Echinocystic Acid Research Articles

Gleditsiae Sinensis Fructus ingredients and mechanism in anti-asthmatic bronchitis research

BackgroundGleditsiae Sinensis Fructus (GSF) is commonly used in traditional medicine to treat respiratory diseases such as bronchial asthma. However, there is a lack of research on the chemical composition of GSF and the pharmacological substance and mechanism of action for GSF in treating bronchial asthma. PurposeThe chemical constituents of GSF were analyzed using ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In this study, we combined network pharmacology, molecular docking techniques, and experimental validation to explore the therapeutic efficacy and underlying mechanism of GSF in the treatment of bronchial asthma. MethodsCharacterization of the chemical constituents of GSF was conducted using UHPLC-Q-Orbitrap HRMS. The identified chemical components were subjected to screening for active ingredients in the Swiss Absorption, Distribution, Metabolism, and Excretion (ADME) database. Relevant databases were utilized to retrieve target proteins for the active ingredients and targets associated with bronchial asthma disease, and the common targets between the two were selected. Subsequently, the protein-protein interaction (PPI) network was constructed using the String database and Cytoscape software to identify key targets. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database. The "component-common target" network was constructed using Cytoscape to identify the primary active ingredients. Molecular docking validation was conducted using AutoDock software. The bronchial asthma mouse model was established using ovalbumin (OVA), and the lung organ index of the mice was measured. Lung tissue pathological changes were observed using hematoxylin and eosin (HE), Periodic Acid-Schiff (PAS), and Masson staining. The respiratory resistance (Penh) of the mice was assessed using a pulmonary function test instrument. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IgE, IL-4, IL-5, and IL-13 in the mouse serum. Immunofluorescence staining was performed to detect the protein expression levels of AKT and PI3K in the lung tissues. An in vitro experiment was performed to observe the effects of echinocystic acid (EA) on IL-4 stimulated Human ASMCs (hASMCs). Cell viability was measured using a CCK-8 assay to calculate the IC50 value of the EA. A wound healing test was conducted to observe the effect of EA on degree of healing. RT-qPCR was performed to detect the influence of EA on the mRNA expression levels of ALB, SRC, TNF-α, AKT1, and IL6 in the cells. ResultsA total of 95 chemical constituents were identified from the GSF. Of these, 37 were identified as active ingredients. There were 169 overlapping targets between the active ingredients and the disease targets. A topological analysis of the protein-protein interaction (PPI) network identified the core targets as IL6, TNF, ALB, AKT1, and SRC. An enrichment analysis revealed that the treatment of bronchial asthma with GSF primarily involved the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway, among others. The primary active ingredients included 13(s)-HOTRE, linolenic acid, and acacetin. The molecular docking results demonstrated a favorable binding activity between the critical components of GSF and the core targets. Animal experimental studies indicated that GSF effectively improved symptoms, lung function, and lung tissue pathological changes in the OVA-induced asthmatic mice, while alleviating inflammatory responses. GSF decreased the fluorescent intensity of the AKT and PI3K proteins. The IC50 value of EA was 30.02μg/ml. EA (30) significantly promoted the proliferation of IL4-stimulated hASMCs cells. EA (30) significantly increased the expression of ALB and SRC mRNA and decreased the expressions of TNF-α, AKT, and IL6 mRNA. ConclusionThe multiple active ingredients found in GSF exerted their anti-inflammatory effects through multiple targets and pathways. This preliminary study revealed the core target and the mechanism of action underlying its treatment of bronchial asthma. These findings provided valuable insights for further research on the pharmacological substances and quality control of GSF.

Multi-omics analysis of five species of milk and specific composition links within each species

The gold standard of milk is human milk, not cow milk. The present study expects to explored the comprehensive nutritional value of different kinds of milk and the differences between them through multi-omics analysis and found functional components that are more similar to human milk. This study employed untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D label-free proteomics analysis techniques. The findings revealed substantial disparities in metabolites, lipids, and proteins among the five types of milk. Notably, pig milk exhibited a remarkable abundance of N-acetylneuraminic acid (Neu5Ac) and specific polar lipids. Yak milk stood out with significantly elevated levels of creatine and lipoprotein lipase (LPL) compared to other species. Buffalo milk boasted the highest concentrations of L-isoleucine, echinocystic acid, and alkaline phosphatase, tissue-nonspecific isozyme (ALPL). The concentrations of iminostilbene and osteopontin (OPN) were higher in cow milk.

