Ethanol Extract of Carica papaya Leaf Can Increase Breast Milk in Lactating Rat

Abstract

BACKGROUND: Carica papaya leaves (Carica papaya L) have been used empirically and traditionally as a galactogogue, but their mechanism as galactogogue is still unknown.
 AIM: This study aimed to analyze the effect of ethanol extract from papaya leaves on blood prolactin levels, prolactin receptor (prlr) gene expression, the number of breast alveoli and lobes of lactating rats.
 METHODS: This in vivo true experimental study with a post-test control group design was conducted on 24 rats with the same lactating period. They were divided into four groups consisting of six rats each. The control group was given daily standard food, whereas the three treatment groups were, respectively, given additionally ethanol extract of 0.95 mg, 1.9 mg, and 3.8 mg/200 g BW/day from day 1 to day 14 of lactation. On day 14, all of the rats were sacrificed, blood prolactin levels were measured by ELISA, prlr gene expressions were measured using RT-PCR, and numbers of breast alveoli and lobes were microscopically observed through staining histological specimens. A statistical analysis was carried out using one-way ANOVA, Tukey's test, Games–Howell test, and path analysis at 95% confidence level.
 RESULTS: Levels of blood prolactin levels, prlr gene expression, the number of breast alveoli, and lobes of all treatment rat groups were significantly above those of the control group (p < 0.05). The increases of all parameters were consistent; the most effective dose was 1.9 mg/200 g BW.
 CONCLUSION: The Carica papaya leaf ethanol extract had a galactogogue effect on lactating rats by increasing blood prolactin levels, prlr gene expression, and numbers number of breast alveoli and lobes.

Carica papaya leaf ethanol extract effect on milk volume, β-casein gene (Csn2) expression, β-casein levels, and milk total protein levels

“…The previous study shows that papaya leaf ethanol extract can increase prolactin level in blood plasma, the prolactin receptor (prlr), the number of lobes and alveoli of mammae epithelial cell in lactating rats 37 . The increasing of prlr in mammary epithelial cells can induce ductal side branching, alveolar budding, and milk secretion through specific transcription factors such as STAT5 38 .…”

“…Varghese's study showed that prlr internalization is dependent on K63 polyubiquitination of the receptor, whereas elevated PRL signaling would be promote the downregulation of prlr 58 . From the previous study, we know that administration of D3 also causes a decrease of prlr gene expression 37 . Thus, it will indirectly cause a decrese of β-casein (Csn2) gene expression, then a decrease of β-casein levels, total protein levels, and milk volume which unknown mechanism.…”

Narrative Review of Known Plants which Have Potential Benefits as Natural Galactagogues in Indonesia

“…However, papaya leaves contain flavonol components (kaempferol and quercetin), which positively aff ect phytoestrogens because they can activate prolactin receptors to increase milk production (Setyono et al, 2016). Table 6 summarized selected in vivo studies of papaya leaves as a galactagogue using lactating rats (Herawati et al, 2021) and humans (Ikhlasiah et al, 2020;Khasanah et al, 2021;Pratiwi, 2018). Herawati et al (2021) showed that papaya leaves ethanol extract significantly increased prolactin level, prolactin receptors gene expression, and the number of breast alveoli and lobules in lactating rats compared to the control.…”

“…Table 6 summarized selected in vivo studies of papaya leaves as a galactagogue using lactating rats (Herawati et al, 2021) and humans (Ikhlasiah et al, 2020;Khasanah et al, 2021;Pratiwi, 2018). Herawati et al (2021) showed that papaya leaves ethanol extract significantly increased prolactin level, prolactin receptors gene expression, and the number of breast alveoli and lobules in lactating rats compared to the control. A dosage of 1.9 mg/200 g body weight/day of papaya leaves ethanol extract was the most eff ective treatment since it gave the highest increase.…”

Molecular docking analysis of Carica papaya leaf’s bioactive components as prolactin production modulator

“…Based on the liquid chromatography mass spectroscopy (LCMS)/MS analysis, it is known that papaya leaves also contain flavonoids (unpublished data). An in vivo study has shown that papaya leaves can increase plasma prolactin levels in lactating rats [30]. This study aims to explain the molecular mechanism of active compounds from papaya leaves in regulating or influencing the production of the prolactin hormone using a docking technique as a tool for virtual screening and optimizing the combination of active compounds (ligands) with estrogen, leptin, and aromatase as the target proteins.…”