[Effect of Naotaifang on microglial polarization and glial scar following cerebral ischemia reperfusion injury].

This study aims to investigate the effect of Naotaifang(NTF) on the proteins associated with microglial polarization and glial scar in the rat model of cerebral ischemia reperfusion injury(CIRI). The CIRI model was established by middle cerebral artery occlusion/reperfusion. The 48 successfully modeled rats were randomized into model 7 d, model 14 d, NTF 7 d, and NTF 14 d groups(n=12). In addition, 12 SD rats were selected as the sham group. The NTF group was administrated with NTF suspension at 27 g·kg~(-1)·d~(-1) by gavage, and the sham, model 7 d, and model 14 d groups were administrated with the same volume of normal saline every day by gavage for 7 and 14 days, respectively. After the intervention, Longa score was evaluated. The infarct volume was measured by 2,3,5-triphenyl-2H-tetrazolium chloride(TTC) staining. Morris water maze and open field tests were carried out to evaluate the spatial learning, memory, cognitive function, and anxiety degree of rats. Hematoxylin-eosin(HE) staining was employed to observe the morphological structure and damage of the brain tissue. The immunofluorescence assay was employed to measure the expression of glial fibrillary acidic protein(GFAP) and glial scar. Western blot was employed to determine the protein levels of GFAP, neurocan, phosphacan, CD206, arginase-1(Arg-1), interleukin(IL)-1ß, IL-6, and IL-4. Compared with the sham, model 7 d and model 14 d groups showed cerebral infarction of different degrees, severe pathological injury of cerebral cortex and hippocampus, neurological impairment, reduced spatial learning and memory, cognitive dysfunction, severe anxiety, astrocyte hyperplasia, thickening penumbra glial scar, and up-regulated protein levels of IL-1ß, IL-6, GFAP, neurocan, phosphacan, CD206, and Arg-1(P<0.01). Compared with the model group, NTF 7 d and NTF 14 d groups improved spatial learning, memory, and cognitive function, reduced anxiety, improved nerve function, reduced cerebral infarction volume, reduced astrocyte hyperplasia, thinned penumbra glial scar, down-regulated the protein levels of GFAP, neurocan, phosphacan, IL-6, and IL-1ß, and up-regulated the protein levels of IL-4, CD206, and Arg-1(P<0.05 or P<0.01). NTF exerts a neuroprotective effect on CIRI by inducing the M2 polarization of microglia, inhibiting inflammatory response, and reducing the formation of glial scar.

Anti-cervical cancer effects of Compound Yangshe granule through the PI3K/AKT pathway based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Yangshe granule is a characteristic Chinese preparation against cervical cancer used at Fudan University Shanghai Cancer Center, and it consists of Hedyotis Diffusae Herba, Solani Lyrati Herba, Rubiae Radix et Rhizoma, Echinopsis Radix, Angelicae Sinensis Radix, Codonopsis Radix and Atractylodis Macrocephalae Rhizoma. AIM OF THE STUDY: The objective of the current study was to investigate the preclinical efficacy of compound Yangshe granule against cervical cancer and elucidate the underlying mechanisms. MATERIALS AND METHODS: Antitumor effect of the preparation was investigated in U14 cells in vitro and subcutaneous xenograft mice in vivo. The underlying mechanisms were investigated by through network pharmacological analysis and identified by in vitro study. The components of compound Yangshe granule were collected from the Traditional Chinese Medicine Systems Pharmacology database, and the corresponding targets were predicted by the SwissTargetPrediction database. The targets involved in cervical cancer were collected from the GeneCards, Online Mendelian Inheritance in Man and DrugBank databases. A protein‒protein interaction network was constructed by using the String platform. The drug-disease-target network was plotted by Cytoscape software. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed to investigate hub targets. RESULTS: After treatment with 0.5-10 mg/mL compound Yangshe granule, the survival rates of U14 cells gradually declined to 53.32% for 24 h, 23.62% for 48 h, and 12.81% for 72 h. The apoptosis rates of U14 cells gradually increased to 15.52% for 24 h, 23.87% for 48 h, and 65.01% for 72 h after treatment with 2-10 mg/mL compound Yangshe granule. After oral administration of compound Yangshe granule by xenograft mice, the tumor inhibition rates reached 52.27%, 74.62%, and 82.70% in the low, middle, and high dose groups, respectively. According to the network pharmacological analysis, quercetin, luteolin and naringenin were the most bioactive ingredients of the preparation. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that compound Yangshe granule may combat cervical cancer through the PI3K/AKT pathway. CONCLUSION: In summary, network pharmacology combined with biological experiments demonstrated that the main bioactive components including quercetin, luteolin and naringenin could inhibit the tumor growth by regulating the PI3K/AKT pathway and Bcl-2 family. Thus, compound Yangshe granule may be a promising adjuvant therapy for cervical cancer.

