Antipruritic Effects of 1,4-Naphthoquinones and Related Compounds.

Abstract

The number of patients with allergic disease has recently been increasing. To treat such diseases, we have isolated natural compounds with antianaphylactic, 1,2) antihistaminic, 3) and anti-platelet-activating factor (PAF) 4) activity using in vivo assay systems that we have developed. However, in cases of allergic disease with chronic and severe pruritus, such as atopic dermatitis, not only treatment of the allergy but also inhibition of scratching at the lesion is very important. We therefore searched for natural compounds with antipruritic activity using our in vivo assay systems.5) We discovered that a 2-hydroxy-1,4-naphthoquinone (lawsone) (1) isolated from Impatiens balsamina L., could significantly inhibit scratching behavior 5) induced in mice by histamine-releasing agents, such as Dextran T40 and compound 48/80 (COM). We were also able to show that 1 can be effective as an antipruritic agent against atopic dermatitis, because it inhibited 6) chronic and serious scratching behavior in atopic dermatitis model NC mice with dermatitis.Here we report the antipruritic effects of natural and synthesized 1,4-naphthoquinones and related compounds for new antipruritic medicines that can be effective for the treatment of allergic disease. MATERIALS AND METHODS General Experimental ProceduresMelting points were determined with a Yanagimoto micro melting point apparatus. IR spectra were recorded on a Shimadzu 435 spectrometer and UV absorption spectra with a Hitachi 323 spectrometer.1 H-NMR and 13 C-NMR spectra were recorded with JEOL JNM-GSX 400 spectrometers (using tetramethylsilane (TMS) as an internal reference). Electron-impact (EI)-MS spectra (70 eV) were obtained with a JEOL JMS-DX 303 spectrometer.Materials COM was obtained from Sigma. 2,3-Dihydroxy-1,4-naphthoquinone (2), 2-hydroxy-3-methoxy-1,4-naphthoquinone (3), and 2-hydroxy-3-(2-hydroxyethyl)-1,4-naphthoquinone (4) were synthesized by known methods. 7,8) Compound 1, p-hydroxybenzoic acid (6), p-coumaric acid (7), ferulic acid (8), scopoletin (9), 2,2Ј-methylenebis(3-hydroxy-1,4-naphthoquinone) (10), and 2,2Ј-ethylidenebis(3-hydroxy-1,4-naphthoquinone) (impatienol) (11) were isolated from I. balsamina using methods described previously. 1,9,10) Balsaquinone (5) was isolated from the pericarp of I. balsamina as described in the following section.Isolation and Identification of Compound 5 Fresh pericarp (75 g) of I. balsamina was extracted with 50% ethanol 400 ml over 3 d at room temperature and filtered. The extract (2.9 g) was subjected to silica gel chromatography using a CHCl 3 -MeOH gradient system followed by TLC to give compound 5 (6 mg). The UV spectrum showed characteristic absorption maxima of 1,4-naphthoquinone. The IR spectrum suggested the presence of a hydroxyl group and an a,b-unsaturated function. The EI-MS spectrum exhibited a [M] ϩ at m/z 232. The 1 H-and 13 C-NMR spectral data were similar to those of 2-methoxy-1,4-naphthoquinone except for the presence of the hydroxyethyl group and absence of 3-H, suggesting that 5 is 2-methoxy-1,4-n...

Antioxidant and Antimicrobial Properties of Various Solvent Extracts from Impatiens balsamina L. Stems

“…In some areas of China, this plant has been used as a vegetable or anticancer herb, although there are currently no reports confirming the efficacy of this practice (Ding and others 2008). According to previous studies, a number of active compounds have been isolated from different organs of I. balsamina including peptides, quinones, flavonoids, and coumarins associated with antifungal, antibacterial, antidermatitis, antianaphylactic, antipruritic, and antihistaminic properties (Oku and Ishiguro 2001; Yang and others 2001; Oku and others 2002; Thevissen and others 2005; Ding and others 2008; Sakunphueak and Panichayupakaranant 2011). The stem of I. balsamina is a famous herbal medicine known in China by the name of “Fèng Xiān Tòu Gǔ Cǎo”, commonly processed by stripping the aerial parts of I. balsamina and removing the leaves, flowers and seeds, then being washed and dried (Nanjing University of Chinese Medicine 2005).…”

In Vitro Activity of 2‐methoxy‐1,4‐naphthoquinone and Stigmasta‐7,22‐diene‐3β‐ol from Impatiens balsamina L. against Multiple Antibiotic‐Resistant Helicobacter pylori

“…The plant Swertia calycina (Gentianaceae) was also found to contain this compound [11]. Some bioactivities were demonstrated in MeONQ including antipruritic [12], antiinflammatory, antiallergic [13] and anticancer [14] activities. Furthermore, reducing oral lesion recurrence in human immunodeficiency virus patients was also reported for this compound [15].…”

Cyclooxygenase-2 Inhibitory 1,4-Naphthoquinones from Impatiens balsamina L.

“…The IC 50 values of 1 and 2 against COX-2 were 0.2 mM and 9.4 mM, respectively. The inhibitory activity of 1 was the same as that of NS-398, 15) a selective COX-2 inhibitor. These selectivities against COX-2 show that 1 and 2 may have the potential to be COX-2-selective inhibitors.…”

“…Material Impatienol (3) and 2-methoxy-3-(2-hydroxyethyl)-1,4-naphthoquinone (balsaquinone) were isolated 14,15) from the aerial parts of I. balsamina L. Extraction and Isolation Fresh corollas (1.5 kg) of white flowers were extracted twice with 35% EtOH (15 l) at room temperature for 1 d to afford crude yellow crystals (kaempferol). After the kaempferol had been obtained by filtration, the alcoholic solution was evaporated in vacuo to remove the EtOH, followed by successive extraction with EtOAc.…”