Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: therapeutic targets and clinical perspective

Abstract

Background: Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can be suitable candidates to be assessed regarding their effects in CIPN. Current paper reviews the available preclinical and clinical studies on the efficacy of herbal medicines in CIPN.

Methods: Electronic databases including PubMed, Scopus, and Cochrane library were searched with the keywords "neuropathy" in the title/abstract and "plant", "extract", or "herb" in the whole text. Data were collected from inception until April 2018.

Results: Plants such as chamomile (Matricaria chamomilla L.), sage (Salvia officinalis L.), cinnamon (Cinnamomum cassia (L.) D. Don), and sweet flag (Acorus calamus L.) as well as phytochemicals like matrine, curcumin, and thioctic acid have demonstrated beneficial effects in animal models of CIPN via prevention of axonal degeneration, decrease in total calcium level, improvement of endogenous antioxidant defense mechanisms such as superoxide dismutase and reduced glutathione, and regulation of neural cell apoptosis, nuclear factor-ĸB, cyclooxygenase-2, and nitric oxide signaling. Also, five clinical trials have evaluated the effect of herbal products in patients with CIPN.

Conclusions: There are currently limited clinical evidence on medicinal plants for CIPN which shows the necessity of future mechanistic studies, as well as well-designed clinical trial for further confirmation of the safety and efficacy of herbal medicines in CIPN. Graphical abstract Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

Keywords: Chemotherapeutic agents; Clinical studies; Inflammation; Medicinal plants; Neuropathy; Pain; Phytochemicals; Phytotherapy.

Graphical abstract

Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

Fig. 1

Flow diagram of study selection process

Fig. 2

Structures of some chemotherapeutic agents causing neurotoxicity

Fig. 3

Chemical structure of phytochemicals assessed in chemotherapy-induced peripheral neuropathy

Fig. 4

Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction