Combining use of Phillyrin and autophagy blocker alleviates laryngeal squamous cell carcinoma via AMPK/mTOR/p70S6K signaling

Wang, Da-hua; He, Xi; He, Qiuming

doi:10.1042/bsr20190459

Cited by 4 publications

(3 citation statements)

References 40 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yang et al [ 11 ] showed that forsythin could reduce neutrophil infiltration and tissue necrosis of the zebrafish induced by lipopolysaccharide (LPS) through regulating the expression of inflammatory cytokines (IL-6, IL-1 β , and NF-kB). Another study has indicated that forsythin combined with autophagy blockers could inhibit the proliferation of human laryngeal carcinoma epithelial cells (HEp-2 cells) and induced their apoptosis, which may be a novel strategy in treatment of laryngeal squamous cell carcinoma [ 12 ]. However, the safety of forsythin has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Han

Guo

Meng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Introduction. Forsythin is the main ingredient of Forsythia suspensa and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use. Methods. Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of Salmonella typhimurium were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin. Results. Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture ( p > 0.05 ). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture ( p > 0.05 ). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method. Conclusion. Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.

show abstract

Section: Introductionmentioning

confidence: 99%

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Han

Guo

Meng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…A growing number of studies have shown that various inflammatory factors lead to the occurrence and metastasis of tumors by participating in and changing the formation of the microenvironment [59]. Combined with the anti-inflammatory effect of phillyrin, this induction of autophagy in tumor cells may be related to the AMPK/mTOR/p70S6K pathway [44]. From another study of Lewis lung carcinoma, in vivo experiments in mice showed that phillyrin inhibited VEGF specifically expressed in lung cancer tissue, thereby inhibiting further tumor angiogenesis.…”

Section: Anti-cancer Effectsmentioning

confidence: 99%

Review on the Pharmacological Properties of Phillyrin

Zhou

Cheng

et al. 2022

Molecules

View full text Add to dashboard Cite

Phillyrin is an effective lignan glycoside extracted from a traditional Chinese medicine Forsythia suspensa (Thunb.) Vahl (Oleaceae). It mainly exists in the roots, stems, leaves and fruits of the plant, with the highest content in the leaves. In terms of its medicinal application, there are a large number of experimental data proving its pharmacological effects in vitro and in animal models, such as anti-inflammatory, anti-obesity, anti-tumor, etc. Furthermore, pharmacokinetic experiments have also shown phillyrin’s high effectiveness and low toxicity. Despite more than one thousand studies in the literature on phillyrin retrievable from Web of Science, PubMed, and CNKI, few reviews on its pharmacological activities have been presented conclusively. In this paper, we aimed to summarize the pharmacological and pharmacokinetic characteristics of phillyrin from the current literature, focusing on its anti-inflammatory, anti-aging, antiviral, antibacterial, hepatoprotective and anti-cancer effects, hoping to come up with new insights for its application as well as future studies.

show abstract

“…Forsythia has more than 150 main chemical components, including lignans, phenylethanoid glycosides, pentacyclic triterpenoids and avonoids and so on. In recent years, the antiin ammatory activity and mechanism of many active ingredients of Forsythia Fructus, such as phillyrin, have been reported [11][12][13][14]. However, another active ingredient in Forsythia Fructus is phillygenin (PHI) (4-[(3S,3aR,6R,6aR)-6-(3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro [3,4-c]furan-3-yl]-2methoxyphenol) that is often overlooked (Fig.…”

Section: Introductionmentioning

confidence: 99%

Based on Proteomics Reveals the Anti-inflammatory Mechanism of Phillygenin by Inhibition NF-κB Pathway

Zhou¹,

Tang²,

Liao³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Inflammation is a common pathological phenomenon when homeostasis is seriously disturbed. Phillygenin (PHI) is a lignin component isolated from Forsythiae Fructus, which showed a good anti-inflammation effect. However, the mechanisms of PHI on anti-inflammation have not yet been systematically elucidated.Methods: In the study, the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to investigate mechanisms of PHI on inflammation. The effect of PHI on LPS-induced IL-1β and PGE2 inflammatory factors was detected by ELISA, and the mRNA expression of IL-1β, IL-6 and TNF-α was detected by RT-qPCR. Proteomics studies the signaling pathways that may be affected by PHI. Molecular docking technology was used to study the possible targets of PHI on NF-kB pathway. Western blot was performed to detect progressive changes in protein expression.Results: The research showed that PHI significantly inhibited the robust increase of IL-1β and PGE2, and lowered the transcriptional level of inflammatory genes including IL-6, IL-1β and PGE2 in LPS-stimulated RAW264.7 cells. Proteomics results indicated that PHI was involved in the regulation of multiple signaling pathways. Molecular docking results indicated that PHI has an affinity for most proteins in NF-kB pathway. Western blot analysis showed that PHI inhibited LPS-induced NF-κB pathway activation. Conclusion: PHI inhibits the activation of NF-κB pathway, thereby inhibiting the expression of related inflammatory genes and the release of cytokines, thus showing remarkable anti-inflammatory effect.

show abstract

Combining use of Phillyrin and autophagy blocker alleviates laryngeal squamous cell carcinoma via AMPK/mTOR/p70S6K signaling

Cited by 4 publications

References 40 publications

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Review on the Pharmacological Properties of Phillyrin

Based on Proteomics Reveals the Anti-inflammatory Mechanism of Phillygenin by Inhibition NF-κB Pathway

Contact Info

Product

Resources

About