Batatasin I, a Naturally Occurring Phenanthrene Derivative, Isolated from Tuberous Roots of <i>Dioscorea batatas</i> Suppresses Eicosanoids Generation and Degranulation in Bone Marrow Derived-Mast Cells

Abstract

To find anti-inflammatory compounds from the tuberous roots of Dioscorea batatas, we isolated 6-hydroxy-2,4,7-trimethoxyphenanthrene (batatasin I) from the dichloromethane (CH 2 Cl 2 ) fraction of this plant. Batatasin I inhibited both the generation of prostaglandin D 2 (PGD 2 ), leukotriene C 4 (LTC 4 ) and degranulation reaction in mouse bone marrow-derived mast cells (BMMCs). This compound inhibited cyclooxygenase-2 (COX-2) dependent PGD 2 generation in a dose dependent manner, with IC 50 values of 1.78 m mM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in the quantity of the PGD 2 generation was accompanied by a decrease in the COX-2 protein level. In addition, this compound also inhibited the production of 5-lipoxygenase (5-LOX) dependent LTC 4 in a dose dependent manner (IC 50 , 1.56 m mM). Batatasin I also inhibited the mast cell degranulation reaction (IC 50 , 6.7 m mM) in BMMCs. This result indicates that batatasin I could be developed as an anti-inflammatory agent through further investigation.

Phenanthrenes: A Promising Group of Plant Secondary Metabolites

“…Both compounds inhibited mast cell degranulation and exhibited dose-dependent inhibition of 5-LOX-dependent LTC 4 generation, suggesting that batatasin I and 6-hydroxy-2,7-dimethoxy-1,4-phenanthraquinone may have antiallergic potential. Therefore, these compounds should be considered for the development of new COX-2/5-LOX inhibitors. , …”

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

“…Truly, a vast number of natural compounds have been assessed regarding their capability to inhibit the enzymes of AA metabolism (reviewed in ) and valuable multitargeting leads were described among natural products . In these analyses, many phytochemicals were then identified as dual COX/5‐LOX inhibitors (Table ) . Moreover, plant extracts have been used in traditional medicine for ages and many have been described to impair the AA metabolism through both COX and 5‐LOX pathways .…”

Quantitative Analysis of Bioactive Phenanthrenes in Dioscorea batatas Decne Peel, a Discarded Biomass from Postharvest Processing

“…In addition, its medicinal value is significant because it contains numerous bioactive constituents such as polysaccharides, allantoin, and polyphenols including flavonoids [3]. Previous studies have demonstrated that the Chinese yam exerts strong anti-oxidative [4], cholesterol-lowering [5], growth hormone-releasing activity [6], and protective effects against ethanol-induced gastric ulcers [7]. Recent studies have revealed intimate relations between bioactivities and their responsible secondary metabolites including allantoin, saponins and phenanthrenes.…”

“…Phenanthrene-containing plants including the Dioscorea genus have been widely used for the treatment of several diseases in Africa, Asia, and South America [11]. Since the discovery of antifungal phenanthrenes from D. rotundata [12], anti-inflammatory [6,13,14], anticholinesterase [15], and triglyceride accumulation inhibitory [16] activity have been reported as medicinal or health-promoting effects of phenanthrenes discovered from the Dioscorea genus. In addition to their bioactivity, phenanthrenes have been suggested to be a non-polar standard marker for the Dioscorea genus, as their structures are distinguished from common phytochemicals and they are not difficult to analyze with the conventional high performance liquid chromatography with ultraviolet detection (HPLC-UV) method compared to other phytochemicals found in the Dioscorea genus such as allantoin and saponins [17].…”