Anti-hemorrhoidal activity of Lian-Zhi-San, a traditional Chinese medicine, in an experimental hemorrhoidal model in rats.

OBJECTIVE: Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats. METHODS: HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations. RESULTS: In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1ß, interleukin-6 and tumor necrosis factor-α). CONCLUSION: This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.

Zhujie Hewei Granules Ameliorated Reflux Esophagitis in Rats.

BACKGROUND: Gastroesophageal reflux disease (GERDs) is a common chronic digestive system disease, in which the symptoms of reflux esophagitis (RE) seriously affect the quality of life. AIMS: We aimed to study the therapeutic effect of Zhujie Hewei granules (ZHG) on reflux esophagitis in model rats. MATERIALS AND METHODS: A rat model of RE was established with the steps of half pylorus ligation, cardiotomy, and hydrochloric acid perfusion. The rats in treatment groups were orally administered with 1.30, 2.60, or 5.20 g/kg ZHG once daily for 28 days. Histopathological changes of the esophagus were observed with hematoxylin-eosin staining. The content of total bilirubin and pH in gastric juice was determined. Esophageal mucosal injury was assessed by macroscopic observation scores, mucosal injury index scores, and esophageal inflammation scores. The levels of gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP) in serum were evaluated by using ELISA kits. RESULTS: After treatment with ZHG, the body weight of RE rats tended to increase drastically, the macroscopic observation scores of the esophagus mucous membrane decreased (P < 0.05), the mucosal injury index scores decreased (P < 0.05), the gastric pH values increased (P < 0.05), and the levels of serum MTL and VIP decreased (P < 0.05). In addition, the high dose of the ZHG-treated group showed lower serum GAS (P < 0.05), while the high and middle doses of the ZHG-treated groups showed lower esophageal inflammation scores (P < 0.05). CONCLUSIONS: ZHG was effective in treating RE in rats due using mechanisms including improving the pH value of gastric contents, decreasing the gastrointestinal hormones (including GAS, MTL, and VIP), and improving the inflammatory damage.

Progress in Experimental and Clinical Research of the Diabetic Retinopathy Treatment Using Traditional Chinese Medicine.

Diabetic retinopathy (DR), one of the most common microvascular complications of diabetic mellitus, is currently the main cause of adult-acquired blindness. The pathogenesis of DR is complex and the current clinical application of various treatment methods cannot completely prevent the development of this disease. Many reports have been published regarding the treatment of DR with Traditional Chinese Medicine (TCM), which has received increasing attention from medical practitioners worldwide. Studies published between 1994 and April 2017 were collected from the CNKI, VIP, Medline and Web of Science databases, as well as from Chinese traditional books and Chinese Pharmacopoeia, subsequently obtaining more than 550 studies. Thereafter, the status quo of DR treatment using TCM had been summarized according to four aspects - compound formula therapy, Chinese herbal medicine extracts and monomer therapy, integrated traditional Chinese and Western medicine therapy, and Chinese medicine external treatment. According to the literature reviewed herein, TCM has had definite effects on the prevention and treatment of DR, especially when used in combination with modern medical methods. However, the lack of a unified standard on the syndrome differentiation of DR and the lack of support of evidence-based medicine theory in clinical practice have been consistent concerns in previous research studies and needs to be addressed in subsequent studies.

[Evaluation criteria for rat skin anaphylactoid test].

