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

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.