查找使用阿拉丁产品的科研文献

Efficient extraction of Licochalcone a with deep eutectic solvent: A promising drug for the treatment of dermatophytosis

Chunlan Sun,Liping Wang,Binjie Zhou,Xialin Jiang,Haiyan Li,Zhangguo Liu

Uncontrolled breeding and improper management of pet cats and dogs have led to the spread of zoonotic Microsporum canis ( M. canis ) infection, which poses challenges to clinical medication. Therefore, there is an urgent need to explore and discover potential fungicides against M. canis . In this study, licochalcone A (LicoA) was prepared by a green and efficient deep eutectic solvent method based on ultrasonic assisted extraction (DES-UAE). The DES-UAE process with choline chloride and propionic acid as solvent was optimized by response surface method with the extraction amount of LicoA as the objective. Following separation and purification, the purity of LicoA reached 99.79 %. Additionally, LicoA demonstrated significant antifungal activity against M. canis with MIC of 4 μg/mL. LicoA inhibited the synthesis of ergosterol in the fungal membrane, destroy the integrity of the cell membrane, lead to the increase of membrane permeability, the release of intracellular electrolytes, the leakage of nucleic acids and proteins, and affect the normal growth of hyphae. ATPase activity was reduced, and mitochondrial membrane potential (MMP) was reduced, resulting in increased levels of ROS, which eventually induced apoptosis in M. canis . Further transcriptome analysis revealed that LicoA treatment affected “cell integrity”, “energy metabolism”, and “oxidative stress” metabolic pathways in M. canis , including cell wall synthesis, ergosterol synthesis, tricarboxylic acid cycle, electron transport chain, and ribosome metabolism, leading to fungal cell apoptosis. These studies establish an efficient method for LicoA extraction and provide a basis for its use as a novel antifungal agent for the treatment of dermatophytosis.

Antioxidant Mechanisms of Echinatin and Licochalcone A

Minshi Liang,Xican Li,Xiaojian Ouyang,Hong Xie,Dongfeng Chen

Echinatin and its 1,1-dimethyl-2-propenyl derivative licochalcone A are two chalcones found in the Chinese herbal medicineGancao. First, their antioxidant mechanisms were investigated using four sets of colorimetric measurements in this study. Three sets were performed in aqueous solution, namely Cu2+-reduction, Fe3+-reduction, and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-scavenging measurements, while 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•)-scavenging colorimetric measurements were conducted in methanol solution. The four sets of measurements showed that the radical-scavenging (or metal-reduction) percentages for both echinatin and licochalcone A increased dose-dependently. However, echinatin always gave higher IC50values than licochalcone A. Further, each product of the reactions of the chalcones with DPPH• was determined using electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS). The UPLC-ESI-Q-TOF-MS/MS determination for echinatin yielded several echinatin–DPPH adduct peaks (m/z662, 226, and 196) and dimeric echinatin peaks (m/z538, 417, and 297). Similarly, that for licochalcone A yielded licochalcone A-DPPH adduct peaks (m/z730, 226, and 196) and dimeric licochalcone A peaks (m/z674 and 553). Finally, the above experimental data were analyzed using mass spectrometry data analysis techniques, resonance theory, and ionization constant calculations. It was concluded that, (i) in aqueous solution, both echinatin and licochalcone A may undergo an electron transfer (ET) and a proton transfer (PT) to cause the antioxidant action. In addition, (ii) in alcoholic solution, hydrogen atom transfer (HAT) antioxidant mechanisms may also occur for both. HAT may preferably occur at the 4-OH, rather than the 4′-OH. Accordingly, the oxygen at the 4-position participates in radical adduct formation (RAF). Lastly, (iii) the 1,1-dimethyl-2-propenyl substituent improves the antioxidant action in both aqueous and alcoholic solutions.Keywords:antioxidant;echinatin;licochalcone A;1,1-dimethyl-2-propenyl;α,α-dimethyl-β-propenyl;radical adduct formation;dimer

Glycyrrhiza acid-Licochalcone A complexes for enhanced bioavailability and anti-melanogenic effect of Licochalcone A: cellular uptake and in vitro experiments

