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The Shuanghuanglian formula (SF) is a famous antimicrobial and antiviral traditional Chinese medicine that is made of Lonicera japonica Thunb., Scutellaria baicalensis Georgi, and Forsythia suspensa (Thunb.) Vahl. According to the Chinese Pharmacopoeia, the SF is commonly administered in the forms of oral liquid, tablets, and injection. It has long been used to treat acute respiratory tract infections, especially lung infection.
AIM OF THE STUDY:
In the light of the increasing incidence of multidrug resistance to conventional antibiotics, the aim of this study was to screen potential anti-virulence agents against Pseudomonas aeruginosa from the extract of the SF.
MATERIALS AND METHODS:
The SF was used for effective compounds screening via the combination of the molecule docking approach and ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Fifty-one anti-virulence-related proteins were docked, 26 identified compounds were from SF. Subsequently, the top-scoring screened compound was assessed via bioactive-related assays, including the quantification of alginate biosynthesis, anti-biofilm assays, and the A549 human lung cells infection.
A flavonoid Lonicerin was found to be bonded with the active site of the alginate secretion protein (AlgE) with the highest score in molecule docking. Furthermore, we validated that Lonicerin could significantly reduce alginate secretion (25 μg/mL) and biofilm formation (12.5 μg/mL) at a sub-MIC concentration without inhibiting the proliferation of P. aeruginosa or influencing the expression of AlgE, which suggested that Lonicerin may directly inhibit AlgE. In addition, Lonicerin was proven to inhibit the infection of P. aeruginosa in the A549 cells.
This work reported on the first potential AlgE antagonist that was derived from herbal resources. Lonicerin was proven to be an effective inhibitor in-vitro of P. aeruginosa infection.
Copyright © 2019 Elsevier B.V. All rights reserved.
AlgE; Alginate; Lonicerin; Molecule docking; Pseudomonas aeruginosa
Lonicerin, an anti-algE flavonoid against Pseudomonas aeruginosa virulence screened from Shuanghuanglian formula by molecule docking based strategy.
Xu Z1, Li K2, Pan T3, Liu J1, Li B1, Li C1, Wang S4, Diao Y5, Liu X6.
2019 Jul 15
Acute lung injury (ALI) is a life-threatening condition caused by severe inflammation of lung tissues. We hypothesized that lipopolysaccharide induced acute lung inflammation and injury in mice might be controlled by lonicerin (LCR), a plant flavonoid that impacts immunity, oxidative stress, and cell proliferation. LCR reduced pathological changes including pulmonary edema, elevation of protein in bronchoalveolar lavage, inflammation, pro-inflammatory gene expression, expression of toll-like receptor 4/nuclear factor-kappa B, apoptosis, and significantly reduced mortality. Together, the results suggest that LCR might be a potential and effective candidate for the treatment of ALI that acts by inhibiting inflammation and apoptosis.
Lonicerin prevents inflammation and apoptosis in LPS-induced acute lung injury.
Gu LZ1, Sun H2.
2020 Jan 1
Fungal arthritis is a potentially serious disease resulting in rapid destruction of the joint. Among the various Candida species, Candida albicans is the most commonly associated with fungal arthritis. In the present study, we examined the effect of lonicerin, a flavonoid isolated from Lonicerae Flos, on an arthritis caused by C. albicans cell wall (CACW) in mice. To examine the effect, an emulsified mixture of CACW and complete Freund’s adjuvant (CACW/CFA) was injected into BALB/c mice via hind footpad route on days -3, -2, and -1. On Day 0, mice with the swollen footpad received lonicerin at 1 or 2 mg/dose/time intraperitoneally 3 times every other day. The footpad-swelling was measured for 20 days. Results showed that the lonicerin treatment reduced the edema at all dose levels, and, furthermore, there was app. 54% edema reduction in animals given the 2 mg-dose at the peak (day 10) of septic arthritis (p < 0.05). Since the peak, the edema was reduced in similar rates. This antiarthritic activity appeared to be mediated by lonicerin's ability to suppress T cell proliferation, nitric oxide production from macrophages, and shift of cellular immunity from Th1- toward Th2-type responses, all of which are beneficial to treat arthritis. In addition, the flavonoid had anticandidal activity (p < 0.01). These data suggest that lonicerin alone, which has both anti-arthritic and antifungal activities, can result in a combination therapy for the treatment of fungal arthritis due to C. albicans infection.
Antiarthritic effect of lonicerin on Candida albicans arthritis in mice.
Lee JH1, Han Y.