Xanthohumol and echinocystic acid induces PSTVd tolerance in tomato.

Tomato is a popular vegetable worldwide; its production is highly threatened by infection with the potato spindle tuber viroid (PSTVd). We obtained the full-length genome sequence of previously conserved PSTVd and inoculated it on four genotypes of semi-cultivated tomatoes selected from a local tomato germplasm resource. SC-5, which is a PSTVd-resistant genotype, and SC-96, which is a PSTVd-sensitive genotype, were identified by detecting the fruit yield, plant growth, biomass accumulation, physiological indices, and PSTVd genome titer after PSTVd inoculation. A non-target metabolomics study was conducted on PSTVd-infected and control SC-5 to identify potential anti-PSTVd metabolites. The platform of liquid chromatography-mass spectrometry detected 158 or 123 differential regulated metabolites in modes of positive ion or negative ion. Principal component analysis revealed a clear separation of the global metabolite profile between PSTVd-infected leaves and control regardless of the detection mode. The potential anti-PSTVd compounds, xanthohumol, oxalicine B, indole-3-carbinol, and rosmarinic acid were significantly upregulated in positive ion mode, whereas echinocystic acid, chlorogenic acid, and 5-acetylsalicylic acid were upregulated in negative ion mode. Xanthohumol and echinocystic acid were detected as the most upregulated metabolites and were exogenously applied on PSTVd-diseased SC-96 seedlings. Both xanthohumol and echinocystic acid had instant and long-term inhibition effect on PSTVd titer. The highest reduction of disease symptom was induced by 2.6mg/L of xanthohumol and 2.0mg/L of echinocystic acid after 10days of leaf spraying, respectively. A superior effect was seen on echinocystic acid than on xanthohumol. Our study provides a statistical basis for breeding anti-viroid tomato genotypes and creating plant-originating chemical preparations to prevent viroid disease.

Structure-Activity Relationship of Oleanane-Type Pentacyclic Triterpenoids on Nuclear Factor κB Activation and Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure-activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,β-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins.

In silico and pharmacokinetic assessment of echinocystic acid effectiveness in Alzheimer's disease like pathology.

Aim: Alzheimer's disease causes dementia which impairs the cognitive domains. Methodology: The pharmacokinetic characteristics and biological activity of echinocystic acid are predicted in this work using in silico or computational approaches, including pkCSM, Swiss ADME, OSIRIS® property explorer, PASS online web resourceand MOLINSPIRATION® software. Results & discussion: The compound has lipid metabolism regulating property as major role in decreasing the progression of Alzheimer's disease and it has no major side effects and ADR. The drug also has anti-inflammatory properties which can help in regulating the innate immunity that plays a major role in Alzheimer's disease. Conclusion: From the computational screening, we infer that, echinocystic acid can regulate memory loss, cognitive disability and also slow down the progression of Alzheimer's disease-like pathology.

Interactions of oleanane pentacyclic triterpenoids with human organic anion transporting polypeptide 1B1 and 1B3

Oleanane pentacyclic triterpenoids have been widely used in clinical practice. However, studies on their interactions with hepatic transporters remain limited. In this study, we systematically investigated the inhibitory effects of 14 oleanane pentacyclic triterpenoids on organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), two liver-specific uptake transporters. Through fluorescence-based cellular uptake assays, we identified three potent OATP1B1 inhibitors (saikosaponin B1, saikosaponin A and 18β-glycyrrhetinic acid) and five potent OATP1B3 inhibitors (echinocystic acid, 3-oxo-16α-hydroxy-olean-12-en-28β-oic acid, chikusetsu saponin IVa, saikosaponin B1 and 18β-glycyrrhetinic acid). Structural analysis revealed that free oleanane triterpenoids inhibited OATP1B1/1B3 more potently than triterpene glycosides. Despite their similar structures, 18β-glycyrrhetinic acid exhibited much stronger inhibition on OATP1B1/1B3 than 18α-glycyrrhetinic acid, while both were substrates of OATP1B3. Interestingly, OATP1B3 overexpression significantly increased reactive oxygen species (ROS) levels in HepG2 cells after treatment with 18β-glycyrrhetinic acid. To conclude, this study highlights the potential interactions of oleanane pentacyclic triterpenoids with OATP1B1/1B3, and provides novel insights into the anti-cancer activity of 18β-glycyrrhetinic acid.

