Anti-inflammatory iridoid glycosides from Paederia scandens (Lour.) Merrill.

Eight previously undescribed iridoid glycosides together with 20 known congeners were isolated from the aerial parts of Paederia scandens (Lour.) Merrill (Rubiaceae). Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of NMR data, HR-ESI-MS spectrometry, and ECD data. The potential anti-inflammatory activities of the isolated iridoids were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound 6 significantly inhibited the production of nitric oxide with an IC50 value of 15.30 µM. The results of immunoblotting, qPCR, and immunofluorescence staining assays revealed that compound 6 exhibited anti-inflammatory activity by suppressing nuclear translocation of NF-κB and reducing the expression of COX-2, iNOS, IL-1ß, and IL-6. These results provide a basis for further development and utilization of P. scandens as a natural source of potential anti-inflammatory agents.

Network pharmacology-based approach uncovers the JAK/STAT signaling mechanism underlying paederia scandens extract treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease. Paederia scandens (Lour.) Merr is a common folk remedy used in Hainan, China, to dispel the wind and dampness associated with RA. METHODS: The active components of Paederia scandens were extracted using network pharmacology. The potential targets of active components were used to determine activated pathways, and the in vitro effects of Paederia scandens extracts were verified in RA fibroblast-like synoviocytes (HFLS-RA). RESULTS: We identified 27 active components using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS). Among the major target genes with high connectivity, IL-1ß, PI3K, TNF, and JAK2 are known to play key roles in RA development. High-affinity interactions were identified between active compounds in Paederia scandens extract and Janus kinase JAK 2, which are key components of the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In HFLS-RA cells, Paederia scandens extract treatment reduced the mRNA levels of IL-6, IL-1ß, and IL-17. Paederia scandens extract treatment also significantly inhibited the phosphorylation of JAK 2 and STAT3, regulating cell proliferation. CONCLUSIONS: Based on these results, we confirmed that Paederia scandens has potential for application as a therapeutic and preventive food and acts through the modulation and suppression of JAK-STAT pathway activation to control the inflammatory response in RA.

Ultrasonic-assisted extraction of polyphenolic compounds from Paederia scandens (Lour.) Merr. Using deep eutectic solvent: optimization, identification, and comparison with traditional methods.

Ultrasonic-assisted extraction (UAE) coupled with deep eutectic solvent (DES) is a novel, efficient and green extraction method for phytochemicals. In this study, the effects of 16 DESs coupled with UAE on the extraction rate of polyphenols from Paederia scandens (Lour.) Merr. (P. scandens), an edible and medicinal herb, were investigated. DES synthesised with choline chloride and ethylene glycol at a 1:2 M ratio resulted in the highest extractability. Moreover, the effects of extraction parameters were investigated by using a two-level factorial experiment followed by response surface methodology The optimal parameters (water content in DES of 49.2%, the actual ultrasonic power of 72.4 W, and ultrasonic time of 9.7 min) resulted in the optimal total flavonoid content (TFC) (27.04 mg CE/g DW), ferric-reducing antioxidant power (FRAP) value (373.27 µmol Fe(Ⅱ)E/g DW) and 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS+) value (48.64 µmol TE/g DW), closely matching the experimental results. Furthermore, a comparison study demonstrated that DES-UAE afforded the higher TFC and FRAP value than traditional extraction methods. 36 individual polyphenolic compounds were identified and quantified by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) in P. scandens extracts, and of which 30 were found in the extracts obtained by DES-UAE. Additionally, DES-UAE afforded the highest sum of individual polyphenolic compound content. These results revealed that DES-UAE enhanced the extraction efficiency for polyphenols and provided a scientific basis for further processing and utilization of P. scandens.

UPLC-Q-TOF-MS Analysis of Chemical Constituents of Paederiae Herba for Folk Use / 中国实验方剂学杂志

Objective:The chemical constituents of ethanol extracts from Paederia scandens，P. scandens var.tomentosa，P. stenophylla and P. foetida used in folk were identified. And the differences of chemical constituents among the four kinds of ethanol extracts were compared. Method:The chemical constituents of four species of Paederia were qualitatively and rapidly analyzed by UPLC-Q-TOF-MS. The data were analyzed manually and matched through databases to determine the differences among the chemical constituents of four species of Paederia. Result:Twenty-three compounds were identified from four species, including 12 iridoid glycosides，such as paederoside，paederosidic acid，asperuloside，asperulosidic acid，paederosidic acid methyl ester and monotropein.5 quinic acid derivatives, such as 1-O-caffeoylquinic acid，chlorogenic acid，cryptochlorogenic acid,and 5 flavonoid glycosides，such as quercetin-3-O-rutinoside-7-O-glucoside,quercetin-3-O-rutinoside-7-O-xyloside，rutin and simple compoundkinsenoside. Conclusion:Based on the UPLC-Q-TOF-MS analysis of the chemical components of four kinds of Paederia，the four peaks with the highest response intensity were paederoside，paederosidic acid，asperuloside and asperulosidic acid，all of which were iridoid glycosides.

Characterization of the complete chloroplast genome of Paederia scandens (Rubiaceae): a Chinese folk medicinal plant.

Paederia scandens has been used as a traditional medicine in Asian countries to treat jaundice, dysentery, and the pain of rheumatism. The complete chloroplast (cp) genome sequence of P. scandens was reported and characterized in this study. The cp genome is 153,626 bp in length, composed of a pair of 26,513 bp inverted repeat (IR) regions separated by a large single-copy (LSC) region of 83,712 bp and a small single-copy (SSC) region of 16,888 bp. There were 131 predicted genes (86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes) in the genome, and the overall GC content of the genome is 37.7%. Phylogenetic analysis based on the cp genome data showed that P. scandens was sister to the clade formed by Galium mollugo and G. aparine.

