Scutellariae Radix (SR), the dried root of Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine, has been widely applied for the treatment of fever, ulcer and bronchitis symptoms for thousands of years [1]. Modern researches have revealed that the therapeutic efficacy of SR is predominantly attributed to a serious of flavonoids, such as baicalein, wogonin and baicalin [2]. These compounds possess a remarkable spectrum of bioactivities including antitumor [3], anti-inflammatory, antiviral [4], neuroprotection and regulating immunity [5]. Baicalin, a signature flavonoid primarily present in SR, could suppress adipose tissue inflammation to mitigate insulin resistance in obesity [6]. Additionally, baicalin, has been recognized as the quality control marker as mandated by the Chinese Pharmacopoeia (2020 edition) [7]. Therefore, the establishment of a simple and efficient method for extracting and quantifying these bioactive compounds is particularly crucial for the clinical application and quality control of SR.

At present, there are numerous methods such as heating reflux, maceration, ultrasonic extraction and steam distillation for extracting active components from SR [[8], [9]–10]. However, these traditional extraction techniques restrict their popularity and pose environmental and health risks because of time-consuming, low efficiency and the use of toxic organic solvents [11,12]. Therefore, there is an increasingly urgent need to develop an efficient and sustainable extraction method for the extraction of bioactive components in SR.

Matrix solid-phase dispersion (MSPD) as a universal and efficient technique for sample pretreatment could be applied to the extraction of analytes from a variety of solid samples [13]. This method integrates the homogenization and extraction processes into a single step, which could increase the efficiency of isolating target analytes, as well as reduce the usage of extraction solvents [14]. It has been widely applied in sample preparation in numerous fields as natural products, food, biological analysis [15,16]. Molecular sieve is an aluminosilicate material with highly regular pore structure [17]. Its characteristic structure endows molecular sieve with large specific surface areas and excellent adsorption capacity. Moreover, the advantages of adjustable polarity, good hydrothermal stability and thermal stability make molecular sieve have broad application prospects in the fields of adsorption separation, industrial catalysis, biomass conversion and fuel cells [[18], [19], [20]–21].

With the rise of the concept of green chemistry, more efficient approaches applying the sustainable and safer extraction solvents have been proposed, such as deep eutectic solvents (DESs) [22], ionic liquids (ILs) [23]and biomass-derived solvents [24]. The utilization of green extraction solvents will be conductive to the elimination of toxic substances and volatile organic solvents. Notably, as a novel class of green solvents, DESs have been extensively applied in natural product extraction [25], sustainable catalysis [26], detection of pollutants [27], and electrochemistry [28] due to their low toxicity, recycling possibility and thermal stability. DESs are green solvent systems formed by eutectic mixtures of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs), typically derived from natural metabolites to ensure low environmental impact [29,30]. Generally, this stable deep eutectic mixture can be produced from the self-association of HBD and HBA under the condition of continuous heating [31]. Hydrogen bonding and van der Walls interactions are the main driving force of this process [32]. Changing the combination of HBD and HBA could customize the chemical and physical properties of this sustainable solvent [33]. Recently, classical computer simulation methods were applied for interpreting the interaction mechanism of DES and helping create better DES, including density functional theory (DFT) [34], electrostatic potential (ESP) distributions [35] and machine learning [36]. These techniques could guide eco-friendly solvent designs, reducing lab experiments while improving extraction efficiency for bioactive components [37,38].

Deep eutectic solvents-based ultrasound-assisted matrix solid phase dispersion (DES-UAMSPD) is a novel green microextraction technique that synergistically combines the sustainable properties of DES, the efficient dispersion capability of MSPD, and the enhanced mass transfer effect facilitated by ultrasound-assisted technology [39,40]. In this study, an efficient and sustainable extraction method of computer aided analysis combined with DES-UAMSPD was proposed to extract five flavonoids in SR (Fig. 1). The mechanism of DES synthesis and analytes extraction process with DES was elucidated through ESP, DFT and Independent Gradient Model based on Hirshfeld partition (IGMH). To demonstrate the sustainable and green characteristics of the developed procedure, the Analytical Eco-Scale (AES) and Green Analytical Procedure Index (GAPI) evaluation were conducted. This work applies a synergistic strategy that bridges computer aided mechanism elucidation with experimental optimization, establishing a sustainable extraction procedure for natural bioactive compounds through reasonable integration of DES system and microextraction. This study provides new insights for designing sustainable extraction protocols of bioactive components.