Mechanisms of Salvia miltiorrhiza Health Products in Blood Lipid Management: Insights from Data Mining, Network Pharmacology, and Molecular Docking

Abstract

Background: This work aims to systematically investigate the formulation rules and potential mechanisms of Salviae Miltiorrhizae Radix et Rhizoma (SM)-containing health products to support healthy blood lipid levels.

Materials and methods: Data on SM-containing health products were retrieved from official databases. Formulation patterns were analyzed using frequency statistics and association rule mining. An integrated network pharmacology strategy was then used to explore potential regulatory mechanisms, including active compound screening, target prediction, protein–protein interaction (PPI) network construction, and functional enrichment analysis. Results were further validated using molecular docking.

Results: A total of 477 approved products were analyzed, with “helping maintain blood lipid levels” as the primary health function claim. These products contained 160 compatible medicinal herbs, which are mainly mild-cold in nature and sweet in flavor. They are commonly used for “deficiency tonification” and “blood-activating and stasis-resolving” in traditional Chinese medicine (TCM). A total of 267 compounds and 181 key targets were identified for the lipid-regulating function of SM. These targets were enriched in peroxisome proliferator-activated receptor (PPAR) signaling, Lipid and Atherosclerosis, and the Regulation of Lipolysis in adipocytes. Eight targets, including AKT1 and peroxisome proliferator-activated receptor gamma (PPARG), were identified as core targets. Finally, molecular docking results suggested potential binding affinities between primary active components and core targets.

Conclusion: This study demonstrated that SM exerts its lipid-regulating effects via multi-component, multi-target, and multi-pathway mechanisms. These findings provided a theoretical basis for the rational development and application of relevant health products.

Graphical abstract

Keywords

Salviae Miltiorrhizae Radix et Rhizoma / health products / data mining / network pharmacology / blood lipid

Introduction

Dyslipidemia is a major modifiable risk factor for cardiovascular diseases, posing a significant global public health challenge. In recent years, dietary patterns and lifestyles have driven a sharp rise in metabolic disorders, affecting 35.6% of Chinese adults[1]. Although conventional lipid-lowering agents are effective, there is a growing demand for safe, long-term preventive options. Accordingly, natural nutraceuticals, particularly those from traditional medicine, have gained attention for their safety, multi-target properties, and homeostatic benefits. In this context, Salvia miltiorrhiza Bge. (Lamiaceae), commonly known as Danshen (Salviae Miltiorrhizae Radix et Rhizoma, SM), has emerged as a promising candidate. In traditional Chinese medicine (TCM), SM has a bitter taste and slightly cold nature, and acts on the heart and liver meridians, promotes blood circulation and resolves blood stasis, and alleviates chest impediment and cardiac pain[2]. Phytochemical investigations have identified liposoluble tanshinones (e.g., tanshinone IIA, cryptotanshinone) and water-soluble salvianolic acids (e.g., salvianolic acid B) as the primary components[3–6]. These compounds exhibit cardiovascular protective, anti-inflammatory, and antioxidant effects[7–10].

Since its official approval for use in Chinese health foods in 2002[11], SM has been widely incorporated into commercial formulations for lipid management. Despite its extensive market applications, two critical knowledge gaps persist in the research on SM-containing health products. First, formulation principles are poorly defined; no systematic analysis has yet elucidated compatibility rules or core herbal combinations. Second, potential underlying mechanisms for lipid-regulating efficacy remain unclear. Existing evidence mostly derives from fragmented pharmacological reports, lacking an integrated analysis of multi-component, multi-target networks driving these effects.

Therefore, this study aims to decode the formulation logic of SM-containing health products and map their regulatory networks for lipid metabolism. Specifically, we seek to identify the formulation rules and core herb pairings in approved SM-containing products and to elucidate the multi-target biological mechanisms, focusing on how potential active components interact with related targets in lipid homeostasis. By linking market application patterns to molecular networks, this study establishes a scientific rationale for SM-based lipid management, offering a theoretical foundation for product optimization and application.