[Role of SIRTs in cerebral ischemia reperfusion injury and targeted intervention of Chinese medicine].

Cerebral ischemia-reperfusion injury(CIRI) is a complex cascade process and seriously hinders the recovery of patients with acute ischemic stroke, which has become an urgent public health issue to be addressed. Silent information regulators(SIRTs) are a family of nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, capable of deacylating the histone and non-histone lysine groups. Accumulating evidence has demonstrated that SIRTs are able to regulate the pathological processes such as oxidative stress, inflammatory response, mitochondrial dysfunction, and programmed cell death of CIRI through post-translational deacetylation, and exert the neuroprotection function. In this study, we reviewed the papers about the role and regulatory mechanisms of SIRTs in the pathological process of CIRI published in the past decade. Further, we summarized the research advance in the prevention and treatment of CIRI with Chinese medicine targeting SIRTs and the related signaling pathways. This review will provide new targets and theoretical support for the clinical application of Chinese medicine in treating CIRI during the occurrence of ischemic stroke.

[Research advances in prevention and treatment of cerebral ischemia-reperfusion injury by targeting mitochondrial quality control].

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.

An Integrated Transcriptomics and Lipidomics Analysis Reveals That Ergosterol Is Required for Host Defense Against Bacterial Infection in Drosophila.

Animals adjust their lipid metabolism states in response to pathogens infection. However, the underlying molecular mechanisms for how lipid metabolism responds to infection remain to be elusive. In this study, we assessed the temporal changes of lipid metabolism profiles during infection by an integrated transcriptomics and lipidomics analysis. Ergosterol is identified to be required for proper host defense to pathogens. Notably, ergosterol level is increased in the hemolymph upon bacterial infection. We show that the increase of ergosterol level by food supplement or genetic depletion of Acsl, a long-chain fatty acid-CoA synthetase, promotes host survival against bacterial challenges. Together, our results suggest a critical role of lipid metabolism adaption in the process of host defense against invading pathogens.

Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in vitro Experiments.

AIM AND OBJECTIVE: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. MATERIALS AND METHODS: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. RESULTS: Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 µmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). CONCLUSION: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

[Advance in mechanisms of glial scarring after stroke and intervention of traditional Chinese medicine].

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.

Orally Deliverable Dual-Targeted Pellets for the Synergistic Treatment of Ulcerative Colitis.

PURPOSE: The effective treatment of ulcerative colitis (UC) poses substantial challenges, and the aetiopathogenesis of UC is closely related to infectious, immunological and environmental factors. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract. METHODS: Berberine (BBR) and Atractylodes macrocephala Koidz (AM) volatile oil, derived from the Chinese herbs Coptis chinensis Franch and Atractylodes macrocephala Koidz, have anti-inflammatory and immunomodulatory activities. In this study, we prepared colon-targeted pellets loaded with BBR and stomach-targeted pellets loaded with AM volatile oil for the synergistic treatment of UC. The Box-Behnken design and ß-cyclodextrin inclusion technique were used to optimize the enteric coating formula and prepare volatile oil inclusion compounds. RESULTS: The two types of pellets were spherical and had satisfactory physical properties. The pharmacokinetic results showed that the AUC and MRT values of the dual-targeted (DPs) pellets were higher than those of the control pellets. In addition, in vivo animal imaging confirmed that the DPs could effectively deliver BBR to the colon. Moreover, compared with sulfasalazine and monotherapy, DPs exerted a more significant anti-inflammatory effect by inhibiting the expression of inflammatory factors including IL-1ß, IL-4, IL-6, TNF-α and MPO both in serum and tissues and enhancing immunity by decreasing the production of IgA and IgG. CONCLUSION: The DPs play a synergistic anti-UC effect by exerting systemic and local anti-inflammatory and provide an effective oral targeted preparation for the treatment of UC.

Hybrid Membrane-Coated Biomimetic Nanoparticles (HM@BNPs): A Multifunctional Nanomaterial for Biomedical Applications.

