Table 1.
Summary of the effect of CHMs against chemotherapy-induced side effects.
| Types of side effect | Chinese herbal medicine (formulas or herbs) | Main ingredient/herbs | Evidence |
|---|---|---|---|
| Neurotoxicity | Astragali Radix (Di Cesare Mannelli et al., 2015, 2017; Deng et al., 2016a) | Pre-clinical: Reduce oxaliplatin-induced cold hypersensitivity, block the onset of the pro-allodynia effect, and relieve neuro-damage-induced; Down-regulate the expression of the activating transcription factor 3 in the dorsal root ganglia. | |
| Tumeric (Al Moundhri et al., 2013; Mendonça et al., 2013; Sharma et al., 2014) | Curcumin | Pre-clinical: Reducing the high plasma neurotensin and platinum accumulation in the sciatic nerve. | |
| Guilong Tongluo Decoction (Liu et al., 2013a) | Ramulus Cinnamomi, Astragali Radix, Earthworm, Carthamus Tinctorius, Radix Angelicae Sinensis, Ligusticum, Spatholobus, Radix Paeoniae Alba, Rhizoma Curcumae, and Glycyrrhizae Radix. | Clinical: alleviate the development of grades 1-2 neurotoxicity after 6 cycles of adjuvant oxaliplatin-based chemotherapy in CRC patients, and delayed the onset time of grades 1-4 neurotoxicity. | |
| Niuche Shenqi Wan (Kono et al., 2011, 2013, 2015; Ushio et al., 2012) | Rehmannia Viride Radix, Achyranthis Bidentatae Radix, Corni Fructus, Dioscorea Opposita Rhizoma, Plantaginis Semen, Alismatis Rhizoma, Moutan Cortex, Cinnamomi Cortex, Aconiti Lateralis Praeparata Tuber and Poria Alba. | Pre-clinical: Increase peripheral blood flow, stimulate spinal kappa-opioid receptors, and inhibit oxidative stress or activation of the C fiber. Clinical: Decrease the incidence and delay the development of grade 2 and above oxaliplatin-induced neurotoxicity in CRC after 8 cycles of oxaliplatin-based chemotherapy. | |
| Wenluotong Decoction (Deng et al., 2016b; Noh et al., 2018) | Epimedium Brevicornum Maxim, Geranium Wilfordii Maxim, Cinnamomum Cassia Presl and Carthamus Tinctorius. | Pre-clinical: Reverse both glial activation in the spinal dorsal horn and nociceptive sensitization of oxaliplatin-resultant chronic neuropathic pain in rats. | |
| Guizhi Jiazhufu Decoction (Hosokawa et al., 2012) | Cinamomi Cortex, Aconiti Lateralis Praeparata Tuber, Zingiberis Rhizoma, Jujubae Fructus, Glycyrrhizae Radix, and Atracylodis Macrocephalae Rhizoma | Clinical: Reduce neuropathy in metastatic CRC patients undergoing the FOLFOX regimen. | |
| Shaoyao Gancao Decoction (Hosokawa et al., 2012; Andoh et al., 2017) | Paeonia Alba Radix and Glycyrrhizae Radix. | Pre-clinical: Suppress transient receptor melastatin 8 mRNA expression in the mouse dorsal root ganglia. Clinical: Response rate was reported to be 65% in advanced CRC patients with oxaliplatin-related neuropathy. | |
| Huangqi Guizhi Wuwu Decoction (Jun et al., 2013; Cheng et al., 2017) | Astragali Radix, Cinnamomi Cortex, Radix Paeoniae Alba, Zingiberis Rhizoma and Jujubae Fructus. | Pre-clinical: Down-regulate inflammation and immune responses. Clinical: Lower the incidence and relieve the severity of neurotoxicity in patients undergoing the FOLFOX regimen. | |
| Oral mucositis | Banxia Xiexin Decoction (Matsuda et al., 2015; Nishikawa et al., 2018) | Pinellia Ternata, Scutellaria Baicalensis Radix, Panax Ginseng, Rhizoma Coptidis, Glycyrrhizae Radix, Zingiberis Rhizome and Jujubae Fructus. | Clinical: Reduce the severity grade (≥2) and the duration of chemotherapy-induced oral mucositis in gastric cancer and CRC patients. |
| Lonicerae Flos (Schröder et al., 2013) | Pre-clinical: Suppress the expression of COX-2, IL-1 and IL-6. | ||
