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ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MSE） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg-1·d-1） or AAⅠ（5 mg·kg-1·d-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization（ESI+） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.
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Asari Radix et Rhizoma （AR） is a traditional Chinese medicine with a history of more than 2 000 years of medication and has been included in ancient herbal works in the past dynasties. It is effective in releasing the exterior， dispersing cold， dispelling wind， relieving pain， opening orifices， warming the lung， and resolving fluids， and is still widely used in the clinical treatment of influenza， coronavirus disease-2019 （COVID-19） pneumonia， asthma， allergic rhinitis， eye pain， headache， toothache， oral ulcer， eczema， etc. Modern pharmacological studies have shown that AR has antipyretic， anti-inflammatory， analgesic， antibacterial， antiviral， relieving cough and asthma， anti-allergy， and other effects. AR contains a variety of chemical components， in which essential oil is not only associated with functions such as dispelling cold， relieving heat， relieving pain， and resisting inflammation and allergy， but is also toxic. AR also contains lignans， flavonoids， amides， phenanthrenes， alkaloids， and other non-volatile oil components， which play an important role in immunity regulation， anti-inflammation， pain relief， heart strengthening， and blood vessel expansion. The phenanthrene compounds are mainly aristolochic acid analogues， such as aristolochic acid Ⅳa and aristolochic lactam Ⅰ. Aristolochic acid Ⅳa has been proven to have a significant anti-inflammatory effect. The toxicity of AR is related to safrole， aristolochic acids and their analogues， and is also affected by many factors， such as preparation method， dosage， origin， collection time， medicinal part， and decocting time， which should be comprehensively considered in clinical application. Based on the relevant literature in China and abroad， the present study reviewed the correlation of chemical composition and pharmacological and toxicological effects of AR， and the safety of AR， aristolochic acid， safrole， and other components to provide a new perspective for an objective understanding of AR safety， as well as references for rational clinical application， production risk prevention and control， and drug scientific supervision of AR.
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Objective: To explore the structural relationship of social support,loneliness and internet addiction tendency.Methods: Questionnaires were used to investigate 355 college students.Results: The internet addiction tendency of college students had significant negative correlation with social support total scores and subjective social support,and positive correlation with the total scores and every dimensions of loneliness;college students’ social support had significant negative predictive effect on internet addiction tendency;loneliness of college student played a completely mediating role between social support and internet addiction tendency.Conclusion: Loneliness of college students plays a completely mediating role between social support and internet addiction tendency.