연교

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections present a global health crisis, with escalating resistance to last-line antibiotics. Traditional Chinese medicines (TCMs) demonstrate multi-component synergy against resistant pathogens. This study deciphered the antibacterial mechanisms of bioactive TCM components targeting MDR-KP through integrative pharmacology and experimental validation. Four core TCMs (Scutellaria baicalensis, Forsythia suspensa, Lonicera japonica, Aloe vera) were screened via Chinese Pharmacopoeia and TCMSP database. Network pharmacology identified core components and enriched pathways. Clinically isolated MDR-KP strains (resistant to meropenem, polymyxin E, and tigecycline) were characterized. Synergistic effects were evaluated using checkerboard assays, biofilm quantification, and membrane permeability assays. Molecular docking and RT-qPCR analyzed target interactions, while ELISA and CCK-8 assessed anti-inflammatory activity and cytotoxicity. Consequently, luteolin, wogonin, and kaempferol were identified as key components targeting PI3K/AKT and MAPK pathways. Their triple combination (2/4/8 μg/mL) exhibited potent synergy (FIC = 0.38), reducing biofilm biomass by 68% (p < 0.001) and extracellular polysaccharide thickness from 15.1 μm to 3.1 μm (p < 0.001). Flow cytometry confirmed a 144.8% increase in membrane permeability. Molecular docking revealed high-affinity binding to PI3K (- 6.78 kcal/mol), AKT1 (- 6.60 kcal/mol), and MAPK1 (- 7.24 kcal/mol), with RT-qPCR showing significant downregulation of these genes (p < 0.001). The combination suppressed LPS-induced TNF-α and IL-6 release by 72% and 65%, respectively, while maintaining 95.5% cell viability at therapeutic concentrations. In Conclusion, this study unveils a triple-action mechanism of luteolin-wogonin-kaempferol against MDR-KP, simultaneously disrupting resistance pathways, biofilms, and hyperinflammation. The regimen offers a safe, multi-target therapeutic strategy for combating drug-resistant infections. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Forsythia suspensa extract (FSE) has been demonstrated to attenuate physiological stress induced by high temperature or high stocking density. This experiment was conducted with 144 male Arbor Acre broilers (1-d-old, weighing 42.7 ± 1.7 g) to determine the effects of FSE on performance, nutrient digestibility, antioxidant activities, serum metabolites, and immune parameters for birds treated with corticosterone (CS). The birds were randomly allotted to 1 of 4 treatments in a 2 × 2 factorial arrangement that included FSE supplementation (0 or 100 mg/kg) and CS administration (0 or 20 mg/kg of diet for 7 consecutive days starting on d 14). The feeding program consisted of a starter diet from d 1 to 21 and a finisher diet from d 22 to 42. Corticosterone administration decreased (P < 0.01) ADG and impaired (P < 0.01) feed conversion ratio in both phases and overall, which were alleviated (P < 0.01) by dietary FSE supplementation in the finisher phase and overall. At d 21, CS administration caused decreases (P < 0.05) in the apparent digestibility of energy, relative weight of bursa and thymus, total antioxidant capacity, superoxide dismutase (SOD) activity, and antibody titers to Newcastle disease virus (NDV); however, serum malondialdehyde and uric acid were increased. All of these changes were attenuated (P < 0.05) by dietary FSE supplementation. At d 42, FSE supplementation improved (P < 0.05) the apparent digestibility of DM and CP, relative weights of bursa, SOD activity, and antibody titers to NDV, which were impaired by CS administration. Interactions (P < 0.05) were noted between CS and FSE for ADG and feed conversion ratio in the finisher phase and overall, as well as total antioxidant capacity, SOD activity, uric acid, and antibody titers to NDV at d 21, as well as relative weights of thymus at d 42. In conclusion, dietary FSE supplementation enhanced nutrient digestibility and performance of broiler possibly by reducing oxidative stress and immune depression challenged by CS. © 2014 Poultry Science Association Inc.

Forsythoside A is the main active ingredient in the Chinese medicine Forsythia suspensa, which has antiviral, anti-inflammatory, antioxidation, and immunoregulatory effects. It is reported that Forsythoside A can significantly inhibit the replication of the avian infectious bronchitis virus(IBV) in cells, but there is no report in chickens. The present study aimed to investigate the effect of Forsythoside A on IBV-M41, experiments were designed using 120 chickens at 12 days of age. The chickens were randomly divided into eight groups: Forsythoside A high-, medium-, and low-dose prevention groups, Forsythoside A high-, medium-, and low-dose treatment groups, model control group and normal control group. All chickens, except the normal control group, were inoculated with 0.2 ml of IBV-M41 at 15 days of age.The antiviral effects were evaluated by clinical signs, weight, histopathology, T-,B-lymphocyte proliferation, T-lymphocyte subsets and cytokine levels.The results showed that the infection rate in each Forsythoside A prevention group was significantly lower than that in the treatment group and model control group (P < 0.05). The recovery rate in each Forsythoside A treatment group was significantly higher than that in the model control group (P < 0.05), and the recovery rate in high- and medium-dose treatment group was the highest, at up to 86.67%. Lymphocytic transformation ability significantly improved in the prevention and treatment groups. Forsythoside A significantly improved the CD3+, CD4+, and CD8+ T-lymphocyte of infected chickens. The cytokine level was able to maintain high concentrations of IL-2 and IFN-α for a long time and maintain a dynamic IL-4-concentration balance. A number of results showed that Forsythoside A had both preventive and therapeutic effects in IBV-M41-infected chickens, among which the high-dose (80 mg/kg/d) prevention group，the high- (80 mg/kg/d) and medium (40 mg/kg/d) -dose treatment group had significant effects.

A 42-d trial was conducted with 252 broiler chickens (d 1 of age, 38.8 +/- 1.3 g of BW) to determine the effects of Forsythia suspensa extract on growth performance, nutrient digestibility, and antioxidant activities under high ambient temperature (32 +/- 1 degrees C). The feeding program consisted of a starter diet from d 1 to 21 of age and a finisher diet from d 22 to 42 of age. Dietary treatments included a negative control group (NC) fed a cornsoybean meal based diet without vitamin C or Forsythia suspensa extract, a positive control group fed a diet with 200 mg of vitamin C/kg, and a test group (FS) fed with 100 mg of Forsythia suspensa extract/kg. There were 14 cages per treatment and 6 birds per cage during the study. Birds had free access to diets and water during the entire period. Body weight and feed intake were measured at d 21 and 42. Blood and tissue samples were collected at d 21 and 42 for assay of antioxidant indices. Growth performance did not differ among treatment groups during the starter period. In the finisher phase, birds in FS had greater (P < 0.05) average daily gain, feed conversion, and apparent digestibility of energy, CP, calcium, and phosphorus than birds in NC. Furthermore, birds in FS had greater (P < 0.05) total antioxidant capacity and superoxide dismutase activity and lower (P < 0.05) malondialdehyde activity in the serum than birds in NC. The FS birds had greater (P < 0.05) muscle superoxide dismutase activity and lower (P < 0.05) malondialdehyde than NC birds. During the entire period, hepatic superoxide dismutase activity of FS birds was greater (P < 0.05) than that of NC birds. Dietary supplementation with Forsythia suspensa extract can enhance nutrient digestibility and growth performance possibly by reducing oxidative stress of broiler chickens under high ambient temperatures.

