Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells.

Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively. We further revealed that the naringin-loaded coatings facilitated adhesion, proliferation and late differentiation, and mineralization of MSCs. Our findings provided a novel strategy to engineer the coatings with controlled release of naringin and emphasized the bioactivity of naringin for the osteogenic differentiation of MSCs.

Upregulating mTOR/ERK signaling with leonurine for promoting angiogenesis and tissue regeneration in a full-thickness cutaneous wound model.

Wound therapy remains a clinical challenge due to the poor vascularization during the healing process and the high demand to achieve functional and aesthetically satisfactory scars. Newly-formed blood vessels are necessary for wound healing since they can deliver nutrients and oxygen to the wound area. In this study, the role of leonurine (LN), a traditional Chinese medicine isolated from Herba leonuri, in promoting angiogenesis and its function in wound healing have been investigated. The results of co-culture with human umbilical vein endothelial cells (HUVECs) demonstrated that LN treatment (5-20 µM) could promote the proliferation and migration and enhance the ability of in vitro angiogenesis through up-regulating the mTOR/ERK signaling pathway. Furthermore, a full-thickness cutaneous wound model was used to investigate the healing effect of LN in vivo. Intragastric administration of 20 mg per kg per day LN stimulated the regeneration of more blood vessels at the wound sites, which confirmed the in vitro results of promoting angiogenesis. Due to fast vascularization, the collagen matrix deposition and remodeling processes were also accelerated in LN treated wounds, resulting in efficient wound healing. In summary, LN promoted angiogenesis of endothelial cells in vitro by activating the mTOR/ERK pathway, and could efficiently enhance the angiogenesis and collagen deposition of the regenerated tissue, together with facilitating the wound healing process in vivo. This study provides evidence for LN-stimulated angiogenesis and tissue regeneration in skin wounds, especially in ischemic wounds.

Monotropein promotes angiogenesis and inhibits oxidative stress-induced autophagy in endothelial progenitor cells to accelerate wound healing.

Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation. Moreover, Mtp accelerated wound healing in rats, as indicated by reduced healing times, decreased macrophage infiltration and increased blood vessel formation. In summary, Mtp promoted mobilization and differentiation of BM-EPCs and protected against apoptosis and autophagy by suppressing the AMPK/mTOR pathway, improving wound healing in vivo. This study revealed that Mtp is a potential therapeutic for endothelial injury-related wounds.

Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling.

Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Treatment of human umbilical vein endothelial cells (HUVECs) with ASA VI (20-80 µg/mL) dose-dependently promoted the proliferation, migration and enhanced their angiogenic ability in vitro, which were associated with the up-regulated HIF-1α/VEGF signaling. Full-thickness cutaneous wound model rats were injected with ASA VI (20 mg·kg-1·d-1, iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound healing, and more blood vessels were observed in the regenerated tissue. Due to rapid vascularization, the cellular proliferation status, granulation tissue formation, collagen matrix deposition and remodeling processes were all accelerated, resulting in efficient wound healing. In summary, ASA VI promotes angiogenesis of HUVECs in vitro via up-regulating the HIF-1α/VEGF pathway, and efficiently enhances the vascularization in regenerated tissue and facilitates wound healing in vivo. The results reveal that ASA VI is a potential therapeutic for vessel injury-related wounds.

Endoplasmic Reticulum Stress and NF-[Formula: see text]B Pathway in Salidroside Mediated Neuroprotection: Potential of Salidroside in Neurodegenerative Diseases.

Microglial activation leads to increased production of proinflammatory enzymes and cytokines, which is considered to play crucial role in neurodegenerative diseases, however there are only a few drugs that target microglia activation. Recent studies have indicated that the Traditional Chinese Medicine, salidroside (Sal), exerted anti-inflammatory effects. According to this evidence, our present study aims to explore the effect of the Sal (a phenylpropanoid glycoside compound which is isolated from rhodiola), on microglia activation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Our results showed that Sal could significantly inhibit the excessive production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) in LPS-stimulated BV2 cells. Moreover, Sal treatment could suppress the mRNA and protein expressions of inflammatory enzymes, including Inducible Nitric Oxide Synthase (iNOS) and Cyclooxygenase-2 (COX-2). The mechanisms may be related to the inhibition of the activation of Nuclear Factor-kappaB (NF-[Formula: see text]B) and endoplasmic reticulum stress. Our study demonstrated that salidroside could inhibit lipopolysaccharide-induced microglia activation via the inhibition of the NF-[Formula: see text]B pathway and endoplasmic reticulum stress, which makes it a promising therapeutic agent for human neurodegenerative diseases.

Paeonol Inhibits IL-1ß-Induced Inflammation via PI3K/Akt/NF-κB Pathways: In Vivo and Vitro Studies.

Paeonol, the main active component isolated from the root of Paeonia suffruticosa, has been reported to have anti-inflammatory properties. However, the effects of paeonol on osteoarthritis (OA) remain unclear. The aim of this study was to investigate the anti-inflammatory effects and mechanism of paeonol in IL-1ß-induced human OA chondrocytes as well as mice OA models. Human OA chondrocytes were pretreated with different concentrations of paeonol 2 h prior to IL-1ß (10 ng/mL) stimulation for 24 h. Nitric oxide (NO) production was determined by Griess method. The levels of prostaglandin E2 (PGE2), matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 were assessed by ELISA. Inducible nitric oxide synthase (INOS), COX-2, and PI3K/Akt/NF-κB-related signaling molecules production were measured by Western blot. In vivo, mice OA models were established by destabilization of the medial meniscus. One month after surgery, mice in paeonol-treated group were given intraperitoneal injection of paeonol in 30 mg/kg every day, while mice of vehicle-treated group were injected with DMSO under the same conditions. Hematoxylin and eosin as well as Safranin-O staining were applied to assess the severity of cartilage lesions. The results showed that pretreatment with paeonol could inhibit IL-1ß-induced NO and PGE2 production. Meanwhile, the overproduction of INOS, COX-2, MMP-1, MMP-3, and MMP-13 were also reversed by paeonol. Moreover, paeonol was found to inhibit IL-1ß-induced NF-κB activation, PI3K, and AKT phosphorylation. In vivo, treatment with paeonol exhibited less cartilage degradation and lower Osteoarthritis Research Society International scores in mice OA models. In conclusion, these results suggest that paeonol may be a potential therapeutic agent in the treatment of OA.