Cistanche deserticola polysaccharides protect against cyclophosphamide-induced premature ovarian failure in mice by regulating the JAK-STAT pathway

Abstract

Ethnopharmacological relevance

Classical Chinese medical texts, notably the Compendium of Materia Medica (Ben Cao Gang Mu) and Zhong Hua Ben Cao (Chinese Herbal Medicine), have historically documented Cistanche deserticola's application as a tonic herb for addressing reproductive disorders including male impotence, reduced fertility and female menstrual infertility, among other conditions. Polysaccharides from Cistanche deserticola are recognized as the plant's principal bioactive components. Nevertheless, the therapeutic potential and mechanistic actions of Cistanche deserticola polysaccharides (CDPs) in premature ovarian failure (POF) remain unexplored.

Aim of the study

This study aimed to determine the protective role of CDPs in POF and to elucidate the underlying mechanisms.

Material and methods

POF mouse models were developed through intraperitoneal administration of cyclophosphamide (CTX) at a high dose of 120 mg/kg/day and followed by 8 mg/kg/day (low maintenance dose) administered daily for 14 consecutive days. In a prophylactic therapeutic regimen, CDPs received pre-treatment initiation two weeks before model establishment, with phased administration maintained throughout three distinct temporal parameters (2-, 6-, and 8-week intervals) during pharmacological intervention. Upon anesthetization of the mice, ovarian tissues were collected for subsequent histopathological and molecular investigations. These analyses included immunohistochemistry to detect apoptotic proteins, Proliferative index mapping through Ki67 immunofluorescence, and electron microscopy to assess mitochondrial status and other pertinent indicators. RNA-seq elucidated the core regulatory pathway governing POF and potential protective targets for CDPs.

Results

Experimental evidence established that intragastric administration of CDPs ameliorate histopathological ovarian lesions and rescue endocrine homeostasis, thereby enhancing the health of offspring in CTX-induced POF mice. This effect is facilitated by the promotion of follicular development, the proliferation of follicles, and the suppression of granulosa cell apoptosis. Furthermore, CDPs significantly attenuation of oxidative stress via ROS scavenging and restore mitochondrial morphology and function. In conclusion, the protective role of CDPs are closely linked to the JAK-STAT signaling pathway in POF models.

Conclusion

Our findings demonstrate that CDPs are capable of protecting protect the ovary tissue against CTX-induced damages through suppression of the activation of the JAK-STAT pathway and attenuation of granulosa cells (GCs) apoptosis.