**1. Introduction**

Nowadays, incidences of metabolic syndrome-related diseases have rapidly increased all over the world, such as oxidative damage, diabetes, obesity, hypertension, and cardiovascular disease [1]. Food nutritionists have revealed that oxidative stress and high-calorie diets was closely related to the development of chronic disease [2]. To some extent, chemical drugs have good curative effect for relieving these chronic diseases, but they may also bring seriously side effects and drug dependence to the human body. Polyphenolics, as one of the ubiquitous secondary metabolites

in plants, have been proven to possess important physiological functions including anti-oxidant, anti-diabetes, anti-inflammatory, anti-carcinogenic, anti-obesity, and anti-proliferative activities [3,4]. Currently, many scientists have pointed out that phytochemicals (especially phenolics and flavonoids, etc.) from the plant-based foods may be used as natural antioxidants, which can inhibit oxidative damage. Moreover, long-term intake of plant-based foods enriched in polyphenolics compounds is conducive to prevent the occurrence of chronic diseases caused by oxidative stress [5,6].

Raspberry (*Rubus idaeus* L.) belongs to the *Rosaceae* family, which is widely cultivated in Asia, Europe, and North America [7]. Fruits of raspberry are widely consumed as fresh fruits, functional beverages, and fermented wine due to its attractive color, delicious taste, and excellent nutritional properties (enriched in anti-oxidative phenolics) [8]. The leaves of raspberry have also received considerable attention for its human health benefits including anti-oxidant, anti-diabetes, and anti-inflammatory activities, and have been made into tea product and its consumption has been also increasing [9–11]. Raspberry seeds are also good raw materials for food industries, but there is little research focused on the its phyto-constituents and bio-activities [12]. Qin et al. (2018) have reported that raspberry fruits and seeds include large amounts of anti-oxidative bound phenolics. During in vitro digestion, the released bound phenolics (non-extractable) possessed antioxidant activities and the inhibitory effect of α-glucosidase [13]. Moreover, different extraction methods for releasing the non-extractable phenolics in the leaves and seeds of raspberry have been investigated in our previous work [14]. To the best of our knowledge, the characterization and bio-activities (especially their antioxidant activities and the inhibitory properties on digestive enzymes) of phenolic extracts in different parts of raspberry have not been compared and investigated systematically.

The aim of the present work was to systematically investigate the phenolic profiles and in vitro antioxidant activities of leaves, fruit pulp, and seeds extracts of raspberry. Meanwhile, the inhibitory effects against digestive enzymes (α-glucosidase and α-amylase) were also evaluated. Importantly, the inhibition mechanisms of the main phenolic molecules toward digestive enzymes were investigated by molecular docking analysis. This work may supply important evidence for the comprehensive utilization of raspberry in food industries.

#### **2. Materials and Methods**

#### *2.1. Chemicals and Reagents*

The Folin–Ciocalteu phenol reagen<sup>t</sup> and chemicals used for the antioxidant activity assay were purchased from Aladdin Industrial Corporation (Shanghai, China). Phenolic standards, trolox, *p*-Nitrophenyl-α-D-glucopyranoside (*p*-NPG, > 99.8%), porcine pancreatic α-amylase (13 U/mg), and α-glucosidase (≥ 58 U/mg solid) from *Saccharomyces cerevisiae* were all purchased from Sigma-Aldrich (St. Louis, MO, USA). Analytical-grade materials were purchased from Guangzhou Reagent Co. (Guangzhou, China). Formic acid and acetonitrile used for the HPLC analysis were of chromatography grade. Water was purified by the Milli-Q (Millipore, MA, USA) system and filtered through membranes with a pore size of 0.22 μm before use.