Zhuxian Wang,Yaqi Xue,Quanfu Zeng,Zhaoming Zhu,Yuan Wang,Yufan Wu,Chunyan Shen,Hongxia Zhu,Cuiping Jiang,Li Liu,Qiang Liu

Licochalcone A (LicA) is a natural chalcones , well-known for its anti-melanogenic activity, however, its poor solubility leads to a limited topical bioavailability and clinical outcomes. Therefore, LicA-encapsulated glycyrrhiza acid (GA) (GA-LicA) micelles were formulated for higher cellular uptake and improved cutaneous applications. The physicochemical properties (morphology, size and charge), topical penetration, endocytic pathways, cellular uptake amount (CUA) and intracellular distribution of the GA-LicA micelles were studied. Moreover, the anti-melanogenic mechanisms including antioxidant properties, melanogenesis-mediated enzymes and melanin generation as well as cell apoptosis in A375 cells were demonstrated. We found that significant increase amount of LicA was obtained into the epidermis after encapsulated in GA micelles, and the hair follicles were the preferential route for LicA permeation. Moreover, HaCaT and melanocytes possessed a significantly higher effective uptake and CUA for GA-LicA micelles than that of the crude LicA. Caveolae-mediated and actin filaments-mediated endocytosis, caveolae-mediated endocytosis were respectively involved in cellular uptake of GA-LicA micelles for HaCaT cells and melanocytes. Furthermore, GA-LicA micelles possessed a synergistic anti-melanogenic effect by scavenging the free radicals, reducing the activity of α-glucosidase and tyrosinase , and inducing the cell apoptosis. Taken together, GA micelles can enhance the bioavailability and anti-melanogenic effect of LicA, and the article provided principles for rational design of formulations in whitening cosmetics.

SMEDDS for improved oral bioavailability and anti-hyperuricemic activity of licochalcone A

Zhongan Zhu,Jing Liu,Yuhang Yang,Michael Adu-Frimpong,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu

Preparation, characterization, pharmacokinetics, and antirenal injury activity studies of Licochalcone A-loaded liposomes

Jing Liu,Zhongan Zhu,Yuhang Yang,Michael Adu-Frimpong,Lin Chen,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu

A liposome of Licochalcone A (LCA-Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA-Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z-potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA-liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z-potential and EE of LCA-Liposomes were 71.78 ± 0.99 nm, −38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA-Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA-Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA-related functional products. Practical applications As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA-Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future.

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects

Ci-Qin Li,Jin-Hui Shi,Jie Mu,An-Qi Wang,Li-Wei Zou,Guang-Bo Ge

A set of 22 analogs of licochalcone A was designed and synthesized to explore their potentials as dipeptidyl peptidase 4 (DPP4) inhibitors with anti-inflammatory effects. The anti-DPP4 effects of these analogs were evaluated using the fluorescent substrate Gly-Pro-N-butyl-4-amino-1,8-naphthalimide (GP-BAN). The nitro-substituted analogue 27 exhibited the most potent activity (Ki = 0.96 μM). A structure–activity relationship investigation revealed that 4-hydroxyl and 5-chloro substituents are essential for DPP4 inhibition, while the 3′-nitro substituent improved both DPP4 inhibition and microsomal stability. Furthermore, compound 27 demonstrated good selectivity for DPP4 over other proteases, including dipeptidyl peptidase 9 (DPP9), thrombin, prolyl endopeptidase (PREP), and fibroblast activation protein (FAP). The cytotoxic effect of 27 was evaluated in cancer cell lines HepG-2 and Caco-2 and in somatic RAW264.7 cells and RPTECs. Compound 27 showed no toxicity to normal cells and weak toxicity to cancer cells. In a living cell imaging assay, 27 blocked the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells. This compound also dose-dependently suppressed the expression levels of the chemokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).

