Analgesic Effects of Ephedra Herb Extract, Ephedrine Alkaloids–Free Ephedra Herb Extract, Ephedrine, and Pseudoephedrine on Formalin-Induced Pain

Abstract

The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids-free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0-5 min; second phase, 10-45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, "authentic" EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse-and at 4 to 6 h after administration of EHE-Ts-only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4-6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.

Regulatory science of natural products

“…NGF is an inflammatory mediator and NGF-Trk A signalling is involved in inducing pain and itching [ 134 ]. Therefore, we investigated the analgesic effect of herbacetin using the formalin test [ 139 ]. The results suggested herbacetin suppressed the second phase of formalin-induced pain in a dose-dependent manner.…”

Quality Evaluation and Characterization of Fractions with Biological Activity from Ephedra Herb Extract and Ephedrine Alkaloids-Free Ephedra Herb Extract

“…Recently, we found that EFE relieves inflammatory pain. 13,14) Therefore, we examined the analgesic effects of each fraction isolated from EFE using the formalin test in vivo. The formalin test is widely used to evaluate analgesic effects.…”

“…7). 13 C-NMR spectra were measured for the Fr. (a) that showed significant c-Met inhibitory activity.…”

“…12) EFE exerted analgesic, anti-influenza, and anticancer effects in the same manner as EHE. 13,14) We reported that EHE has adverse effects such as excitation, insomnia, and arrhythmias; however, EFE does not elicit these adverse effects. 15) Moreover, our clinical trial suggested that EFE is safer than EHE.…”

Ephedra alata extracts exhibits anti-obesity, anti-hyperlipidaemic, anti-hyperglycemia, anti-antipyretic and analgesic effects through the inhibition of lipase, α-amylase and inflammation

“…Ephedra alata was an important source of several pharmaceutical compounds such of cardiac glycosides, reducing sugars, avonoids, phenolic compounds, and alkaloids; and as Signi cant medicinal properties of this genus were reported such as antimicrobial, antioxidant, antidiabetic, hepatoprotective, cardiovascular, and anticancer effects [13][14][15][16]. Previous studies have reported that Ephedra Herb may have applications in cancer therapy and suppressed cancer metastasis by inhibiting cancer cell motility [17,8,9] and prevented hepatocyte growth factor (HGF)-induced cancer cell motility by inhibiting phosphorylation of the c-Met receptor [17].…”