- 1. Multicompartment micelle-structured peptide nanoparticles: A new biocompatible gene- and drug-delivery tool.
Self-assembled, biodegradable materials that embed fragile, soluble or insoluble compounds of therapeutic interest have potential use as drug delivery systems. The bead-forming peptide Ac-X3 -gT can embed hydrophobic and hydrophilic payloads. Loaded peptide beads were internalized by THP-1 macrophages, THP-1 monocytes, and hepatocellular carcinoma cells (Huh7). Furthermore, paclitaxel and doxorubicin co-encapsulated in the peptide beads were delivered to THP-1 monocytes, causing a decrease in cell viability due to the activity of the anti-cancer drugs. In addition to the bead-forming peptide Ac-X3 -gT, the use of a positively charged peptide analogue increased the RNA/DNA embedding efficiency to 99% by charge compensation and micellar complexation. Internalization of the resulting gene delivery systems by Huh7 cells led to specific gene silencing either by embedded siRNA or plasmid encoding shRNA delivered in cells. The new class of purely peptidic material caused no measurable toxicity during in vitro experiments, thereby indicating potential use as a drug delivery system for multi-drug delivery and gene therapy....(more)
Oubotér DD, et al. J Biomed Mater Res A 2013 May 3.
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- 2. CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity.
PURPOSE: Paclitaxel is used for the treatment of several solid tumors and displays a high inter- individual variation in exposure and toxicity. Neurotoxicity is one of the most prominent side-effects of paclitaxel. This study explores potential predictive pharmacokinetic and pharmacogenetic determinants for the onset and severity of neurotoxicity. EXPERIMENTAL DESIGN: In an exploratory cohort of patients (n=261) treated with paclitaxel, neurotoxicity incidence and severity, pharmacokinetic parameters and pharmacogenetic variants were determined. Paclitaxel plasma concentrations were measured by HPLC or LC-MS/MS, and individual pharmacokinetic parameters were estimated from previously developed population pharmacokinetic models by non-linear mixed effects modeling (NONMEM). Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n=239). RESULTS: Exposure to paclitaxel (logAUC) was correlated with severity of neurotoxicity (P <0.00001). Female CYP3A4*22 carriers were at increased risk of developing neurotoxicity (P = 0.043) in the exploratory cohort. CYP3A4*22 carrier status itself was not associated with pharmacokinetic parameters (CL, AUC, Cmax, or T>0.05) of paclitaxel in males or females. Other genetic variants displayed no association with neurotoxicity. In the subsequent independent validation cohort, CYP3A4*22 carriers were at risk of developing grade 3 neurotoxicity (odds ratio = 19.1; P = 0.001). CONCLUSIONS: Paclitaxel exposure showed a relationship with the severity of paclitaxel-induced neurotoxicity. In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. These observations may guide future individualization of paclitaxel treatment....(more)
de Graan AJ, et al. Clin Cancer Res 2013 May 2.
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- 3. Clinical Outcomes after Treating Acute Coronary Syndrome Patients with a Drug-Eluting Stent: Results from REWARDS-EMI (Endeavor® for Myocardial Infarction Registry).
BACKGROUND:
Drug-eluting stents have shown promising clinical results in the treatment of acute coronary syndrome (ACS) patients. We aimed to evaluate the long-term outcome of Endeavor® zotarolimus-eluting stent (EZES) implantation in an ACS population and to compare these results with those obtained in patients treated with sirolimus-eluting (SES) and paclitaxel-eluting stents (PES).
METHODS:
This prospective study included 1481 consecutive ACS patients (72% myocardial infarction, age 65±13 years, 62% male) treated with a drug-eluting stent: (SES, n=925; PES, n=417; EZES, n=139). The primary end point was major adverse cardiac events (MACE) at 2 years, defined as the composite of death, myocardial infarction, and target vessel revascularization. Two-year follow-up was obtained in all patients.
RESULTS:
Baseline clinical and angiographic characteristics were mostly similar. Unadjusted 2-year MACE and death rates were lower in the EZES group than in the SES and PES groups (MACE: 18.7% vs. 25.3% vs. 30.2%, p=0.02; death: 10.1% vs. 16.4% vs. 22.2%, p=0.002, respectively). The rate of definite stent thrombosis at 2 years was lower in the EZES group without statistically significant difference (0.7% vs. 2.9% SES vs. 1.7% PES, p=0.16). After adjusting for differences in baseline characteristics, EZES use was an independent correlate for 2-year MACE (vs. SES, hazard ratio 0.65, p=0.049; vs. PES, hazard ratio 0.57, p=0.01).
CONCLUSION:
In an ACS patient population, a lower long-term MACE rate was observed in patients treated with an EZES when compared to treatment with first-generation drug-eluting stents. The use of EZES in contemporary practice has excellent long-term outcome in terms of low rates of revascularization and clinical events.
Copyright © 2013. Published by Elsevier Inc....(more)
Dvir D, et al. Cardiovasc Revasc Med 2013 May 1.
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- 4. Phase II open-label study of bevacizumab combined with neoadjuvant anthracycline and taxane therapy for locally advanced breast cancer.
BACKGROUND:
Neoadjuvant anthracycline- and taxane-based chemotherapy is frequently administered in breast cancer. Pathological complete response (pCR) rates vary according to clinical disease stage and biology of breast cancer. The critical role of angiogenesis in the progression of breast cancer, together with significantly improved efficacy when bevacizumab is combined with chemotherapy in the metastatic setting, provides a strong rationale for evaluating the integration of bevacizumab into neoadjuvant chemotherapy regimens.
METHODS:
A single-arm, multicentre, phase II, open-label study evaluated four 3-weekly cycles of FEC (5-fluorouracil 600 mg/m<sup>2</sup>, epirubicin 90 mg/m<sup>2</sup> and cyclophosphamide 600 mg/m<sup>2</sup>) followed by 12 cycles of weekly paclitaxel (80 mg/m<sup>2</sup>) in combination with bevacizumab 10 mg/kg every 2 weeks as neoadjuvant therapy for HER2-negative stage III locally advanced or inflammatory breast carcinoma. The primary endpoint was pCR rate.
