PMID: 

J Cancer. 2019 ;10(13):3012-3020. Epub 2019 Jun 2. PMID: 31281478

Abstract Title: 

Triptolide sensitizes cisplatin-resistant human epithelial ovarian cancer by inhibiting the phosphorylation of AKT.

Abstract: 

Advanced and chemotherapy-resistant ovarian cancer causes high mortality of ovarian cancer, and it is important to find safe and effective drugs to reduce the chemotherapeutic resistance of ovarian cancer. In our study, we attempted to clarify the resistance mechanisms of SKOV3/DDP cellsand evaluated the sensitization to triptolide (TPL). Our results indicated that the overexpression of AKT and p-AKT greatly enhanced the cisplatin (DDP) tolerance of SKOV3/DDP, and the combination of DDP+TPL had a significant tumour inhibition effect compared to DDP treatment (p

read more

PMID: 

Am J Transl Res. 2019 ;11(6):3750-3760. Epub 2019 Jun 15. PMID: 31312385

Abstract Title: 

Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling.

Abstract: 

BACKGROUND: This study aimed to investigate roles of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling in triptolide (TPL)-induced sensitivity of pancreatic cancer cells to gemcitabine (GEM).METHODS: , pancreatic cancer PANC-1 cells were treated with lipopolysaccharide (LPS) to activate TLR4, TLR4-siRNA, GEM alone, or GEM plus TPL., nude mice bearing PANC-1 cell xenografts were treated with GEM, TPL, or both. Cell proliferation was detected by MTT assay and Ki-67 staining. Apoptosis was assessed by flow cytometry and TUNEL assay. A double luciferase reporter gene was used to detect NF-κB activity.RESULTS: The sensitivity of PANC-1 cells to GEM was reduced by LPS but enhanced by TLR4-siRNA. TPL inhibited expression of TLR4/NF-κB signaling components, which was reversed by LPS. The TPL+GEM group showed more apoptosis than the LPS+TPL+GEM group. Moreover, the activity of NF-κB and the expression of TLR4, p-p65 Survivin, CyclinD1 and Bcl-2 in the TPL+GEM group were lower than in the LPS+TPL+GEM group, whereas Bax expression was higher. The volume of transplanted tumors in the TPL+GEM group was lower than that in the TPL or GEM group. Phospho-p65, Survivin, CyclinD1 and Bcl-2 expression in transplanted tumors was lower in TPL+GEM group than in either single drug group. The Ki-67 staining score of the TPL+GEM group was lower and tumor cells apoptosis rate was increased when compared with TPL or GEM alone.CONCLUSIONS: TPL enhances the sensitivity of pancreatic cancer PANC-1 cells to GEM by inhibiting TLR4/NF-κB signaling.

read more

PMID: 

Mol Biol Rep. 2019 Jun 21. Epub 2019 Jun 21. PMID: 31228042

Abstract Title: 

Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy.

Abstract: 

Pancreaticβ cell damage is one of the crucial factors responsible for the development of type 2 diabetes mellitus (T2DM). Previous studies have suggested that puerarin (PR) could regulate the activities of the mitochondrial respiratory chain complex in diabetic nephropathy (DN); however, whether PR can inhibit pancreatic β-cell apoptosis in T2DM remains to be elucidated. In the present study, T2DM mice induced by high-fat diet and streptozotocin (STZ) injection were used as a working model to investigate the mechanism of PR on pancreatic β cell apoptosis. The results showed that PR decreased the serum fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels but significantly increased the fasting blood insulin (FINS) and high-density lipoprotein (HDL) levels. Furthermore, decreased caspase-3, 8, 9 and apoptosis-inducing factor (AIF) proteins in the pancreas were detected by Western blot analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining demonstrated that the pancreatic β cell apoptosis was inhibited by PR. Furthermore, PR improved the histopathological changes in pancreatic tissue in T2DM mice. Collectively, the data show that PR can protect the β cells from apoptotic death in a mouse model of T2DM through regulating the expression of apoptosis-related protein-AIF and caspase family proteins.

read more

PMID: 

Pharm Biol. 2019 Dec ;57(1):407-411. PMID: 31230510

Abstract Title: 

Effects of puerarin on the pharmacokinetics of triptolide in rats.

