Interaction of Vietnamese Medicinal Plant Extracts with Recombinantly Expressed Human Neurokinin-1 Receptor

Abstract

!A primary functional receptor screening assay was performed to examine the effects of methanolic extracts from ten Vietnamese medicinal plants on the human neurokinin-1 receptor expressed from Semliki Forest virus vectors in Chinese hamster ovary cells. Extracts from Piper nigrum, Stephania cambodica and Styphnolobium japonicum were found to exert inhibition on agonist-induced human neurokinin-1 receptor activity. Secondary assays and high performance liquid chromatography of the lead compounds addressed a possible association between pharmacological responses and these chemical compounds. Strong inhibition of human neurokinin-1 receptor was observed for extracts revealing the highest inhibitory potency for rotundine (tetrahydropalmatine) in S. cambodica extracts with IC 50 of 0.88 µM, followed by piperine and capsaicin in P. nigrum extracts with IC 50 values of approximately 2 µM, whereas rutin in S. japonicum extracts failed to inhibit hNK1R up to 100 µM. [4]. Since the hNK1R is known to be present in both the CNS and a number of other tissues and has been the target for development of drugs for migraine, emesis, anti-inflammation and psychiatric disorders [5,6], the potential interaction between plant extracts and the hNK1R is of significant interest. In this study, we employed the SFV system for overexpression of the hNK1R in CHO cells to investigate the effects of plant extracts on agonist-induced receptor activity. The methanolic extracts of the ten Vietnamese medicinal plants were subjected to a preliminary screening for their effects on receptors in presence of the agonist Substance P (SP). Extracts from three species, namely P. nigrum, S. japonicum and S. cambodica, were further selected and examined for probable associations between different geographical locations (accessions) with biological activity. Moreover, lead compounds of plant extracts from these three species were analyzed by HPLC and examined in functional receptor assays to elucidate whether extracts derived from different locations exert different activities in relation to their concentrations of lead compounds. HPLC was applied to determine the amount of piperine and capsaicin in P. nigrum, rotundine in S. cambodica, and rutin in S. japonicum collected from five different geographical locations (l " Fig. 1 and Table 1). The fruit extracts from P. nigrum, capsaicin and piperine showed the most consistent amounts of analyzed compounds ranging between 0.14 ± 0.01 % and 0.24 ± 0.01 % and between 1.51 ± 0.11 % and 2.22 ± 0.08 %, respectively. For tuber and root extracts from S. cambodica, the range of rotundine was between 0.98 ± 0.18 % and 4.69 ± 0.15 %, and moderately variable. In flower bud extracts from S. japonicum, rutin ranged from 0.17 ± 0.01 % to 6.14 ± 0.18 % showing the largest variation among analyzed compounds. The degree of variability within each species appeared to be influenced by not only the genotype, but also the plant parts examined. In this context, extracts of fruits (P. nigrum) showed the least variation, tu...

Interaction of Plant Extracts with Central Nervous System Receptors

“…For instance, it was demonstrated that samples from Ligularia fischeri leaves collected in summer (June) showed higher phenolic compounds, stronger anti-oxidative, and anti-microbial activity than samples collected in winter (December) [ 64 ]. Moreover, the location plays an important role as demonstrated for the differences in potency of NK1 receptor inhibition for Vietnamese plants collected from different parts of the country [ 26 ]. Furthermore, fruit from high-bush blueberries ( Vaccinium corymbosum ) and low-bush blueberries ( Vaccinium angustifolium ) showed differences in the contents of anthocyanins and total phenolic compounds [ 65 ].…”

“…Relatively potent binding inhibition was observed for extracts from E. indica and P. vulgaris , whereas the other plant extracts showed only weak or no inhibition. More recently, functional screening of 10 Vietnamese medicinal plants on SFV-based expression of the NK1 receptor in CHO cells demonstrated agonist-induced activity for extracts from Piper nigrum , Stephania cambodica , and Styphnolobium japonicum [ 26 ].…”

Chemical profiling of the tuber of Stephania cambodica Gagnep. (Menispermaceae) and analytical control by UHPLC-DAD

“…In Vietnam, the tuber of S. cambodica is used in combination with other plants for treatment of various diseases such as depression, asthma, hypertension… (Do et al 1999). Despite its well-established use, few phytochemical studies have been undertaken on S.cambodica (Thanh and Hung 2011;Dinh et al 2015).…”

“…Rotundine (l-tetrahydropalmatine) the main alkaloid isolated from S. cambodica tuber has been shown to be responsible for the inhibition of neurokinine-1 receptor gene expression (Dinh et al 2015). The presence of rotundine in S. cambodica tuber could justify its traditional use as an anxiolytic remedy in Cambodia since in Vietnam and China, rotundine is used as an anxiolytic and hypnotic drug (Wang and Mantsch 2014).…”