1.
Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species.
Yuan, H, Houck, KL, Tian, Y, Bharadwaj, U, Hull, K, Zhou, Z, Zhu, M, Wu, X, Tweardy, DJ, Romo, D, et al
PloS one. 2015;(12):e0143964
Abstract
BACKGROUND Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. OBJECTIVE We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. RESULTS PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. CONCLUSIONS PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.
2.
Effects of Quyu xiaoban capsules on clinical outcomes and platelet activation and aggregation in patients with unstable angina pectoris.
Liu, YF, Yu, HM, Zhang, C, Yang, RX, Yan, FF, Liu, Y, Zhang, Y, Zhao, YX
Journal of alternative and complementary medicine (New York, N.Y.). 2007;(3):369-74
Abstract
OBJECTIVES To investigate the effects of the Traditional Chinese Medicine (TCM) Quyu Xiaoban capsules (QYXB) on clinical outcomes and platelet activation and aggregation in patients with unstable angina pectoris (UAP) and phlegm and blood stasis syndrome. DESIGN Ninety patients with UAP were randomly divided into two groups: a control group that received a loading dose of 300 mg aspirin and a maintenance dose of 100 mg of aspirin plus baseline therapy for 4 weeks, and a trial group that received the same doses of aspirin and baseline therapy plus QYXB for 4 weeks. The severity of anginal attacks, alterations of TCM symptoms and signs, and electrocardiographic (ECG) changes were assessed in all patients before and after treatment. The plasma platelet aggregation (PAG) rate and P-selectin level were measured in all patients at baseline and at the end of the fourth week of treatment. RESULTS After treatment for 4 weeks, both group of patients showed improvement in the severity of angina pectoris and TCM symptoms and signs, but there was a significant difference in the two groups' rates of clinical improvement, whereas the rate of ECG improvement of the two groups showed no difference. As compared with the baseline value, the PAG rate in both groups decreased significantly at the end of the fourth week (63.74 +/- 11.18% vs. 55.69 +/- 10.40% in the control group, and 63.83 +/- 12.70% vs. 50.04 +/- 8.91% in the trial group). Similar changes in P-selectin levels were observed in the two groups (9.40 +/- 1.25 ng/mL vs. 8.90 +/- 1.34 ng/mL in the control group, and 9.56 +/- 1.16 ng/mL vs. 7.80 +/- 0.98 ng/mL in the trial group). However, both the PAG rate and P-selectin level decreased to a greater extent in the trial group than in the control group after treatment, and the difference between the two groups was significant (both p < 0.05). Nevertheless, these biochemical changes were too small to fully explain the beneficial clinical outcomes achieved with QYXB capsules. CONCLUSIONS In comparison with both the respective baseline values and with aspirin therapy, QYXB capsules significantly attenuated anginal attacks and improved TCM symptoms and signs in patients with UAP. The exact mechanisms underlying these therapeutic effects remain to be explored.