Can Medical Herbs Stimulate Regeneration or Neuroprotection and Treat Neuropathic Pain in Chemotherapy-Induced Peripheral Neuropathy?

Table 1

Medical herbs tested for CIPN.

Section no.	Medical herb(s)	Study design	Chemotherapy	Outcome	Author/year
Single herbs or single compounds
3.1.1	Acorus calamus rhizoma (hydroalcoholic extract)	Rat model	Vincristine	Improvement of neuropathic pain	Muthuraman and Singh, 2011 [70]
3.1.2	Cannabis-Receptor agonists, R-AM1241 and Am-1714	Rat model	Paclitaxel	Allodynia, antinociceptive	Rahn et al., 2008 [71] multiple trials for neuropathic pain not due to chemotherapy, for example, Ellis et al. [72], Karst et al. [73], Ware et al. [74], Rog et al. [75], Blake et al. [76], Berman et al. [77], Wilsey et al. [78] with Cannabis sativa
3.1.3	Matricariachamomilla (hydroalcoholic extract)	Mouse model	Cisplatin	Improvement of neuropathic pain	Abad et al. 2011 [85]
3.1.4	Ginkgo biloba (alcoholic extract)	(1) Mouse model; (2) Retrospective study (𝑛=17)	Oxaliplatin	(1) Neuroprotection; (2) Improvement of neuropathic pain	(1) Oztürk et al., 2004 [86]; (2) Marshall et al., 2004 [87]
3.1.5	Salvia officinalis (hydroalcoholic extract)	Mouse model	Vincristine	Improvement of neuropathic pain	Abad et al., 2011 [88]
3.1.6	Sweet bee venom (pharmacopuncture)	(1) Case series (𝑛=5); (2) Case series (𝑛=11)	Taxol, paclitaxel, or carboplatin	Injection into acupoint (Zusanli, St 36); (1) Effect on pain and neuropathy scales; (2) Effect on VAS and HRQOL scores	(1) Park et al., 2011 [89]; (2) Yoon et al., 2012 [90]
3.1.7	Verticinone, hydroalcoholic extracted from Fritillaria bulbus	Mouse model and; rat model	Paclitaxel	Inflammatory and neuropathic pain, dose dependent, no tolerance	Xu et al., 2011 [91]
Herbal combinations
3.2.1	Bu Yang Huan Wu ∗1 (decoction)	Randomized trial, 𝑛=44, control = 40	Oxaliplatin	Improvement of clinical scales	Sun et al., 2008 [92]
3.2.2	modified Bu Yang Huan Wu plus Liuwei Di Huang ∗2 (decoction)	Randomized trial, 𝑛=32, control Vit. B1 = 32	Different chemotherapies	Improvement of clinical scales	Deng and Zou, 2007 [93]
3.2.3	modified Chai Hu Long Gu Mu Li Wan ∗3 (decoction)	Randomized trial, 𝑛=26, control = 22	Paclitaxel	neuroprotection	Pan et al., 2012 [94]
3.2.4	Geranii herba plus Aconiti radix (granule)	(1) Rat model; (2) Randomized, prospective trial 𝑛=30, control = 28	(1) Oxaliplatin; (2) Oxaliplatin, taxol or capecitabine	(1) Allodynia; (2) Neuropathic pain, paraesthesia, selling.; external washing	Sima and Pan, 2009 [95]
3.2.5	Goshajinkigan = Niu Che Sen Qi Wan ∗4 (granule)	(1) Rat model; (2) Rat/mouse model	(1) Paclitaxel; (2) Oxaliplatin	(1) No neurogeneration, improvement of allodynia; (2) Improvement of neuropathic pain, no neuroregeneration	(1) Hashimoto et al., 2004 + 2006 [96, 97]; (2) Ushio et al., 2012 [98]
		(1) Noncontrolled study 𝑛=14; (2) Retrospective study; GJG = 22, control = 23; (3) Retrospective study; GJG = 45, control = 45; (4) Retrospective study 𝑛=82; (5) Randomized prospective study Vit B12 = 14, VitB12/GJG = 15	(1) Oxaliplatin; (2) Folfox∗8; (3) Folfox∗8; (4) Paclitaxel; (5) Paclitaxel/; carboplatin	(1) Reduced acute neurotoxicity; (2) Neuroprotection; (3) Neuroprotection; No change of anticancer activity; (4) Neuroprotection, better when administered early; (5) Less severe neurotoxicity, better CPT in GJG group	(1) Shindo et al., 2008 [99]; (2) Nishioka et al., 2011 [100]; (3) Kono et al., 2011 [101]; (4)Yamamoto et al., 2009 [102]; (5) Kaku et al., 2012 [103]
3.2.6	Keishikajutsubuto = Gui Zhi Jia Shu Fu Tang∗5 (granule)	Uncontrolled study 𝑛=15 (3 dropouts)	Folfox∗8	76.6% mean improvement on VAS	Yamada et al., 2012 [104]
3.2.7	Ogikeishigomotsuto = Huang Qi Wu Wu Tang∗6 (granule)	Case report 𝑛=1	Oxaliplatin	neuropathic pain	Tatsumi et al., 2009 [105]
3.2.8	Shakuyakukanzoto = Shao Yao Gan Cao Tang∗7 (granule)	(1) Mouse model; (2) Retrospective case analysis 𝑛=23; (3) Retrospective clinical study, comparison GJG = 20, SYK = 24	(1) and (2) paclitaxel; (3) Folfox∗8	(1) Allodynia, hyperalgesia; (2) Effect on neuropathic pain; (3) 50% response in Shakuyu-kanzoto and 65% in Goshajinkigan on prevention of neurotoxicity	(1) Hidaka et al., 2009 [106]; (2) Fujii et al., 2004 [107]; (3) Hosokawa et al., 2012 [108]