Forsythoside A, a natural phenylethanoid glycoside extracted from the weeping forsythia (Forsythia suspensa), exhibits a wide range of pharmacological activity, including antibacterial, hepatoprotective, antioxidant, neuroprotective, antiviral, and anti-inflammatory. The aim of this study was to determine its anti-hyperglycaemic and antioxidative effects in a diabetic mouse model (created by administering high-fat diet alongside successive low doses of streptozotocin) by measuring fasting blood glucose levels, body weight, food and water intake, oxidative stress, and histopathological changes. Diabetic mice received either forsythoside A (30 or 60 mg/kg bw) or metformin (150 mg/kg) as standard type 2 diabetes medication for comparison. After four weeks of administration, forsythoside A significantly increased body weight and reduced food and water intake at both doses, while the higher, 60 mg/kg dose also significantly reduced fasting blood glucose and had a similar effect on all these parameters as metformin. The higher, 60 mg/kg dose also had similar antioxidative effects as metformin in lowering malondialdehyde (MDA) and reactive oxygen species (ROS) and in elevating the antioxidant superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels. Moreover, at 60 mg/kg forsythoside A attenuated lipid accumulation in diabetic mice by elevating high-density lipoprotein cholesterol (HDL-C) and lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), showing comparable effect to metformin. Similar improvements were observed by histopathological changes in the liver. Forsythoside A also lowered insulin levels in diabetic mice by up-regulating p-IRS-1 and inhibited the mitogen-activated protein kinase (MAPK) pathway by lowering the expressions of the p-p38 and p-JNK proteins. At the same time, it promoted the Nrf2 pathway by increasing Nrf2 and HO-1 expressions relative to untreated diabetic mice. In conclusion, forsythoside A demonstrated therapeutic effects akin to those of 150 mg/kg metformin and may be a promising candidate for clinical application. Publisher: Forsitozid A prirodni je feniletan

Respiratory syncytial virus (RSV) imposes a substantial health burden, particularly among pediatric and elderly populations. The RSV fusion (F) protein, a critical mediator of viral entry and syncytium formation, represents a promising and rational target for antiviral drug development. Forsythia suspensa (Lianqiao in Chinese), a traditional Chinese medicinal herb, has been empirically employed for decades in the prevention of viral infections; however, its pharmacologically active constituents remain poorly characterized. The present investigation developed a high-expression F protein cell membrane chromatography system, and integrated with UHPLC-MS, to screen pharmacological substances from FS and verified the anti-viral potential against RSV in vivo. Our study pinpointed Forsythoside A, Forsythoside B, Phillygenin, and Phillyrin as potential anti-RSV compounds in FS. The research findings suggest that Forsythoside A, Forsythoside B, and Phillygenin exhibit considerable suppressive effects on cell fusion induced by RSV, concurrently effectively diminishing the expression level of the F protein gene. In contrast, the inhibitory impact of Phillyrin seems relatively less potent. In conclusion, our findings provide a convenient, fast, and accurate method to screen potential anti-RSV ingredients in natural herbal medicines. These results may facilitate the development of RSV treatment. © 2026 Wiley‐VCH GmbH.

In this study, a green and efficient extraction methodology was developed by leveraging the unique properties of chitosan-namely its non-toxicity, biocompatibility, and adhesive nature-to enhance the recovery of bioactive ingredients from Forsythia suspensa leaves. The core mechanism involves the formation of complexes between chitosan and the target bioactive ingredients, which significantly boosts their extraction efficiency. To substantiate this mechanism, comprehensive characterization was performed using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and molecular docking analyses. The results provided robust evidence of a strong interaction between chitosan and the bioactive ingredients, leading to a marked enhancement in both the stability and aqueous solubility of the target compounds. For process optimization, a multi-objective approach was implemented using the Non-dominated Sorting Genetic Algorithm II (NSGA-II) to simultaneously maximize the extraction yields of phillyrin and forsythoside A. The algorithm identified the optimal parameters as a leaf-to-chitosan mass ratio of 10:11.75, a solid-to-liquid ratio of 1:52 g/mL, a temperature of 80 °C, and a duration of 120 min. Under these optimized conditions, the corresponding extraction yields for phillyrin and forsythoside A were 1.68 ± 0.16% and 3.23 ± 0.27%, respectively. These findings collectively indicate that chitosan-assisted extraction represents a highly promising and advanced technology for the sustainable and effective extraction of bioactive ingredients from botanical sources.

Forsythia suspensa (Thunb.) Vahl, a widely used medicinal plant, especially its fruits in the green fruit stage, is called "Qingqiao" (QQ). However, the effects of climate change on the quality of QQ have not been reported. Therefore, this study conducts an analysis from the perspective of quality distribution and further proposes future stable distribution areas. In this study, F. suspensa distribution data were collected through field surveys and online sources. Phillyrin and forsythoside A contents from selected QQ production areas were then combined and analyzed via the maximum entropy model alongside stepwise regression equations to assess the potential effects of future climate on QQ quality. The results suggest that under various representative concentration pathway (RCP2.6, RCP4.5, and RCP8.5), the QQ quality areas, which are based on the two key contents, decreased. The environmental factors influencing the phillyrin content were significantly negatively correlated with the soil texture classification and precipitation of the driest quarter, whereas the forsythoside A content was significantly negatively correlated with the mean diurnal range and precipitation of the driest quarter. The stable quality regionalization prediction of F. suspensa is expected to remain mainly in North China, with a northward shift of the centroid suggesting a potential response to global warming. These findings provide a foundation for F. suspensa conservation and sustainable development of these resources. © 2025. The Author(s).

Glioblastoma (IDH-wildtype) (GBM), the most common high-grade glioma, is a highly invasive and malignant tumor in the brain. Currently, there is no effective treatment for GBM, highlighting the urgent need to find novel therapeutic drugs. Forsythoside B (FB), as a phenylethanoid glycosides compound extracted from Forsythia suspensa, has shown pharmacological functions such as anti-inflammation and anti-bacteria. However, its effects and mechanisms in GBM remain unclear. By performing several in vitro assays, we found that FB suppressed the proliferation of GBM cells in dose- and time-dependent manners. Furthermore, FB arrested the cell cycle at the G0/G1 phase and induced apoptosis in GBM cells. FB also significantly inhibited GBM cells migration. Mechanistically, RNA sequencing results showed that FB treatment remarkably upregulated the expression of PTPRN (a protein-coding gene that plays an important role in the progression of various cancers) in GBM cells. Consistent with this finding, PTPRN expression was downregulated in GBM samples from the Chinese Glioma Genome Atlas (CGGA) and other databases. Knockdown of PTPRN partially restored the inhibitory effects of FB on GBM cells, whereas, overexpression of PTPRN enhanced FB-induced suppression of GBM cell growth and migration. Finally, we found that FB slowed down the growth of tumor in a GBM orthotopic mice model through upregulating PTPRN expression in vivo, with no significant toxicity to other organs. Taken together, these results suggest that FB exerts its anticancer effects on GBM via increasing the expression of PTPRN, which may provide a potential new therapeutic strategy for the treatment of GBM.

Forsythoside A (FTA) is a key component found in the fruit and leaves of Forsythia suspensa, having anti-inflammatory and antioxidant properties. However, it is unclear whether FTA can have a protective effect against acute alcoholic liver injury (ALI) and how it may exert this effect. This research examined the potential protective effects of FTA against acute ALI using cell and animal models. The protective properties of FTA against acute ALI were attributed to its anti-inflammatory and antioxidant actions by detecting the markers of oxidative stress and inflammation. The underlying mechanism was explored through the utilization of Western blotting, Molecular Docking, and Microscale Thermophoresis techniques. The results showed that pretreatment with high doses of FTA had a significant protective effect on acute ALI in both cell and animal models. The pretreatment with high doses of FTA inhibited alcohol-induced oxidative stress and inflammation, raising antioxidative enzyme activity in both models. Furthermore, FTA has been shown to bind to TLR4, thereby inhibiting alcohol-induced activation of the NF-κB signaling pathway, leading to a decrease in cellular oxidative stress and inflammatory reactions. This interaction also facilitates the ubiquitination-mediated degradation of TLR4, ultimately diminishing its regulatory impact on the NF-κB signaling cascade. FTA has a significant protective effect on acute ALI. It binds to TLR4 to inhibit the activation of the NF-κB signaling pathway by alcohol, thereby reducing oxidative stress and inflammation and exerting a protective effect. The results of our study provide a theoretical basis for the development of FTA for the prevention and treatment of acute ALI. © 2025 John Wiley & Sons Ltd.

Non-alcoholic fatty liver disease (NAFLD) is a long-term metabolic condition marked by unusual fat buildup in the liver, with an increasing occurrence worldwide. Forsythoside A (FA), a bioactive component of Forsythia suspensa, has anti-inflammatory, antioxidative, and hepatoprotective effects. This study investigates the mechanisms by which FA may treat NAFLD. Using bioinformatics tools, 35 potential targets of FA were identified, and a protein-protein interaction network was constructed. KEGG and GO enrichment analyses highlighted important pathways associated with NAFLD. The effects of FA were confirmed using both in vitro and in vivo NAFLD models. Matrix Metalloproteinase 9 (MMP9), and Tumour Necrosis Factor Alpha (TNFɑ), were identified as core targets. KEGG analysis showed that FA affects metabolic, TNF signalling, and insulin resistance pathways. In vitro and in vivo, FA reduced lipid accumulation and modulated TNFɑ, MMP9, and ALB expression. FA may treat NAFLD by modulating the TNFɑ/MMP9/ALB pathway, providing new therapeutic targets and insights for NAFLD treatment.

Dihydrotestosterone (DHT), an androgen derivate, is known to be a key factor involved in androgenetic alopecia. DHT suppresses the growth of outer root sheath cells and induces apoptosis of hair keratinocytes, thereby causing hair follicle miniaturization and hair regrowth inhibition. Forsythoside A, a natural substance derived from Forsythia suspensa, has been shown to reduce DHT-induced apoptosis in human hair cells and suppress hair regrowth inhibition induced by DHT in mice. However, the molecular mechanism underlying the action of forsythoside A remains unclear. Here, we report that the alleviation of androgenetic alopecia by natural phenylethanoid glycoside forsythiaside A involves the selective inhibition of warmth-sensitive Ca2+-permeable transient receptor potential vanilloid-3 (TRPV3) channels. TRPV3 mRNA and protein expressions are upregulated in the skin of a mouse model of androgenetic alopecia induced by DHT. Ablation of the Trpv3 gene or subcutaneous injection of forsythoside A alleviates DHT-induced hair regrowth inhibition. In whole-cell patch clamp recordings, forsythoside A selectively inhibits macroscopic TRPV3 currents in a concentration-dependent manner with an IC50 value of 40.1 ± 4.8 μM. At the single-channel level, forsythoside A also reduces the channel open probability and open frequency without significantly altering the channel unitary conductance. Molecular docking combined with site-directed mutagenesis reveals two residues T636 and T665 critical for forsythoside A-mediated inhibition of TRPV3. Taken together, our findings demonstrate that TRPV3 inhibition is an important a mechanism by which natural forsythoside A ameliorates DHT-induced hair regrowth. Topical TRPV3 inhibitors may hold promise as a new therapeutic approach for treating androgenetic alopecia.

Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties. However, there is currently no report or research on the effectiveness of FTS·B treatment for EAE. The aim of this study was to investigate the neuroprotective properties of (FTS·B) on EAE and reveal its potential mechanisms. Myelin oligodendrocyte glycoprotein-induced EAE mice were randomly categorized into the control, EAE model, and FTS·B treatment groups. Behavioral testing, pathology, immunohistochemistry, immunofluorescence staining, and western blot analysis of spinal cord tissue were used to determine the effects and mechanisms of FTS·B on EAE in mice. We found that FTS·B treatment could significantly alleviate and reduce the clinical symptoms and morbidity of EAE, respectively. In addition, FTS·B administration reduced inflammatory response and demyelination by inhibiting glial cell activation in the spinal cord of EAE mice. Further experiments confirmed that FTS·B inhibited the formation of NLRP3 inflammasome in microglia and astrocytes, thereby suppressing neuroinflammation and GSDMD-mediated pyroptosis. Altogether, these results suggest that FTS·B treatment attenuates central neuroinflammation and pyroptosis by inhibiting NLRP3 inflammasome of glial cells in EAE mice.

Making health-enhancing tea from Forsythia suspensa leaves has been a tradition of Chinese folk culture for centuries. However, these leaves were not officially recognized as a new food source until 2017 by the Chinese government. In this study, ethyl acetate fractions from Forsythia suspensa fruit and leaves exhibited excellent antioxidant activity in vitro antioxidant assays and in vivo D-galactose-induced aging mice model. The antioxidant activity of the leaves was higher than that of fruit both in vitro and in vivo. The chemical constituents present in these ethyl acetate fractions were comprehensively analyzed using UHPLC-Q-Exactive-Orbitrap/MS. A total of 20 compounds were identified, among which forsythoside E, (+)-epipinoresinol, dihydromyricetin, chlorogenic acid, and ursolic acid were exclusively detected in the ethyl acetate fraction of Forsythia suspensa leaves, but absent in the ethyl acetate fraction derived from its fruit. This study provides theoretical support for the utilization of Forsythia suspensa fruit and leaves.

CONTEXT: Forsythoside A (FSA) was extracted from Forsythia suspensa, a traditional Chinese medicine, which has been demonstrated to exert anti-inflammatory, antibacterial, and other pharmacological effects. However, the anticancer effect of FSA in esophageal squamous cell carcinoma (ESCC) has not been documented. OBJECTIVE: The present study aimed to elucidate the mechanism of FSA against ESCC. MATERIALS AND METHODS: Network pharmacology and molecular docking were employed to predict the mechanism. FSA was utilized to treat ESCC cell lines KYSE450 and KYSE30, followed by CCK-8 assay, cell cloning formation assay, flow cytometry, Western blot, RNA-seq analysis, and subsequent in vivo experiments. RESULTS: Network pharmacology and molecular docking predicted that the therapeutic effect of FSA in ESCC is mediated through proteins such as BCL2 and BAX, influencing KEGG pathways associated with apoptosis. In vitro experiments showed that FSA inhibited cell proliferation and plate clone formation, promoted cell apoptosis and impacted the cell cycle distribution of G2/M phase by regulating BCL2, BAX, and p21. Further RNA-seq in KYSE450 cells showed that FSA regulated the expression of 223 genes, specifically affecting the biological process of epidermal development. In vivo experiments showed that gastric administration of FSA resulted in notable reductions in both tumor volume and weight by regulating BCL2, BAX, and p21. 16S rRNA sequencing showed that FSA led to significant changes of beta diversity. Abundance of 11 specific bacterial taxa were considerably changed following administration of FSA. CONCLUSIONS: This study presents a novel candidate drug against ESCC and establishes a foundation for future clinical application.

The fruits of Forsythia suspensa (F. suspensa) have been used as a traditional Chinese medicine for 2000 years. Currently, the quality control of F. suspensa strictly follows the instructions of Chinese Pharmacopeia, which mainly controls the content of forsythoside A, phillyrin, and volatile oil. In this study, air pressure MALDI mass spectrometry imaging (AP-MALDI MSI) was used to evaluate the quality of F. suspensa fruits and the distribution of dozens of active ingredients. The variation of active ingredients was measured for more than 30 batches of samples, regarding harvest time, cultivated environment, shelf-life, and habitat. Fifty-three active ingredients could be detected in F. suspensa fruits with AP-MALDI MSI. Seven active ingredients were upregulated, four ingredients downregulated, and 15 ingredients did not change in ripe fruits. A sharp variation of active ingredients in late September was observed for the Caochuan fruits harvested in 2019, which is closely related to the appearance of the ginger color of the pericarp under the microscope observation. The microscope observation is a reliable way to classify ripe and green fruits instead of outlook. Just considering forsythoside A and phillyrin, it is found that wild fruits are better than cultivated fruits, but cultivated fruits have high contents of other ingredients. The shelf-life of F. suspensa fruits is proposed to be 3 years, considering the 26 ingredients investigated. It was found that Luoning wild fruits are better than those from Caochuan with a new evaluation method. Mass spectrometry imaging is an easy, objective, and effective method to evaluate the quality of F. suspensa fruits. © 2024 John Wiley & Sons Ltd.

With the proposal of the 2030 Agenda for Sustainable Development, the Chinese medicine extraction technology has been innovatively improved to prioritize low energy consumption, sustainability, and minimized organic solvent utilization. Forsythia suspensa (FS) possesses favorable pharmacological properties and is extensively utilized in traditional Chinese medicine. However, due to the limitations of the composition and extraction methods, its potential has not been fully developed. Thus, a combination of ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), and β-cyclodextrin extraction (β-CDE) was employed to isolate and purify rutin, phillyrin, and forsythoside A from FS. The results demonstrated that the efficiency of extracting enzymatic and ultrasound assisted β-cyclodextrin extraction (EUA-β-CDE) was highly influenced by the temperature and duration of hydrolysis, as well as the duration of the extraction process. According to the results of the single-factor experiment, Box-Behnken design (BBD) in Response surface method (RSM) was used to optimize the experimental parameters to achieve the maximum comprehensive evaluation value (CEV) value. The EUA-β-CDE compared with other extraction methods, has good extraction effect and low energy consumption by high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), calculation of power consumption and CO2 emission The EUA-β-CDE compared with other extraction methods, has good extraction effect and low energy consumption by HPLC, SEM, calculation of power consumption and CO2 emission. Then, the structural characteristics of EUA-β-CDE of FS extract had significant interaction with β-CD by Fourier infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In addition, EUA-β-CDE extract has good antioxidant and anti-inflammatory activities. The establishment of EUA-β-CDE of FS provides a new idea for the development and application of other sustainable extraction methods of traditional Chinese medicine.

BACKGROUND: Pulmonary fibrosis (PF) is an end-stage change in many interstitial lung diseases, whereas no proven effective anti-pulmonary fibrotic treatments. Forsythoside A (FA) derived from Forsythia suspensa (Thunb.) Vahl, has been found to possess lung-protective effect. However, studies on its anti-pulmonary fibrosis effect are limited and its mechanism of action remains unknown. PURPOSE: This study aimed to explore the underlying mechanism of FA on PF. METHODS: Male C57BL/6 mice were randomized into normal (CON), model (BLM), pirfenidone (PFD), low- and high-dose FA (FA-L, FA-H, respectively). Except for the CON group, which was injected with the same dose of saline, the model of PF was established by intratracheal instillation of BLM, during which the survival rate and body weight changes of the mice were measured. The lung histopathology was evaluated by Hematoxylin-eosin, Sirius red, and Masson staining. Transcriptome analysis was performed to screen for the differential genes associated with the role of FA in PF. Differential genes in normal and pulmonary fibrosis patients with the GSE2052 dataset were analyzed in the GEO database. The levels of CTGF, α-SMA, MMP-8 in lung and TNF-α in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The levels of HYP in lungs were detected by digestion. The mRNA and protein levels of MMP-7, E-cadherin, CD31, α-SMA, TGF-β1, IL-6, β-catenin, ZO-1, PTPRB, E-cadherin, and vimentin in lungs were detected by RT-qPCR and Western blot. The expression of CD31, α-SMA, TGF-β1 and ZO-1 were detected by immunofluorescence. TGF-β1-stimulated HFL1 cells and human umbilical vein endothelial cells (HUVECs) were used in an attempt to explore the possible role of protein tyrosine phosphatase receptor type B (PTPRB) involved in FA-induced improvement of PF. RESULTS: The results showed that FA could improve the survival rate and body weight of PF mice. FA could alleviate the symptoms of alveolar wall thickening, inflammatory cell infiltration, blue collagen fiber deposition, collagen fiber type Ⅰ and type Ⅲ in mice with PF. In addition, FA could reduce the levels of HYP, CTGF, α-SMA, TGF-β1, TNF-α, β-catenin and MMP8, and regula

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

This study aims to characterize and identify the chemical constituents in 11 parts of Forsythia suspensa by using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with a self-established chemical constituent database, including leaves, flowers, fruits, green F. suspensa, old F. suspensa, and seeds. The quality attributes and differences of different parts of F. suspensa were evaluated by principal component analysis, partial least square discriminant analysis, and other stoichiometric methods. A total of 79 compounds were identified, including 13 phenylethanol glycosides, 10 lignans, 12 flavonoids, 10 organic acids, 14 terpenoids, and 20 other types of compounds. Among them, 34 compounds were the main variables of difference between the different parts of F. suspensa, and the content of each component was relatively higher in the leaves and green F. suspensa. The LPS-induced inflammation model of RAW264.7 cells was applied to study the anti-inflammatory activity of the extracts of the different parts of F. suspensa and the main constituents. The results show that the extracts of green F. suspensa, flower, twig, and stem exhibited anti-inflammatory activity, and the constituents such as forsythoside A, phyllyrin, phillygenin, and(+)-pinoresinol-β-D-glucopyranoside could significantly inhibit anti-inflammatory activity released by NO. The chemical constituent in different parts of F. suspensa is analyzed comprehensively, and the anti-inflammatory activity is evaluated in this study, which provides a reference for the development and comprehensive utilization of F. suspensa resources.

Tenuigenin is a kind of the main active ingredients in roots of Polygala tenuifolia Willd. (a species in the genus Polygala, family Polygalaceae) and forsythoside A (FA) is one of the main active ingredients of Forsythia suspensa (Thunb.) Vahl. (a species in the genus Forsythia, family Meliaceae). The studies have shown that tenuigenin-based Polygala tenuifolia Willd. extract (YZ) and FA have protective effects on nervous damage. In the study the combination (YF) of YZ and FA showed synergistic neuro-protective effects on PC12 cell model of Alzheimer's disease (AD). YF (2:1) which was made up of 2/3 YZ and 1/3 FA increased cell viability, inhibited AChE expression and activity, alleviated apoptosis and slowed Aβ aggregation, while YF (1:2) which consisted of 1/3 YZ and 2/3 FA depressed inflammation and oxidative stress. There was no obvious synergistic effect of YF on Tau phosphorylation.

Kawasaki disease (KD), an acute exanthematous febrile pediatric illness involving systemic non-specific inflammatory reactions in small- and medium-sized arteries, poses a significant risk of coronary artery and myocardial inflammatory injury. Developing new KD treatments with improved safety and fewer side-effects is highly desirable. Forsythoside B (FTS-B), extracted from the Forsythia suspensa plant, exerts anti-inflammatory activity by inhibiting NF-κB, which is regulated by SIRT1, the reduced expression of which is strongly associated with cardiovascular disease. However, it has yet to be established whether FTS-B influences KD-related inflammatory damage. In this study, we investigated the effects of FTS-B on inflammation in cellular and murine models of KD. Our findings revealed that KD is associated with cardiac dysfunction and inflammatory injury to myocardial and human coronary artery endothelial cells (HCAECs), resulting in a pyroptosis-feedback loop. Both cellular and KD models were characterized by reduced SIRT1 expression and increased NF-κB p65 expression. Contrastingly, the rates of pyroptosis in both murine model myocardial tissues and HCAECs were significantly alleviated in response to FTS-B treatment. Also in both models, we detected an increase of SIRT1 expression and a decrease in the expression of p65. Further examination of the protective mechanism of FTS-B using the SIRT1-specific inhibitor, EX 527, revealed that this inhibitor blocked the palliative effects of FTS-B on inflammatory injury-induced pyroptosis. These results highlight the potential utility of the SIRT1-NF-κB-p65 pathway as a therapeutic target for KD treatment and demonstrate that FTS-B can alleviate KD-induced cardiac and HCAEC inflammatory injury via inhibition of pyroptosis.

Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p-NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

INTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerular disease. The traditional Chinese formula Mahuang Lianqiao ChixiaoDou Decoction (MLCD) has been demonstrated to alleviate IgAN. However, the potential mechanism remains to be explored. This study was designed to investigate the mechanism of MLCD in improving IgAN through transcriptomics analysis, network pharmacology, and experimental validation. METHODS: The mouse model of IgAN treated with MLCD and a positive control was established. After 8-week treatment, biochemical indicators of renal function and kidney histology were measured. MLCD regulating the potential genes at the transcript level was analyzed. A network pharmacology based on the main components of MLCD identified by HPLC‒MS/MS was adopted. Then, integrated network pharmacology, together with transcriptomics, was performed to predict the potential pathway of MLCD in improving IgAN, which was also validated by ELISA, qRT-PCR, and Western blotting. RESULTS: MLCD significantly ameliorated kidney damage in IgAN model mice by decreasing the levels of 24-hour proteinuria, serum creatinine, and blood urea nitrogen. The integration of transcriptomics analysis with network pharmacology suggested that the regulation of the MAPK pathway might be a crucial mechanism of action. In vivo experiments confirmed that MLCD attenuated the expression of renal proteins (TLR9, MyD88, IRAK4, p38MAPK, and NF-κB) and reduced the release of inflammatory cytokines (TGF-βand IL-6) in mice. DISCUSSION: This study clarifies the mechanism of MLCD in treating IgAN; however, further in vitro experiments are needed. CONCLUSION: MLCD can reduce the inflammatory response and improve kidney function in IgAN models by regulating the TLR9/MAPK/NF-κB signaling pathway.

BACKGROUND: Inflammation is a critical process in both physiological defense and the pathogenesis of numerous diseases. While current anti-inflammatory drugs such as NSAIDs and corticosteroids are effective, their long-term use is associated with significant adverse effects, highlighting the need for safer alternatives. Phillyrin, a primary bioactive lignan extracted from the traditional Chinese medicine Forsythiae Fructus (Lianqiao), has emerged as a promising natural anti-inflammatory agent. METHODS: Data regarding the pharmacology, pharmacokinetics, and toxicology of phillyrin were collected through PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. In this review, we conducted relevant searches using the key words "phillyrin", "forsythin (synonym of phillyrin)", "Forsythiae Fructus", "Forsythia, Forsythia suspensa", "lianhua qingwen", "shuanghuanglian", "pharmacokinetics", "bioavailability", "application", "molecular mechanism", "adverse reactions", "preclinical and clinical trial", and "animal study", and included studies reported up to and including October 2025. RESULTS: Available toxicological data from animal studies and early-phase clinical trials indicate that phillyrin has a favorable safety profile, with only mild and transient adverse effects reported. Preclinical studies reveal that phillyrin exerts potent anti-inflammatory effects across a broad spectrum of acute and chronic conditions, including viral pneumonia, acute lung injury, arthritis, colitis, and central nervous system injuries. Phillyrin exerts multi-target effects, primarily by suppressing key pro-inflammatory signaling pathways such as NF-κB and MAPK, and by inhibiting the NLRP3 inflammasome. Furthermore, phillyrin shows protective effects on vital end-organs like the heart, liver, and kidneys in chronic metabolic and cardiovascular diseases. CONCLUSIONS: Phillyrin represents a promising multi-target anti-inflammatory candidate. However, challenges such as phillyrin's low bioavailability, limited mechanistic insights, and the lack of validation in large-scale clinical trials must be addressed to fully realize its therapeutic potential.

PURPOSE: Through network pharmacological prediction and in vitro experimental verification, the mechanism of action of Lianqiao Jinbei Decoction (LJD) in inhibiting HER2-positive breast cancer cells was clarified, providing experimental evidence for its treatment of HER2-positive breast cancer. METHODS: Network pharmacology method was used to construct the potential target network of LJD in the treatment of HER2+ breast cancer. After cell culture in vitro, the proliferation of HER2+ SK-BR3 breast cancer cells was investigated using CCK-8 technique. The apoptotic potential of SK-BR3 cells was detected by flow cytometry, and the migration of SK-BR3 cells was detected by cell scratch assay. The expression of HER2 protein in SK-BR3 breast cancer cells was detected by ELISA. RESULTS: HER2 was identified as the central gene and quercetin, β-sitosterol, and luteolin were the primary active ingredients using network pharmacology analysis. Serum-containing LJD medication can stop SK-BR3 cells from proliferating (P<0.05). Serum-containing LJD drugs at high, medium, and low concentrations may induce SK-BR3 cell death (P<0.05). LJD serum at high, medium, and low concentrations reduced the migration of SK-BR3 cells (P<0.05). The expression of HER2 protein was decreased by LJD high, medium, and low concentration drug-containing serum (P<0.05). CONCLUSION: Regarding treating HER2-positive breast cancer, LJD has a multi-component, multi-target, and multi-pathway mode of action. The primary target of LJD's activity is the HER2 protein. Serum-containing LJD medication can prevent SK-BR3 cells from proliferating and migrating while encouraging their apoptosis. This effect may be attained by preventing HER2 protein expression. © 2025 Li et al.

