Comprehensive Transcriptome Sequencing Analysis of Hirudinaria manillensis in Different Growth Periods.

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of Hirudinaria manillensis (H. manillensis) in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from H. manillensis larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM (HIRM2) genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of H. manillensis also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of H. manillensis; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of HIRM2 might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.

Molecular mechanisms underlying hematophagia revealed by comparative analyses of leech genomes.

BACKGROUND: Leeches have been used in traditional Chinese medicine since prehistoric times to treat a spectrum of ailments, but very little is known about their physiological, genetic, and evolutionary characteristics. FINDINGS: We sequenced and assembled chromosome-level genomes of 3 leech species (bloodsucking Hirudo nipponia and Hirudinaria manillensis and nonbloodsucking Whitmania pigra). The dynamic population histories and genome-wide expression patterns of the 2 bloodsucking leech species were found to be similar. A combined analysis of the genomic and transcriptional data revealed that the bloodsucking leeches have a presumably enhanced auditory sense for prey location in relatively deep fresh water. The copy number of genes related to anticoagulation, analgesia, and anti-inflammation increased in the bloodsucking leeches, and their gene expressions responded dynamically to the bloodsucking process. Furthermore, the expanded FBN1 gene family may help in rapid body swelling of leeches after bloodsucking, and the expanded GLB3 gene family may be associated with long-term storage of prey blood in a leech's body. CONCLUSIONS: The high-quality reference genomes and comprehensive datasets obtained in this study may facilitate innovations in the artificial culture and strain optimization of leeches.

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Structurally diverse polyprenylated acylphloroglucinols from Hypericum uralum Buch.-Ham. ex D. Don.

Uralins A - D, four undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring an unprecedented fused hexacyclic architecture, a unique monocyclic tetra-seco-tetranor-b-PPAP, an oxidative b-PPAP and a rare norspiroindane-type m-PPAP, respectively, were isolated from the aerial parts of Hypericum uralum, along with ten known PPAPs. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques (MS, NMR, [α]D, CD), conceivable biogenetic pathways and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Biological assays showed three b-PPAPs had moderate antioxidative damage activities, while spiroindanes exhibited moderate cytotoxic effects.

Two new xanthones from Lomatogonium carinthiacum / 中国天然药物

AIM@#To study the chemical constituents of Lomatogonium carinthiacum (Wulfen) Rchb.@*METHOD@#The CHCl3-soluble fraction was separated by chromatography and the structures of the new compounds were elucidated by spectral experiments.@*RESULTS@#Two new xanthones, 1, 8-dihydroxy-4, 5-dimethoxy-6, 7-methylenedioxyxanthone (1), 1, 4, 8-trimethoxyxanthone-6-O-β-D-glucoronyl-(1→6)O-β-D-glucoside (2) were isolated from the whole plant of Lomatogonium carinthiacum.@*CONCLUSION@#Compounds 1 and 2 are new natural products.

[Effect of oxygen therapy on the morphology of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication].

OBJECTIVE: To evaluate the effects of different oxygen therapy technique (different concentrations of normobaric oxygen and the hyperbaric oxygen) on the ultrastructure of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication. METHODS: One hundred healthy male Wistar rats were randomly divided into five groups: normal control group (A), poisoned group (B), oxygen therapy group (C), oxygen therapy group (D) and oxygen therapy group (E). After the exposure to 300 ppm H2S for 60 min in a static exposure tank (1 m3), the rats were treated with oxygen therapy, C, D and E groups were given 33% oxygen, 50% oxygen of atmospheric oxygen and hyperbaric oxygen therapy for 100 min, respectively. The rats in normal control group inhaled air under the same environment. After exposure and therapy, the tissues of lung, heart and liver were observed under light microscope and electron microscope. RESULTS: The results of light microscope examination showed that the broken and not well aligned cardiac myofilaments, cytoplasmic edema and pyknosis could be seen in group B. The well aligned and clear cardiac myofilaments appeared in group C, D and E. The alveolar hemorrhage, edema and inflammatory cells exudation could not be seen in group A. Alveolar epithelial cell edema, unsmooth alveolar edge and alveolar inflammatory cells exudation could be found in group B. The unsmooth alveolar septal borders and pulmonary edema could be seen occasionally in group C and D, the alveolar inflammatory cells exudation could not be seen in group E. The regular hepatic boards and the uniform hepatic cellular nuclei were found in group A. The disordered hepatic boards, widened cellular gaps and cytoplasmic edema could be seen occasionally in group B. The irregular hepatic boards and ballooning degeneration could be seen in group C and D. The regular hepatic boards and uniform cytoplasm could be found in group E. The results of electron microscope examination indicated that the mitochondrial swelling, autolyzing, fuzzy and breakage of myocardial cells were observed in group B; the clear mitochondrial structure appeared in group E. The apoptosis and organelle vacuole of alveolar epithelial cells could be observed in group B. The relatively normal nuclei of alveolar epithelial cells could be seen in group E. The lax cytoplast structure of hepatocytes, unclear nuclear membrane, lumped chromatin, slightly swelled mitochondria and phagosomes were observed in group B. However, no improved change was observed in group C, D and E. CONCLUSION: Hydrogen sulfide could induce the extensive and severe damage of myocardial mitochondria, alveolar epithelial cells and hepatocytes, the oxygen therapy in good time could reduce significantly the myocardial injury, and improve the lung injury to some extent. High-pressure oxygen therapy is better than the normobaric oxygen therapy.

[Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia].

OBJECTIVE: To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot. METHODS: Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured. RESULTS: The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05). CONCLUSION: Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.

[Evaluation of different oxygen therapies on therapeutic effects in rats with acute carbon dioxide poisoning].

OBJECTIVE: To study therapeutic effects by using different oxygen therapies in rats with acute carbon dioxide poisoning, to select the best oxygen therapy technology for patients with acute carbon dioxide poisoning on the spot. METHODS: Sixty healthy male Sprague-Dawley rats were randomized into normal control group, carbon dioxide exposure group, hyperbaric oxygen treatment group (pressure 2 ATA, FiO(2)100%), high concentration of atmospheric oxygen treatment group (FiO(2)50%), low concentration of atmospheric oxygen treatment group (FiO(2)33%). After treated with different oxygen in rats with acute carbon dioxide poisoning, arterial pH, PO2 and PCO2 of rats were detected, in addition observe pathological changes of lung tissue and brain tissue. RESULTS: The arterial pH (7.31 ± 0.06) and PO2 [(68.50 ± 15.02) mm Hg] of carbon dioxide exposure group were lower than those of control group [pH (7.42 ± 0.02) and PO2 (92.83 ± 8.27) mm Hg], PCO2 [(71.66 ± 12.10) mm Hg] was higher than that of control group [(48.25 ± 2.59) mm Hg] (P < 0.05); the arterial pH (hyperbaric oxygen treatment group 7.37 ± 0.02, high concentration of atmospheric oxygen treatment group 7.39 ± 0.03, low concentration of atmospheric oxygen treatment group 7.38 ± 0.02) and PO2 of oxygen treatment groups [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (82.25 ± 12.98), (84.75 ± 11.24), (83.75 ± 16.77) mm Hg, respectively] were higher than that of carbon dioxide exposure group, PCO2 [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (52.25 ± 4.95), (51.75 ± 4.82), (52.66 ± 5.61) mm Hg, respectively] was lower than that of carbon dioxide exposure group (P < 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 between oxygen treatment groups and control group (P > 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 among oxygen treatment groups (P > 0.05). There was large area of bleeding of lungs in rats with carbon dioxide poisoning, the bleeding of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment was better than the rats with carbon dioxide poisoning, there was no abnormal appearance of lungs in rats with hyperbaric oxygen treatment. The light microscope observation showed that there were diffuse bleeding and exudation of lungs in rats with carbon dioxide poisoning, the bleeding and exudation of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment were better than the rats with carbon dioxide poisoning, there were only minor bleeding and exudation of lungs in rats with hyperbaric oxygen treatment. There was no difference of brain in anatomy and microscopy among all groups, there were no significant bleeding, edema, cell degeneration and necrosis. CONCLUSIONS: Lung pathology in acute carbon dioxide poisoning rats with hyperbaric oxygen treatment is better than the rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment, there is no significant difference of effect between high concentration of atmospheric oxygen treatment group and low concentration of atmospheric oxygen treatment group, however, the results of blood gas analysis and lung pathology than the exposure group improved, so qualified medical unit for hyperbaric oxygen therapy as soon as possible, hyperbaric oxygen treatment facilities in the absence of circumstances, the emergency treatment of early oxygen is also a good measure.

Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot.</p><p><b>METHODS</b>Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured.</p><p><b>RESULTS</b>The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05).</p><p><b>CONCLUSION</b>Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.</p>

Effect of oxygen therapy on the morphology of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of different oxygen therapy technique (different concentrations of normobaric oxygen and the hyperbaric oxygen) on the ultrastructure of cardiac muscle, lung and liver in rats with acute hydrogen sulfide intoxication.</p><p><b>METHODS</b>One hundred healthy male Wistar rats were randomly divided into five groups: normal control group (A), poisoned group (B), oxygen therapy group (C), oxygen therapy group (D) and oxygen therapy group (E). After the exposure to 300 ppm H2S for 60 min in a static exposure tank (1 m3), the rats were treated with oxygen therapy, C, D and E groups were given 33% oxygen, 50% oxygen of atmospheric oxygen and hyperbaric oxygen therapy for 100 min, respectively. The rats in normal control group inhaled air under the same environment. After exposure and therapy, the tissues of lung, heart and liver were observed under light microscope and electron microscope.</p><p><b>RESULTS</b>The results of light microscope examination showed that the broken and not well aligned cardiac myofilaments, cytoplasmic edema and pyknosis could be seen in group B. The well aligned and clear cardiac myofilaments appeared in group C, D and E. The alveolar hemorrhage, edema and inflammatory cells exudation could not be seen in group A. Alveolar epithelial cell edema, unsmooth alveolar edge and alveolar inflammatory cells exudation could be found in group B. The unsmooth alveolar septal borders and pulmonary edema could be seen occasionally in group C and D, the alveolar inflammatory cells exudation could not be seen in group E. The regular hepatic boards and the uniform hepatic cellular nuclei were found in group A. The disordered hepatic boards, widened cellular gaps and cytoplasmic edema could be seen occasionally in group B. The irregular hepatic boards and ballooning degeneration could be seen in group C and D. The regular hepatic boards and uniform cytoplasm could be found in group E. The results of electron microscope examination indicated that the mitochondrial swelling, autolyzing, fuzzy and breakage of myocardial cells were observed in group B; the clear mitochondrial structure appeared in group E. The apoptosis and organelle vacuole of alveolar epithelial cells could be observed in group B. The relatively normal nuclei of alveolar epithelial cells could be seen in group E. The lax cytoplast structure of hepatocytes, unclear nuclear membrane, lumped chromatin, slightly swelled mitochondria and phagosomes were observed in group B. However, no improved change was observed in group C, D and E.</p><p><b>CONCLUSION</b>Hydrogen sulfide could induce the extensive and severe damage of myocardial mitochondria, alveolar epithelial cells and hepatocytes, the oxygen therapy in good time could reduce significantly the myocardial injury, and improve the lung injury to some extent. High-pressure oxygen therapy is better than the normobaric oxygen therapy.</p>

Evaluation of different oxygen therapies on therapeutic effects in rats with acute carbon dioxide poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study therapeutic effects by using different oxygen therapies in rats with acute carbon dioxide poisoning, to select the best oxygen therapy technology for patients with acute carbon dioxide poisoning on the spot.</p><p><b>METHODS</b>Sixty healthy male Sprague-Dawley rats were randomized into normal control group, carbon dioxide exposure group, hyperbaric oxygen treatment group (pressure 2 ATA, FiO(2)100%), high concentration of atmospheric oxygen treatment group (FiO(2)50%), low concentration of atmospheric oxygen treatment group (FiO(2)33%). After treated with different oxygen in rats with acute carbon dioxide poisoning, arterial pH, PO2 and PCO2 of rats were detected, in addition observe pathological changes of lung tissue and brain tissue.</p><p><b>RESULTS</b>The arterial pH (7.31 ± 0.06) and PO2 [(68.50 ± 15.02) mm Hg] of carbon dioxide exposure group were lower than those of control group [pH (7.42 ± 0.02) and PO2 (92.83 ± 8.27) mm Hg], PCO2 [(71.66 ± 12.10) mm Hg] was higher than that of control group [(48.25 ± 2.59) mm Hg] (P < 0.05); the arterial pH (hyperbaric oxygen treatment group 7.37 ± 0.02, high concentration of atmospheric oxygen treatment group 7.39 ± 0.03, low concentration of atmospheric oxygen treatment group 7.38 ± 0.02) and PO2 of oxygen treatment groups [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (82.25 ± 12.98), (84.75 ± 11.24), (83.75 ± 16.77) mm Hg, respectively] were higher than that of carbon dioxide exposure group, PCO2 [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (52.25 ± 4.95), (51.75 ± 4.82), (52.66 ± 5.61) mm Hg, respectively] was lower than that of carbon dioxide exposure group (P < 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 between oxygen treatment groups and control group (P > 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 among oxygen treatment groups (P > 0.05). There was large area of bleeding of lungs in rats with carbon dioxide poisoning, the bleeding of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment was better than the rats with carbon dioxide poisoning, there was no abnormal appearance of lungs in rats with hyperbaric oxygen treatment. The light microscope observation showed that there were diffuse bleeding and exudation of lungs in rats with carbon dioxide poisoning, the bleeding and exudation of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment were better than the rats with carbon dioxide poisoning, there were only minor bleeding and exudation of lungs in rats with hyperbaric oxygen treatment. There was no difference of brain in anatomy and microscopy among all groups, there were no significant bleeding, edema, cell degeneration and necrosis.</p><p><b>CONCLUSIONS</b>Lung pathology in acute carbon dioxide poisoning rats with hyperbaric oxygen treatment is better than the rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment, there is no significant difference of effect between high concentration of atmospheric oxygen treatment group and low concentration of atmospheric oxygen treatment group, however, the results of blood gas analysis and lung pathology than the exposure group improved, so qualified medical unit for hyperbaric oxygen therapy as soon as possible, hyperbaric oxygen treatment facilities in the absence of circumstances, the emergency treatment of early oxygen is also a good measure.</p>

