Chemical constituents and pharmacological effects of Lonicerae japonicae

Lonicera japonica,also known as honeysuckle,is an evergreen shrub in the family of Syzygium.By consulting Sciencedirect databases and Web of Science databases,79 related articles were found,of which 22 were related to chemical composition and pharmacological activity.These articles show that L.japonica has a wide range of pharmacological activities,including antiviral,anti-tumor,and antioxidant effects.These activities have important applications in the pharmaceutical,food,and fragrance industries.This review focuses on the chemical composition and pharmacological effects of L.japonicae,which is of great significance to the development of new drugs and therapeutic methods.

Screening hepatoprotective effective components of Lonicerae japonica Flos based on the spectrum-effect relationship and its mechanism exploring

Lonicerae japonicae Flos(LF)is a kind of healthcare food with hepatoprotective function.This study was designed to explore the spectrum-effect relationships between UPLC fingerprints and the hepatoprotective effects of LF.Fingerprints of ten batches of LF were established by UPLC-PDA.The inhibitory levels of AST and ALT were used as pharmacological indexes,and secoxyloganin,isochlorogenic acid A and isochlorogenic acid C were screened as hepatoprotective active compounds by grey relational analysis(GRA)and partial least squares regression analysis(PLSR).Caspase-3 was obtained by network pharmacology as a key target of hepatoprotective active compounds.Molecular docking is used to explore the interaction between small molecules and proteins.This work provided a general model of the combination of UPLC-PDA and hepatoprotective effect to study the spectrum-effect relationship of LF,which can be used to considerable methods and insight for the fundamental research of the material basis of similar healthcare food.

Chemical compositions and biological activities of Flos lonicerae

Flos lonicerae is the dry flower bud of Lonicera japonica Thunb,and it is a very important Chinese herbal medicine in China.In ancient times,it was widely used to treat the exopathogenic wind-heat,epidemic febrile diseases,sores,carbuncles and some infectious diseases.Modern pharmacological research has indicated that it has anti-inflammatory,anti-bacterial,anti-viral and anti-oxidation activities.This paper reviews the chemical compositions and biological activities of Flos lonicerae in order to provide reference for its application in clinical practice in the future.

Short-term Prediction of Occurrence Period of Main Diseases and Pests of Flos lonicerae using Phenoecology

The occurrence periods of Semiaphis heraclei Takahashi,Frankliniella sp.,Haptonchus luteolus and Microsphara linicerae Enchson wint.in Rabenh.causing damage on Flos lonicerae were investigated in F.lonicerae planting area in XinCheng county of Guangxi Province during 2008-2010,which were coincided with the occurrence periods of related phenology of local Prunus persica Rootstock.With P.persica Rootstock as indicator plant,the occurrence periods of three species of pests and one species of disease were predicted,respectively,and the method was simple and accurate,which could be the foundation for preventing these pests and diseases in the local field.

Main Diseases and Pests of Lonicerae japonica in Guangxi Province and Fluctuation Pattern of Their Natural Enemies

[ Objective ] The paper was to study the main diseases and pests in Lonicerae japonica in Guangxi Province and fluctuation pattern of their natural ene- mies. [Method] The population change of main diseases and pests, and main predatory naturaI enemies of pests in different species of Lonicerae japonica in Xincheng County of Guangxi Province were systematically investigated during 2008 -2010. [ Result ] The variation cycle of population number of Semiaphis heraclei （Takahashi） belongs to single peak type, and it has large occurrence in April. The variation cycle of population number of Franklinlella sp. and Haptonchus luteo- ius （Erichson） belongs to double peak type, and they have large occurrence at April and September. The variation cycle of disease severity of Microsphaera lonicerae （ Wint. ） belongs to double peak type, and the disease index will be larger at April and September. The variation cycle of diseased shoot rate belongs to single peak type; diseased shoot rote of Lonicera dasystyla Rehd. and Loniccra hvpolzlauca Miquel is relatively high during April to June, while the index of Lonice- ra confusa （Sweet） DC. is relatively high during February to May. The variation cycle of population number of main natural enemies such as Lemnia biplagiata （ Swartz）, Coccinella septcmpunctata （ Linnaeus ） and Harmonia axyridis （Pallas） belongs to double peak type, and they have large occurrence at April and Sep- tember. [ Conclusion] The results could provide scientific basis for determination of optimum control period against major diseases and pests in Loniceraejaponica and development of integrated control programs.

