Research progress on the treatment of diabetic nephropathy with leech and its active ingredients.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.

Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS.

Systemic iron overload is a common clinical challenge leading to significantly serious complications in patients with acute myeloid leukemia (AML), which affects both the quality of life and the overall survival of patients. Symptoms can be relieved after iron chelation therapy in clinical practice. However, the roles and mechanisms of iron overload on the initiation and progression of leukemia remain elusive. Here we studied the correlation between iron overload and AML clinical outcome, and further explored the role and pathophysiologic mechanism of iron overload in AML by using two mouse models: an iron overload MLL-AF9-induced AML mouse model and a nude xenograft mouse model. Patients with AML had an increased ferritin level, particularly in the myelomonocytic (M4) or monocytic (M5) subtypes. High level of iron expression correlated with a worsened prognosis in AML patients and a shortened survival time in AML mice. Furthermore, iron overload increased the tumor load in the bone marrow (BM) and extramedullary tissues by promoting the proliferation of leukemia cells through the upregulation of FOS. Collectively, our findings provide new insights into the roles of iron overload in AML. Additionally, this study may provide a potential therapeutic target to improve the outcome of AML patients and a rationale for the prospective evaluation of iron chelation therapy in AML.

The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer.

Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.

Icaritin Promotes Myelination by Simultaneously Enhancing the Proliferation and Differentiation of Oligodendrocyte Precursor Cells.

Myelin repair, which is known as remyelination, is critical to the treatment of neurodegenerative diseases, and myelination depends on not only the differentiation of oligodendrocyte precursor cells toward oligodendrocytes but also the renewal of oligodendrocyte precursor cells under pathological conditions. However, simultaneously promoting the differentiation and proliferation of oligodendrocyte precursor cells in lesions remains an unmet challenge and might affect demyelinating diseases. Kidney-tonifying herbs of traditional Chinese medicine (TCM) are effective in improving the symptoms of degenerative patients. However, herbs or compounds with dual functions are unverified. The purpose of this study was to find a kidney-tonifying TCM that synchronously improved the differentiation and proliferation of oligodendrocyte precursor cells under pathological conditions. Compounds with dual functions were screened from highly frequently used kidney-tonifying TCM, and the effects of the obtained compound on remyelination were investigated in an in vitro oligodendrocyte precursor cell differentiation model under pathological conditions and in demyelinating mice in vivo. The compound icaritin, which is an active component of Yin-Yang-Huo (the leaves of Epimedium brevicornu Maxim), demonstrated multiple effects on the remyelination process, including enhancing oligodendrocyte precursor cell proliferation, facilitating the differentiation of neural progenitor cells toward oligodendrocyte precursor cells and further toward oligodendrocytes, and maturation of oligodendrocytes under corticosterone- or glutamate-induced pathological conditions. Importantly, icaritin effectively rescued behavioral functions and increased the formation of myelin in a cuprizone-induced demyelination mouse model. The multiple effects of icaritin make it a promising lead compound for remyelination therapy.

Pinellia genus: A systematic review of active ingredients, pharmacological effects and action mechanism, toxicological evaluation, and multi-omics application.

The dried tuber of Pinellia ternata (Thunb.) Breit, Pinelliae Rhizoma (PR, also named 'Banxia' in Chinese), is widely used in traditional medicine. This review aims to provide detail summary of active ingredients, pharmacological effects, toxic ingredients, detoxification strategies, and omic researches, etc. Pharmacological ingredients from PR are mainly classified into six categories: alkaloids, amino acids, polysaccharides, phenylpropanoids, essential oils, and glucocerebrosides. Diversity of chemical composition determines the broad-spectrum efficacy and gives a foundation for the comprehensive utilization of P. ternata germplasm resources. The pharmacological compounds are involved in inhibition of cancer cells by targeting various pathways, including activation of immune system, inhibition of proliferation and cycle, induction of apoptosis, and inhibition of angiogenesis. The pharmacological components of PR act on nervous system by targeting neurotransmitters, activating immune system, decreasing apoptosis, and increasing redox system. Lectins, one major class of the toxic ingredients extracted from raw PR, possess significant toxic effects on human cells. Inflammatory factors, cytochrome P450 proteins (CYP) family enzymes, mammalian target of rapamycin (mTOR) signaling factors, transforming growth factor-ß (TGF-ß) signaling factors, and nervous system, are considered to be the target sites of lectins. Recently, omic analysis is widely applied in Pinellia genus studies. Plastome genome-based molecular markers are deeply used for identifying and resolving phylogeny of Pinellia genus plants. Various omic works revealed and functional identified a series of environmental stress responsive factors and active component biosynthesis-related genes. Our review summarizes the recent progress in active and toxic ingredient evaluation, pharmacological effects, detoxification strategies, and functional gene identification and accelerates efficient utilization of this traditional herb.

