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Diarylheptanoids from Dioscorea villosa (Wild Yam)

Shi-Hui DongDejan NikolićCharlotte SimmlerFeng QiuRichard B. van BreemenDjaja D. SoejartoGuido F. Pauli, and Shao-Nong Chen*

Abstract

A fractionation methodology aimed at the metabolomic mining of new phytoconstituents for the widely used botanical, wild yam (Dioscorea villosa), makes use of 1D qHNMR and 2D NMR profiles along the preparative fractionation pathway. This quantifiable and structural guidance led to the isolation of 14 diarylheptanoids (114), including five new compounds (15) with a tetrahydropyrano core skeleton. The structures, including the absolute configurations of both new and previously known diarylheptanoids, were assigned by a combination of HRESIMS, 1D and 2D NMR, 1H iterative full spin analysis (HiFSA), and the Mosher’s ester method. The isolation yields were consistent with yields predicted by qHNMR, which confirms the (semi-)quantifiable capabilities of NMR-based preparative metabolomic mining. The qHNMR-aided approach enabled the identification of new and potentially significant chemical entities from a small fraction of the plant extract and, thereby, facilitated the characterization of the residual complexity of the D. villosa secondary metabolome. LC-MS profiling of different D. villosa accessions further confirmed that the diarylheptanoids represent genuine secondary metabolites, which can serve as a new class of markers for botanical integrity analysis of D. villosa.

The genus Dioscorea in the family Dioscoreaceae comprises over 600 species, which are found throughout the tropical and temperate regions of the world. Dioscorea species are widely used as botanical dietary supplements. These plants are well known for containing steroidal saponins, which have been used as marker compounds for quality control of the botanical products.1 The roots and rhizomes of Dioscorea villosa L. are known as “wild yam”. This species, native to North America, is a twining tuberous vine. Since the 18th century, herbalists have been using wild yam to treat menstrual cramps and problems related to childbirth, as well as for upset stomach and coughs.2 In 1940, the rhizomes of D. villosa were discovered to be an important source of diosgenin,3 a phytoestrogen that acts on the mammary epithelium of ovariectomized mice and can be chemically converted into the mammalian hormone, progesterone.46 Subsequently, diosgenin was used as starting material for the synthesis of cortisone and norethindrone.7 The latter became known as a highly potent and orally active progestational agent and was the key ingredient in the first birth control pills in the 1960s.7

Today, dietary supplements containing wild yam extracts are popular among women for the alleviation of menopausal symptoms and are widely used as alternatives to hormone replacement therapy, although no direct evidence exists for the estrogenic activity of wild yam extracts.8,9 A comprehensive literature survey reveals that phytochemical information on wild yam is limited in chemical diversity: so far, only 12 steroidal saponins and two flavan-3-ol glycosides having been reported as major secondary metabolites.1,3,1012 From both chemotaxonomic and metabolomic perspectives, Dioscorea species can also be considered underexplored and likely contain other classes of secondary metabolites. The relatively narrow spectrum of known phytoconstituents limits our current understanding of the significance of wild yam as a dietary supplement, in particular with regard to the potential relief of menopausal symptoms. In addition to considering the relevance of residual complexity (RC; see ref 13 and S1, Supporting Information) in the assessment of phytoconstituents from D. villosa, and plant metabolomes in general, the present study also took into account the role of alternative chromatography in the discovery of new classes of secondary metabolites, as has been shown for well-studied plants such as black cohosh (Actaea racemosa (L.) Nutt., syn. Cimicifuga racemosa L.).14 As part of the research in the UIC/NIH Botanical Center, aimed at the metabolomic mining of new and potentially interesting bioactive constituents, the present study explores preparative fractionation methodology, which utilizes the combination of both 1D and 2D NMR spectral profiles and diversified chromatography. One starting point was the 1H NMR spectrum of the MeOH extract of wild yam, which is dominated by the signals of the steroidal saponins and saturated lipids in the range between δ 0.5 and 6.0. Figure 1 shows that, under higher sensitivity NMR conditions, numerous minor resonances can be detected between δ 6.0 and 8.5, which cannot be assigned to known Dioscorea constituents. Using qHNMR, an enrichment efficiency parameter (see Results and Discussion) was established to guide the fractionation workflow toward the isolation of the putatively new aromatic metabolites

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710746/

Wild Yam

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