Xiaofang Huang's research while affiliated with Shenyang Pharmaceutical University and other places

A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It was also found 15a produced more than 8 µM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death through both endogenous and exogenous pathways.

Objectives: The aim of this study was to investigate the molecular mechanisms of the efficacy of lignin compound dehydrodiconiferyl alcohol (DHCA) isolated from Silybum marianum (L.) Gaertn in improving wound healing. These findings preliminarily brought to light the promising therapeutic potential of DHCA in skin wound healing. Methods: First, the effect of DHCA on healing in vivo was studied using a full-thickness scalp wound model of mice by topical administration. Histopathological examinations were then conducted by haematoxylin and eosin (H&E), Masson's trichrome staining and the immunofluorescence assay. Second, we further examined the anti-inflammatory mechanism of DHCA in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by immunofluorescence assay and Western blot analysis. Key findings: DHCA could promote scalp wound healing in mice by enhancing epithelial cell proliferation and collagen formation and reducing inflammatory cells infiltration. Moreover, the NF-κB nuclear translocation was suppressed remarkably by DHCA administration in connective tissue of healing area. DHCA was also shown to inhibit production of nitric oxide (NO) and interleukin (IL)-1β with downregulated inducible nitric oxide synthase (iNOS) expression in LPS-induced RAW 246.7 cells. More importantly, DHCA administration upregulated p-IκBα expression and induced nuclear translocation of NF-κB without affecting its expression. Conclusions: Our study indicated that DHCA exerted anti-inflammatory activity through inactivation of NF-κB pathways in macrophages and subsequently improved wound healing.

Motivated by our interest in hydrogen sulfide bio-chemistry and ent-kaurane diterpenoid chemistry, 14 hydrogen sulfide donating derivatives (9, 11a-c, 12a-c, 13, 14, 16a-c and 17a-b) of ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane were designed and synthesized. Four human cancer cell lines (K562, Bel-7402, SGC-7901 and A549) and two normal cell lines (L-02 and PBMC) were selected for antiproliferative assay. Most derivatives showed more potent activities than the lead ent-kaurane oridonin. Among them, compound 12b exhibited the most potent antiproliferative activities, with IC50 values of 1.01, 0.88, 4.36 and 5.21 μM against above human cancer cell lines, respectively. Further apoptosis-related mechanism study indicated that 12b could arrest Bel-7402 cell cycle at G1 phase and induce apoptosis through mitochondria related pathway. Through Western blot assay, 12b was shown to influence the intrinsic pathway by increasing the expression of Bax, cleaved caspase-3, cytochrome c and cleaved PARP, meanwhile suppressing procaspase-3, Bcl-2, Bcl-xL and PARP.