Materials and methods

Data sources

A systematic search for registered SM-containing health products was conducted using the Special Food Information Query Platform of the State Administration for Market Regulation and Yaozhi Network. The search terms included “Salviae Miltiorrhizae Radix et Rhizoma” and its common name “Danshen”, covering all records up to August 21, 2025.

Inclusion and exclusion criteria

Included products met both the following requirements: (1) claiming approved health functions under the non-nutritional supplement categories specified in the official “List of Health Functions Permitted for Declaration of Health Food (2023 Edition)”[12]; and (2) having their raw-material compositions explicitly documented. Duplicate records were merged into a single entry. Records related to license renewals, product modifications, or failure to satisfy the inclusion criteria were excluded.

Data standardization

Data were standardized according to the following guidelines: (1) Health function. Claims were standardized according to the official 2023 health function list. For example, “auxiliary lipid-lowering” and “lipid regulation” were standardized as “help to maintain healthy blood lipid (cholesterol/triglyceride) levels”; “enhancing immunity” and “immune regulation” were standardized as “help to enhance immunity”. (2) TCM characteristics. Nomenclature, medicinal properties (four natures and five flavors), meridian tropism, and dosage forms were standardized according to the Chinese Pharmacopoeia (2020 Edition)[2]. For instance, “Salviae Miltiorrhizae Radix et Rhizoma extract” was standardized to “Salviae Miltiorrhizae Radix et Rhizoma”; both “raw Polygoni Multiflori Radix” and “Polygoni Multiflori Radix Praeparata” were standardized to “Polygoni Multiflori Radix”. (3) Exclusions. Non-herbal excipients and chemical additives (e.g., magnesium stearate, calcium carbonate) were excluded from the raw material composition analysis.

Database construction

To ensure data accuracy, a dual independent data entry procedure was adopted. For each product, information including name, herbs, efficacy, TCM properties, meridian tropism, dosage form, health function, and suitable/unsuitable populations was systematically recorded on Microsoft Excel and the Ancient and Modern Medical Case Cloud Platform (v3.0). This process generated a dedicated, standardized database for SM-containing health products.

Data analysis

All records were analyzed for frequency using Microsoft Excel. To elucidate herbal formulation patterns, association rule mining was performed via the Ancient and Modern Medical Case Cloud Platform (v3.0) to calculate support, confidence, and lift values. Data were visualized using network diagrams.

Network pharmacology analysis

Collection of active components and target prediction

Active components of SM were retrieved from traditional Chinese medicine systems pharmacology database (TCMSP), high-throughput experiment and reference-assisted chemical-biology database (HERB), SymMap, traditional Chinese medicine integrated database (TCMID), encyclopedia of traditional Chinese medicine (ETCM) 2.0, and herbal ingredients’ targets (HIT) database, supplemented by comprehensive literature search of China National Knowledge Infrastructure (CNKI) and PubMed databases. Components were screened based on pharmacokinetic properties, including oral bioavailability (OB) ≥ 55%[13] and high intestinal absorption criteria. After deduplication, canonical simplified molecular-input line-entry system (SMILES) were downloaded from PubChem. Potential targets were predicted using SwissTargetPrediction and standardized via the UniProt database.

Screening of health function-related targets

Potential targets related to the function of “help maintain healthy blood lipid (cholesterol/triglyceride) levels” were retrieved from GeneCards, NCBI Gene, PathCards databases, and standardized via UniProt.

Identification of potential key targets

Targets of SM were intersected with the health function-related targets to identify key functional targets, and the results were visualized as a Venn diagram using the MicroBioinformatics Platform.

Construction of a protein–protein interaction (PPI) network and screening of core targets

The intersected key targets were submitted to the Search Tool for the Retrieval of Interacting Genes (STRING) database to construct a PPI network. The species was set to “Homo sapiens”, with a minimum required interaction score of 0.400[14]. The network was visualized using Cytoscape (v3.10.0), and core targets were identified using CytoHubba[15], which were ranked primarily by their degree values.

Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis

GO and KEGG enrichment analyses of the key targets were conducted using the Metascape database and the MicroBioinformatics Platform.

Molecular docking verification

To validate potential binding interactions, molecular docking was performed. Two-dimensional (2D) structures of compounds were obtained from PubChem and optimized into three-dimensional (3D) conformations using Chem3D (v15.0). The 3D structures of target proteins were retrieved from the PDB database. Protein structures were preprocessed by removing water molecules and native ligands in PyMOL (v3.1). Subsequent hydrogen addition and charge assignment were completed in AutoDockTools. The grid box was centered at X = 28.716 Å, Y = −40.208 Å, Z = 1.389 Å, with dimensions of 67.6 Å × 64.1 Å × 55.5 Å. The exhaustiveness value was set to 8 (the default value of AutoDock Vina). Molecular docking was executed using AutoDock Vina. The conformation with the lowest binding affinity was selected for interaction analysis. The resulting binding conformations and interactions were visualized using PyMOL (v3.1)[16] and ProteinsPlus[17].

Results

A total of 518 health products were initially identified, of which 477 met the inclusion criteria and were included in the final analysis.

Annual and provincial approvals of SM-containing health products

Among the 477 included products, 476 were domestically approved, and one was an imported product. As shown in (Figure 1a), product approvals exhibited three major peaks during 2004–2006 (38, 24, and 25 products, respectively), 2013–2015 (26, 42, and 21 products, respectively), and 2023–2024 (41 and 29 products, respectively). Geographically, approvals were concentrated in a few provinces (Figure 1b). The top four provinces were Beijing (76 products), Guangdong (55), Shaanxi (45), and Shandong (39).

High-frequency herbs and their properties

There were 206 raw materials used in the 477 products, of which 160 were TCMs with a cumulative frequency of 2444. Thirty raw materials with a usage frequency ≥ 20 were defined as high-frequency ingredients (Table 1). Among them, 15 TCMs were used no fewer than 40 times. The top five most frequently used herbs were SM (477 times), Puerariae Lobatae Radix (116), Lycii Fructus (83), Astragali Radix (79), and Notoginseng Radix et Rhizoma (71). Regarding TCM efficacy, herbs with the functions of “deficiency tonification” (719 times) and “blood-activating and stasis-resolving” (573 times) were the most frequently used (Figure 1c). These functions were predominantly observed in formulations comprising 3–7 raw materials (Figure 1d). Among the herbs, “mild-cold” was the dominant property among the four natures (624 times; Figure 1e), while “sweet” (1451 times) and “bitter” (1028 times) were the most frequent among the five flavors (Figure 1f). Furthermore, the liver (1435 times), heart (1184 times), and lung (859 times) were the primary targeted meridians (Figure 1g).

Frequency analysis of dosage forms of health products

Analysis of the 477 health products revealed 12 dosage forms. Capsules were the predominant form (n = 286), accounting for 59.96% of the total (Table 2).

Analysis of health function frequency and correlation

The number of claimed health functions per product varied: two products claimed three functions, 85 claimed two, and 390 claimed a single function. Nineteen health functions were identified, with a cumulative frequency of 569. The three most frequent health functions were “help maintain healthy blood lipid (cholesterol/triglyceride) levels” (137 times), “help enhance immunity” (85 times), and “assist in protecting against chemical liver damage” (82 times) (Table 3; Figure 2a). These functions were most commonly found in formulations containing 3–7 raw materials (Figure 2b).

Frequency analysis of suitable and unsuitable populations

There were 567 indications for suitable populations and 996 contraindications for unsuitable populations across all products. The higher frequency of contraindications compared to indications reflects a cautious approach to product labeling. A detailed breakdown of these specific populations is provided in (Table 4 and 5).

Core raw material combinations in health products containing SM and those with different health functions

After excluding single-ingredient formulations, 476 SM-containing products were included in the analysis. Among these, 137 products claimed the function of “help maintain healthy blood lipid (cholesterol/triglyceride) levels”, and 85 claimed “help enhance immunity”.

The results of the association rule analysis are presented in (Table 6). The network of high-frequency raw materials across all SM-containing health products is illustrated in (Figure 2c), where SM is the absolute core node, and its most frequent co-occurring herbs are Puerariae Lobatae Radix and Lycii Fructus. The networks for products targeting blood lipid maintenance and immune enhancement are shown in (Figure 2d and e), respectively. The top three co-occurring herbs with SM are Gynostemmatis Herba, Ginkgo Folium, and Crataegi Fructus in (Figure 2d); Astragali Radix, Lycii Fructus, and Notoginseng Radix et Rhizoma in (Figure 2e).

Results of network pharmacology

We identified 267 active components of SM and predicted 396 potential protein targets for these components.

Based on the results in Section analysis of health function frequency and correlation, “help maintain healthy blood lipid (cholesterol/triglyceride) levels” was the most frequent health function. Therefore, we selected this function for in-depth network pharmacology analysis and collected 1990 potential targets related to this function.

The intersection between SM-related targets and blood lipid-related targets is shown in (Figure 3a), revealing 181 overlapping targets as the key targets for SM in maintaining healthy blood lipid levels. A PPI network was constructed from these 181 targets, resulting in a network of 4026 edges (Figure 3b). Subsequently, all targets were ranked by degree values.

The top 20 targets were screened to identify those most relevant to lipid regulation as core targets for validation. Eight targets were selected: AKT1, PPARA, PPARG, GSK3B, CD36, ESR1, PRKACA, and NR3C1. These targets are known to regulate key aspects of lipid metabolism: AKT1, GSK3B, and CD36 are involved in hepatic lipid accumulation, fatty acid uptake, and de novo lipogenesis[18–20]; PPARA and PPARG act as classic nuclear receptor regulators of lipid homeostasis[21,22]; ESR1 mediates estrogen-dependent lipid regulation[23]; PRKACA participates in hepatocyte lipogenesis, fatty acid oxidation, and lipolysis[24]; and NR3C1 regulates lipid metabolic homeostasis and is linked to non-alcoholic fatty liver disease (NAFLD) and atherosclerosis[25,26]. These targets were used for subsequent molecular docking validation.

GO enrichment analysis revealed that SM modulates blood lipid homeostasis through multiple mechanisms (Figure 3c). In Biological Process (BP) (1629 terms), significant enrichment was observed in circulatory system processes, carboxylic acid metabolic processes, and cellular responses to lipids. For Cellular Component (CC) (95 terms), key localizations included membrane rafts, membrane microdomains, and vesicle lumens. Molecular Function (MF) analysis (243 terms) highlighted nuclear receptor activity, ligand-modulated transcription factor activity, and oxidoreductase activity.

Among the 182 enriched KEGG pathways, the top 30 are shown in (Figure 3d). The key pathways through which SM maintained healthy blood lipid levels included the PI3K-Akt, Rap1, and peroxisome proliferator-activated receptor (PPAR) signaling pathways, as well as the Lipid and Atherosclerosis pathway.

Results of molecular docking

Based on database mining, literature review, and the Chinese Pharmacopoeia (2020 Edition), five active components were selected for molecular docking: tanshinone IIA, tanshinone I, cryptotanshinone, salvianolic acid B[2], and salianic acid A[3,27–29]. Their interactions with eight core targets were evaluated based on binding energies, with values ≤ −5.0 kcal/mol suggesting spontaneous binding and values ≤ −7.0 kcal/mol indicating strong affinity[30].

All components showed favorable affinities for the eight targets (Figure 4a), with binding energies below −5.0 kcal/mol and most below −7.0 kcal/mol (Table 7). The tanshinone I–AKT1 complex had the lowest energy (−11.339 kcal/mol), confirming a highly stable interaction.

