The distinct plastisphere microbiome in the terrestrial-marine ecotone is a reservoir for putative degraders of petroleum-based polymers.

Research into plastic-degrading bacteria and fungi is important for understanding how microorganisms can be used to address the problem of plastic pollution and for developing new approaches to sustainable waste management and bioplastic production. In the present study, we isolated 55 bacterial and 184 fungal strains degrading polycaprolactone (PCL) in plastic waste samples from Dafeng coastal salt marshes, Jiangsu, China. Of these, Jonesia and Streptomyces bacteria also showed potential to degrade other types of petroleum-based polymers. The metabarcoding results proved the existence of plastisphere as a distinct ecological niche regardless of the plastic types where 27 bacterial and 29 fungal amplicon sequence variants (ASVs) were found to be significantly (p < 0.05) enriched, including some belonging to Alternaria (Ascomycota, Fungi) and Pseudomonas (Gammaproteobacteria, Bacteria) that were also mined out by the method of cultivation. Further assembly analyses demonstrated the importance of deterministic processes especially the environmental filtering effect of carbon content and pH on bacteria as well as the carbon and cation content on fungi in shaping the plastisphere communities in this ecosystem. Thus, the unique microbiome of the plastisphere in the terrestrial-marine ecotone is enriched with microorganisms that are potentially capable of utilizing petroleum-based polymers, making it a valuable resource for screening plastic biodegraders.

Phytochemical Profiles, Antioxidant Activity and Antiproliferative Mechanism of Rhodiola rosea L. Phenolic Extract.

The phenolic profiles, antioxidant activity, antiproliferative property and the underlying molecular mechanisms of cell apoptosis of Rhodiola rosea free phenolic (RFE) were analyzed in this work. Overall, Rhodiola rosea rhizome phenolic extract (RE) contained Rhodiola rosea rhizome free phenolic extract (RFE) and Rhodiola rosea rhizome bound phenolic extract (RBE). Compared with RBE, RFE contained higher phenolic contents and possessed stronger antioxidant activity. High-performance liquid chromatography (HPLC) results demonstrated that the main phenolics of were epigallocatechin (EGC), epigallocatechin gallate (EGCG), gallic acid (GA) and catechin. Gas chromatography-mass spectrometry (GC-MS) analysis found that Rhodiola rosea L. was rich in volatile phytochemicals. In addition, many types of vitamin E and a few kinds of carotenoids were found in Rhodiola rosea. In addition, the main compounds in RFE (GA, EGC, EGCG) and RFE all exhibited excellent antiproliferative activity, indicating the antiproliferative activity of RFE was partly attributed to the synergy effects of the main compounds. Further study confirmed that RFE could block 16.99% of HepG2 cells at S phase and induce 20.32% programmed cell death compared with the control group. Specifically, RFE dose-dependently induced cell apoptosis and cell cycle arrest via modulating the p53 signaling pathway including up-regulation of the expression of p53 and Bax while down-regulation of the Bcl-2, cyclin D1 and CDK4 levels. Therefore, RFE exhibited the potential of being developed as an auxiliary antioxidant and a therapeutic agent for cancer.

The multi-omics and analysis to reveal thermal processing enhanced anti-rheumatoid arthritis efficacy of Radix Clematidis in rats.

Radix Clematidis (RC) is the roots and rhizomes of Clematis chinensis Osbeck, which has potent effects for expelling wind and dispelling dampness. Processing RC with yellow wine is a traditional processing method. This study aimed to investigate thermal and yellow wine processing influences on potential effective components of RC and its anti-rheumatoid arthritis enhancement mechanisms. Different thermal and wine processing were adopted to get different RC samples. Scanning electron microscope and mercury intrusion porosimetry were used to measure fractal parameters of pore structure. Based on ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), main constituents were identified and quantified. Besides, the correlation between fractal parameters and main constituents was investigated. The anti-rheumatoid arthritis effect was researched in adjuvant-induced arthritis (AIA) rats. The levels of inflammatory cytokine were determined with ELISA kits. Non-targeted serum metabolomics was performed with UPLC-QTOF/MS. 35 compounds were identified in RC, mainly triterpenoid saponins, also including organic acids and lignanoids. The extraction yield of four active triterpenoid saponins significantly increased because looser tissue and wider pore size distribution. Fractal dimension and total surface area significantly increased while total porosity and total volume decreased. In AIA rats, thermal and wine processed RC could markedly inhibit inflammatory cytokines IL-6, IL-1ß, TNF-α, and VEGF. Besides, tryptophan and lipid metabolism disorders were ameliorated. Thermal and yellow wine treatments engendered complex pore structure to increase the contents of four active triterpenoid saponins of RC, leading to greater anti-rheumatoid arthritis efficacy.

