The Baihu decoction is made from Anemarrhena asphodeloides, Glycyrrhizae, Japonica rice, and Gypsum. Lv ^[1][38] used high-speed centrifugation and dialysis technology for the phase splitting of the Baihu decoction. Then, they used HPLC to determine the contents of the effective ingredients in the Baihu decoction in different phases. The results showed that the main components of each phase of the Baihu decoction were basically the same, and the content of active ingredients in the nanophase was significantly higher than that in the other phases. Therefore, it is speculated that the supramolecules in the nanophase of the Baihu decoction have a solubilizing effect on the main antipyretic components. In order to study the mechanism of the formation of the supramolecules in the Baihu decoction, particle size, salinity, conductivity, surface tension, TEM, and fingerprint of the supramolecules were measured. Based on the results, it is speculated that the four traditional Chinese medicines in the Baihu decoction all played important roles in the formation of the supramolecules. The macromolecules, such as proteins and polysaccharides, produced by the boiling of Japonica rice form particles with pores that can serve as the main structure of the supramolecules, allowing the chemical components in the decoction to be embedded. Anemarrhena asphodeloides contain many antipyretic-related medicinal ingredients, such as neomangiferin and mangiferin, which are poorly water-soluble. Gypsum contains many inorganic ions. On the one hand, Fe²⁺ and Fe³⁺ form iron oxides or iron hydroxides with high surface energy that can serve as the central cores of supramolecules. The insoluble components attracting by cores are highly enriched at the periphery of the core, thereby exerting a solubilization effect. On the other hand, Ca²⁺, Mg²⁺, and Zn²⁺ act as zeta-potential regulators that are adsorbed in the supramolecules to regulate the stability of the structure. There are many saponins in Glycyrrhizae, such as glycyrrhizic acid and glycyrrhetinic acid, which are important surface-active substances that can improve the solubility of mangiferin and neomangiferin and regulate the stability of the supramolecules ^[2][3][19,39]. An efficacy test showed that the antipyretic effect on rabbits and the effect of reducing the level of inflammatory factors in the serum were better for supramolecules than for the components in true-solution phase because of supramolecules was easily ingested by cells and targeted the brain and lungs, indicating that the supramolecules are key to the antipyretic mechanism of the Baihu decoction ^[4][40].

The Huanglian Jiedu decoction is composed of four commonly used medicinal herbs, namely, Coptidis Rhizoma, Radix Scutellariae, Phellodendri Cortex, and Gardeniae Fructus. There was obvious precipitation in the decoction, and the precipitation rate reached 7.13% ^[5][41]. Fang ^[6][42] used the HPLC method to determine the precipitation components of the Huanglian Jiedu decoction and found that 81% of the precipitation was organic acids and alkaloids, of which baicalin accounted for 42.12% and berberine accounted for 31.17%. This study revealed that the compound precipitation from the Huanglian Jiedu decoction was mainly composed of an acid–alkali complex. Baicalin is acidic due to the presence of carboxyl groups in its structure, and it is prone to precipitation reactions with alkaloids such as berberine. Therefore, from the perspective of molecular thermodynamics, all the sources of precipitation, parameters of interaction, and binding abilities of different medical combinations during the formation of the precipitate in the Huanglian Jiedu decoction were explored. The original decomposed-recipe experiment indicated that the combinations that could produce obvious precipitates when they were mixed were Scutellariae Radix–Coptidis Rhizoma and Scutellariae Radix–Phellodendri Chinensis Cortex. The amount of precipitation for the Scutellariae Radix–Coptidis Rhizoma was the highest. Then, isothermal titration calorimetry (ITC) was used to determine the binding heat and thermodynamic parameters of the binding reactions, and the results show that the precipitation-formation process is a chemical reaction that drives the non-covalent bonding of enthalpy, rather than a simple physical aggregation and adsorption precipitation. Therefore, it is believed that the precipitate in the Huanglian Jiedu decoction is formed by self-assembly ^[7][43]. The compositions of both the supernatant and naturally supramolecules of the Huanglian Jiedu decoction were further analyzed by UHPLC–Q–Orbitrap HRMS. The results showed that the compositions of the supernatant and the supramolecules were the same. Due to the self-assembly complexation, the supramolecule’s content of baicalin and berberine was significantly higher than that of the supernatant ^[8][44]. Based on these studies, Zhang ^[9][14] used baicalin and berberine to synthesize and form the precipitate in the Huanglian Jiedu decoction and found that baicalin and berberine formed complex molecules at a molar ratio of 1:1 through electrostatic attraction. From the basic unit, further assembly forms the supramolecules in the Huanglian Jiedu decoction. Cobalt chloride was used to induce PC12 cells to establish a nerve-injury model. The supramolecular precipitate in the Huanglian Jiedu decoction and the simulated synthetic baicalin–berberine supramolecules showed good protective effects.

