Research progress of berberine mediated photodynamic therapy

Abstract

Berberine (BBR) is a plant secondary metabolite that has been used in photodynamic therapy (PDT) in the last few decades. The present review aimed to discuss the research progress of BBR-mediated photodynamic actions. The following key words were searched in several databases: 'Berberine' combined with 'photodynamic therapy', 'sonodynamic therapy (SDT)', 'ultraviolet', 'reactive oxygen' and 'singlet oxygen'. The results demonstrated that both type I and type II reactions participated in the photodynamic progression of BBR derivatives. In addition, the photochemical characteristics of BBR derivatives were affected by the polarity, pH and O₂ content of solvents. DNA binding increases the lifespan of the photoexcited BBR state and generation of singlet oxygen (¹O₂). The chemical properties of substituents in different positions of the BBR skeleton are pivotal for its photochemical properties, particularly the methylenedioxy group at the C-2 and C-3 positions. BBR is a promising agent for mediating both PDT- and SDT-treated diseases, particularly in tumors. However, further studies are required to validate their biological effects. In addition, the molecular mechanisms underlying the antitumor effects of BBR-PDT remain unclear and warrant further investigation. The structural modification and targeted delivery of BBR have made it possible to broaden its applications; however, experimental verification is required. Overall, BBR acts as a sensitizer for PDT and has promising development prospects.

Keywords: berberine; photodynamic therapy; reactive oxygen species; target drug delivery.

Figure 1.

Coptis chinensis Franch and structural formula of BBR. (A) The root and stem of Coptis chinensis Franch. (B) Structural formula of BBR. BBR, berberine.

Figure 2.

Graphical illustration of type I and type II photochemical reactions of BBR. The value of absorption and fluorescence was detected in MeCN. BBR, berberine; ¹BBR*, excited state of BBR; ³BBR*, triple excited state of BBR; ¹O_2, singlet oxygen; ³O₂, triplet oxygen; O₂^•−, superoxide radical anion; H₂O₂, hydrogen peroxide; ^•OH, hydroxyl radicals.

Figure 3.

Effects of functional groups on the photoactivities of BBR. Chemical properties of substituents in different positions of the BBR skeleton are pivotal for its photochemical properties, particularly the methylenedioxy group at C-2 and C-3 positions, C-7 methyl group and the 9-O-position of the isoquinoline chromophore. BBR, berberine.

Figure 4.

Biological effects of BBR-PDT. BBR-PDT exhibits destructive effects in different cells, including human tumor cells. The illumination parameters involved in relevant studies are presented. BBR, berberine; PDT, photodynamic therapy.