Main Active Compounds Research Articles

Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification. Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS. This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results. This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

Amentoflavone from Selaginella tamariscina inhibits SARS-CoV-2 RNA-dependent RNA polymerase

The SARS-CoV-2 pandemic caused millions of deaths due to its prominent infectivity and mortality. Although the vaccines and medicines for SARS-CoV-2 are on the market, new coronavirus variants like influenza are expected to reemerge continuously. Therefore, effective and inexpensive medicines will be required to respond to SARS-CoV-2 variants. Here, we used herbal plant extracts to search for effective compounds that can interfere with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and found that Selaginella tamariscina extract (STE) can reduce SARS-CoV-2 RdRp activity. The HCoV-OC43 beta coronavirus model was used to examine whether STE treatment could inhibit coronavirus replication and reduce coronavirus-induced cytotoxicity. Next, we searched the active compound of STE and found that amentoflavone is the main active compound of STE. Finally, we demonstrated that amentoflavone inhibits SARS-CoV-2 RdRp and coronavirus replication. Our results collectively indicate that amentoflavone from STE is possibly beneficial in responding to coronavirus-related diseases, including SARS-CoV-2.

Phenylpropanoid-rich maize root extract serves as a natural antidepressant

BackgroundDepression is a serious and complex mental disease that has attracted worldwide attention because of its high incidence rate, high disability rate and high mortality. Excitotoxicity is one of the most important mechanisms involved in the pathophysiological process of depression. In our previous studies, n-butanol extract from maize roots was found to have good neuroprotective effects due to its antioxidative activity. However, the antidepressive effective constituents, efficacy in vivo and mechanism of action of maize root extracts have not been determined. PurposeThis study aimed to determine the main active neuroprotective compound in maize root extract and investigate its antidepressant effects and possible underlying mechanism in vitro and in vivo. MethodsSixteen extracts were isolated and purified from maize roots. The active components of the most active extracts of maize roots (hereafter referred to as EM 2) were identified using UF-HPLC-QTOF/MS. In vitro cell models of NMDA-induced excitotoxicity in SH-SY5Y cells were used to analyze the anti-excitatory activity of the extracts. The MTT assay and Annexin V-FITC/PI Apoptosis Detection were used to evaluate cell viability. Several network pharmacological strategies have been employed to investigate the potential mechanism of action of EM 2. The effects of EM 2 on depressive-like behaviors were evaluated in CUMS mice. Changes in the levels of related proteins were detected via western blotting. ResultsAmong the 16 extracts extracted by n-butanol, EM 2 was determined to be the most active extract against NMDA-induced excitotoxicity by n-butanol extraction. Meanwhile, seventeen compounds were further identified as the main active components of EM 2. Mechanistically, EM 2 inhibited NMDA-induced excitatory injury in SH-SY5Y cells and alleviated the depressive-like behaviors of CUMS mice by suppressing NR2B and subsequently mediating the downstream CREB/TRKB/BDNF, PI3K/Akt and MAPK pathways, as well as the Nrf2/HO-1 antioxidant signaling pathway. ConclusionThe study indicated that EM 2 could potentially be developed as a potential therapeutic candidate to cure depression in NMDA-induced excitatory damage.

Effect of Torilis japonica Fruit Extract for Endothelium-Independent Vasorelaxation and Blood Pressure Lowering in Rats.

Torilis japonica (TJ) fruit, is a herb that is traditionally used for erectile dysfunction (ED). Given the shared mechanisms of ED and hypertension through vascular smooth muscle, we hypothesized that TJ would be effective in vasodilation and blood pressure reduction. This study confirmed the authenticity of TJ samples via DNA barcoding and quantified the main active compound, torilin, using HPLC. TJ was extracted with distilled water (TJW) and 50% ethanol (TJE), yielding torilin contents of 0.35 ± 0.01% and 2.84 ± 0.02%, respectively. Ex vivo tests on thoracic aortic rings from Sprague-Dawley rats showed that TJE (3-300 µg/mL) induced endothelium-independent, concentration-dependent vasodilation, unlike TJW. Torilin caused concentration-dependent relaxation with an EC50 of 210 ± 1.07 µM. TJE's effects were blocked by a voltage-dependent K+ channel blocker and alleviated contractions induced by CaCl2 and angiotensin II. TJE inhibited vascular contraction induced by phenylephrine or KCl via extracellular CaCl2 and enhanced inhibition with nifedipine, indicating involvement of voltage-dependent and receptor-operated Ca2+ channels. Oral administration of TJE (1000 mg/kg) significantly reduced blood pressure in spontaneously hypertensive rats. These findings suggest TJ extract's potential for hypertension treatment through vasorelaxant mechanisms, though further research is needed to confirm its efficacy and safety.