This study aims to investigate the mechanism of Mahuang Lianqiao Chixiaodou Decoction(MHLQ) and its main active components in treating immunoglobin A nephropathy(IgAN). The rat model of IgAN was established by a combination of measures including gavage of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. The modeled rats were randomized into model, low-, medium-, and high-dose(1.773, 3.545, and 7.090 g·kg~(-1), respectively) MHLQ, phillyrin(PHI, 0.020 g·kg~(-1)), pseudoephedrine(PSE, 0.020 g·kg~(-1)), and losartan potassium(LP, 9.003 mg·kg~(-1)) groups, and Wistar rats were used as the control. Rats were administrated with corresponding drugs by gavage, and those in the control and model groups received an equal volume of normal saline. All the groups were treated for 4 consecutive weeks. Urine, serum, liver, and kidney samples were collected from rats in each group at the end of drug administration. The 24 h urine protein and renal function were examined, and staining was performed to observe the pathological changes in the renal tissue. The immunofluorescence assay was employed to detect the expression of IgA and complement C3/C3b/C3c in the renal tissue. Electron microscopy was employed to observe the ultrastructure of the renal tissue. Enzyme-linked immunosorbent assay was performed to determine the expression of complement C3 and sublytic C5b-9 in the serum and renal tissue. Western blot was performed to determine the expression levels of hepatic and renal complement C3/C3b/C3c, C5/C5a, C5b-9, and complement factor B(CFB). Immunohistochemistry(IHC) was employed to measure the expression of complement C3 in the renal tissue. The results showed that compared with the control group, the model group had elevated levels of blood urea nitrogen and serum creatinine, proliferation of glomerular mesangial cells and extracellular matrix, and glomerular deposition of IgA immune complexes or electron-dense material. In addition, the model group showcased increased serum C3 levels and up-regulated expression of CFB, C3/C3b/C3c, C5/C5a, and C5b-9 in the renal tissue and C3/C3b/C3c and C5b-9 in the hepatic

OBJECTIVE: To explore the differences in Traditional Chinese Medicine (TCM) diagnosis and treatment rules for coronavirus disease 2019 (COVID-19) between Northern and Southern China based on the real-world data from 982 COVID-19 patients. METHODS: All consecutive cases of COVID-19 admitted to the TCM department of designated COVID-19 hospitals in eight provinces and cities were retrospectively analyzed. Patients were divided into a Northern and a Southern group according to the location of the admitting hospital. The symptoms, syndrome elements, syndrome distribution and herbal treatments were analyzed. The core prescriptions were extracted using the multiscale backbone-based network comparison algorithm (msbNC). RESULTS: The distribution of syndrome elements showed that dampness was common in Northern and Southern China, wind and heat were more often present in the South, while fire toxin and spleen deficiency were more often encountered in the North. The distribution of syndromes showed that the South was dominated by heat dampness accumulating in the lung (55.69%), while the North was dominated by dampness-toxin stagnating in the lung (44.90%).The results of core prescription mining showed that dispelling dampness, dispersing wind, clearing heat and strengthening spleen were the common treatment methods in Northern and Southern China. For mild cases, Jinyinhua (Flos Lonicerae) and Lianqiao (Fructus Forsythiae Suspensae) were often used in the South to clear heat and relieve exterior symptoms, while Chaihu (Radix Bupleuri Chinensis) and Huangqin (Radix Scutellariae Baicalensis) were often used in the North to relieve muscles by expelling heat. For moderate cases, Chaihu (Radix Bupleuri Chinensis), Qinghao (Herba Artemisiae Annuae), and Shigao (Gypsum Fibrosum) were often used to clear heat of Tri-jiao Channel and stomach in the South, while Fuling (Poria), Chenpi (Pericarpium Citri Reticulatae), and Dangshen (Radix Codonopsis) were often used to invigorate spleen and remove dampness in the North. For severe cases, spleen invigoration and dampness removal as well as relaxing the bowels and discharging heat were often used in the North. CONCLUSION: There were ce

OBJECTIVE: To compare the anti-inflammatory, antitumor and anti-bacterial effects of the single extract (in granules) and the prepared drug in pieces of Forsythia Suspense (Lianqiao, a traditional Chinese herbal medicine). METHODS: In zebrafish embryo models of CuSO4 exposure, tail transection and LPS microinjection-induced inflammation, the anti-inflammatory effects of 10 μg/mL DEX, single extract of Forsythia Suspense, and the water extract of the prepared drug (400, 600, and 800 μg/mL) were evaluated by observing neutrophil counts, RT- qPCR, HE staining and survival analysis. Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining. The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs. RESULTS: In the zebrafish embryo models of inflammation, both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation, reduced the mRNA expressions of TNF-α, IL-6, P38, Jnk, Erk and P65, and increased the survival rate of zebrafish. They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells (HCT116), pancreas adenocarcinoma cells (PANC-1), lung cancer cells (A549), liver cancer cells (Hep3B) and cervical carcinoma cells (Hela) in zebrafish embryos, and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL. CONCLUSION: The two dosage forms of Forsythia Suspense have similar anti-inflammatory, antitumor and antibacterial effects, but their effects for inhibiting IL-6, P65, and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish. 目的: 采用斑马鱼体内模型实验和体外抗菌实验比较连翘配方颗粒和饮片的抗炎、抗肿瘤和抑菌的药效差异。 方法: 将斑马鱼胚胎分为空白组、模型对照组、10 μg/mL地塞米松处理组、连翘饮片处理组（剂量为400、600、800 μg/mL）和连翘配方颗粒处理组（剂量为400、600、800 μg/mL），分别构建硫酸铜、尾鳍横断和LPS显微注射斑马鱼炎症模型，采用中性粒细胞观察、病理组织切片、生存分析和实时定量荧光PCR实验评价连翘配方颗粒与饮片的抗炎药效差异，并从MAPK和NF-κB信号通路角度探讨其抗炎作用机理差异。将斑马鱼胚胎分为模型对照组、250 nmol/L索拉菲尼处理组、连翘饮片处理组（400、600、800 μg/mL）和连翘配方颗粒处理组（400、600、800 μg/mL），采用斑马鱼异种移植肿瘤细胞模型，通过荧光观察和病理组织切片评价连翘配方颗粒与饮片抗肿瘤的药效差异。将实验分为空白组、连翘饮片处理组（1.95、3

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characteristized by the presence of dyskinesia and the progressive loss of dopaminergic neurons. Although certain drugs can mitigate the symptoms of PD, they are unable to delay the disease progression, and their prolonged use may result in complications. Therefore, there exists an urgent necessity to identify potential agents that can effectively delay PD progression with fewer side effects. Recent research has unveiled that several traditional Chinese medicines (TCM) exhibit neuroprotective properties in various models pertinent to PD. Forsythoside A (FSA), the primary bioactive compound derived from TCM Lianqiao, has undergone extensive research in animal models of Alzheimer's disease and cerebral ischemia. However, the investigation into the impact of FSA on PD is limited in existing research. In this study, we aimed to evaluate the neuroprotective effects of FSA on MPTP-induced PD mouse model. FSA demonstrated significant improvements in the behavioral and neuropathological changes triggered by MPTP in mice. Furthermore, it exerted a suppressive effect on the activations of astrocyte and microglia. Meanwhile, Tandem mass tag (TMT)-based quantitative proteomics of striatal tissue and bioinformatics analysis were performed to elucidate the underlying mechanisms of FSA on PD mouse model. Proteomics demonstrated a total of 68 differentially expressed proteins (DEPs) were identified between HFSA and MPTP groups including 26 upregulated and 42 downregulated. Systematic bioinformatics analysis of the 68 DEPs illustrated that they were predominantly related to estrogen signaling pathway and calcium signaling pathway. The related DEPs (PLCβ4, Grm2, HPAC and Cox4i1) expression levels were verified by Western blot. FSA effectively restored the altered expression of the four DEPs induced by MPTP. Summarily, FSA exerted remarkable neuroprotective effects in MPTP-induced mice. Further, our research may provide proteomics insights that contribute to the further exploration of FSA as a potential treatment for PD.