Licochalcone a Induces ROS-Mediated Apoptosis through TrxR1 Inactivation in Colorectal Cancer Cells

Peng Wu,Ting Yu,Jun Wu,Junfeng Chen

Licochalcone A (LCA) exhibited anticancer activity through modulating reactive oxygen species (ROS) levels in some cancer cells and has been evidenced to suppress colorectal cancer (CRC) formation and progression. However, whether LCA mediates the progression of CRC by regulating ROS production remains unclear. To address this, HCT-116 cells were treated with LCA, resulting in G0/G1 phase arrest, apoptosis, and high ROS generation, which were attenuated by N-acetyl-L-cysteine, a ROS inhibitor. In addition, LCA suppressed the expression of thioredoxin reductase 1 (TrxR1) in HCT-116 cells, leading to high ROS levels and apoptosis. Moreover, LCA administration combined with TrxR1 inhibition further enhanced the production of ROS and apoptosis in HCT-116 cells compared to LCA administration or TrxR1 inhibition alone. These results demonstrated that LCA might enhance the production of ROS by targeting TrxR1, leading to apoptosis in HCT-116 cells, which provides potential insight for the interventional treatment of CRC.

Licochalcone A inhibits the assembly function of β-barrel assembly machinery in Escherichia coli

Liangwan Wei,Zhe Wang,Yindi Chu,Kun Cai,Wei Li,Piying Huang,Youcai Qin,Dailin Liu,Xiaocui Zhuang,Mingquan Guo,Xinbo Song,Enguo Fan

Antimicrobial resistance (AMR) crisis urges the development of new antibiotics. In the present work, we for the first time used bio-affinity ultrafiltration combined with HPLC-MS (UF-HPLC-MS) to examine the interaction between the outer membrane β-barrel proteins and natural products. Our results showed that natural product licochalcone A from licorice interacts with BamA and BamD with the enrichment factor of 6.38 ± 1.46 and 4.80 ± 1.23, respectively. The interaction was further confirmed by use of biacore analysis, which demonstrated that the Kd value between BamA/D and licochalcone was 6.63/28.27 μM, suggesting a good affinity. To examine the effect of licochalcone A on BamA/D function, the developed versatile in vitro reconstitution assay was used and the results showed that 128 μg/mL licochalcone A could reduce the outer membrane protein A integration efficiency to 20%. Although licochalcone A alone can not inhibit the growth of E. coli , but it can affect the membrane permeability , suggesting that licochalcone A holds the potential to be used as a sensitizer to combat AMR.

Licochalcone a Disrupted Mitochondrial Function to Promote Cuproptosis in Glioblastoma Through Regulating RAS/MAPK Pathway

Zhou Fengfeng,Li Chenglin,Che Fengyuan

To explore the effect of Licochalcone A on cuproptosis in glioma and the underlying mechanism, U87 MG and U251 cells were treated with 10, 20, and 30 µM Licochalcone A for 24 h. Key assays including immunofluorescence, TEM, mitochondrial membrane potential and morphological analysis, as well as other cuproptosis-related indexes were detected. Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used. An in vivo nude mouse xenograft model was established. Our results demonstrated that Licochalcone A triggered cuproptosis in a dose-dependent manner, and in U87 and U251 cells, 30 µM Licochalcone A treatment increased the Cu²⁺ accumulation by 2.86 ± 0.67 folds and 1.96 ± 0.39 folds, elevated pyruvic acid levels by 2.15 ± 0.23 folds and 2.57 ± 0.46 folds, reduced mitochondrial membrane potential by 34.13 ± 1.70% and 40.43 ± 9.05%, downregulated the protein expression of FDX1 and LIAS, and increased cellular ROS levels by 4.74 ± 0.85 folds and 5.10 ± 2.16 folds, respectively. These changes were accompanied by obvious mitochondrial swelling and cristae disruption, resulting in a significant inhibition of cell proliferation. Mechanistically, it promoted cuproptosis by inactivating RAS/ERK. In vivo, 10 mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.