RESULTS:
Planned treatment was completed in 49 of the 56 enrolled patients. In the intent-to-treat population, the pCR rate was 21% and the clinical response rate was 59%. Breast-conserving surgery was achieved in 34% of patients. In the subgroup of 15 patients with triple-negative disease, the pCR rate was 47%. Grade 3 adverse events in ≥5% of patients were neutropenia, leucopenia, asthenia, and rash. One case each of hypertensive retinopathy and post-operative wound complication, both after treatment completion, were considered probably related to bevacizumab. There were no treatment-related deaths and no cardiac function abnormalities.
CONCLUSIONS:
This study indicates that FEC followed by weekly paclitaxel with bevacizumab is an active neoadjuvant regimen for locally advanced breast cancer, with no major safety concerns.
CLINICAL TRIAL REGISTRATION:
NCT00559845.
Copyright © 2013 Elsevier Ltd. All rights reserved....(more)
Clavarezza M, et al. Breast 2013 Apr 30.
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- 5. Chemoradiation with Paclitaxel and Carboplatin in high-risk cervical cancer patients after radical hysterectomy: a korean gynecologic oncology group study.
PURPOSE:
To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer.
METHODS AND MATERIALS:
Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m(2), carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment.
RESULTS:
This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%.
CONCLUSIONS:
Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Lee TS, et al. Int J Radiat Oncol Biol Phys 2013 Jun 1;86(2):304-10.
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- 6. Vasculitis resulting from a superficial femoral artery angioplasty with a paclitaxel-eluting balloon.
Drug-eluting balloons (DEBs) coated with the antiproliferative agent paclitaxel may improve primary patency by reducing recurrent luminal stenosis. A proportion of the active drug and excipient coating are known to embolize distally, but until now, there have been no reports of adverse events resulting from their use. We report an unusual case of a painful nodular, biopsy specimen-proven vasculitic rash that afflicted the ipsilateral lower limb of a patient after superficial femoral artery treatment with a DEB. This adverse event may have implications for the use of DEB in this and other vascular territories....(more)
Thomas SD, et al. J Vasc Surg 2013 May 1.
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- 7. Enmein-type diterpenoid analogs from natural kaurene-type oridonin: Synthesis and their antitumor biological evaluation.
A series of enmein-type diterpenoid analogs (11-20) derived from natural kaurene-type diterpenoid oridonin were synthesized and biologically evaluated. All target compounds showed improved anti-proliferative activities against four human cancer cell lines compared with natural oridonin and parent compound 10. Some compounds were more potent than positive control Taxol. Furthermore, mechanistic investigation showed that the representative compound 17 affected cell cycle and induced apoptosis at low micro-molar level in human hepatoma Bel-7402 cells, via an oxidative stress triggered mitochondria-related caspase-dependent pathway....(more)
Li D, et al. Eur J Med Chem 2013 Apr 11;64C:215-221.
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- 8. Outcome of patients treated with palliative weekly Paclitaxel plus Cetuximab in recurrent head and neck cancer after failure of platinum-based therapy.
Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55 % was observed, with median response duration of 5.0 months (95 % CI 3.3-11.1). The median PFS was 4.0 months (95 % CI 2.9-5.0) and the median OS time was 10.0 months (95 % CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients....(more)
Sosa AE, et al. Eur Arch Otorhinolaryngol 2013 May 4.
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- 9. A coronary pseudoaneurysm within a restenotic stent treated by implantation of a pericardium-covered stent and drug-eluting balloon.
Coronary pseudoaneurysm after bare-metal stent implantation is a rare event. Observation, surgical resection, or implantation of another stent, bare or covered, are alternative and equivalent management options. Since no option prevails over the other, the most appropriate treatment should be evaluated in every single patient. We report the case of a pseudoaneurysm within a stent with diffuse restenosis, treated with implantation of a pericardium-covered stent, followed by postdilation with a paclitaxel-eluting balloon....(more)
Vaghetti M, et al. J Invasive Cardiol 2013 May;25(5):E93-5.
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- 10. Evaluation of Melphalan, Oxaliplatin, and Paclitaxel in Colon, Liver, and Gastric Cancer Cell Lines in a Short-term Exposure Model of Chemosaturation Therapy by Percutaneous Hepatic Perfusion.
BACKGROUND:
The goal of this study was to determine whether liver, gastric, or colonic cancer may be suitable targets for chemosaturation therapy with percutaneous hepatic perfusion (CS-PHP) and to assess the feasibility of utilizing other cytotoxic agents besides melphalan in the CS-PHP system.
MATERIALS AND METHODS:
Forty human cell lines were screened against three cytotoxic chemotherapeutic agents. Specifically, the dose-dependent effect of melphalan, oxaliplatin, and paclitaxel on proliferation and apoptosis in each cell line was evaluated. These agents were also evaluated for their ability to induce apoptosis in normal primary human hepatocytes. A high-dose short-term drug exposure protocol was employed to simulate conditions encountered during CS-PHP.
RESULTS:
The average concentration of melphalan required for inducing significant apoptosis was 61 μM, or about 3-fold less than the theoretical concentration of 192 μM, achieved in the hepatic artery during CS-PHP dosing with melphalan. Additionally, we found that gastric cancer cell lines were 2-5 fold more sensitive to apoptosis than liver cancer cell lines to all three compounds, suggesting that in addition to colonic and gastric cancer metastases to the liver, primary gastric cancer may also be amenable to management by CS-PHP using an appropriate therapeutic agent. Significantly, at concentrations that are predicted using the CS-PHP system, these agents caused apoptosis of colonic, gastric, and liver cancer cells but were not toxic to primary human hepatocytes.
CONCLUSION:
The compounds tested are potential candidates for use in the CS-PHP system to treat patients with gastric and colonic metastases, and primary cancer of the liver....(more)
Uzgare RP, et al. Anticancer Res 2013 May;33(5):1989-2000.
