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Aim To investigate the therapeutie effect thritis (CIA) rats based on the variation of gut micro- of active ingredient group ( AIG) in the compounds biota.Methods CIA model rats were induced by in- from Periploca forrestii Schltr.on collagin-induced ar- jection of emulsion containing bovine type II collagen.anrl enzyme-linked immunosorbent assay ( ELISA) was used to investigate the changes of TNF-a and IL-6 in ankle joint of rats in each group.Meanwhile, the gut microbial communities were measured using 16s rRNA high-throughput sequencing technology and its function was predicted by KEGG.Results AIG could signifi¬cantly restrain inflammatory cell infiltration and tissue proliferation in synovial tissues of CIA rats,and allevi¬ate joint swelling while significantly reducing the con¬tents of IL-6 and TNF-a in ankle joint of CIA rats.The analysis of gut microbial communities showed that AIG could increase the relative abundances of Bacte- roidetes, Alloprevotella and Prevotella _9 , and decrease the relative abundances of 1 1 genera such as Dubosiel- la, Lachnospiraceae_NKAA 136_group, etc.in CIA rats.The functional prediction showed that AIG coulrl influ¬ence apoptosis and other signaling pathways.Conclu¬sions AIG can obviously alleviate joint swelling, re¬strain inflammatory cell infiltration and tissue prolifera¬tion in joint synovium of CIA rats,and repair the disor¬dered gut microbiota structure of CIA rats, while affecting its apoptosis pathway and restore the body immunity.
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Objective: To establish a pharmacokinetic (PK)-pharmacodynamic (PD) model of Periploca forrestii. Methods: The right hindfoot footpad of rats were 0.1 mL complete Freund's Adjuvant (CFA) to establish adjuvant arthritis (AA) rat model. Rats were ig P. forrestii extract (87 g/kg, twice a day for 14 d) and blood were collected via tail vein at 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after the last administration. The concentrations of 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid in plasma samples were detected by HPLC-mass spectrometry (HPLC-MS/MS) to obtain the drug concentration-time curve. The level of interleukin-1β (IL-1β), rheumatoid factor (RF), tumor necrosis factor-α (TNF-α) in plasma samples were determined by kit to obtain the time-effect curve. WinNonLin software was used to fit the PK parameters of P. forrestii, and the time-effect relationship was fitted to obtain the PD parameters. According to the PD parameters, the PK-PD model of P. forrestii was established. Results: The PK-PD model of P. forrestii according to the WinNonLin software was fitted in accordance with the Inhibitory Effect Sigmoid E0 model, in which the blood concentrations of 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid could be calculated based on the potency values, and the potency values could be calculated based on the blood concentrations. Conclusion: There was a correlation between the concentrations of IL-1β, RF, TNF-α and 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid and 5-O-caffeoylquinic acid. These three components in P. forrestii extract could inhibit the secretion of IL-1β, RF and TNF-α to treat rheumatiod arthritis.
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Objective: To study the chemical constituents of Periploca Radix. Methods: The chemical constituents of Periploca forrestii were separated using various chromatographic techniques. Their structures were elucidated by spectral analysis. Results: Nineteen compounds were isolated from the 70% ethanol extract of P. forrestii, and identified as 3-O-caffeoylquinic acid methyl ester (1), 4-O-caffeoylquinic acid methyl ester (2), 5-O-caffeoylquinic acid methyl ester (3), 3-O-caffeoylquinic acid (4), 4-O-caffeoylquinic acid (5), 5-O-caffeoylquinic acid (6), 1, 3-di-O-caffeoylquinic acid (7), 3, 4-di-O-caffeoylquinic acid (8), 3, 5-di-O- caffeoylquinic acid (9), 4, 5-di-O-caffeoylquinic acid (10), protocatechuic aldehyde (11), p-hydroxybenzoic acid (12), o-hydroxybenzoic acid (13), syringic acid (14), vanillic acid (15), periforgenin A (16), Δ5-pregnene-3β, 17α, 20α-triol (17), periforgenin C (18), and periplogenin (19). Conclusion: Compounds 1-12 are isolated from the plants of genus Periploca Linn. for the first time, and compound 13 is isolated from P. forrestii for the first time.
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<p><b>OBJECTIVE</b>To determine the anti-inflflammatory effects of an ethanol fraction of Periploca forrestii Schltr. (EFPF) and to investigate the potential mechanisms underlying in vivo and in vitro models.</p><p><b>METHODS</b>The antiinflflammatory effects of EFPF were evaluated using the xylene-induced mouse ear edema and carrageenan-induced rat paw edema models in vivo. In vitro, RAW264.7 cells were exposed to 0-800 μg/mL EFPF and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then cells were treated with different concentrations of EFPF (100-400 μg/mL) and stimulated with lipopolysaccharide (LPS, 1 μg/mL) for 24 h. The supernatant was analyzed for nitric oxide (NO) using the Griess reagent, and the levels of inflflammatory mediators and cytokines were determined using enzyme-linked immunosorbent assays for prostaglandin E(PGE), tumor necrosis factor α (TNF-α), interleukin (IL) 6, and IL-10. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK were examined by Western blot.</p><p><b>RESULTS</b>Compared with the control group, EFPF signifificantly reduced mouse ear edema and rat paw edema rate (P<0.05 or P<0.01). Compared with the LPS group, EFPF signifificantly inhibited the LPS-stimulated production of NO, PGE, TNF-α and IL-6 (P<0.05 or P<0.01), and increased the IL-10 production (P<0.05). EFPF also signifificantly inhibited LPS-induced protein expressions of iNOS and COX-2, suppressed the phosphorylation and degradation of inhibitor of NF-κB-α, decreased p65 level, and inhibited the phosphorylation of p38, ERK1/2 and JNK P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>EFPF exerted anti-inflflammatory effect by reducing protein expressions of iNOS and COX-2 and the production of the inflflammation factors, including TNF-α, IL-6, NO and PGE, mainly through inhibition of LPS-mediated stimulation of NF-κB and MAPK signaling pathways.</p>
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Objective:To investigate the effects of periploca forrestii schltr in the treatment of acute gout arthritis.Methods:60 healthy male SD rats were equally randomly divided into 6 groups:normal control group( NC) ,model group( M group) ,colchicine group (C group),high doses group of periploca forrestii schltr(HD group),middle doses group of periploca forrestii schltr(MD group) and low doses group of periploca forrestii schltr( LD group).Except the normal control group,model of gouty arthritis was induced in other groups by uric acid salt,colchicine(positive control) and different dose of periploca forrestii schltr were given by intragastric ad minis-tration.Swelling dimension of joints were observed at 3,5,7 days after treatment.All rats were killed after 7 days of treatment and ankle joint tissue was taken for pathological examination and the peripheral blood of rats was prepared for detecting the expression of interleukin 1β(IL-1β),IL-6,IL-8 and tumor necrosis factor(TNF-α) using enzyme linked immunosorbent test(ELISA).Results:The ankle joint swelling of periploca forrestii schltr group was significantly lower than that in the model group,and the effect of high doses group was much better than the low doses group after 7 days treatment(P<0.05);compared with model group,the inflammatory cells of each treatment groups were decreased and high doses group did not differ from that of normal control group;the levels of IL-1β,IL-6,IL-8 and TNF-αin periploca forrestii schltr group were dramatically lower than those in the model group in a dose-dependent manner.Conclusion:Periploca forrestii schltr has good therapeutic effect in rats with acute gouty arthritis and shows a dose-dependent response,and the mechanism may relate to the inhibition of inflammatory cytokines expression.