Effects of SLCO1B1 on elimination and toxicities of high-dose methotrexate in pediatric acute lymphoblastic leukemia.

Aim: To evaluate the association between SLCO1B1 polymorphisms and elimination/toxicities of high-dose methotrexate (MTX). Methods: SLCO1B1 rs11045879 and rs4149056 polymorphisms were retrospectively genotyped in 301 children with newly diagnosed acute lymphoblastic leukemia. MTX concentration, doses of leucovorin rescue and toxicities were recorded. Results: SLCO1B1 rs11045879C carriers (CC + CT) had higher plasma MTX levels at 96 hr, and longer MTX elimination time. The number of leucovorin rescue doses in rs4149056C carriers (CC + CT) was more than those in TT ones. Moreover, SLCO1B1 polymorphisms were associated with HDMTX toxicities including thrombocytopenia, renal toxicity and anal mucositis, but not associated with MTX level at other time points or delayed elimination. Conclusions: Our data demonstrate that genotyping of SLCO1B1 might be useful to optimize MTX therapy.

Integrating Enhanced Profiling and Chemometrics to Unveil the Potential Markers for Differentiating among the Leaves of Panax ginseng, P. quinquefolius, and P. notoginseng by Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry.

The leaves of Panax species (e.g., Panax ginseng-PGL, P. quinquefolius-PQL, and P. notoginseng-PNL) can serve as a source for healthcare products. Comprehensive characterization and unveiling of the metabolomic difference among PGL, PQL, and PNL are critical to ensure their correct use. For this purpose, enhanced profiling and chemometrics were integrated to probe into the ginsenoside markers for PGL/PQL/PNL by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS). A hybrid scan approach (HDMSE-HDDDA) was established achieving the dimension-enhanced metabolic profiling, with 342 saponins identified or tentatively characterized from PGL/PQL/PNL. Multivariate statistical analysis (33 batches of leaf samples) could unveil 42 marker saponins, and the characteristic ginsenosides diagnostic for differentiating among PGL/PQL/PNL were primarily established. Compared with the single DDA or DIA, the HDMSE-HDDDA hybrid scan approach could balance between the metabolome coverage and spectral reliability, leading to high-definition MS spectra and the additional collision-cross section (CCS) useful to differentiate isomers.

Multi-level fingerprinting and cardiomyocyte protection evaluation for comparing polysaccharides from six Panax herbal medicines.

The role of polysaccharides in quality control of ginseng is underestimated. Large-scale comparison on the polysaccharides of Panax ginseng (PG), P. quinquefolius (PQ), P. notoginseng (PN), Red ginseng (RG), P. japonicus (ZJS), and P. japonicus var. major (ZZS), was performed by both chemical and biological approaches. Holistic fingerprinting at polysaccharide and the hydrolyzed oligosaccharide and monosaccharide levels utilized various chromatography methods, while OGD and OGD/R models on H9c2 cells were introduced to evaluate the protective effects on cell viability and mitochondrial function. Polysaccharides from six ginseng species exhibited remarkable content difference (RG > PG/ZZS/ZJS/PQ > PN), but weak differentiations in molecular weight distribution and oligosaccharide profiles, while Glc and GalA were richer for monosaccharide compositions of PG and RG polysaccharides, respectively. RG polysaccharides (25/50/100 µg/mL) showed significant cardiomyocyte protection by regulating mitochondrial functions. These new evidences may provide support for the supplementary role of polysaccharides in quality control of ginseng.

