Bioscience Evidence 2024, Vol.14, No.4, 184-194 http://bioscipublisher.com/index.php/be 188 Table 2 Target gene prediction No. Target Common name Uniprot ID Target Class 1 Alcohol dehydrogenase alpha chain ADH1A P07327 Oxidoreductase 2 Steroid 5-alpha-reductase 1 SRD5A1 P18405 Oxidoreductase 3 Alcohol dehydrogenase beta chain ADH1B P00325 Oxidoreductase 4 Alcohol dehydrogenase gamma chain ADH1C P00326 Oxidoreductase 5 Prostaglandin-endoperoxide synthase 1 PTGS1 P23219 Oxidoreductase 6 Peroxisome proliferator-activated receptor alpha PPARα Q07869 Nuclear receptor 7 Nuclear receptor subfamily 1 group H member 3 NR1H3 Q13133 Nuclear receptor 8 Vitamin D receptor VDR P11473 Nuclear receptor 9 Carbonic anhydrase II CA2 P00918 Lyase 10 Carbonic anhydrase I CA1 P00915 Lyase 11 Carbonic anhydrase IV CA4 P22748 Lyase 12 Alcohol dehydrogenase 4 ADH4 P08319 Enzyme 13 UDP-glucuronosyltransferase 2B7 UGT2B7 P16662 Enzyme 14 Cytochrome P450 19A1 CYP19A1 P11511 Cytochrome P450 15 Cannabinoid receptor 2 CNR2 P34972 Family A G protein-coupled receptor 16 Acetylcholinesterase ACHE P22303 Hydrolase 17 Cathepsin D CTSD P07339 Protease 18 Sex hormone binding globulin SHBG P04278 Secreted protein 19 Transient receptor potential cation channel subfamily V member 1 TRPV1 Q8NER1 Voltage-gated ion channel Among the proteins interacting with α-Campholenal, CTSD deficiency is associated with the pathogenesis of neuronal lipidosis and may be related to the mechanism of Alzheimer's disease (Siintola et al., 2006). The TRPV1 protein is the receptor for capsaicin, selectively activating sensory neurons that transmit nociceptive signals to the central nervous system, causing a burning sensation (Caterina et al., 1997). This indicates that CTSD and TRPV1, as targets of α-Campholenal in Cypress cone BVOCs, may participate in nerve signal transmission, thereby influencing central nervous system function. Among these interacting proteins, CNR2 and PPARα are particularly noteworthy as they interact with multiple BVOCs from Cypress shells, including α-Pinene and D-Limonene. CNR2 is involved in the central nervous system effects induced by cannabinoids, such as changes in mood and cognition (Onaivi et al., 2008; Ishiguro et al., 2010). It is hypothesized that multiple components of Cypress cone BVOCs, including α-Pinene, may interact with the CNR2 target protein, influencing central nervous system functions through the modulation of CNR2. PPARα is a member of the nuclear receptor superfamily involved in the expression of genes related to cell proliferation, differentiation, and immune and inflammatory responses (Tai et al., 2002). Modern clinical studies have found that patients with delayed sleep phase syndrome (DSPS) have significant difficulty falling asleep, and DSPS is associated with circadian clock gene polymorphisms and PPARα (Mezhnina et al., 2022). The interaction between multiple BVOCs from Cypress cone shells, including α-Pinene, and the PPARα target protein suggests that Cypress shells may alleviate insomnia symptoms by influencing circadian rhythm proteins. 2.4 Molecular interaction modeling of BVOCs and protein targets The binding site between a target and small molecule is the specific region where the two interact, often possessing a high degree of stereoconfiguration specificity, ensuring that the binding between the small molecule and target is specific and reversible. At the binding site, the small molecule interacts with the target through various forces, including electrostatic interactions, hydrogen bonds, and hydrophobic interactions, enabling specific recognition and binding of the target. The study illustrated the interaction models between α-Pinene, β-Caryophyllene, and the PPARα and CNR2 protein molecules (Figure 3), highlighting the significant amino acid residues surrounding the binding site. Six amino acid residues of the PPARα protein, Phe94, Phe106, Lys109, His95, Ile110, and Phe91, form hydrophobic
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