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- 11. Paeoniflorin, a monoterpene glycoside, attenuates lipopolysaccharide-induced neuronal injury and brain microglial inflammatory response.
Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Paeoniflorin (PF), a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, such as anti-oxidant, anti-inflammatory, and anti-cancer effects. Neuroprotective potential of PF has also been demonstrated in animal models of neuropathologies. Here, we have examined the efficacy of PF in the repression of inflammation-induced neurotoxicity and microglial inflammatory response. In organotypic hippocampal slice cultures, PF significantly blocked lipopolysaccharide (LPS)-induced hippocampal cell death and productions of nitric oxide (NO) and interleukin (IL)-1β. PF also inhibited the LPS-stimulated productions of NO, tumor necrosis factor-α, and IL-1β from primary microglial cells. These results suggest that PF possesses neuroprotective activity by reducing the production of proinflammatory factors from activated microglial cells....(more)
Nam KN, et al. Biotechnol Lett 2013 Apr 5.
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- 12. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis.
Combination use of methotrexate (MTX) and leflunomide (LEF) has been proved effective in the treatment of active rheumatoid arthritis (RA). However, previous trials have documented that both are associated with increased incidence of liver toxicity. As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall, total glucosides of paeony (TGP) have been shown to have anti-inflammatory, hepatoprotective and immuno-regulatory activities, without evident toxicity or side effects. In this 24-week, open label, randomized multicenter clinical trial, we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA. A total of 204 patients with active RA (DAS28>3.2) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy (MTX 10 mg/week plus LEF 20 mg/day) with or without TGP for up to 24 weeks by randomization. Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal (ULN) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Significantly less frequent hepatotoxicity was observed in patients with TGP than those without (9.5% vs 34.8%, p < 0.001) at 12 weeks. The proportion of patients whose ALT or AST levels were > 1.5 to ≤2 times and >2 to ≤3 times the ULN were lower in TGP group than the control (1.9% vs 10.1%, 2.9% vs 12.4%, p < 0.05 respectively). More patients in the TGP group achieved a European League Against Rheumatism (EULAR) good response or moderate response at 12 weeks, although there is no statistical significance. Similar results were observed at 24 weeks. Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA.
Copyright © 2013 Elsevier B.V. All rights reserved....(more)
Chen Z, et al. Int Immunopharmacol 2013 Mar;15(3):474-7.
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- 13. Paeoniflorin acts as a liver X receptor agonist.
Paeoniflorin is one of the active ingredients of Paeonia lactiflora Pall., a novel traditional herbal medicine exerting pharmacological effects including antihyperlipidemic, neuroprotective, and anti-hepatofibrosis effects. Liver X receptor (LXR) acts as a ligand-activated transcription factor to exhibit antihyperlipidemic and neuroprotective effects. In this study, the activity of paeoniflorin against LXR was evaluated by the mammalian one-hybrid and transient transfection reporter assays. The results showed that paeoniflorin transactivated GAL4, rat cholesterol 7 α-hydroxylase, phospholipid transfer protein, and ATP-binding cassette A1 gene promoters in dose-dependent manner. Furthermore, the docking study demonstrated that paeoniflorin resided in the LXR ligand-binding pocket in the similar manner as GSK 3987, a novel LXR agonist. These results indicated that paeoniflorin might exert pharmacological effects through LXR pathway....(more)
Lin HR. J Asian Nat Prod Res 2013;15(1):35-45.
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- 14. Years-identification mathematical model of Paeonia lactiflora Pall. based on the allometric-scaling.
The fixed number years-identification of Chinese material medicinal was a difficulty in the process of the traditional Chinese pharmacology, the phenomenon was found in our study of telomerase that the speed of the vascular cambium outside expanding growth fluctuated in a definite value. Based on it, we put forward a hypothesis that the radial length of the vascular cambium to expand (Δb)and the radius of cross section (Δr) are constant in every activity cycle if the external environment factors unchanged every year. Therefore, We defined that the proportion (k) of Δr and Δb is constant (Δr/Δb = k). Then, each of Δb and Δr fluctuating in a fixed value in every year, because of the different rainfall, temperature, and sunniness every year. The hypothesis was proved correct within the domain of definition range, through the extrapolation of mathematical method. Hence, the telomerase experimental results just become effective evidence on mechanism. The conclusion we obtained include the following three: the telomerase experimental show that the activity gradually decreased in the Paeonia overall taproot, while, the it does not seem significantly change in the parts of the cambium cells with increasing age; Microscopy studies and mathematical models exploration gave us an identification method which can determine the growth years of Chinese medicinal materials (Refers to a kind of herbs exclusive which contains taproot), and, for example, we can use the mathematical model y = 0.02x(-0.5) (P = (0.08)/(k(2)nΔb)-(0.0016)/(Δb(2)n(2)k(2))) to identify the years of the Paeonia lactiflora Pall; the power function of allometric-scaling explored at microscopic cellular-level firstly. Ginseng, for example, more definitive proved a mathematical relationship of the allometric scaling in the taproot of plants.
Copyright © 2012 Wiley Periodicals, Inc....(more)
Cheng C, et al. Microsc Res Tech 2013 Feb;76(2):201-8.
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- 15. Paeoniflorin attenuates lipopolysaccharide-induced permeability of endothelial cells: involvements of F-actin expression and phosphorylations of PI3K/Akt and PKC.
This study aimed to investigate the effects of paeoniflorin, the main active ingredient of the medicinal plant Paeonia lactiflora Pall., on the permeability of endothelial cells induced by lipopolysaccharide (LPS) and the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were stimulated by LPS. Extravasated FITC-dextran reflecting permeability was assessed by multimode microplate reader, and the migration of bis-carboxyethyl-carboxyfluorescein acetoxy-methyl-labeled human acute monocytic leukemia cell line and leukemia cell line cells through HUVECs were analyzed by fluorescence microscopy. The phosphorylations of phosphatidylinositol 3-kinase (PI3K)/Akt, protein kinase C (PKC), and cofilin in HUVECs were assessed by western blotting, and the F-actin level was detected by laser scanning confocal microscopy. After LPS stimulation, inflammatory endothelial cells exhibited significantly increased permeability. Paeoniflorin (10, 30, and 100 μM) inhibited dextran extravasation and leukocyte migration through HUVECs induced by LPS in a concentration-dependent manner. Moreover, paeoniflorin was able to suppress the phosphorylations of PI3K/Akt, PKC, and cofilin, as well as F-actin reorganization in HUVECs induced by LPS. These findings revealed that paeoniflorin partly blocked LPS-induced endothelium permeability, supporting a new explanation for its anti-inflammatory effects....(more)
Xu H, et al. Inflammation 2013 Feb;36(1):216-25.