Efficacy and safety of Qi and Blood Tonic Chinese Medicines in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) is a sudden public event affecting all human beings, with the rapid transmission, extensive groups affected, many complications, and high mortality. Traditional Chinese Medicine has a long history of preventing and treating infectious diseases, and numerous studies have shown that Traditional Chinese Medicine, especially herbal medicine, has a positive effect on the prevention, treatment, and post-healing recovery of this COVID-19, and herbal medicines to supplement qi and blood often occupy a certain proportion of it. However, there is no relevant meta-analysis to date. Therefore, this study aims to evaluate the efficacy and safety of qi and blood tonic herbal medicines in the treatment of COVID-19 through Systematic Review and meta-analysis to provide a reference basis for widespread clinical application. METHODS: We will search from the following databases for the period from the time of database construction to March 1st, 2023. The English databases include: PubMed, MEDLINE, EMBASE, Cochrane library, WOS, Google Scholar, and CENTRAL; The Chinese databases include: China National Knowledge Infrastructure, China Biomedical Literature Database, Technology Journal Database, and Wanfang. Randomized controlled trials in English or Chinese that include Chinese herbal medicines for tonifying Qi and Blood in the treatment of patients with COVID-19 will be included. Data were independently screened and collected by 2 investigators. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.3 software was used for the meta-analysis of the data. Primary outcome indicators included cure, mortality, and exacerbation rates (change in disease severity category, patient admission to ICU, etc.). Secondary outcome indicators included recovery rate or duration of major symptoms (e.g., fever, cough, fatigue, and weakness, etc.), rate or duration of nucleic acid conversion for severe acute respiratory syndrome coronavirus-2, improvement or recovery of chest CT performance, length of hospital stay, and other adverse events. RESULTS: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P guidelines to ensure clarity and completeness of reporting in all phases of the systematic review. CONCLUSION: This study will provide evidence regarding the efficacy and safety of Qi and Blood Tonic Chinese Medicines for the treatment of COVID-19. PROSPERO REGISTRATION NUMBER: CRD42022361822 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361822).

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking.

OBJECTIVE: To investigate the mechanism of action of Datura metel in the treatment of sinus bradycardia based on network pharmacology and molecular docking. METHODS: The active ingredients and targets of Datura metel were collected by TCMSP database, and the Cytoscape software was used to map to show the interrelationship. Use 5 databases: GeneCards, PharmGKB, OMIM, DisGeNET, and Drugbank to obtain targets related to sinus bradycardia; establish a protein-to-protein interaction network with the help of the STRING platform; GO and Kyoto Encyclopedia of Genes and Genomes analysis of the selected core targets using the Metascape platform; Finally, the AutoDock platform was used for molecular docking and the results were displayed through Pymol. RESULTS: 27 kinds of active ingredients of the drug were screened, including 10 kinds of main ingredients; 198 drug targets and 1059 disease targets. There are 54 targets of action in the treatment of sinus bradycardia, of which 19 targets such as AKT1, IL6, TNF, and VEGFA are the core targets of Datura metel in the treatment of sinus bradycardia. Kyoto Encyclopedia of Genes and Genomes obtained 18 results suggesting that AGE-RAGE, hepatitis C, relaxin, and JAK-STAT may be key signaling pathways. Molecular docking shows that most components of the drug have good docking ability with the core target, indicating that the prediction results have certain reliability. CONCLUSION: This study preliminarily explores the potential active ingredients and possible mechanisms of action of Datura metel in the treatment of sinus bradycardia and provides a basis for in-depth investigation of its medicinal material basis and mechanism of action.

Size-Transformable Hyaluronan Stacked Self-Assembling Peptide Nanoparticles for Improved Transcellular Tumor Penetration and Photo-Chemo Combination Therapy.

