Protective roles and mechanisms of rosmarinic acid in cyclophosphamide‐induced premature ovarian failure

Yao, Yang; Xu, Yinglei; Wang, Yong

doi:10.1002/jbt.22591

Cited by 17 publications

(12 citation statements)

References 37 publications

(36 reference statements)

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“…This last protein can eventually produce the maturation and release of IL-1β [3]. In previous studies, RA was shown to inhibit inflammasome activation in experimental models of inflammation in epidermal keratinocytes [38], neuroinflammatory injury [39], atherosclerosis [40] and premature ovarian failure [41]. Despite these findings, there is no previous evidence that RA may exert its anti-inflammatory effects through suppression of inflammasome activation in UC.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome

et al. 2021

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Ulcerative colitis (UC), one of the two main types of inflammatory bowel disease, has no effective treatment. Rosmarinic acid (RA) is a polyphenol that, when administered orally, is metabolised in the small intestine, compromising its beneficial effects. We used chitosan/nutriose-coated niosomes loaded with RA to protect RA from gastric degradation and target the colon and evaluated their effect on acute colitis induced by 4% dextran sodium sulphate (DSS) for seven days in mice. RA-loaded nanovesicles (5, 10 and 20 mg/kg) or free RA (20 mg/kg) were orally administered from three days prior to colitis induction and during days 1, 3, 5 and 7 of DSS administration. RA-loaded nanovesicles improved body weight loss and disease activity index as well as increased mucus production and decreased myeloperoxidase activity and TNF-α production. Moreover, RA-loaded nanovesicles downregulated protein expression of inflammasome components such as NLR family pyrin domain-containing 3 (NLRP3), adaptor protein (ASC) and caspase-1, and the consequent reduction of IL-1β levels. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression increased after the RA-loaded nanovesicles treatment However, these mechanistic changes were not detected with the RA-free treatment. Our findings suggest that the use of chitosan/nutriose-coated niosomes to increase RA local bioavailability could be a promising nutraceutical strategy for oral colon-targeted UC therapy.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome

et al. 2021

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“…Detailed comparisons were conducted between the control group and the low-dose rapamycin group after 30 days. A single dose of 120 mg/kg CTX was commonly used to establish a mouse model of ovarian dysfunction[ 16 , 17 ]. To determine the underlying mechanism of rapamycin against CTX-mediated ovarian dysfunction, 48 mice were randomly divided into four groups: control group (CC: equal volume saline containing equivalent DMSO), rapamycin treatment group (RC: 5 mg/kg rapamycin for 30 days), CTX-treated group (MC: a single dose of 120 mg/kg CTX at day 24), and rapamycin intervention group (RM: 5 mg/kg rapamycin for 30 days with a single dose of 120 mg/kg CTX at day 24).…”

Section: Methodsmentioning

confidence: 99%

Rapamycin maintains the primordial follicle pool and protects ovarian reserve against cyclophosphamide-induced damage

Chen

Tang

Guan

et al. 2022

Journal of Reproduction and Development

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Any abnormal activation of primordial follicles and subsequent depletion can irreversibly diminish the ovarian reserve, which is one of the major chemotherapy-induced adverse effects in young patients with cancer. Herein, we investigated the effects of rapamycin on the activation and development of ovarian follicles to evaluate its fertility-sparing therapeutic value in a cyclophosphamide (CTX)-treated mouse model. Based on ovarian histomorphological changes and follicle counting in 50 SPF female C57BL/6 mice, daily administration of 5 mg/kg rapamycin for 30 days was deemed an ideal dosage and duration for administration in subsequent experiments. Compared with the control group, rapamycin treatment inhibited the activation of quiescent primordial follicles, with no obvious side effects observed. Finally, 48 mice were randomly divided into four groups: control, rapamycin-treated, cyclophosphamide-treated, and rapamycin intervention. Body weight, ovarian histomorphological changes, number of primordial follicles, DDX4/MVH expression, apoptosis of follicular cells, and expression of apoptosis protease-activating factor (APAF)-1, cleaved caspase 3, and caspase 3 were monitored. Co-administration of rapamycin reduced primordial follicle loss and the development of follicular cell apoptosis, thereby rescuing the ovarian reserve after CTX treatment. On analyzing the mTOR signaling pathway, we observed that rapamycin significantly decreased CTX-mediated overactivation of mTOR and its downstream molecules. These findings suggest that rapamycin exhibits potential as an ovarian-protective agent that could maintain the ovarian primordial follicle pool and preserve fertility in young female patients with cancer undergoing chemotherapy.

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“…With the help of fluorescence immunohistochemistry, histological analysis, Western blot analysis and polymerase chain reaction, RA (40 mg/kg) was investigated to effectively attenuate the abnormal situations of the model including injured ovarian, increased ovarian index, and serum sex hormone levels, the overexpression of the nucleotide-binding oligomerization domain receptor protein-3 (NLRP3) inflammasome, and apoptosis-related proteins in the ovarian. The findings indicate that RA might have a bright prospect in POF treatment in the future [ 274 ].…”

Section: Pharmacologymentioning

confidence: 99%

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

et al. 2022

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Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

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Protective roles and mechanisms of rosmarinic acid in cyclophosphamide‐induced premature ovarian failure

Cited by 17 publications

References 37 publications

Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome

Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome

Rapamycin maintains the primordial follicle pool and protects ovarian reserve against cyclophosphamide-induced damage

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

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