This study is to explore characteristic indexes in evaluation criteria for rat skin anaphylactoid test comparing skin blue spot OD values at the treated position and the control position in the same animal. Common contrast agents, traditional Chinese medicine injections and injections' active pharmaceutical ingredients or excipients in the existing clinical anaphylactoid reaction reports were taken as test drugs in the rat skin anaphylactoid test to define the K value: K > 2 represents positive anaphylactoid reaction, 1.2 ≤ K ≤ 2 represent doubtable anaphylactoid; K < 1.2 represents negative anaphylactoid reaction, which were taken as the criteria for evaluating anaphylactoid of tested drugs. The evaluation result and that for classic criteria were compared to study the applicability of K value. According to the comparison, K value, as the evaluation criteria in the rat skin anaphylactoid test, can more truly reflect the actual situation of skin aizen and minimize the error caused by animal individual factors. Compared with positive and negative two-level criteria for blue spot diameter, K value's positive, doubtable and negative three-level criteria are more objective and accurate. Therefore, K value can be used as the evaluation criteria in the rat skin anaphylactoid test.

A review of experimental research on herbal compounds in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease worldwide, leading to progressive muscle atrophy and paralysis. The limited success of conventional treatment for ALS has prompted investigations into complementary and alternative therapies. Herbal remedies provide good prospects of ALS prevention and treatment, with advantages such as multiple targets, multiple links, and few side effects. Studies in vitro and in vivo have shown that herbs have a great potential for treatment of ALS, with therapeutic effects against oxidative stress, excitatory amino acid toxicity, neuroinflammation, and calcium cytotoxicity. Active monomers or ingredients extracted from herbs are considered promising candidates for ALS. Therefore, we review recent experimental research on monomers and compounds isolated from herbal remedies for preventing and treating ALS.

[Application of factor analysis to evaluate deformation behaviors of frequently-used tablet excipients].

The present work is to investigate the correlation between physical properties and deformation behaviors of tablet excipients, and rank them according to their plastic performances during compaction. The excipients selected were compacted using Korsch XP1 after measuring their physical properties where the compression parameters for evaluating deformation behaviors were Heckle equation, compression work and elastic stretch in die. The correlations between compaction descriptors and physical parameters were analyzed by canonical correlation analysis, and factor analysis was simultaneously employed to synthetically assess deformation behaviors for all our samples. The canonical variables show that true density (Pa) correlated negatively with plastic coefficient (PL) and positively with yield pressure (YP); compression degree (Cp) correlated negatively with fast elastic stretch (FES) as well as YP and positively with PL. When factor scores were used in combination with original data, the plasticity of our samples was sorted and ranked as high (-0.56 < F' < 0.21), intermediate (-0.16 < F' < 0.36), or low (0.38 < F' < 0.84), which are in accord with plasticity rankings previously reported in literature. This study indicates factor analysis can be an approach to evaluate deformation behaviors of pharmaceutical powders.

[Multiple mechanisms of depression].

Depression is a grievous mental disease with an increasing high morbidity year by year and a serious social harm. The pathogenesises of depression is complicated and involves with multi-mechanisms and multi-organs. Recent studies demondtrate that in the nerval system and endocrine system there are many types of neurotransmitters and hormones, as well as their receptors, involved in depression. This paper reviews the research progress of depression in recent years.

[Comparative study on mathematical set-based drug release kinetics method and Kalman filter method applied in evaluating drug release of multi-component traditional Chinese medicine preparations].

OBJECTIVE: To provide a mathematical set-based method for evaluating drug release kinetics of multi-component traditional Chinese medicine preparations. METHOD: With Fuzheng Huayu prescription as the study model, a mathematical set-based method for evaluating drug release kinetics was established to guide the preparation of drug release system of Fuzheng Huayu prescription, and a quantitative evaluation was made for its multi-component drug release characteristics. Its accuracy was verified by Kalman filtering method. RESULT: The comparison between the two showed that the sample No. 4 of Fuzheng Huayu drug release system showed synchronized drug release with its reference preparation Fuzheng Huayu capsules. CONCLUSION: The results verified the accuracy and rationality of the evaluation method based on mathematics set. Meanwhile, it displayed the release of target preparations according to asynchronous coefficient (k) and other parameters, and found the orientation of regulating and improving the unit drug release dosage from relevant error parameters of various characteristic peak information, in order to purposefully regulate relevant components, and enable target preparations to meet the synchronized drug release requirements of the reference preparation. Meanwhile, it provided an effective measure for evaluating the quantitative characterization and synchronized release behavior of multi-component traditional Chinese medicines.