Size-transformable nanomedicine has the potential to overcome systemic and local barriers, leading to efficient accumulation and penetration throughout the tumor tissue. However, the design of this type of nanomedicine was seldom based on active targeting and intracellular size transformation. Here, we report an intracellular size-transformable nanosystem, in which small and positively charged nanoparticles (<30 nm) prepared from the self-assembly of an amphiphilic hexadecapeptide derivative was coated by folic acid- and dopamine-decorated hyaluronan (HA) to form large and negatively charged nanoparticles (∼130 nm). This nanosystem has been proven to improve the blood circulation half-life of the drug and prevent premature intravascular drug leakage from the nanocarrier. Once accumulated in the tumor, the nanoparticles were prone to HA- and folic acid-mediated cellular uptake, followed by intracellular size transformation and discharge of transformed small nanoparticles. The size-transformable nanosystem facilitated the transcytosis-mediated tumor penetration and improved the internalization of nanoparticles by cells and the intracellular release of 7-ethyl-10 hydroxycamptothecin. With an indocyanine green derivative as the intrinsic component of the amphiphilic polymer, the nanosystem has exhibited additional theranostic functions: photoacoustic imaging, NIR-laser-induced drug release, and synergistic chemotherapy and phototherapy, leading to a 50% complete cure rate in a subcutaneous B16 melanoma model. This nanosystem with multimodalities and efficient tumor penetration has shown potentials in improving anticancer efficacy.

Effects of Ganoderma, Rhodiola and grape seed extracts on the glucuronidation and oral bioavailability of resveratrol in rats.

Herb extracts were shown to inhibit the activity of UDP-glucuronosyltransferases (UGTs) in vitro. However, the actual in vivo effect of the inhibitory ability on oral bioavailability is yet verified. In this study, resveratrol (RES) was used as a model drug to study the effect of three Chinese herb extracts, Ganoderma, Rhodiola and grape seed, on the in vitro and in vivo inhibition of glucuronidation and the in vivo bioavailability of RES. Overall, although herb extracts might show inhibition on glucuronidation of RES in vitro and in vivo, the inhibition of glucuronidation did not necessarily mean to improve the in vivo bioavailability of RES.

Chiral ß-HgS quantum dots: Aqueous synthesis, optical properties and cytocompatibility.

ß-HgS quantum dots (QDs) have drawn enormous attention due to the size-tunable bandgap and the lowest quantum state in conduction band which have been applied to semiconductor transistor and photodetector. Though ß-HgS is the essential component of Tibetan medicine, the potential toxicity of ß-HgS limits its applications, especially in bio-application. Herein, chiral biomolecule enantiomers N-isobutyryl-L(D)-cysteine (L(D)-NIBC) and L(D)-cysteine (L(D)-Cys) were introduced into HgCl2 and Na2S aqueous solution to synthesize chiral ß-HgS QDs in one-pot, which significantly improved their water-solubility and cytocompatibility. Notably, all chiral ß-HgS QDs showed none cytotoxicity even at high concentration (20 mg·L-1), and the cytocompatibility of D-ß-HgS QDs was better than corresponding L-ß-HgS QDs at the concentration of 20 mg·L-1. This cytotoxicity discrimination was associated with the chirality inversion of chiral ß-HgS QDs compared with the corresponding chiral ligands. In-situ real-time circular dichroism (CD) monitoring indicated that the chirality of ß-HgS QDs originated from the asymmetrical arrangement of chiral ligands on the achiral core surface. Their chiroptical activity, near-infrared optical absorption (800 nm), fluorescence emission (900-1000 nm), high-performance photothermal conversion and good cytocompatibility, implied chiral ß-HgS QDs could be used as a candidate material for photothermal therapy or a near-infrared fluorescent probe in organism, which brings a novel insight for bio-application of ß-HgS QDs.

Identification of Confusable Herbal Medicines by Mapping of Partial Degradation Products from Herbal Medicine Polysaccharides.

Partial degradation products (PDPs) of herbal medicine (HM) polysaccharides with precolumn derivatization using 1-phenyl-3-methy-5-pyrazolone (PMP) were mapped by high performance liquid chromatography (HPLC), and three groups of confusable HMs were differentiated using the PDP fingerprints assisted with cluster analysis (CA). Three variables of HPLC mobile phase, i.e. acetonitrile proportion, buffer concentration and pH value were optimized with PDP of ß-cyclodextrin. Radix Glehniae and Radix Adenophorae; Radix Sophorae Tokinensis and Rhizoma Menispermi; Radix Achyranthis Bidentatae and Radix Cyathulae were successfully distinguished by the method, respectively. The results involving mass spectrometry analysis showed that these PDPs primarily included oligosaccharides and a few monosaccharides. The method can be used as an effective approach for the identification and quality control of HMs, and can also facilitate the in-depth study of biological activity and further development of HM polysaccharides to some extent.

