Tribulosin

Acta Pharmacologica Sinica, 2010, 31(6):671-678.

Tribulosin protects rat hearts from ischemia/reperfusion injury.[Reference: WebLink]

To investigate the protective effect of Tribulosin, a monomer of the gross saponins from Tribulus terrestris, against cardiac ischemia/reperfusion injury and the underlying mechanism in rats.
METHODS AND RESULTS:
Isolated rat hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion using Langendorff's technique. The hearts were assigned to seven groups: control, ischemia/reperfusion (I/R), treatment with gross saponins from Tribulus terrestris (GSTT) 100 mg/L, treatment with Tribulosin (100, 10, and 1 nmol/L) and treatment with a PKC inhibitor (chelerythrine) (1 micromol/L). Infarct size was assessed by triphenyltetrazolium chloride staining. Malondialdehyde (MDA), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) contents as well as superoxide dismutase (SOD) and creatine kinase (CK) activities were determined after the treatment. Histopathological changes in the myocardium were observed using hematoxylin-eosin (H&E) staining. Apoptosis was detected with terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. Bcl-2, Bax, caspase-3, and PKCepsilon protein expression were examined using Western blotting. Tribulosin treatment significantly reduced MDA, AST, CK and LDH contents, and increased the activity of SOD. The infarct size of I/R group was 40.21% of the total area. GSTT and various concentrations of Tribulosin treatment decreased the infarct size to 24.33%, 20.24%, 23.19%, and 30.32% (P<0.01). Tribulosin treatment reduced the myocardial apoptosis rate in a concentration-dependent manner. Bcl-2 and PKCepsilon protein expression was increased after Tribulosin preconditioning, whereas Bax and caspase-3 expression was decreased. In the chelerythrine group, Bcl-2 and PKCepsilon expression was decreased, whereas Bax and caspase-3 expression was increased.
CONCLUSIONS:
Tribulosin protects myocardium against ischemia/reperfusion injury through PKCepsilon activation.

Journal of Asian Natural Products Research, 2011, 13(12):1135-1145.

Tribulosin suppresses apoptosis via PKC epsilon and ERK1/2 signaling pathway during hypoxia/reoxygenation in neonatal rat ventricular cardiac myocytes.[Reference: WebLink]

Tribulosin (tigogenin 3-O-β-d-xylopyranosyl(1–2)-[β-d-xylopyranosyl (1–3)]-β-d-glucopyranosyl (1–4)-[a-l-rhamnopyranosyl(1–2)]-β-d-galactopyranoside), a component of gross saponins of Tribulus terrestris, has been shown to produce cytoprotective effects in heart. Yet, the precise mechanisms are not fully understood.
METHODS AND RESULTS:
We examined the mechanisms of Tribulosin on myocardial protection. Ventricular myocytes were isolated from the heart of neonatal rats and were exposed to 3 h of hypoxia followed by 2 h reoxygenation. Apoptosis was induced by hypoxia/reoxygenation (H/R), and the expression of protein kinase C epsilon (PKCϵ) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured neonatal rat cardiac myocytes was detected. The results indicated that treatment with Tribulosin in the culture medium protected cardiac myocytes against apoptosis induced by H/R. PKCϵ and ERK1/2 expression increased after pretreated with Tribulosin. In the presence of PKCϵ inhibitor co-treated with Tribulosin, the expression of ERK1/2 was decreased in H/R cardiac myocytes. While preconditioned with PD98059, ERK1/2 inhibitor, no effects on the expression of PKCϵ were detected.
CONCLUSIONS:
Tribulosin has protective effects on cardiac myocytes against apoptosis induced by H/R injury via PKCϵ and ERK1/2 signaling pathway.