To illustrate the binding modes and interaction mechanisms, four representative complexes were visualized (Figures 4b–e). These four representative complexes were selected to cover the two major active component categories of SM (liposoluble tanshinones and water-soluble phenolic acids) and distinct functional types of core targets (serine/threonine kinase, fatty acid transporter, and nuclear receptor), with priority given to complexes with strong binding affinity and well-documented lipid-regulatory roles. Salvianolic acid B stably occupies the ATP-binding pocket of the AKT1 kinase domain (Figure 4b), forming multiple hydrogen bonds with Trp80, Ser205, Asn54, and Gln79, along with extensive hydrophobic interactions with Val270, Leu264, and Met227. Tanshinone I binds tightly to the hydrophobic ligand-binding pocket of the CD36 extracellular domain (Figure 4c), driven by hydrogen bonds with Asn247 and Gln265 and hydrophobic contacts with Tyr276, Val263, and Ile275. Tanshinone IIA anchors within the C-terminal ligand-binding domain of PPARA (Figure 4d), forming hydrogen bonds with Ser280 and Thr283 and strong hydrophobic interactions with Met220, Leu321, and other key residues. Cryptotanshinone binds securely within the ATP-binding pocket of the PRKACA catalytic domain (Figure 4e) via a hydrogen bond with Glu128 and hydrophobic interactions with Val58, Ala71, and Leu174.

In the 3D models, protein receptors are shown as slate cartoons and ligands in cyan. Hydrogen-bonding residues are displayed as green sticks, hydrogen bonds as yellow lines, and active-pocket residues in orange. In the 2D diagrams, black dashed lines represent hydrogen bonds; green dashed lines indicate π–π stacking or π-cation interactions; green arcs denote hydrophobic regions; and green dots mark the π-electron cloud centers of aromatic rings. Residues are labeled as [Amino acid abbreviation][Residue number][Chain] (e.g., Gln265A represents glutamine 265 on chain A).

Discussion

Formulation rules and pharmacological basis

Formulation analysis revealed that most herbs are for deficiency tonification, heat-clearing, blood-activating, and stasis-resolving. The most frequently used herbs were SM, Puerariae Lobatae Radix, Lycii Fructus, Astragali Radix, and Notoginseng Radix et Rhizoma.

The high-frequency herbal combinations reflect the TCM principle of “tonifying deficiency and activating blood circulation”, which targets the pathogenesis of dyslipidemia characterized by “phlegm turbidity” and “blood stasis”[31]. The pair of SM and Astragali Radix tonifies Qi and activates blood circulation in dyslipidemia via the advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE)/mitogen-activated protein kinase (MAPK) signaling pathway[32]. Similarly, the combination of SM and Crataegi Fructus promotes blood circulation without damaging blood vessels in atherosclerosis by regulating the nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways and preventing lipid deposition[33,34].

Regarding dosage forms, capsules are the mainstream form, which is consistent with other herbal health products, such as those containing Ganoderma and Epimedii Folium[16,35]. Encapsulation protects easily oxidizable components, such as salvianolic acid B and tanshinone IIA, from air and moisture. Furthermore, it masks the bitter taste of SM, improving consumer compliance[36] and making it suitable for long-term daily use.

Synergistic mechanisms of core herb pairs

For SM-containing health products targeting “help maintain healthy blood lipid (cholesterol/triglyceride) levels”, association rule analysis revealed the five most frequent herb pairs: SM–Gynostemmatis Herba, SM-Ginkgo Folium, SM–Crataegi Fructus, SM-Puerariae Lobatae Radix, and SM-Notoginseng Radix et Rhizoma. These pairs reflect clinically common compatibility patterns as well. In TCM theory, SM promotes blood circulation and removes stasis. Gynostemmatis Herba clears heat, resolves turbidity and tonifies deficiency. Together, they synergistically resolve phlegm and activate blood circulation. Ginkgo Folium and Puerariae Lobatae Radix dredge meridians and resolve turbidity, enhancing SM’s efficacy in blood circulation, stasis removal, and pain relief. Crataegi Fructus resolves turbidity and blood stasis; its combination with SM promotes digestion, resolves stasis and turbidity, and harmonizes the spleen and stomach. Notoginseng Radix et Rhizoma reinforces SM’s actions in activating blood, resolving stasis, stopping bleeding, and relieving pain.