The Gegen Qinlian decoction is composed of four traditional Chinese medicines: Pueraria lobata, Scutellaria baicalensis, Coptis chinensis, and Glycyrrhizae. The changes in the content of active ingredients before and after the formulation of the Gegen Qinlian decoction was determined by HPLC. The results showed that, when Pueraria lobata was decoctioned with Coptis chinensis and Scutellaria baicalensis, respectively, it could solubilize berberine, palmatine, baicalein, and wogonin. Among them, the reason Puerariae promotes the dissolution of baicalein and wogonin may be the formation of molecular complexes ^[10][45]. Hu ^[11][21] found that puerarin, daidzein, and daidzein are the main components of supramolecules in the Gegen Qinlian decoction and have good activity in vitro. Guo ^[12][46] used ultrafiltration centrifuge tubes to filter the Gegen Qinlian decoction. After intercepting most of the supramolecule particles, the ingredients in the decoction were tested. The results showed that the contents of several main active ingredients in the decoction were reduced to varying degrees after ultrafiltration. This shows that the supramolecules in the decoction are an important substance that exerts medicinal effect. Experiments by Lin also proved this point. The supramolecules showed stronger activities than the supernatant on many tests. In vivo experiments showed that the supramolecules of the Gegen Qinlian decoction showed a stronger hypoglycemic effect. In vitro experiments showed that the supramolecules in the decoction had stronger antioxidant effects, better protective effects on cells, and were basically non-toxic. High absorption rates of baicalin indicated that the supramolecules changes pharmacokinetics of Gegen Qinlian decoction and improves the bioavailability of insoluble phytochemicals, like baicalin, may be essential for the synergistic actions in the herbal decoction. It showed that the supramolecules in the Gegen Qinlian decoction had a better medicinal effect ^[13][20]. When investigating the protein self-assembly behavior during the Gegen Qinlian decoction, Lin separated Pueraria protein and Coptis protein and found that the two proteins could form supramolecules under simulated decoction conditions. The experimental results showed that the efficiency of Pueraria protein encapsulated puerarin was 33.88%, and the efficiency of Coptis protein encapsulated berberine hydrochloride was 44.2% ^[14][47].

The Maxing Shigan decoction is a classic prescription consisting of Ephedra, Radix Glycyrrhizae, Semen Armeniacae Amarum, and Gypsum. Studies have found that the chemical components of the Maxing Shigan decoction intertwine to form a new physical phase during the decoction process, which leads to the heterogeneous distribution of the ingredients of the decoction. Pharmacodynamic experiments showed that the supramolecular structure of the Maxing Shigan decoction has good antibacterial activity, and the composition test showed that the supramolecules contain organic active small molecules such as ephedrine; amygdalin and glycyrrhizic acid; Ca, K, and Mg; and other inorganic ingredients ^[15][34]. Research by Zhou showed that ephedrine (99.7%) and pseudoephedrine (95.5%) in the Maxing Shigan decoction are mainly present in supramolecules. It is speculated that amphiphilic molecules, such as ephedrine and pseudoephedrine, are adsorbed on the supramolecules through hydrogen bonding, electrostatic interactions, and van der Waals attraction ^[16][22]. Du ^[17][48] compared the in vitro change in antiviral activity in the Maxing Shigan decoction, determined by the MTT method, before and after filtration with a 0.45 μm cellulose acetate film. The results showed that the antiviral activity of the decoction was significantly reduced after filtration. The reason is that a large number of supramolecules are removed by filtration, which proves that the anti-influenza-virus activity of the Maxing Shigan decoction is related to its supramolecules.

