Prophylactic administration of an extract from Plantaginis Semen and its major component aucubin inhibits mechanical allodynia caused by paclitaxel in mice

Abstract

The chemotherapeutic agent paclitaxel (PTX) causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan (牛車腎氣丸 niú chē shèn qì wán), but not hachimijiogan (八味地黃丸 bā wèi dì huáng wán), which lacks two of the constituents of goshajinkigan, inhibited PTX-induced mechanical allodynia in mice. Thus, the herbal medicines Plantaginis Semen (車前子 chē qián zǐ) or Achyranthis Radix (牛膝 niú xī) may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced mechanical allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293–297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS) or Achyranthis Radix (EAR) would relieve PTX-induced mechanical allodynia in mice. A single intraperitoneal injection of PTX caused mechanical allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced mechanical allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced mechanical allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin) or catalpol (a metabolite of aucubin) did not prevent the exacerbation of mechanical allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced allodynia.

A case of unresectable pancreatic cancer successfully treated with Gosha-jinki-gan for muscle cramps related to administration of S-1

“…Seven GJG, an aqueous extract of a combination of 10 herbs, is widely used in Japan for the treatment of lumbago, edema of the lower extremities, numbness, blurred vision, lower urinary tract symptoms, diabetic neuropathy and pain in people with diminished physical strength 9) . Recently, preventive effects of oral GJG on chronic oxaliplatin-induced hypoesthesia 10) and paclitaxel induced allodynia 11) in animal models were reported. Clinically, GJG could show the preventive effect of paclitaxel induced peripheral neuropathy for patients with ovarian or endometrial cancer who underwent chemotherapy by a multicenter study 12) .…”

Aucubin protects against pressure overload‐induced cardiac remodelling via the β3‐adrenoceptor–neuronal NOS cascades

“…is a famous traditional Chinese medicine that exhibits antioxidative stress and neuroprotective effects (Andoh et al, 2017). is a famous traditional Chinese medicine that exhibits antioxidative stress and neuroprotective effects (Andoh et al, 2017).…”

“…is a famous traditional Chinese medicine that exhibits antioxidative stress and neuroprotective effects (Andoh et al, 2017). Previous studies have explored the therapeutic potential of aucubin for many other diseases, such as diabetes mellitus (Jin et al, 2008), skin fibrosis (Ho et al, 2005) and peripheral neuropathy (Andoh et al, 2017). Previous studies have explored the therapeutic potential of aucubin for many other diseases, such as diabetes mellitus (Jin et al, 2008), skin fibrosis (Ho et al, 2005) and peripheral neuropathy (Andoh et al, 2017).…”

“…Aucubin, a major compound found in E. ulmoides Oliv., has been shown to regulate oxidative stress (Xue et al, 2009), ER stress (Lee et al, 2013), autophagy and apoptosis . Aucubin has been reported to exert antioxidative effects in neurons (Xue et al, 2009), liver and kidneys (Jin et al, 2008) and to exert anti-ER stress effects in peripheral Schwann cells (Andoh et al, 2017) and HepG2 cells (Lee et al, 2013). Aucubin has been reported to exert antioxidative effects in neurons (Xue et al, 2009), liver and kidneys (Jin et al, 2008) and to exert anti-ER stress effects in peripheral Schwann cells (Andoh et al, 2017) and HepG2 cells (Lee et al, 2013).…”

Prophylactic Administration of Aucubin Inhibits Paclitaxel-Induced Mechanical Allodynia <i>via</i> the Inhibition of Endoplasmic Reticulum Stress in Peripheral Schwann Cells

“…9) We also showed that aucubin, which is an iridoid glycoside and the main component of Plantaginis Semen, plays an important role in the anti-allodynic action of goshajinkigan. 10) However, the mechanisms underlying the anti-allodynic activity of aucubin are not understood completely. It was reported in a previous study that paclitaxel decreased peripheral blood flow and induced mechanical allodynia in mice.…”