Screening of soluble epoxide hydrolase inhibitory ingredients from traditional Chinese medicines for anti-inflammatory use

Abstract

Ethnopharmacological relevance Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. Aim of the study To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo. Materials and Methods In vitro inhibition assay of the sEH was conducted for the methanol and ethanol extracts of 27 anti-inflammatory TCMs. Two potent extracts were subject to further separation guided by bioassay to afford promising AI against sEH in vitro [Fr.5 of the crude ethanol extract of Rhizoma coptidis (FFCERC)]. Finally, the in vivo anti-inflammatory effect and sEH inhibitory potency of FFCERC was evaluated in a lipopolysacchride (LPS)-challenged murine model of acute systemic inflammation. The inflammatory status was characterized by the inflammatory cytokines TNF-α and interleukine-6 (IL-6) and sEH inhibitory function was evaluated by the plasma levels of epoxyeicosantrienoic acids (EETs) and dihydroxyeicosantrienoic acids (DHETs), which are the sEH mediated substrates and products, respectively. Results At the concentration of 25µg/mL, the crude ethanol extracts of 6 TCMs including Herba Asari, Radix Polygalae, Fructus Amomi, Radix Astragali, Radix Scutellariae, and Rhizoma Coptidis were potent against sEH. The crude extracts of Herba Asari and Rhizoma Coptidis were selected for further separation to afford FFCERC as the most promising AI for in vivo evaluation. Oral administration of FFCERC attenuated the significant increase in TNF-α and IL-6 caused by LPS challenge in a dose-dependent manner. In parallel, oral administration of FFCERC shifted the changes in plasma levels of EETs and DHETs caused by LPS-challenge like a synthetic sEH inhibitor. Conclusions A sEH inhibitory AI from Rhizoma Coptidis is anti-inflammatory and the inhibition of sEH contributes to this biological effect, indicating that sEH may be at least one of multiple therapeutic targets for relevant TCMs.

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

“…Belyanskaya and coworkers deployed the encoded library technology (ELT) for the discovery and early clinical development of an inhibitor of the enzyme soluble epoxide Research on natural product-based sEHIs development has sought to address the typical drawbacks of synthetic small molecule inhibitors. A plethora of natural products, including stilbenes, carbazole, anthraquinones, selaginellin, cycloartane triterpene, capsaicin, dihydrocapsaicin, anthocyanin derivatives and phenolic glycosides derivatives, possess sEHI activity ( Figure 6) [107][108][109][110][111][112][113][114][115][116][117][118][119]. Interestingly, very few natural products bear the urea or carbamate groups that form the mainstay of synthetic sEHIs.…”

A combination of clinical study and Network Pharmacology approach to explore the efficacy and mechanism of Buxue Yimu Pills on gynecological anemia

“…The previous study has found a negative correlation between Hb concentration and in ammatory markers, especially interleukin 6 (IL-6) 9 . As mentioned before, Buxue Yimu Pills can reinforce qi and nourish the blood, whose main components have previously been observed to have different e cacies of promoting hematopoiesis and anti-in ammatory effects [12][13][14] . After treatment, with decreased in ammation and increased hematopoiesis, iron in nonhematopoietic cells can be transported to erythroid precursors more e ciently; subsequently, levels of circulating iron decrease.…”

“…Buxue Yimu Pills (BYP), a TCM with primary e cacy of Qi-reinforcing and nourishing blood, consists of Angelicae Sinensis Radix (Danggui), Hedysarum Multijugum Maxim (Huangqi), Colla Corii Asini (Ejiao), Leonuri Herba (Yimucao), and Citrus Reticulata (Chenpi) according to Pharmacopoeia of the People's Republic of China. Previous studies have shown that Yimucao promoted uterine contractions, thus reducing vaginal bleeding; Ejiao, Danggui, Huangqi, and Chenpi could bene t Qi, activate blood circulation and promote hematopoiesis 12 ; Huangqi and Danggui exerted anti-in ammatory effects 13,14 . Therefore, we hypothesized that BYP could treat GA through a variety of mechanisms.…”

Identification of a Multicomponent Traditional Herbal Medicine by HPLC–MS and Electron and Light Microscopy

“…Recent investigations confirmed the effects of Sha-Ren for relieving abdominal spasms, bloating, and pain [ 17 , 18 ]. Rhizoma Pinelliae has antiemetic, glandular, antitussive, secretion-inhibiting, and antitumor effects, according to modern pharmacological studies [ 19 ].…”