Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary kidney disease, which is featured by progressively enlarged bilateral fluid-filled cysts. Enlarging cysts destroy the structure of nephrons, ultimately resulting in the loss of renal function. Eventually, ADPKD develops into end-stage renal disease (ESRD). Currently, there is no effective drug therapy that can be safely used clinically. Patients progressed into ESRD usually require hemodialysis and kidney transplant, which is a heavy burden on both patients and society. Therefore, looking for effective therapeutic drugs is important for treating ADPKD. In previous studies, herbal medicines showed their great effects in multiple diseases, such as cancer, diabetes and mental disorders, which also might play a role in ADPKD treatment. Currently, several studies have reported that the compounds from herbal medicines, such as triptolide, curcumin, ginkolide B, steviol, G. lucidum triterpenoids, Celastrol, saikosaponin-d, Sparganum stoloniferum Buch.-Ham and Cordyceps sinensis, contribute to the inhibition of the development of renal cysts and the progression of ADPKD, which function by similar or different mechanisms. These studies suggest that herbal medicines could be a promising type of drugs and can provide new inspiration for clinical therapeutic strategy for ADPKD. This review summarizes the pharmacological effects of the herbal medicines on ADPKD progression and their underlying mechanisms in both in vivo and in vitro ADPKD models.
Highlights
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with the current incidence of 1/1,000–1/400 worldwide
This review summarizes the pharmacological effects of the herbal medicines on ADPKD progression and their underlying mechanisms in both in vivo and in vitro ADPKD models
Pkd1 and Pkd2 are two main genes participating in the pathogenesis of ADPKD, which encode protein polycystin 1 (PC1) and polycystin 2 (PC2), respectively (Cornec-Le Gall et al, 2019)
Summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with the current incidence of 1/1,000–1/400 worldwide. A signal of liver toxicity risk emerged with tolvaptan application, which is marked by extremely elevated ALT level and needs to be carefully monitored during the therapy Another drug of vaptans, Lixivaptan, which is a newer, nonpeptide, oral V2Rspecific antagonist, exhibits relatively preserved renal function (stage 1 and 2) and moderately impaired renal function (stage 3). MTOR inhibitors (everolimus and sirolimus), metformin (an agonist of AMPK), 2-deoxy glucose (2DG) (a glucose analog that can paralyze the glycolytic pathway), tyrosine kinase inhibitors (bosutinib and tesevatinib) and caloric restriction diet are all reported to retard cyst growth in ADPKD patients to different extent (Testa and Magistroni, 2020) None of these drugs mentioned above is considered as satisfactory therapeutic agents for ADPKD for their drawbacks, such as unstable effects on slowing the progression of the disease, restricted applications of the aquaretic type drugs and little effect on the loss of renal function. We summarized the pharmacological effects of several herbal medicines on ADPKD and the underlying mechanisms (Figure 1), expecting to provide new prospectives for ADPKD treatment
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