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Graphical abstract Highlights • Platycodon grandiflorum Saponins (PGS) ameliorated scrotal heat-induced spermatogenic damage in mice. • Platycodon grandiflorum Saponins (PGS) inhibited heat stress (HS)-induced oxidative stress and apoptosis in mice. • Platycodon grandiflorum Saponins (PGS) partly regulated the MAPK signaling pathway in HS mice. Abstract The aim of the present study was designed to investigate that Platycodon grandiflorum saponins (PGS) exerted protective effects against testicular injury induced by scrotal hyperthermia. PGS (15, 30 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43 °C for 18 min on the 7th day. Heat stress (HS) induced spermatogenic damage was associated with a significant loss of leydig cells and the changes of serum testosterone, oxidative stress and apoptosis markers, and activated MAPK signaling pathway. In contrast, PGS treatment normalized HS-induced histopathological changes and prevented the activation of MAPK signaling pathway, which was contributed to oxidative stress and apoptosis in the testis of treated mice. In conclusion, our findings clearly demonstrated that PGS exhibited a significant protective effect against HS-induced testicular dysfunction, largely dependent upon the inhibition of oxidative stress associated apoptosis via partly regulation of MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exploring the regulatory effect of PD on CP-induced intestinal injury. • Demonstrating that PD exerts a certain protective effect on intestinal damage caused by CP. • Revealing that PD for alleviating CP-induced intestinal damage might be related to PERK-eIF2ɑ-ATF4 signaling pathway. The current study aimed to reveal the inhibitory effect of Platycodin D (PD) on intestinal cell apoptosis mediated by ER stress. Treatment with PD alleviated pathological changes of the intestine and reduced secretion of intracellular enzyme Diamine oxidase (DAO) in the upper villi of the small intestinal mucosa in Cisplatin (CP) intestinal injury model and increased expression of key protein Occludin and ZO-1 of the intestinal mechanical barrier. PD inhibited ER stress in a dose-dependent in CP-caused IEC-6 cells and the level of phosphorylation of Protein kinase R-like ERK kinase (PERK) and Eukaryotic initiation factor-2 alpha (eIF2α) reduced. Besides, the ER stress inhibitor 4-PBA was used to confirm that PD alleviated the ER stress in vitro. In conclusion, PD exerted an intestinal protective effect through the inhibition of ER stress in CP-treated mice and IEC-6 cells. These data indicated that PD was a promising natural medicine for intestinal protection. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is one of the most common chemotherapeutic drugs. Cisplatin-induced toxicity gives rise to gastrointestinal cell damage, subsequent diarrhea and vomiting, leading to the discontinuation of its clinical application in long-term cancer chemotherapy. Panax quinquefolium L., also known as American ginseng, has many pharmacological activities such as improving immunity, anti-tumor, anti-radiation and blood sugar lowering.Purpose: Previously, our laboratory reported that American ginseng berry extract could alleviate chemotherapeutic agents-induced renal damage caused by cisplatin. Hence, this study further explored the protective effect of P. quinquefolium saponins (PQS) on cisplatin-induced intestinal injury in mice and the possible molecular mechanisms.Methods: Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze intestinal injury based on various molecular mechanisms.Results: We demonstrated the destruction of the intestinal barrier caused by cisplatin exposure by detecting the activity of diamine oxidase (DAO) and the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Meanwhile, cisplatin exposure changed SOD and MDA levels in the small intestine, causing oxidative damage to the intestinal mucosa. The inflammation associated-intestinal damage was further explored by the measurement of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and analysis of nuclear factor-kappa B (NF-κB) inflammatory pathway protein expression. Moreover, apoptotic cells labeled with TUNEL staining-positive cells and activated caspase family proteins suggest that cisplatin induces intestinal apoptosis. Interestingly, PQS pretreatment significantly reversed these situations.Conclusion: These evidences clearly suggest that PQS can alleviate cisplatin-induced intestinal damage by inhibiting oxidative stress, reducing the occurrence of inflammation and apoptosis, and improving intestinal barrier function. [ABSTRACT FROM AUTHOR]