Separation and Purification of Macranthoidin B and Dipsacoside B from Flos Lonicerae by HP-20 and HP-SS Macroporous Resin

[Objective] This study was conducted to develop a method for rapidly separating macranthoidin B and dipsacoside B from Flos Lonicerae. [Method] HP-20 and HP-SS macroporous resin were applied to separate and purify macranthoidin B and dipsacoside B from Flos Lonicerae. The extract of Flos Lonicerae was first loaded onto an HP-20 column to enrich saponins, which were then separated by an HP-SS macroporous resin column to get pure macranthoidin B and dipsacoside B.[Result] The optimal HP-20 purification conditions included： a concentration of sample liquid at 4.8 mg/ml, a sample volume of 2 BV, an adsorption flow rate at 1.5BV/h, an ethanol concentration for desorption at 60%, a desorption volume of 3 BV,and a desorption flow rate at 1.5 BV/h. Total saponins were then separated by an HP-SS macroporous resin column which was eluted sequentially by water, 20%ethanol, 30% ethanol, 40% ethanol and 50% ethanol. Two purified compounds were obtained in fractions eluted by 40% ethanol and 50% ethanol, respectively. The two compounds were identified as macranthoidin B and dipsacoside B by13 C and1H nuclear magnetic resonance spectroscopy. [Conclusion] The combination of HP-20 and HP-SS macroporous resin could efficiently separate macranthoidin B and dipsacoside B from Flos Lonicerae.

Effect of chlorogenic acid on antioxidant activity of Flos Lonicerae extracts

Flos Lonicerae is a medically useful traditional Chinese medicine herb. However, little is known about the antioxidant properties of Flos Lonicerae extracts. Here the antioxidant capacity of water, methanolic and ethanolic extracts prepared from Flos Lonicerae to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduce Fe3+ to Fe2+ is examined. Chlorogenic acid, a major component of Flos Lonicerae, is identified and further purified from 70% ethanolic extract with high performance liquid chromatography (HPLC) and its antioxidant capacity is characterized. The total phenolic compounds and chlorogenic acid con-tents in Flos Lonicerae are determined. The present results demonstrate that the Flos Lonicerae extracts exhibit antioxidant ac-tivity and chlorogenic acid is a major contributor to this activity.

Lonicerae Flos:A Review of Chemical Constituents and Biological Activities

Lonicerae flos,a widely used traditional Chinese medicine(TCM),has been used for several thousand years in China.As a famous traditional Chinese herbal medicine,it was used as heat-clearing drug and alexipharmic agent and was widely cultivated in Hunan province.L.flos mainly contains biologically active compounds such as caffeic acid derivatives,essential oil,flavonoids,iridoid glycosides and terpenoids.A range of biological activities has been reported from plant extracts including anti-inflammatory,antitumor,antioxidant,antiallergy,immunomodulating and antibacterial activity.In this study,the author investigated ancient books of TCM and nowadays reports,summarized the chemical constituents,biological activity of L.flos to provide a comprehensive systematic review.

Extraction process of chlorogenic acid in flos lonicerae by enzymatic treatment

A new method of extracting chlorogenic acid from flos lonicerae, and treating the materials with enzyme before being extracted by ethanol is developed, and the optimum conditions are also investigated in detail. Three important factors, enzyme dosage, treatment time and treatment temperature are adapted to optimize the extraction process. The experimental results show that the extract yield of flos lonicerae and chlorogenic acid can be obviously increased by the cellulase treatment, 61.5 mg chlorogenic acid is obtained from 1.00 g flos lonicerae at most. The optimal temperature of enzymatic treatment is 40 50 ℃. Compared with the use of single cellulase, the combined treatment of cellulase and pectinase increase the extract yield obviously but fail to improve that of chlorogenic acid.

Application of near-infrared spectroscopy for the rapid analysis of Lonicerae Japonicae Flos solution extracted by water

A rapid quantitative analytical method for three components of Lonicerae Japornicae Flos solution(Lonicera Japonica Thumb.)extracted by water was developed using near-infrared(NIR)spectroscopy and the partial least-squares(PLS)method.The NIR spectra of 81 samples collected from a production line were obtained.The concentrations of secologanic acid,chlorogenicacid and galuteolin were detemmined by using high-performance liquid chromatography-diodearray detection as the reference method.Several pretreatment methods for the NIR spectra wereusedi during PLS calibration.The most appropriate latent variable number of the PLS factor wasselected based on the standard error of cross-validation(SECV).The performance of the finalPLS models was evaluated according to SECV,standard error of predliction(SEP)and deter-mination coeficient(R^(2)).The compounds secologanic acid,chlorogenic acid and galuteolin hadSEP values of 0.030,0.061 and 1.668μg/mL,respectively and R^(2) values over 0.85.This workshows that NIR spectroscopy is a rapid and convenient method for the analysis of LoniceraeJaponicae Flos solution extracted by water.The proposed method can help in the application ofprocs analytical technology in the pha maceutical industry,particularly in tra ditional Chinesemedicine injections.