The Siwu decoction is composed of Rehmannia glutinosa, Angelica sinensis, Paeonia lactiflora, and Ligusticum chuanxiong. Zhang used differential centrifugation to obtain supramolecules with a particle size distribution of 100–1000 nm in the Siwu Decoction. Assays showed that the supramolecules contained a large amount of protein and polysaccharides and a small amount of DNA. Pharmacological studies showed that heme synthesis, degradation, and protein binding were closely related with the supramolecules, and it had regeneration-promoting effects on the damage of hematopoietic function. Therefore, it is speculated that supramolecules greatly contribute to the medicinal effect of the Siwu Decoction ^[18][23].

The Shaoyao Gancao decoction is composed of two traditional Chinese medicines: Paeoniae Radix and Glycyrrhizae Radix. The main active components of the monarch medicine Paeoniae Radix are monoterpene glycosides. These glycosides are more polar and difficult to absorb in the gastrointestinal tract. However, when it is combined with Glycyrrhizae Radix, the absorption efficiency for the active ingredients of Paeoniae Radix is effectively improved ^[19][49]. Particle-size analysis and morphological observation showed that there were supramolecules with a particle size of approximately 200 nm in the Shaoyao Gancao decoction, and the supramolecules were irregularly spherical under TEM observation. The experimental results showed that the supramolecules in the Shaoyao Gancao decoction could effectively encapsulate the active ingredients in Paeoniae Radix. After entering the body, it not only exerts a sustained release effect but also improves the absorption efficiency for the drug in the ileum ^[20][24]. Shen prepared paeoniflorin-loaded glycyrrhizic acid supramolecules using the ultrasonic dispersion method to improve the oral absorption of paeoniflorin. The in vivo pharmacokinetics showed that the C_max and AUC0–t values of paeoniflorin encapsulated by supramolecules formed by glycyrrhizic acid were approximately 2.18 and 3.64 times higher than those of paeoniflorin in solution ^[21][50].

Aconiti Laterdis and Glycyrrhizae Radix, a classic medicinal combination, can reduce the toxicity and increase the effects after compatibility, but the mechanism is not yet clear. In analyzing the differences in the physicochemical properties of the Aconiti Laterdis and Glycyrrhizae Radix decoction before and after combination, Chen found that the particle size of the combined decoction was larger than that of the single decoction. Therefore, it is speculated that the supramolecules produced by the combined decoction may be the material basis for synergism and detoxification after compatibility ^[22][51]. Then, they used HPLC–MS to identify 36 components from the supramolecules in the combined decoction, among which there were 11 compounds from Glycyrrhizae Radix and 25 compounds from Aconiti Laterdis. According to these confirmed compounds, the alkaloid compounds in the combined decoction were significantly different from those of the single decoction. This shows that there were some changes in the alkaloid compounds in the decoction after the combination of Glycyrrhizae Radix ^[23][52]. The contents of six ester alkaloids in the supramolecules formed before and after compatibility were compared simultaneously using the HPLC–TOF–MS method, and the supramolecular changes were identified using FTIR and second-derivative spectra. The results showed that, in the process of co-decocting, a large number of ester alkaloids in Aconiti Laterdis combined with the components in Glycyrrhizae Radix to form a supramolecule. It is speculated that the mechanism may be the association between the tertiary amine N in the alkaloid and the carboxyl in the glycyrrhizic acid ^[24][53]. Zhang ^[25][54] investigated the intestinal absorption and pharmacokinetic characteristics of the three diester-types diterpene alkaloids in the supramolecules of the co-decoction. The results showed that the diester-type diterpene in the supramolecules prevents dose dumping and prolongs the average residence time, thereby effectively reducing the toxicity of aconite after oral administration.

Apart from acid–base neutralization, studies have shown that glycyrrhizae protein is also an entry point to clarifying the mechanism of reducing toxicity. Rao ^[26][27][25,55] found that glycyrrhizae protein could be separated by anion-exchange chromatography. When the pH was 5, the glycyrrhizae protein could form supramolecules with a stable particle size with aconitine, and the embedding rate was 28.22%. Acute toxicity experiments in mice showed that glycyrrhizae protein attenuated the toxicity after embedding aconitine.

Glycyrrhizae Radix–Coptis Chinensis has a wide range of clinical applications, but the drug pair produces a large amount of self甘草科板蓝根-precipitation when co黄芩具有广泛的临床应用，但该药物对在共煮沸时会产生大量的自沉淀。在研究甘草-decocted. When studying the supramolecules of the co-decocting of Glycyrrhizae Radix–Coptis Chinensis, it was found that the components in the supramolecules of the combined decoction were significantly different from those of the single decoctions, and the combined decoction contained more active ingredients ^[28]. 黄芩共煎的超分子时发现，联合煎剂的超分子成分与单一煎剂的超分子有显著差异，并且联合煎剂含有更多的活性成分[56]。Zhao ^[29] used [57]使用HPLC to detect the components in the supramolecular precipitate检测超分子沉淀物中的组分; the results showed that it was mainly small molecules such as glycyrrhizic acid and berberine. The investigation of the solubility of supramolecular precipitates in digestive conditions showed that the supramolecules formed by the compatibility of Glycyrrhizae Radix and Coptis Chinensis allowed for the slow release of berberine. The formed supramolecules not only ensure the therapeutic effect of berberine but also prevent the side effects of Coptis Chinensis inhibiting yang, damaging the spleen and stomach, confirming the rationality of the compatibility law for Glycyrrhizae Radix and Coptis Chinensis. 结果表明，它主要是小分子，如甘草酸和小檗碱。对超分子沉淀物在消化条件下的溶解度的研究表明，由甘草板蓝根和黄连的相容性形成的超分子允许小檗碱的缓慢释放。所形成的超分子不仅保证了小檗碱的治疗效果，而且防止了黄连抑制阳气、损害脾胃的副作用，证实了甘草和黄连相容规律的合理性。Li ^[30] found that Glycyrrhizae Radix crude protein and berberine could form spherical supramolecular particles under the induction of weak bonds, such as electrostatic attractions and hydrophobic interactions, after co[26]发现甘草根粗蛋白和小檗碱在共煎煮后，在弱键的诱导下，如静电吸引力和疏水相互作用，可以形成球形超分子颗粒。超分子的抗菌活性明显优于小檗碱和机械混合物。甘草蛋白表面的氨基酸残基可以使自身吸附在金黄色葡萄球菌上。因此，甘草素蛋白-decoction. The antibacterial activity of the supramolecules is significantly better than that of berberine and mechanical mixtures. The amino acid residues on the surface of glycyrrhizae protein could make itself adsorbed on Staphylococcus aureus. Therefore, glycyrrhizae protein–berberine supramolecules may adhere to the bacterial surface after interacting with bacteria, and the supramolecules continuously release berberine, which increases the concentration of berberine around the bacteria and increases the uptake, resulting in a stronger antibacterial effect. These experiments indicating that the interaction between glycyrrhizae protein and berberine during the heating process promotes a better effect of the medicinal ingredients.小檗碱超分子在与细菌相互作用后可能粘附在细菌表面，超分子不断释放小檗碱，从而增加细菌周围小檗碱的浓度并增加摄取，从而产生更强的抗菌作用。这些实验表明，甘草素蛋白和小檗碱在加热过程中的相互作用促进了药用成分的更好效果。