Abstract: 

Puerarin and triptolide are sometimes used together for the treatment of disease in Chinese clinics; however, the drug-drug interaction between puerarin and triptolide is still unknown.This study investigates the effects of puerarin on the pharmacokinetics of triptolide in rats and clarifies its main mechanism.The pharmacokinetic profiles of oral administration of triptolide (1 mg/kg) in Sprague-Dawley rats with (test group, = 6) or without pretreatment (control group, = 6) with puerarin (100 mg/kg/day for seven days) were investigated. The effects of puerarin on the transport and metabolic stability of triptolide were also investigated using Caco-2 cell transwell model and rat liver microsomes.The results showed that puerarin could significantly increase the peak plasma concentration (from 187.25 ± 15.36 to 219.67 ± 21.52 ng/mL), and decrease its oral clearance (from 4.92 ± 0.35 to 62.46 ± 3.75 ± 0.19 L/h/kg). The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of triptolide from 2.70 to 1.33, and the intrinsic clearancerate of triptolide was decreased by the pretreatment with puerarin (38.8 ± 4.7 vs. 32.9 ± 6.5 μL/min/mg protein).Puerarin could significantly change the pharmacokinetic profiles of triptolide in rats, and it might exert these effects through increasing the absorption of triptolide by inhibiting the activity of, or through inhibiting the metabolism of triptolide in rat liver. The results also showed that the dose of triptolide should be decreased when these drugs were co-administered.

read more

PMID: 

PLoS One. 2019 ;14(6):e0218490. Epub 2019 Jun 24. PMID: 31233515

Abstract Title: 

Puerarin prevents high-fat diet-induced obesity by enriching Akkermansia muciniphila in the gut microbiota of mice.

Abstract: 

Growing evidence indicates that the gut microbiota plays a significant role in the pathophysiological processes of obesity and its related metabolic symptoms in the host. Puerarin, an active ingredient in the root of Pueraria lobate has been suggested to have a potent anti-obesity effect. Herein, we tested whether this effect of puerarin is associated with changes in the gut microbiota. In addition to reducing body weight, inflammation, and insulin resistance, puerarin administration significantly altered the composition of the gut microbiota. Notably, puerarin treatment greatly increased the abundance of Akkermansia muciniphila, a mucin-degrading bacterium known to be beneficial for host metabolism and significantly downregulated in high-fat diet-fed mice. Further experiments revealed that puerarin increased intestinal expression levels of Muc2 and Reg3g and protected intestinal barrier function (normal permeability) by increasing the expression of ZO-1 and occludin in vivo and in vitro. These data suggest that puerarin's enriching effect on A. muciniphila is mediated, at least in part, by a host cellular response to protect the host from diet-induced metabolic disorders and other diseases.

read more

PMID: 

Exp Ther Med. 2019 Jul ;18(1):133-138. Epub 2019 Apr 30. PMID: 31258646

Abstract Title: 

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide-induced hepatic fibrosis in rats.

Abstract: 

Liver fibrosis is a complex pathological process and an early step in the progression of liver cirrhosis, which can eventually develop into hepatocellular carcinoma. Currently, there is no effective treatment for liver fibrosis. Puerarin is a traditional Chinese herb, which is commonly used in the treatment of various diseases. In addition, it is also believed to have a therapeutic effect in liver fibrosis. However, whether puerarin reduces liver fibrosis via the ERK1/2 signaling pathway to inhibit the activation of hepatic stellate cell (HSC) and excessive collagen deposition in liver fibrosis remains unknown. The aim of the current study was to establish a liver fibrosismodel by intraperitoneal injection of thioacetamide (TAA) and investigate the effect of puerarin in the treatment of liver fibrosis. Hematoxylin and eosin and Van Gieson's staining were used to examine histopathological changes associated with liver fibrosis. Liver hydroxyproline content was examined to determine the total amount of collagen in the liver. The relative protein expression levels of transforming growth factorβ1 (TGFβ1), α-smooth muscle actin (α-SMA), collagen type I, fibronectin, ERK1/2 and p-ERK1/2 were determined by western blot analysis. In the TAA group, histopathological changes and collagen fiber content in rat liver tissue samples were significantly increased compared with the control group (P

read more

PMID: 

Exp Ther Med. 2019 Jul ;18(1):543-549. Epub 2019 May 17. PMID: 31258692

Abstract Title: 

Puerarin suppresses cell growth and migration in HPV-positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway.

Abstract: 

Puerarin is an effective component that is present in high concentrations in theplant and is extensively distributed throughout nature. Puerarin possesses a number of pharmacological effects and has strong pharmacological activity with few side effects and extensive clinical applications. The aim of the present study was to explore the effects of Puerarin on the apoptosis of human papillomavirus (HPV)-positive cervical cancer cells and the underlying molecular mechanisms. MTT assay, lactate dehydrogenase activity and Annexin V/fluorescein isothiocyanate/propidium iodide analysis were used to analyze cell growth of HPV-positive HeLa cervical cancer cells treated with Puerarin. Western blotting was performed to measure protein expression in the treated cells. Puerarin significantly reduced cell proliferation and induced apoptosis in HeLa cells. In addition, it was observed that Puerarin significantly enhanced caspase-3/9 activities and significantly increased B-cell lymphoma 2-asscoiate X protein expression in HeLa cells. Puerarin suppressed phosphatidylinositol-3 kinase (PI3K), phosphorylated (p)-protein kinase B (Akt) and p-mammalian target of rapamycin (mTOR) protein expression in HeLa cells. These results indicate that Puerarin induces apoptosis in HPV-positive HeLa cervical cancer cells via inhibiting PI3K/Akt/mTOR signaling.

read more

PMID: 

Curr Stem Cell Res Ther. 2019 Jul 3. Epub 2019 Jul 3. PMID: 31269886

Abstract Title: 

Puerarin for OVX-induced postmenopausal osteoporosis in murine model: systematic review and meta-analysis.