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- 16. Effects of shade on plant growth and flower quality in the herbaceous peony (Paeonia lactiflora Pall.).
Herbaceous peony (Paeonia lactiflora Pall.) is an important ornamental plant used in urban green spaces, but little is known about whether it can grow in a shaded environment or understory. In this study, effects of shade on plant growth and flower quality in the herbaceous peony were investigated. The results showed that P. lactiflora morphology parameters, including plant height, leaf number, stem diameter, branch number, node number and plant crown width, were higher in plants grown with sun exposure compared to those grown in shade; however, opposite trends were observed for the top and middle leaf areas of the plant. Compared with sun exposure, shade decreased P. lactiflora photosynthetic capacity, light saturation point (LSP) and light compensation point (LCP) and increased the apparent quantum yield (AQY), mainly due to declined stomatal conduction (Gs). These decreases caused the soluble sugar, soluble protein and malondialdehyde (MDA) contents to decline, which led to delayed initial flowering date, prolonged flowering time, reduced flower fresh weight, increased flower diameter and faded flower color. Through cloning and expression analysis of anthocyanin biosynthetic genes, we determined that the fading of flower color was the result of reduced anthocyanin content, which was caused by the combined activity of anthocyanin biosynthesis genes and, in particular, of the upstream phenylalanine ammonialyase gene (PlPAL) and chalcone synthase gene (PlCHS). These results could provide us with a theoretical basis for further application of P. lactiflora in the greening of urban spaces and an understanding of the mechanisms behind the changes induced by shade.
Copyright © 2012 Elsevier Masson SAS. All rights reserved....(more)
Zhao D, et al. Plant Physiol Biochem 2012 Dec;61:187-96.
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- 17. Flower color diversity revealed by differential expression of flavonoid biosynthetic genes and flavonoid accumulation in herbaceous peony (Paeonia lactiflora Pall.).
Herbaceous peony (Paeonia lactiflora Pall.) is an important ornamental plant which contains different flower colors. In this paper, eight genes encoding phenylalanine ammonialyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), UDP-glucose: flavonoid 3-o-glucosyltransferase (UF3GT) were isolated. Moreover, the expression patterns of these eight genes and UF5GT in the flowers were investigated in three cultivars, that is, 'Hongyanzhenghui', 'Yulouhongxing' and 'Huangjinlun' with purplish-red, white and yellow flower respectively. Furthermore, flavonoid accumulation in the flowers was also analyzed. The results showed that in different organs, most of genes expressed higher in flowers than in other organs. During the development of flowers, all genes could be divided into four groups. The first group (PlPAL) was highly expressed in S1 and S4. The second group (PlCHS and PlCHI) was at a high expression level throughout the whole developmental stages. The third group (PlF3H, PlF3'H, PlDFR, PlANS and PlUF5GT) gradually decreased with the development of flowers. The fourth group (PlUF3GT) gradually increased during the flower development. In addition, anthoxanthins and anthocyanins were detected in 'Hongyanzhenghui' and 'Yulouhongxing', chalcones and anthoxanthins were found in 'Huangjinlun'. When different color flowers were concerned, low expression level of PlCHI induced most of the substrate accumulation in the form of chalcones and displaying yellow, changing a small part of substrates to anthoxanthins, and there was no anthocyanin synthesis in 'Huangjinlun' because of low expression level of DFR. In 'Yulouhongxing', massive expressions of upstream genes and low expression of DFR caused synthesis of a great deal of anthoxanthins and a small amount of colorless anthocyanins. In 'Hongyanzhenghui', a large number of colored anthocyanins were changed from anthoxanthins because of PlDFR, PlANS and PlUF3GT high expressions. These results would provide us a theoretical basis to understand the formation of P. lactiflora flower colors....(more)
Zhao D, et al. Mol Biol Rep 2012 Dec;39(12):11263-75.
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- 18. Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys.
Total glucosides of paeony (TGP) is the major active constituent of Paeonia lactiflora Pall., which has shown renoprotection in experimental diabetic nephropathy. Activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage. Macrophages also play an essential role in the pathogenesis of diabetic nephropathy. Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. TGP (50, 100, and 200 mg/kg) was administered orally once a day for eight weeks. Levels of p-JAK2 and p-STAT3 were determined by Western blot analysis. Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. The elevated 24-h urinary albumin excretion rate was markedly attenuated by treatment with 50, 100, and 200 mg/kg TGP. Western blot analysis showed that the significantly increased levels of p-JAK2, p-STAT3 proteins in the kidneys of diabetic rats were significantly inhibited by 50, 100, and 200 mg/kg TGP treatment. The marked accumulation and proliferation of macrophages in diabetic kidneys were significantly inhibited by TGP treatment. ED-1+/p-STAT3+ cells were significantly increased in the kidneys from the model group but were significantly inhibited by TGP treatment. These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action....(more)
Wang K, et al. Am J Chin Med 2012;40(3):521-36.
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- 19. Effects of inflorescence stem structure and cell wall components on the mechanical strength of inflorescence stem in herbaceous peony.