Chemical characterization, safety profile and antileiomyoma effects of Tetrapleura tetraptera Taubert (Fabaceae) fruit ethanol extract in Sprague Dawley rats

BackgroundTetrapleura tetraptera Taubert (Fabaceae) fruits are employed by herbal practitioners in the management of uterine leiomyoma, but its usage in this regard and level of safety in chronic administration has not been sufficiently established. This study evaluated the toxicity effects of T. tetraptera ethanol fruit extract and explored its antileiomyoma effect in female Sprague Dawley (SD) rats.MethodsSub-chronic toxicity test of the extract was done, with biochemical and hematological changes as well as histopathology of organs assessed. Leiomyoma formation was induced in SD rats with monosodium glutamate (MSG) and the extract given at 100, 200 and 400 mg/kg doses, following both the preventive and curative methods. Total serum cholesterol, protein and estradiol were determined, as well as histopathology assessment of the uterus. Phytochemical profiling of the extract was evaluated by analytical high-performance liquid chromatography (HPLC).ResultsNo significant alterations were seen in the biochemical and hematological indices in the toxicity test. The vital organs showed no changes at 200 mg/kg, but at 800 mg/kg it appeared to induce multiplication of glandular epithelium and stromal fibrosis in the uterus, and induced perivascular inflammation around the vessels of the heart. Total serum cholesterol and estradiol were significantly elevated (P ≤ 0.05) on treating normal female rats with 800 mg/kg MSG. Preventive and curative treatment of MSG-treated animals with the extract significantly decreased the elevated serum cholesterol (P ≤ 0.01) and estradiol (P ≤ 0.05). Histological studies of the uterus showed an amelioration of the proliferating fibroid cells with administration of the extract, which was more evident in the curative treatment. Result of HPLC analysis of the extract revealed rich composition in bioactive compounds such as umbelliferone, ferulic acid, aridanin, echinocystic acid, naringenin and hentriacontane.ConclusionThe ethanol fruit extract of T. tetraptera is relatively safe in Sprague Dawley rats in low doses and has antifibroid potential as seen in its significant reduction in the elevated total cholesterol and estradiol content as well as its ability to decrease uterine leiomyoma proliferation, which may be due to its array of phytochemical constituents.

Discovery of Potential Natural STAT3 Inhibitors: An in silico Molecular Docking and Molecular Dynamics Study

Cancer is a mechanistically complex and diverse disease with a plethora of fundamental genetic and epigenetic factors. Signal transducer and activator of transcription-3 (STAT3) is a transcription factor, and its constitutive activation executes promotion of cellular proliferation, cell cycle, angiogenesis, metastasis, immunosuppression, and chemo-resistance in cancer cells. Here, we aimed to design natural potential STAT3 inhibitors. For this purpose, we investigated 92 phytochemical compounds by molecular docking studies because they are diversified, multitargeted, affordable, easily available, and less- or non-toxic. We selected only 6 compounds such as sarsasapogenin (L3), peiminine (L9), solasodine (L10), tormentic acid (L23), obacunone (L29), and echinocystic acid (L34) due to their greater binding affinity than reference STAT3 inhibitor (S3I-201) with STAT3. The study was further continued by molecular dynamic (MD) simulations and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The results of molecular docking showed that all selected ligands exhibited binding affinity range from -9.3 Kcal/mol to -7.9 Kcal/mol and predicted inhibition constant ([Formula: see text].) values range from 0.14 [Formula: see text]M to 1.5 [Formula: see text]M. These compounds showed effective hydrogen bonding and hydrophobic interactions with DNA binding domain as well as SH2-domain of STAT3. The MD simulations performed by nanoscale molecular dynamics (NAMD) calculated root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration ([Formula: see text]), solvent accessible surface area (SASA) and number of hydrogen bond dynamics. All selected ligands with protein exhibited stability over 120 ns by MD simulation. Moreover, these ligands showed favorable ADMET profiling and drug likeness. So, our current computational investigations showed that these novel drug candidates can be potential STAT3 inhibitors and evoke the scientific interest for their further verification by in vitro and in vivo studies.

Modulation of Kv7 Channel Currents by Echinocystic Acid.

Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-7.5). Pentacyclic triterpenes display extensive pharmacological activities including anti-tumor, anti-inflammatory, and anti-depression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and ⍺-boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC50) of 2.5 µM. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid non-selectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. Significance Statement Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and anti-depression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a non-selective manner.

