Theasaponin E1

Fitoterapia. 2013 Jan;84:321-325.

Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis[Pubmed: 23266730]

The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as Theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4μg/ml. So it can be concluded that tea seed especially the compound 1 (Theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure-activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly.

Molecules . 2020 May 16;25(10):2334.

Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells[Pubmed: 32429462]

Alzheimer's disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose of the current study was to evaluate the effects of Theasaponin E1 on the inhibition of Aβ producing β-, γ-secretases (BACE1, PS1 and NCT) and acetylcholinesterase and activation of the non-amyloidogenic APP processing α-secretase (ADAM10). Additionally, Theasaponin E1 effects on Aβ degrading and clearing proteins neprilysin and insulin degrading enzyme (IDE). The effect of Theasaponin E1 on these crucial enzymes was investigated by RT-PCR, ELISA, western blotting and fluorometric assays using mouse neuroblastoma cells (SweAPP N2a). Theasaponin E1 was extracted and purified from green tea seed extract via HPLC, and N2a cells were treated with different concentrations for 24 h. Gene and protein expression in the cells were measured to determine the effects of activation and/or inhibition of Theasaponin E1 on β- and γ-secretases, neprilysin and IDE. Results demonstrated that Theasaponin E1 significantly reduced Aβ concentration by activation of the α-secretase and neprilysin. The activities of β- and γ-secretase were reduced in a dose-dependent manner due to downregulation of BACE1, presenilin, and nicastrin. Similarly, Theasaponin E1 significantly reduced the activity of acetylcholinesterase. Overall, from the results it is concluded that green tea seed extracted saponin E1 possess therapeutic significance as a neuroprotective natural product recommended for the treatment of Alzheimer's disease.

Biomed Res Int . 2021 Nov 12;2021:2521273.

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways[Pubmed: 34812408]

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and Theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

Food Res Int . 2018 Mar;105:982-988.

Preservative effect of Camellia sinensis (L.) Kuntze seed extract in soy sauce and its mutagenicity[Pubmed: 29433297]

The purpose of this study was to investigate the applicability of green tea seed (GTS) extract as a natural preservative in food. Food preservative ability and mutagenicity studies of GTS extract and identification of antimicrobial compounds from GTS extract were carried out. The GTS extract showed only anti-yeast activity against Candida albicans with MIC value of 938μg/mL and Zygosaccharomyces rouxii with a MIC of 469μg/mL. The active compounds were identified as Theasaponin E1 (1), assamsaponin A (2), and assamsaponin B (3). And GTS extracts didn't show mutagenicity because there were no dose-dependent changes in colonies of Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA regardless of the metabolic activation system. And GTS extract also showed a potent food preservation affect which eliminated all yeast below the MIC value in application test at soy sauce. Overall, these results indicate that GTS extract could be a safe and effective food preservative with anti-yeast activity.

Chem Pharm Bull (Tokyo) . 2000 Nov;48(11):1720-1725.

Bioactive saponins and glycosides. XVII. Inhibitory effect on gastric emptying and accelerating effect on gastrointestinal transit of tea saponins: structures of assamsaponins F, G, H, I, and J from the seeds and leaves of the tea plant[Pubmed: 11086901]

Following the investigation of assamsaponins A, B, C, D, and E, four new saponins termed assamsaponins F, G, H, and I were isolated from the seeds of the tea plant (Camellia sinensis L. var. assamica PIERRE), while assamsaponin J was isolated from its leaves. The structures of assamsaponins F-J were elucidated on the basis of chemical and physicochemical evidence and found to be 16,22-O-diacetyl-21-O-angeloyltheasapogenol E 3-O-[beta-D-galactopyranosyl (1-->2)][beta-D-glucopyranosyl(1 -->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-angeloyl-22-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1-->3)]- beta-D-glucopyranosiduronic acid, 21-O-angeloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1-->2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-tigloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, and 16,21-O-diacetyl-22-O-cinnamoyltheasapogenol B 3-O-[beta-D-galactopyranosyl(l-->2)][beta-D-rhamnopyranosy(1-->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, respectively. The saponin mixture from the seeds of the tea plant was found to exhibit an inhibitory effect on gastric emptying and an accelerating effect on gastrointestinal transit in mice. Theasaponin E1 the principle saponin of the tea plant, showed potent activity, while theasaponin E2 showed none, so that the position of the acyl groups in the sapogenin moiety is important from a pharmacological point of view.

Chem Pharm Bull (Tokyo) . 1999 Dec;47(12):1759-1764.