A review of Aconiti Lateralis Radix Praeparata (Fuzi) for kidney disease: phytochemistry, toxicology, herbal processing, and pharmacology.

Aconiti Lateralis Radix Praeparata, commonly known as Fuzi in. traditional Chinese medicine (TCM), is widely utilized in clinical practice despite its inherent toxicity. Since ancient times, TCM practitioners have explored various processing techniques to broaden its clinical applications and enhance its safety profile. This review aims to summarize the effects of processing on the chemical composition, toxicity, and pharmacological properties of Fuzi, as well as investigate potential underlying mechanisms. Data on phytochemistry, toxicology, pharmacology, and processing methods of Fuzi were gathered from the literature of electronic databases, including Web of Science, PubMed, and CNKI. Fuzi contains over 100 kinds of chemical compounds, including alkaloids, flavonoids, and polysaccharides, among which alkaloids are the main active compounds. Diester-diterpenoid alkaloids are the main contributors to Fuzi's toxicity and have side effects on some organs, such as the heart, liver, kidneys, nervous system, and reproductive system. The chemical composition of aconite, particularly its alkaloid content, was changed by hydrolysis or substitution reaction during processing to enhance its efficacy and reduce its toxicity. Salted aconite could enhance the therapeutic efficacy of Fuzi in treating kidney diseases and influence its pharmacokinetics. Processing plays an important role in increasing the efficiency and decreasing toxicity of aconite. Further studies are needed to elucidate the changes of aconite before and after processing and the underlying mechanisms of these changes, thereby providing evidence for the clinical safety of drug use.

Investigation the effect of the aqueous extract of Chara vulgaris (L.) on visceral leishmaniasis.

Visceral leishmaniasis (VL) is a parasitic disease that affects public health. It is described by weight reduction, irregular fever bouts, anemia, and amplification of the spleen and liver. Three concentrations (15.6, 31.2, and 62.5 μg/mL) were used to find the potency of an aqueous extract of Chara vulgaris algae in the treatment of VL. A cytotoxicity assay was performed to show the cytotoxic effect of this extract on human cells. High-performance liquid chromatography (HPLC) test was done to determine the active compounds in the extract. Histopathological sections for infected liver and spleen were performed, as were liver function tests (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), which were assessed after 1 month of treatment. As cytotoxicity assay, results showed that there were no significant differences between the cells treated and those not treated with the extract. HPLC test demonstrated that phenolic and terpene compounds are the main active compounds in the extract. P-coumaric acid and ursolic acid present the highest percent among other phenolic and terpene compounds (21.84%, 17.82%), respectively. Histopathological sections showed that this extract had a significant effect in the treatment of infected tissues, and this effect was very clear after the end of the treatment period. As for the liver function tests, a significant increase (P < 0.01) in the studied liver enzymes was found in the infected group of mice compared to the healthy group, whereas in the infected and treated groups, a clear and gradual decrease in the level of enzymes was observed.

Widely targeted metabolomics reveals differential metabolites between root tuber and leaf of Fallopia multiflora

This study aims to reveal the differences in the species and relative content of metabolites in the leaf and root tuber of Fallopia multiflora and improve the comprehensive utilization rate of F. multiflora resources. The metabolites in the root tubers and leaves of F. multiflora were detected by widely targeted metabolomics based on ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). The principal component analysis, hierarchical cluster analysis, and orthogonal partial least squares-discriminant analysis were carried out to screen the differential metabolites between the leaf and root tuber of F. multiflora. The result showed that a total of 1 942 metabolites in 15 categories were detected in the leaf and root tuber of F. multiflora, including 1 861 metabolites in the root tuber, 1 901 metabolites in the leaf, and 1 820 metabolites in both. The metabolites were mainly phenolic acids, flavonoids, amino acids and derivatives, and alkaloids. A total of 1 200 differential metabolites were screened out, accounting for 65.9% of the total metabolites. Among these differential metabolites, 813 and 387 showed higher content in the leaf and root tuber, respectively. Flavonoids were the metabolites with the largest number and the most significant differences between the leaf and root tuber, and stilbenes and anthraquinones as the main active compounds mainly existed in the root tuber. The KEGG enrichment results suggested that the differential metabolites were mainly enriched in flavonoid and flavonol biosynthesis pathways and linoleic acid metabolism pathway. This study discovered abundant metabolites in F. multiflora. The metabolites were similar but had great differences in the content between the leaf and root tuber. The research results provide theoretical guidance for the development and utilization of F. multiflora resources.

Identification and functional characterization of candidate genes involved in biosynthesis of ginsenoside Rg_1

Panax ginseng is a perennial herb with the main active compounds of ginsenosides. Among the reported ginsenosides, ginsenoside Rg_1 not only has a wide range of medicinal functions and abundant content but also is one of the major ginsenoside for the quality evaluation of this herb in the Chinese Pharmacopoeia. The main biosynthesis pathway of ginsenoside Rg_1 in P. ginseng has been clarified, which lays a foundation for the comprehensive and in-depth analysis of the biosynthesis and regulatory mechanism of ginseno-side Rg_1. However, the biosynthesis of ginsenoside Rg_1 is associated with other complex processes involving a variety of regulatory genes and catalyzing enzyme genes, which remain to be studied comprehensively. With the transcriptome data of 344 root samples from 4-year-old P. ginseng plants and their corresponding ginsenoside Rg_1 content obtained in the previous study, this study screened out 217 differentially expressed genes(DEGs) with Rg_1 content changes by DEseq2 analysis in R language. Furthermore, the weighted gene co-expression network analysis(WGCNA) revealed 40 hub genes among the DEGs.Pearsoncorrelation analysis was further perforned to yield 20 candidate genes significantly correlated with ginsenoside Rg_1 content, and these genes were annotated to multiple metabolic processes including primary metabolism and secondary metabolism. Finally, the treatment of P. ginseng adventitious roots with methyl jasmonate indicated that 16 of these genes promoted the biosynthesis of ginsenoside Rg_1 in response to methyl jasmonate induction. Finally, one of the 16 genes was randomly selected to verify the function of the gene by genetic transformation and qRT-PCR and to confirm the rationality of the methodology of this study. The above results lay a foundation for studying the mechanism for regulation on the synthesis of ginsenoside Rg_1 and provide genetic resources for the industrial production of ginsenoside Rg_1.

Anti-Influenza A Potential of Tagetes erecta Linn. Extract Based on Bioinformatics Analysis and In Vitro Assays.

Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound-target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1β). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza.

Antibacterial activity and mechanism of luteolin isolated from Lophatherum gracile Brongn. against multidrug-resistant Escherichia coli.

Infections caused by multidrug-resistant (MDR) bacteria have become a major challenge for global healthcare systems. The search for antibacterial compounds from plants has received increasing attention in the fight against MDR bacteria. As a medicinal and edible plant, Lophatherum gracile Brongn. (L. gracile) has favorable antibacterial effect. However, the main antibacterial active compound and its antimicrobial mechanism are not clear. Here, our study first identified the key active compound from L. gracile as luteolin. Meanwhile, the antibacterial effect of luteolin was detected by using the broth microdilution method and time-kill curve analysis. Luteolin can also cause morphological structure degeneration and content leakage, cell wall/membrane damage, ATP synthesis reduction, and downregulation of mRNA expression levels of sulfonamide and quinolones resistance genes in multidrug-resistant Escherichia coli (MDR E. coli). Furthermore, untargeted UPLC/Q-TOF-MS-based metabolomics analysis of the bacterial metabolites revealed that luteolin significantly changed riboflavin energy metabolism, bacterial chemotaxis cell process and glycerophospholipid metabolism of MDR E. coli. This study suggests that luteolin could be a potential new food additive or preservative for controlling MDR E. coli infection and spread.

Network Pharmacology and Molecular Docking Validation to Explore the Pharmacological Mechanism of Zhuling Decoction against Nephrotic Syndrome.