The application of nanoparticles in the diagnosis and treatment of diseases has undergone different developmental stages, but phagocytosis and nonspecific distribution have been the main factors restricting the transformation of nanobased drugs into clinical practice. In the past decade, the design of membrane-coated nanoparticles has gained increasing attention. It is hoped that the combination of the cell membrane's natural biological properties and the functional integration of synthetic nanoparticle systems can compensate for the shortage of traditional nanoparticles. The membrane coating gives the nanoparticles unique biological functions such as immune evasion and targeting capability. However, when the encapsulation of monotypic membranes does not meet the diverse demands of biomedicine, the combination of different cell membranes may offer more possibilities. In this review, the composition, preparation, and advantages of biomimetic nanoparticles coated with hybrid cell membranes are summarized, and the applications of hybrid membrane-coated biomimetic nanoparticles (HM@BNPs) in drug delivery, phototherapy, liquid biopsy, tumor vaccines, immune therapy, and detoxification are reviewed. Finally, the current challenges and opportunities with regard to HM@BNPs are discussed.

Exploring the effect of Gupi Xiaoji Prescription on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments.

AIM AND OBJECTIVE: To study the effect of Gupi Xiaoji Prescription (GXP) on hepatitis B virus(HBV)-related liver cancer through network pharmacology coupled with in vitro experiments and explore their related mechanisms. MATERIALS AND METHODS: Gupi Xiaoji Prescription's chemical constituents and the action targets of its six medicinal components were identified using several databases. These included the Traditional Chinese Medicine Systems Pharmacology Database （TCMSP), the Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM), and the Traditional Chinese Medicine Integrated Database (TCMID), while GeneCards and OMIM were used to compile relevant liver cancer disease targets. Pathway enrichment of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), analysis of potential targets, and analysis of the enriched pathways in literature were executed in R. The Hepatocellular carcinoma (HCC)-derived HepG2.2.15 cell line stably expresses and replicates HBV. In vitro experiments with HepG2.2.15 were used to verify GXP's effects on HBV-related liver cancer, while the human liver cancer cell line HepG2 was used as the control. RESULTS: 171 active ingredients and 259 potential drug targets were screened from GXP, involving 181 pathways in vitro. These assays identified Polyphyllin I as an effective GXP component. Notably, GXP inhibited cell proliferation and metastasis in a concentration-dependent manner (P < 0.01). In comparison with the vehicle group, the fluorescence intensity of each drug group was significantly weakened (P < 0.01), while the drug group Mitofusins 1(MFN1) and protein expression level of Mitofusins 2 (MFN2) increased significantly. The protein expression level of Mitochondrial fission protein 1 (FIS1) and Optic Atrophy 1 (OPA1) also showed significant decreases (P < 0.01). Molecular docking revealed Fructus saponins I's high affinity with FIS1, MFN1, MFN2, and OPA1. CONCLUSION: The network pharmacology results indicate that Gupi Xiaoji Prescription may treat liver cancer by regulating mitochondrial division and fusion of key genes to disrupt liver cancer cells' energy metabolism. In vitro experiments also verified that GXP could inhibit the proliferation and migration of HepG2.2.15 cells by up-regulating MFN1 and MFN2, down-regulating the expression of FIS1 and OPA1 in addition to damaging mitochondria. Consistent with network pharmacology and molecular docking results, Polyphyllin I may be the most active compound of the formula's components. It also shows that Traditional Chinese medicine (TCM) plays a significant, targeted role in the treatment of HBV-related liver cancer.

Effects of light irradiation on essential oil biosynthesis in the medicinal plant Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim) Kitag.

Asarum heterotropoides Fr. var. mandshuricum (Maxim) Kitag (Chinese wild ginger) is an important medicinal herb. Essential oil extracted from its roots is the key ingredient and is mainly composed of phenylpropanoid compounds. As a skiophyte plant, light is a crucial factor for A. heterotropoides var. mandshuricum growth and metabolism. To investigate the effects of light irradiation on the essential oil biosynthesis in A. heterotropoides var. mandshuricum, the plants were cultivated in four light irradiation treatments (100, 50, 24 and 12% full sunlight). The photosynthetic capacity, essential oil content and composition, activities of several enzymes and levels of some secondary metabolites involved in the shikimic acid and cinnamic acid pathways were analyzed. The leaf mass per area, average diurnal net photosynthetic rate, and the essential oil content increased significantly with increasing light intensity. Phenylalanine, cinnamic acid, and p-coumaric acid in the cinnamic acid pathway were at their highest levels in plants cultivated in 100% full sunlight. The highest content of shikimic acid in the shikimic acid pathway was obtained in plants grown in 50% sunlight transmittance. The activity of the enzymes 3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase, phenylalanine ammonia lyase, cinnamate-4-hydroxylase and 4-coumarate:CoA ligase increased proportionally with light intensity. Overall, we conclude that high light irradiation promotes high net photosynthetic rate, high activity of enzymes and high amounts of phenylpropanoid precursor metabolites leading to significant biosynthesis of essential oil in A. heterotropoides var. mandshuricum.