Herbaceous peony (Paeonia lactiflora Pall.) is a traditional famous flower, but its poor inflorescence stem quality seriously constrains the development of the cut flower. Mechanical strength is an important characteristic of stems, which not only affects plant lodging, but also plays an important role in stem bend or break. In this paper, the mechanical strength, morphological indices and microstructure of P. lactiflora development inflorescence stems were measured and observed. The results showed that the mechanical strength of inflorescence stems gradually increased, and that the diameter of inflorescence stem was a direct indicator in estimating mechanical strength. Simultaneously, with the development of inflorescence stem, the number of vascular bundles increased, the vascular bundle was arranged more densely, the sclerenchyma cell wall thickened, and the proportion of vascular bundle and pith also increased. On this basis, cellulose and lignin contents were determined, PlCesA3, PlCesA6 and PlCCoAOMT were isolated and their expression patterns were examined including PlPAL. The results showed that cellulose was not strictly correlated with the mechanical strength of inflorescence stem, and lignin had a significant impact on it. In addition, PlCesA3 and PlCesA6 were not key members in cellulose synthesis of P. lactiflora and their functions were also different, but PlPAL and PlCCoAOMT regulated the lignin synthesis of P. lactiflora. These data indicated that PlPAL and PlCCoAOMT could be applied to improve the mechanical strength of P. lactiflora inflorescence stem in genetic engineering....(more)
Zhao D, et al. Int J Mol Sci 2012;13(4):4993-5009.
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- 20. Effect of calcium sprays on mechanical strength and cell wall fractions of herbaceous peony (paeonia lactiflora pall.) inflorescence stems.
Calcium is an essential element and imparts significant structural rigidity to the plant cell walls, which provide the main mechanical support to the entire plant. In order to increase the mechanical strength of the inflorescence stems of herbaceous peony, the stems are treated with calcium chloride. The results shows that preharvest sprays with 4% (w/v) calcium chloride three times after bud emergence are the best at strengthening "Da Fugui" peonies' stems. Calcium sprays increased the concentrations of endogenous calcium, total pectin content as well as cell wall fractions in herbaceous peonies stems, and significantly increased the contents of them in the top segment. Correlation analysis showed that the breaking force of the top segment of peonies' stems was positively correlated with the ratio of water insoluble pectin to water soluble pectin (R = 0.673) as well as lignin contents (R = 0.926) after calcium applications....(more)
Li C, et al. Int J Mol Sci 2012;13(4):4704-13.
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- 21. Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFβ/Smads and NF-κB pathways.
Cardiac remodeling is a key determinant in the clinical course and outcome of heart failure and characterized by cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis and inflammation. The anti-inflammatory, anti-apoptotic and anti-fibrotic effects of paeoniflorin have been identified in various types of tissue and cells. However, the role of paeoniflorin in cardiac remodeling remains unclear. We performed aortic banding (AB) in mice to induce a cardiac remodeling model in response to pressure overload. Paeoniflorin (20 mg/kg) was administered by daily intraperitoneal (i.p.) injection. Paeoniflorin treatment promoted the survival rate and improved cardiac function of mice at 8 weeks post surgery. AB-induced cardiac hypertrophy, as assessed by heart weight, gross heart, HE and WGA staining, cross-sectional area of cardiomyocyte and mRNA expresssion of hypertrophic makers, was attenuated by paeoniflorin. Paeoniflorin also inhibited collagen deposition, expression of TGFβ, CTGF, collagen Iα and collagen IIIα, and phosphorylation of Smad2 and Smad3 in the heart exposed to pressure overload. Cardiomyocyte apoptosis and induction of Bax and cleaved caspase3 in response to AB were suppressed by paeoniflorin. Furthermore, paeoniflorin decreased the quantity of CD68+ cells, protein levels of TNF-α and IL-1β, and phosphorylation of IκBα and NFκB-p65 in the heart after AB. In conclusion, paeoniflorin attenuated cardiac hypertrophy, fibrosis, apoptosis and inflammation, and improved left ventricular function in pressure overloaded mice. The cardioprotective effect of paeoniflorin is associated with the inhibition of TGFβ/Smads and NF-κB pathways....(more)
Zhou H, et al. J Mol Histol 2013 Feb 17.
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- 22. Pharmacokinetic study of multiple active constituents after oral gavage of Guizhi decoction in rats using a LC-MS/MS method.
Guizhi decoction (GZD) is a classic traditional Chinese medicine formula, clinically used for the treatment of influenza, common cold, and other pyretic conditions. A sensitive, specific, and validated liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed to investigate the pharmacokinetic properties of cinnamic acid, hippuric acid, paeoniflorin, and glycyrrhetic acid in rat. After single dose oral administration of 7.9 g extract/kg body weight GZD in rats, plasma concentrations of cinnamic acid, hippuric acid, paeoniflorin, and glycyrrhetic acid were measured by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data. The values of AUC(0-t), half-life (t (1/2)), and C (max) were 7.2 ± 2.3 μg h/mL, 1.2 ± 0.3 h, and 9.2 ± 5.2 μg/mL for cinnamic acid, 53 ± 31 μg h/mL, 2.8 ± 2.0 h, and 17 ± 3 μg/mL for hippuric acid, 1.1 ± 0.5 μg h/mL, 1.9 ± 1.1 h, and 0.6 ± 0.3 μg/mL for paeoniflorin, and 11 ± 6 μg h/mL, 6.6 ± 2.5 h, and 0.9 ± 0.6 μg/mL for glycyrrhetic acid, respectively. The results would offer useful information for effective components of GZD in vivo....(more)
Chen Y, et al. Eur J Drug Metab Pharmacokinet 2013 Feb 21.
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- 23. Paeoniflorin, a Natural Neuroprotective Agent, Modulates Multiple Anti-Apoptotic and Pro-apoptotic Pathways in Differentiated PC12 Cells.