In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling Decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear. This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking. Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets. Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2. In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.

Strong antagonism of an endophyte of Fraxinus excelsior towards the ash dieback pathogen, Hymenoscyphus fraxineus, is mediated by the antifungal secondary metabolite PF1140.

Ash dieback, caused by the fungal pathogen Hymenoscyphus fraxineus (Helotiales, Ascomycota), is threatening the existence of the European ash, Fraxineus excelsior. During our search for biological control agents for this devastating disease, endophytic fungi were isolated from healthy plant tissues and co-cultivated with H. fraxineus to assess their antagonistic potential. Among the strains screened, Penicillium cf. manginii DSM 104493 most strongly inhibited the pathogen. Initially, DSM 104493 showed promise in planta as a biocontrol agent. Inoculation of DSM 104493 into axenically cultured ash seedlings greatly decreased the development of disease symptoms in seedlings infected with H. fraxineus. The fungus was thus cultivated on a larger scale in order to obtain sufficient material to identify active metabolites that accounted for the antibiosis observed in dual culture. We isolated PF1140 (1) and identified it as the main active compound in the course of a bioassay-guided isolation strategy. Furthermore, its derivative 2, the mycotoxin citreoviridin (3), three tetramic acids of the vancouverone type (4-6), and penidiamide (7) were isolated by preparative chromatography. The structures were elucidated mainly by NMR spectroscopy and high-resolution mass spectrometry (HRMS), of which compounds 2 and 6 represent novel natural products. Of the compounds tested, not only PF1140 (1) strongly inhibited H. fraxineus in an agar diffusion assay but also showed phytotoxic effects in a leaf puncture assay. Unfortunately, both the latent virulent attributes of DSM 104493 observed subsequent to these experiments in planta and the production of mycotoxins exclude strain Penicillium cf. manginii DSM 104493 from further development as a safe biocontrol agent.IMPORTANCEEnvironmentally friendly measures are urgently needed to control the causative agent of ash dieback, Hymenoscyphus fraxineus. Herein, we show that the endophyte DSM 104493 exhibits protective effects in vitro and in planta. We traced the activity of DSM 104493 to the antifungal natural product PF1140, which unfortunately also showed phytotoxic effects. Our results have important implications for understanding plant-fungal interactions mediated by secondary metabolites, not only in the context of ash dieback but also generally in plant-microbial interactions.

Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug – temozolomide – in the most responsive cell line – SK-MEL-147 – and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 μg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 μg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Phytochemistry, pharmacology, toxicology and detoxification of Polygonum multiflorum Thunb.: a comprehensive review.

Polygonum multiflorum Thunb. (PM), a kind of perennial plant, belongs to the genus Polygonum of the family polygonaceae.The dry root of PM (also called Heshouwu), is a traditional Chinese medicine, which has a series of functions and is widely used in clinic for hair lossing, aging, and insomnia. While, PM also has some toxicity, its clinical drug safety has been concerned. In this paper, the chemical components, toxic mechanisms and detoxification strategies of PM were reviewed in order to provide evidence for its clinical application. We conducted a systematic review of published literature of PM, including English and Chinese databases, such as PubMed, Web of Science, CNKI, and Wanfang. PM contains a variety of chemical compounds, including stilbenes, quinones, flavonoids, phospholipids, and has many pharmacological activities such as anti-aging, wound healing, antioxidant, and anti-inflammatory properties. The PE has certain therapeutic effect, and it has certain toxicity like hepatotoxicity, nephrotoxicity, and embryotoxicity at the same time, but.these toxic effects could be effectively reduced by processing and compatibility. It is necessary to further explore the pharmacological and toxicological mechanisms of the main active compounds of PE.This article provides scientific basis for the safe clinical application of PM.

A Transcriptomic and Metabolomic Study on the Biosynthesis of Iridoids in Phlomoides rotata from the Qinghai-Tibet Plateau.

Phlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1, IDI1, 8-HGO1, and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata. The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata.

