Table 2.

Mechanisms of processing of representative CHMs

Decoction pieces		Purpose and major mechanisms of processing	References
Crude CHM	Processed CHM (processing method)
Aconiti Radix, Chuanwu 川烏	Aconiti Radix Cocta, Zhichuanwu 制川烏 (soaking, boiling or steaming)	Purpose Reducing toxicity Mechanisms Structural transformation of toxic constituents: (1) highly toxic diester diterpene alkaloids hydrolyze or decompose into monoester diterpene alkaloids of low toxicity or non-toxic non-esterified diterpene alkaloids. (2) Diester diterpene alkaloids react with components in Glycyrrhizae Radix to generate lipo-alkaloids of low-toxicity. On the other hand, the resultant alkaloids have considerable anti-inflammatory and analgesic effects	[18–20]
Aconiti Lateralis Radix, Nifuzi 泥附子	Aconiti Lateralis Radix Praeparata, Yanfuzi 鹽附子 (soaking)
	Aconiti Lateralis Radix Praeparata, Danfupian 淡附片 (soaking in salt water, boiling with Glycyrrhizae Radix and black bean)
	Aconiti Lateralis Radix Praeparata, Heishunpian 黑順片 (soaking in salt water, staining and steaming)
	Aconiti Lateralis Radix Praeparata, Baifupian 白附片 (soaking in salt water, peeling and steaming)
	Paofupian炮附片 (sand-scorch of Heishunpian or Baifupian)
Aconiti Kusnezoffii Radix, Caowu 草烏	Aconiti Kusnezoffii Radix Cocta, Zhicaowu 制草烏 (soaking in water and boiling)
Pinelliae Rhizoma, Banxia 半夏	Pinelliae Rhizoma Praeparatum, Fabanxia 法半夏 (soaking with water and then with Glycyrrhizae Radix juice)	Purpose Reducing toxicity Mechanisms (1) Physically changed crystal structure: alum solution changes the structure of needle-like calcium oxalate crystals and dissolves the lectin in the crystals, which decreases the side effect. (2) Detoxifying components from excipients: a compound gingerol from ginger juice can effectively inhibit Banxia-induced inflammation	[21–25]
	Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine, Jiangbanxia 姜半夏 (soaking with water, boiling with ginger and alum)
	Pinelliae Rhizoma Praeparatum Cum Alumine, Qingbanxia 清半夏 (soaking with alum solution)
Typhonii Rhizoma, Baifuzi 白附子	Zhibaifuzi 制白附子 (soaking with alum solution)
Rhei Radix et Rhizoma, Dahuang 大黃	Jiudahuang 酒大黃 (stir-frying with alcohol)	Purpose Changing functions and reducing toxicity Mechanisms (1) Decomposing of conjugated anthraquinones into the corresponding free anthraquinones; (2) reduced contents of tannins; (3) after processing, Dahuangtan has no effect on blood circulation	[26–28]
	Shudahuang 熟大黃 (steaming or steaming with alcohol)
	Dahuangtan 大黃炭 (charring)
Angelicae Sinensis Radix, Danggui 當歸	Jiudanggui 酒當歸 (stir-frying with alcohol)	Purpose Enhancing efficacy Mechanisms (1) Increasing the solubility of ferulic acid; (2) decreasing the content of Z-ligustilide. Both ferulic acid and Z-ligustilide are biological constituents, but high concentration of Z-ligustilide is irritant	[10, 29–31]
Ginseng Radix et Rhizoma, Renshen 人參	Ginseng Radix et Rhizoma Rubra, Hongshen 紅參 (steaming)	Purpose Enhancing efficacy and reduced side effect Mechanisms (1) Structural transformation of ginsenosides via hydrolysis of sugar moieties and/or epimerization of 20(S)-type into 20(R)-type; (2) Maillard reaction on reducing sugars and amino acids to form phenol compounds; (3) degradation of dencichine which has neurotoxicity. These changes contribute to enhanced anti-oxidant, anti-cancer and immue-modulating effects, and reduced side effect	[32–37]