Numerous studies have shown robust neuroprotective effects of paeoniflorin (PF), a natural compound derived from the herbal medicine Paeony radix. In the present study, we determined associations of PF neuroprotection with its modulation of various apoptotic and anti-apoptotic pathways. PF (50-400 μM) pretreatment significantly improved viability of differentiated PC12 cells exposed to methyl-4-phenylpyridine ion (MPP(+)), a neurotoxin, and inhibited over-release of lactate dehydrogenase, a biomarker of neuronal cell death. PF also ameliorated MPP(+)-induced nuclear and mitochondrial apoptotic alteration and intracellular calcium overload. PF treatment reversed MPP(+) suppression of activity of B cell lymphoma-extra large, which is a mitochondrial membrane molecule that protects cells from DNA damage-induced apoptosis, and strikingly inhibited the enhanced level of cleaved poly(ADP-ribose)polymerase, which is involved in the process of apoptosis. PF alone and coadministration with MPP(+) enhanced phospho activation of extracellular signal-regulated kinases, Akt, and its downstream element glycogen synthase kinase-3, but the effects were completely abolished in the presence of their blockers PD98059 and LY294002. The presence of the blockers also diminished the potency of PF in improving viability of MPP(+)-exposed cells. These results indicate that neuroprotective effects of PF are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways, including blockade of intracellular calcium overload, prevention of mitochondrial membrane integrity, inhibition of pro-apoptotic molecules, and up-regulation of anti-apoptotic proteins associated with cell survival and proliferation. The study provides evidence supporting PF as a potential therapeutic agent used for the treatment of neurodegenerative diseases and neural injury....(more)
Wang D, et al. Cell Mol Neurobiol 2013 May;33(4):521-9.
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- 24. The emerging antineoplastic effects of paeoniflorin.
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- 25. Chemical fingerprinting and quantitative constituent analysis of Siwu decoction categorized formulae by UPLC-QTOF/MS/MS and HPLC-DAD.
BACKGROUND:
Siwu decoction categorized formulae (SWDCF) are widely used for treating gynecological diseases. This study aims to elucidate the differences of bioactive constituents in SWDCF by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC - QTOF - MS /MS) and HPLC-DAD.
METHODS:
An efficient method based on UPLC - QTOF - MS /MS was developed for identifying the chemical profiles of SWDCF. HPLC-DAD method was used for quantifying seven chemical markers in SWDCF.
RESULTS:
Eighty four components were identified or characterized, including ten organic acids, thirty glycosides (monoterpene or iridoid or phenylpropanoids glycosides), fourteen lactones, eighteen flavonoids, and eleven alkaloids in the complex system. The datasets of tR-m/z pairs, ion intensities and sample codes were processed with supervised orthogonal partial least squared discriminant analysis to compare these decoction samples. After a clear classification was established, OPLS-DA was performed and 16 common components with relative quantity in SWDCF samples were determined. Gallic acid, protocatechuic acid, vanillic acid, caffeic acid, paeoniflorin, ferulic acid, and senkyunolide I were selected as the chemical markers to identify SWDCF by HPLC-DAD.
CONCLUSION:
The chemical profiles with 84 components in SWDCF, including monoterpene glycosides, acetophenones, galloyl glucoses, even some isomers in the complex system were characterized by UPLC-QTOF-MS/MS....(more)
Su S, et al. Chin Med 2013 Mar 1;8(1):5.
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- 26. Antidepressant-like effects of paeoniflorin on the behavioural, biochemical, and neurochemical patterns of rats exposed to chronic unpredictable stress.
We have previously demonstrated that the total glycosides of peony exert antidepressant-like effects in animal models. Paeoniflorin is the main active glycoside of peony. The purpose of this study was to evaluate the antidepressant-like effects of paeoniflorin in a rat model of chronic unpredictable stress (CUS) and its active mechanisms. The results showed that CUS-exposed rats exhibited depressive-like behaviour with reduced weight, low motor activity as well as reduced consumption of sucrose, biochemical changes with increased concentrations of corticosterone and adrenocorticotropic hormone and neurochemical changes with reduced monoamine neurotransmitter levels. Paeoniflorin treatment markedly increased sucrose consumption and decreased serum corticosterone and adrenocorticotropic hormone levels in the CUS-treated rats. Furthermore, paeoniflorin treatment significantly attenuated CUS-induced reductions in noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid as well as CUS-induced increases in the ratio between the latter two factors. These results suggest that the modulation of the hypothalamic-pituitary-adrenal axis and up-regulation of serotonergic and noradrenergic systems are important mechanisms underlying the antidepressant-like effects of paeoniflorin in CUS-treated rats....(more)
Qiu FM, et al. Neurosci Lett 2013 Apr 29;541:209-13.
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- 27. Phosphatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon H2O2-induced neural progenitor cell injury.
Promoting neural stem/progenitor cell (NSC/NPC) survival in the pro-apoptotic environment is critical to stem cell replacement for neurodegenerative disease therapy. Paeoniflorin (PF), one of the principal bioactive components in Paeoniae Radix, has been used widely in central nervous system (CNS) diseases treatment and serves as an antioxidant to protect neurons against oxidative stress. The present study investigated the protective effects of PF on NPC injury induced by hydrogen peroxide (H2O2). After challenge with 200μM H2O2 for 2h, loss of cell viability and excessive apoptotic cell death were observed in cultured NPC, PF treatment conferred protective effects against the loss of cellular viability in a concentration-dependent manner. PF pretreatment also inhibited NPC apoptosis induced by H2O2 by reversing the decreased level of Procaspase-3 and balancing Bcl-2 and Bax expression. Furthermore, PF-mediated NPC protection was associated with an increase in phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt-1) phosphorylation in a time- and concentration-dependent manner. Selective inhibition of PI3K using LY294002 abolished PF-mediated phosphorylation of Akt-1 and NPC protection upon oxidative stress. These data suggest that PF-mediated NPC protection on H2O2 injury is reliant on the activation of the PI3K/Akt-1 pathway, giving insight to an essential role of PF in NPC protection....(more)
Wu YM, et al. Neuroscience 2013 Jun 14;240:54-62.
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- 28. Determination of chemical variability of phenolic and monoterpene glycosides in the seeds of Paeonia species using HPLC and profiling analysis.