Ge-Gen-Qin-Lian decoction alleviates the symptoms of type 2 diabetes mellitus with inflammatory bowel disease via regulating the AGE-RAGE pathway

BackgroundThis study aimed to explore the mechanism of Ge-Gen-Qin-Lian decoction (GGQLD) in the alleviation of symptoms of type 2 diabetes mellitus (T2DM) with inflammatory bowel disease (IBD) by network pharmacology and experimental validation.MethodsThe active components and targets of GGQLD were identified from the TCMSP database. The potential therapeutic targets of T2DM and IBD were identified from the GEO database and 4 online disease target databases. The PPI network and KEGG/GO analyses were performed with the common targets among GGQLD, T2DM and IBD. Molecular docking was carried out between the core compounds and hub targets. To verify the above results, UHPLC-MS technology was used to identify the chemical compounds in GGQLD, and a T2DM with IBD rat model was used to explore the mechanism by which GGQLD treats T2DM with IBD.ResultsTotally, 70 potential therapeutic targets were identified among GGQLD, T2DM and IBD. Ten hub genes were selected from the PPI network. KEGG analysis revealed that GGQLD is tightly involved in the AGE-RAGE signaling pathway. Berberine, baicalein, wogonin, and quercitrin are the main active compounds of GGQLD. Animal experiments showed that GGQLD could decrease blood glucose and alleviate intestinal inflammation. Notably, the concentrations of AGEs, the expression of RAGE, c-JUN and NF-κB and the expression of inflammatory cytokines were decreased by GGQLD.ConclusionsOur study initially demonstrated that GGQLD has favorable anti-hyperglycemic and anti-intestinal inflammation effects in a T2DM with IBD rat model, and the AGE-RAGE pathway plays a vital role in this process.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study

Ethnopharmacological relevanceDioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. Aim of the studyThis study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. Materials and methodsThe active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. ResultsCYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1β. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. ConclusionThis study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

Physalis Calyx seu Fructus inhibited pulmonary fibrosis through regulating Wnt/β-catenin signaling pathway

BackgroundPulmonary fibrosis is a chronic and advancing interstitial lung disease, and there is an urgent need for novel agents for its therapy. Physalis Calyx seu Fructus (PCF) has been utilized in traditional Chinese medicine to treat respiratory disorders with a long history, however, the therapeutic effect and mechanism of PCF against pulmonary fibrosis are still unclear. PurposeTo assess therapeutic efficacy and underlying mechanism of 75 % ethanol extract of PCF (PCF-EtOH) against pulmonary fibrosis, as well as to discover active constituents in PCF. MethodsA bleomycin-stimulated mice model was established to assess potential therapy of PCF-EtOH against pulmonary fibrosis in vivo. A lipopolysaccharide-induced inflammatory model in RAW 264.7 cells and a transforming growth factor β1-induced fibrosis model in MRC-5 cells were established to assess potential therapy and mechanisms of purified constituents in PCF-EtOH. UPLC-MS/MS analysis was adopted to ascertain the constituents of PCF-EtOH. Network pharmacology was employed to forecast targets of PCF against pulmonary fibrosis. ResultsPCF-EtOH ameliorated bleomycin-induced pulmonary fibrosis through repressing inflammatory response and extracellular matrix deposition. Meanwhile, PCF-EtOH inhibited Wnt/β-catenin pathway through decreasing β-catenin nuclear accumulation and promoting phosphorylation. Furthermore, withanolides and flavonoids were presumed to be main active compounds of PCF against pulmonary fibrosis based on the network pharmacology. Importantly, we found an extensive presence of withanolides in PCF-EtOH. Physapubescin, a typical withanolide in PCF-EtOH, inhibited the inflammatory response, extracellular matrix deposition, and Wnt/β-catenin pathway. Notably, physapubescin demonstrated a more potent antifibrotic effect than pirfenidone, a clinically approved antifibrotic drug, in the tested model. ConclusionWithanolides and flavonoids are responsible for the inhibitory effect of PCF-EtOH against pulmonary fibrosis. Withanolides may represent a class of promising therapeutic agents against pulmonary fibrosis, and an in-depth exploration is warranted to validate this proposition.

The role of TrkB signaling-mediated synaptic plasticity in the antidepressant properties of catalpol, the main active compound of Rehmannia glutinosa Libosch.

