New Monoterpene-Conjugated Phenolic Constituents from Nutmeg and Their Autophagy Modulating Activities

Abstract

The seed of Myristica fragrans Houtt (nutmeg) is one of the important spices that have been extensively used in the culinary, food, beverage, and also in medicinal products industry. Previous phytochemical studies on nutmeg were mainly focused on lignans and neolignans. However, the other constituents have been poorly studied. In this study, 11 new monoterpene-conjugated phenolic derivatives, named myrifratins A–K (1–11), and five known compounds were isolated from nutmeg. The novel neolignan–diarylnonanoid–monoterpene conjugates (1 and 2) were first isolated in nature. Compounds 3–7 were rarely monoterpene–diarylnonanoid-conjugated derivatives, and 8–11 were the first examples of monoterpene–neolignan conjugates. Compounds 4–6, 12, and 13 showed potent autophagy inhibitory activities in a concentration-dependent manner. Our findings showed an uncommon class of monoterpene-conjugated phenolic derivatives in nature and reported their autophagy inhibition activities for the first time, which may give a new insight into the benefits or safety of nutmeg in foods.

Neolignans and Diarylnonanoid Derivatives with Anti-inflammatory Activity from Myristica fragrans Houtt. Seeds

“…Subfraction 21-5 was applied again to a Sephadex LH-20 column eluted with MeOH–H 2 O (3:10 → 100% MeOH) to obtain 67 subfractions (21-5-1 to 21-5-67). Myricone E ( 5 , 4.2 mg), myricone F ( 6 , 6.2 mg), giganteone A ( 26 , 3.1 mg), giganteone B ( 28 , 2.3 mg), and giganteone C ( 27 , 2.1 mg) from subfraction 21-5-61, myricone A or myrifragranone B ( 1 , 46.2 mg), myricone B ( 2, 34.8 mg), myricone C ( 3 , 21.6 mg), myricone D ( 4 , 13.3 mg), myricone G ( 7 , 1.3 mg), myrifragranone A ( 8 , 4.3 mg), malabaricone B , ( 23, 19.1 mg), and malabaricone C , ( 24 , 113.3 mg) from subfraction 21-5-63, the mixture of myricone H, I ( 9a and 9b , 11.5 mg), myricone K ( 10 , 5.3 mg), myricone L ( 11 , 6.4 mg), myricone M ( 12 , 5.7 mg), and myricone N ( 13 , 1.4 mg) from subfraction 21-5-65; myricone O ( 14 , 7.5 mg), myricone P ( 15 , 7.3 mg), myricone R ( 16 , 1.2 mg), myricone Q ( 17, 3.1 mg), myricone T ( 18, 3.3 mg), myricone X ( 19, 2.9 mg), myricone Z ( 21, 2.1 mg), and myricone W ( 22, 1.1 mg) from subfraction 21-5-60, myrifratin D ( 38 , 1.6 mg), myrifratin E ( 39 , 1.8 mg), malabaricone A ( 40 , 2.9 mg), myricone J ( 41 , 5.6 mg), myricone S ( 42 , 1.6 mg), and myricone U ( 43 , 2.3 mg) from subfraction 21-5-57, myfracone G ( 50 , 1.7 mg), myfracone H ( 51 , 1.9 mg), and myfracone I ( 52 , 0.7 mg) from subfraction 21-5-58 were purified using preparative MPLC with ACN/H 2 O (isocratic, 70% ACN, flow rate 8 mL/min). Fraction MFMC-28 (550 mg) was separated on a Sephadex LH-20 column eluted with MeOH–H 2 O (3:10 → 100% MeOH), then purified using preparative MPLC with ACN/H 2 O (gradient, flow rate 5 mL/min) to afford trans -3,4-dimethoxycinnamic acid ( 37, 2.5 mg), promalabaricone B ( 25 , 1.9 mg), and myricone Y ( 20 , 2.2 mg).…”

“…This article is licensed under CC-BY-NC-ND 4h i b i t e d .new 1,4-benzodioxane neolignan (49), and 31 new diarylnonanoid derivatives(2−7, 9−19, 21, 22, 41−48, and 50− 52), as well as known compounds(1,8,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). The compounds(1−19, 21−22, 41−48, and 50−52) isolated in this study were categorized into six groups (I−VI) based on the manner in which structural part 2 was substituted in structural part 1 and the specific properties of part 2 (seeChart 1,.…”