The extract from Agkistrodon halys venom protects against lipopolysaccharide (LPS)-induced myocardial injury.

BACKGROUND: Snake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups (10 rats per group): control group, LPS group and LPS + extract group. Rats in control and the LPS groups were intravenously injected with sterile saline solution, and rats in the LPS + extract group with the extract. After 2 h, rats of the control group were intraperitoneally injected sterile saline solution, and rats in the LPS and the LPS + extract groups were treated with LPS (20 mg per kg body weight). Levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were determined. Anti-inflammation of the extract was analyzed via determination of TNF-α and IL-6 in serum, and expression of TNF-α, IL-6, COX-2 and p-ERK protein in hearts. Heme oxygenase-1 (HO-1) and p-NF-κB protein expression in hearts, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum were used to evaluate the anti-oxidative properties of the extract. RESULTS: Extract pretreatment significantly decreased the level of serum CK and LDH, reduced the generation of inflammatory cytokines such as TNF-α and IL-6, and also reduced serum level of MDA in the LPS + extract group compared with the LPS group. In addition, the extract increased SOD activity in serum, HO-1 protein expression in hearts, and decreased TNF-α, IL-6, COX-2, p-NF-κB and p-ERK1/2 protein expression. CONCLUSION: Our results suggested that beneficial effect of this extract might be associated with an improved anti-oxidation and anti-inflammatory effect via downregulation of NF-κB/COX-2 signaling by activating HO-1/CO in hearts.

[Regulation Mechanism of Ginkgo-Dipyridamolum for Calcium Homeostasis on Cardioprotective Effect During Ischemia Reperfusion Injury].

OBJECTIVE: To explore regulatory mechanism of Ginkgo-dipyridamolum (GD) for calcium homeostasis on cardioprotective effect during ischemia reperfusion injury in the isolated rat heart. METHODS: 40 male SD-rats were randomly divided into five groups (n = 8): normal control group (NC), ischemia reperfusion group (IR), GD precondition group (GD + IR), Nicardipine and GD precondition group( Nic + GD + IR), and LaCl3 and GD precondition group (LaCl, + GD +IR). The hearts of rats were isolated after anesthesia and performed to profuse with Langendorff equipment. The heart functional indexes (HR, LVSP and ± dp/dt(max)) were detected at the five time points (stabilize point, ischemia 30 min, reperfusion 5 min, reperfusion 30 min, and reperfusion 60 min). The coronary effluents were also collected at the five time points. The activities of LDH and CK were measured, respectively, as well as the Ca2+ contents. After the experiments were finished,the myocardial mitochondria were isolated, homogenated and then the Ca2+ concentrations, the activities of IDH and α-OGDH were detected. The pathologic changes in myocardial tissues were also observed by histologic section. RESULTS: Compared with IR group, the heart functional indexes ( LVSP x HR and ± dp/dt(max)) of GD + IR group were improved at the five time points; the enzymes (LDH and CK) release, the Ca2+ concentrations, the activities of IDH and α-OGDH were reduced in mitochondrion. However, the protective effects above could be inhibited by Nic and LaCl3. Histologic sections showed that the myocardial tissue in IR group was damaged obviously, the damaged myocardial tissues were repaired in GD + IR, Nic + GD + IR and LaCl, + GD + IR) groups, especially in GD + IR group. CONCLUSION: Ginkgo-dipyridamolum can alleviate the myocardial ischemia reperfusion injury, the mechanism is probobaly related to maintaining calcium homeostasis and mitochondrial energy metabolism function.