Comparative analysis of volatile constituents between herbal pair flos lonicerae-caulis lonicerae and its single herbs

Gas chromatography-mass spectrometry(GC-MS) and the chemometric resolution method(alternative moving window factor analysis,AMWFA) were used for comparative analysis of volatile constituents in herbal pair(HP) flos lonicerae-caulis lonicerae(FL-CL) and its single herbs.The temperature-programmed retention index(PTRI) was also employed for the identification of compounds.In total,44,39,and 50 volatile chemical components in volatile oil of FL,CL and HP FL-CL were separately determined qualitatively and quantitatively,accounting for 87.22%,94.54% and 90.08% total contents of volatile oil of FL,CL and HP FL-CL,respectively.The results show that there are 32 common volatile constituents between HP FL-CL and single herb FL,33 common volatile constituents between HP FL-CL and single herb CL,and 10 new constituents in the volatile oil of HP FL-CL.

Quality Analysis and High-Performance Liquid Chromatographic Fingerprint Analysis of New Cultivated Kind of <i>Lonicerae japonicae</i>Flos “Hua Jin 6” from Different Harvest Times

Lonicerae japonicaeFlos (LJF) is widely used in traditional Chinese medicines for the treatment of various diseases, which is now in great demand every year and has a broad development prospect. However, the flowering phase of common LJF varieties is so short, which seriously restricts the development of LJF industry. As a new cultivated kind of Lonicerae japonicae Flos, “Hua Jin 6” has characteristics in long flowering phase and conveniently picking, which makes it have a broad development prospect. The aim of this study is to provide scientific guidance for its suitable harvest period by measuring yield and quality of “Hua Jin 6” from different harvest time. Studies show that flower size had a slowly rising trend from the first day to the seventh day, and then slowly declined or kept stable. There were no significant differences of total phenolic acid contents in different samples from different days, but contents of total flavonoids were on the rise and up to maximum in the ninth day. The contents of total iridoids had an increasing tendency from the first day to the fifth day and then kept relatively stable in other days. We demonstrated that the quality of “Hua Jin 6” is relatively stable and suitable for harvesting in all flower buds white stage in term of HPLC fingerprints. Our findings can make it possible to select the suitable time for different harvest purpose.

In vivoand in vitroanti-arthritic efficacy of a herbal formula consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos

OBJECTIVE Rheumatoid arthritis(RA)is the most common inflammatory autoimmune disease,affecting around 1% of the world population.Toll-like receptor 4(TLR4)signalling has been found to be involved in the pathogenesis of RA.It is a potential therapeutic target for RA treatment.A herbal formula(RL)consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos has traditionally been used in treating various inflammatory disorders.In this study,we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis(CIA)in rats and investigate the involvement of TLR4 signaling in the mode of action of RL in vivo and in vitro.METHODS In vivo anti-arthritic efficacy was evaluated using CIA rats induced by bovine typeⅡ collagen.The treatment groups were treated with various concentrations of RL or positive control indomethacin for 35 d.Clinical signs(hind paw volume and arthritis severity scores),changes in serum inflammatory mediators,histological and radiographic changes of joints were investigated.Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats.The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats,murine RAW264.7macrophages and human THP-1 monocytic cells.RESULTS The severity of arthritis in the CIA rats was significantly attenuated by RL.Histological score and radiographic score were efficiently improved by RL.RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats.RL significantly inhibited the production of various pro-inflammatory mediators,the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines.CONCLUSION RL possesses anti-arthritic effect on collagen-induced arthritis in rats.The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum.The inhibition of the TLR4/TAK1/NF-κB and TLR4/TAK1/MAPK pathways participate in the anti-arthritic effects of RL.This provides a pharmacological justification for the use of RL in the control of various arthritic diseases.Further investigation should be done to develop RL into a modern anti-arthritic agent.

