The mechanism of andrographolide induced AKI is unclear. Some authors have postulated that andrographolide induced AKI may be caused by its intrinsic nephrotoxicity, its high distribution in kidney tubular, and its unstable water solubility originating from diterpene lactone structure with conjugated

double bond in it.[37] However, none of these hypotheses have been approved. In our idea, since the manifestation of andrographolide induced AKI is similar to suprofen induced AFPS, their mechanism might share some similarities also. It is believed that the inhibitory effects of NSAIDs on prostaglandin FDA approved Drug Library synthesis play important roles in AFPS.[33-36] A recent study shows that andrographolide also has inhibitory effects on prostaglandin E2 (PGE2) production,[38] which hints that andrographolide induced AKI and suprofen induced AFPS may share this similar mechanism. The limitations

of our study are obvious. Because this is a study using spontaneously reported cases, some important data are missing or inadequate. For example, creatine kinase levels were absent in nearly all the cases; however, the possibility of rhabdomyolysis was scarce according to the authors’ judgment. Second, the number of 26 cases is not large; however, andrographolide induced AKI may be underreported, JQ1 mouse as it is an adverse event. An efficient pharmacovigilance system may be lacking, as it is common for traditional medicine. It is hard to know the true country-wide incidence of this situation. However, the frequent occurrence of this adverse event does result in a strong reaction from the official authorities like CFDA,[13, 14] and

causes much academic concern in China. Furthermore, some cases exist but were not included in this analysis. For instance, 80 cases of Palmatine AKI had been reported to CFDA to 2007,[37] but detailed data were not available. There are also some cases of andrographolide induced AKI reported as case series, however, they were not included in this analysis due to the lack of sufficient individual patient information.39,40 Third, our review was limited to Chinese-language literature. Although we also searched English-language literature and retrieved zero results, it should be noted that there may be published, non-Chinese and non-English reports available, especially in Asian areas other than China, where andrographolide was also widely used, such as India, Thailand, and Malaysia etc.[9] Overall, our work represents the first summary of spontaneously reported cases of andrographolide induced AKI in English literature. Although the number of 26 cases is not large, the results are sufficient to raise the concern on the safety of andrographolide, particularly AKI induced by andrographolide. The high incidence of flank pain and subsequently reversible renal failure makes it similar to suprofen induced AFPS.