Aim: To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Methods: The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginsenosides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. Results: Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibitory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 position of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these positions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. Conclusion: The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhibition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure
Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides—echinacoside, tubuloside A, and acteoside—were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10−6 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin.
Psoriasis is a chronic inflammatory skin disease with hyperproliferation and aberrant differentiation of keratinocytes in association with the elevation of interleukin-17A (IL-17A) and IL-23 levels. In an animal model, psoriasis-like dermatitis was induced on the shaved dorsal skin of BALB/c mice by topical application of imiquimod (IMQ), a synthetic ligand of Toll-like receptor 7. Administration of bitter Pu’er tea significantly reduced psoriasis-like dermatitis in IMQ-treated mice, including a reduction in dorsal skin lesions, splenomegaly and the mRNA expression levels of IL-17A and IL-23. To examine putative antipsoriatic constituents, three major compounds in bitter Pu’er tea, strictinin, theacrine and epigallocatechin gallate (EGCG), were separately given as supplements to IMQ-treated mice. The results showed that all the three compounds attenuated the severity of psoriasis by reducing epidermal thickness. Only theacrine significantly attenuated splenomegaly. All the three compounds inhibited the expression of IL-23 mRNA in the skin as well as reduced the content of IL-17A+CD4+ T cells in the spleen, and strictinin was found to be relatively effective. It seemed that the antipsoriatic activity of bitter Pu’er tea was attributed to the additive effects of its multiple active compounds.
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