Echinocystic acid induces the apoptosis, and inhibits the migration and invasion of non-small cell lung cancer cells.

An increasing amount of evidence has demonstrated the anticancer activity of triterpenes extracted from traditional medicines. Echinocystic acid (EA), a natural triterpene isolated from Eclipta prostrata (L.) L., has previously been shown to exhibit anticancer activity in HepG2 and HL-60 cells. The aim of the present study was to investigate the anticancer activity of EA in non-small cell lung cancer (NSCLC) cells. For this purpose, the viability and proliferation of A549 cells were determined using a Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The migratory and invasive ability of the A549 cells were measured using wound healing and Transwell assays. Hoechst staining was also performed to detect the apoptosis of A549 cells. The proliferation of A549 cells and the distributions of different growth phases were determined using a flow cytometer. Western blot analysis was used to detect the expression levels of cyclin D, partitioning defective 3 homolog (Par3), PI3K, Akt, mTOR, Bax, Bcl-2 and caspase-3. EA inhibited the proliferation, and the migratory and invasive abilities of cultured lung carcinoma cells (A549 cells), and induced cell cycle arrest in the G1 phase of the cell cycle. Treatment with EA upregulated Par3 expression and inhibited the PI3K/Akt/mTOR pathway in vitro. In addition, EA treatment inhibited tumor growth, suppressed proliferation and induced the apoptosis of tumor cells in NSCLC tumor xenografts in mice. On the whole, these results suggest that EA may represent a potential therapeutic agent for NSCLC.

Echinocystic acid prevents obesity and fatty liver via interacting with FABP1.

Long-term high-fat diet (HFD) will lead to obesity and their complications. Echinocystic acid (EA), a triterpene, shows anti-inflammatory and antioxidant effects. We predict that EA supplementation can prevent obesity, diabetes, and nonalcoholic steatohepatitis. To test our hypothesis, we investigated the effects of EA supplementation on mice with HFD-induced obesity in vivo and in vitro by adding EA to the diet of mice and the medium of HepG2 cells, the protein target of EA was analyzed by molecular docking. The results showed that EA ameliorated obesity and inhibited blood triglyceride and liver triglyceride concentrations than those in the HFD groups. The data on molecular docking indicated that FABP1 was a potential target of EA. Further experimental results confirmed that EA affected the triglyceride level by regulating the function of FABP1. This study may provide a new potential inhibitor for FABP1 and a new strategy for the treatment of obesity.

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway.

Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

Echinocystic Acid Ameliorates Arthritis in SKG Mice by Suppressing Th17 Cell Differentiation and Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Inflammation

Echinocystic acid (EA), a pentacyclic triterpene, exhibits anti-inflammatory, antioxidant, and analgesic activities to counteract pathological effects in various diseases. Here, we aimed to determine the immunomodulatory effect of EA on zymosan-induced arthritis in SKG mice and how it would influence Th17 differentiation and human rheumatoid arthritis fibroblast-like synoviocytes inflammation. Our results showed that EA (10 and 25 mg/kg) attenuated arthritis symptoms, including high arthritis scores, infiltrating inflammatory cells, synovial hyperplasia, bone erosion, and the high levels of proinflammatory cytokines, such as TNF-α, interleukin (IL)-6, and IL-1β in paw tissues, and reduced the number of splenic Th17 cells. Mechanistically, we found that in vitro treatment of EA inhibited both IL-6- and transforming growth factor-β (TGF-β)-induced Th17 cell differentiation by suppressing the phosphorylation of signal transducers and transcriptional activators, especially STAT3. In line with the in vivo result, EA significantly reduced the protein and mRNA expression of IL-6 and IL-1β in human RA-FLA cells, MH7A cells. Furthermore, the production of both cytokines was confirmed with the downregulation of mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways under the stimulation of TNF-α. In conclusion, these findings revealed that EA was capable of amelioration of arthritic disorders in SKG mice through inhibiting Th17 cell differentiation and synovial fibroblast inflammation, supporting that EA is a promising therapeutic candidate for treating RA patients.

Echinocystic Acid Bidesmoside Saponins from Microglossa afzelii O. Hoffm and Their Cytotoxic Activity against the CAL-27 Oral Squamous Carcinoma Cell Line.

