Abstract
The global prevalence of type 2 diabetes is increasing rapidly; consequently there is great need for new and novel therapeutic options. Gynostemma pentaphyllum (GP) is a traditional medicinal plant, mainly present in Southeast Asian countries, that has been reported to exert antidiabetic effects, by stimulating insulin secretion. The specific compound responsible for this effect is however as yet unidentified. Screening for discovery and identification of bioactive compounds of an herbal GP extract, was performed in isolated pancreatic islets from spontaneously diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes, and from non-diabetic control Wistar rats. From this herbal extract 27 dammarane-type saponins, including two novel compounds, were isolated and their structure was elucidated by mass spectrometry and NMR spectroscopy. One of the dammarane-type triterpenoid showed a glucose-dependent insulin secretion activity. This compound, gylongiposide I, displays unique abilities to stimulate insulin release at high glucose levels (16.7 mM), but limited effects at a low glucose concentration (3.3 mM). Further studies on this compound, also in vivo, are warranted with the aim of developing a novel anti-diabetic therapeutic with glucose-dependent insulinogenic effect.
Highlights
Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae), Gynostemma Pentaphyllum (GP), a traditional medicinal plant found in China, Vietnam, Korea and Japan, is known for containing a large amount of biologically active saponins known as dammarane-type glycosides[1,2]
The extract was fractionated by repeated preparative chromatography and the fractions were further purified by a final isocratic elution
GP extract fractions or compounds isolated from the fractions were incubated with pancreatic islets of either W or GK rats to determine effects on insulin release at low (3.3 mM) and high (16.7 mM) glucose concentrations
Summary
In order to isolate and characterize the maximum number of saponin structures in the extract, an optimized chromatographic method was developed using a C-18 reverse-phase column (Fig. 1). Compound 20B (Fig. 5) showed beneficial biological activity by only stimulating the insulin secretion at high glucose concentration (Fig. 6) This compound (20B) known as gylongiposide I has been isolated and its structure reported previously but has not been studied for its anti-diabetic activity[17,18,19,20]. Compound 20A (3β,20S,23R)-3,20,23trihydroxydammar-24-en-21-oic acid-21,23-lactone 3-O-[α-L-rhamnopyranosyl-(1 → 2)]-[β-Dxylopyranosyl-(1 → 3)]-α-L-arabinopyranoside [M + Na]+; measured 919.4625 refs[21,22]. (3β,20S,23S)-3,20,23-trihydroxydammar-24-en-21-oic acid-21,23-lactone 3-O-[α-L-rhamnopyranosyl-(1 → 2)]-[β-Dxylopyranosyl-(1 → 3)]-6-O-acetyl-β-D-glucopyranoside [M + Na]+; measured 977.5021 ref.[8]. In the HMBC spectrum, two and three bond correlations of H3-18/C-7, C-8, C-9, and C-14; H-19/C-1, C-5, C-9, and C-10; H3-27/C-24, C-25 C-26; H3-28, H3-29/C-3, C-4, and C-5; H3-30/C-8, C-13, C-14, and C-15; H2-22/C-17, C-20, C-21, C-23, and C-24, together with the chemical shift of all protons and carbons, reveal that compound 12 had a 3,20,23,26-tetrahyd roxydammar-24-en-21-oic acid-21,23-lactone aglycone structure. Compound 34 were assigned to be 3β,20-dihydroxydammar-23,25-diene-21-carboxylic acid 3-O[α-L-rhamnopyranosyl-(1 → 2)]-[β-D-xylopyranosyl-(1 → 3)]-β-D-6-O-acetylglucopyranoside
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