An aminocaproic acid-grafted chitosan derivative with superior antibacterial and hemostatic properties for the prevention of secondary bleeding.

Uncontrolled bleeding is one of the leading causes of human mortality. Existing hemostatic materials or techniques cannot meet the clinical requirements for safe and effective hemostasis. The development of novel hemostatic materials has always been of great interest. Chitosan hydrochloride (CSH), a derivative of chitin, is extensively used on wounds as an antibacterial and hemostatic agent. However, the formation of intra- or intermolecular hydrogen bonds between hydroxyl and amino groups limits its water solubility and dissolution rate and affects its effectiveness in promoting coagulation. Herein, we covalently grafted aminocaproic acid (AA) to the hydroxyl and amino groups of CSH via ester and amide bonds, respectively. The solubility of CSH in water (25 °C) was 11.39 ± 0.98 % (w/v), whereas the AA-grafted CSH (CSH-AA) reached 32.34 ± 1.23 % (w/v). Moreover, the dissolution rate of CSH-AA in water was 6.46 times higher than that of CSH. Subsequent studies proved that CSH-AA is non-toxic, biodegradable, and has superior antibacterial and hemostatic properties to CSH. Additionally, anti-plasmin activity can be exerted by the dissociated AA from the CSH-AA backbone, which can help to lessen secondary bleeding.

Efficacy of Aeschynomene indica L. leaves for wound healing and isolation of active constituent.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection, hepatitis, enteritis, dysentery, nyctalopia, conjunctivitis, urticaria, and furuncle. However, no scientific investigation has been conducted on its wound healing potential. AIM OF THE STUDY: To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. MATERIALS AND METHODS: The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68, CCR7 (CD197), CD163, TGF-ß1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. RESULTS: We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-ß1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. CONCLUSION: Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-ß1 and α-SMA expression.

Design, synthesis and cytotoxicity of novel podophyllotoxin derivatives.

A series of novel podophyllotoxin derivatives were designed using association strategy and synthesized by coupling either podophyllotoxin (1) or 4beta-amino podophyllotoxin (3) with substituted indol-3-yl-glyoxyl chlorides. Their structures were identified using spectroscopic techniques. These novel derivatives have been evaluated for cytotoxicity in vitro against four human cancer cell lines with comparison to the parent compounds 1, 3 and indibulin (2). Some of the compounds (7a, 7c) showed comparable cytotoxicity to that of podophyllotoxin.

Effects of PLAB on apoptosis and Smad signal pathway of hypertrophic scar fibroblasts.

Pseudolaric acid-B (PLAB), a diterpene acid, was isolated from the root and trunk barks of Pseudolarix kaempferi. It has shown antifungal and anti-fertility effects and cytotoxic activities in previous studies. Our goals are to study the effects of PLAB on cell proliferation and Smad signal pathway of hypertrophic scar fibroblasts. Our results showed that PLAB induced apoptosis in hypertrophic scar fibroblasts and inhibited cell proliferation of hypertrophic scar fibroblast. MTT assay showed that its IC(50) value toward hypertrophic scar fibroblasts was 12.9+/-1.20 micromol/L. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by PLAB in hypertrophic scar fibroblast was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical "Sub-G1 peak" was also checked through flow cytometry. The Smad2 and Smad7 mRNA levels of 48-h PLAB treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) 48 h later. RT-PCR showed that Smad7 mRNA level increased and significant differences were observed between control group and experimental group (P<0.05); While there is no significant difference in Smad2 mRNA between the two groups. Our results showed that PLAB interfered with the microtubule dynamics of tubulin polymerisation and depolymerisation, which results in the inhibition of chromosomal segregation in mitosis and consequently the inhibition of cell division. These results suggest that PLAB inhibits hypertrophic scar fibroblast growth through apoptosis and Smad signal pathway.