ETHNOPHARMACOLOGICAL RELEVANCE: Mahuang-Lianqiao-Chixiaodou decoction (MLCD) is a traditional Chinese medicinal (TCM) formula recorded in the Treatise on Febrile Diseases. It is commonly used for clinical treatment of atopic dermatitis (AD). However, the potential mechanisms of MLCD intervention in AD combined with mental disorders behaviors such as anxiety and depression remain elusive and deserves further investigation. AIM OF THE STUDY: The study aims to observe the effect of MLCD on anxiety- and depression-like behaviors in AD mice and explore the possible neuroinflammatory mechanism of NOD-like receptor 3 (NLRP3) inflammasome. MATERIALS AND METHODS: The chemical components of MLCD extracts were identified using UHPLC-MS. The AD mice were induced by 2,4-dinitrofluorobenzene and treated with MLCD or mometasone furoate (MF, as a positive control) for 7 days. The pathological changes in their skin tissue and brain hippocampus were observed by hematoxylin-eosin staining. Elevated plus-maze test (EPM), open field test (OFT), and the suspended tail (TST) were used to measure the anxiety- and depressive-like behaviors in AD mice. Expression of NLRP3 inflammasome-related proteins in brain hippocampus were measured by the quantitative real-time polymerase chain reaction (qPCR) and western blotting (WB). RESULTS: We found that MLCD contain many active ingredients, including ephedrine, Forsythoside A, phillyrin, glycyrrhizic acid, etc. Both MLCD and MF alleviated skin lesions and promoted positive histopathological changes in the hippocampus of AD mince to varying degrees. MLCD however, could further increase their proportion of open arm entry times (Oentries%) in EPM, residence time in the central area (Ctime) and the proportion of the number of times in the central area (Centries%) in OFT significantly. MLCD also reduces their immobility time in TST considerably. Mechanistically, MLCD downregulated the relative mRNA expression and protein level of NLRP3, Caspase-1, IL-1β, and IL-18 in hippocampal tissue compared to the model group. CONCLUSIONS: MLCD can alleviate anxiety-like and depression-like behaviors in AD mice by intervening in the gene and protein expression o

ETHNOPHARMACOLOGICAL RELEVANCE: The Antiviral Granules (AG) are derived from the classical famous prescription, which is composed of 9 traditional Chinese medicines, namely Radix Isatidis (called Banlangen, BLG in Chinese), Forsythiae Fructus (called Lianqiao, LQ in Chinese), Gypsum fibrosum, Anemarrhenae Rhizoma (called Zhimu, ZM in Chinese), Phragmitis Rhizoma (called Lugen, LG in Chinese), Rehmanniae Radix (called Dihuang, DH in Chinese), Pogostemonis Herba (called Guanghuoxiang, GHX in Chinese), Acori Tatarinowii Rhizoma (called Shichangpu, SCP in Chinese), and Curcumae Radix (called Yujin, YJ in Chinese), and has shown an excellent therapeutic effect in clinical treatment of influenza. However, there are few studies on the anti-influenza mechanism of AG, and the mechanism of action is still unclear. AIM OF THE STUDY: The purpose is to provide the latest information about the clinical efficacy, pharmacodynamic composition and mechanism of AG based on scientific literature, so as to enhance the utilization of AG in the treatment of influenza and related diseases, and promote the development and innovation of novel anti-influenza drugs targeting the influenza virus. MATERIALS AND METHODS: Enter the data retrieval room, search for Antiviral Granules, as well as the scientific names, common names, and Chinese names of each Chinese medicine. Additionally, search for the relevant clinical applications, pharmacodynamic composition, pharmacological action, and molecular mechanism of both Antiviral Granules and single-ingredient medicines. Keywords includes terms such as "antiviral granules", "influenza", "Isatis indigotica Fort.", "Radix Isatidis", "Banlangeng", "pharmacology", "clinical application", "pharmacologic action", etc. and their combinations. Obtain results from the Web of Science, PubMed, Google Scholar, Sci Finder Scholar, CNKI and other resources. RESULTS: AG is effective in the treatment of influenza and is often used in combination with other drugs to treat viral diseases. Its chemical composition is complex, including alkaloids, polysaccharides, volatile oils, steroid saponins, phenylpropanoids, terpenoids and other compounds. These compounds have a

BACKGROUND: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases. METHODS: The LPS/D-GalN-induced ALF mice model and the CCl4+LPS/D-GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses. RESULTS: MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment. CONCLUSIONS: Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.

Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called "Qingqiao" and "Laoqiao" referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.

OBJECTIVE: To study the possible role of traditional Chinese medicine (TCM) of Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae), Jinyinhua (Flos Lonicerae), and Lianqiao (Fructus Forsythiae Suspensae) in absorption of lung lesions in Corona Virus Disease 2019 (COVID-19) patients. METHODS: A cohort of COVID-19 cases was recruited. During hospitalization, chest computed tomographic (CT) scan and real time polymerase chain reaction (RT-PCR) test were performed every three days. Comparison was held (Western Medicine, WM vs WM plus TCM) on absorption of lung lesions, time interval from admission to negative test result of RT-PCR (ATN), and medical expense. Multivariate cox regression models were built to identify the possible prognostic factor of delayed absorption of lung lesion. RESULTS: The medical expenditure (1163 ± 379 vs 1137 ± 498, P = 0.863) and ATN (13 ± 4 vs 10 ± 4, P = 0.055) were comparable between cases treated with WM plus TCM and cases only received WM. Multivariate cox regression model showed that cases receiving extra TCM had lower risk of delayed absorption of lung lesions [Hazard ratio = 0.24, 95% confidence Interval (0.06, 0.96), P = 0.043]. CONCLUSION: Compared to WM, the treatment of WM plus TCM facilitates the recovery of pulmonary infiltration on COVID-19 cases without significantly increasing medical expense.

