Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula “Goshajinkigan”

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (1-4) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

“…The efficacy of complementary therapies in the prevention and treatment of CIPN has also been a subject of research. Herbal medicinal therapies (e.g., Acorus calamus, Cannabis species, Matricaria chamomilla, Ginkgo biloba, Curcuma longa, Camellia sinensis) counteract phenomena underlying CIPN, i.e., they reduce oxidative stress and attenuate inflammation in animals [163], but their utility for CIPN prevention requires further investigation to confirm their efficacy and safety [164][165][166][167].…”

Phenylpropanoid conjugated iridoids with anti-malarial activity from the leaves of Morinda morindoides

“…In the course of identifying the responsible bioactive compound in the crude drug materials used in the traditional medicine [23][24][25], we focused on the leaves of M. morindoides. Both in vitro and in vivo antimalarial activity of the leaf extract of this plant have been reported [9,26].…”

Gabapentin and Duloxetine Prevent Oxaliplatin- and Paclitaxel-Induced Peripheral Neuropathy by Inhibiting Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Phosphorylation in Spinal Cords of Mice

“…For an adult human body weighing 60 kg, the paclitaxel dose is 5.9 mg/kg [ 30 ]. Moreover, the dose required to induce peripheral neuropathy with paclitaxel is 4–10 mg/kg in mice [ 31 , 32 , 33 , 34 , 35 ]. Therefore, we selected a dose of 6 mg/kg oxaliplatin and paclitaxel in mice.…”