University of Hawai'i at Hilo

Physalis peruviana L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer.

To study the chemical composition and potential medicinal properties of Poha.

The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; 1) from the edible fruit, and seven withanolides (2-8), including a rare chlorinated withanolide (physalolactone; 2) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (2a-6a), and the compounds were evaluated with in vitro assays indicative of anti-inflammatory activity.

The structure of 1 was elucidated through NMR spectroscopic analyses. The absolute configuration of compound 2 was determined using single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC₅₀ values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds 1-3 reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC₅₀ values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound 4, wherein the IC₅₀ values in the NF-κB and NO assays were reduced from 11.0 to 0.33 μM, and 1.8 to 0.24 μM, respectively.

These findings enhance our understanding of Poha's constituents and potential medicinal properties. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.

The marine macroalga, Halymenia hawaiiana, holds significant commercial potential due to its culinary uses among various ethnic groups in Hawai'i and its success in aquaculture.

To investigate the chemical components and potential medicinal properties of H. hawaiiana.

Dried, ground H. hawaiiana was sequentially extracted with three solvents: ethyl acetate, methanol, and n-butanol. Chromatographic procedures were sequentially applied, leading to the isolation of several compounds. Structure determination of these compounds was performed using spectroscopic methods. The isolated compounds were then assessed through several in vitro assays.

A total of 11 compounds were isolated and identified: two nucleosides (1 and 2), a cytosine analog (3), five saturated long-chain fatty acids (4-8), cholesterol (9), and two of its derivatives (10-11) were isolated. Compounds 10 and 11 displayed promising antimicrobial activity against Staphylococcus aureus, both exhibiting MIC values of 8 μg/mL, and methicillin-susceptible S. aureus, with MIC values of 32 and 64 μg/mL, respectively. Furthermore, using a cell culture model, compounds 9, 10, and 11 exhibited significant anti-inflammatory effects as indicated by their inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with IC₅₀ values ranging from 50.2 to 60.8 µM. These compounds also effectively inhibited the generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) in RAW 264.7 mouse macrophage cells with IC₅₀ values of 55-73.7 µM without inducing cytotoxicity. Compounds 9-11 also exhibited mild cytotoxicity against the non-small cell lung cancer cell line A549, with compound 10 eliciting the strongest response (IC₅₀ 86.1 µM).

This study uncovered a diverse array of constituents from H. hawaiiana. Notably, compounds 10 and 11, which feature peroxide side chains, show significant promise as lead compounds for the development of novel anti-inflammatory and antimicrobial agents.

The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes an emerging infectious disease known as neuroangiostrongyliasis or rat lungworm disease. This study evaluates the efficacy of a vaccine developed for a related species, Angiostrongylus costaricensis, to A. cantonensis in the definitive rat host. Wild-caught rats (Rattus rattus) (n = 28) were mated in captivity to produce uninfected F1 progeny. A total of 43 F1 rats were involved in this trial; 20 non-vaccinated, 21 vaccinated, and two unvaccinated, uninfected. F1 offspring in the vaccinated group were intranasally vaccinated with two doses of PP2 A vaccine, a serine/threonine phosphatase 2 A at a dose of 4 μg vaccine and 4 μg adjuvant/25 g body weight at >3 mos. of age. Unvaccinated rats similarly received 4 μg adjuvant/25 g body weight. Rats were gavaged with 50 L3 stage larvae at ~four weeks post-treatment. Necropsies were conducted at 47-50 days post-live challenge and spleen weight, spleen length, lung and heart weights, and the numbers of worms in heart and lungs were recorded. An average of 23.17 adult worms were found among all F1 rats. We found no significant differences between vaccinated and unvaccinated rats in rat body weight (p = 0.883), spleen weight (p = 0.963), spleen length (p = 0.830), lung weight (p = 0.830), heart weight (p = 0.849), and number of worms in heart and lungs (p = 0.621). A TaqMan™ Custom Array (Applied Biosystems) cytokine assay was used to evaluate gene expression of 12 different cytokines in spleen tissue from 23 rats and no significant differences in cytokine (C_T) levels were observed between vaccinated and unvaccinated rats (p values range 0.154-0.988). Thus, the A. costaricensis PP2A vaccine, under these conditions, did not provide adequate protective immunity to guard against infection by A. cantonensis in wild rats.