Discovery of components in honeysuckle for treating COVID-19 and diabetes based on molecular docking, network analysis and experimental validation.

Molecular docking screening identified ochnaflavone, madreselvin B and hydnocarpin as key components for treating COVID-19 with diabetes in honeysuckle using 3 C-like protease (Mpro), angiotensin-converting enzyme 2 (ACE2), and dipeptidyl peptidase 4 (DPP4) as molecular docking targets, ACE2, DPP4, IL2, NFKB1, PLG, TBK1, TLR4 and TNF were the core targets, and multiple antiviral and anti-inflammatory signalling pathways were involved. Further, the levels of IL-1ß and DPP4 in cell supernatant that had been activated by LPS was decreased by hypnocarpin, and ACE2 protein and DPP4 mRNA in cells were down-regulated. Overall, we have identified three components from honeysuckle that have potency to treat COVID-19 combined with diabetes. SARS-CoV-2 transcription may be inhibited by these components in honeysuckle, reducing virus invasion, inhibiting inflammatory factors, and improving immune response. Our findings could provide a basis for the clinical application and further development of honeysuckle.

Optimization of the fermentation process and antioxidant activity of mixed lactic acid bacteria for honeysuckle beverage.

The aim of the research was to obtain a high healthcare honeysuckle beverage with strong antioxidant activity. Honeysuckle (Lonicera japonica Thunb) was used as the raw material in this experiment. The effects of fermentation temperature, fermentation time, lactic acid bacteria inoculation amount, and sugar addition amount on the sensory quality of honeysuckle beverage were investigated by single factor test and orthogonal test, and the best process was obtained. The physicochemical indexes and antioxidant activity of honeysuckle beverages fermented with lactic acid bacteria were studied. The results showed that the fermentation temperature of the beverage was 37 °C, the fermentation time was 24 h, the inoculation amount of Lactiplantibacillus plantarum and Lactobacillus acidophilus mixed starter (1:1) was 3%, and 8% white granulated sugar was added. The highest sensory score was 87.30 ± 0.17, which was the optimal process. The honeysuckle liquid mixed inoculation with Lactiplantibacillus plantarum and Lactobacillus acidophilus was fermented for 24 h. The number of viable bacteria reached 9.84 ± 0.02 lg cfu/mL, the pH value was 3.10 ± 0.01, and the total polyphenol content was 7.53 ± 0.03 mg GAE/g. The number of lactic acid bacteria, pH, total polyphenol content, and free radical scavenging rate were significantly increased (p < 0.05) compared with the non-inoculated and single-inoculated lactic acid bacteria. To sum up, it was concluded that a better quality beverage could be obtained by fermenting a solution of honeysuckle with Lactiplantibacillus plantarum and Lactobacillus acidophilus mixed fermentation agent, providing a new approach and new ideas for the development of deep processing and fermented beverages using honeysuckle.

Long-term effects of a tornado: Impacts on woody native vegetation and invasive Amur honeysuckle (Lonicera maackii) in an urban forest.

As tornados become increasingly common with global climate change, recovery of the woody vegetation in temperate forests is imperative to maintain an intact ecosystem. In many urbanized landscapes, invasive species are also increasing and could interfere with natural recovery from environmental disturbance. We quantified the impact and 17-year recovery from a major tornado in a temperate deciduous forest. We used vegetational surveys in southwestern Ohio at the Harris M. Benedict Nature Preserve, where approximately a third of this site was damaged by a tornado in 1999. Plots were established in the tornado-damaged area and the nearby undisturbed forest to examine forest recovery of trees/saplings, shrubs and vines, and tree seedlings during 2003, 2006, 2010, and 2016/2017. The number of tree saplings, shrubs, and vines increased immediately after the tornado, but then declined by 2010, relative to the undisturbed forest. Forest tree recruitment was lower in tornado-damaged sites with fewer tree seedlings, but more saplings. Tree diversity was also affected by Agrilus planipennis (Emerald Ash borer) which targeted native ash trees within this time period. Despite an initial increase in shrubs and vines in the damaged area, the diversity and density of shrubs approached equality in both sites by 2016. Most shrubs in both sites were the invasive Lonicera maackii (Amur honeysuckle). In tornado sites, honeysuckle thinned out over time, leaving larger shrubs with greater mean basal diameter compared to the undisturbed forest. Other woody invasive species were also more prevalent in the damaged area, but increased in number in both locations by 2017. The forest has the capability to begin to recover from the initial tornado, but its future composition may differ from its initial trajectory due to invasive species, loss of ash trees, and anthropogenic impacts within the urban landscape.

Chemical Characterization of Honeysuckle Polyphenols and Their Alleviating Function on Ultraviolet B-Damaged HaCaT Cells by Modulating the Nrf2/NF-κB Signaling Pathways.

Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation-reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC-MS/MS, and the mechanisms underlying HPs' antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells (p < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1ß). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.

Study on the ameliorative effect of honeysuckle on DSS-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Honeysuckle, first documented in the Miscellaneous Records of Famous Physicians, is known for its ability to expel toxin and cool blood to stop diarrhea. Modern pharmacological research has shown that honeysuckle has anti-inflammatory, antibacterial, antioxidant, and immune-regulating effects and is widely used in clinical practice. However, the effect of honeysuckle on ulcerative colitis (UC) is still not fully understood, which presents challenges for quality control, research and development. AIM OF THE STUDY: This study aimed to determine the anti-inflammatory properties and mechanism of action of aqueous extracts of honeysuckle in the treatment of ulcerative colitis. MATERIALS AND METHODS: The dextran sodium sulfate (DSS) induced-ulcerative colitis mouse model was established, and the mice were divided into five groups: the control group, the model group, and the low, medium, and high dose honeysuckle treatment groups. RESULTS: All dose groups of honeysuckle were found to significantly reduce IL-6 and TNF-α levels and regulate DSS-induced mRNA levels of CLDN4, COX-2, IL-6, INOS, MUC-2, occludin and NLRP3. The high-dose group displayed the most effective inhibition, and a differentially expressed mRNA detection indicated abnormal mRNA expression. The 16sRNA sequencing revealed that the honeysuckle was able to significantly upregulate the abundance of beneficial bacteria and downregulate the abundance of harmful bacteria. The study of short-chain fatty acids revealed that the levels of acetic, propionic, isobutyric, valeric and isovaleric acids were significantly increased after administering honeysuckle at medium and high doses. CONCLUSION: Honeysuckle reduces the production of pro-inflammatory cytokines, increases the content of short-chain fatty acids and restores the intestinal ecological balance, resulting in better therapeutic effects.

Molecular mechanism of honeysuckle + forsythia in treatment of acute lung injury based on network pharmacology.

The pathogenesis of acute lung injury (ALI) is complex and it is a common critical illness in clinical practice, seriously threatening the lives of critically ill patients, for which no specific molecular marker exists and there is a lack of effective methods for the treatment of ALI. The present study aimed to investigate the mechanism of action of honeysuckle and forsythia in treatment of acute lung injury (ALI) based on network pharmacology and in vitro modeling. The active ingredients and targets of honeysuckle and forsythia were predicted using traditional Chinese medicine systems pharmacology, PubChem and Swiss Target Prediction databases, and the Cytoscape 3.7.2 software was used to construct a drug-component-potential target network. The potential targets were imported into the Search tool for recurring instances of neighboring genes) database to obtain protein-protein interactions and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Targets analysis using Database for Annotation, Visualization, and Integrated Discovery. AutoDock Vina 1.1.2 software was used for docking between key active ingredients and the target proteins to analyze the binding ability of the active ingredients to the primary targets in honeysuckle and forsythia. A total of 64 male BALB/c mice were randomly divided into control, model, positive drug (Lianhua-Qingwen capsule), honeysuckle, forsythia, honeysuckle + forsythia high-, medium- and low-dose groups. Lipopolysaccharide (LPS) was used to induced an ALI model. The lung tissues of the mice were stained with hematoxylin-eosin and the serum levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured 4 h after the LPS administration. Reverse transcription-quantitative PCR and western blotting were used to detect NF-κB mRNA and protein expression, respectively. Active ingredients of honeysuckle and forsythia acted on 265 common targets in ALI, which regulated NF-κB, tumor necrosis factor-α (TNF-α) and PI3K-AKT signaling pathway, HIF-1 signalling pathway to slow the inflammatory response in treatment of ALI. In the positive drug group, honeysuckle, forsythia group, honeysuckle + forsythia high-, medium- and low-dose groups, lung tissue damage were significantly decrease compared with the model group, and inflammatory cell infiltration was reduced. Compared with the model group, honeysuckle + forsythia groups experienced decreased damage caused by the LPS and inflammation in the lung tissues and significantly decreased TNF-α and NF-κB and MDA concentration and significantly increased the SOD and GSH-Px activities. The mechanism of the effect of honeysuckle and forsythia on ALI may be mediated by inhibition of TNF-α and NF-κB expression and the activation of antioxidant mechanisms to decrease production of pro-inflammatory cytokines in lung tissue, thus treating ALI.