Network Pharmacology-Based Analysis on the Effects and Mechanism of the Wang-Bi Capsule for Rheumatoid Arthritis and Osteoarthritis.

Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.

Thermal and wine processing enhanced Clematidis Radix et Rhizoma ameliorate collagen â ¡ induced rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Clematidis Radix et Rhizoma, a kind of traditional Chinese medicine, is derived from Clematis chinensis Osbeck, Clematis hexapetala Pall. and Clematis manshurica Rupr. This herb shows great effects on expelling wind and dispelling dampness in ancient and it has anti-inflammatory and analgesic activity in modern clinical application. AIM OF THE STUDY: This experiment aimed to research anti-rheumatoid arthritis effect of crude and wine processed RC based on glycolysis metabolism to provide new ideas treating RA. MATERIALS AND METHODS: Network pharmacology was applied to preliminarily forecast the potential pathways of common targets of RC and RA. RAW264.7 macrophages were induced by LPS, NO production, glucose uptake, lactate production, ROS and MMP were detected as instructions in vitro. ELISA was used to measure the content of HK2, PKM2 and LDHA involving in glycolysis process. Gut microbiota was analyzed by 16S rRNA gene amplicon sequencing in CIA rats. RESULTS: Crude and wine processed RC had good anti-inflammatory effect by reducing NO in RAW264.7 macrophages and ameliorating inflammatory infiltration and cartilage surface erosion in CIA rats. Whether in LPS-induced macrophages or CIA rats, crude and wine processed RC could inhibit glycolysis by down-regulating the expression of PKM2, causing less glucose uptake and lactic acid, which lead to less ROS and higher MMP to normal. PI3K-AKT and HIF-1α pathways were deduced to possibly play a crucial part in controlling glycolysis metabolism by network pharmacology analysis. Besides, it was displayed that Firmicutes and Bacteroidetes were prominent gut microbiota in CIA rats feces. CC-H and PZ-H groups could both increase the relative abundance of Firmicutes and decrease Bacteroidetes. These microbiota also played a role in RA pathological process via involving in energy metabolism, carbohydrate metabolism and immune system. CONCLUSION: Crude and wine processed RC have a good influence in ameliorating rheumatoid arthritis by inhibiting glycolysis and modulating gut microbiota together.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herb couple Angelicae pubescentis radix (APR) and Notopterygii rhizoma et radix (NRR), composition of two traditional Chinese medicinal herbs, has been used clinically in China for the treatment of rheumatoid arthritis (RA) over years. APR and NRR contain coumarins and phenolic acids, which have been reported to have analgesic and anti-inflammatory activities. AIM OF THE STUDY: The active ingredients combination (AIC) and potential therapeutic mechanism of APR and NRR (AN) herb couple remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on RA. MATERIALS AND METHODS: Firstly, a novel strategy of in vitro experiments, computational analysis, UPLC-QTOF-MS and UPLC-QQQ-MS was established to confirm the optimum ratio of AN herb couple samples and identified the AIC. Then, the anti-arthritis effects of the optimal herb couple and AIC were studied with Collagen II induced rheumatoid arthritis (CIA) rats in vivo. Finally, an integrated model of network pharmacology, metabolomics, gut microbiota analysis and biological techniques were applied to clarify the underlying mechanism through a comprehensive perspective. RESULTS: AN7:3 herb couple was regarded as the optimal ratio of AN herbal samples, and AIC was screened as osthole, columbianadin, notopterol, isoimperatorin, psoralen, xanthotoxin, bergapten, nodakenin and bergaptol respectively. Additionally, AIC exerted similar therapeutic effects as AN 7:3 in CIA rats. Moreover, AIC ameliorated RA might via regulating MAPK signaling pathway, altering metabolic disorders and gut microbiome involved autoimmunity. CONCLUSIONS: our findings provided scientific evidence to support that AIC of AN herb couple could be used as a prebiotic agent for RA. Importantly, this research provided a systematic and feasible strategy to optimize the proportion of medicinal materials and screen AIC from multi-component traditional Chinese herb couples or Chinese medicine formulae. Moreover, it provided a comprehensive perspective to discover AIC, clarify the overall effects and understand the mechanisms for natural products through the perspective of database and multi-omics integration.

