Immunomodulatory and anti-inflammatory properties of dictamnine-free phytopharmaceuticals from Dictamni Cortex with phototoxicity evaluation

Abstract

Ethnopharmacological relevance: Dictamni Cortex (Dictamnus dasycarpus root barks) has been widely applied across Asia for inflammatory dermatological conditions, including eczema, pruritus, allergies, and urticaria. Among the active compounds in Dictamni Cortex, dictamnine exhibits notable anti-inflammatory and antipruritic properties, contributing to its therapeutic effects against skin inflammation. However, dictamnine, a furoquinoline alkaloid, shares a structural framework with linear furanocoumarines such as 8-methoxypsoralen and 5-methoxypsoralen, which are known for their photoactive properties. Similar to psoralens, dictamnine also demonstrates phototoxic characteristics.

Aim of the study: This research focused on developing safer plant-based medicines derived from Dictamni Cortex by formulating extracts devoid of dictamnine analogues (DDE-A1 and DDE-B1) and evaluating their potential as novel therapeutic agents. The investigation focused on their immunomodulatory and anti-inflammatory effects, as well as their phototoxicities. Correspondingly, alkaloid-rich fractions containing dictamnine (DDE-A2 and DDE-B2) were also prepared to compare their phototoxic effects.

Materials and methods: To isolate pure compounds from the potential fraction (DDE) of Dictamni Cortex, column chromatography was performed using silica, C18-reversed phase silica gels, and gel filtration resin as stationary phases. Two novel DDE formulations free from dictamnine alkaloids (DDE-A1 and DDE-B1) were obtained using acid-base extraction and acidic resin (Dowex® 50WX4 hydrogen form) column separation methods. Immunomodulatory effects were assessed using Th17/IL-17 and Th2/IL-4 cell models, while anti-inflammatory effects were evaluated by analyzing TNF-α- or IL-17A-induced IL-6 and IL-8 levels in HaCaT cells. Phototoxicity was tested in HaCaT cells with and without UV exposure.

Results: Two novel DDE formulations lacking dictamnine alkaloids (DDE-A1 and DDE-B1) were successfully prepared by aforementioned two methods, respectively. Experimental results indicated that DDE-A1 and DDE-B1 exhibited no phototoxicity while retaining immunomodulatory and anti-inflammatory potential. Conversely, the dictamnine alkaloid-rich fractions (DDE-A2 and DDE-B2) showed significant phototoxicity, exceeding the toxicity of dictamnine alone. These findings suggest that DDE-A1 and DDE-B1 as promising candidates for safe and effective therapeutic agents for dermatitis.

Conclusions: This pilot study successfully developed detoxified and bioactive phytopharmaceuticals (DDE-A1 and DDE-B1) and photosensitive dictamnine-rich alkaloid formulations (DDE-A2 and DDE-B2) from Dictamni Cortex. The DDE-A1 and DDE-B1 formulations demonstrated robust immunomodulatory and anti-inflammatory effects without phototoxicity, paving the way for the development of safer, plant-based dermatological drugs.

Keywords: Dictamni Cortex; Dictamnine analogues; Dictamnusdasycarpus; Immunomodulatory and anti-inflammatory effects; Phototoxicity.