors. This receptor has a role in increasing susceptibility to tobacco dependence, namely nicotine and smoking-related diseases, especially lung cancer.[12] Another receptor that plays a role in overcoming nicotine addiction is nAChRα7. The nAChRα7 receptor is associated with nicotine addiction therapy and is a receptor target for varenicline treatment. [13] International Journal of Scientific Advances ISSN: 2708-7972 Volume: 3 | Issue: 1 | Jan - Feb 2022 Available Online: www.ijscia.com DOI: 10.51542/ijscia.v3i1.5