Objective To characterize the material basis of Mahuang Xixin Fuzi Decoction (麻黄细辛附子汤, MXF) and Mahuang Gancao Fuzi Decoction (麻黄甘草附子汤, MGF), and explore the differences in intervention effects and mechanisms of MXF and MGF on mouse models of kidney-yang deficiency and external infection syndrome, and provide basic research basis for clinical precision medication. Methods The chemical composition of MXF and MGF was analyzed using ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ/MS). A total of 60 BALB/c mice were randomly divided into control group (12 mice) and kidney-yang deficiency syndrome model group (48 mice). A mouse model of kidney-yang deficiency syndrome was established by ip estradiol benzoate, and then intranasal infection with H1N1 influenza virus was performed to establish a mouse model of kidney-yang deficiency and external infection syndrome. The successfully modeled mice were randomly divided into model group, MXF (1.8 g/kg) group, MGF (1.8 g/kg) group and oseltamivir (22.53 mg/kg) group, with 12 mice in each group. After continuous administration for 7 d, changes in body weight, anal temperature, survival rate, organ indexes, lung tissue pathology, levels of secretory immunoglobulin A (SIgA) in tracheal and bronchoalveolar lavage fluid, lung viral load, and serum inflammatory cytokine levels of mice in each group were detected. Results A total of 15 components including ephedrine, aconitine, sesamin ester and asarinin were detected in MXF, and 18 components including ephedrine, aconitine and liquiritin were detected in MGF. The content of ephedra alkaloids in MXF was higher than that in MGF. Compared with model group, all treatment groups were able to restore the body weight and anal temperature of mice, and the recovery effect was oseltamivir > MXF > MGF; There were no mouse deaths in oseltamivir and MXF groups, while one mouse died in MGF group; The lung index of oseltamivir group and MXF group were significantly decreased (P < 0.05, 0.01); The lung tissue lesions of mice in each treatment group were reduced, with the degree of reduction being oseltamivir > MXF > MGF; MXF had a higher clearance rate of lung viruses in mice; MGF significantly increased the level of SIgA in lung lavage fluid (P < 0.05); Oseltamivir, MXF and MGF could effectively reduce the total value of pro-inflammatory and anti-inflammatory factors, the ratio of pro-inflammatory and anti-inflammatory factors, and the proportion of pro-inflammatory factors, alleviate the body’s inflammatory response, and MGF had higher anti-inflammatory and immune enhancing effects than MXF; According to the box plot analysis of comprehensive therapeutic effects, MXF was superior to MGF. Conclusion Different adjuncts [Xixin (Asari Radix et Rhizoma/Gancao (Glycyrrhizae Radix et Rhizoma)] in MXF and MGF affect the contents of common components (ephedra alkaloids, aconitum alkaloids) in the formula; Both MXF and MGF could effectively treat kidney-yang deficiency and external infection syndrome and reduce the damage caused to the body by viral infection. Comparing the two, MXF has better comprehensive pharmacological effects, but MGF has better effects on inflammatory factors and immune regulation.

Mahuang Xixin Fuzi Decoction  /  Mahuang Gancao Fuzi Decoction  /  kidney-yang deficiency and external infection syndrome  /  inflammatory factors  /  pseudoephedrine  /  ephedrine  /  methylephedrine  /  aconine  /  benzoylhypacoitine  /  benzoylmesaconine  /  benzoylaconine  /  hypaconitine  /  neoaconitine  /  aconitine