Sustainable Pest Management Using Novel Nanoemulsions of Honeysuckle and Patchouli Essential Oils against the West Nile Virus Vector, Culex pipiens, under Laboratory and Field Conditions.

Essential oils are natural plant products that are very interesting, as they are important sources of biologically active compounds. They comprise eco-friendly alternatives to mosquito vector management, particularly essential oil nanoemulsion. Therefore, the aim of this study is to evaluate the effectiveness of 16 selected essential oils (1500 ppm) in controlling mosquitoes by investigating their larvicidal effects against the larvae and adults of the West Nile virus vector Culex pipiens L. (Diptera: Culicidae); the best oils were turned into nanoemulsions and evaluated under laboratory and field conditions. The results show that honeysuckle (Lonicera caprifolium) and patchouli (Pogostemon cablin) essential oils were more effective in killing larvae than the other oils (100% mortality) at 24 h post-treatment. The nanoemulsions of honeysuckle (LC50 = 88.30 ppm) and patchouli (LC50 = 93.05 ppm) showed significantly higher larvicidal activity compared with bulk honeysuckle (LC50 = 247.72 ppm) and patchouli (LC50 = 276.29 ppm) oils. L. caprifolium and P. cablin (100% mortality), followed by Narcissus tazetta (97.78%), Rosmarinus officinalis (95.56%), and Lavandula angustifolia (95.55%), were highly effective oils in killing female mosquitoes, and their relative efficacy at LT50 was 5.5, 5.3, 5.8, 4.1, and 3.2 times greater, respectively, than Aloe vera. The results of the field study show that the honeysuckle and patchouli oils and their nanoemulsions reduced densities to 89.4, 86.5, 98.6, and 97.0% at 24 h post-treatment, respectively, with persistence for eight days post-treatment in pools. Nano-honeysuckle (100% mortality) was more effective than honeysuckle oils (98.0%). Our results show that honeysuckle and patchouli oils exhibited promising larvicidal and adulticidal activity of C. pipiens.

Evaluation and control of Alternaria tenuissima causing leaf spots in blue honeysuckle in China.

Blue honeysuckle is emerging as a popular edible fruit and folk medicine. However, from June to August 2021, a serious leaf-spot disease affected the yield and quality of blue honeysuckle in Harbin, Heilongjiang Province, China; the species and characteristics of the pathogens responsible for the disease are unknown. In this study, 30 fungal isolates were obtained from infected blue honeysuckle leaves, identified as Alternaria tenuissima based on morphological and molecular characteristics and phylogenetic analyses. To the best of our knowledge, this is one of the first studies to identify A. tenuissima as the causal agent of blue honeysuckle leaf spots in China. Pathogenicity tests of the isolates revealed that most isolates exhibited moderately pathogenic. All blue honeysuckle cultivars tested were found to be susceptible to 30 A. tenuissima isolates. In addition, elder, Dahurian rose fruit, sea-buckthorn, rowan, hawthorn, bird cherry, and sorb could be infected by A. tenuissima isolates, while European cranberry bush and nanking cherry were not infected. A. tenuissima isolates were highly sensitive to prochloraz (EC50 ≤ 0.50 µg·ml-1) with 86.21% efficacy at 400 µg·ml-1 in the field trials. Therefore, the application of rotation and chemical fungicides are considered to control the disease-causing leaf spots in blue honeysuckle. These results provide a basis for controlling A. tenuissima in blue honeysuckle in China.

Characterization of polysaccharide from Lonicera japonica Thunb leaves and its application in nano-emulsion.

