Effective Components of Panax notoginseng- Salvia miltiorrhiza in the Treatment of Melasma and Its Experimental Study

Abstract

Purpose: The main purpose of this study was to predict and verify the active ingredients of Panax notoginseng-Salvia miltiorrhiza in melasma based on network pharmacology analysis and experimental verification.

Materials and methods: Panax notoginseng-Salviae miltiorrhizae was investigated by network pharmacology, GEO database analysis, and molecular docking techniques to screen its active ingredients. The active components of Panax notoginseng-Salviae miltiorrhizae were further validated by an in vitro α-melanin-induced B16F10 melanoma cell model and an in vivo UV irradiation combined with a progesterone injection-induced melasma rat model.

Results: Network pharmacology analysis and molecular docking showed that salvianolic acid B might be the key active ingredient. In vitro cellular experiments revealed that salvianolic acid B inhibits tyrosinase activity in B16F10 cells at concentrations of 60-90 nmol/mL. In vivo animal experiments found that TYR, MDA, and TNF-α were decreased in the skin and serum of rats in the group of the low-, medium-, and high-dose groups of salvianolic acid B, and the expression of GSH-Px and SOD was increased. The high-dose groups of salvianolic acid B showed the best therapeutic effect.

Conclusion: In this study, experiments collectively show that salvianolic acid B in Panax notoginseng-Salvia miltiorrhiza slows down the process of melasma by inhibiting lipid peroxidation in the organism, increasing the antioxidant capacity of the skin, decreasing the activity of tyrosinase, and providing anti-inflammation. This highlights the successful application of network pharmacology and provides a scientific basis for the clinical citation of Panax notoginseng-Salvia miltiorrhiza in treating melasma.

Figure 1

Venn diagram of Panax notoginseng–Salviae miltiorrhizae worked targets and melasma-related genes.

Figure 2

PPI network analysis of 28 potential targets.

Figure 3

GO enrichment of 7 potential targets.

Figure 4

KEGG pathway enrichment of 7 potential targets.

Figure 5

Molecular docking of cryptotanshinone to PGR (a), salvianolic acid B to TYR (b), Luteolin to TYR (c), and methylrosmarinate to ESR1 (d).

Figure 6

Effect of different concentrations of salvianolic acid B on the cell proliferation rate.

Figure 7

Effect of different concentrations of salvianolic acid on tyrosinase activity.

Figure 8

Apparent skin changes in rats (note: A: control group; B: model group; C, D, and E: low, medium, and high dose treatment groups of salvianolic acid B, respectively).

Figure 9

Detection of MDA, SOD, GSH-Px, TYR, and TNF-α in serum and skin tissues of rats (*p <0.05 **p < 0.01 ***p < 0.001 ****p < 0.0001).

Figure 10

Therapeutic mechanism of salvianolic acid B diagram (salvianolic acid B may inhibit melanin synthesis by increasing the activity of SOD and GSH-Px, reducing the production of ROS, modulating the MAPK signaling pathway to reduce the activity of ERK, JNK, or p38, and down-regulating the expression of MITF, or modulating the NF-kB signaling pathway to down-regulate the expression of pro-inflammatory cytokines, such as TNF-α, to regulate inflammatory responses, which may inhibit the activity of melanocytes and decrease the melanin synthesis).