Phillyrin

Food Chem. 2013 Jan 15;136(2):415-25.

Phillyrin attenuates high glucose-induced lipid accumulation in human HepG2 hepatocytes through the activation of LKB1/AMP-activated protein kinase-dependent signalling.[Pubmed: 23122079]

Phillyrin, an active constituent found in many medicinal plants and certain functional foods, has anti-obesity activity in vivo. The aim of our study was to provide new data on the molecular mechanism(s) underlying the role of Phillyrin in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes.
METHODS AND RESULTS:
We found that Phillyrin suppressed high glucose-induced lipid accumulation in HepG2 cells. Phillyrin strongly inhibited high glucose-induced fatty acid synthase (FAS) expression by modulating sterol regulatory element-binding protein-1c (SREBP-1c) activation. Moreover, use of the pharmacological AMP-activated protein kinase (AMPK) inhibitor compound C revealed that AMPK is essential for suppressing SREBP-1c expression in Phillyrin-treated cells. Finally, we found that liver kinase B1 (LKB1) phosphorylation is required for the Phillyrin-enhanced activation of AMPK in HepG2 hepatocytes.
CONCLUSIONS:
These results indicate that Phillyrin prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1/AMPK activation, suggesting that Phillyrin is a novel AMPK activator with a role in the prevention and treatment of obesity.

Xenobiotica . 2017 Apr;47(4):297-303.

Effects of phillyrin and forsythoside A on rat cytochrome P450 activities in vivo and in vitro[Pubmed: 27310729]

Abstract 1. Phillyrin and forsythoside A are two important active ingredients in Forsythia suspensa. However, the effects of Phillyrin and forsythoside A on the activities of cytochrome P450 (CYP450) remain unclear. 2. This study aimed to investigate the effects of Phillyrin and forsythoside A on the activities of CYP1A2, CYP2C11, CYP2D1 and CYP3A1/2 by cocktail probe drugs in rats both in vivo and in vitro. 3. Many pharmacokinetic parameters of caffeine and metoprolol in Phillyrin pretreatment group, caffeine and tolbutamide in forsythoside A pretreatment group were affected significantly. In rat liver microsomal incubation system, the concentrations of acetaminophen and dextrophan in the Phillyrin pretreatment group are higher than blank control group by 207.69% and 125.00%, however, the concentrations of 4-hydroxytolbutamide and 6β-hydroxytestosterone were not significantly altered. The concentrations of acetaminophen and 4-hydroxytolbutamide in the forsythoside A pretreatment group are higher than blank control group by 223.07% and 154.16%, whereas the concentrations of dextrophan and 6β-hydroxytestosterone were not significantly altered. 4. These results indicated that Phillyrin had potential inductive effects on rat CYP1A2 and CYP2D1 activities, without affecting CYP2C11 and CYP3A1/2 activities. Moreover, forsythoside A had inductive effects on the activities of CYP1A2 and CYP2C11, without affecting CYP2D1 and CYP3A1/2 activities. Keywords: CYP1A2; CYP2C11; CYP2D1; CYP3A1/2; cytochrome P450; forsythoside A; Phillyrin.

Zhong Yao Cai. 2005 Feb;28(2):123-4.

[Effect of phillyrin on the anti-obesity in nutritive obesity mice].[Pubmed: 15981888]

To study on the anti-obesity effect of Phillyrin in nutritive obesity mice.
METHODS AND RESULTS:
The alimentary obesity model was established by hyperalimentation. The wet weight of fat, fat index, number of fat cells per unit visual field, Lee's index, jejunum microvillus area, serum triglyceride and cholesterol were selected to observe the anti-obesity effect of Phillyrin. Phillyrin could lower wet weight of fat (P < 0.01), fat index (P < 0.05 or P < 0.01), diameter of fat cell and Lee's index (P < 0.05), decrease the jejunum microvillus area, lower the level of serum triglyceride and cholesterol.
CONCLUSIONS:
Phillyrin has anti-obesity effect in nutritive obesity mice.

Arch Pharm Res . 2016 Jul;39(7):998-1005.

Protective effects of phillyrin against influenza A virus in vivo[Pubmed: 27323762]

Abstract Influenza A virus infection represents a great threat to public health. However, owing to side effects and the emergence of resistant virus strains, the use of currently available anti-influenza drugs may be limited. In order to identify novel anti-influenza drugs, we investigated the antiviral effects of Phillyrin against influenza A virus infection in vivo. The mean survival time, lung index, viral titers, influenza hemagglutinin (HA) protein and serum cytokines levels, and histopathological changes in lung tissue were examined. Administration of Phillyrin at a dose of 20 mg/kg/day for 3 days significantly prolonged the mean survival time, reduced the lung index, decreased the virus titers and interleukin-6 levels, reduced the expression of HA, and attenuated lung tissue damage in mice infected with influenza A virus. Taken together, these data showed that Phillyrin had potential protective effects against infection caused by influenza A virus. Keywords: Influenza A virus; Mouse; Phillyrin.