Rhodiola extract promotes longevity and stress resistance of Caenorhabditis elegans via DAF-16 and SKN-1.

The effects of Rhodiola extract (RE) on longevity and stress resistance in Caenorhabditis elegans (C. elegans), and the underlying molecular mechanisms were explored in the present study. Results showed that the lifespan of C. elegans was remarkably prolonged by 37.1% after treated with high-dose RE (480 µg mL-1). Intervention with RE alleviated aging-related declines in the C. elegans model, and enhanced the stress resistance against heat shock, ultraviolet radiation and paraquat. Moreover, RE reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT). RE also upregulated the gene expression of sod-3, gst-4, daf-16, skn-1 in C. elegans, downregulated the gene expression of daf-2 and age-1, and accelerated the translocation of DAF-16 and SKN-1 into the nucleus. Furthermore, the daf-16(mu86) and skn-1(zu169) mutants reversed the extension of lifespan triggered by RE, indicating that these genes were involved in RE-regulated longevity. These results demonstrated that RE could enhance lifespan extension, healthspan and stress resistance of C. elegans via insulin/IGF signaling and SKN-1 pathways. Therefore, the present findings suggested Rhodiola as a potential candidate to ameliorate the symptoms of aging.

Integrated network pharmacology and zebrafish model to investigate dual-effects components of Cistanche tubulosa for treating both Osteoporosis and Alzheimer's Disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis (OP) and Alzheimer's disease (AD) are common geriatric concurrent diseases, and many studies indicate the connection of their pathogenesis. Cistanche tubulosa (Schenk) Wight (CT) is a widely used traditional Chinese medicine and has been extensively applied to treat OP and AD, respectively. However, the active ingredients for both concurrent diseases simultaneously and underlying mechanisms are limited. AIM OF STUDY: This work aimed at establishing an effective and reliable network screening method to find dual-effects compounds in CT that can protect AD and OP concurrently. And it will provide new perspectives of the link between OP and AD on molecular mechanisms. MATERIAL AND METHODS: The dual-effects of CT were systematically analyzed with integrating multiple databases and extensive analysis at a network pharmacology level. Classified drug-target interaction network was constructed to reveal differences in effects between different types of compounds. To prove the effectiveness of this network, some compounds were selected to verify in Pre-induced OP model and AlCl3-induced AD model of zebrafish according to the topological parameters. RESULTS: 22 dual-effects active ingredients in CT were initially screened out via network pharmacology with a closely connection with 81 OP and AD-related targets. Classified network analysis found the better bioactivities of phenylethanoid glycosides and flavonoids. The dual-effects of four selected compounds demonstrated that the network is reasonable and effective, suggesting the dual-effects of the remaining 18 compounds. Moreover, we identified 9 putative targets and two pathways that were significantly related to OP and AD. CONCLUSIONS: We successfully identified 22 dual-effects active components in CT. This systematic screening strategy provided a new protocol to objectively discover multi-effects compounds of traditional Chinese medicine, and even a macroscopic perspective that will improve our understanding of the link between OP and AD on molecular mechanisms.

Three new ent-kaurane diterpenes from the herbs of Wedelia prostrata.

Three new ent-kaurane diterpenes, 3α-angeloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (1), 3α-tigloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (2) and 3α-cinnamoyloxykaur-9(11),16-dien-19-oic acid (3), along with five known compounds (4-8), were isolated from the herbs of Wedelia prostrata (Asteraceae). The structures were determined by extensive analysis of their spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolated compounds were evaluated for their cytotoxic activity on human hepatocellular carcinoma HepG2 cells. Among them, all isolates exhibited cytotoxic activities with IC50 values ranging from 9.55 ± 0.45 to 53.92 ± 1.22 µM.