| Delayed onset of diarrhea | Banxia Xiexin Decoction (Takasuna et al., 1995; Kase et al., 1997; Mori et al., 2003; Komatsu et al., 2010) | As described above. | Pre-clinical: Inhibit β-glucuronidase activity and prostaglandin E2 synthesis. Clinical: Delay the onset of diarrhea in patients treated with cisplatin and irinotecan. Reduce the frequency of severe diarrhea (grade 3 or 4). |
| Shengjiang Xiexin Decoction (Deng et al., 2017; Guan et al., 2017) | Pinellia Ternata, Scutellaria Baicalensis Radix, Panax Ginseng, Rhizoma Coptidis, Glycyrrhizae Radix, Zingiberis Rhizome, Zingiberis Rhizoma Recens and Jujubae Fructus. | Pre-clinical: Inhibit intestinal cell apoptosis, as well as triggering intestinal injury repair by promoting intestinal stem cell proliferation and inhibiting β-glucuronidase activity. | |
| Huangqin Decoction (Farrell and Kummar, 2003; Lam et al., 2010, 2015; Kummar et al., 2011) | Scutellaria Baicalensis Radix, Glycyrrhizae Radix, Radix Paeoniae Alba and Jujubae Fructus. | Pre-clinical: Restore intestinal epithelial damage through enhancing intestinal progenitor or stem cell regeneration; Induce anti-inflammatory activity in mice by down-regulating the expression of TNF-α, NF-κB and COX-2 in neutrophils and macrophages; potentiate Wnt3a activity. | |
| Clinical: Alleviate nausea and diarrhea in metastatic CRC patients undergoing irinotecan, 5-Fu, and LV (5-Fu/LV) regimens. | |||
| Intestinal mucositis | Chimonanthus nitens var. salicifolius (Liu et al., 2013b) | Pre-clinical: Alleviate 5-Fu induced diarrhea and hemafecia, maintain the intestinal length, reduce villus shortening, and inhibit apoptosis and inflammation in the small intestine. | |
| Pianzaihuang (Fu et al., 2017) | Moschus,Calculus Bovis, Snake Gall and Radix Notoginseng. | Pre-clinical: Reduce 5-Fu-induced intestinal crypt damage through inhibiting the expression of apoptotic proteins. | |
| Buzhong Yiqi Decoction (Jeong et al., 2010; Chao et al., 2014; Gou et al., 2016) | Astragali Radix, Atractylodes Macrocephala, Cimicifugae Rhizoma, Citri Reticulatae Pericarpium, Bupleuri Radix, Panax Ginseng, Glycyrrhizae Radix and Radix Angelicae Sinensis. | Pre-clinical: Restore villi shortening, crypt destruction, reduce apoptosis and necrosis, alleviate neutrophil infiltration in intestinal mucosal epithelia, and inhibit up-regulated inflammatory factors, such as TNF-α and IL-1β. | |
| TJ-114 (Coates et al., 1983; Kato et al., 2015) | Bupleuri Radix, Pinelliae Tuber, Alismatis Rhizome, Scutellariae Radix, Ginseng Radix, Zizyphi Fructus, Poria, Polyporus, Atractylodis Lanceae Rhizome, Cinnamomi Cortex, Glycyrrhizae Radix, and Zingiberis Rhizoma. | Pre-clinical: Lower the diarrhea score and alleviated villi shortening and crypt destruction. Also, it can inhibit apoptosis and lower the secretion of pro-inflammatory cytokines, such as TNF-α and IL-1β. | |
| Nausea and vomiting | Liujunzi Decoction (Takeda et al., 2008; Tominaga et al., 2011; Ohnishi et al., 2017) | Codonopsis Pilosula, Poria Cocos, Atractylodes Macrocephala, Pinellia Ternata, Citri Reticulatae Pericarpium and Glycyrrhiza Radix. | Pre-clinical: Antagonize the 5-HT3 receptor, the 5-hydroxytryptamine receptor 2B and 5-hydroxytryptamine receptor 2C to avoid the cisplatin-induced reduction in ghrelin levels. Clinical: Alleviate CNIV in patients undergoing cisplatin and paclitaxel regimen. |
| Ginger (Ernst and Pittler, 2000; Shukla and Singh, 2007; Ryan et al., 2009) | Clinical: Ginger combined with standard 5-HT3 receptor antagonists and dexamethasone can reduce acute CINV compared with the application of placebo in combination with the standard 5-HT3 receptor antagonists and dexamethasone. |