Recent pharmacological studies on individual herbs support these roles to some extent. Gynostemmatis Herba modulates PPAR-γ to ameliorate hepatocellular steatosis and lower lipids[37]. Ginkgo Folium improves vascular endothelial function and inhibits platelet aggregation[38]. Crataegi Fructus inhibits hepatic lipase activity and protects against obesity-related metabolic disorders and NAFLD[39]. Puerarin, the active component of Puerariae Lobatae Radix, regulates lipid homeostasis via the AMP-activated protein kinase (AMPK) pathway[40,41]. Panax notoginseng saponins inhibit platelet-activating factor (PAF)[42], contributing to antithrombotic effects.

Although definitive synergistic or additive effects require further validation on complete formulas, the targets and pathways associated with these individual herbs overlap substantially with the core lipid-regulating targets and pathways identified in this study. Therefore, we hypothesize that these herb pairs may exert synergistic lipid-regulating effects by modulating shared or complementary biomolecular networks, thereby providing a basis for future pharmacological research on these formulas.

Molecular mechanisms underlying lipid homeostasis

Here, AKT1, PPARA, PPARG, GSK3B, CD36, PRKACA, ESR1, and NR3C1 were identified as mediators of SM-induced lipid regulation. Based on existing literature, these targets can be divided into two categories to regulate specific lipid phenotypes: nuclear receptor-mediated transcription and intracellular kinase signaling.

Within nuclear receptor-mediated transcription, PPARA and PPARG are ligand-activated transcription factors that form heterodimers with RXR. They initiate target gene transcription, enhance fatty acid oxidation, and upregulate CPT1 and CYP7A1, thereby lowering serum TC, TG, and LDL-C while elevating HDL-C[21,22,43,44]. This significantly ameliorates atherosclerosis and lipid accumulation. Similarly, ESR1 suppresses SREBP-1 signaling to reduce lipid deposition[23]. NR3C1 mediates transcriptional crosstalk between metabolic and inflammatory stress, playing a key role in alleviating NAFLD and systemic dyslipidemia[25]. Within the kinase network, AKT1, GSK3B, and CD36 form a regulatory axis in hepatic lipid metabolism. Activation of AKT1 inhibits GSK3B and downregulates CD36, thereby suppressing excessive fatty acid uptake and lowering circulating triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C)[18]. Moderate activation of the PI3K-Akt pathway enhances the hepatocellular insulin response, inhibits de novo lipogenesis, and regulates adipocyte proliferation and differentiation[45]. The AMPK pathway induces lipophagy and optimizes energy metabolism by inhibiting mTOR signaling[46], while the Rap1 pathway balances lipid synthesis and oxidation by regulating transcription of lipid metabolism genes[47,48]. This pathway modulates vascular wall lipid balance through dual control of apolipoprotein B-containing lipoprotein retention and HDL-mediated clearance[49]. GSK3B inhibition also reduces hepatic lipogenesis via STAT3 signaling[19], whereas CD36 drives de novo lipogenesis via INSIG2-dependent SREBP1 processing[20]. In addition, PRKACA halts lipogenesis and promotes fatty acid oxidation by phosphorylating and inhibiting ACC1[24].

These two functional categories were confirmed by our GO and KEGG enrichment results, which showed significant involvement of the carboxylic acid metabolic process and nuclear receptor activity. Therefore, we propose that SM exerts multi-dimensional lipid-regulating effects through a complex network centered on the PPAR, PI3K-Akt, and lipid metabolism signaling pathways (Figure 5). Within this network, both liposoluble and water-soluble components of SM synergistically act on hub targets, modulating downstream biological processes such as cellular energy homeostasis, inflammatory responses, and autophagy, ultimately facilitating lipid regulation and alleviating atherosclerosis.