Isatis indigotica Fort is one of the few Chinese medicines with good antiviral effects. 堡垒是为数不多的具有良好抗病毒作用的中药之一。Lin ^[31] tracked and compared the changes in the components of [27]跟踪并比较了灌煮前后Isatis indigotica before and after decoction and found that spherical polymers formed during the boiling process. 组分的变化，发现在煮沸过程中形成了球形聚合物。超分子是由煎剂中固有的天然成分（如蛋白质，糖，氨基酸和脂肪酸）通过自组装形成的。The supramolecules were formed by the inherent natural components in the decoction, such as proteins, sugars, amino acids, and fatty acids, through self-assembly. The characterization results from TEM and laser particle size analysis showed that the supramolecules were composed of a series of particles of different sizes. Further research has shown that the EM和激光粒径分析的表征结果表明， 超分子由一系列不同尺寸的颗粒组成.进一步的研究表明，靛蓝靛雳煮沸过程中缓冲液的pH of the buffer during the boiling of Isatis indigotica determines the 值决定了超分子的pH res响应，这种ponse of the supramolecules, and this pH response is microscopically manifested as the aggregation and dispersion of the supramolecules. Among them, the H响应在显微镜下表现为超分子的聚集和分散。其中，当pH值接近中性时，Banlangen decoction shows the lowest light-scattering intensity when the pH is close to neutral, and the light-scattering intensity increases under acid and alkali conditions, indicating that the particles of supramolecules become larger. Experiments show that the supramolecules of different forms have different antiviral effects. He ^[32] used gel chromatography to separate and purify the supramolecules in the 煎剂表现出最低的光散射强度，并且在酸碱条件下光散射强度增加，表明超分子的颗粒变大。实验表明，不同形式的超分子具有不同的抗病毒作用。他[58]使用凝胶色谱法分离和纯化Banlangen decoction and found that this su煎剂中的超分子，发现这种超分子不仅表现出pramolecule shows not only pH responsiveness but also temperature responsiveness. Zhou ^[33] identified two constitutive glycosylated proteins from supramolecules in the H响应性，还表现出温度响应性。Zhou[59]在Banlangen decoction. The 煎剂中鉴定出两种来自超分子的组成性糖基化蛋白。N-terminal amino acid sequences are V–X–R–E–V–V–K–D–I and V–V–R–E–V–V–K–D–I–A–G–A–V–Q–T–N–E–Q–Y. In order to clarify the structure, cDNA cloning and glycosylation–site analysis were carried out. The primary-structure comparison showed that the two glycosylated proteins have high homology, representing allelic variants of the same gene. Based on this, they obtained the highly homologous amino acid sequence of the non-glycosylated protein. Furthermore, they used pepsin hydrolysis and MS to identify four possible glycosylation adducts in the supramolecules. From these studies, it could be observed that the supramolecules isolated from the 端氨基酸序列是V-X-R-E-V-V-K-D-I和V-V-R-E-V-V-K-D-I-A-G-A-V-Q-T-N-E-Q-Y。为了澄清结构，进行了cDNA克隆和糖基化位点分析。一级结构比较表明，两种糖基化蛋白具有高同源性，代表同一基因的等位基因变异。基于此，他们获得了非糖基化蛋白的高度同源氨基酸序列。此外，他们使用胃蛋白酶水解和MS来鉴定超分子中四种可能的糖基化加合物。从这些研究中可以观察到，从Banlangen decoction were a smart nanocomponent composed of a boiling-stable protein, which was pH responsive and temperature responsive, and could be used as a prototype in the future to develop a smart, safe, and stable drug-delivery vehicle.煎剂中分离出的超分子是由沸腾稳定蛋白组成的智能纳米组分，其pH响应性和温度响应性，并且可以在未来用作原型，以开发智能，安全，稳定的药物输送载体。

Cai ^[34] separated the supramolecules in the Taizishen decoction by gel-filtration chromatography and analyzed their immune activity. They found that the isolated supramolecules could stimulate the proliferation of mouse spleen cells and promote the secretion of the immune factors 蔡[28]通过凝胶过滤色谱法分离了太子神煎剂中的超分子，并分析了它们的免疫活性。他们发现分离的超分子可以刺激小鼠脾细胞的增殖，并促进免疫因子IL–-10, IL–13, TNF–α, and IFN–γ. This proved that the supermolecule is the main medicinal ingredient of the Taizishen decoction. Weng ^[35] obtained the crude protein from the Taizishen decoction using ammonium sulfate sedimentation technology. After heating at ，IL-13，TNF-α和IFN-γ的分泌。这证明，超分子是太子神汤的主要药用成分。翁[60]利用硫酸铵沉降技术从太子神煎煮中获得粗蛋白。在100 °C for 下加热30 min and adjusting the pH to 5.70, supramolecules with a particle size of approximately 70 nm were obtained, which could effectively improve the solubility of curcumin.并将pH调节至5.70后，得到粒径约为70 nm的超分子，可有效提高姜黄素的溶解度。