Cell Mol Neurobiol. 2014 Nov;34(8):1165-73.

Protective effects of phillyrin on H2O 2-induced oxidative stress and apoptosis in PC12 cells.[Pubmed: 25146667]

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. We sought to elucidate possible effects of Phillyrin, an active constituent isolated from the Chinese medicinal herb Forsythia suspense, on hydrogen peroxide (H2O2)-induced cell death and determine the underlying molecular mechanisms in neuron-like PC12 cells.
METHODS AND RESULTS:
By MTT assay and lactate dehydrogenase (LDH) leakage assay, we found that Phillyrin treatment effectively protected PC12 cells against H2O2-induced cell damage. H2O2 exposure induced oxidative stress in PC12 cells, as revealed by enhanced oxidative stress and decreased activities of antioxidative enzymes, which were inhibited by Phillyrin pretreatment. ROS activated mitochondria-dependent apoptosis. The anti-apoptotic effects of Phillyrin were also confirmed by acridine orange/ethidium bromide (AO/EB) staining. Mitochondrial membrane potential decrease, cytochrome c release, caspases activation, activation of AIF and Endo G were observed in H2O2-treated cells by rhodamine 123 or western blot. Interestingly, Phillyrin effectively suppressed these changes. Moreover, Phillyrin could inhibit H2O2-induced up-regulation of Bax/Bcl-2 ratio.
CONCLUSIONS:
In conclusion, Phillyrin effectively inhibited H2O2-induced oxidative stress and apoptosis in PC12 cells.

Eur J Drug Metab Pharmacokinet. 2009 Apr-Jun;34(2):79-83.

Pharmacokinetics of phillyrin and forsythiaside following iv administration to Beagle dog.[Pubmed: 19645216]

The objective of the present study was to firstly investigate the in vivo pharmacokinetics of Phillyrin and forsythiaside in beagle dog.
METHODS AND RESULTS:
On I.V. administration, a rapid distribution was observed and followed by a slower elimination for Phillyrin and forsythiaside. The mean t(1/2Z) was 49.99, 34.87 and 43.81 min for 0.19, 0.70 and 1.43 mg/kg of Phillyrin, and 60.90, 64.30, 57.99 min for 0.62, 1.39 and 5.52 mg/kg of forsythiaside respectively. And the AUC(o-t) increased linearly from 36.51 to 160.22 microg x min/ml of Phillyrin and from 50.63 to 681.08 microg x min/ml after the three dosage administrated. In the range of the dose examined, the pharmacokinetics of Phillyrin and forsythiaside in beagle dog was based on first order kinetics.
CONCLUSIONS:
Although both drugs were widely distributed to various tissues in the dog, no concerns about extensive binding to tissues that may be consumed by the public should a dog be exposed to Phillyrin and forsythiaside according to the rapid elimination.

Fitoterapia. 2013 Oct;90:132-9.

Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice.[Pubmed: 23751215]

Phillyrin (Phil) is one of the main chemical constituents of Forsythia suspensa (Thunb.), which has shown to be an important traditional Chinese medicine. We tested the hypothesis that Phil modulates pulmonary inflammation in an ALI model induced by LPS.
METHODS AND RESULTS:
Male BALB/c mice were pretreated with or without Phil before respiratory administration with LPS, and pretreated with dexamethasone as a control. Cytokine release (TNF-α, IL-1β, and IL-6) and amounts of inflammatory cell in bronchoalveolar lavage fluid (BALF) were detected by ELISA and cell counting separately. Pathologic changes, including neutrophil infiltration, interstitial edema, hemorrhage, hyaline membrane formation, necrosis, and congestion during acute lung injury in mice were evaluated via pathological section with HE staining. To further investigate the mechanism of Phil anti-inflammatory effects, activation of MAPK and NF-κB pathways was tested by western blot assay. Phil pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by Phil pretreatment. In addition, Phil decreased the production of the proinflammatory cytokines including (TNF-α, IL-1β, and IL-6) and the concentration of myeloperoxidase (MPO) in lung tissues. Phil pretreatment also significantly suppressed LPS-induced activation of MAPK and NF-κB pathways in lung tissues.
CONCLUSIONS:
Taken together, the results suggest that Phil may have a protective effect on LPS-induced ALI, and it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways. Phil may be a new preventive agent of ALI in the clinical setting.