This paper describes eight new triterpenoid saponins, including afzeliioside A (1), four acetylated afzeliiosides as pairs of inseparable regioisomers, called afzeliiosides B/C (2/3) and D/E (4/5), afzeliiosides F-H (6-8), and a known impatiprin C (9), which were isolated from the n-BuOH fraction of the liana of Microglossa afzelii. Their structures were established mainly by extensive spectroscopic analysis, including 1D and 2D NMR, HRFAB-MS, tandem ESI-MS/MS, and chemical methods, as well as a comparison of their spectral data with those of related compounds. All the isolates were screened for their cytotoxic activity against the CAL-27 oral squamous carcinoma cell line. Only compounds 4/5 (EC50 = 36.0 μg/mL (32.7 μM)) exhibited moderate cytotoxic activity. This work presents the first chemical and biological investigation of Microglossa afzelii and reports, for the first time, on the isolation of saponins in the genus Microglossa.

Disease Burden and Current Therapeutical Status of Leprosy with Special Emphasis on Phytochemicals.

Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while "reemergence" is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.

Effects of Echinocystic Acid on Atopic Dermatitis and Allergic Inflammation of the Skin and Lungs

BackgroundEchinocystic acid (ECA), a pentacyclic triterpene enriched in various herbs, promotes anti-inflammatory and antioxidant activity; however, its therapeutic effects on atopic dermatitis (AD) or atopic march and the underlying mechanisms of action have not yet been fully elucidated. PurposeThis study aimed to elucidate the effects and molecular mechanisms of ECA on AD and allergic inflammation. MethodsWe evaluated the inhibitory effects of ECA using a house dust mite (HDM)-induced AD mouse model and human keratinocytes. ResultsThe results revealed that ECA improved AD symptoms by decreasing epidermal/dermal thickness, immune cell infiltration, and restoring skin barrier function, as well as an imbalanced immune response. In addition, repeated epicutaneous HDM challenges aggravated allergic inflammation in mice lungs, which was caused by the infiltration of immune cells and collagen deposition, whereas ECA alleviated these symptoms. Moreover, ECA suppressed the expression of T helper cell-derived cytokines, phosphorylation of extracellular signal-regulated kinase, and signal transducer and activator of transcription 1 in the skin and lungs of mice with HDM-induced AD, as well as inhibited the translocation of nuclear factor-κB in HaCaT keratinocytes. ConclusionThis is the meaningful study to demonstrate that ECA improves allergic inflammation of the skin and lungs through recovery of the skin barrier, regulation of immune balance, and alleviation of lung inflammation, suggesting that ECA has therapeutic potential as an antiatopic and antiallergic agent that blocks the progression of AD to atopic march.

Combination of Ligustri Lucidi Fructus with Ecliptae Herba and their phytoestrogen or phytoandrogen like active pharmaceutical ingredients alleviate oestrogen/testosterone-induced benign prostatic hyperplasia through regulating steroid 5-α-reductase

BackgroundBenign prostatic hyperplasia (BPH) is a urinary system disease with high prevalence among the middle and elder men. In BPH, proliferation of prostate cells and the imbanlance between androgen and estrogen are both important inducers. Previous studies have demonstrated that compounds from Ligustri Lucidi Fructus (LLF) and Ecliptae Herba (EH) are of phytoestrogenic or phytoandrogenic activities. The combination of LLF with EH at the ratio of 1:1 on crude drugs quantity is called Erzhi formula (EZF), which is used for in vivo research of our study. PurposeThis study aimed to investigate potential mechanisms of EZF and its active pharmaceutical ingredients on BPH in vitro and in vivo. MethodsTherapeutic effects of EZF was evaluated in E2/testosterone (1:100) induced BPH rats model. The pathological changes of prostate, concentrations of testosterone, DHT, E2, PSA in rats’ plasma and prostate were detected. The expressions of PCNA, AR, ERα, ERβ, SRD5A1, SRD5A2 were measured in BPH rat prostates and E2-stimulated human benign prostatic epithelial cells (BPH-1). ResultsEZF treatment significantly attenuated rat prostate enlargement, alleviated BPH pathological features, and decreased the expression of PCNA. The up-regulation of AR, ERα, SRD5A1/2 expressions, and down-regulation of ERβ expression at prostate of rat BPH model were significantly blocked by EZF administration. The expression levels of testosterone, DHT, E2, PSA were strongly inhibited by EZF treatment. At the cellular level, ligustrosidic acid and echinocystic acid inhibited E2-induced BPH-1 cell proliferation and PCNA expressions, which were consistent with the results in vivo. And these two ingredients also down-regulated the expressions of AR, ERα, SRD5A1/2 and up-regulated the expression of ERβ in BPH-1 cells. ConclusionEZF, ligustrosidic acid from LLF and echinocystic acid from EH showed inhibitive effects on BPH via down-regulating prostatic AR, ERα, SRD5A1/2 expressions and up-regulating ERβ expression.

