Effects of Goshajinkigan, Hachimijiogan, and Rokumigan on Mechanical Allodynia Induced by Paclitaxel in Mice

Abstract

Peripheral neuropathy is a major dose-limiting side effect of the chemotherapeutic agent paclitaxel. This study examined whether the three related traditional herbal formulations, goshajinkigan (GJG; 牛車腎氣丸 Niú Chē Shèn Qì Wán), hachimijiogan (HJG; 八味地黃丸 Bā Wèi Dì Huáng Wán), and rokumigan (RMG; 六味丸 Liù Wèi Wán), would relieve paclitaxel-induced mechanical allodynia in mice. A single intraperitoneal injection of paclitaxel (5 mg/kg) induced mechanical allodynia, which peaked on day 14 after injection. On day 14 after paclitaxel injection, oral administration of GJG (0.1-1.0 g/kg) produced a significant inhibition of established allodynia, but HJG and RMG did not affect the allodynia. Repeated oral administration of GJG (0.1-1.0 g/kg) starting from the day after paclitaxel injection did not affect allodynia development, but significantly inhibited allodynia exacerbation. Repeated oral administration of HJG produced a slight inhibition of allodynia exacerbation, but that of RMG did not. These results suggest that prophylactic administration of GJG is effective in preventing the exacerbation of paclitaxel-induced allodynia. The herbal medicines Plantaginis Semen (車前子 Chē Qián Zǐ) and Achyranthis Radix (牛膝 Niú Xī), which are present in GJG but not in HJG, may contribute to the inhibitory action of GJG on the exacerbation of paclitaxel-induced allodynia.

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy

“…daily) in mice, although Jesengshingi-Hwan could not suppress cancer-induced allodynia [43]. Andoh et al [111] also reported that Jesengsingi-Hwan (0.1-1.0 g/kg, p.o.) markedly inhibited paclitaxel-induced mechanical allodynia in mice.…”

Somatostatin Receptor–Mediated Specific Delivery of Paclitaxel Prodrugs for Efficient Cancer Therapy

“…However, serious drawbacks hamper the clinical application of PTX. First, PTX lacks selective cytotoxicity against cancer cells and frequently leads to serious side effects . Poor water solubility of PTX (0.3 μg/mL) is another concern that significantly reduces its wider clinical application.…”

“…First, PTX lacks selective cytotoxicity against cancer cells and frequently leads to serious side effects. 2 Poor water solubility of PTX (0.3 :g/mL) is another concern that significantly reduces its wider clinical application. To enhance its water solubility, PTX is currently formulated as a 50:50 mixture of Cremophor EL and ethanol (Taxol).…”

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

“…In our preliminary experiments, a single administration of aucubin did not alleviate paclitaxelinduced allodynia at day 14 after the paclitaxel injection (data not shown), which was similar to the effect observed with goshajinkigan. 9) This suggests that aucubin requires repetitive administration to produce an anti-allodynic effect. In addition, the results of the present study show that repetitive administration of aucubin, but not its metabolite catalpol, inhibits the exacerbation of paclitaxel-induced mechanical allodynia, which complements the results in our previous report.…”

“…7,8) Our previous study has been shown that repetitive administration of goshajinkigan extract as a prophylactic inhibits the exacerbation of paclitaxel-induced mechanical allodynia in mice. 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.…”