Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides (1-5) and two new sesquiterpene glycosides (6 and 7) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.

Rapid separation and characterization of the in vitro metabolites of moscatilin by ultra-high performance liquid chromatography coupled to hybrid quadrupole orbitrap tandem mass spectrometry.

Moscatilin, a bioactive ingredient isolated from Dendrobium moscatum, has been demonstrated to have excellent anti-cancer activity. The goals of the present study were to investigate the metabolic profiles of moscatilin and to identify and characterize its metabolites. In vitro studies were performed by incubating moscatilin (10 µM) with rat, dog, monkey, and human liver microsomes (0.5 mg protein/ml) to generate the metabolites. An analytical method of liquid chromatography combined with hybrid quadrupole orbitrap high-resolution mass spectrometry in full mass/data-dependent tandem mass spectrometry scan was utilized to separate and identify the metabolites in accordance with their accurate masses, formulas, and tandem mass spectrometry fragment ions determination. A total of six phase I metabolites were detected and structurally characterized. The phase I metabolic pathways of moscatilin were hydroxylation, demethylation, and dehydrogenation. In glutathione-supplemented liver microsomes, nine glutathione conjugates were detected and identified. Our results demonstrated that moscatilin was susceptible to bioactivation with the result of ortho quinone and quinone-methide intermediates. The present study provided an overview of the in vitro metabolic profiles of moscatilin, which will aid in the understanding of the efficacy and safety of this active compound.

The molecular pathogenesis of triptolide-induced hepatotoxicity.

Triptolide (TP) is the major pharmacologically active ingredient and toxic component of Tripterygium wilfordii Hook. f. However, its clinical potential is limited by a narrow therapeutic window and multiple organ toxicity, especially hepatotoxicity. Furthermore, TP-induced hepatotoxicity shows significant inter-individual variability. Over the past few decades, research has been devoted to the study of TP-induced hepatotoxicity and its mechanism. In this review, we summarized the mechanism of TP-induced hepatotoxicity. Studies have demonstrated that TP-induced hepatotoxicity is associated with CYP450s, P-glycoprotein (P-gp), oxidative stress, excessive autophagy, apoptosis, metabolic disorders, immunity, and the gut microbiota. These new findings provide a comprehensive understanding of TP-induced hepatotoxicity and detoxification.

Systematic Evaluation of the Mechanisms of Mulberry Leaf (Morus alba Linne) Acting on Diabetes Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Diabetes mellitus is one of the most common endocrine metabolic disorder- related diseases. The application of herbal medicine to control glucose levels and improve insulin action might be a useful approach in the treatment of diabetes. Mulberry leaves (ML) have been reported to exert important activities of anti-diabetic. OBJECTIVE: In this work, we aimed to explore the multi-targets and multi-pathways regulatory molecular mechanism of Mulberry leaves (ML, Morus alba Linne) acting on diabetes. METHODS: Identification of active compounds of Mulberry leaves using Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was carried out. Bioactive components were screened by FAF-Drugs4 website (Free ADME-Tox Filtering Tool). The targets of bioactive components were predicted from SwissTargetPrediction website, and the diabetes related targets were screened from GeneCards database. The common targets of ML and diabetes were used for Gene Ontology (GO) and pathway enrichment analysis. The visualization networks were constructed by Cytoscape 3.7.1 software. The biological networks were constructed to analyze the mechanisms as follows: (1) compound-target network; (2) common target-compound network; (3) common targets protein interaction network; (4) compound-diabetes protein-protein interactions (ppi) network; (5) target-pathway network; and (6) compound-target-pathway network. At last, the prediction results of network pharmacology were verified by molecular docking method. RESULTS: 17 active components were obtained by TCMSP database and FAF-Drugs4 website. 51 potential targets (11 common targets and 40 associated indirect targets) were obtained and used to build the PPI network by the String database. Furthermore, the potential targets were used for GO and pathway enrichment analysis. Eight key active compounds (quercetin, Iristectorigenin A, 4- Prenylresveratrol, Moracin H, Moracin C, Isoramanone, Moracin E and Moracin D) and 8 key targets (AKT1, IGF1R, EIF2AK3, PPARG, AGTR1, PPARA, PTPN1 and PIK3R1) were obtained to play major roles in Mulberry leaf acting on diabetes. And the signal pathways involved in the mechanisms mainly include AMPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, insulin signaling pathway and insulin resistance. The molecular docking results show that the 8 key active compounds have good affinity with the key target of AKT1, and the 5 key targets (IGF1R, EIF2AK3, PPARG, PPARA and PTPN1) have better affinity than AKT1 with the key compound of quercetin. CONCLUSION: Based on network pharmacology and molecular docking, this study provided an important systematic and visualized basis for further understanding of the synergy mechanism of ML acting on diabetes.

Integrated network pharmacology and molecular docking strategy to explore the mechanism of medicinal and edible Astragali Radix-Atractylodis Macrocephalae Rhizoma acting on pneumonia via immunomodulation.

