Huahua Zhang

Publications (2)4.25 Total impact

• Article: Japonicone A antagonizes the activity of TNF-α by directly targeting this cytokine and selectively disrupting its interaction with TNF receptor-1.

  Zhenlin Hu, Jiangjiang Qin, Huahua Zhang, Dan Wang, Yaping Hua, Jieping Ding, Lei Shan, Huizi Jin, Junping Zhang, Weidong Zhang
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  ABSTRACT: Anti-TNF biologics are effective therapies for various inflammatory diseases. Unfortunately, their clinical use is associated with an increased risk of infections. Selectively inhibiting TNF receptor-1 (TNFR1)-mediated signaling while preserving TNFR2 signaling may reduce inflammation yet maintain host immune response to pathogens. However, few small molecules that selectively target the TNF/TNFR system have been discovered. In the present study, we identified Japonicone A (Jap A), a nature compound derived from Inula japonica Thunb, as a novel TNF-α antagonist, as it reduced the TNF-α-mediated cytotoxicity on L929 cells and inhibited the binding of (125)I-labeled TNF-α to L929 cell surface. Furthermore, Jap A could directly bind to TNF-α rather than TNFR1 as determined by surface plasmon resonance. More importantly, Jap A could effectively inhibit the binding of TNF-α to TNFR1, while displaying only marginal inhibitory effects on that to TNFR2. Jap A also could block TNFR1-mediated signaling as it inhibited TNF-α-induced NF-κB activation in 293 cells. In addition, Jap A suppressed TNF-α-induced expressions of adhesion molecules (ICAM-1, VCAM-1) and chemokine (MCP-1) in the endothelial cells by blocking TNF-α-triggered multiple signaling pathways. Data from in vivo experiments demonstrated that Jap A protected mice from acute hepatitis induced by TNF-α/d-galactosamine, but did not compromise host antiviral immunity in adenovirus-infected mice. These results indicate that Jap A can directly target TNF-α, selectively disrupt its interaction with TNFR1, and antagonize its pro-inflammatory activities without compromising host defense against virus, thus emphasizing the potential of Jap A as an interesting lead compound for development of new anti-inflammatory drugs.
  Biochemical pharmacology 09/2012; · 4.25 Impact Factor
• Source

  Available from: PubMed Central

  Article: Baicalin induced dendritic cell apoptosis in vitro.

  Huahua Zhang, Qingqing Jiao, Qianfeng Gong, Yan Zhang, Weidong Zhang, Zhenlin Hu
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  ABSTRACT: This study was aimed to investigate the effects of baicalin (BA), a major flavonoid constituent found in the herb Baikal skullcap, on dendritic cells (DCs). DCs were generated by culturing murine bone marrow (BM) cells for 6 days with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4, and lipopolysaccharide (LPS) was added on day 5 to stimulate DCs maturation. The expression levels of DC maturity markers (CD80/CD86) were assessed by flow cytometry using direct immunofluorescence method. IL-12 levels in the culture supernatants were assayed by ELISA. Apoptosis of DCs was analyzed by flow cytometry after annexin V/propidium iodide staining. The mitochondrial membrane potential (Δψ(m)) changes were measured by using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Exposure of DCs to BA (2-50 μM) during BM cell differentiation showed no effects on the up-regulation of CD80/CD86 expression on DCs in response to LPS stimulation, but reduced DCs recovery by inducing apoptosis, and significantly inhibited the release of IL-12 to culture supernatants. BA-induced DC apoptosis in a time- and dose-dependent way, and immature DCs were more sensitive for BA-induced apoptosis than mature DC. BA also induced Δψ(m) changes in DCs. These results demonstrate that BA induces selective apoptosis in immature DCs possibly through mitochondria-mediated pathway.
  Frontiers in pharmacology. 01/2011; 2:15.