Table 8.

The effect of compatible drugs on aconite toxicity and its causes.

Compatible drugs	Number of articles	Toxic effect on aconite	Reason	Reference
Licorice	28	Reduce toxicity	① Glycyrrhizic acid and glycyrrhetinic acid in licorice can neutralize with the aconite alkaloids in aconite, and the flavonoids in licorice can also combine with aconitum alkaloids to form a precipitate, both of which can delay or reduce the absorption of toxic alkaloids such as aconitine. ② Glycyrrhizic acid in the gastrointestinal tract can be converted into glycyrrhetinic acid and flavonoids. Licorice flavonoids contain multiple hydroxyl groups, which can combine with alkaloids in aconite to form ester alkaloid precipitation, reduce the content of toxic alkaloids.	Yang et al. [69]
Dried ginger	11	Reduce toxicity	The chemical components in dried ginger can convert the more toxic diester alkaloids in aconite into less toxic ester alkaloids and can antagonize the central inhibitory effect of aconitine, thereby achieving the purpose of detoxification	Yue et al. [70]
Ginseng	8	Reduce toxicity	Ginsenosides in ginseng can increase the SOD activity of cardiomyocytes, reduce MDA content and LDH release rate, and can inhibit the apoptosis of aconite on cardiomyocytes and effectively inhibit its toxic effects.	Wang et al. [27]
Pinellia	6	Toxic increase/decrease	① The compatibility of aconite with qing pinellia, pinellia ginger, and raw pinellia can inhibit the hydrolysis reaction of the alkaloids in aconite, resulting in a significant increase in the content of diester alkaloids. ② The compatibility of aconite and pinellia ternata is attenuated and can make the toxicity more toxic. Large diester alkaloids are transformed into less toxic monoester alkaloids. ③ Compatibility of aconite and pinellia can inhibit CYP1A2 and CYP3A1 enzyme activity, inhibit drug metabolism, and enhance the toxicity.	Huang [71] Jin et al. [72]
Ephedra and Fuzi licorice soup	5	Reduce toxicity	It can significantly reduce the content of diester alkaloids, and the codecocting effect of the three is the best.	Wang and Wan [73]
Ephedra	5	Reduce toxicity	After the two are compatible, the content of monoester alkaloids-benzoyl neoaconitine and benzoyl hypoaconitine is reduced, thereby generating a new ester alkaloid-8-linoleoyl-14- benzoyl hypoaconitine and 8-linoleyl-14-benzoyl aconitine reduces the toxicity.	Pi et al. [74]
Rhubarb	4	Reduce toxicity	During the decoction, the tannins and aconite alkaloids contained in rhubarb produce aconitine salt of tannic acid that is not absorbed by the intestine, thereby reducing the toxicity of aconite, and the content of aconitine decreases as the dose of rhubarb increases. Those are linearly related, and its attenuation effect also increases with the increasing dose of rhubarb.	Wang et al. [75]
Fritillaria Zhejiang/Fritillaria Chuan	4	Toxic increase/decrease	① After codecoction of aconite and fritillaria, the content of aconitine, hypoaconitine, and neoaconitine increased significantly, and the dissolution rate of toxic components of aconitine increased. ② After the compatibility of aconite and fritillaria cirrhosa, the amount of the three diester alkaloids aconitine, mesaconitine, and hypoaconitine was significantly reduced or undetectable, and the toxicity was reduced.	Bian et al. [76] Dong et al. [77]
Trichosanthes kirilowii	2	Increase toxicity	The combination of aconite and Trichosanthes kirilowii showed serious toxic effects, including promoting heart and kidney inflammation, increasing myocardial fibrosis, and activating β2-AR/PKA signal.	Sun et al. [78]
Astragalus	2	Reduce toxicity	① Compatible with astragalus can reduce the 6 alkaloids of aconite to varying degrees (benzoyl hypoaconitine BHA, benzoyl neoaconitine BMA, benzoyl aconitine BAC, hypoaconitine HA, new aconitine MA, aconitine AC) plasma concentration. ② Astragalus inhibits the absorption of aconite alkaloids that may be related to the expression of astragalus-induced efflux transporter. ③ Astragalus promotes the clearance of aconite that may be related to the induction of corresponding metabolic enzymes (CYP3A4, CYP3A4, astragalus, CYP1A1, CYP2E1); activity is related.	Liu et al. [79] Zhang et al. [80] Lou et al. [81]
White Peony	1	Reduce toxicity	The diester-type alkaloids in aconite react with the chemical components in the white peony root, so that hypoaconitine, which is not easily hydrolyzed, generates lipid alkaloids. The lipid exchange reaction leads to a decrease in the content of hypoaconitine, thereby achieving attenuation.	Yue et al. [70]
Guizhi	1	Reduce toxicity	The compatibility of Aconite with Guizhi can reduce the total alkaloids and ester alkaloids of aconite, thereby reducing the poisonousness of aconite, and may be able to guide aconite to dispel cold and relieve pain and warm meridians and improve the pulse.	Ye et al. [82]
Cinnamon	1	Unknown	The compatibility of aconite with cinnamon can promote the dissolution of the effective components of aconite and can better guide the aconite to play the role of warming yang and igniting fire.	Ye et al. [82]
Windproof	1	Reduce toxicity	Improve LD50 and TD50	Zhang et al. [83]
Polygala	1	Reduce toxicity	Improve LD50 and TD50	Zhang et al. [83]
Dogwood	1	Reduce toxicity	Enhance the effect of “Wen tongxinyang” of aconite, and reduce its cardiotoxicity.	Jin et al. [84]
Trichosanthin	1	Reduce toxicity	Subacute toxicity experiments in mice show that the toxicity of aconite and Trichosanthes is less than that of aconite single decoction.	Yang et al. [85]
Rifampin	1	Reduce toxicity	Rifampicin is a liver drug enzyme inducer, which induces aconite metabolism to accelerate and significantly reduces the acute toxicity of aconite.	Chen et al. [86]
Dry Rehmannia	1	Reduce toxicity	Induces CYP1A2 and CYP3A4 enzyme activity, increases CYP450 enzyme content, accelerates the metabolism of toxic components of aconite, and achieves aconite attenuation [53].	Li et al. [33]