| Description: |
Bergapten is a psoralen that can be photoactivated and is capable of crossing-linking DNA, covalently modifying proteins and lipids, and consequently inhibiting cell replication. Bergapten has anti-inflammatory and anti-tumor agent, it exhibits significant inhibition of the production of pro-inflammatory cytokines, namely tumour necrotic factor-α(TNF-α) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide in a concentration-dependent manner. Bergapten effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival via apoptotic response of osteoclasts and their precursors. |
| Targets: |
TGF-β/Smad | Caspase | TNF-α | IL Receptor | PI3K | p53 | Akt | p21 |
| In vitro: |
| Int Orthop. 2014 Mar;38(3):627-34. | | Bergapten prevents lipopolysaccharide mediated osteoclast formation, bone resorption and osteoclast survival.[Pubmed: 24305787] |
METHODS AND RESULTS:
To investigate the effect of Bergapten on osteoclastic bone resorption, RAW264.7 cells were treated with Bergapten for six days in the presence of LPS, and the area of bone resorption was analyzed with Image Pro-Plus. Next, we examined apoptosis of RAW264.7 cells after Bergapten incubation for 48 hours by flow cytometer using annexin V/propidium iodide (PI) double labeling. Finally, osteoclast survival was observed by Hoechst 33342 labeling and Western blotting after Bergapten treatment for 24 hours. RESULTS: Data showed that Bergapten (5-40 μmol/L) dose-dependently inhibited LPS-induced osteoclast formation and bone resorption. Treatment with Bergapten triggered apoptotic death of osteoclast precursor RAW264.7 cells in a dose-dependent manner. Furthermore, Bergapten significantly reduced the survival of mature osteoclast, as demonstrated by emergence of apoptotic nuclei and activation of apoptotic protein caspase 3/9.
CONCLUSIONS:
These findings suggest that Bergapten effectively prevents LPS-induced osteoclastogenesis, bone resorption and survival via apoptotic response of osteoclasts and their precursors. The study identifies Bergapten as an inhibitor of osteoclast formation and bone resorption and provides evidence that Bergapten might be beneficial as an alternative for prevention and treatment of inflammatory bone loss. | | Nat Prod Res. 2011 Sep;25(15):1444-9. | | Effect of bergapten from Heracleum nepalense root on production of proinflammatory cytokines.[Pubmed: 19662568] | In the present investigation, the anti-inflammatory activity of isolated bergapten from hydroalcoholic extract of Heracleum nepalense root was evaluated in vitro using human peripheral blood mononuclear cells (PBMCs).
METHODS AND RESULTS:
Bergapten exhibited significant inhibition of the production of pro-inflammatory cytokines, namely tumour necrotic factor-α (TNF-α) and interleukin-6 (IL-6) by PBMCs stimulated with lipopolysaccharide in a concentration-dependent manner. |
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| In vivo: |
| J Am Acad Dermatol. 1988 Feb;18(2 Pt 1):333-8. | | 5-Methoxypsoralen (Bergapten) for photochemotherapy. Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation.[Pubmed: 3279089] | In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy.
METHODS AND RESULTS:
With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely.
CONCLUSIONS:
We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases. |
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