[Determination of rhynchophylline and isorhynchophylline in Uncaria rhynchophylla by HPLC].

OBJECTIVE: To explore an HPLC method for determination of rhnchophylline and isorhnchophylline in Uncaria rhnchophylla. METHOD: An HPLC method has been developed for determination of rhnchophylline and isorhnchophylline. The transformation of rhnchophylline and isorhnchophylline after heating was also studied by HPLC-ESI-MS. RESULT: Good linearities of rhynchophylline and isorhynchophylline were 0.064-5.100, 0.064-5.110 mg, respectively. The average recoveries were from 87.51% to 88.83% for rhynchophylline and from 107.9% to 113.9% for isorhynchophylline. The recoveries of rhynchophylline and isorhnchophylline reference solutions after extraction were 12.60% and 40.00% in the reflux extraction procedure, respectively. While in the ultrasonic extraction procedure, the average recoveries of rhynchophylline and isorhynchophylline was from 99.48% to 103.2% and from 97.00% to 99.59%, resepectively. The recoveries of rhynchophylline and isorhnchophylline reference solutions after extraction were 47.08% and 51.03%, respectively. The unqualified recovery could be elucidated by HPLC-ESI-MS analysis, indicating that trhynchophylline could be transformed mostly into isorhynchophylline and a little amount of unkown composition, while isorhynchophylline could be transformed into rhynchophylline isocorynoxeine, corynoxeine and 22-O-beta-D-glucopyranosyl isocorynoxeinic acid during the extraction procedure. CONCLUSION: Ultrasonic extraction procedure was more sutble for HPLC determination of the content of rhynchophylline and isorhynchophylline in U. rhnchophylla, however, the recovery problems should be paid attention to when it comes to the determination.

[Discrimination of traditional Chinese medicinal materials with different tastes based on electronic tongue].

OBJECTIVE: To investigate the use of the electronic tongue in the evaluation of traditional Chinese medicinal materials with sour, bitter, sweet or salty tastes, and assess the possible application of the sensor in the evaluation of different tastes of traditional Chinese medicinal materials. METHOD: Aqueous extracts of 22 traditional Chinese medicinal materials were measured by the electronic tongue. The data collected with the tongue was evaluated for discrimination of the samples with multivariate statistical methods: principal component analysis (PCA) and discriminant factor analysis (DFA). RESULT: The electronic tongue was capable of discriminating between samples with different taste modalities and could also distinguish different samples eliciting the same basic taste. Twenty-two traditional Chinese medicinal materials could be classified into five clusters based on PCA. These differences seem to derive from the different tastes. DFA was applied to construct a model to discriminate traditional Chinese medicinal materials with different tastes. And the samples yielded about 88.2% accuracy for cross-validation. CONCLUSION: We confirmed that the electronic tongue may provide an analytical procedure for classification of the samples with respect to tastes of the traditional Chinese medicinal materials.

Two new compounds from Hicriopteris glauca and their potential antitumor activities.

Chemical examination of the EtOAc extract from the stems of Hicriopteris glauca (Thunb) Ching. led to the isolation of two new compounds: lunularic acid 4'-glucoside and 2,9-dihydroxy-4,7-megastigmadiene-3-O-ß-glucoside. Their structures were elucidated on the basis of spectral analysis and by comparing their spectral data with those in literature. Two compounds, along with the petroleum ether, chloroform, EtOAc, and n-BuOH extracts, were tested for cytotoxic activities. Only the n-BuOH extract showed antitumor activity against human melanoma A375 cells with IC50 values of 0.80 µg/ml.

MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action. AIM OF STUDY: In this study, we examined the effects of a water-soluble ß-d-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model. MATERIALS AND METHODS: MDG-1 was extracted from the tube root of O. japonicus and purified as described previously (Xu et al., 2005). The KKAy mice were gavaged once daily with either distilled water, MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined. RESULTS: MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3-kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3ß expression. CONCLUSIONS: These data indicate that MDG-1 has remarkable anti-diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM.

[Influence of combination on the specific chromatogram of Glycyrrhiza in sini decoctions by HPLC].

The paper is to report the establishment of an HPLC specific chromatogram of Glycyrrhiza in Sini decoctions and the influence of combination on the specific chromatogram. The RP-HPLC method was used with a Phenomenex Gemini C18 column (250 mm x 4.6 mm ID, 5 microm), and acetonitrile-0.05% trifluoroacetic acid (gradient elution) as mobile phase. Flow rate was 0.8 mL x min(-1) and the detection wavelength was set at 232 nm. The temperature of column was 30 degrees C. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions. Twenty peaks were selected as specific peaks in Sini Decoction with liquiritin peak as the reference peak. Six of them were from Glycyrrhiza and the other 6 peaks were from both Glycyrrhiza and Ganjiangfuzi Decoction. The areas of specific peaks of Sini Decoctions were smaller than those in the chromatogram of Glycyrrhiza. The specific chromatogram of Glycyrrhiza in Sini Decoctions is markedly influenced by Radix Aconiti Carmichaeli and Rhizoma Zingiberis. The areas of the specific peaks in Sini Decoctions were reduced obviously. The method is stable and reliable with a good reproducibility, it can be used to determine the specific chromatogram of Glycyrrhiza in Sini Decoctions.

[Multivariate analysis of relationships between material properties and hygroscopicity of Chinese medicine raw materials].

Material properties and hygroscopicity were determined. Principal component analysis and partial least squares regression were applied to evaluate relationships between material properties and hygroscopicity of Chinese medicine raw materials. The results showed that hygroscopicity was correlated with water content, particle size distribution, water soluble characteristic and cohesion. Balanced moisture content was positively correlated with water content, particle size distribution, water soluble characteristic and cohesion. Moisture absorption velocity was negatively correlated with particle size distribution, protruding degree and positively correlated with water soluble characteristic and cohesion. Moisture absorption acceleration was positively correlated with water content, particle size distribution and negatively correlated with water soluble characteristic and cohesion. Hygroscopicity of Chinese medicine raw materials is interpreted in terms of physics.

Pharmacokinetics, tissue distribution and metabolism of senkyunolide I, a major bioactive component in Ligusticum chuanxiong Hort. (Umbelliferae).

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort. (Umbelliferae) is widely prescribed for treatment of cardiovascular diseases in China for centuries. One of the major bioactive components in L. chuanxiong is senkyunolide I (SEI), which shows pharmacological activities in anti-migraine and anti-oxidative damage. MATERIALS AND METHODS: The aim of this study was to investigate in vivo pharmacokinetics, tissue distribution and metabolism of SEI in rats. The concentrations of SEI in plasma and tissues were determined by a high performance liquid chromatography (HPLC) method, and the pharmacokinetic parameters were calculated using and non-compartmental analysis. The metabolites were identified using high performance liquid chromatography tandem mass (HPLC-ESI-MS/MS) method. RESULTS: After oral and intravenous administration, SEI was quickly eliminated from plasma and its oral bioavailability (BA) was about 37.25%, which was smaller than intraportal BA (81.17%), but similar to intraduodenal BA (36.91%), suggesting that gastric first-pass effect of SEI is negligible, and hepatic first-pass effect was approximately 18.83%. After oral administration, SEI could penetrate blood brain barrier and extensively distribute in tested tissues, with the descending order of AUC being kidney, liver, lung, muscle, brain, heart, thymus, and spleen in rat. The parent compound and nine metabolites were found and identified in rat bile after oral administration of SEI (36 mg/kg). The metabolic mechanism of SEI in rat mainly involves methylation, glucuronidation and glutathione conjugation during the phase II biotransformation pathway in rats. CONCLUSIONS: The information gained here may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.

