Damulin B

Dammarane-type saponins from Gynostemma pentaphyllum and their cytotoxicities.[Pubmed:32037885]

Nat Prod Res. 2020 Feb 10:1-9.

Heat-processed Gynostemma pentaphyllum has shown strong activity against human lung carcinoma A549 cells. In this study, two dammarane-type saponins together with two known compounds were isolated from the ethanol extract of the heat-processed leaves of G. pentaphyllum. They were identified as 2alpha,3beta,12beta-trihydroxydammar-20(22),24-diene-3-O-beta-D-glucopyranoside (1, namely damulin E), 2alpha,3beta,12beta-trihydroxydammar-20,24-diene-3-O-beta-D-glucopyranoside (2, namely damulin F), damulin A (3) and Damulin B (4), respectively, using NMR and mass spectra. Damulin E and damulin F showed moderate activity against A549, H1299, T24, SH-SY5Y and K562 cell lines in vitro using CCK-8 assay.

Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.[Pubmed:30562828]

Planta Med. 2019 Mar;85(5):394-405.

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of Damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to Damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, Damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that Damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, Damulin B has potential therapeutic efficacy against lung cancer.

Determination by UPLC-MS of four dammarane-type saponins from heat-processed Gynostemma pentaphyllum.[Pubmed:25036687]

Biosci Biotechnol Biochem. 2014;78(2):311-6.

Heat-processed Gynostemma pentaphyllum and its main dammaran-type saponins, gypenoside L, gypenoside LI, Damulin B, and damulin A, possess non-small cell lung carcinoma A549 cell inhibitory activity. We established in this study a method by ultra-high performance liquid chromatography with tandem mass spectrometry for determination of the saponins and also investigated their content change in heat-processed G. pentaphyllum. The main saponins increased with increasing heating temperature and time. Further investigation showed that they were produced from gypenoside XLVI and gypenoside LVI by undergoing hydrolysis during the heat treatment.

Dammarane-type saponins from heat-processed Gynostemma pentaphyllum show fortified activity against A549 cells.[Pubmed:23508742]

Arch Pharm Res. 2013 Jul;36(7):874-9.

An ethanol extract from heat-processed Gynostemma pentaphyllum showed more potent cytotoxic activity against human lung adenocarcinoma A549 cells than that of raw G. pentaphyllum. Four constituents were isolated from heat-processed G. pentaphyllum using resin HP-20, silica gel and reversed ODS column chromatography. They were identified by mass and NMR spectra as damulin A and Damulin B, gypenoside L and gypenoside LI, respectively. To evaluate the efficacy of these four constituents, the MTT cytotoxicity assay was performed using A549 cells. Based on the structure of these four constituents, the results indicate that the hydroxyl group in C-2 and double bond in C20(21) and C20(22) positions are of importance in inhibition of A549 cell proliferation.

New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum.[Pubmed:21978948]

Bioorg Med Chem. 2011 Nov 1;19(21):6254-60.

AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2alpha,3beta,12beta-trihydroxydammar-20(22)-E,24-diene-3-O-[beta-D-glucopyranosyl -(1-->2)-beta-D-glucopyranoside], and Damulin B (2), 2alpha,3beta,12beta-trihydroxydammar-20,24-diene-3-O-[beta-D-glucopyranosyl-(1--> 2)-beta-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased beta-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism.