Traditional Chinese Drug Research Articles

Formulation and Evaluation of In Situ Gelling Systems for Intranasal Administration of Gastrodin

Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

Preparation of monomeric and polymeric β‐cyclodextrin functionalized monoliths for rapid isolation and purification of puerarin from Radix puerariae

Monomeric and epichlorohydrin polymerized β-CD functionalized monoliths were prepared for the rapid isolation and purification of the isoflavonoid puerarin, a well-known traditional Chinese drug, from a crude extract of Radix puerariae (root of the plant Pueraria lobata). Two copolymers poly(isocyanatoethyl methacrylate-co-methyl methacrylate-co-ethylene dimethacrylate) (poly(IEM-co-MMA-co-EDMA)) and poly(glycidyl methacrylate-co-EDMA) (poly(GMA-co-EDMA)) were developed as facile, highly reactive and versatile monolithic matrix. SEM characterization demonstrated that the modified monoliths had homogenous porous structure and morphology. The success of the chemical modification of the monolithic matrix was confirmed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), solid-state (13) C NMR and elemental analysis. It was demonstrated that polymeric β-CD modified monoliths had better separation and selectivity for puerarin, recovering puerarin with a purity of 96% (m%) and a yield of 93% (m%). Compared with poly(glycidyl methacrylate-co-EDMA), poly(isocyanatoethyl methacrylate-co-methyl methacrylate-co-EDMA) monolithic matrix had higher reactivity, which significantly improved the β-CD ligand density and thus the selectivity of the monoliths. Puerarin with a purity of 96% (m%) and with a yield of 89% (m%) was recovered on the monolith.

Advances in research on analgesia by traditional Chinese drugs

With the development of science and technology,more knowledge of pain pathology in the aspects of molecular and cellular levels and neurotransmitter,and analgesic research on traditional Chinese drugs have made new progress.The animal pain models were used for basic screening and study on analgesic active components and analgesic mechanism of traditional Chinese drugs,which provided scientific evidences for the development of new analgesic drugs.In this article,the classical animal pain models are summarized,pain-related substances and their determination methods are reviewed in order to offer a reference for future research on analgesia by chinese drugs.

Protective effects of Radix Codonopsis on ischemia–reperfusion injury in rats after kidney transplantation

Kidney ischemia-reperfusion injury (IRI) after kidney transplant remains a major problem, separate from immune rejection that can lead to kidney transplant failure and graft function loss. Free radicals, disturbance of microcirculation and the inflammatory cascade appear to be the main contributors. Radix Codonopsis, a traditional Chinese drug used in vascular diseases, is an antioxidant and free radical scavenger. This study investigates the protective effect and underlying mechanisms of Radix Codonopsis extract saponins on kidney transplantation. Renal transplantation was performed after rat kidneys had been stored for 1 h at 4°C. Blood urea nitrogen (BUN), serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed; bcl-2 and bax mRNA expression was detected using RT-PCR; bcl-2 and bax protein expression was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to detect apoptotic cells and determine the apoptosis index (AI). Analysis of variance (ANOVA) followed by Dunnett's test was used when more than two groups were compared. Saponin-treated animals showed increased SOD levels accompanied by decreased MDA, Scr and BUN levels (p < 0.05 vs. untreated controls); bcl-2 mRNA and protein levels were increased in transplanted kidney from treated animals, while bax mRNA and protein levels were decreased (p < 0.05 vs. untreated controls). AI was significantly decreased in transplanted kidneys from treated animals relative to untreated controls (p < 0.05 vs. untreated controls). This study clearly demonstrates the protective effects on IRI after kidney transplantation, which may be explained by decreased lipid peroxidation and inhibition of apoptosis.

Scientific supervision of compound preparation of traditional Chinese medicine and chemical drug

The application of the compound preparation of traditional Chinese medicine (TCM) and chemical drug in clinical has a long history. Drug regulatory requirements of the compound preparation of TCM and chemical drug in various periods were compared and analyzed, and the history and status of the way of scientific supervision of this preparation were summarized. This paper discussed the problems and deficiencies of the compound preparation of TCM and chemical drug, and put forward countermeasures and suggestions about to strengthen the scientific supervision of the compound preparation of TCM and chemical drug.

Effects of oren-gedoku-to and unsei-in, Chinese traditional medicines, on interleukin-8 and superoxide dismutase in rats.

This study was conducted to elucidate the mechanisms of action of two Chinese traditional drugs, Oren-gedoku-to and Unsei-in, which have been used for many years in the treatment of inflammatory disorders. In rats with acetic acid-induced inflammation, both drugs reduced interleukin-8 concentrations in the serum. Neither drug significantly affected superoxide dismutase activity in the serum, although Unsei-in increased superoxide dismutase activity in liver after 1 month of administration. Oren-gedoku-to showed no significant effect on liver superoxide dismutase activity. It was considered that these medicines exert their anti-inflammatory effects mainly on the early stages of inflammation, wherein increased capillary permeability and migration of leucocytes occur.

Studies on the dynamic accumulations of Sophora alopecuroides L. Alkaloids in different harvest times and the appropriate harvest time

A sensitive and accurate method for the simultaneous determination of five alkaloids, namely 9α-hydroxymatrine (M1), matrine (M2), sophoridine (M3), oxymatrine (M4), alopecurin A (M5) in different parts (seed, legume, stem, and root) and different harvest times of Sophora alopecuroides L. was developed by high performance liquid chromatography (HPLC) with photodiode array detector (PDA) for the first time. The separation by gradient elution was achieved on Scienhome Kromasil C 18 (4.6 × 250 mm, 5 μm) column at 30 °C with acetonitrile (A)/0.1% phosphatic acid + 0.1% triethylamine (B) as the mobile phase. The detection wavelength was 205 nm. The optimized method provided a good linear relation ( r ≥ 0.9993 for all the target compounds), satisfactory precision (RSD values less than 2.3%) and good recovery (96.4–103.6%). The limits of detection ranged between 0.11 × 10 −3 and 4.70 × 10 −3 μg for the different analytes. The method was successfully applied to analysis and quality control of alkaloid extracts from the traditional Chinese herbal drugs of S. alopecuroides L.

Survey on medical therapy of patients with osteoporotic vertebrae fractures

Objective To evaluate the efficacy of medical therapy in the patients with osteoporotic vertebrae fracture. Methods The patients suffered from vertebrae fracture and had undergone percutaneous vertebroplasty operation were reviewed from May, 2006 to December, 2009. Informations were collected via case evaluation and telephone interview, regarding dual-energy X-ray absorptiometry(DXA), calcium and vitamin D supplementation,and anti-osteoporosis drugs treatment. Patients with fracture induced by trauma and tumor metastasis were excluded. Results Among 253 patients, DXA was performed only in 3.6% of patients. Calcium and vitamin D supplements were prescribed in 9.5% and 6.7% of patients, respectively. Anti-osteoporosis drugs were prescribed in 36% of patients, of them 27.5%, 29.7%, 2.2%, and 3.3% received bisphosphonate, calcitonin, ossotide, and traditional Chinese drugs respectively. 37. 4% of patients could not recall the name of the drug they had received. Conclusions Most patients with osteoporotic vertebrae fracture do not receive adequate anti-osteoporosis drugs or appropriate evaluation. More care should be given to the patients with vertebrae fracture, with regard to adequate drug treatment and appropriate evaluation in order to prevent future fractures. Key words: Osteoporosis; Vertebrae fracture; Medical therapy

Separation and determination of hesperidin in Huoxiangzhengqi water by hollow fiber ultrafiltration-high performance liquid chromatography

A simple hollow fiber based centrifuge ultrafiltration pretreatment procedure has been developed for the analysis of active components with high polarity in Chinese traditional and herbal drugs which usually contain macromolecule impurities. The procedure combined with HPLC was applied to the determination of hesperidin in Huoxiangzhengqi water. Sample solutions were purified by our patent hollow fiber centrifuge ultrafiltration device. Under the effect of the centrifgual force, micromolecules were removed from solution samples, thus it increased the service life of the column. The accuracy and repeatability of this method have also been improved. The separation was carried out on a Promosil C18 column (4.6 mm x 150 mm, 5 microm) with methanol -0.5% acetic acid solution (35:65) as mobile phase at a flow rate of 1.0 mL x min(-1). The detector wavelength was 283 nm and the column temperature was 30 degrees C. A good linear relation was obtained in the range of 4.69 - 150 mg x L(-1) (r = 0.999 7) and the average recovery was 103.0% with RSD of 1.9%. This method is simple, rapid and accurate, and it provides a simple and cheap ultrafiltration means for the analysis of the polar components in Chinese traditional and herbal drugs.

Methodological Framework of Relativity Research on Efficacy and Drug Nature of Cold and Hot of Traditional Chinese Drugs

Abstract This study aimed to analyze and study the efficacy and nature of cold and hot traditional Chinese drugs (TCDs). TCDs of both cold and hot natures have different interventional effects on the constitution and syndromes of cold and hot physical natures of the body. A syndrome-based method for relative research has been conducted on the efficacy of TCDs of both cold and hot natures. The key research conducted on syndrome models includes the study of the relationship between the efficacy and cold and hot nature of the TCDs, in addition to a relative research between the material components and efficacy of TCDs of cold and hot natures. Research was also conducted to determine the characteristic effects of cold and hot TCDs on normal models and on cold- and hot-constitution models. A comparative research of the mechanism of action of cold and hot TCDs was conducted based on the different models. The relative research on the efficacy of cold and hot TCDs also analyzed and summarized the model preparation, indicator observation, and control design.

Novel Learning Algorithm for System Model of Traditional Chinese Drug Fumigation

Using control method to explain medical phenomenon is currently a hot subject of research. The traditional Chinese drug fumigation steaming treat protrusion of protrusion of protrusion of lumbar intervertebral disc with steam generated by boiling medicinal herbs, and this process is a typical non-linear, multivariable, and strong coupling. Experienced nurse and doctor cure patient by their experience. So establish a model of this process can discover more factor of the disease, better treat to protrusion of protrusion of protrusion of lumbar intervertebral disc and reduce of energy consumption. The novel learning algorithm which is combined Ying learning algorithm with fuzzy neural network is proposed in this paper of traditional Chinese drug fumigation fume to cure protrusion of protrusion of protrusion of lumbar intervertebral disc. Proper data pretreatment can improve the accuracy of model. The new way handle of date pretreatment and create a new local space by K-Vector Nearest Neighbors to remove extraneous matter from learning set. This method automatically adjusts fuzzy rules and networks weights based on local space to fit sampling data. The identification model can reveals pathological mechanism of protrusion of protrusion of protrusion of lumbar intervertebral disc. The controller can adjust heater output power based on this model at the state of energy conservation. The simulation results show that the identification model is true and result is feasible. Compared with other methods, the new controller has better dynamics performance and anti-interference capability.

HPLC-based activity profiling for GABAA receptor modulators from the traditional Chinese herbal drug Kushen (Sophora flavescens root)

An EtOAc extract from the roots of Sophora flavescens (Kushen) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes transiently expressing GABA(A) receptors with subunit composition, α (1) β (2) γ (2S). HPLC-based activity profiling of the extract led to the identification of 8-lavandulyl flavonoids, kushenol I, sophoraflavanone G, (-)-kurarinone, and kuraridine as GABA(A) receptor modulators. In addition, a series of inactive structurally related flavonoids were characterized. Among these, kushenol Y (4) was identified as a new natural product. The 8-lavandulyl flavonoids are first representatives of a novel scaffold for the target.

Electrospun Nanoporous Poly(butylenes succinate-co-bytylene terephthalate) Nonwoven Mats

A traditional Chinese drug “Yunnan Baiyao” is used as an additive in poly(butylenes succinate-co-bytylene terephthalate) (PBST) solution, which is a kind of biodegradable aliphatic-aromatic copolyesters, to produce microspheres with nanoporosity by electrospinning; the tunable size of nanoporosity can be controlled by changing the voltage applied in the electrospinning process.

New perspectives on chinese herbal medicine (zhong-yao) research and development.

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.

Efficacy of Transcatheter Arterial Infusion Alone or Combined with Transcatheter Arterial Chemoembolization on Advanced Hepatocellular Carcinoma

Objective: Interventional therapy for advanced hepatocellular carcinoma (HCC) is still controversial. This retrospective study was to evaluate the efficacy of transcatheter arterial infusion (TAI) alone or combined with transcatheter arterial chemoembolization (TACE) on advanced HCC. Methods: The study population consisted of 132 advanced HCC patients with Child-pugh A/B. Tumor in all patients was involved with main trunk of portal vein and/or inferior vena cava, or local lymph node metastasis, or distant metastasis. TAI alone or combined with TACE were performed in 65 patients with advanced HCC (interventional treatment group), 67 patients were treated with traditional Chinese herbal drug (Chinese herb group). The prime end point was overall survival (OS), and prognostic factors were analysed. Results: The median OS was 205 days [95% confidence interval (CI), 155-255 days] in interventional treatment group and 127 days (95% CI, 70-184 days) in Chinese herb group (P <0.05). The 6-month, 1-year, and 2-year OS rates were 58.9%, 29.1%, 7.7% in interventional treatment group, and 33.3%, 12.3%, 1.8% in Chinese herb group. The portal vein thrombosis, ECOG performance status were independent prognostic factors for OS. Conclusion: Interventional treatment could greatly prolong the OS of advanced HCC patients.

HPLC-based activity profiling of Angelica pubescens roots for new positive GABA A receptor modulators in Xenopus oocytes

A petroleum ether extract of the traditional Chinese herbal drug Duhuo (roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan), showed significant activity in a functional two-microelectrode voltage clamp assay with Xenopus oocytes which expressed recombinant γ-aminobutyric acid type A (GABA A) receptors of the subtype α 1β 2γ 2S. HPLC-based activity profiling of the active extract revealed six compounds responsible for the GABA A receptor modulating activity. They were identified by microprobe NMR and high resolution mass spectrometry as columbianetin acetate ( 1), imperatorin ( 3), cnidilin ( 4), osthol ( 5), and columbianedin ( 6). In concentration-dependent experiments, osthol and cnidilin showed the highest potentiation of the GABA induced chloride current (273.6% ± 39.4% and 204.5% ± 33.2%, respectively at 300 μM). Bisabolangelone ( 2) only showed minor activity at the GABA A receptor. The example demonstrates that HPLC-based activity profiling is a simple and efficient method to rapidly identify GABA A receptor modulators in a bioactive plant extract.

The membrane transport of flavonoids from Crossostephium chinense across the Caco‐2 monolayer

The permeation and efflux of six polysubstituted flavonoids isolated from Crossostephium chinense, a Chinese traditional and herbal drug for the treatment of diabetes, were investigated using the Caco-2 cell monolayer. The six flavonoids (selagin, apometzgerin, tricetin-3',4',5'-trimethylether, quercetagetin-3,6,7-trimethylether, hispidulin and quercetagetin) sharing a similar parent skeleton structure with varied substituents in the heterocyclic ring B were selected for the study. Quercetagetin exhibited a low bi-directional permeability comparable to that of atenolol, suggesting a paracellular diffusion mechanism. The remaining compounds exhibited time- and concentration- dependent permeation with apparent permeability coefficient (P(app)) values in the range 10⁻⁶-10⁻⁵ cm/s, suggesting transcellular diffusion pathways. Selagin exhibited significantly larger basolateral to apical P(app) than that of the reverse direction, suggesting the existence of efflux mechanisms. ATP-depletion and probenecid pretreatment led to a significant inhibition of the efflux of selagin, whereas verapamil had no effect on the basolateral to apical transport of selagin, suggesting that multidrug resistance proteins (MRPs) and not P-glycoprotein play a role in the intestinal efflux of selagin. Based on present and previous results, the structure-permeation relationship and the role of MRPs in mediating the efflux of flavonoids are discussed. Experimental results in this study provide useful information for pharmacological applications of the flavonoids from C. chinense.

Protective effect of Salvia Miltiorrhizae injection on N(G)-nitro-d-arginine induced nitric oxide deficient and oxidative damage in rat kidney

N(G)-nitro-D-arginine (d-NNA) could convert into N(G)-nitro-L-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by D-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on D-NNA-induced kidney damage. The rats, induced with D-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with D-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P<0.05), and the levels of BUN, Crea and MDA were significantly lower than that of D-NNA only group (P<0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of D-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates D-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.

Developing a library of authenticated Traditional Chinese Medicinal (TCM) plants for systematic biological evaluation — Rationale, methods and preliminary results from a Sino-American collaboration

While the popularity of and expenditures for herbal therapies (aka “ethnomedicines”) have increased globally in recent years, their efficacy, safety, mechanisms of action, potential as novel therapeutic agents, cost-effectiveness, or lack thereof, remain poorly defined and controversial. Moreover, published clinical trials evaluating the efficacy of herbal therapies have rightfully been criticized, post hoc, for their lack of quality assurance and reproducibility of study materials, as well as a lack of demonstration of plausible mechanisms and dosing effects. In short, clinical botanical investigations have suffered from the lack of a cohesive research strategy which draws on the expertise of all relevant specialties. With this as background, US and Chinese co-investigators with expertise in Traditional Chinese Medicine (TCM), botany, chemistry and drug discovery, have jointly established a prototype library consisting of 202 authenticated medicinal plant and fungal species that collectively represent the therapeutic content of the majority of all commonly prescribed TCM herbal prescriptions. Currently housed at Harvard University, the library consists of duplicate or triplicate kilogram quantities of each authenticated and processed species, as well as “detanninized” extracts and sub-fractions of each mother extract. Each species has been collected at 2–3 sites, each separated geographically by hundreds of miles, with precise GPS documentation, and authenticated visually and chemically prior to testing for heavy metals and/or pesticides contamination. An explicit decision process has been developed whereby samples with the least contamination were selected to undergo ethanol extraction and HPLC sub-fractionation in preparation for high throughput screening across a broad array of biological targets including cancer biology targets. As envisioned, the subfractions in this artisan collection of authenticated medicinal plants will be tested for biological activity individually and in combinations (i.e., “complex mixtures”) consistent with traditional ethnomedical practice. This manuscript summarizes the rationale, methods and preliminary “proof of principle” for the establishment of this prototype, authenticated medicinal plant library. It is hoped that these methods will foster scientific discoveries with therapeutic potential and enhance efforts to systematically evaluate commonly used herbal therapies worldwide.

