Pharmacological efficacy of the traditional Chinese medicinal formula Kun-Tai-1A in the treatment of letrozole-induced polycystic ovary syndrome

Background:Polycystic ovary syndrome(PCOS)is an endocrine disorder that occurs in women of child-bearing age.Moreover,PCOS patients have decreased pregnancy rates and clomiphene citrate resistance.The traditional Chinese medicine formula Kun-Tai-1S(KT1S),consisting of the seahorse species hippocampus,has been reported to elicit therapeutic effects in patients with PCOS.However,given the limited resources and global demand for wild hippocampus,whether KT1S with or without hippocampus can elicit similar therapeutic effects has not been confirmed.Methods:KT1S and Kun-Tai-1A(KT1A,KT1S without dry hippocampus)were used to treat a letrozole-induced rat model of PCOS with an established disease.The serum levels of testosterone,luteinizing hormone,anti-Müllerian hormone,and estradiol were determined,the luteinizing hormone/follicle-stimulating hormone ratio was determined,and the ovarian pathology was evaluated.Results:Similar to the therapeutic effects of cyproterone acetate,both the KT1S and KT1A treatments reduced the body weight and ovarian and uterine indices in the rats with PCOS.The serum levels of testosterone,anti-Müllerian hormone,and luteinizing hormone and the luteinizing hormone/follicle-stimulating hormone ratio were significantly lower in the KT1S and KT1A treatment groups compared to the model group(P<0.01 and P<0.05,respectively).Moreover,the histopathological assessment results suggested that both the KT1S and KT1A treatments significantly ameliorated the PCOS pathology in the rats with an established disease,with a reduced number of cystic and atretic follicles and an increased number of corpora lutea being observed in the ovaries.Notably,there was no obvious difference in the disease outcomes between the KT1S and KT1A-treated groups.Network pharmacology analysis revealed that 4’,7-dihydroxyflavanone,sinpemine A,quercetin,8-isopentenyl-kaempferol,and luteolin in KT1A may promote estrogen signaling;furthermore,the nitric oxide regulation pathway is also closely involved.Conclusion:KT1A and KT1S treatments both significantly ameliorated the PCOS-related pathology in rats,suggesting that the hippocampus component is dispensable for KT1S-mediated amelioration.Given the limited resources and global demand for wild hippocampus for use in complementary medicines,our findings may help conserve this species.Together,our results suggest that KT1A is a promising approach for treating PCOS.

Injectable thermo-responsive nano-hydrogel loading triptolide for the anti-breast cancer enhancement via localized treatment based on “two strikes” effects

The clinical application of triptolide(TPL)in tumor therapy has been greatly limited by its toxicity and inefficient delivery.Herein,a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL.Based on the amphiphilic structure of poly(N-isopropylacrylamide-co-acrylic acid)-g-F68 copolymer,it was able to form nano-micelles to efficiently encapsulate TPL,and then turn into a hydrogel at 37C.TPL@nano-gel exhibited a sustained drug release profile in vitro and a stronger anticancer effect caused by"two strikes".The"first strike"was its enhanced cytotoxicity compared to free TPL,due to the enhanced pro-apoptosis effect observed in both MDA-MB-231 and MCF-7 cells caused by the regulation of endogenous mitochondrial pathways.Furthermore,TPL@nano-gel exhibited a"second-strike"through its anti-angiogenesis capabilities mediated through VEGFR-2 signaling inhibition.As expected,after intra-tumoral injection at a 0.45 mg/kg TPL-equivalent dose three times over 14 days in 4 T1 tumor-bearing mice,TPL@nano-gel led to lower systemic toxicity and higher antitumor efficacy compared to multiple injections of TPL.In this regard,these findings indicate that this injectable thermo-responsive hydrogel carries great potential for TPL as a safe and effective cancer therapy.