The polysaccharides in honeysuckle leaves (PHL) were separated and characterized for the first time. The nano-emulsion stabilized by PHL and whey protein isolate (WPI) were also fabricated based on the ultrasonic method. The results indicated that PHL was mainly composed of glucose (47.40 mol%), galactose (19.21 mol%) and arabinose (20.21 mol%) with the weight-average molecular weight of 137.97 ± 4.31 kDa. The emulsifier concentration, WPI-to-PHL ratio, ultrasound power and ultrasound time had significant influence on the droplet size of PHL-WPI nano-emulsion. The optimal preparation conditions were determined as following: emulsifier concentration, 1.7%; WPI/PHL ratio, 3:1; ultrasonic power, 700 W; ultrasonic time, 7 min. Under the above conditions, the median diameter of the obtained nano-emulsion was 317.70 ± 5.26 nm, close to the predicted value of 320.20 nm. The protective effect of PHL-WPI emulsion on ß-carotene against UV irradiation was superior to that of WPI emulsion. Our results can provide reference for the development of honeysuckle leaves.

Preparation, Antioxidant Activities and Bioactive Components of Kombucha Beverages from Golden-Flower Tea (Camellia petelotii) and Honeysuckle-Flower Tea (Lonicera japonica).

Kombucha is a fermented tea known for its health benefits. In this study, golden-flower tea (Camellia petelotii) and honeysuckle-flower tea (Lonicera japonica) were first used as raw materials to prepare kombucha beverages. The antioxidant activities, total phenolic contents, concentrations of bioactive components, and sensory scores of two kombucha beverages were assessed. Additionally, effects of fermentation with or without tea residues on kombucha beverages were compared. The results found that two kombucha beverages possessed strong antioxidant activities and high scores of sensory analysis. In addition, fermentation with golden-flower tea residues could remarkably enhance the antioxidant activity (maximum 2.83 times) and total phenolic contents (3.48 times), while fermentation with honeysuckle tea residues had a minor effect. Furthermore, concentrations of several bioactive compounds could be increased by fermentation with golden-flower tea residues, but fermentation with honeysuckle-flower tea residues had limited effects. Moreover, the fermentation with or without tea residues showed no significant difference on sensory scores of golden-flower tea kombucha and honeysuckle-flower tea kombucha, and golden-flower tea kombucha had higher sensory scores than honeysuckle-flower tea kombucha. Therefore, it might be a better strategy to produce golden-flower tea kombucha by fermentation with tea residues, while honeysuckle-flower tea kombucha could be prepared without tea residues.

A Comprehensive Quality Analysis of Different Colors of Medicinal and Edible Honeysuckle.

Honeysuckle (the dried flower bud or opening flower of Lonicera japonica Thunb.), a medicinal and edible substance, has is greatly popular among consumers for its remarkable health effects, such as antioxidant, antibacterial, and anti-inflammatory effects. However, due to the influences of processing methods, storage conditions, and other factors, honeysuckles show different colors which can directly reflect the quality and the price on the market. In order to comprehensively compare the quality of different colors, 55 batches of honeysuckle samples were collected and analyzed. Their color parameters, chlorophyll content (chl), total phenol content (TPC), total flavonoid content (TFC), antioxidant activity (AA), main active compounds, and metabolites were measured. As a result, the initial green-white (GW) samples, a kind of highest-quality honeysuckle, had the smallest a* value, largest h*, chl, TPC, TFC, and AA values, and highest content of chlorogenic acid and cynaroside. There was a significant difference between GW samples and a series of discolored samples. As the color darkened or lightened, the quality gradually decreased. The yellow-brown (YB) samples were of the worst quality and were no longer available for clinical and health purposes. A series of differential metabolites, such as quercetin-7-O-glucoside and secologanoside, could be used as important references to evaluate the quality of differently colored samples. The metabolic profile of honeysuckle provided new insights into the process of color change and laid a foundation for further honeysuckle quality control. The correlation results showed that the a* and h* values significantly affect the abovementioned quality indicators and the 10 main active compounds. In other words, the color difference could directly reflect the quality and clinical efficacy. Multiple regression analysis was carried out using combined L*, a*, and b* values to predict the quality of honeysuckle. This is the first time the quality of different color honeysuckle samples on the post-harvest link has been systematically compared and a demonstration of medicinal and edible substances with different colors has been provided.

