###### Abstract  
In this study, chemical components, \(\alpha\)-glucosidasea inhibitory activities, and molecular modelling studies of the essential oil extracted from the _Cleistocalyx operulatus_ leaves were investigated. In total, thirty compounds were identified using GC/MS, representing 98.3% of the oil. Of these, the two most dominant constituents of the essential oil were determined as (\(Z\))-\(\beta\)-ocimene (30.4%) and allo-ocimene (31.6%). The \(\alpha\)-glucosidase inhibitory experiments indicated that the essential oil exhibited potent \(\alpha\)-glucosidase inhibitory activities, with IC\({}_{50}\) values of 61.82 \(\pm\) 3.91 \(\upmu\)g/mL. For further investigation into inhibitory mechanisms, molecular docking simulations were performed to investigate structural interactions between two dominant constituents and the \(\alpha\)-glucosidase protein. The simulation revealed that allo-ocimene (31.6%) and (\(Z\))-\(\beta\)-ocimene (30.4%) have protein binding affinities of \(-\)5.358 and \(-\)5.330 kcal/mol, respectively. Moreover, molecular dynamic simulation indicated that the complexes of two compounds and the target protein were stable over 100 ns. Overall, these findings suggest that the essential oil of _C. operulatus_ leaves could be a natural source of potential \(\alpha\)-glucosidase inhibitors.  
Cleistocalyx operulatus; essential oil; \(\alpha\)-glucosidasea; molecular docking; molecular dynamic simulation +
Footnote †: journal: _Sci._  
0000-0002-0001-999X/0000-0002-0  
diabetes type 2 by delaying the absorption of glucose from carbohydrates [5]. This delay helps prevent rapid spikes in blood sugar after meals, aiding in the management of blood glucose levels [5].  
Inhibitors of \(\alpha\)-glucosidase are compounds utilized to block or decrease the activity of the enzyme. They find applications in the treatment of conditions like type 2 diabetes, and serve as potential targets for drug design [6]. \(\alpha\)-glucosidase inhibitors can bind to the enzyme's active site either competitively or non-competitively, thereby preventing the substrate from binding or interfering with the catalytic mechanism [3]. Well-known inhibitors of \(\alpha\)-glucosidase include acarbose, miglitol, and voglibose [7]. These inhibitors exhibit structural similarity to carbohydrates, enabling them to mimic the binding of carbohydrates to the active site. Understanding the mechanism, active site characteristics, and inhibitors of \(\alpha\)-glucosidase provides valuable insights for the development of therapeutic strategies aimed at regulating carbohydrate metabolism and effectively managing conditions such as diabetes.  
_Cleistocalyx operculatus_ (Roxb.[PERSON] (synonym: _Syzygium nervousum_), also known as \"Voi\" in Vietnamese, has been used in Vietnamese traditional medicine to treat a variety of ailments, such as bloating, diarrhea, acne, chronic colitis, and dysentery. In addition, this plant's extracts and some isolated compounds demonstrated anti-diabetic, anti-obesity, anti-oxidant, anti-viral, anti-inflammatory, anti-microbial, neuroprotective, and cytotoxic activities [8]. Additionally, recent research has shown that the essential oil from the leaves or buds of _C. operculatus_ has anti-inflammatory, anti-microbial, anti-oxidant, and cytotoxic activities [9; 10; 11; 12]. As a part of our studies on the anti-diabetic effect of essential oil from herbs in Vietnam, we report herein the \(\alpha\)-glucosidase enzyme inhibition of the essential oil of _C. operculatus_ growing in Thua Thien Hue, Vietnam. This is the first report of the anti-diabetic activity of _C. operculatus_ leaf essential oil.