Effect of Matrine on Alleviating Retinoic Acid Resisted Acute Promyelocytic Leukemia

AbstractAbstract 4710Acute promyelocytic leukemia (APL) represents 3.3%-17.4% of acute leukemia in adults. With the application of all-trans retinoic acid (ATRA), more than 85% patient can achieve complete remission, however, high rates of relapse still exist if ATRA is used alone. Primary resistance of ATRA in PML-RARα positive APL is rare during induction therapy but the incidence markedly increases after second relapse and results in poor long time survival of patient. Matrine (MAT) is the effective constituent of Radix Sophorae Flavescentis, a commonly used traditional chinese drug, and has proven ability to inhibit carcinoma cell proliferation and can induce differentiation and apoptosis of K562 cells, however its effect on the differentiation of APL cells, especially on ATRA resistant APL cells is unclear. The aim of our research is to explore the effect of MAT on alleviating retinoic acid resistance in APL cells and address possible mechanisms involved. The characteristics of ATRA sensitive APL cell strain NB4 and resistant APL cell strains NB4-R1 and NB4-R2 were described in our former studies. Dose escalation studies using MAT and ATRA was investigated using methyl thiazolyl tetrazolium (MTT) test. The toxicity of MAT increases with increasing concentration of MAT from 0.001 mmol/L to 10 mmol/L, and the 0.1mmol/L was chosen with its inhibition ratio < 10%. IC50 of ATRA was obtained by drawing the restrain curve; the resistance coefficient (RC) of NB4-R1 and NB4-R2 to ATRA was obtained by the ratios of their IC50 to that of NB4 cell, respectively. And the reversal index (RI) was obtained by the ratios of RC of resistant cell line cells cultured with or without 0.1 mmol/L MAT for 72h. Cell differentiation was evaluated by nitro blue tetrazolium chioride (NBT) test and cell morphology. Differential effects on cell differentiation between MAT combined with 1 umol/L ATRA and controls were observed. For these studies, 1umol/L of ATRA was chosen according to the result of IC50 test, which had low toxicity to resistance cell line cells, with the inhibition ratio < 10%. Apoptosis rate of cells treated with MAT combined with 1 umol/L ATRA was tested by flow cytometry with Annexin V-PI staining. Nested PCR was used for PML/RARa PCR reaction. Our results showed, after treated with ATRA along with 0.1 mmol/L MAT, the resistance factor of NB4-R1 to ATRA decreased markedly (RI=4.96±1.15), but no difference was shown in NB4-R2 cells (RI=0.66±0.17). The positive ratio of NBT and the morphologic changes indicated that the differentiation ability of NB4 and NB4-R1was enhanced significantly with the increasing concentration of MAT combined with 1 umol/L ATRA, which reached the peak at 0.1mmol/L (Figure). The apoptosis ratio (Annexin V-FITC kit) of NB4 and NB4-R1 were also increased with increasing concentration of MAT combined with 1 umol/L ATRA, while no changes were observed using the NB4-R2 cell line. The expression of PML-RARα fusion became weak in NB4 and NB4-R1 cells after treated with 0.1 umol/L ATRA alone, and decreased notably when co-treated with 0.1 mmol/L MAT for 72h in NB4-R1, while the fusion gene expression remained negative in NB4-R2 cells exposed to both drugs. From this study, we conclude that MAT, when used together with ATRA as a low non-toxic dose, can improve the differentiation of NB4 cells and inverse the retinoic acid resistance of NB4-R1 cells, but it has no function on NB4-R2 cells. As the mechanism of ATRA resistance in NB4-R1 and NB4-R2 cells is different, with resistance to the former ascribed to abnormal cyclic adenosine monophosphate (cAMP) mediated pathways, leading to altered differentiation of NB4-R1 which can be corrected when cells are cocultured with cAMP and ATRA, and resistance of NB4-R2 is owing to the variation of PML-RARα, which can only be alleviated in the existence of RXR receptor specific agonist, MAT may play its anti-ATRA resistance role in an ATRA dependent pathway, and lead to the inhibition of the PML-RARα fusion gene. This indicates a possible application of MAT in ATRA resistance therapy. Further research will focus on the mechanism of MAT in the regulation and differentiation as well as apoptosis of APL cells. [Display omitted] Disclosures:No relevant conflicts of interest to declare.