Tilianin

Mol Med Rep. 2015 Mar;11(3):2227-33.

Cardioprotective effects of tilianin in rat myocardial ischemia-reperfusion injury.[Pubmed: 25405380 ]

Tilianin, the main effective flavonoid monomer enriched from Dracocephalum moldavuca L., has been shown to have cardioprotective effects. However, the mechanism of Tilianin cardioprotection remains largely unknown. The present study aimed to investigate the effects of Tilianin preconditioning on myocardial ischemia/reperfusion injury and to analyze the possible mechanism of action.
METHODS AND RESULTS:
A total of 48 male Sprague Dawley rats were randomized into sham, model myocardial ischemia/reperfusion injury (MI/RI), propranolol hydrochloride positive control, and high‑, medium‑ and low‑dose Tilianin groups (n=8 each). The results showed that Tilianin preconditioning significantly increased ATPase activity (P<0.01 and P<0.05) as compared with the model group. With regards to the regulation of endothelial function, significant decreases (P<0.01 and P<0.05) were detected in the serum NO levels and myocardial NOS activity when Tilianin was administered to MI/RI rats, as compared with the model group, . In addition, the Tilianin drug groups exhibited dose‑dependent reductions in the serum levels of endothelin 1 and thromboxane B2, and increases in the serum levels of calcitonin gene‑related peptide and 6‑keto prostaglandin F1a as compared with the model group (P<0.01 and P<0.05). Notably, the administration of Tilianin significantly inhibited apoptosis, as evidenced by an increase in Bcl‑2 expression, and reductions in Bax and caspase‑3 mRNA expression levels (P<0.01 and P<0.05).
CONCLUSIONS:
These data indicate that pretreatment with Tilianin exerts potent cardioprotective effects in rats with MI/RI. The anti‑MI/RI effects comprised relieving calcium overload, correction of energy metabolism, improvement of endothelial function and inhibiting cell apoptosis.

Biochem Pharmacol. 2009 Jul 1;78(1):54-61.

Antihypertensive and vasorelaxant effects of tilianin isolated from Agastache mexicana are mediated by NO/cGMP pathway and potassium channel opening.[Pubmed: 19447223]

Current investigation was undertaken to elucidate the mode of action of Tilianin, isolated from Agastache mexicana, as a vasorelaxant agent on in vitro functional rat thoracic aorta test and to investigate the in vivo antihypertensive effect on spontaneously hypertensive rats (SHR).
METHODS AND RESULTS:
Tilianin (0.002-933 microM) induced significant relaxation in a concentration- and endothelium-dependent and -independent manners in aortic rings pre-contracted with noradrenaline (NA, 0.1 microM), and serotonin (5-HT, 100 microM). Furthermore, Tilianin (130 microM) provoked a significant displacement to the left in the relaxation curve induced by sodium nitroprusside (SNP; 0.32 nM to 0.1 microM). Moreover, Tilianin induced significant in vitro NO overproduction (1.49 +/- 0.86 microM of nitrites/g of tissue) in rat aorta compared with vehicle (p < 0.05). In addition, pre-treatment with tetraethylammonium (TEA, 5 mM) and 2-aminopyridine (2-AP, 0.1 microM) shifted to the right the relaxant curve induced by Tilianin (p < 0.05). Finally, a single oral administration of Tilianin (50 mg/kg) exhibited a significant decrease in systolic and diastolic blood pressures (p < 0.05) in SHR model.
CONCLUSIONS:
Results indicate that Tilianin mediates relaxation mainly by an endothelium-dependent manner,probably due to NO release, and also through an endothelium-independent pathway by opening K+ channels, both causing the antihypertensive effect.

Zhongguo Zhong Yao Za Zhi. 2013 Apr;38(7):1079-82.

Study on intestinal absorption of tilianin in rats of single-pass perfusion model.[Pubmed: 23847962]

To study the intestinal absorption mechanism of Tilianin in rats.
METHODS AND RESULTS:
The single-pass perfusion model was established in rats. The concentrations of Tilianin with in situ intestinal perfusion were determined by HPLC. The impact factors, such as verapamil, reserpine, phloridzin and rifampicin, on Ka and Papp of Tilianin in rat jejunum were investigated. Compared with the control group, Ka and Papp in rat jejunum were significantly higher after being added with verapamil and reserpine (P < 0.05). Papp of Tilianin in rat jejunum was significantly lower after being added with phloridzin (P < 0.05). Compared with the control group, both Ka and Papp of Tilianin in rat jejunum were not significantly higher after being added with rifampicin.
CONCLUSIONS:
Tilianin is the substrate of P-gp, BCRP and SGLT1. The effluent effect of P-gp and BCRP is the main mechanism of Tilianin in intestinal absorption, indicating that Tilianin can realize intestinal absorption and transport by relying on SGLT1. Tilianin is not the substrate of bile salt transporter protein.

J Environ Pathol Toxicol Oncol . 2020;39(4):335-344.

Role of Tilianin against Acute Lung Injury in In Vitro LPS-Induced Alveolar Macrophage Cells and an In Vivo C57BL/6 Mice Model[Pubmed: 33389905]

Abstract Acute lung injury (ALI) is a disorder of pulmonary tissue caused by prolonged inflammation and uncontrolled oxidative stress. Tilianin is a natural polyphenol, acknowledged for its anti-inflammatory and antioxidant activities. The goal of this work was to explore the effect of Tilianin in an LPS-challenged ALI model. The mechanistic investigation was carried out using both in vitro and in vivo experiments. The RAW264.7 macrophage cell and C57BL/6 mice were treated with Tilianin (10 and 20 μM) and then induced with LPS (1 μg/mL) overnight. The C57BL/6 mouse was administered LPS intratracheally (2 mg/kg) to induce ALI prior to Tilianin intraperitoneal treatment (10 mg/kg). In vitro, the results showed that Tilianin reduced secretion of LPS-induced proinflammatory cytokine. In vivo, prophylactic treatment with Tilianin attenuated infiltration of macrophages and histopathological changes and improved inflammation as shown by a marked reduction in inflammatory mediators found in bronchoalveolar lavage fluid (BALF). Furthermore, Tilianin effectively suppressed MDA levels and GSH and SOD in ALI were increased. Collectively, these findings suggest that Tilianin is a potential agent for ameliorating LPS-induced ALI.

Biomed Chromatogr . 2018 Apr;32(4).

Simultaneous determination of tilianin and its metabolites in mice using ultra-high-performance liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study[Pubmed: 29144552]

Abstract Tilianin is an active flavonoid glycoside found in many medical plants. Data are lacking regarding its pharmacokinetics and disposition in vivo. The objective of this study was to develop a sensitive, reliable and validated ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify Tilianin and its main metabolites and to determine its pharmacokinetics in wild-type and breast cancer resistance protein knockout (Bcrp1-/-) FVB mice. Chromatographic separation was accomplished on a C18 column by utilizing acetonitrile and 0.5 mm ammonium acetate as the mobile phase. Mass spectrometric detection was performed using electrospray ionization in both positive and negative modes. The results showed that the precision, accuracy and recovery, as well as the stability of Tilianin and its metabolites in mouse plasma, were all within acceptable limits. Acacetin-7-glucuronide and acacetin-7-sulfate were the major metabolites of Tilianin in mouse plasma. Moreover, systemic exposure of acacetin-7-sulfate was significantly higher in Bcrp1 (-/-) FVB mice compared with wild-type FVB mice. In conclusion, the fully validated UHPLC-MS/MS method was sensitive, reliable, and was successfully applied to assess the pharmacokinetics of Tilianin in wild-type and Bcrp1 (-/-) FVB mice. Breast cancer resistance protein had a significant impact on the elimination of the sulfated metabolite of Tilianin in vivo. Keywords: BCRP; UHPLC-MS/MS; pharmacokinetics; Tilianin.

Asian Pac J Trop Med. 2015 Mar;8(3):185-90.

Depressant effects of Agastache mexicana methanol extract and one of major metabolites tilianin.[Pubmed: 25902158]

To determine the depressant-like effects and the possible mechanism of action of Tilianin isolated from active methanol extract of Agastache mexicana (A. mexicana). Also, to establish the pharmacophoric requirements of Tilianin, as a possible ligand of GABAA/BZD receptor, by the alignment of diazepam, CGS-9896 and diindole, using a previously described pharmacophoric model.
METHODS AND RESULTS:
Tilianin (30 to 300 mg/kg, ip. and 300 mg/kg, po.) and methanol crude extract (10 to 300 mg/kg, ip. and 300 mg/kg po.) from A. mexicana were evaluated for potential sedative and anxiolytic-like response drugs by using open-field, hole-board, cylinder of exploration, plus-maze and sodium pentobarbital-induced hypnosis mice methods. Methanol extract and Tilianin showed anxiolytic-like activity from a dosage of 30 mg/kg, ip. or 300 mg/kg, po. and were less potent than diazepam 0.1 mg/kg, a reference anxiolytic drug used. Moreover, depressant activity of both potentiates sodium pentobarbital (SP)-induced sleeping time. The anxiolytic-like effect of 30 mg/kg ip. observed for the extract and Tilianin, by using the plus-maze model, was partially prevented in the presence of flumazenil (a GABAA/BZD antagonist, 5 mg/kg ip.) but not in the presence of WAY 100635 (a selective 5-HT1A receptor antagonist, 0.32 mg/kg, ip.). Pharmacophoric modeling alignments of three agonist of GABAA/BZD allow identify seven chemical features. Tilianin contains six of the seven features previously determined.
CONCLUSIONS:
Results indicate that Tilianin is one of the bioactive metabolites in the anxiolytic-like activity of A. mexicana, reinforcing its central nervous system uses, where GABAA/BZD, but not 5-HT1A, receptors are partially involved.