A polysaccharide from Eclipta prostrata alleviates experimental autoimmune encephalomyelitis through inhibiting Th17 cells.

Eclipta prostrata has long been used as a medicinal herb in China. EAP20-1, a homogeneous polysaccharide with anti-complementary activity had been obtained from E. prostrate by using anion-exchange and size-exclusion chromatography. In this study, we found that EAP20-1 could inhibit in vitro lymphocyte proliferation stimulated by concanavalin-A or anti-CD3/anti-CD28 antibodies. Furthermore, in experimental autoimmune encephalomyelitis (EAE) mice, EAP20-1 treatment relieved the clinical symptoms, accompanied by reduced neuroinflammation and demyelination in spinal cords. Mechanistically, EAP20-1 reduced the mRNA expression of interleukin (IL)-17, IL-22, and RAR-related orphan receptor gamma t (RORγt) in the spleen; inhibited auto-reactive T cell proliferation and decreased the percentage of Th17 cells in response to myelin oligodendrocyte glycoprotein (MOG35-55) ex vivo. Moreover, EAP20-1 directly inhibited naïve CD4 + T cells differentiate into Th17 cells in vitro. These results indicating EAP20-1 could benefit EAE through inhibiting Th17 cell differentiation and suggesting a therapeutic potential of EAP20-1 in MS.

Preparation, Characterization and Pharmacokinetics Evaluation of the Compound Capsules of Ibuprofen Enteric-Coated Sustained-Release Pellets and Codeine Phosphate Immediate-Release Pellets.

The objective of this study was to prepare ibuprofen enteric-coated sustained-release pellets (IB-SRPs) and codeine phosphate immediate-release pellets (CP-IRPs) to play a synergistic role in analgesia. The pellets were developed by extrusion-spheronization and fluidized bed coating technology. The single-factor investigation was used to determine the optimal prescription and process. The sustained-release membrane of IB-SRPs was water-insoluble ethyl cellulose (EC), triethyl citrate (TEC) was used as plasticizer, and hydroxypropyl methylcellulose (HPMCP) was chose as porogen. Besides, the immediate-release layer of CP-IRPs was gastric-soluble coating film. The ibuprofen and codeine phosphate compound capsules (IB-CP SRCs) were prepared by IB-SRPs and CP-IRPs packed together in capsules with the optimum doses of 200 and 13 mg, respectively. The prepared pellets were evaluated by scanning electron microscopy and dissolution test. Pharmacokinetic studies in beagle dogs indicated that the optimized IB-CP SRCs had smaller individual differences and better reproducibility comparing with commercial available tablets. Additionally, IB-CP SRCs achieved consistency with in vivo and in vitro tests. Therefore, IB-CP SRCs could play a great role in rapid and long-term analgesic.

Effects of phenolic constituents of daylily flowers on corticosterone- and glutamate-treated PC12 cells.

BACKGROUND: Daylily flowers, the flower and bud parts of Hemerocallis citrina or H. fulva, are well known as Wang-You-Cao in Chinese, meaning forget-one's sadness plant. However, the major types of active constituents responsible for the neurological effects remain unclear. This study was to examine the protective effects of hydroalcoholic extract and fractions and to identify the active fractions. METHODS: The extract of daylily flowers was separated with AB-8 resin into different fractions containing non-phenolic compounds, phenolic acid derivatives and flavonoids as determined using UPLC-DAD chromatograms. The neuroprotective activity was measured by evaluating the cell viability and lactate dehydrogenase release using PC12 cell damage models induced by corticosterone and glutamate. The neurological mechanisms were explored by determining their effect on the levels of dopamine (DA), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), noradrenaline (NE) and acetylcholine (ACh) in the cell culture medium measured using an LC-MS/MS method. RESULTS: Pretreatment of PC12 cells with the extract and phenolic fractions of daylily flowers at concentrations ranging from 0.63 to 5 mg raw material/mL significantly reversed corticosterone- and glutamate-induced neurotoxicity in a dose-dependent manner. The fractions containing phenolic acid derivatives (0.59% w/w in the flowers) and/or flavonoids (0.60% w/w) exerted similar dose-dependent neuroprotective effect whereas the fractions with non-phenolic compounds exhibited no activity. The presence of phenolic acid derivatives in the corticosterone- and glutamate-treated PC12 cells elevated the DA level in the cell culture medium whereas flavonoids resulted in increased ACH and 5-HT levels. CONCLUSION: Phenolic acid derivatives and flavonoids were likely the active constituents of daylily flowers and they conferred a similar extent of neuroprotection, but affected the release of neurotransmitters in a different manner.