Bioactive saponins and glycosides. XV. Saponin constituents with gastroprotective effect from the seeds of tea plant, Camellia sinensis L. var. assamica Pierre, cultivated in Sri Lanka: structures of assamsaponins A, B, C, D, and E[Pubmed: 10748719]

The saponin fraction from the seeds of the tea plant, Camellia sinensis L. var. assamica Pierre cultivated in Sri Lanka, was found to show a potent protective effect on gastric mucosal lesions induced by ethanol in rats. Nine new acylated polyhydroxyoleanene-type triterpene oligoglycosides called assamsaponins A-I were isolated from the active saponin fraction together with three known saponins, Theasaponin E1 and E2 and camelliasaponin B1. The structures of assamsaponins A-E were elucidated on the basis of chemical and physicochemical evidence. Theasaponin E1 exhibited potent gastroprotective activity.

J Biosci Bioeng . 2000;90(6):637-642.

Theasaponin E1 destroys the salt tolerance of yeasts[Pubmed: 16232924]

Cells of Zygosaccharomyces rouxii in a medium containing a high concentration of NaCl were killed during incubation for 2-4 h with a low concentration of a mixture of saponins from tea seeds (TSS). The higher the concentration of NaCl in the medium, the higher the inhibitory effect of TSS on the growth of the yeast. The above inhibitory effect of TSS on the growth of the yeast was not observed when cells were incubated in hypertonic media composed of nonionic substances such as sugars. The ATPase activity of plasma membrane preparations from the yeast cells was slightly affected by the addition of TSS. It is shown that TSS facilitates leakage of glycerol from the yeast cells under NaCl-hypertonic conditions. The major inhibitor in the mixture of saponins was isolated and identified as Theasaponin E1. Its isomer, theasaponin E2, did not have any effect on the salt tolerance of Z. rouxii or Saccharomyces cerevisiae.

Molecules . 2021 Mar 17;26(6):1681.

Theasaponin E 1 Inhibits Platinum-Resistant Ovarian Cancer Cells through Activating Apoptosis and Suppressing Angiogenesis[Pubmed: 33802884]

Novel therapeutic strategies for ovarian cancer treatment are in critical need due to the chemoresistance and adverse side effects of platinum-based chemotherapy. Theasaponin E1 (TSE1) is an oleanane-type saponin from Camellia sinensis seeds. Its apoptosis-inducing, cell cycle arresting and antiangiogenesis activities against platinum-resistant ovarian cancer cells were elucidated in vitro and using the chicken chorioallantoic membrane (CAM) assay. The results showed that TSE1 had more potent cell growth inhibitory effects on ovarian cancer OVCAR-3 and A2780/CP70 cells than cisplatin and was lower in cytotoxicity to normal ovarian IOSE-364 cells. TSE1 significantly induced OVCAR-3 cell apoptosis via the intrinsic and extrinsic apoptotic pathways, slightly arresting cell cycle at the G2/M phase, and obviously inhibited OVCAR-3 cell migration and angiogenesis with reducing the protein secretion and expression of vascular endothelial growth factor (VEGF). Western bolt assay showed that Serine/threonine Kinase (Akt) signaling related proteins including Ataxia telangiectasia mutated kinase (ATM), Phosphatase and tensin homolog (PTEN), Akt, Mammalian target of rapamycin (mTOR), Ribosome S6 protein kinase (p70S6K) and e IF4E-binding protein 1(4E-BP1) were regulated, and Hypoxia inducible factor-1α (HIF-1α) protein expression was decreased by TSE1 in OVCAR-3 cells. Moreover, TSE1 treatment potently downregulated protein expression of the Notch ligands including Delta-like protein 4 (Dll4) and Jagged1, and reduced the protein level of the intracellular domain (NICD) of Notch1. Combination treatment of TSE1 with the Notch1 signaling inhibitor tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate (DAPT), or the Akt signaling inhibitor wortmannin, showed a stronger inhibition toward HIF-1α activation compared with single compound treatment. Taken together, TSE1 might be a potential candidate compound for improving platinum-resistant ovarian cancer treatment via Dll4/Jagged1-Notch1-Akt-HIF-1α axis.

Chem Pharm Bull (Tokyo) . 1998 Dec;46(12):1901-1906.

Structures of new acylated oleanene-type triterpene oligoglycosides, theasaponins E1 and E2, from the seeds of tea plant, Camellia sinensis (L.) O. Kuntze[Pubmed: 9880909]

Two new acylated oleanene-type triterpene oligoglycosides, theasaponins E1 and E2, were isolated from the seeds of tea plant [Camellia sinensis (L.) O. Kuntze]. The structures of theasaponins E1 and E2 were elucidated on the basis of chemical and physicochemical evidence to be expressed as 21-O-angeloyl-22-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1-->2])[beta-D-xylopyranosyl(1-->2)-alpha-L - arabinopyranosyl (1-->3)]-beta-D-glucopyranosiduronic acid and 21-O-angeloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1-->2)][beta-D-xylopyranosyl (1-->2)-alpha-L-arabinopyranosyl (1-->3)-beta-D-glucopyranosiduronic acid, respectively. Theasaponin E1 was found to show antisweet activity.