Auto-encoder design based on the 1D-VD-CNN model for the detection of honeysuckle from unknown origin.

The disadvantages of the traditional one-dimensional convolution neural network (1D-CNN) model based on honeysuckle near-infrared spectral data (NIRS) include high parameter quantity, low efficiency, and inability to identify unknown categories effectively. In this paper, we propose a one-dimensional very deep convolution neural network (1D-VD-CNN) and design an auto-encoder mechanism for detecting honeysuckle from unexplored habitats. First, the 1D-VD-CNN model uses the efficient very deep (VD) structure to replace the hidden layer structure in the traditional 1D-CNN model. The model can be directly applied to analyze one-dimensional near-infrared spectral data (NIRS). Second, combining the reconstruction error of the auto-encoder, a honeysuckle identification method considering an unknown origin is designed, which can solve the problem of high confidence in convolution neural networks by using an auto-encoder and reconstruction errors of the samples to be tested. Whether the sample is an unknown variety can be determined by comparing the corrected confidence level with the preset threshold value. The results show that the accuracy of the 1D-VD-CNN training set and test set is 100%, and the loss value converges to 0.001. Compared with the traditional 1D-CNN model, the parameters and FLOPs are reduced by nearly 71% and 8%, respectively. At the same time, compared with the NIRS analysis and the PLS-DA method, the 1D-VD-CNN model has higher efficiency and better recognition performance for honeysuckle near-infrared spectral classification. Meanwhile, the accuracy rate of the auto-encoder for the category detection mechanism of honeysuckle from an unknown origin is 98%. The model can quickly and efficiently classify honeysuckle from different habitats and detect honeysuckle from unexplored habitats.

Characterization of key aroma-active compounds in blue honeysuckle (Lonicera caerulea L.) berries by sensory-directed analysis.

Blue honeysuckle (Lonicera caerulea L.) berries are nutritionally rich and unique in flavor. However, its aroma compounds have not been known well. In this study, the key aroma-active compounds in 8 different varieties of blue honeysuckle berries were studied by sensory-directed analysis. Sensory evaluation suggested that the aroma profile of blue honeysuckle berry was fruity, floral, grassy, sweet, and sour. A total of 68 aroma compounds were detected by two-dimensional comprehensive gas chromatography-olfactometry-mass spectrometry analysis (GC × GC-O-MS). Then, aroma extraction dilution analysis (AEDA) and odor activity value (OAV) showed that 12 compounds were indicated to be the major aroma contributors. According to the principal component analysis (PCA) results, eight varieties were divided into three categories for their differences on alcohols and terpenoids content. Finally, the aroma recombination and omission experiments determined that linalool, hexanal, eucalyptol, octanal, nonanal, and ethyl 2-methylbutyrate were the key aroma-active compounds in blue honeysuckle berries.

Comparative genomics of the medicinal plants Lonicera macranthoides and L. japonica provides insight into genus genome evolution and hederagenin-based saponin biosynthesis.

Lonicera macranthoides (LM) and L. japonica (LJ) are medicinal plants widely used in treating viral diseases, such as COVID-19. Although the two species are morphologically similar, their secondary metabolite profiles are significantly different. Here, metabolomics analysis showed that LM contained ~86.01 mg/g hederagenin-based saponins, 2000-fold higher than LJ. To gain molecular insights into its secondary metabolite production, a chromosome-level genome of LM was constructed, comprising 9 pseudo-chromosomes with 40 097 protein-encoding genes. Genome evolution analysis showed that LM and LJ were diverged 1.30-2.27 million years ago (MYA). The two plant species experienced a common whole-genome duplication event that occurred ∼53.9-55.2 MYA before speciation. Genes involved in hederagenin-based saponin biosynthesis were arranged in clusters on the chromosomes of LM and they were more highly expressed in LM than in LJ. Among them, oleanolic acid synthase (OAS) and UDP-glycosyltransferase 73 (UGT73) families were much more highly expressed in LM than in LJ. Specifically, LmOAS1 was identified to effectively catalyse the C-28 oxidation of ß-Amyrin to form oleanolic acid, the precursor of hederagenin-based saponin. LmUGT73P1 was identified to catalyse cauloside A to produce α-hederin. We further identified the key amino acid residues of LmOAS1 and LmUGT73P1 for their enzymatic activities. Additionally, comparing with collinear genes in LJ, LmOAS1 and LmUGT73P1 had an interesting phenomenon of 'neighbourhood replication' in LM genome. Collectively, the genomic resource and candidate genes reported here set the foundation to fully reveal the genome evolution of the Lonicera genus and hederagenin-based saponin biosynthetic pathway.

