Network pharmacology, molecular docking, and experimental pharmacology explored Ermiao wan protected against periodontitis via the PI3K/AKT and NF-κB/MAPK signal pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Ermiao Wan (EMW), a classic and famous traditional Chinese medicine (TCM)-based herbal formula combined Phellodendron chinense C.K.Schneid. (Cortex Phellodendri Chinsis, CP) and Atractylodes lancea (Thunb.) DC. (Rhizoma Atractylodis, RA) with the weight composition of 1:1, has been used for the treatment of periodontitis in China for a long time. However, its efficacy and mechanism of action are still unclear now. AIM OF THE STUDY: This study explored the efficacy and pharmaceutical mechanism of action of EMW against periodontitis. MATERIALS AND METHODS: The efficacy of EMW against periodontitis was evaluated using the ligature-induced periodontitis (LIP) mice, and inflammatory-related factors in gingiva and alveolar bone loss were determined using the qRT-PCR and micro-CT assays. The potential pharmacological mechanisms were predicted by bioinformatics analysis and further confirmed by the qRT-PCR and western blotting assays. RESULTS: EMW exhibited inhibitory effects on periodontitis in the LIP mice. Bio-informational analysis showed the core compounds (berberine and chlorogenic acid) targeted the key genes (AKT, MAPK1, MAPK14, NF-κB, TNF, IL-2, and IL1B) through regulating the PI3K/AKT and NF-κB/MAPK signal pathways, which were validated using the qRT-PCR and western blotting assays. CONCLUSIONS: EMW could eliminate alveolar bone loss and inhibit inflammation, thereby preventing the development of periodontitis. The mechanism of action may be achieved by regulating the PI3K/AKT and NF-κB/MAPK signal pathways. Therefore, EMW was a potential therapy for the treatment of periodontitis.

Exploring Anti-Nonalcoholic Fatty Liver Disease Mechanism of Gardeniae Fructus by Network Pharmacology, Molecular Docking, and Experiment Validation.

Gardeniae fructus (GF), the fruit from Gardenia jasminoides Ellis, is a traditional Chinese medicine used for the treatment of nonalcoholic fatty liver disease (NAFLD) in the clinic. To explore the hepatoprotective mechanism of GF for the treatment of NAFLD, we proposed a novel strategy that integrated in vivo efficacy evaluation, network pharmacology analysis, molecular docking, and experimental validation. A NAFLD animal model induced by high fat diet (HFD) feed was established, then orally administrated with or without GF. The results showed that GF significantly decreased the levels of serum total cholesterol (TC), lipoprotein cholesterol, triglyceride (TG), alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, free fatty acids, glucose, and insulin and the levels of liver TG, TC, and malondialdehyde compared with the nontreated HFD group. Network pharmacology studies showed that quercetin, oleanolic acid, kaempferol, and geniposide were the main biocompounds in GF that targeted the PPARα and PPARγ genes through regulating the PPAR and AMPK signal pathways to protect against NAFLD. The interactions between bioactive compounds and their corresponding target proteins were analyzed by molecular docking and subsequently confirmed using the qRT-PCR assay. Collectively, GF was a therapeutic drug for the treatment of NAFLD.

Network Pharmacology Analysis and Experimental Pharmacology Study Explore the Mechanism of Gambogic Acid against Endometrial Cancer.

Endometrial cancer (EC) is one of the three most common gynecological cancers in female groups. Gambogic acid (GA), a natural caged xanthone, exerts significantly antitumor effects on many cancers. However, its efficacy on EC and pharmacological mechanism of action remain marginal up to now. This study suggested that GA had significant inhibitory effects on EC in vitro and in vivo, and no toxicity to normal cells or mice. In detail, GA suppressed cell proliferation, induced cell apoptosis, and cell cycle arrest at G0/G1 stage, complied with the network pharmacology analysis, showed that the PI3K/Akt pathways were the most important signaling, and their protein and mRNA expression levels were confirmed by qRT-PCR and Western blot experiments. In all, our study first proved that GA could inhibit cell proliferation, induce cell apoptosis, and cell cycle arrest at G0/G1 stage via the PI3K/Akt pathways, so GA would be a good therapy for EC.

Anti-Tumor Xanthones from Garcinia nujiangensis Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells.

BACKGROUND: Ovarian cancer (OC) is a serious public health concern in the world. It is important to develop novel drugs to inhibit OC. PURPOSE: This study investigated the isolation, elucidation, efficiency, molecular docking, and pharmaceutical mechanisms of xanthones isolated from Garcinia nujiangensis. METHODS: Xanthones were isolated, and purified by different chromatography, including silica gel, reversed-phase silica gel (ODS-C18), and semipreparative HPLC, then identified by analysis of their spectral data. Three xanthones were estimated for their efficiency on the human OC cells HEY and ES-2. 2 was found to be the most potent cytotoxic xanthones of those tested. Further, its mechanisms of action were explored by molecular docking, cell apoptosis, and Western blotting analysis. RESULTS: Bioassay-guided fractionation of the fruits of Garcinia nujiangensis led to the separation of a new xanthone named nujiangexanthone G (1) and two known xanthones. Among these, isojacareubin (2) exhibited the most potent cytotoxic compound against the HEY and ES-2 cell lines. The analysis of Western blot suggested that 2 inhibited OC via regulating the PARP, PI3K/AKT/mTOR, and ERK/MAPK signal pathways in the HEY cell lines. CONCLUSION: In conclusion, isojacareubin (2) might be a potential drug for the treatment of OC.