Ethnopharmacological relevanceRehmannia glutinosa Libosch. (RGL) is a famous ethnic medicine contained in antidepressant Chinese medicine formulas and is traditionally clinically used for depression. We have recently confirmed that RGL enhanced synaptic plasticity in a mouse model of Chinese medical syndrome and that catalpol may be the representatively pharmacological component responsible for its improvement in synaptic plasticity and treatment of depression. Impaired synaptic plasticity is closely linked to major depression. Tyrosine kinase receptor B (TrkB) signaling has recently been discovered as a key pathway for synaptic plasticity improvement and antidepressant discovery. However, to date, it is unknown whether the target of catalpol to improve synaptic plasticity involves TrkB and whether its antidepressant mechanism involves synaptic plasticity mediated by TrkB signaling. Aim of studyThis study aims to elucidate the potential antidepressant target and mechanisms of catalpol, the main active compound of RGL, through TrkB signaling-mediated synaptic plasticity. Materials and methodsWe have recently predicted through molecular networking strategy (including network pharmacology, molecular docking, and molecular dynamics simulation) that catalpol may exert its antidepressant effects by regulating TrkB signaling and thus modulating essential synaptic plasticity proteins. Then, this study used classic behavioral tests, targeted diagnostic reagents, Nissl and Golgi staining, immunohistochemical analysis, immunofluorescence analysis, Western blot, enzyme-linked immunosorbent assay, and Real-time PCR to confirm the potential target and signaling of catalpol to improve synaptic plasticity for the treatment of depression. ResultsThe data showed that catalpol could improve synaptic plasticity and depressive behaviors, and its action pathway was predicted to involve TrkB signaling. Subsequently, the blockade of TrkB abolished the improvement of synaptic plasticity by catalpol and its antidepressant properties, which validated that TrkB signaling was the key pathway for catalpol to improve synaptic plasticity and exert antidepressant properties. Inhibition of COX-2 was likely to be a necessary facilitator for the antidepressant efficacy of catalpol via the TrkB target and TrkB-mediated synaptic plasticity. ConclusionTrkB signaling-mediated synaptic plasticity plays a key role in the antidepressant properties of catalpol. This study provides critical information for the development of new and targeted antidepressant therapies or treatment strategies by catalpol. However, considering the existence of sex differences in depression (female depression is 2–3 times than that of males) and not exploring the antidepressant sex specificity of catalpol is a limitation, we will investigate the sex specificity of the antidepressant effects and molecular mechanisms of catalpol on sex-specific animals in the future to provide a preclinical basis for more accurate and targeted medication of catalpol.

Network pharmacology and molecular docking to explore the treatment potential and molecular mechanism of Si-Miao decoction against gouty arthritis.

Gouty arthritis (GA) is a common metabolic rheumatological disease. Si-Miao decoction has therapeutic effects on GA. In our study, we investigated the mechanism of Si-Miao decoction against GA using network pharmacology and molecular docking analytical methods. The Traditional Chinese Medicine Systems Pharmacology Database was used as the basis for screening the main targets and agents of the Si-Miao decoction, and the Genecards, OMIM, and Drugbank databases were used to screen GA-related targets. They were analyzed using Venn with the drug targets to obtain the intersection targets. We used Cytoscape 3.9.1 to draw the "Drugs-Compounds-Targets" network and the String database for creative protein-protein interaction networks of target genes and filtered core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze the core targets. Molecular docking was performed using AutoDockTools to predict the binding capacity between nuclear targets and active components in the Si-Miao decoction. A total of 50 chemically active components containing 53 common targets of Si-Miao decoction anti-GA and 53 potential drug target proteins were identified. Core targets, namely, TNF, STAT3, SRC, PPARG, TLR4, PTGS2, MMP9, RELA, TGFB1, and SIRT1, were obtained through PPI network analysis. GO and KEGG analyses showed that the mechanism of anti-GA in Si-Miao decoction may proceed by regulating biological processes such as inflammatory factor levels, cell proliferation, apoptosis, and lipid and glucose metabolism, and modulating the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Toll-like receptor signaling pathway. We further screened the core targets, including PTGS2, MMP9, and PPAGR, as receptor proteins based on their degree value and molecular docking with the main active compounds in Si-Miao decoction, and found that baicalein had high affinity. In conclusion, Si-Miao decoction, through anti-inflammatory, apoptosis-regulating, and anti-oxidative stress action mechanisms in the treatment of GA.