[Treatment of lower limb ischemia with combination of traditional Chinese medicine and transplantation of autologous bone marrow mononuclear cells: a report of 23 cases].

OBJECTIVE: To evaluate the therapeutic effect of transplantation of autologous bone marrow mononuclear cells combined with traditional Chinese medicine for the treatment of limb ischemia. METHODS: Twenty-three patients with limb ischemia were treated. G-CSF was used to stimulate the bone marrow. The mononuclear cells were separated from the aspirated bone marrow fluid in the stem cell studio. The cell amount was above 1x10(9). The transplantation was performed by the way of intra-muscular multi-injection. Traditional Chinese medicine for replenishing qi to activate blood was prescribed from the first day after operation. The pain, poikilothermia, ulcer or necrosis and ankle/brachial index (ABI) of the ischemic limb were evaluated before and after the treatment. RESULTS: The pain score and poikilothermia score decreased one month after the transplantation, with distinct differences as compared with the scores before the treatment (P<0.05). The ABI increased gradually after the treatment, and one month after the treatment, it was 0.15 higher than that before the treatment. CONCLUSION: Transplantation of autologous bone marrow mononuclear cells combined with traditional Chinese medicine can decrease the symptoms and signs of severe lower limb ischemia effectively, and improve the circulation of the ischemic area.

The stability of insulin-loaded polybutylcyanoacrylate nanoparticles in an oily medium and the hypoglycemic effect in diabetic rats / 药学学报

<p><b>AIM</b>To study the stability of insulin-loaded polybutylcyanoacrylate nanoparticles (IPN) in an oily medium (soybean oil containing 0.5% (v/v) Tween-20 and 5% (v/v) Vitamin E) along with the hypoglycemic effect following their oral administration to streptozotocin (STZ) induced diabetic rats.</p><p><b>METHODS</b>The stability of IPN in the process was appraised by measurement of the amount of undegraded insulin associated to nanoparticles, the average size and the span of IPN, as well as the release of insulin from IPN. IPN in an aqueous medium (containing 0.5% (v/v) Tween-20) at pH 2.0 was also investigated as control.</p><p><b>RESULTS</b>The study showed that IPN in the oily medium was more stable than that in the aqueous medium over one year of storage in the dark at (25 +/- 2) degrees C and the in vitro stability of IPN in the oily medium against degradation by proteolytic enzymes was much better than that in the aqueous medium. The apparent bioavailability of an oral administration of IPN (50 u x kg(-1)) in the oily medium versus an (sc) injection of insulin (2 u x kg(-1)) was 22.4%, much higher than that of IPN in the aqueous medium (15.5%), based on decreased areas above curve (AAC) determination for the blood glucose depression from time zero to 144 h of a single oral administration of IPN to STZ-diabetic rats.</p><p><b>CONCLUSION</b>IPN in soybean oil containing Tween-20 (0.5% v/v) and Vitamin E (5% v/v) could be considered as an effective and stable delivery system for oral insulin.</p>