Abstract: 

AIMS/BACKGROUND: Ovariectomy (OVX)-induced murine model are widely used for post-menopausal osteoporosis study. Our current study was conducted to systematically review and critically assess the bone mass improved effect of puerarin for treating OVX-induced postmenopausal osteoporosis in murine model.METHODS: Literatures from PUBMED, EMBASE, and CNKI were searched from their inception date to January 9th, 2019. Two reviewers independently selected animal studies that evaluated the bone mass improved effect of puerarin compared with control in OVX-induced rats. Extracted data were analyzed by RevMan statistical software, and the methodological quality of each study was assessed.RESULTS: Eight studies with adequate randomization were included in the systematic review. Overall, puerarin could significantly improve bone mass as assessed using the bone mineral density (BMD); (eight studies, n=203; weighted mean difference, 0.05; 95% CI, 0.03-0.07; P

read more

PMID: 

Phytother Res. 2019 Jul 4. Epub 2019 Jul 4. PMID: 31273855

Abstract Title: 

Puerarin protects against high-fat high-sucrose diet-induced non-alcoholic fatty liver disease by modulating PARP-1/PI3K/AKT signaling pathway and facilitating mitochondrial homeostasis.

Abstract: 

As yet, there was no effective pharmacological therapy approved for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to evaluate the therapeutic potential of puerarin against NAFLD and explored the underlying mechanisms. C57BL/6J mice were fed with a high-fat high-sucrose (HFHS) diet with or without puerarin coadministration intragastrically. The levels of hepatocellular injury, steatosis, fibrosis, and mitochondrial and metabolism alteration were detected. First, puerarin ameliorated histopathologic abnormalities due to HFHS. We observed a marked increase in hepatic lipid content, inflammation, and fibrosis level, which were attenuated by puerarin. Possible mechanisms were related to puerarin-mediated activation of PI3K/AKT pathway and further improvement in fatty acid metabolism. Puerarin restored the NAD+ content and beneficially affected the hepatic mitochondrial function, which attenuated HFHS-induced steatosis and metabolic disturbances. Finally, hepatic PARP-1 was activated due to excessive fat intake. Puerarin attenuated the PARP-1 expression in HFHS-fed mice, and PJ34, the PARP inhibitor, could mimic these protections of puerarin. However, pharmacological inhibition of PI3K disabled the protection of puerarin or PJ34 toward NAD+ refilling and mitochondrial homeostasis. In conclusion, our findings indicated that puerarin could be a promising and practical therapeutic strategy in NAFLD through modulating PARP-1/PI3K/AKT signaling pathway and further facilitating mitochondrial function.

read more

PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):2746-2753. PMID: 31282213

Abstract Title: 

Puerarin attenuates hypoxia-resulted damages in neural stem cells by up-regulating microRNA-214.

Abstract: 

Puerarin has been reported to be useful in protection against hypoxia-induced injury. In our current study, we attempted to explore the protective effects of puerarin against hypoxia-caused damages in neural stem cells (NSCs). Additionally, the relative molecular underpinning studies preliminarily proceeded. NSCs were pre-incubated with puerarin before the hypoxic stimulus. MicroRNA-214 (miR-214) inhibitor was transfected into NSCs. Subsequently, the viability of NSCs was assessed by CCK-8 assay. Flow cytometry was employed to detect apoptotic cells after staining. qRT-PCR was performed to quantify miR-214. Western blot was applied for analyzing the expression of apoptosis-relative proteins and regulators. We found that puerarin alleviated hypoxia-induced apoptosis and maintained cell viability. Hypoxia-evoked up-regulation of miR-214 was further enhanced by puerarin. By contrast, miR-214-deficient NSCs showed the reduction in cell viability and the facilitation in apoptosis progress after pre-treatment with puerarin and stimulation in a hypoxia circumstance. Additionally, puerarin restored the phosphorylation of relative regulators, which was originally blunted by hypoxia. However, puerarin did not evidently restore the phosphorylation for response to hypoxia in miR-214-silenced NSCs. In conclusion, puerarin might be applied as a novel agent to ameliorate hypoxia-evoked damages in NSCs. Molecularly, miR-214 might be implicated in the protective roles of puerarin.

read more