Pneumonia refers to a death-causing infection. Astragali Radix (AR) and Atractylodis Macrocephalae Rhizoma (AMR) are widely used as traditional tonic and promising edible immunomodulatory herbal medicine, but the systemic mechanism is not well understood. Therefore, a strategy based on network pharmacology and molecular docking was designed to explore the systemic mechanism of AR-AMR acting on pneumonia. After a series of bioinformatics assays, seven kernel targets were obtained, including TNF, IL6, IFNG, IL1B, IL10, IL4, and TLR9. And seven key compounds were identified as the synergy components of AR-AMR acting on pneumonia, the four key compounds belonging to AR were (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)-7-chromanol, formononetin, quercetin, and kaempferol, the three key compounds belonging to AMR were atractylone, 14-acetyl-12-senecioyl-2E, 8E, 10E-atractylentriol, and α-Amyrin. The crucial pathways were mainly related to three modules, including immune diseases, infectious disease, and organismal systems. Collectively, these observations strongly suggest that the molecular mechanisms of AR-AMR regulating pneumonia were closely related to the correlation between inflammation and immune response. PRACTICAL APPLICATIONS: Astragali radix and Atractylodis macrocephalae rhizoma can be used as "medicine-food homology" for dietary supplement. AR and AMR are widely used as a traditional tonic and promising edible immunomodulatory herbal medicine. The AR-AMR herb pairs are used for compatibility many times in the recommended prescriptions in COVID-19 develop pneumonia in China. However, the ingredients and mechanisms of AR-AMR acting on Pneumonia via immunomodulation are unclear. In this paper, bioinformatics and network biology were used to systematically explore the mechanisms of the AR-AMR herb pairs in treatment of pneumonia, and further analyze the correlation mechanism between it and COVID-19 develop pneumonia. To sum up, our study reveals the interrelationships between components, targets, and corresponding biological processes of AR-AMR acting on pneumonia. Understanding these relationships may provide guidance and theoretical basis for the further application of AR-AMR herb pairs.

Mechanism of Shuang-Huang-Lian Oral Liquid for Treatment of Mycoplasmal Pneumonia in Children on Network Pharmacology.

BACKGROUND AND OBJECTIVE: Mycoplasmal pneumonia (MP) can lead to inflammation, multiple system immune damage, and mixed infection in children. The pathogenesis is still unclear. Shuang-Huang-Lian (SHL) oral liquid can treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. However, our current understanding of the molecular mechanisms supporting its clinical application still lags behind due to the lack of researches. It is difficult to understand the overall sensitization mechanism of SHL oral liquid. The purpose is to explain the mechanism of action of drugs in this study, which is useful to ensure the safety of medication for children. METHODS: The therapeutic mechanism of SHL oral liquid was investigated by a system pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, ADMET, protein-protein interaction worknet, Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes database pathway performance, C-T-P network construction and molecular docking. RESULTS: A total of 18 active ingredients contained in SHL oral liquid and 53 major proteins were screened out as effective players in the treatment of M. pneumoniae disease through some related pathways and molecular docking. The majority of targets, hubs and pathways were highly related to anti-mycoplasma therapy, immunity and inflammation process. CONCLUSION: This study shows that the anti-bacterial effect of SHL oral liquid has multicomponent, multi-target and multi-pathway phenomena. The proposed approach may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.

Virtual Screening of Potential Anti-fatigue Mechanism of Polygonati Rhizoma Based on Network Pharmacology.

BACKGROUND AND OBJECTIVE: A large number of people are facing the danger of fatigue due to the fast-paced lifestyle. Fatigue is common in some diseases, such as cancer. The mechanism of fatigue is not definite. Traditional Chinese medicine is often used for fatigue, but the potential mechanism of Polygonati Rhizoma (PR) is still not clear. This study attempts to explore the potential anti-fatigue mechanism of Polygonati Rhizoma through virtual screening based on network pharmacology. METHODS: The candidate compounds of PR and the known targets of fatigue are obtained from multiple professional databases. PharmMapper Server is designed to identify potential targets for the candidate compounds. We developed a Herbal medicine-Compound-Disease-Target network and analyzed the interactions. Protein-protein interaction network is developed through the Cytoscape software and analyzed by topological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment are carried out by DAVID Database. Finally, we develop Compound-Target-Pathway network to illustrate the anti-fatigue mechanism of PR. RESULTS: This approach identified 12 active compounds and 156 candidate targets of PR. The top 10 annotation terms for GO and KEGG were obtained by enrichment analysis with 35 key targets. The interaction between E2F1 and PI3K-AKT plays a vital role in the anti-fatigue effect of PR due to this study. CONCLUSION: This study demonstrates that PR has multi-component, multi-target and multipathway effects.

Procyanidin B2 protects against d-galactose-induced mimetic aging in mice: Metabolites and microbiome analysis.

To elucidate the possible mechanisms for the preventive effect of procyanidin B2 on aging, a combined analysis of metabolic profile and gut microbiome was carried out in the present study. The mimetic aged mice induced by d-galactose injection (500 mg/kg, sc daily), and the preventive group was fed with the diet plus 0.2% procyanidin B2. After 7 weeks of treatment, the spatial memory was assayed using the Morris water maze test. Procyanidin B2 significantly ameliorated the impaired memory and antioxidant abilities induced by d-galactose. Furthermore, metabolomics analysis of plasma based on LC/Q-TOF-MS demonstrated that phosphatidyl cholines, oleic acid, linoleic acid, carnitine, pantothenic acid, and taurocholic acid were significantly increased in the mice treated with procyanidin B2, and pyruvic acid, hydroxybutyric acid, hippuric acid, and cholic acid were decreased significantly. Together, gut microbiome analysis using Illumina sequencing showed that there were significant differences in the Firmicutes/Bacteroidetes ratio and abundance of Roseburia, Lachnospiraceae, and Bifidobacterium between the aging and supplemental procyanidin B2 groups. In summary, procyanidin B2 possessed potential prevention of the cognitive and oxidative impairment via the metabolic pathway regulation related to citrate cycle, fatty acid, and bile acid in the aged mice, accompanied by remodeling the gut flora.