Comparative Analysis of the Complete Chloroplast Genome Sequences of Four Origin Plants of Lonicerae Flos(Lonicera;Caprifoliaceae)

Lonicerae Flos(LF)derived from the dried flower buds or opening flowers of four Lonicera plants(Lonicera macranthoides,L.hypoglauca,L.confusa,and L.fulvotnetosa),is a popular traditional Chinese medicine.Because the four origin plants are very similar in morphology,it is difficult to control the quality of LF in actual production.Over the past decade,many reports have pointed out the differences among them,including the botanical characteristics and active ingredients.However,there is still a lack of rapid methods that can be applied to the identification of the four origins.In this study,comparative analysis of the four chloroplast genomes was performed,and they showed low diversity(Pi=0.00267),three variation hotspots regions(rbcL-accD,rps12-ndhF and rps12-trnN-trnG)were identified as potentially molecular marker of highly informative.Meanwhile,the most obvious difference in SSR comparative analysis is reverse and complement repeats were only identified in L.confusa and L.hypoglauca,respectively.Lastly,the phylogenetic tree showed that L.confusa is more closely related to L.fulvotnetosa,while L.macranthoides is closer to L.hypoglauca.This study systematically revealed the differences among the four chloroplast genomes,and it provides valuable genetic information for identifying the origin of LF.

Optimization of Extraction Process of Total Flavonoids and Chlorogenic Acid from Flos Lonicerae by Orthogonal Experiment

[Objectives]To explore the process of simultaneous extracting total flavonoids and chlorogenic acid from Flos Lonicerae by pressure assisted extraction.[Methods]Based on the single factor experiment,orthogonal experiments were carried out to investigate the effects of solvent concentration,solid-to-liquid ratio,extraction pressure,extraction time and extraction temperature on the extraction rate of total flavonoids and chlorogenic acid.[Results]The results showed that the extraction pressure had a significant effect on the extraction of two kinds of chemical constituents from F.Lonicerae.The optimum process conditions were as follows:solvent concentration was 60%,solid-liquid ratio was 1∶20(g/mL),extraction pressure was 2 MPa,extraction time was 30 min,extraction temperature was 70℃.The process conditions are stable,and the extraction efficiency is higher than that of ultrasonic assisted extraction method.Under the test conditions,the extraction rates of total flavonoids and chlorogenic acids were respectively 15.66%and 3.89%.[Conclusions]This study provides a new theoretical basis for the development and utilization of F.Lonicerae.

Content Determination of Chlorogenic Acid and Luteoloside in Flos Lonicerae

The contents of chlorogenic acid and luteoloside in Flos Lonicerae from Binhai New Area and Jinnan District of Tianjin were determined to provide basis for the quality identification of this medicinal material. The content of chlorogenic acid was determined by HPLC. In Flos Lonicerae from Binhai New Area and in Flos Lonicerae harvested at different stages from Jinnan District,the contents of chlorogenic acid were 3. 804%,5. 507%( three green stage),4. 855%( silver flower stage) and 4. 220%( golden flower stage),respectively,and the contents of luteoloside were 5. 53%,12. 405%( three green stage),14. 370%( silver flower stage) and 0. 917%( golden flower stage),respectively. The contents of chlorogenic acid in Flos Lonicerae from Jinnan District were higher than that from Binhai New Area. Among different stages,the content of chlorogenic acid was highest in three green stage,followed by that in silver flower stage. As the flowers bloomed,the content of chlorogenic acid in the medicinal material showed a significant downward trend. In Flos Lonicerae from Jinnan District,the content of luteoloside was highest in silver flower stage and lowest in golden flower stage.

Amplifying protection against acute lung injury:Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

