The effect of Piper laetispicum extract (EAE-P) during chronic unpredictable mild stress based on interrelationship of inflammatory cytokines, apoptosis cytokines and neurotrophin in the hippocampus.

BACKGROUD: The Piper laetispicum C.DC. (Piperaceae) is a traditionally used herb in China for invigorating circulation and reducing stasis, detumescence and analgesia, which is distributed in the southern part of China and the southeastern part of Asia. Previous studies demonstrated that the ethyl acetate extract (EAE-P) of P. laetispicum possesses a significant antidepressant-like effect at doses higher than 60 mg/kg in Kunming (KM) mice, and this effect was not due to an increase in locomotive activity. METHODS: To research this mechanism, in the present study, the chronic unpredictable mild stress (CUMS) model in Sprague-Dawley rats was used to further elucidate behavioral changes and corresponding changes in inflammatory cytokines (TNF-α, IL-6, IL-10), apoptosis cytokines (P53, Bax, Bcl2, caspase-3) and neurotrophin (BDNF) in the hippocampus of EAE-P treatment animals. RESULTS AND CONCLUSIONS: The results suggest that EAE-P is beneficial to the behavioral outcome of the CUMS model animals, and decreased amounts of inflammatory cytokine IL-6 contributed to the antidepressant-like activation of EAE-P in every dosage group (15, 30, 60 mg/kg). In the low dosage group, down-regulated apoptosis cytokine p53 is associated with EAE-P effect, but it is inflammatory cytokine TNF-α that is related to the effect of EAE-P in the high dosage group. Meanwhile, the P53-dependent antiapoptotic effect of EAE-P may not be through Bcl-2 and Bax modulation. Furthermore, EAE-P showed up-regulated expression of brain-derived neurotrophic factor (BDNF) mRNA and down-regulated apoptosis cytokine caspase-3 mRNA, which was the same change tendency as with Fluoxetine.

Optimization model research on efficacy in treatment of chronic urticaria by Chinese and Western medicine based on a genetic algorithm.

OBJECTIVE: To investigate the potential rules and knowledge of Traditional Chinese Medicine (TCM) and Western Medicine (WM) treatment on chronic urticaria (CU) based on data-mining methods. METHODS: Sixty patients with chronic urticaria, treated with TCM and WM, were selected. Gray correlation analyses were adopted to determine therapeutic efficacy. Association algorithms were utilized to ascertain the correlation between the disease course and treatment results. A genetic algorithm was applied to discover the optimization model in the TCM and WM treatment on CU. RESULTS: The total symptom scores after 4 weeks and 8 weeks of treatment in the TCM spleen-strengthening group correlated highly with the pretreatment total symptom score. The duration of treatment showed the greatest impact on the total symptom score. A quartic equation was established (y = - 1.6403 x 10 - 6 x(4) + 0.00025576x(3) + 0.0012819 x2 - 1.024x + 79.5879, and x = 106.9518, y = 83.0036) using the genetic algorithm. CONCLUSION: TCM treatment had a better effect in the later stage, whereas WM was better in the early stage. The duration of disease course had an impact on the effects of treatment. If the average total symptom score before treatment was < or = 83.0036, TCM or WM treatment could achieve better efficacy.

Simultaneous determination of ten active components in 12 Chinese Piper species by HPLC.

Piper is a genus that is recently valued for the treatment of central nervous system diseases. The major constituents, amides and lignans, are responsible for the antinociceptive and antidepressant activities. This study developed a RP-HPLC-UV method for the simultaneous determination of eight amides and two lignans in twelve different species of Piper. HPLC separation was accomplished on a C18 analytical column (5 µm, 250 mm × 4.6 mm, i.d.) with a gradient mobile phase consisting of acetonitrile and water at a flow rate of 1.0 ml/min. All the calibration curves showed good linear correlation coefficients (r > 0.9997) over the test ranges. The relative standard deviation of the current method was less than 2.90% for intra- and inter-day assays and the average recoveries were between 98.25% and 103.08%. The HPLC method established is appropriate for quality control purposes and allows for the differentiation of Piper species.

Studies on antidepressant and antinociceptive effects of ethyl acetate extract from Piper laetispicum and structure-activity relationship of its amide alkaloids.

Piper laetispicum C.DC. (Piperaceae), is an endemic climbing, glabrous plant distributed in the southern part of China. A novel alkaloid amide, Laetispicine, from it has been proven to possess antidepressant activity. In this present study, antidepressant and antinociceptive effects of the ethyl acetate extract (EAE) of P. laetispicum have been studied in forced swimming, open field, acetic acid writhing and formalin tests in KM mice. A significantly antidepressant-like effect was showing at doses of higher than 60 mg/kg, which was not due to an increase in locomotive activity. The EAE also presented an analgesic effect, in our studies. At lower doses (30 mg/kg) the antinociceptive effect was likely mediated via peripheral inflammation and changes in central processing, and at higher doses (120 mg/kg) that was due to both central and peripheral pathways. We also quantitatively analyzed the major components of EAE by HPLC and approached the structure-activity relationship between structure of amide alkaloids and its antidepressant activities. The antidepressant effective components of EAE might be Leatispiamide A and Laetispicine. In their molecular structures, the isolated double bond from benzene ring and conjugated double bond located at 2-3 and 4-5 were necessary for its antidepressant activity.

In vivo lymphatic targeting of methylene blue with microemulsion and multiple microemulsion.

Three formulations including methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), and MB multiple microemulsion (MB-MME) were prepared with the aim to evaluate whether the three formulations can carry MB target to regional lymph nodes and show lymphatic tropism after subcutaneous administration. The pseudo-ternary phase diagrams were also studied. The morphology of MB-ME and MB-MME was examined by transmission electron microscopy to characterize the microstructure. The particle size and viscosity were also measured. MB concentrations in plasma, lymph nodes, and limb soles were quantitatively analyzed using HPLC. Results show that MME can target MB to regional lymph nodes, and can be employed as a potential lymph tracer in sentinel lymph node biopsy.