Multi-omics revealed antibacterial mechanisms of licochalcone A against MRSA and its antimicrobic potential on pork meat

Fei Zeng,Shijuan Shao,Zhilu Zou,Siqi Guo,Yu Cai,Chunchao Yan,Yunzhong Chen,Maolin Wang,Tingting Shi

Licorice flavonoids (LFs) exhibit potent antibacterial activities against Gram-positive bacteria. However, the related mechanism remains unclear. This study aims to illustrate the mechanisms of licochalcone A (LA), a main flavonoid in LFs, against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA effect of LA was comprehensively investigated by a combination of proteomics and metabolomics studies. Meanwhile, LA was loaded in glycyrrhizin (GA) micelles (GA@LA micelles) to improve its water solubility. The results demonstrated that LA could disrupt the arginine metabolism and cause the accumulation of intracellular ROS in MRSA. In addition, LA could inhibit the expression of glucokinase in MRSA, which affect the synthesis of ATP, fatty acids, and peptidoglycan. GA@LA micelles have the latent ability to inhibit the growth of MRSA on fresh pork.

Licochalcone A-loaded elastic liposomes/silk fibroin composite hydrogel: A dual-functional transdermal platform for enhanced anti-photoaging efficacy

Zeyao Ouyang,Guannan Yu,Xinying Zhao,Kaiyuan Miao,Yan Meng,Xinyan Chen,Zhaohua Shi

Photoaging is predominantly driven by ultraviolet (UV) radiation, a key factor in extrinsic skin aging. Licochalcone A (LA), a natural flavonoid with antioxidant and anti-inflammatory properties, offers a promising alternative to conventional retinoid-based therapies due to its lower irritation potential. However, the poor skin penetration of LA limits its anti-photoaging application. To overcome this limitation and provide complementary photoprotection, a composite hydrogel with both reparative and photoprotective functions (LA-EL-gel) was developed by physically crosslinking UV-absorbing silk fibroin with LA-loaded elastic liposomes (LA-EL). These liposomes were co-modified with isopropyl myristate (IPM) and polyoxyethylene castor oil (PCO) to enhance the skin penetration of LA. In vitro and in vivo studies confirmed that LA-EL-gel possesses UVB absorption capability, enhances skin retention and penetration of LA, and effectively alleviates UVB-induced photoaging by inhibiting oxidative stress and promoting collagen production. Moreover, LA-EL-gel showed no toxicity to the liver and kidneys in mice and effectively mitigated UVB-induced weight loss and skin moisture reduction. In conclusion, LA-EL-gel is a promising transdermal delivery system with anti-photoaging efficacy and favorable biosafety, thereby offering a new strategy and experimental basis for developing an efficient, low-toxicity, and multifunctional anti-photoaging therapeutic platform. Download: Download high-res image (377KB) Download: Download full-size image

Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with myeloid differentiation factor 2 (MD2)

Weiwei Zhu,Minxiu Wang,Leiming Jin,Bin Yang,Bin Bai,Rumbidzai Natasha Mutsinze,Wei Zuo,Nipon Chattipakorn,Joo Young Huh,Guang Liang,Yi Wang

Background and Purpose Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products have played a fundamental role and provided an abundant pool in drug discovery. Experimental Approach A compound library containing 160 natural products was used to screen potential anti-inflammatory compounds. Mice with LPS-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds. Key Results Licochalcone A was discovered from the anti-inflammatory screening of natural products in macrophages. A qPCR array validated the inflammation-regulatory effects of licochalcone A and indicated that the potential targets of licochalcone A may be the upstream proteins in LPS pro-inflammatory signalling. Further studies showed that licochalcone A directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to licochalcone A. In vivo , licochalcone A treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway and inflammatory cytokine induction. Conclusion and Implications In summary, our study identified MD2 as a direct target of licochalcone A for its anti-inflammatory activity and suggested that licochalcone A might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy. Graphical Licochalcone A directly binds with MD2 whereas LEU61 and PHE151 are two key residues for conformational stabilization. This interaction blocks the biological function of MD2 in transducing the signalling from the LPS-induced TLR4 pathway, subsequently restrains both TBK1/IRF3 and TAK1/MAPKs/NF-κB activation and inflammatory cytokines, chemokines, interferons, and so on overexpression, thus decreasing the immune cell infiltration in lung tissue and improving the acute lung injury.