∗1Astragalus membranaceus radix, Angelica sinensis radix, Prunus persicae semen, Paeoniae rubra radix, Ligustici chuanxiong rhizoma, Lumbricus terrestris, Spatholobi caulis, Curcuma radix, Chaenomeles lagenaria fructus, and Achyranthes bidentata.
∗2Astragalus membranaceus radix, Ligustrum lucidum fructus, Paeoniae rubra radix, Lumbricus terrestris, Prunus persicae semen, Rehmanniae viridae radix, Corni officinalis fructus, Dioscorea opposita radix; and Alismatis rhizoma, Poria alba, Spatholobi caulis, Scolopendra, Mori fructus, Glycyrrhizae Radix, Dipsaci fructus, Lycii fructus, Coicis semen, Atractylodis rhizoma, Phellodendri cortex, Scorpio, Mori ramulus, and Cyathula officinalis.
∗3Pseudostellaria heterophylla, Pinelliae rhizoma, Glycyrrhizae radix, Scutellaria baicalensis radix, Bupleuri radix, Fossilia ossis mastodia draconis, Ostrae concha, Rubiae cordifoliae radix, Scutellariae barbatae herba, and Fritillaria thunbergii bulbi. The external washing was done with Astragali radix, Angelica sinensis radix, Paeoniae rubra radix, Lumbricus terrestris, Ligustici chuanxiong rhizoma, Prunica persicae semen, and Carthami flos.
∗4Rehmannia viride radix, Achyranthis bidentatae radix, Corni fructus, Dioscoreaopposita rhizome, Plantaginis semen, Alismatis rhizoma, Moutan cortex, Cinnamomi cortex, Aconiti lateralis praeparata tuber, and Poria alba.
∗5Cinnamomi cortex, Aconiti lateralis praeparata tuber, Zingiberis rhizoma, Jujubae fructus, Glycyrrhizae radix, and Atracylodis macrocephalae rhizoma.
∗6Astragali membranaceus radix, Cinnamomi cortex, Paeonia alba radix, Jujubae fructus, and Zingiberis rhizoma.
∗7Paeonia alba radix and Glycyrrhizae radix.
∗8Chemotherapeutic regime with FOL: Folinic acid (leucovorin), F: Fluorouracil (5-FU), and OX: Oxaliplatin (Eloxatin).