| Description: |
Khellin, as photosensitizer, together with ultraviolet A (UVA) irradiation, it can treat vitiligo patients; it does not induce skin phototoxicity with UVA but it induces repigmentation similar to psoralens. Khellin exhibits significant Epidermal Growth Factor Receptor (EGFR) inhibitory activity, it has anti-inflammatory, and analgesic properties, it may be beneficial in the management of kidney stone disease caused by hyperoxaluria. |
| Targets: |
EGFR | P450 (e.g. CYP17) |
| In vitro: |
| J Enzyme Inhib Med Chem. 2013 Dec;28(6):1171-81. | | Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors.[Pubmed: 23025406] | Khelline is naturally occurring furochromone exhibited significant Epidermal Growth Factor Receptor (EGFR) inhibitory activity. The newly synthesized compounds 2-5 displayed the most potent EGFR inhibitory activity on MCF-7 and HeLa.
METHODS AND RESULTS:
In vitro study against 59 different human tumour cell lines derived from nine cancer type in NCI (USA), which was presented and documented. Molecular docking simulation was performed to position compounds 1-5 into the EGFR active site to determine the probable binding mode. | | PLoS One. 2013 Sep 19;8(9):e74917. | | Khellin and visnagin differentially modulate AHR signaling and downstream CYP1A activity in human liver cells.[Pubmed: 24069365] | Khellin and visnagin are two furanochromones that can be frequently found in ethnomedical formulations in Asia and the Middle East. Both compounds possess anti-inflammatory and analgesic properties, therefore modern medicine uses these compounds or structurally related derivatives for treatment of vitiligo, bronchial asthma and renal colics.
Despite their frequent usage, the potential toxic properties of visnagin and khellin are not well characterized up-to-now. Many natural compounds modulate the expression and activity of cytochrome P450 1A1 (CYP1A1), which is well-known to bioactivate pro-carcinogens.
The expression of this enzyme is controlled by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor and regulator of drug metabolism.
METHODS AND RESULTS:
Here, we investigated the influence of both furanochromones on AHR signaling in human HepG2 hepatocarcinoma cells and primary human hepatocytes. Both compounds transactivated xenobiotic response element (XRE)-driven reporter gene activity in a dose-dependent manner and induced CYP1A1 transcription in HepG2 cells and primary hepatocytes. The latter was abolished in presence of a specific AHR antagonist. CYP1A enzyme activity assays done in HepG2 cells and primary hepatocytes revealed an inhibition of enzyme activity by both furanochromones, which may become relevant regarding the metabolism of xenobiotics and co-administered therapeutic drugs.
CONCLUSIONS:
The observed induction of several other members of the AHR gene battery, whose gene products are involved in regulation of cell growth, differentiation and migration, indicates that a further toxicological characterization of visnagin and khelllin is urgently required in order to minimize potential drug-drug interactions and other toxic side-effects that may occur during therapeutic usage of these furanochromones. |
|
| In vivo: |
| J Eur Acad Dermatol Venereol. 2011 Jan;25(1):74-81. | | Treatment of vitiligo with khellin liposomes, ultraviolet light and blister roof transplantation.[Pubmed: 20477914 ] | Various surgical and non-surgical methods are available to treat vitiligo. Surgical techniques such as epidermal blister graft transplantation may be effective for the re-pigmentation of stable, but refractory vitiligo areas. Khellin has phototherapeutic properties that are similar to those of the psoralens, but with substantially lower phototoxic effects and DNA mutation effects. Its penetration into the hair follicles is enhanced by encapsulating it into liposomes. Subsequent activation of the khellin with UV light stimulates the melanocytes in the hair follicles.
The first objective was to evaluate the additional value of combining blister roof transplantation (BRT) with khellin in liposomes and ultraviolet light (KLUV) in the treatment of recalcitrant vitiligo patches. The second objective was to assess patients' satisfaction.
METHODS AND RESULTS:
Nineteen patients with vitiligo lesions which did not respond to KLUV treatment for at least a year were treated with BRT followed by KLUV. The transplantation was performed by creating blisters with a suction device, preparing the target site with Erbium laser ablation and the actual transplantation. Locations where randomly assigned. A blinded observer established the results.
CONCLUSIONS:
Seventy-five percent of the patients were satisfied with the cosmetic result. All of the patients would recommend the treatment to other vitiligo patients. More than 75% re-pigmentation of the vitiligo areas was noted in 47% of the patients according to the blinded evaluation of photographs taken before and after the treatment. | | J Am Acad Dermatol. 1988 Apr;18(4 Pt 1):693-701. | | Treatment of vitiligo with khellin and ultraviolet A.[Pubmed: 3270995] | Twenty-eight patients with vitiligo were treated with a new photochemotherapeutic regimen using khellin, a furanochromone, as photosensitizer, together with ultraviolet A (UVA) irradiation.
METHODS AND RESULTS:
Twenty-five patients received khellin orally and three patients were treated with topical khellin. Treatments were given three times weekly. As opposed to psoralens, khellin did not induce skin phototoxicity with UVA but it induced repigmentation similar to psoralens. The treatment success strongly depended on the number of treatments. More than 70% repigmentation was achieved in 41% of the patients who had received 100 to 200 treatments. This success rate is comparable to the rate obtained with psoralens. Seven patients experienced a mild elevation of liver transaminases within the early treatment phase and their treatments were discontinued. No long-term internal organ or skin toxicity was observed. The major advantage of khellin is that it does not lead to phototoxic skin erythema and thus can be considered safe for home treatment.
CONCLUSIONS:
Because of its photochemistry it may be considered less hazardous than psoralens regarding mutagenicity and carcinogenicity. |
|
Cell. 2018 Jan 11;172(1-2):249-261.e12. doi: 10.1016/j.cell.2017.12.019.IF=36.216(2019)
Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002.IF=22.415(2019)
Mol Cell. 2017 Nov 16;68(4):673-685.e6. doi: 10.1016/j.molcel.2017.10.022.IF=14.548(2019)
ACS Nano. 2018 Apr 24;12(4): 3385-3396. doi: 10.1021/acsnano.7b08969.IF=13.903(2019)
Nature Plants. 2016 Dec 22;3: 16206. doi: 10.1038/nplants.2016.205.IF=13.297(2019)
Sci Adv. 2018 Oct 24;4(10): eaat6994. doi: 10.1126/sciadv.aat6994.IF=12.804(2019)
