# Antihyperglycemic Potential of Mace Water Extract from _Myristica_ fragments [PERSON]
## 1 Introduction  
Diabetes mellitus (DM) is a chronic metabolic disease that can be recognized clinically by the presence of one or more typical symptoms such as polyuria, polydipsia, polyphagia, and weight loss that does not improve. Hyperglycemia, one of the abnormal glycemic conditions that is closely related to DM, is mainly caused by endocrine pancreatic cell deficiency and/or subsensitivity to insulin in target cells [1, 2]. Blood glucose, glycated hemoglobin (HbA1c), oral starch/glucose tolerance, and some other biochemical parameters can be used to evaluate glycemic status [1, 3]. Globally, DM is a disease that has a high prevalence and is expected to increase from year to year [4]. Therefore, effective glycemicstatus management and monitoring strategies and efforts are of great importance for public health [2].  
Traditionally, parts of plants have long been used as a source of medicine and have been widely studied regarding their effects on DM [1]. Their effects originate from the phytochemical compounds they contain and can be an alternative choice when synthetic antidiabetic agents cause undesirable side effects [5]. Nutmeg (_Myristica fragrans_ [PERSON]) is one of the plants that has been widely used in traditional medicine [6].  
Mace is the part of the nutmeg fruit (_Myristica fragrans_ [PERSON]) that covers the seed shell and is generally red when the fruit is ripe. The biological activities of mace include antioxidant, anti-inflammatory, anticancer, anti-cariogenic, hepatoprotective, and osteoblast proliferation-stimulating properties [7; 8]. The phytochemical compounds contained in mace include tannins, alkaloids, saponins, flavonoids, steroids/terpenoids, and quinones [9; 10]. Mace also contains some lignans and neoligans, which have many pharmacological activities [11]. This group of phytochemical compounds is thought to provide antidiabetic effects, as has been reported in several studies, especially through controlling blood glucose levels [12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25].  
A systematic review of the effects of nutmeg on the glycemic status of rats and mice found that mace has the potential to reduce blood glucose levels by more than 50% [3]. Giving ethyl alcohol extract of _Myristica fragrans_ mace (400 mg/kg BW) for 10 weeks to obese Wistar rats led to the reduction of blood glucose levels by up to 60.76% [26]. Research exploring the effects of mace on glycemic status is still limited. Only two articles were found that used mace, each extracted with methanol and ethanol [26; 27]. The use of organic solvents (including methanol) in the production of food products is generally limited due to safety considerations, while in vivo studies using water as a safer solvent for extracting mace are not yet available. In fact, the mace water extract (ME) in previous in vitro studies was proven to have antioxidant activity and act as an \(\alpha\)-amylase inhibitor (IC\({}_{50}\) DPPH RSA 2.79 \(\pm\) 0.05 mg total phenolics from extract/L; FRAP 9.16 \(\pm\) 0.86 g Trolox equivalent/100 g total phenolics from extract; IC\({}_{50}\)\(\alpha\)-amylase inhibition 360.18 \(\pm\) 6.83 mg total phenolics from extract/L) [28]. Therefore, an in vivo study on the antihyperglycemic effect of mace extract extracted using water needs to be carried out to confirm the possibility of applying mace extract to safer food products. This in vivo study was conducted to investigate the antihyperglycemic potential of ME. Oral starch and glucose tolerance tests, measurements of fasting blood glucose, glycated hemoglobin (HbA1c), body weight, water consumption, and relative weight of organs (pancreas, liver, and kidney) were carried out to evaluate the effect of ME on normal and streptozotocin-induced hyperglycemic Sprague Dawley rats.