Cytochromes P450 Inhibitory Excipient-Based Self-Microemulsions for the Improved Bioavailability of Protopanaxatriol and Protopanaxadiol: Preparation and Evaluation.

Protopanaxatriol and protopanaxadiol exhibit limited oral bioavailability due to the poor solubility and intestinal cytochromes P450-mediated metabolism. This study set out to develop a novel cytochromes P450 inhibitory excipient(s)-based self-microemulsion to encapsulate protopanaxatriol and protopanaxadiol so as to enhance the in vivo bioavailability by inhibiting intestinal metabolism. After screening the inhibitory effect of pharmaceutical excipients on the cytochromes P450-mediated metabolism, two self-microemulsions, SME-1 and SME-2, with similar physicochemical properties were prepared by using either active inhibitory excipients or corresponding inactive excipients. The results showed that no significant difference existed in the profiles of in vitro release, cellular uptake, and permeability in Caco-2 cells, and in vivo lymphatic transport between self-microemulsion-1 and self-microemulsion-2. The in vivo pharmacokinetic experiments indicated that self-microemulsion-1 conferred to significantly higher absolute bioavailability of protopanaxatriol (19.55 %) and protopanaxadiol (100.07 %) than those of the free drug (2.21 % and 23.70 %, respectively) or of self-microemulsion-2 (4.95 % and 45.35 %, respectively). The present work demonstrated that the presence of cytochromes P450 inhibitory excipients in self-microemulsion-1 tended to inhibit intestinal cytochromes P450-mediated metabolism and subsequently improved the oral bioavailability of protopanaxatriol and protopanaxadiol.

Optimized hydrolysis and analysis of Radix Asparagi polysaccharide monosaccharide composition by capillary zone electrophoresis.

Using orthogonal design, optimized conditions for the hydrolysis of the polysaccharide from Radix Asparagi were determined, as well as its monosaccharide composition. Optimized hydrolysis conditions were a temperature of 100°C in 1.5 M sulfuric acid solution for 5 h. The resulting monosaccharides were derivatized with 1-phenyl-3-methyl-5-pyrazolone, then separated by capillary zone electrophoresis in 40 mM sodium tetraborate buffer (pH 10.1), and detected by ultraviolet absorption at 245 nm. Results indicate that the polysaccharide from Radix Asparagi is composed of xylose, arabinose, glucose, rhamnose, mannose, galactose, glucuronic acid, and galacturonic acid, which differs from published findings. Moreover, xylose, glucuronic acid, and galacturonic acid have not been previously reported in Radix Asparagi polysaccharide. This method is simple, fast, and yields a highly efficient separation. As well, these findings can be applied to quality control of Radix Asparagi and for in-depth study of the biological activity of Radix Asparagi polysaccharide.

Pulmonary delivered polymeric micelles--pharmacokinetic evaluation and biodistribution studies.

Polymeric micelles represent interesting delivery systems for pulmonary sustained release. However, little is known about their in vivo release and translocation profile after delivery to the lungs. In the present study, curcumin acetate (CA), which is an ester prodrug of curcumin, or the mixture of CA and Nile red was encapsulated into PEG­PLGA micelles by a solvent evaporation method. The micellar formulation increased the stability of CA in water and physiologically relevant fluids and led to a sustained drug release in vitro. Following intratracheal (IT) administration to rats, CA loaded micelles achieved not only prolonged pulmonary retention with AUC values almost 400-fold higher than by IV route, but also local sustained release up to 24 h. In addition, IT delivery of micelles appeared to facilitate the uptake into the pulmonary vascular endothelium and efficiently translocate across the air­blood barrier and penetrate into the brain. Co-localization of CA and Nile red confirmed that micelles in lung and brain tissue were still intact. This study is the first to demonstrate that aerosolized PEG­PLGA micelles are a promising carrier for both pulmonary and non-invasive systemic sustained release of labile drugs.