Xianxiang Xu

Polysaccharide of Radix Pseudostellariae Improves Chronic Fatigue Syndrome Induced by Poly I:C in Mice

Radix Pseudostellariae is used as a tonic drug in traditional Chinese medicine with immunomodulating and anti-fatigue activities, and the polysaccharide is considered as the main active component. The purpose of this study is to examine the effect of the polysaccharide isolated from Radix Pseudostellariae (PRP) on mouse chronic fatigue syndrome (CFS) induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a double-stranded synthetic RNA. It has shown that the fatigue symptom of mice lasted at least 1 week as evaluated by forced swimming time. PRP (100, 200, 400 mg kg−1), orally administered 3 days before poly I:C injection, showed dose-dependent anti-fatigue effects. In addition, poly I:C led to evident alternations in neuroendocrine and immune systems of mice, such as reduced spontaneous activity and learning ability, declined serum level of corticosterone, increased weight indexes and T lymphocyte numbers in thymuses and spleens, and increased CD4+/CD8+ ratio but decreased proliferation ability of T lymphocytes in spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to normal conditions. The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms of action involve neuroendocrine and immune systems.

Prevention of FGF-2-induced angiogenesis by scopoletin, a coumarin compound isolated from Erycibe obtusifolia Benth, and its mechanism of action.

Previous work in our laboratory has shown that scopoletin, one of the main bioactive constituents of Erycibe obtusifolia Benth stems, exerts anti-arthritic activity in vivo partly by preventing synovial angiogenesis. The present study was performed to further investigate the anti-angiogenic potential of scopoletin, focusing on the mechanisms of action in vitro. In the aortic ring sprouting assay, scopoletin (10, 30 and 100 μM) significantly inhibited the growth of endothelial sprouts in a concentration-dependent manner. As to human umbilical vein endothelial cells (HUVECs), scopoletin could inhibit their proliferation, migration and tubule formation induced by FGF-2, especially the proliferation. It also remarkably decreased the expression of VEGF at mRNA and protein levels, and the phosphorylations of IKKα and IκB but not Akt, as well as the degradation of IκB caused by FGF-2 in HUVECs. These findings suggest that scopoletin is substantially able to attenuate FGF-2-induced angiogenesis, and it might act by directly preventing the stimulation action of FGF-2 and by indirectly decreasing the production of VEGF. Scopoletin down-regulated the VEGF expression through NF-κB rather than PI-3K/Akt signaling pathway.

Madecassoside induces apoptosis of keloid fibroblasts via a mitochondrial-dependent pathway†

Centella asiatica herb is a frequently prescribed drug in southeastern Asia and China that can simultaneously facilitate wound healing and prevent scar formation. The active constituents and underlying mechanisms responsible for these biphasic actions remain unknown. Previous studies in our laboratory demonstrated that madecassoside, the main active triterpene saponin in C. asiatica herbs, was able to treat trauma‐caused scars in rabbit ear and facilitate burn wound healing in mice. As the formation and progression of keloid scars is closely related to the excessive proliferation and insufficient apoptosis of dermal fibroblasts, the effects of madecassoside on the proliferation and apoptosis of keloid fibroblasts (KFs) were examined in the present study. Primary KFs, originating from human earlobe keloids, were purified and cultured, and then treated with increasing concentrations of madecassoside (10, 30, and 100 µM) for 48 h. Madecassoside inhibited the proliferation of KFs in a time‐and concentration‐dependent manner, and induced KF apoptosis as revealed by Hoechst 33258 staining and flow cytometry analysis. Furthermore, madecassoside activated caspase‐9 and caspase‐3 rather than caspase‐8, depolarized the mitochondrial membrane potential, and regulated expression of Bcl‐2 family members in KFs. These findings suggest that madecassoside induced the apoptosis of KFs through a mitochondrial‐dependent pathway. Drug Dev Res 72: 315–322, 2011.  © 2010 Wiley‐Liss, Inc.

Qi-Shao-Shuang-Gan, a Combination of Astragalus membranaceus Saponins with Paeonia lactiflora Glycosides, Ameliorates Polymicrobial Sepsis Induced by Cecal Ligation and Puncture in Mice

The present study was performed to investigate the anti-septic effects of Qi-Shao-Shuang-Gan (QSSG), a combination of Astragalus membranaceus saponins (SAM) and Paeonia lactiflora glycosides (GPL), in septic mice induced by cecal ligation and puncture. QSSG was shown to elevate the survival rate of mice, decrease infiltration of polymorphonuclear leukocytes into livers and lungs, lower serum levels of myeloperoxidase, nitric oxide, and lactate dehydrogenase, and decrease mRNA expressions of inducible nitric oxide synthase and interleukin-1β in livers. It also restored the impaired expressions of protein C (PC) mRNA in mouse livers and expressions of thrombomodulin and endothelial PC receptor mRNA in endothelial cells. Neither SAM nor GPL alone could significantly increase the survival rate of septic mice. The findings indicate that QSSG exerts protective action against polymicrobial sepsis by inhibiting systemic inflammatory response and upregulating PC pathway, and there are synergistic effects between SAM and GPL.