Effect of honeysuckle leaf extract on the physicochemical properties of carboxymethyl konjac glucomannan/konjac glucomannan/gelatin composite edible film.

Honeysuckle leaves are rich in bioactive ingredients, but often considered as agro-wastes. In this study, honeysuckle leaf extract (HLE) was added to the carboxymethyl konjac glucomannan/konjac glucomannan/gelatin composite edible film (CMKH). Compared to films without HLE addition (CMK), the water vapor barrier properties of CMKH slightly decreased, but the transmittance of the CMKH films in UV region (200-400 nm) as low as zero. The elongation at break of CMKH film was 1.39 âˆ¼ 1.5 fold higher than those of CMK films. The DPPH and ABTS scavenging activity of CMKH-Ⅱ was 85.75% and 90.93%, respectively, which is similar to the equivalent content of Vc. The inhibition rate of CMKH-Ⅰ and CMKH-Ⅱ against Escherichia coli and Listeria monocytogenes were close to 90%, and the inhibition rate against Staphylococcus aureus were up to 96%. The results emphasized that the composite film containing 25% (v/v) HLE has potential application value in food preservation.

TMT proteomics analysis reveals the mechanism of bleomycin-induced pulmonary fibrosis and effects of Ginseng honeysuckle superfine powdered tea.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic and potentially fatal lung disease and disorder. Although the active ingredients of ginseng honeysuckle superfine powdered tea (GHSPT) have been proven to have anti-inflammatory and antioxidant effects, the mechanism of GHSPT on PF remains unclear. The present study was to explore the underlying mechanism of GHSPT in treating PF based on proteomics and network pharmacology analysis and to confirm it in vivo. MATERIALS AND METHODS: We used intratracheal instillation of bleomycin to induce the PF mouse model and GHSPT (640 mg/kg) intragastrically administrated to PF mice for 21 days. The lung tissues were harvested for TMT-based proteomics. The UPLC-Q-Exactive MS/MS analyze the serum migrant compounds of GHSPT in the PF mice. Moreover, components of GHSPT were harvested from the pharmacology database of the TCMSP system. PF-related targets were retrieved using NCBI and GeneCards databases. RESULTS: Our results showed that GHSPT significantly alleviated PF mice. Proteomics analysis showed that 525 proteins had significantly changed in the lung of untreated PF mice. Among them, 19 differential proteins were back-regulated to normal levels after GHSPT therapy. Moreover, 25 compounds originating from GHSPT were identified in the serum sample. Network analysis showed 159 active ingredients and 92 drug targets against PF. The signaling pathways include apoptosis, ferroptosis, cytokine-cytokine receptor, P53, and PI3K-Akt signaling pathway. CONCLUSION: The evidence suggests that GHSPT might play an effective role in the treatment of PF by multi-target interventions against multiple signaling pathways.

Enzyme activity- and chemometrics-assisted comprehensive two-dimensional liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry for the analysis of honeysuckle.

A unique and effective comprehensive two-dimensional liquid chromatography system was established and applied for the analysis of bioactive components in honeysuckle. Under the optimal conditions, Eclipse Plus C18 (2.1 × 100 mm, 3.5 µm, Agilent) and SB-C18 (4.6 × 50 mm, 1.8 µm, Agilent) columns were chosen for the first dimension (1D) and the second dimension (2D) separation. The optimal flow rates of 1D and 2D were 0.12 mL/min and 2.0 mL/min, respectively. Additionally, the proportion of organic solution was optimized to enhance orthogonality and integrated shift, and full gradient elution mode was adopted to improve chromatographic resolution. Furthermore, a total of 57 compounds were identified by molecular weight, retention time and collision cross-section value obtained from ion mobility mass spectrometry. Based on the data obtained from the principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis, the categories of honeysuckle in different regions were significantly different. Moreover, the half maximal inhibitory concentration values of most samples were between 0.37 and 1.55 mg/mL, and most samples were potent α-glucosidase inhibitors, which is better for the evaluation of the quality of drugs from two aspects of substance content and activity.

Transcriptomic and metabolomic analyses reveal molecular mechanisms associated with the natural abscission of blue honeysuckle (Lonicera caerulea L.) ripe fruits.

Blue honeysuckle (Lonicera caerulea L.) is rich in phenolic compounds and has an extremely high nutritional value. Fruit abscission in the ripe period significantly impacts production and economic benefits. However, the mechanism associated with the abscission of blue honeysuckle fruit remains largely unknown. The easy-abscission cultivar 'HSY' and the hard-abscission cultivar 'Berel' were selected as plant materials. Anatomical changes of the 'HSY' fruit abscission zone (FAZ) during the abscission mainly included cell expansion, detachment, and collapse. Active changes in cell wall-degrading enzyme activity between 39 days postanthesis (DPA) and 55 DPA in 'HSY' FAZ, but not in 'Berel', suggest a critical role for cell-wall-degrading enzymes in regulating abscission. Transcriptome and metabolome analyses revealed that the genes and metabolites responding to abscission mainly act on pathways such as plant hormone signal transduction, starch and sucrose metabolism, pentose and glucuronate interconversions, and phenylpropanoid biosynthesis. The regulatory pathways of fruit abscission are mainly summarized into two parts: phytohormone synthesis and signal transduction, FAZ cell wall metabolism. In this study, 46 key genes related to plant hormone response, 45 key genes involved in FAZ cell wall metabolism, and 73 transcription factors were screened. Quantitative real-time PCR (qRT-PCR) assessed the expression pattern of 12 selected candidate genes, demonstrating the accuracy of the transcriptome data and elucidating the expression patterns of key candidate genes during growth and development. This study will provide an essential resource for understanding the molecular regulatory mechanism of fruit abscission in the blue honeysuckle.

C3G quantified method verification and quantified in blue honeysuckle (Lonicera caerulea L.) using HPLC-DAD.

Blue honeysuckle is a source of anthocyanins with great potential as a food colorant, and a healthy and functional food material, and contains much cyanidin 3-glucoside (C3G), which has many benefits for human health. A rapid, reliable, accurate quantification method of anthocyanin content in different varieties of blue honeysuckle is critical to help in breeding and selecting excellent varieties which are used in the food processing industry and healthcare industry. Our objective was to verify the modified quantification method of C3G and quantified C3G content in three blue honeysuckle varieties of 'Berel', 'Lanjingling' and 'Wulan' using the modified HPLC method by Agilent 1200 system and CAPCELL PAK C18 column (150 mmⅹ4.6 mm, I. D., 5 µm, Japan), with detection at 530 nm, the solvent flow rate was 1 mL/min, the temperature of the column chamber is 35 °C. The results indicated that the modified method was validated in terms of linearity (R2 = 0.999), precision (RSD = 0.61%), stability (RSD = 5.23%), and recovery with a good level, and C3G can be quickly quantified in blue honeysuckle. In addition, 'Wulan' contains the highest C3G level compared with 'Lanjingling' and 'Berel'.

Chemical Composition of Honeysuckle (Lonicerae japonicae) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals.

Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both honeysuckle extracts inhibited the binding of SARS-CoV-2 spike protein to ACE2, as well as ACE2 activity. The ethanol extract exhibited a 100% inhibition on binding of the SARS-CoV-2 spike protein to ACE2 at 100 mg botanical equivalent/mL, whereas the water extract had a 65% binding inhibition at the same concentration. Furthermore, the water extract exhibited 90% ACE2 activity inhibition, which was stronger than that of the ethanol extract (62% inhibition) at the same botanical weight concentration. In addition, higher total phenolic contents and greater scavenging activities against hydroxyl (HO•), DPPH•, and ABTS•+ radicals were observed in the water extract than the ethanol extract counterpart on a dry botanical weight concentration basis. These findings suggest honeysuckle has the potential to reduce the risk of SARS-CoV-2 infection and the development of severe COVID-19 symptoms.