A rapid, sensitive, and accurate HPLC-DAD method was developed and validated for simultaneous determination of one phenolic glycoside and seven monoterpene glycosides, including 1-O-β-d-(4-hydroxybenzoyl)glucose (1), pyridylpaeoniflorin (2), (8R)-piperitone-4-en-9-O-β-d-glucopyranoside (3), oxypaeoniflorin (4), 6'-O-β-glucopyranosylalbiflorin (5), albiflorin (6), β-gentiobiosylpaeoniflorin (7), and paeoniflorin (8), in 44 batches of peony seeds from nine Paeonia species collected from different areas. Using the optimised method, separations were conducted with a YMC-pack ODS-A column with water/formic acid and methanol as the mobile phase. All eight analytes demonstrated good linearity (r(2)>0.9993). The recoveries, measured at three concentration levels, varied from 98.20% to 103.81%. Six compounds including 1 and 4-8 occur ubiquitously in all the seeds of nine Paeonia species, and compounds 2 and 3 showed undetectable levels or very low content in several samples. The seed samples were classified into several groups, which coincide with the taxonomy of Paeonia at the section level. Peony seed might be a useful resource in developing new herbal or food products....(more)
He C, et al. Food Chem 2013 Jun 15;138(4):2108-14.
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- 29. Qualitative and quantitative analysis of the major constituents in Chinese medicinal preparation Dan-Lou tablet by ultra high performance liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.
A rapid ultra high performance liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry (UPLC-DAD-QTOF) method and a ultra high performance liquid chromatography coupled with diode-array detector (UPLC-DAD) method were developed for qualitative and quantitative analyses of the major chemical constituents in Dan-Lou tablet. Sixty-eight compounds including flavonoids, phenolic acids, tanshinones, protostane triterpenoids, lactones, and paeoniflorins were unambiguously or tentatively identified by comparing their retention times and accurate mass measurement in 40min with references or literature data. Among them, 19 compounds: gallic acid, danshensu, 5-hydroxymethyl-2-furaldehyde, 3'-hydroxy puerarin, puerarin, 3'-methoxy puerarin, mirificin, daidzin, paeoniflorin, calycosin-7-O-β-D-glucoside, naringin, genistin, rosmarinic acid, salvianolic acid B, salvianolic acid A, formononetin, calycosin, cryptotanshinone and tanshinone IIA were further quantified in 30min as marker substances. It was found that the calibration curves for all analytes showed good linearity (R(2)>0.9997) within the test ranges. The overall limits of detection (LODs) and limits of quantification (LOQs) were 0.0073-0.34μg/mL and 0.022-1.04μg/mL, respectively. The relative standard deviations (RSDs) for intra- and inter-day precisions were below 1.90% and 2.85%, respectively. The results of repeatability were less than 2.74%. The sample was stable for at least 48h. The mean recovery rates ranged from 95.5% to 105% with the relative standard deviations (RSDs) less than 2.96%. The results showed that the developed quantitative method was linear, sensitive, and precise for quality control of Dan-Lou tablet....(more)
Dong J, et al. J Pharm Biomed Anal 2013 Jun;80:50-62.
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- 30. Identification of NF-κB Inhibitors in Xuebijing injection for sepsis treatment based on bioactivity-integrated UPLC-Q/TOF.
ETHNOPHARMACOLOGICAL EVIDENCE:
Inflammation plays an important role in sepsis, and NF-κB is a key mediator of inflammation. Xuebijing (XBJ) injection is a traditional Chinese medicine injection that was widely used in the treatment of sepsis in China. However, the active constituents and mechanism responsible for its actions have not been investigated experimentally.
AIM OF THE STUDY:
To screen the anti-inflammatory components in XBJ injection and investigate the modulation of NF-κB in the treatment of sepsis.
MATERIALS AND METHODS:
In this study, the effect of XBJ was assessed in the cecal ligation and puncture (CLP) -induced sepsis model. Subsequently, a bioactivity-integrated ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF) assay system was established for screening potential anti-inflammatory ingredients in XBJ. Ultimately, six active ingredients were confirmed through an in vitro test.
RESULTS:
XBJ significantly reduced the mortality rate, anal temperature and expression of TNF-α, IL-1β and IL-6 induced by CLP. Nine potential anti-inflammatory ingredients, including gallic acid, danshensu, protocatechualdehyde, hydroxysafflor yellow A, oxypaeoniflorin, paeoniflorin, safflor yellow A, senkyunolide I and benzoylpaeoniflorin, were found based on the bioactivity-integrated UPLC-Q/TOF assay system. Among these compounds, the NF-κB inhibitor activity of senkyunolide I, safflor yellow A, oxypaeoniflorin, and benzoylpaeoniflorin are first reported here.
CONCLUSIONS:
XBJ showed significant efficacy in the treatment of sepsis induced by CLP. Multiple targets of the different components were related to these anti-inflammatory effects, which contributed to the treatment of sepsis by XBJ in a clinical setting.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved....(more)
Jiang M, et al. J Ethnopharmacol 2013 May 20;147(2):426-33.
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- 31. The joint action of destruxins and botanical insecticides (rotenone, azadirachtin and paeonolum) against the cotton aphid, Aphis gossypii Glover.
The joint action of destruxins and three botanical insecticides, rotenone (Rot), azadirachtin (Aza) and paeonolum (Pae) against the cotton aphid, Aphis gossypii, was bioassayed. In laboratory experiment, several synergistic groups of destruxins with botanical insecticides were found by means of Sun's Co-toxicity Coefficients (CTC) and Finney's Synergistic Coefficient (SC). The best synergistic effect was discovered in the ratio group Des/Rot 1/9 with the CTC or SC and LC values of 479.93 or 4.8 and 0.06 μg/mL, respectively. The second and third synergistic effects were recorded in the ratio groups Des/Rot 7/3 and 9/1. Although the ratio groups Des/Aza 6/4, Des/Pae 4/6, 3/7 and 2/8 indicated synergism by Sun's CTC, they were determined as additive actions by Finney's SC. Additive actions were also found in most of the ratio groups, but antagonism were recorded only in three ratio groups: Des/Pae 9/1, 7/3 and 6/4. In greenhouse tests, the highest mortality was 98.9% with the treatment Des/Rot 1/9 at 0.60 μg/mL, meanwhile, the treatments Des/Pae 4/6 and Des/Aza 6/4 had approximately 88% mortality....(more)
Yi F, et al. Molecules 2012 Jun 18;17(6):7533-42.
