Pseudohypericin

Pseudohypericin is a major naphthodianthrone photosensitive pigment found in plants of the genus Hypericum. Pseudohypericin exerts antiretroviral activity by specifically inhibiting protein kinase C (PKC) or interfering with the assembly and maturation of viral particles. Additionally, upon ultrasonic activation, it induces the generation of reactive oxygen species (ROS), thereby triggering cell apoptosis through the mitochondrial-caspase pathway.

PKC:15 μg/mL, Pancreatic lipase:0.94 ± 0.11 μM

Method: Since hypericin has been proposed as a photosensitizer for photodynamic cancer therapy, the photocytotoxicity of its congener Pseudohypericin has been investigated. The presence of foetal calf serum (FCS) or albumin extensively inhibits the photocytotoxic effect of Pseudohypericin against A431 tumour cells, and is associated with a large decrease in cellular uptake of the compound. These results suggest that Pseudohypericin, in contrast to hypericin, interacts strongly with constituents of FCS, lowering its interaction with cells[1].
Method: Human acute T cell leukemia Jurkat cells were treated with photoactivated pseudohypericin (PH) (50–800 ng/mL) for 2 hours, followed by exposure to visible light (520–750 nm, 5 J/cm²). The cells were then cultured for an additional 24 hours. Cell proliferation was assessed using the [³H]-TdR incorporation assay, and apoptosis was evaluated by detecting oligonucleosomal fragments.
Result: Photoactivated PH inhibited Jurkat cell proliferation in a dose-dependent manner, with an IC₅₀ of 200 ng/mL. Additionally, PH dose-dependently induced apoptosis in Jurkat cells. Non-photoactivated PH exhibited no significant effects at the tested concentrations [2].
Methods: THP-1 macrophages were co-cultured with Pseudohypericin, and cell viability, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), opening of the mitochondrial permeability transition pore (mPTP), as well as levels of apoptotic and necrotic cells were measured.
Results: Pseudohypericin induced apoptosis in THP-1 macrophages. The Pseudohypericin group showed a significant increase in ROS levels, leading to mPTP opening and loss of ΔΨm, which subsequently triggered apoptosis [3].

Method:
FV infection model: 6-week-old BALB/c mice were intravenously injected with FV (approximately 10⁶ ffu) and pseudohypericin (50 μg/mouse, single intravenous administration). After 10 days, spleen weight, serum RT activity, and the infectivity of spleen homogenates were measured, and survival was monitored for 120 days.
RadLV infection model: B10.T(6R) mice were intrathymically inoculated with RadLV, and 24 hours later, pseudohypericin (40–120 μg/mouse) was administered intraperitoneally. After 10 days, thymocytes were collected and H-2D⁴ antigen expression was detected by flow cytometry.
Result:
FV model: Pseudohypericin (50 μg, single intravenous dose) completely inhibited splenomegaly, resulted in undetectable serum RT activity and no infectious virus in the spleen, and achieved a 120-day survival rate of 44%.
RadLV model: Pseudohypericin at 120 μg inhibited H-2D⁴ antigen expression, with an inhibition rate of 47.1%[4].