Strychni Semen, Maqianzi 馬錢子	Zhimaqianzi 制馬錢子 (stir-frying with sand)	Purpose Reducing toxicity Mechanisms Decomposition and oxidation of highly-toxic strychnine and brucine to generate isostrychnine, isobrucine, brucine N-oxide and strychnine N-oxide	[38–41]
Mylabris, Banmao 斑蝥	Mibanmao 米斑蝥 (stir-frying with rice)	Purpose Reducing toxicity Mechanisms Reducing contents of toxic constituents: stir-frying of Banmao facilitates sublimation of cantharidin when the processing temperature reaches 120 °C, and the content of cantharidin is significantly reduced	[42]
Crotonis Fructus, Badou 巴豆	Crotonis Semen Pulveratum, Badoushuang 巴豆霜 (partially removal of croton oil)	Purpose Reducing toxicity Mechanisms Reduced contents of toxic constituents: processing via removal of Crotonis oil which contains toxic constituents reduces toxicity of Badou	[43]
Atractylodis Macrocephalae Rhizoma, Baizhu 白術	Fuchaobaizhu 麩炒白術 (stir-frying with bran)	Purpose Enhancing efficacy Mechanisms Structural transformation via decomposing atractylone into Atractylenolide I and II during processing	[44, 45]
Genkwa Flos, Yuanhua 芫花	Cuyuanhua 醋芫花 (stir-frying with vinegar)	Purpose Reducing toxicity and enhancing efficacy Mechanisms (1) The contents of Yuanhuacine and genkwadaphnin which are highly toxic are decreased; (2) the contents of bioactive flavonoids, including genkwanin, 3′-hydroxy-genkwanin and apigenin, are increased, likely due to the transformation of flavonoid glycosides into the respective glycones	[46]
Glycyrrhizae Radix et Rhizoma, Gancao 甘草	Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Zhigancao 炙甘草 (stir-frying with honey)	Purpose Enhancing efficacy Mechanisms Hydrolysis of glycosides such as glycyrrhizin, liquiritin apioside and isoliquiritin apioside into glycyrrhetinic acid, liquiritigenin and isoliquiritigenin, respectively, with enhanced anti-inflammatory effect	[47]
Calamina, Luganshi 爐甘石	Duanluganshi 煆爐甘石 (calcining)	Purpose Enhancing efficacy Mechanisms Decomposing ZnCO3 into ZnO which has better antimicrobial activity	[48, 49]
Leaves of Baphicacanthus cusia (Nees) Bremek., Polygonum tinctorium Ait. or Isatis indigotica Fort.	Indigo Naturalis, Qingdai 青黛	Purpose Enhancing efficacy Mechanisms Decomposing isatan B or indole glycoside and further condensed to form indigos and indirubin, the active constituents	[50]
Kansui Radix, Gansui 甘遂	Cugansui 醋甘遂 (stir-frying with vinegar)	Purpose Reducing toxicity Mechanisms (1) Conversion of the highy-toxic 3-Acyl ester components into the non-toxic 20-acyl ester components; (2) reaction of diterpenes with acetic acid to form acetylated diterpenes with poor solubility which decreases toxicity	[51, 52]
Sinapis Semen, Jiezi 芥子	Chaojiezi 炒芥子 (Stir-frying)	Purpose Reducing side effect Mechanisms Inactivation of myrosase via heating to retain the glucosinolates, including sinalbrin	[53]
Xanthii Fructus, Cang’erzi 蒼耳子	Chaocang’erzi 炒蒼耳子 (stir-frying)	Purpose Reducing toxicity Mechanisms Decomposing β-d-Fructofuranosyl-α-d-glucopyranoside and other glycosides	[54]
Epimedii Folium, Yinyanghuo 淫羊藿	Zhiyinyanghuo 炙淫羊藿 (stir-frying with mutton fat)	Purpose Enhancing efficacy Mechanisms Decomposing flavonoid glycosides to form secondary glycosides or aglycones, which results in enhanced gonadal function	[55, 56]
Coptidis Rhizoma, Huanglian 黃連	Jiuhuanglian 酒黃連 (stir-frying with alcohol)	Purpose Enhancing efficacy Mechanisms (1) Increased solubility of the contents of berberine, palmatine, coptisine and jatrorrhizine; (2) decomposing of berberine to form a novel compound berberubine which has anticancer activity	[57, 58]