Thioredoxin-2 impacts the inflammatory response via suppression of NF-κB and MAPK signaling in sepsis shock.

Sepsis is a progressive disease characterized by excessive inflammatory responses, severe tissue injury and organ dysfunction, ultimately leading to mortality. In this study, we demonstrated that thioredoxin-2 (TRX-2) expression is reduced in macrophages stimulated with lipopolysaccharide (LPS). Overexpression of TRX-2 significantly attenuated interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production induced by LPS. TRX-2 inhibited LPS-induced inflammatory responses through suppressing activation of the NF-κB and MAPK signaling pathways. Furthermore, TRX-2 induced a significant decrease in mortality in mouse sepsis models in association with reduced inflammatory cytokine production and attenuation of organ injury. Our data collectively support a role of TRX-2 as a critical regulator of sepsis that influences survival by protecting the host from excessive inflammatory damage.

A new cytotoxic polycyclic polyprenylated acylphloroglucinol from Garcinia nujiangensis screened by the LC-PDA and LC-MS.

A new polycyclic polyprenylated acylphloroglucinol (1), nujiangefolin D, together with five known analogues (2-6), were isolated from the fruits of Garcinia nujiangensis. Compound 1 was screened by the LC-MS and LC-PDA. The structure of 1 was elucidated on the basis of extensive spectroscopic techniques including 1 D and 2 D NMR and MS analyses. The compounds isolated were evaluated for their cytotoxic activities against three cancer cell lines, 1 showed moderate cytotoxic activity against Hela, PANC-1, and MDA-MB-231 cell lines with IC50 values of 5.6 ± 0.1, 9.1 ± 0.2, and 8.3 ± 0.2 µM, respectively. The antitumor mechanism was explained via virtual docking of 1 to the main sites in the human serine/threonine-protein kinase mTOR (mTOR) crystal structure (PDB code: 4DRI). Furthermore, 1 may inhibit Hela cell proliferation through mTOR by the western blotting analysis. Taken together, 1 may be a potential mTOR inhibitor used for the treatment of cervical cancer.

Sulfated neo-clerodane diterpenoids and triterpenoid saponins from Sheareria nana S. Moore.

Three novel neo-clerodane diterpenoids Sheareria A-C (1-3) together with three known triterpenoid saponins were isolated from the whole herb of Sheareria nana S. Moore. Their structures were established by spectroscopic and chemical method. This is the first natural sulfated neo-clerodane diterpenoids. This is the first report of all these compounds from this plant. These neo-clerodane diterpenoids and triterpenoid saponins from S. nana S. Moore may be considered as chemotaxonomic markers for the genus. The compounds isolated were evaluated for their cytotoxic effects against three cancer cell lines, the test substances demonstrated selectivity toward the cancer cells. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from S. nana S. Moore.

Scoring systems used to predict mortality in patients with acute upper gastrointestinal bleeding in the ED.

OBJECTIVE: Acute upper gastrointestinal bleeding (UGIB) is a potentially life-threatening condition that requires rapid assessment in the emergency department (ED). We aimed to compare the performance of the AIMS65, Glasgow-Blatchford (Blatchford), preendoscopic Rockall (pre-Rockall), and preendoscopic Baylor bleeding (pre-Baylor) scores in predicting 30-day mortality in patients with acute UGIB in the ED setting. METHODS: Consecutive patients with acute UGIB who were admitted to the ED ward during 2012-2016 were retrospectively recruited. Data were retrieved from the admission list of the ED using international classification of disease codes via computer registration. The predictive accuracy of these four scores was compared using the area under the receiver operating characteristic curve (AUC) method. RESULTS: Among the 395 patients included during the study period, the total 30-day mortality rate was 10.4% (41/395). The AIMS65 and Glasgow-Blatchford scores performed better with an AUC of 0.907 (95% confidence interval (CI), 0.852-0.963; P<0.001) and 0.870 (95% confidence interval, 0.833-0.902; P<0.001) compared with other scoring systems (preendoscopic Rockall score: AUC, 0.709; 95% CI, 0.635-0.784; P<0.001; preendoscopic Baylor score: AUC, 0.523; 95% CI, 0.472-0.573; P>0.05). CONCLUSION: In patients with acute UGIB in the ED, the AIMS65 and Glasgow-Blatchford scores are clinically more useful for predicting 30-day mortality than the preendoscopic Rockall and preendoscopic Baylor scores. The AIMS65 score might be more ideal for risk stratification in the ED setting.

Four new cytotoxic xanthones from Garcinia nujiangensis.

Bioassay-guided fractionation of the acetone extract of the twigs of Garcinia nujiangensis resulted in the isolation of four new prenylated xanthones, nujiangexanthones C-F (1-4), and ten known related analogues. The structures of compounds 1-4 were elucidated by interpretation of their spectroscopic data. The compounds isolated were evaluated for their cytotoxic effects against three cancer cell lines, the test substances demonstrated selectivity toward the cancer cells.

A new anthraquinone glycoside from the root of Rheum officinale Baill.

A new and a known anthraquinone glycosides were isolated from the ethanol extract of the roots of Rheum officinale Baill. The extract was purified by various chromatographies, such as silica gel, Sephadex LH-20, RP-C18 column chromatography and HPLC. Two compounds were identified by the spectroscopic techniques of NMR, MS, and chemical method. In addition, they were tested for their cytotoxic effects against HepG2 cell. Unfortunately, they showed no or weak activity.