Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract.

PURPOSE: We have previously reported that the Australian Northern Kaanju (Kuuku I'yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. METHODS: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). RESULTS: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. CONCLUSIONS: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo.

Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1ß production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.

[Effects of Alternanthera philoxeroides Griseb against respiratory syncytial virus infection in mice].

OBJECTIVE: To investigate the effect of an oral preparation of Alternathera philoxeroides Griseb (APG) against respiratory syncytical virus (RSV) in mice. METHODS: APG preparation was administered orally in RSV-infected mice at different daily doses (2.5, 4.5 and 6.5 g/kg) to observe the therapeutic effect of the preparation. RESULTS: Distinct differences were observed between the death rate of the mice treated with APG at daily dose of 4.5 and 6.5 g/kg and that of the untreated mice with infection. After AGP treatment of the mice at 6.5 g/kg, the detection rate of the virus was 31.3% in the blood and 37.5% in the lung tissue, significantly lower than that in the untreated mice. The virus detection rate was 43.8% in the lung tissues of mice treated with APG at 4.5 g/kg, also significantly lower than that in the untreated control. APG treatment at the 3 doses resulted in different lung indices from that of the control. CONCLUSION: APG may be effective for treatment of RSV infection.

[Effects of Alternanthera philoxeroides Griseb against dengue virus in vitro].

OBJECTIVE: To investigate the effects of Alternanthera philoxeroides Griseb extracts against dengue virus in vitro. METHODS: MTT assay and observation of cytopathic effect (CPE) were carried out to determine the cytotoxicity of Alternanthera philoxeroides Griseb on C6/36 cell lines and its effects on dengue virus. RESULTS: None of the 4 kinds of Alternanthera philoxeroides Griseb extracts exhibited obvious cytotoxicity on the cells at different concentrations with the exception of that over 320 microg/ml. The 4 extracts all showed inhibitory effects on dengue virus. Statistical analysis of TD(50) and ED(50) by Probit regression method suggested that extracts from coumarin had the lowest toxicity on the cells (TD(50)=535.91), whereas extracts from petroleum ether showed the strongest inhibitory effects on dengue virus (ED(50)=47.43) among the 4 extracts. CONCLUSION: Alternanthera philoxeroides Griseb possesses antiviral effects on dengue virus in vitro.