Characterization using LC/MS of the absorption compounds and metabolites in rat plasma after oral administration of a single or mixed decoction of Shaoyao and Gancao.

Shaoyao-Gancao decoction (SGD), a traditional Chinese formulation containing Paeoniae Radix (SY) and Glycyrrhizae Radix (GC), is commonly used to relieve abdominal pain. However, the absorption and metabolites of the characteristic constituents of the two herbs in vivo have been reported rarely. The purpose of this study was to investigate the compatibility rationality and the mechanism of the enhanced efficiency of SGD. A single or a mixed decoction (SG and S+G, respectively) was orally administered to rats. Blood samples were collected at different intervals following treatment and analyzed by liquid LC/MS. A total of fifteen ingredients (denoted as M1 to M15) were found in both rat plasma after treatment with the two decoctions. Furthermore, the proposed structures of the remained twelve ingredients were obtained except M9, M10 and M15. The quality of the ingredients in the rat plasma showed no significant difference between the two decoctions. However, the quantity of twelve ingredients differed greatly, indicating that the absorption of SG was greater than that of S+G except M7, M12 and M15. As the compositions associated with the efficacy of SG and S+G were inconsistent, the degree of the absorption of the 15 ingredients by the gastrointestinal tract were different, which caused a significantly enhanced efficacy of certain ingredients. This study presents an exploration of the mechanism behind the improved efficacy of individual components in traditional Chinese medicine therapies through combination with other components.

Pharmacokinetics of characteristic effective ingredients from individual and combination Shaoyao and Gancao treatment in rats using HPLC fingerprinting.

Shaoyao-Gancao decoction, a traditional Chinese formulation composed of Paeoniae Radix and Glycyrrhizae Radix, is commonly used to relieve abdominal pain. In this paper, the compatibility rationality of this decoction was investigated. Shaoyao-Gancao decoction, Shaoyao decoction and Gancao decoction were orally administered to rats, respectively. Blood samples were collected at pre-determined times after administration and analyzed by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters of characteristic peaks were analyzed and the statistical significance of the obtained parameters was determined. Paeoniflorin (12.0 min) and compounds at retention times of 4.7 and 5.2 min were all significantly higher in the Shaoyao-Gancao decoction than in the Shaoyao decoction (P < 0.05). In contrast, in the Gancao decoction, the compound at a retention time of 14.6 min was significantly lower than in the Shaoyao-Gancao decoction (P < 0.01). However, the compounds at retention times of 17.1 and 18.1 min were significantly higher in the Gancao decoction than in the Shaoyao-Gancao decoction (P < 0.05). These results indicate that poor compatibility of the compounds in the Shaoyao-Gancao decoction could result in poor absorption. The compatibility of the component compounds of the Shaoyao-Gancao decoction was revealed in the pharmacokinetic characteristics of the decoction. Generally, the absorption of Shaoyao components was increased in the Shaoyao-Gancao decoction, while the absorption of Gancao components was time dependent. In the Shaoyao-Gancao decoction, the increased absorption of some Shaoyao components may be related to a reduction in absorption of some Gancao components.

A polysaccharides MDG-1 augments survival in the ischemic heart by inducing S1P release and S1P1 expression.

Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed the anti-ischemic properties of a water-soluble ß-D-fructan (MDG-1) from O. japonicus. The sphingosine 1-phosphate (S1P) signaling pathway is involved in its cytoprotective effects. Herein, we explore the role of the S1P signaling pathway in the anti-ischemic effect of MDG-1 and assess one possible mechanism by which it induces S1P release and sphingosine 1-phosphate receptor 1 (S1P(1)) expression in human microvascular endothelial cells (HMEC-1) and cardiomyocytes. Our evidence demonstrates that MDG-1 promotes sphingosine kinase (SPHK) activity in HMEC-1 cells. An analytical method for measuring the mass of S1P using ESI/MS/MS was developed and we found that MDG-1 increases intracellular S1P levels. Meanwhile, MDG-1 is protective during hypoxia and ischemia through mechanisms that require S1P(1) receptor activation, which was confirmed both in oxygen glucose deprivation (OGD) and coronary artery ligation models by using transfection of cloned human S1P(1) receptor and RNA interference. These data indicate that the increase of intracellular S1P generation, particularly by activation of the SPHK enzyme, coupled with the autocrine and paracrine stimulation of cell surface S1P receptors, is a potential mechanism in the anti-ischemic and cell protective effect of MDG-1.

Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by PEGylation.

BACKGROUND: Radix ophiopogonis polysaccharide (ROP) has been found to be effective against myocardial ischemia. One of main problems with its use is its short in-vivo half-life, which makes the development of an effective delivery system necessary. To achieve better therapeutic effects and patient compliance by prolonging its retention in plasma and increasing its distribution in targets, ROP was PEGylated (PEG, polyethylene glycol) in this study. METHODS: Through a moderate coupling reaction between hydroxyl-activated ROP and amino-terminated methoxy-PEG (mPEG) (30 or 40 kDa), together with a greater than 1 molar ratio of ROP to mPEG in reaction, long-circulating and potentially bioactive PEGylated ROPs, with PEG grafting number of ~1.0, were prepared, characterized, and the pharmacokinetics evaluated. RESULTS: Relative to ROP, whose half-life was approximately 0.7 hours, the two conjugates prepared, following intravenous administration, showed markedly prolonged retention in systemic circulation with half-lives in blood of 78.4 and 88.3 hours, respectively. When given subcutaneously, their in-vivo mean residence times were further markedly prolonged by the slow absorption phase. They were found to be well absorbed after subcutaneous administration, with absolute bioavailability being 75.4% and 43.9%, respectively. CONCLUSION: With apparent molecular masses not exceeding 43 kDa, the conjugates prepared have been and will be demonstrated to have prominent advantages for ROP delivery, such as: the good absorption following subcutaneous, intramuscular, or other ways of administration; the effective utilization of the enhanced permeability and retention effect caused by ischemia; and the rapid diffusion within target tissues.

Comparison of tissue distribution of a PEGylated Radix Ophiopogonis polysaccharide in mice with normal and ischemic myocardium.

PEGylation was found to be a promising approach to improve the anti-myocardial ischemic activity of Radix Ophiopogonis polysaccharide (ROP) by prolonging its retention in plasma. To fully evaluate the effectiveness and safety of this strategy, the tissue distribution of PEGylated ROP was investigated in this study. A long-circulating and bioactive PEGylated ROP with 1.04 mol 20-kDa mPEG per mol ROP ((1.04)P(20k)-R) was prepared by a moderate coupling reaction between the hydroxyl-activated ROP and the amino-terminated mPEG. Its tissue distribution in mice with normal and ischemic myocardium was studied and compared with ROP. The results show that the descending order of tissue distribution of (1.04)P(20k)-R ranked by AUC was kidney, lung, heart, liver, and brain in normal mice and kidney ≈ lung ≈ heart, liver and brain in mice with myocardial ischemia. With the exception of the heart, myocardial ischemia did not cause obvious changes in the distribution of (1.04)P(20k)-R in the other tissues studied. Owing to the enhanced permeability and retention effect caused by ischemia, the AUC of (1.04)P(20k)-R in ischemic hearts was approximately 1.6-fold greater than in normal hearts. Compared with ROP in rats, the distribution tendency of (1.04)P(20k)-R in mouse kidney, brain, and lung was reduced by approximately 42, 1.6, and 1.3 times, respectively, whereas it was increased by approximately 1.3-fold in the liver. The results of this study are highly instructive for the further pharmaceutical development of PEGylated ROP.