Ethanolic Extracts of Adlay Testa and Hull and Their Active Biomolecules Exert Relaxing Effect on Uterine Muscle Contraction through Blocking Extracellular Calcium Influx in Ex Vivo and In Vivo Studies

Abstract

Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2α), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2α. 3,5,6,7,8,3′,4′-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 µM, respectively. The experimental results showed that treatment with ATE-EA at 30 mg/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.

The Establishment of a Mouse Model of Recurrent Primary Dysmenorrhea

“…As mentioned above, many metabolites are relevant to mitochondrial function, so it can be speculated that mitochondria are an important target in PD research. Studies also showed that intracellular calcium was significantly increased in uterine smooth muscles after oxytocin stimulation [ 67 , 68 ]. Endoplasmic reticulum membrane is essential for intracellular calcium homeostasis, and here, it might contribute to PD development through regulating intracellular calcium [ 69 , 70 ].…”

Adlay Seed (Coix lacryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract Fractions and Subfractions Induce Cell Cycle Arrest and Apoptosis in Human Breast and Cervical Cancer Cell Lines

“…These four parts extracted using ethanol to obtain Coix husk ethanol extract (AHE), Coix seed coat e extract (ATE), Coix bran ethanol extract (ABE) and polished Coix seed ethanol (PAE). These four ethanol extracts are then divided into the n-hexane layer (He acetate layer (Ea), n-butanol layer (Bu) and water layer (Wa) using solvents of d polarities [12]. Following the use of the MTT analysis method to explore the antip ative effects of these test samples at different concentrations (0, 12.5, 25, 50 and 100 μ on breast cancer cells (MCF-7) and cervical cancer cells (HeLa) for 72 h, the res vealed that the most effective subfractions were those extracted from AHE and AT previous study, the treatment of blood cancer cells HL-60 and U937 with a metha tract of Coix shell (AHM) for 72 h significantly inhibited cell growth with IC50 va 70 and 61 μg/mL, respectively.…”

“…Coix has been among the first-class materials used as medicinal and dietary supplements since ancient times. Recent studies have also pointed out that Coix has antitumor [8], anti-allergic [9], hypolipidemic [10], hypoglycemic [11], anti-oxidant [12] and ovulation-inducing effects [13].…”

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health

“…Adlay seed coixol has an analgesic effect [ 6 ]. Adlay seeds (flavonoids, phytosterols, and fatty acids) can inhibit uterine contractions and relieve dysmenorrhea in vitro and in vivo [ 113 ]. Adlay has been used as therapeutic agent for dysmenorrhea as its naringenin and quercetin inhibit PGF 2α -induced uterine contractions and inhibited uterine contraction by blocking external Ca 2+ influx, leading to a decrease in the intracellular Ca 2+ concentration [ 114 ].…”

“…Adlay and its extracts are rich in 30 ingredients with more than 20 health effects. The effect of adlay on human health has been confirmed by PubMed and Google search, including its anti-cancer [ 46 , 167 ], anti-inflammation [ 97 ], anti-obesity [ 11 , 12 , 97 ], liver protection [ 140 ], anti-virus [ 8 , 105 , 106 ], cardiovascular protection [ 11 ], anti-hypertension [ 11 , 108 ], heart disease prevention [ 11 , 70 ], endocrine regulation [ 75 ], anti-diabetes [ 132 ], osteoporosis prevention [ 12 ], and analgesic effects [ 113 ].…”