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- 32. [Simultaneous determination of four active compounds in tiangou capsules by HPLC].
OBJECTIVE:
To establish a method for quantitative analysis of gastrodin, baicalin, paeonolum and pinoresinol diglucoside in Tiangou capsules by HPLC.
METHOD:
The separation was performed on SinoChrom ODS-BP column (4.6 mm x 150 mm, 5 microm). The mobile phase consisted of acetonitrile and 0.2% phosphoric acid aqueous solution with gradient elution program. The flow rate was 1.0 ml x min(-1) and the column temperature was 30 degrees C. UV detection wavelength was set at 230 nm.
RESULT:
The linear ranges of gastrodin, baicalin, paeonolum and pinoresinol diglucoside were 0.1168-1.1680, 0.1142-1.1420, 0.0512-0.5120, 0.0556-0.5560 microg, respectively. The average recoveries of gastrodin, baicalin, paeonolum and pinoresinol diglucoside were 100.3% (RSD 0.53%), 99.96% (RSD 1.15%), 99.90% (RSD 1.17%), 99.97% (RSD 1.62%), respectively.
CONCLUSION:
The method is accurate, simple, feasible and reliable, and is available for the quality control of Tiangou capsules....(more)
Wang X, et al. Zhongguo Zhong Yao Za Zhi 2011 Apr;36(7):868-70. Chinese.
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- 33. Safety evaluation of main alkaloids from Rhizoma Coptidis.
ETHNOPHARMACOLOGICAL RELEVANCE:
Rhizoma Coptidis (RC), a widely used traditional Chinese medicine, has been used for the treatment of heat-clearing and detoxifying, but there is very little information on its safety.
AIM OF THE STUDY:
To provide information on the safety of RC, we evaluated the toxicity of the crude RC and RC alkaloids (berberine, coptisine, palmatine and epiberberine) including cytotoxicity, acute toxicity in mice and sub-chronic toxicity in rats.
MATERIALS AND METHODS:
The cytotoxicity of RC alkaloids was tested in HepG2 and 3T3-L1 cells by the MTT assay. The acute toxicity of RC alkaloids was tested in mice and the mortality was calculated at the end of experiment. For sub-chronic toxicity study, the rats were treated with the RC alkaloids at a dose of 156 mg/kg/day and RC at a dose of 521 mg/kg/day for 90 days. Mortality, clinical signs, body weight changes, organ weights, urinalysis and hematological parameters, gross necropsy and histopathology were monitored during the study period.
RESULTS:
The cell assay indicates that the IC(50) values of berberine, coptisine, palmatine and epiberberine in HepG2 cells were 48.17, 64.81, 112.80 and 120.58 μg/mL, which in 3T3-L1 cells were 41.76, 56.48, 84.32 and 104.18 μg/mL, respectively. In the acute toxicity assay, the LD(50) values of four alkaloids were 713.57, 852.12, 1533.68 and 1360 mg/kg, respectively. However, in the sub-chronic toxicity study, no mortality and morbidity were observed which could be related to RC alkaloids and RC treatment. Besides, there was no abnormality in clinical signs, body weights, organ weights, urinalysis, hematological parameters, gross necropsy and histopathology in any of the animals after the oral administration of RC alkaloids and RC.
CONCLUSIONS:
Taking these results together, we came to the conclusion that the toxicity of berberine is the maximum and palmatine is the minimal in four RC alkaloids. The currently recommended doses of RC alkaloids and RC consumed are relatively safe.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved....(more)
Yi J, et al. J Ethnopharmacol 2013 Jan 9;145(1):303-10.
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- 34. Preparation of micropipette tip-based molecularly imprinted monolith for selective micro-solid phase extraction of berberine in plasma and urine samples.
A novel berberine-imprinted polymer (MIP) monolith was prepared for extraction of berberine in aqueous medium. The MIP monolith was prepared inside a polypropylene micropipette tip by using dimethylsulfoxide as porogen, acrylamide (AA) as functional monomer and ethyleneglyol dimethacrylate (EGDMA) as cross-linker. Polymerization conditions were optimized and good permeability and selectivity was obtained when the ratio of berberine/AA/EGDMA was 1:5:30. Cross-reaction was also studied by three compounds (palmatine, coptisine, and jatrorrhizine) with similar structure. A molecularly imprinted micro solid-phase extraction (MI-μ-SPE) method was developed for selective extraction of berberine in aqueous solutions. Extraction parameters were investigated, such as sample pH value, sample flow rate, sample volume and elution solvent. By combining with HPLC/UV, MI-μ-SPE method showed a good linear range of 3-800 ng/mL with a low limit of detection limit of 1.0 ng/mL. The method was also applied for the pretreatment of berberine in human plasma and urine samples. The result showed that proteins and other biological matrix were successfully eliminated and berberine was selectively enriched. Recoveries were tested in plasma and urine samples, and calculated to be 90.6-103.2% with relative standard deviations less than 4.7%....(more)
Zhang W, et al. Talanta 2013 Jan 15;103:103-9.
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- 35. Anti-diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut-4 in L6 myotubes.
Tinospora cordifolia is a well reported plant possessing numerous medicinal values including anti-diabetic property. Aim of the present study is to study the mechanism of action of Tinospora cordifolia and its active compound in differentiated myocytes, L6 cells. Key marker of diabetes in cells is the insulin dependent glucose transporter-4 (Glut-4) which also responds to exogenous chemicals, and is over expressed up to 5- and 4-fold, by Tinospora cordifolia and palmatine, respectively. Next to Glut-4, the predominant protein influencing glucose metabolism is PPARα and γ whose expressions were also positively modulated. Further, the inhibitors of insulin pathway prevented glucose uptake mediated by Tinospora cordifolia and palmatine which shows that the activity is majorly mediated through insulin pathway....(more)
Sangeetha MK, et al. Phytomedicine 2013 Feb 15;20(3-4):246-8.
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