Phenylpropanoid glucosides from Tadehagi triquetrum inhibit oxLDL-evoked foam cell formation through modulating cholesterol homeostasis in RAW264.7 macrophages.[Pubmed: 29199477]

The phenylpropanoid glucosides from Tadehagi triquetrum were found to be beneficial to glucose and lipid metabolism in vitro. Herein, we investigated the effects of these compounds on oxidised low-density lipoprotein (oxLDL)-induced foam cell formation in RAW264.7 macrophages, aiming to evaluate their potential utility in prevention of atherosclerosis. Our results showed that three out of seven phenylpropanoid glucosides significantly inhibited oxLDL-evoked foam cell formation. These three compounds remarkably inhibited cholesterol influx and enhanced cholesterol efflux. Treatment with compounds 3, 4 and 7 significantly down-regulated the expression of scavenge receptors 1 (SR-1) and cluster of differentiation 36 (CD36) and increased the expression ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1). Analyses of structure-activity relationships revealed that cinnamyl group was the most pivotal group for their activities. This work provided phenomenon that these phenylpropanoid glucosides are effective regulator of cholesterol influx/efflux and may be useful in leading for development of anti-atherosclerotic agents.

Tadehaginosides A-J, Phenylpropanoid Glucosides from Tadehagi triquetrum, Enhance Glucose Uptake via the Upregulation of PPARγ and GLUT-4 in C2C12 Myotubes.[Pubmed: 27100993]

Ten new phenylpropanoid glucosides, tadehaginosides A-J (1-10), and the known compound tadehaginoside (11) were obtained from Tadehagi triquetrum. These phenylpropanoid glucosides were structurally characterized through extensive physical and chemical analyses. Compounds 1 and 2 represent the first set of dimeric derivatives of tadehaginoside with an unusual bicyclo[2.2.2]octene skeleton, whereas compounds 3 and 4 contain a unique cyclobutane basic core in their carbon scaffolds. The effects of these compounds on glucose uptake in C2C12 myotubes were evaluated. Compounds 3-11, particularly 4, significantly increased the basal and insulin-elicited glucose uptake. The results from molecular docking, luciferase analyses, and ELISA indicated that the increased glucose uptake may be due to increases in peroxisome proliferator-activated receptor γ (PPARγ) activity and glucose transporter-4 (GLUT-4) expression. These results indicate that the isolated phenylpropanoid glucosides, particularly compound 4, have the potential to be developed into antidiabetic compounds.

A new lignan with hypoglycemic activity from Tadehagi triquetrum.[Pubmed: 25612052]

A new lignan named tadehaginosin, together with a known compound 3,4-dihydro-4-(4'-hydroxyphenyl)-5,7-dihydroxycoumarin, was isolated from the aerial part of Tadehagi triquetrum. The new structure was determined by various spectroscopic techniques ((1)H and (13)C APT, HSQC, HMBC, (1)H-(1)HCOSY, NOESY and HR-ESI-MS). The two isolates were evaluated for their hypoglycemic effects in vitro. Biological investigation showed that both of them possessed the capability to increase glucose consumption by HepG2 cells.

Tadehaginoside modulates lipogenesis and glucose consumption in HepG2 cells.[Pubmed: 25589148]

Tadehaginoside (TS) is a phenylpropanoid glycoside found in Tadehagi triquetrum, a medicinal plant with multiple biological activities. This study investigated the effect of TS on lipogenesis and glucose consumption in HepG2 cells. Treatment with TS inhibited lipid accumulation in a dose-dependent manner. This inhibition was closely associated with the downregulation of lipogenic genes such as SREBP-1a, SREBP-2 and their downstream targets (FAS, ACC, HMGR) and the upregulation of lipolytic gene PPARα as revealed by real-time quantitative PCR. Further investigation showed that TS significantly stimulated glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes, which could be partially explained by the upregulation of PPARγ. Collectively, these results clearly indicate that TS is an effective regulator of lipogenesis and glucose consumption, which could be useful in treatment of obesity and diabetes.

Antihepatotoxic effect of tadehaginoside, extracted from Tadehagi triquetrum (L.), against CCl4-lesioned rats through activating the Nrf2 signaling pathway and attenuating the inflammatory response.[Pubmed: 24448843]

Recently, an increasing number of studies suggest that oxidative stress and inflammation are associated with hepatocellular injuries. Thus, we aimed to evaluate the potential hepatoprotective role of tadehaginoside (TA) on liver lesions induced by carbon tetrachloride (CCl4). The results in vitro suggested that TA dose-dependently suppressed the cell proliferation of HepG2 cells, whereas the phosphorylated level of IκBα in cells was effectively inactivated. The study in vivo showed that TA significantly lowered the serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin E (IgE), and leukotriene (LT) in CCl4-lesioned rats. Pathological examination indicated that CCl4-induced hepatocellular damage was effectively mitigated by TA treatment. Meanwhile, the contents of γ-glutamylcysteine synthetase (γ-GCS), glutathione (GSH), and catalase (CAT) in liver tissue were gradually elevated. In addition, cytochrome c oxidase (COX) mRNA expression in hepatocytes was markedly upregulated, and nuclear factor E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels were progressively increased. Furthermore, the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB)-expressed protein were downregulated. These findings demonstrate that tadehaginoside effectively protects against CCl4-induced oxidative injury and inflammatory reaction in hepatocytes, in which the underlying mechanisms are involved in activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway, thereby attenuating oxidative stress and reducing the inflammation in liver cells.

Four new prenylated isoflavonoids in Tadehagi triquetrum.[Pubmed: 15656660]

Investigation on the anthelminthic bioactive compounds of the ethanol extract of Tadehagi triquetrum resulted in the isolation of three new prenylated isoflavones, triquetrumones A (1), B (2), and C (3), and one new prenylated biisoflavanone, (R)-triquetrumone D (4), along with 16 known compounds, cyclokievitone (5), yukovanol (6), aromadendrin (7), kaempferol (8), astragalin (9), 2-O-methyl-l-chiro-inositol (10), galactitol (11), p-hydroxycinnamic acid (12), ursolic acid (13), betulinic acid (14), beta-sitosterol (15), daucosterol (16), stigmasterol (17), stigmasta-5,22-dien-3-O-beta-d-glucopyranoside (18), saccharose (19), and docosanoic acid (20). The structures of 1-4 were elucidated on the basis of spectroscopic and spectrometric methods. Compounds 1-3 displayed mild anthelminthic bioactivity, and compound 3 showed a significant binding ability to the estrogen receptor.