Forsythiae Fructus (Lianqiao in Chinese) is widely used in traditional Chinese medicine. The lipid components in Forsythiae Fructus are the basis of plant growth and active metabolism. Samples were collected at two growth stages for a comprehensive study. Transcriptome and lipidomics were performed by using the RNA-seq and UPLC-Q-TOF-MS techniques separately. For the first time, it was reported that there were 5802 lipid components in Lianqiao comprised of 31.7% glycerolipids, 16.57% phospholipids, 13.18% sphingolipids, and 10.54% fatty acids. Lipid components such as terpenes and flavonoids have pharmacological activity, but their content was low. Among these lipids which were isolated from Forsythiae Fructus, 139 showed significant differences from the May and July harvest periods. The lipids of natural products are mainly concentrated in pregnenolones and polyvinyl lipids. RNA-Seq analysis revealed 92,294 unigenes, and 1533 of these were differentially expressed. There were 551 differential genes enriched in 119 KEGG pathways. The de novo synthesis pathways of terpenoids and flavonoids were explored. Combined with the results of lipidomics and transcriptomics, it is hypothesized that in the synthesis of abscisic acid, a terpenoid, may be under the dynamic regulation of genes EC: 1.1.1.288, EC: 1.14.14.137 and EC: 1.13.11.51 in balanced state. In the synthesis of gibberellin, GA20-oxidase (GA20ox, EC: 1.14.11.12), and GA3-oxidase (GA3ox, EC: 1.14.11.15) catalyze the production of active GAs, and EC: 1.14.11.13 is the metabolic enzymes of active GAs. In the synthesis of flavonoids, MF (multifunctional), PAL (phenylalanine ammonia-lyase), CHS (chalcone synthase), ANS (anthocyanidin synthase), FLS (flavonol synthase) are all key enzymes. The results of the present study provide valuable reference information for further research on the metabolic pathways of the secondary metabolites of Forsythia suspensa.

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the &quot;active ingredient-core targets&quot; network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAP

METHODS: The targets of antineoplastic drugs with cardiotoxicity were obtained from the National Center for Biotechnology Information (NCBI) database, China national knowledge infrastructure (CNKI) database, and Swiss Target Prediction platform. Then, the cardiotoxicity-related targets were derived from the Gene Cards, Disgenet, OMIM, and DrugBank databases, as well as the drug of current clinical guidelines. The targets both in these two sets were regarded as potential targets to alleviate ADIC. Then, candidate compounds and herbs were matched via Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Cytoscape3.7.1 was used to set up the target-compound-herb network. Molecular docking between core targets and compounds was performed with AutodockVina1.1.2. The rules of herbs were summarized by analyzing their property, flavor, and channel tropism. RESULTS: Twenty-one potential targets, 332 candidate compounds, and 400 kinds of herbs were obtained. Five core targets including potassium voltage-gated channel subfamily H member 2 (KCNH2), cyclin-dependent kinase 1 (CDK1), matrix metalloproteinase 2 (MMP2), mitogen-activated protein kinase1 (MAPK1), and tumor protein p53 (TP53) and 29 core compounds (beta-sitosterol, quercetin, kaempferol, etc.) were collected. Five core herbs (Yanhusuo, Gouteng, Huangbai, Lianqiao, and Gancao) were identified. Also, the TCM against ADIC were mainly bitter and acrid in taste, warm in property, and distributed to the liver and lung meridians. CONCLUSION: TCM against ADIC has great potential. Our study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating ADIC.

Comment in Pharmacol Res. 2020 Oct;160:105181. doi: 10.1016/j.phrs.2020.105181. Currently, coronavirus disease 2019 (COVID-19), which can lead to severe respiratory failure and death, is now a global pandemic with no specific anti-viral drugs or vaccines. However, It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China since outbreak, bringing new hope for the prevention and control of COVID-19. A comprehensive literature searching was conducted in 7 electronic databases from their inception up to June 21, 2020 to evaluate the efficacy and safety of CHM for COVID-19. Eighteen randomized controlled trials (RCTs) involving 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquoric Root (Gancao, Radix Glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellariae Baicalensis), Pinellia Rhizome (Banxia, Rhizoma Pinelliae Tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae Suspensae), and Bitter Apricot Seed (Kuxingren, Semen Armeniacae Amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Our meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein). Besides, no severe adverse effects was identified by CHM. CHM, especially classical Chinese herbal formulas, could be used as potential candidates for COVID-19 in this battle.

INTRODUCTION: Shuanghuanglian (SHL) oral liquid is a well-known traditional Chinese medicine preparation administered for respiratory tract infections in China. However, the underlying pharmacological mechanisms remain unclear. The present study aims to determine the potential pharmacological mechanisms of SHL oral liquid based on network pharmacology. METHODS: Network pharmacology-based strategy including collection and analysis of putative compounds and target genes, network construction, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) enrichment, identification of key compounds and target genes, and molecule docking was performed in this study. RESULTS: A total of 82 bioactive compounds and 226 putative target genes of SHL oral liquid were collected. Of note, 28 hub target genes including 4 major hub target genes: estrogen receptor 1 (ESR1), nuclear receptor coactivator 2 (NCOA2), nuclear receptor coactivator 1 (NCOA1), androgen receptor (AR) and 5 key compounds (quercetin, luteolin, baicalein, kaempferol and wogonin) were identified based on network analysis. The hub target genes mainly enriched in pathways including PI3K-Akt signaling pathway, human cytomegalovirus infection, and human papillomavirus infection, which could be the underlying pharmacological mechanisms of SHL oral liquid for treating diseases. Moreover, the key compounds had great molecule docking binding affinity with the major hub target genes. CONCLUSION: Using network pharmacology analysis, SHL oral liquid was found to contain anti-virus, anti-inflammatory, and "multi-compounds and multi-targets" with therapeutic actions. These findings may provide a valuable direction for further clinical application and research. © 2020 Elsevier GmbH. All rights reserved.

Forsythiae Fructus( Lianqiao) is classed from near-mature fruit and hyper-mature fruit,which are named as Qingqiao and Laoqiao,respectively. This article was based on the different views of which was better,Qingqiao or Laoqiao. Acorrding to the naming,varieties,habitat,harvesting and processing,used parts,medicinal properties and clinical efficacy,the herbalogical study was carried out. The results showed that Lianqiao had been sourced from the areial part of Hypericum ascyron and H. erectum of Clusiaceae before Tang Dynasty. Beside the former,and the fruit of Forsythia suspensa of Oleaceae was newly used as Lianqiao during the Southern and Northern Dynasties to the Tang Dynasty. The later had been the only origin of Lianqiao since the Song Dynasty. With the change of the medicinal varieties,the habitats of Lianqiao has also changed. The varieties of Clusiaceae were mainly produced in the Yellow River Basin from the Han Dynasty to the Tang Dynasty. After the Song Dynasty,they were produced in the south of the Yangtze River. The variety of Oleaceae was mainly produced in Shanxi,Henan,Shandong,Shaanxi,and northern Sichuan from the Tang and Song Dynasties. Currently,Shanxi and Henan have the largest output. Traditionally,there were two commercial varieties including Qingqiao and Laoqiao of Lianqiao based on the harvesting time. In traditional Chinese medicine( TCM) theory,Lianqiao removes evil heat and relieves toxicity,removes swelling and resolves enlarged nodes. Accroding to the effects of Lianqiao,Qingqiao was considered to be better than Laoqiao in TCM clinic. The modern research on main medicinal constituents and pharmacodynamic effects also confirmed the above mentioned facts. This paper can provide literature support for the rationalities of Qingqiao&apos;s mainstream medication and assay standard of Lianqiao in the Chinese Pharmacopoeia.

OBJECTIVE: Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies. METHODS: Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases. RESULTS: The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24-0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao). CONCLUSIONS: Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.