The Daniel K. Inouye College of Pharmacy Scripts: Poha Berry (Physalis peruviana) with Potential Anti-inflammatory and Cancer Prevention Activities

摘要

The Daniel K. Inouye College of Pharmacy, during a historic event in Spring 2016, graduated the first two students in the Pacific region to earn a PhD in pharmaceutical sciences at the University of Hawai‘i at Hilo. The college offers PhD programs in these five disciplines: Cancer Biology, Medicinal Chemistry, Pharmaceutics, Pharmacognosy, and Pharmacology. One of the Pharmacognosy dissertations focused on plant-derived natural products with potential anti-inflammatory and cancer chemopreventive activities. Physalis peruviana (Pp) L. originated in tropical South America. It has become naturalized and is found readily on the Island of Hawai‘i. The edible fruits are commonly known as cape gooseberry or poha in Hawai‘i. In part of our study, three new withanolides, physaperuvin G (1), physaperuvins I–J (2–3), along with four known withanolides, namely, 4β-hydroxywithanolide E (4), withaperuvin C (5), and physalactone (6), coagulin (7) were isolated from the aerial parts of P. peruviana. In addition, two known compounds, phyperunolide F (8), and withanolide S (9), were isolated and identified from the poha berry fruits. The structures and absolute stereochemistry of new compounds from poha were elucidated by several spectroscopy methods: Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray diffraction, and mass spectrometry analyses. All isolated poha compounds (aerial parts and fruits) were evaluated for their anti-inflammatory activity with lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells, and tumor necrosis factor alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) with transfected human embryonic kidney cells 293. Most of the isolated natural compounds showed activity with these assays. Additional studies were performed with models of colon cancer. Specifically, 4β-hydroxywithanolide E (4HWE) inhibited the growth of colon cancer monolayer and spheroid cultures. The compound induced cell cycle arrest at low concentrations and apoptosis at higher concentrations. These data suggest the ingestion of poha berries may have some effect on the prevalence of colon cancer. Additionally, poha isolates compounds were evaluated for their growth inhibitory effects with U251MG glioblastoma and MDA-MB-231 breast cancer cells that harbor aberrantly-active signal transducer and activation of transcription 3 (STAT3), compared to normal NIH-3T3 mouse fibroblasts. This work has led to the filing of three provisional patents with the University of Hawai‘i Office of Technology Transfer and Economic Development.