Identify old drugs as selective bacterial ß-GUS inhibitors by structural-based virtual screening and bio-evaluations.

Irinotecan (CPT-11) is a cytotoxic drug that has wide applicability and usage in cancer treatment. Despite its success, patients suffer dose-dependent diarrhea, limiting the drug's efficacy. No effective therapy is available for this unmet medical need. The bacterial ß-glucuronidase (ß-GUS) plays pivotal role in CPT-11-induced diarrhea (CID) via activating the non-toxic SN-38G to toxic SN-38 inside intestine. By using structural-based virtual screening, three old drugs (N-Desmethylclozapine, Aspartame, and Gemifloxacin) were firstly identified as selective bacterial ß-GUS inhibitors. The IC50 values of the compounds in the enzyme-based and cell-based assays range from 0.0389 to 3.6040 and 0.0105 to 5.3730 µM, respectively. The compounds also showed good selectivity against mammalian ß-GUS and no significant cytotoxicity in bacteria. Molecular docking and molecular dynamics simulations were performed to further investigate the binding modes of compounds with bacterial ß-GUS. Binding free energy decomposition revealed that the compounds formed strong interactions with E413 in catalytic trail from primary monomer and F365' on the bacterial loop from the other monomer of bacterial ß-GUS, explaining the selectivity against mammalian ß-GUS. The old drugs identified here may be used as bacterial ß-GUS inhibitors for CID or other bacterial ß-GUS-related disorders.

A novel macrophage-mediated biomimetic delivery system with NIR-triggered release for prostate cancer therapy.

BACKGROUND: Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO. RESULTS: At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo. CONCLUSIONS: The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.

Recent Developments of Phototherapy Based on Graphene Family Nanomaterials.

Graphene-based nanomaterials have drawn abundant interest in various fields such as biomedicine in recent years. Thanks to the ultra-high surface area of single-layered graphene, higher molecular loading is obtained. In addition, easy modifications were acquired because of its ample oxygen-content functional groups. Owing to its excellent physical- chemical properties, graphene-based nanomaterials have been widely explored as novel nanovectors for disease theranostics. In this article, we gave a comprehensive review of graphenebased nanomaterials, including introduction about different members of graphene family nanomaterials (GFNs), various modifications, toxicity and biomedical applications of graphene- based derivatives. More attentions were given to phototherapy in this paper. The mechanisms of photothermal and photodynamic therapy were also offered. Finally, the prospects and challenges of the graphene-based nanomaterials were discussed in this review.

Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model.

Cancer pain management is a challenge for which Chinese herbal medicine might be useful. To study the spinal mechanisms of the Chinese medicated gel Long-Teng-Tong-Luo (LTTL), a 7-herb compound, on bone cancer pain, a bone cancer pain model was made by inoculating the tibias of female rats with Walker 256 cells. LTTL gel or inert gel, 0.5 g/cm(2)/d, was applied to the skin of tumor-bearing tibias for 21 days beginning a day after the inoculation. Mechanical threshold and paw withdrawal latency to thermal stimulation was measured. Transient receptor potential (TRP) cation channels in lumbar dorsal root ganglia (DRG) were immunostained and counted, and lumbar spinal cord interleukin-17A (IL-17A) was measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TRP antagonists and interleukin (IL)-17A antibodies were intrathecally administered to determine their effects on bone cancer pain. The gel significantly (P < .05) alleviated cancer-induced mechanical allodynia and thermal hyperalgesia and inhibited cancer-enhanced expression of IL-17A in spinal astrocytes and the TRP subfamily members V1, A1, and V4 in lumbar DRG. Intrathecal TRP antagonists at 10 µg significantly (P < .05) attenuated mechanical allodynia, thermal hyperalgesia, and IL-17A expression, indicating that TRP channels facilitate spinal IL-17 expression and cancer pain. IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes such pain. The data show that LTTL gel inhibits cancer pain, and this might be accounted for by the decrease in expression of DRG TRP channels and spinal astrocyte IL-17A.

