Inhibitory effects of atractylodis lanceae rhizoma and poria on collagen- or thromboxane A2-induced aggregation in rabbit platelets.

Biol Pharm Bull. 2009 May; 32(5): 856-60Nasu Y, Iwashita M, Saito M, Fushiya S, Nakahata NKami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation.

Isolation of a chemical inhibitor against K-Ras-induced p53 suppression through natural compound screening.

Int J Oncol. 2009 Jun; 34(6): 1637-43Lee SJ, Jung YS, Lee SH, Chung HY, Park BJThe strong tumor suppressor p53 shows loss of function in large portion of human cancer. In addition to genetic mutation, biological function of p53 is suppressed by signaling distortion or elevated expression of p53 inhibitors (such as overexpression of MDM2 or deletion of p14/ARF). In this study, we demonstrate that K-Ras, a frequently altered oncogene in human cancers including pancreatic cancer (about 80%), colon cancer (45%) and lung cancer (45%), suppresses p53. Based on this fact, we perform Western blot analysis-based chemical screening to isolate a K-Ras-specific activator of p53. From 117 kinds of chemicals (34 kinds of natural compounds that are obtained from herbal plants, 53 kinds of flavonoid, and 31 kinds of phenolic compounds), we find that quercetin works as an activator of p53 in K-Ras mutated cells but not in wild-type cells. Treatment with quercetin can induce p53 target genes such as PUMA and p21. These results suggest that although quercetin has limitations for use as a therapeutic drug due to its broad effects, specific function of it on K-Ras-p53 may be useful for K-Ras-induced cancer prevention and therapy through further development.

Immunosuppressive Effects of Demethylzeylasteral in a Rat Kidney Transplantation Model.

Int Immunopharmacol. 2009 Apr 18; Xu W, Lin Z, Yang C, Zhang Y, Wang G, Xu X, Lv Q, Ren Y, Dong YIn this study, we examined the immunosuppressive activity of demethylzeylasteral (T-96), isolated from the traditional Chinese herbal medicine, Tripterygium wilfordii Hook f. Its immunosuppressive effect was investigated using mouse splenocytes in vitro, and in an in vivo rat kidney transplant model. T-96 inhibited mouse splenocyte proliferation in a dose dependent manner. In the rat kidney transplant study, rats were randomly divided into eight groups following kidney transplantation, and different doses of T-96 or cyclosporin A (CsA) were administered to each group. T-96 alone at doses of 10 or 20 mg/kg/day significantly prolonged the survival of kidney-transplanted rats, compared with transplanted but untreated control rats. A combination of T-96 and prednisone also significantly prolonged survival: 10 mg/kg/day T-96 with 10 mg/kg/day prednisone increased the survival time to 31.8+/-6.5 days. Moreover, the combination of T-96 and prednisone was also effective in suppressing rejection of rat transplanted kidneys. These results demonstrate the strong immunosuppressive activity of T-96 and suggest a possible clinical use for T-96 as an immunosuppressive agent in the fields of organ transplantation and autoimmune disorders.

Induction of multiple pro-inflammatory cytokines by respiratory viruses and reversal by standardized Echinacea, a potent antiviral herbal extract.

Antiviral Res. 2009 Apr 29; Sharma M, Anderson SA, Schoop R, Hudson JBSeveral viruses associated with upper respiratory diseases have been shown to stimulate the secretion of pro-inflammatory cytokines, including chemokines, sometimes in the absence of viral cytopathology. We evaluated the ability of a standardized preparation of the popular herbal medicine Echinacea (Echinaforce((R)), an ethanol extract of herb and roots of E. purpurea, and containing known concentrations of marker compounds) to inhibit the viral induction of various cytokines in a line of human bronchial epithelial cells (BEAS-2B), and in two other human cell lines. All of the viruses tested, rhinoviruses 1A and 14, influenza virus, respiratory syncytial virus, adenovirus types 3 and 11, and herpes simplex virus type 1, induced substantial secretion of IL6 and IL8 (CXCL8), in addition to several other chemokines, depending on the virus, although only viable viruses were able to do this. In every case however Echinacea inhibited this induction. The Echinacea preparation also showed potent virucidal activity against viruses with membranes, indicating the multifunctional potential of the herb. These results support the concept that certain Echinacea preparations can alleviate "cold and flu" symptoms, and possibly other respiratory disorders, by inhibiting viral growth and the secretion of pro-inflammatory cytokines.

[Pathological study on autopsy died of tripterygium intoxication--report of 4 cases]

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009 Feb; 29(2): 165-8Huang GZ, Li L, Liu LThe Tripterygium preparation, a Chinese herbal medicine, has been widely used to treat various autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Its significant clinical effects have received a great praise and attention by the public health in China, but its toxicity also definitely exists, with the therapeutic dosage approaching the minimal toxic dosage. In order to provide reference for the safe use of Tripterygium preparation in clinical practice, the pathological changes of 4 autopsy cases by Tripterygium poisoning were reported in this paper. In them, 2 cases died of acute cardiogenic shock caused by myocardial damage, showing hydropic degeneration of the myocardial cells, even with obvious contraction band necrosis in the papillary muscles; the other 2 died of severe acute renal failure due to severe acute toxic nephrosis; cerebral edema and gastrointestinal inflammatory changes were found in all cases. The authors suggested that careful dosage control is the key step to prevent Tripterygium intoxication during the medical treatments; directly using the crude Tripterygium in clinics should be prohibited; and the Tripterygium preparation used should be produced by the pharmaceutical companies regulated by the government.