Eclipta prostrata (L.) L. (uses and bioactivities)

Eclipta prostrata has been long used by humans as traditional medicine and hair fertilizer. This study aims to explain the relationship between utilization and bioactivity of E. prostrata. The method used is a literature review of articles published online on Google Scholar using the keywords E. prostrata, uses E. prostrata, and bioactivity of E. prostrata. Ethnobotanically, E. prostrata is used to treat liver disorders, liver tonic, respiratory disorders (asthma, cough), hepatitis, snake venom poisoning, and gastritis. In the field of beauty E. prostrata is used to nourish hair and treat baldness. The E. prostrata has bioactivity to treat neurodegeneration, asthma, anti-cancer, overcoming baldness, anti-diabetes mellitus, anti-oxidant, anti-inflammatory, anti-microbial, hepatoprotective, anti-osteoporosis, and anti-hypercholesterolemia. The bioactivity of E. prostrata is related to the content of its secondary metabolite compounds. Echinocystic acid and ecclalbasaponin II from E. prostrata are associated with anti-cancer activity.

Echinocystic Acid Inhibits Inflammation and Exerts Neuroprotective Effects in MPTP-Induced Parkinson's Disease Model Mice.

Parkinson’s disease (PD), the second primary neurodegenerative disease affecting human health, is mainly characterized by dopaminergic neuron damage in the midbrain and the clinical manifestation of movement disorders. Studies have shown that neuroinflammation plays an important role in the progression of PD. Excessively activated microglia produce several pro-inflammatory mediators, leading to damage to the surrounding neurons and finally inducing neurodegeneration. Echinocystic acid (EA) exhibits an anti-inflammatory effect in peripheral tissues. However, whether it inhibited neuroinflammation remains unclear. Therefore, the current study investigates the effect of EA on neuroinflammation and whether it can improve PD symptoms through inhibiting neuroinflammation. In our experiments, we discovered that EA inhibited the production of pro-inflammatory mediators in LPS-exposed BV2 cells. Further mechanism-related studies revealed that EA inhibited inflammation by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in LPS-induced BV2 cells. Research revealed that EA eases microglia-mediated neuron death in SN4741 and SHSY5Y cells. In in vivo studies, the results demonstrated that EA improves weight loss and behavioral impairment in MPTP-induced mice. Further studies have revealed that EA inhibited dopaminergic neuron damage and inflammation in the mice midbrain. In conclusion, our study demonstrated that EA inhibits neuroinflammation and exerts neuroprotective effects by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in vivo and in vitro.

Two new triterpenoid saponins from the flowers of Albizia lebbeck

The chemical investigation of the fresh flowers of Albizia lebbeck (L.) Benth. (Fabaceae, Mimosoideae) led to the isolation of two new echinocystic acid saponins. They were isolated by using chromatographic methods and their structures were elucidated by detailed 1H and 13C NMR spectral data including 2 D-NMR (COSY, HSQC, HMBC and APT) spectroscopic techniques, high-resolution electrospray ionization mass spectrometry (HRESIMS) and acid hydrolysis. Their structures were established as 16-hydroxy-3-[[O-β-D-xylopyranosyl-(1→2)-O-α-L-arabinopyranosyl-(1→6)-2-(acetylamino)-2-deoxy-β-D-glucopyranosyl]oxy]-(3β,16α)-olean-12-en-28-oic acid O-6-deoxy-α-L-mannopyranosyl-(1→4)-O-6-deoxy-α-L-mannopyranosyl-(1→2)-β-D-glucopyranosyl ester (1) and 16-hydroxy-3-[[O-β-D-xylopyranosyl-(1→2)-O-α-L-arabinopyranosyl-(1→6)-2-(acetylamino)-2-deoxy-β-D-glucopyranosyl]oxy]-(3β,16α)-olean-12-en-28-oic acid 6-O-[(2S,3R,4R)-tetrahydro-3-hydroxy-4-(hydroxymethyl)-2-furanyl]-β-D-glucopyranosyl ester (2). Additionally, the permeability property and the capacity of interaction with biological membranes of compounds 1 and 2 were investigated.