[Therapeutic effect of total triterpenoids of Chaenomeles speciosa combined with omeprazole on gastric ulcer induced by indomethacin in rats].

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1ß, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1ß, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1ß and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.

[Cardioprotective Effect and Its Mechanism of Total Saponins of Panacis Majoris Rhizoma in Myocardial Infarction Rats].

OBJECTIVE: To explore the cardioprotective effect and its mechanism of total saponins of Panacis Majoris Rhizoma in myocardial infarction (MI) rats. METHODS: The MI model rats induced by ligating anterior descending branch of coronary artery were randomly divided into four group:model group, total saponins of Panacis Majoris Rhizoma (100 and 200 mg/kg) groups and compound Danshen dripping pills group. The rats were orally administrated with drugs once a day for four weeks. Another rats were selected as sham operation group. After four weeks intervention, cardiac function was examined, the serum levels of TNF-α, IL-1ß, IL-6 and IL-8 were measured by using ELISA, respectively. The myocardial hypertrophy index was investigated, the myocardial infarct size, degree of ventricular dilatation, myocardial interstitial collagen volume fraction and tissue morphology were investigated by HE, Masson, picric acid-sirius red staining and observing with alight microscope and electron microscope. Protein expressions of phosphorylation IκB-α( pIκB-α) and NF-κB p65 in heart tissue were detected by Western blotting. RESULTS: Total saponins of Panacis Majoris Rhizoma might significantly decrease the levels of serum TNF-α, IL-1ß, IL-6 and IL-8; decrease myocardial hypertrophy indexes, myocardial infarct size, degree of ventricular dilatation and myocardial interstitial collagen volume fraction; improve heart tissue morphology and cardiac function; downregulate protein expression of pIκB-α and NF-κBp65; and upregulate protein expression of SIRT1. The aforementioned action effects of total saponins of Panacis Majoris Rhizoma (200 mg/kg) were similar with compound Danshen dripping pills. CONCLUSION: Total saponins of Panacis Majoris Rhizoma possesses cardioprotective effect against ligating left anterior descending branch induced MI in rats. The mechanism may be related to strengthening SIRT1 expression, inhibiting the phosphorylation of IκB-α, and finally inhibiting the activation of NF-κB and proinflammatory production.