Objective:Acute lung injury(ALI)is characterized by inflammation and currently lacks an efficacious pharmacological intervention.The medicine combination of Lonicerae Japonicae Flos(LJF)and Forsythiae Fructus(FF)demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory symptoms.In previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ALI.However,there have been no reports of LJF and FF pairing for lung injury.The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF)with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism involved.Methods:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury severity.Alveolar exudate cells(AECs)were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow cytometry.Myeloperoxidase(MPO)activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and ELISA.The effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1βproteins in bone marrow derived macrophages(BMDMs)supernatant was assessed using Western blot method under various inflammasome activation conditions.In addition,the concentration of IL-1βand changes in lactatedehydrogenase(LDH)release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ELISA.Furthermore,the effects of LJF,FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by Western blot,and the mRNA changes of IFN-β,TNF-α,IL-6 and CXCL10 in BMDMs were detected by qPCR.Results:LF significantly attenuated the damage to alveolar structures,pulmonary hemorrhage,and infiltration of inflammatory cells induced by LPS.This was evidenced by a decrease in lung index score and wet/dry weight ratio.Treatment with LF significantly reduced the total number of neutrophil infiltration by 75%as well as MPO activity by 88%.The efficacy of LF in reducing inflammatory factors IL-1β,TNF-α,and IL-6 in the lungs surpasses that of LJF or FF,approaching the effectiveness of dexamethasone.In BMDMs,the co-administration of 0.2 mg/mL of LJF and FF demonstrated superior inhibitory effects on the expression of nigericin-stimulated Caspase-1 and IL-1β,as well as the release levels of LDH,compared to individual treatments.Similarly,the combination of 0.5 mg/mL LJF and FF could better inhibit the phosphorylation levels of STING and IRF3 and the production of IFN-β,TNF-α,IL-6,and CXCL10 in response to ISD stimulation.Conclusion:The combination of LJF and FF increases the therapeutic effect on LPS-induced ALI,which may be mechanistically related to the combined effect inhibition of cyclic-GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)and NOD-like receptor family protein 3(NLRP3)inflammasomes pathways by LJF and FF.Our study provides new medicine candidates for the clinical treatment of ALI.

Extraction Condition Optimization and Identification of Phenols from Lonicerae flos

Polyphenols were obtained from the natural dried Lonicerae flos by ultrasound-assisted extraction with ethanol as the solvent.Single factor experiment and response surface methodology were employed to optimize the extraction conditions.Ultra-performance liquid chromatrography(UPLC)-tandem mass spectrometry(MS/MS)was employed to identify polyphenols based on the plant widely targeted metabolomics database in a qualitative and quantitative manner.The results showed that the optimal extraction conditions for total phenols from Lonicerae flos were ultrasound-assisted extraction with a solid-to-liquid ratio of 10∶1 g/mL and 57%ethanol at 70 W and 60°C for 11 min.The yield of total phenols extracted under the optimal conditions reached 71.08 mg/g.The phenols in Lonicerae flos were mainly chlorogenic acid isomers,and the flavonoids were mainly nobiletin,galuteolin,and homoarbutin.

Comparison of anti-inflammatory effects of Lonicerae Japonicae Flos and Lonicerae Flos based on network pharmacology

Objective:In Chinese herbal medicine(CHM)history,Lonicerae Japonicae Flos and Lonicerae Flos were used clinically as one drug,but now they are admitted as two herbal medicines in Chinese Pharmacopoeia(2010 edition).This study used network pharmacology to investigate whether the two can be used interchangeably for the treatment of inflammatory diseases in TCM clinical practice.Methods:Lonicerae Japonicae Flos and Lonicerae Flos were compared in the inflammation mechanism including core targets,Gene Ontology(GO),pathway and principle chemical components by the method of network pharmacology.Results:Lonicerae Japonicae Flos and Lonicerae Flos shared in six targets accounting for 66.7%of the entire core targets and more than half of the GO terms and pathways are similar.Organic acids are dominent compounds responsible for anti-inflammatory effects.Three of the compounds that bind to core targets including luteolin,quercetin and kaempferol,are shared in both herbs.Conclusion:Due to high similarity between Lonicerae Japonicae Flos and Lonicerae Flos,we believe that they can be used interchangeably for the inflammation in clinical treatment.

Simultaneous quantification of ten phenolic acids in Lonicerae Japonicae Flos by HPLC-DAD

A reverse-phase HPLC-DAD method was developed for simultaneous quantification of ten phenolic acids （caffeic acid, chlorogenic acid, neochlorogenic acid, 4-O-caffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid methyl ester, 3,4-O-dicaffeoylquinic acid methyl ester, and 4,5-0- dicaffeoylquinic acid methyl ester） in the dried flower buds of Lonicera japonica Thunb. （Lonicerae Japonicae Flos; LJF）. An optimal sample preparation method was established as 30-min ultrasonication with 100 times 50% （v/w） ethanol aqueous solution based on the orthogonal test results. The chromatographic separation of the ten phenolic acids was achieved with an AQ-C18 column （4.6 mm x 250 mm, 5 p.m） and a gradient elution of acetonitrile, methanol and 0.1% formic acid aqueous solution within 55 rain. All calibration curves showed good linearity （r2〉0.999） within test ranges. The average recoveries were in the range of 98.57%-103.22% with RSD less than 3%. The method developed was accurate, sensitive and reproducible for determination of ten phenolic acids in LJF.