Protective effects of Paederia scandens extract on rheumatoid arthritis mouse model by modulating gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Paederia scandens (Lour.) Merr. (P. scandens) has been traditionally used to treat the pain of rheumatism. AIM OF THE STUDY: The purpose of this study was to investigate the possible influences of P. scandens on the progression of rheumatoid arthritis (RA), inflammatory responses and gut bacterial communities in RA mouse model. MATERIALS AND METHODS: collagen-induced arthritis (CIA) mice were orally administered with P. scandens extract (PSE) for 24 days. Then, pro-inflammatory cytokine levels in the serum were measured, and gut microbiota was examined with Illumina HiSeq. RESULTS: Compared with the vehicle group, PSE significantly inhibited paw swelling and reduced arthritis score. Histological examination of ankle soft tissue of demonstrated PSE effectively inhibited the tissue fibrosis and inflammatory cell infiltration. The increased serum levels of TNF-α, IL-1ß, IL-6, IL-7, and IL-23 in RA mice were significantly suppressed by PSE. Moreover, PSE treatment help restore gut microbial ecosystem altered in RA mice including decreasing relative abundance of inflammatory related microorganisms, Desulfovibrio, Mucispirillum, Helicobacter, and Lachnospiraceae. CONCLUSION: These results suggest that PSE has therapeutic effects in RA mice with CIA, showing the potential as anti-arthritis reagent.

Hepatoprotective activity of total iridoid glycosides isolated from Paederia scandens (lour.) Merr. var. tomentosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently, human liver is susceptible to injury caused by alcohol and virus infiltration, resulting in hepatitis, cirrhosis, and even hepatocellular carcinoma. Paederia scandens (Lour.) Merr. var. tomentosa (Rubiaceae) has been used as traditional medicine in Asian countries to treat jaundice, dysentery, and abdominal mass. Furthermore, the abundance of iridoid glycosides in Paederia species indicates their notable hepatoprotective potential. MATERIALS AND METHODS: Total iridoid glycosides (TG) was prepared, and constituents of TG were analyzed by HPLC. TG and silymarin (positive) were orally administered for 15 days. Then, acute liver injury rats was induced by intraperitoneally injection (i.p.) of 10% CCl4 (0.12%, v/v, dissolved in olive oil, 10 mL/kg, body weight). Rats were sacrificed at 16 h after CCl4 injection. Liver tissues and blood were collected. Serum samples were prepared to determine the activities of alanine transaminase (ALT) and aspartate transaminase (AST), whereas liver tissue sections were prepared for the purpose of examining possible liver histopathological changes. In addition, antioxidant enzyme activities in liver tissues were also evaluated. RESULTS: Our results demonstrated that TG significantly decreased the levels of AST and ALT, compared with those in control rats. In addition, pre-treatment of the rats with TG clearly alleviated their liver tissue injuries. What's more, the activities of GSH, GAT and SOD in the groups of TG-treated rats were significantly increased compared with those of rats in the control group, whereas the levels of MDA were decreased. CONCLUSIONS: Our present research indicated that TG possessed notable hepatoprotective activity via decreasing oxidative stress level in liver tissues.

UPLC/Q-TOF-MS analysis of iridoid glycosides and metabolites in rat plasma after oral administration of Paederia scandens extracts.

A rapid and validated UPLC-MS method was developed for investigating the absorbed components of Paederia scandens (Lour.) Merrill (P. scandensy) in rat plasma. The bioactive constituents in plasma samples from rats administrated orally with P. scandens extract were analyzed by Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Four prototype compounds were identified in rat serum as potential bioactive components of P. scandens by comparing their retention times and mass spectrometry data or by mass spectrometry analysis and retrieving the reference literatures. Glucuronidation after deglycosylation was the major metabolic pathway for the iridoid glycosides in P. scandens. These results showed that the methods had high sensitivity and resolution and were suitable for identifying the bioactive constituents in plasma after oral administration of P. scandens. providing helpful chemical information for further pharmacological and mechanistic researched on the P. scandens.

UPLC/Q-TOF-MS analysis of iridoid glycosides and metabolites in rat plasma after oral administration of Paederia scandens extracts / 中国天然药物

A rapid and validated UPLC-MS method was developed for investigating the absorbed components of Paederia scandens (Lour.) Merrill (P. scandensy) in rat plasma. The bioactive constituents in plasma samples from rats administrated orally with P. scandens extract were analyzed by Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Four prototype compounds were identified in rat serum as potential bioactive components of P. scandens by comparing their retention times and mass spectrometry data or by mass spectrometry analysis and retrieving the reference literatures. Glucuronidation after deglycosylation was the major metabolic pathway for the iridoid glycosides in P. scandens. These results showed that the methods had high sensitivity and resolution and were suitable for identifying the bioactive constituents in plasma after oral administration of P. scandens. providing helpful chemical information for further pharmacological and mechanistic researched on the P. scandens.

Anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats.

This study was designed to evaluate the anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats. In the present study, anticonvulsant activities of paederosidic acid were evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity tests in mice were used to evaluate the sedative effects of paederosidic acid. Finally, the mechanism of paederosidic acid was explored by evaluating the contents of Glu and GABA in the brain, and Western blot was used to measure GAD65 expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip) had significant anticonvulsant and sedative effects. Moreover, paederosidic acid increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain, and it up-regulated expressions of GAD 65. In conclusion, our results suggest that paederosidic acid may be a promising future therapeutic agent for treatment of epilepsy.