[Development of Tripterygium glycosides nano-carries based on "nanoemulsion-gels" and its pharmacodynamics].

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.

Topical treatment with Tong-Luo-San-Jie gel alleviates bone cancer pain in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown. AIM OF THE STUDY: To investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model. MATERIALS AND METHODS: A bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague-Dawley rats (150-170 g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5 g/cm(2)/day) or inert gel control for 21 day (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks. RESULTS: TLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment. CONCLUSION: The present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity.

[Effect of magnesium isoglycyrrhizinate on allergy contact dermatitis (ACD) in mice].

OBJECTIVE: To investigate the effect of magnesium isoglycyrrhizinate (MgIG) on allergy contact dermatitis (ACD) in mice. METHOD: The model of ACD was sensitized and challenged by 1% dinitrofluorobenzene(DNFB).48 SPF grade mice were divided into 6 groups randomly: a control group, a model group, three dosage groups and a positive group. The drug was injected through vena caudalis. The change of ear's swelling and the scores of ear's thickness and erythema of each mouse was observed. The level of INF-gamma, IgE, IL-4 in serum was detected by ELISA method. Then the pathologic change of mice ears was using HE staining examined under light microscope. RESULT: MgIG could decrease (P < 0.05) the ear's swelling, the scores of ear's thickness and erythema, and INF-gamma and IgE level in mice serum. It was observed that MgIG could significantly alleviate the infiltrate of inflam cell and the hemangiectasis in ear tissue. CONCLUSION: Certain concentration of MgIG has significant therapeutic effect on ACD in mice. Therapeutic mechanism of MgIG may be relevant with the suppression of INF-gamma and IgE.

[Preparation of paeonol microemulsion gel its and transdermal characterization in vitro].

OBJECTIVE: To prepare paeonol microemulsion and microemulsion gel, and investigate its content, physical and chemical properties. Their transdermal properties in vitro were studied as well. METHOD: IPM acted as oil phase, lecithin/APG as surfactant, 1,2-propanediol as cosurfactant, water was added dropwise to the oil phase to prepare paeonol microemulsion at room temperature using magnetic stirring. HPLC method were used to determine the content of paeonol in paeonol microemulsion. Transmission electron microscopy and laser particle size analyzer were used to determine the shape and size of the microemulsion. Carbopol 940 was uesd as substrate to prepare paeonol microemulsion gel. Franz diffusion cell was used for characterizing the microemulsion and gel transdermal properties in vitro. RESULT: The paeonol microemulsion was O/W microemulsion. Its uniform particle size was 32 nm and was with roundness appearance and stable content. The steady-state permeation rates of paeonol saturated aqueous solution, microemulsion, and microemulsion gel were 47.846, 103.760, 70.401 microg x cm(-2) x h(-1), and their 12 h cumulative amount of infiltration were 657.179, 1 266.484, 881.217 microg x cm(-2), respectively. CONCLUSION: The 12 h cumulative infiltration and infiltration rate of paeonol microemulsion and microemulsion gel are better than the saturated aqueous solution. Paeonol microemulsion gel is a new dosage form for transdermal drug delivery.

[Studies on cutaneous permeation in vitro of Kushen recipe gel].

OBJECTIVE: To establish a suitable dosage form for a traditional anti-anaphylaxis Chinese medicine of Kushen recipe, and investigate the effect of cutaneous permeation in vitro of the recipe. METHOD: Techniques of extracting with ethanol and purifying with absorbent resin to obtain alkaloids from Kushen recipe were adopted, while volatile oil was extracted by steam distillation. The extraction was made to gel. The skin from SD rats' abdomen was used as permeability barriers. Then effects of permeation of the aqueous extraction, the purifying extraction and the gel were compared by Valia-Chien and Franz diffusion cell method. HPLC was utilized to quantitate the alkaloids in permeating liquid. RESULT: In view of the permeation cumulation quantity, the permeation velocity and the lag time of the four kinds of alkaloids, the effect of permeation of purifying extraction was better than the aqueous extraction, and the purifying extraction gel surpassed both the aqueous extraction and the purifying extraction. CONCLUSION: It was certified that the purifying extraction gel had improved the effect of cutaneous permeation of alkaloids, and it is the befitting dosage form for Kushen recipe to treat anaphylaxis disease in skin.