Molecular docking offered predictive structural insights into this multi-target network. The results demonstrated that representative bioactive components of SM could spontaneously bind to the core targets with favorable affinities[30]. Detailed binding modes of four representative compounds revealed the structural basis for these interactions. Salvianolic acid B and cryptotanshinone stably occupied the conserved ATP-binding pockets of AKT1 and PRKACA, respectively (Figure 4b and e). The occupancy suggested they act as potential ATP-competitive inhibitors, blocking ATP sites and interfering with kinase activities, thereby modulating downstream PI3K-Akt[50] and cAMP/PKA[51] signaling. In parallel, lipophilic tanshinones exhibit targeted affinities toward transcription factors and transporters. Tanshinone IIA could deeply anchor into the C-terminal ligand-binding domain (LBD) of PPARA (Figure 4d). Since the LBD is the orthosteric site responsible for mediating receptor activation[52], this stable occupancy indicates that tanshinone IIA could act as a putative PPARA modulator. Tanshinone I tightly binds to the hydrophobic pocket of the CD36 extracellular domain (Figure 4c), which is the functional interface for recognizing and capturing long-chain fatty acids and oxidized low-density lipoprotein[53]. The targeted occupancy suggests that it may act as a steric inhibitor, physically obstructing this lipid-binding site and competitively hindering the internalization of extracellular lipids.

The systematic regulatory network predicted in this study aligns with previous single-component studies and extends their conclusions. Existing literature shows that tanshinone IIA alleviates NAFLD via the PPAR pathway[54]; salvianolic acid B inhibits atherosclerosis via the NF-κB/NLRP3 pathway and improves dyslipidemia via AMPK activation[28,55]; danshensu protects against NAFLD by enhancing fatty acid β-oxidation[56]; cryptotanshinone inhibits adipogenesis and stabilizes atherosclerotic plaques[57,58]; tanshinone I improves vascular and adipocyte function[59]; protocatechualdehyde ameliorates lipid deposition via the AMPK/SREBP2/PCSK9/LDLR pathway[60]; and SM-containing Danlou Tablet extracts alleviate atherosclerosis via NF-κB downregulation and PPARα/ABCA1 pathway activation[61]. These studies support the regulatory effects of SM’s bioactive components on the core nodes in our predicted network. While previous studies mapped isolated nodes, our study integrates these fragmented findings into a systematic regulatory framework, providing a comprehensive rationale for the multi-component, multi-target, and multi-pathway lipid-regulating synergy of SM.

Novelty, limitations, and future perspectives

This study integrates multi-method strategies to establish a lipid-regulating framework for SM-containing health products, linking real-world formulation data with biological molecular networks. By bridging market applications data and molecular mechanisms, this work provides theoretical support for the rational development of TCM-based health products and daily adjuvant management of lipid disorders.

However, several limitations should be acknowledged. First, data mining was limited to approved health product databases, which may introduce selection bias by excluding products under development. Second, network pharmacology predictions inherently carry a risk of false positives. Furthermore, molecular docking provides only static binding simulations, which cannot fully replicate the conditions of in vitro and in vivo experiments.

Future studies should focus on validation through the following approaches: (1) determining the combination index (CI) of core herb pairs (e.g., SM-Crataegi Fructus) in vitro to identify optimal synergistic ratios; (2) validating regulatory effects on key pathways (e.g., PPAR and PI3K-Akt) using hyperlipidemia or atherosclerosis animal models; and (3) confirming the specific binding and functional regulation of component-target pairs via surface plasmon resonance technology and functional rescue assays.

Conclusion

In summary, this study employed data mining and association rule analysis to profile the TCM ingredients formulated with SM in registered health products. This analysis of usage frequency, medicinal properties, meridian tropism, and compatibility patterns provided scientific insights for the future development of SM-based health products.

Furthermore, using network pharmacology and molecular docking, this work provided potential multi-target and multi-pathway mechanisms underlying the lipid-regulating effects of SM. The predicted core targets and key signaling pathways offered a preliminary theoretical basis for using SM to help maintain healthy blood lipid (cholesterol/triglyceride) levels and supported its continued development as functional foods.

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