Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Abstract

Ethnopharmacological relevance: There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. Materials and Methods:In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action.The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. Results:The results showed that PS extracts (100, 200 mg/kg) and PSY (12.5, 25, 50 mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20 mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. Conclusions:These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.

Piper Species: A Comprehensive Review on Their Phytochemistry, Biological Activities and Applications

“…Functional properties of P. sarmentosum as antidepressant were exhibited in rodent animal model by means of hypothalamic-pituitary-adrenal axis regulation [373]. In the study of Li et al [373] these properties of the P. sarmentosum extract and its ethyl acetate fraction (PSY) were investigated by using several parameters including forced swimming test, open field test, and tail suspension test in mice.…”

“…Functional properties of P. sarmentosum as antidepressant were exhibited in rodent animal model by means of hypothalamic-pituitary-adrenal axis regulation [373]. In the study of Li et al [373] these properties of the P. sarmentosum extract and its ethyl acetate fraction (PSY) were investigated by using several parameters including forced swimming test, open field test, and tail suspension test in mice. The results showed that treatment of mice with either P. sarmentosum extracts at 100 and 200 mg/kg or PSY at 12.5–50 mg/kg doses resulted in potent antidepressant effects, which is similar to response obtained by 20 mg/kg conventional therapeutic drug fluoxetine.…”

The efficacy and safety of Anyu Peibo Capsule in the treatment of patients with major depressive disorder in China: study protocol for a randomized placebo-controlled trial

“…Anyu Peibo Capsule is a new antidepressant, extracted from Piper Laetispicum C.D C. (Piperaceae) which is a climbing glabrous plant grows in the south of China and has been used for invigorating circulation and reducing detumescence, stasis, and analgesic [8,9,10,11] . The pharmacodynamics of Anyu Peibo Capsule were assessed in health volunteers.…”

Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress

“…NR2B-containing channels predominantly signal via extracellular signal-regulated kinase (ERK) (17), a pivotal transcription regulator of the mitogen-activated protein kinase family (18). One potential effector of ERK signaling involved in CUMS-induced depression is cAMP response element binding protein, a transcription factor essential for neurogenesis, neuronal survival, and neuroplasticity (19) and, for which, the activity (20) and phosphorylation (21) are linked to the responsiveness to antidepressants.…”