Quantification and Bioaccessibility of California Pistachio Bioactives

The content of carotenoids, chlorophylls, phenolics, and tocols in pistachios (Pistacia vera L.) has not been methodically quantified. The objective of this study was to first optimize extraction protocols for lipophilic nutrients and then quantify the content of two phenolic acids, nine flavonoids, four carotenoids, two chlorophylls, and three tocols in the skin, nutmeat, and whole nut of California pistachios. The dominant bioactives in whole pistachios are lutein [42.35 μg/g fresh weight (FW)], chlorophyll <i>a</i> (142.24 μg/g FW), γ-tocopherol (182.20 μg/g FW), flavan-3-ols (catechins) (199.18 μg/g FW), luteolin (217.89 μg/g FW), myricetin (135.18 μg/g FW), and cyanidin-3-galactose (38.34 μg/g FW) in each nutrient class. Most phenolics are present in the skin, while the lipophilic nutrients are dominantly present in the nutmeat. Digestion with a gastrointestinal mimic showed <10% of most hydrophilic compounds are released from pistachio matrices. In conclusion, 9 lipophilic and 11 hydrophilic bioactives in pistachios are systematically quantified

Synthesis and Biological Evaluation of Novel Gigantol Derivatives as Potential Agents in Prevention of Diabetic Cataract

<div><p>As a continuation of our efforts directed towards the development of natural anti-diabetic cataract agents, gigantol was isolated from Herba dendrobii and was found to inhibit both aldose reductase (AR) and inducible nitric oxide synthase (iNOS) activity, which play a significant role in the development and progression of diabetic cataracts. To improve its bioefficacy and facilitate use as a therapeutic agent, gigantol (compound <b>14f</b>) and a series of novel analogs were designed and synthesized. Analogs were formulated to have different substituents on the phenyl ring (compounds <b>4</b>, <b>5</b>, <b>8</b>, <b>14a-e</b>), substitute the phenyl ring with a larger steric hindrance ring (compounds <b>10</b>, <b>17c</b>) or modify the carbon chain (compounds <b>17a</b>, <b>17b</b>, <b>21</b>, <b>23</b>, <b>25</b>). All of the analogs were tested for their effect on AR and iNOS activities and on D-galactose-induced apoptosis in cultured human lens epithelial cells. Compounds <b>5</b>, <b>10</b>, <b>14a</b>, <b>14b</b>, <b>14d</b>, <b>14e</b>, <b>14f</b>, <b>17b</b>, <b>17c</b>, <b>23</b>, and <b>25</b> inhibited AR activity, with IC₅₀ values ranging from 5.02 to 288.8 μM. Compounds <b>5</b>, <b>10</b>, <b>14b</b>, and <b>14f</b> inhibited iNOS activity with IC₅₀ ranging from 432.6 to 1188.7 μM. Compounds <b>5</b>, <b>8</b>, <b>10</b>, <b>14b</b>, <b>14f</b>, and <b>17c</b> protected the cells from D-galactose induced apoptosis with viability ranging from 55.2 to 76.26%. Of gigantol and its analogs, compound <b>10</b> showed the greatest bioefficacy and is warranted to be developed as a therapeutic agent for diabetic cataracts.</p></div

Synthesis of 17, 21, 23, and 25.

<p>Reagents and conditions: a. TsOH, ethanol; 0°C, NaBH₄; b. K₂CO₃, ethanol; c. Pd/C, H₂, RT, 12 h; d. BBr₃, CH₂Cl₂, -20°C, 2 h; RT, 4 h. e. Et₃N, CH₂Cl₂; f. 180°C, neat, N₂.</p

Inhibitory effect of gigantol and its analogs on AR activity¹.

<p>¹The results are expressed as mean ± SD (n = 3).</p><p>Abbreviation: NA, no activity</p><p>*<i>P</i> < 0.01, vs. Extractive gigantol.</p><p>Inhibitory effect of gigantol and its analogs on AR activity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141092#t001fn001" target="_blank">¹</a>.</p

Gigantol analogs at 0.1, 0.5, and 1.0 μg·mL^-1 on viability of HLECs treated with 250 mmol·L^-1 D-galactose for 72 h.

<p>Cell viability was determined by the MTT assay in the absence (Con) and presence (all other groups) of D-galactose. Ext-G refers to gigantol extracted from dendrobii. Viability (mean ± SD, n = 3) is expressed as the percentage of viable cells in the treatment to those of the Con. ^#<i>P</i> < 0.01 vs. Con, *<i>P</i> < 0.05 vs. D-galactose.</p

Synthesis of 4, 5, 8, 10, 14, and gigantol.

<p>Reagents and conditions: a. NaBH₄, MeOH; b. PBr₃, pyridine, 0°C; c. P(OEt)₃, 120°C; d. different aldehydes, CH₃ONa, 0°C to room temperature (RT), 12 h; e. Pd/C, H₂, RT, 12 h; f. BBr₃, CH₂Cl₂, -20°C, 2 h; RT, 4 h; g. NaH, ethanethiol, DMF, N₂, reflux; h. MOMCl, <i>i</i>-Pr₂NEt, CH₂Cl₂, 0°C, 1 h; RT, 12 h; i. diethyl naphthalen-1-ylmethylphosphonate, CH₃ONa, 0°C, 1 h; rt, 12 h; j. 2 M HCl, methanol, 50°C, 1 h; k. BnBr, 18-crown-6, K₂CO₃, reflux, 9 h.</p

Inhibitory effect of gigantol and its analogs on iNOS activity¹.

<p>¹The results are expressed as mean ± SD (n = 3). Abbreviation: NA, no activity.</p><p>Inhibitory effect of gigantol and its analogs on iNOS activity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141092#t002fn001" target="_blank">¹</a>.</p