Determinants of Rutin, Myricetin, Quercetin and Kaempferol Compounds in Ethanol Extracts of Sauropus androgynus, Moringa oleifera Lam and Coleus amboinicus Lour: To Sustain Exclusive Breastfeeding
Sukmayati Alegantina1, Efriwati Efriwati2, Ani Isnawati3, Nanang Yunarto4,
Ariyani Noviantari5, Maratu Soleha6, Lucie Widowati7, Dian Sundari8, Suharmiati Suharmiati9,
Ifa Manzila10, Putri Reno Intan11
1Research Center for Pharmaceutical Ingredients and Traditional Medicine,
Research Organization for Health, National Research and Innovation Agency, Bogor, Indonesia.
2Research Center for Public Health and Nutrition, Research Organization for Health,
National Research and Innovation Agency, Bogor, Indonesia.
3Research Center for Pharmaceutical Ingredients and Traditional Medicine,
Research Organization for Health, National Research and Innovation Agency, Bogor, Indonesia.
4STIKES Widya Dharma Husada, Tangerang, Indonesia.
5Center for Biomedical Research, Research Organization for Health,
National Research and Innovation Agency, Bogor, Indonesia.
6Research Center for Pharmaceutical Ingredients and Traditional Medicine,
Research Organization for Health, National Research and Innovation Agency, Bogor, Indonesia.
7Research Center for Pharmaceutical Ingredients and Traditional Medicine,
Research Organization for Health, National Research and Innovation Agency, Bogor, Indonesia.
8Research Center for Public Health and Nutrition, Research Organization for Health,
National Research and Innovation Agency, Bogor, Indonesia.
9Research Center for Pharmaceutical Ingredients and Traditional Medicine, Research Organization for Health, National Research and Innovation Agency, Bogor, Indonesia.
10Research Center for Horticultural and Estate Crops, Research Organization for Agriculture and Food, National Research and Innovation Agency, Bogor, Indonesia.
11Center for Biomedical Research, Research Organization for Health,
National Research and Innovation Agency, Bogor, Indonesia.
12Animal Biomedical Study Program, School of Veterinary Medicine and Biomedical Sciences,
IPB University, Bogor, Indonesia.
*Corresponding Author E-mail: sukm004@brin.go.id, efri003@brin.go.id, anii001@brin.go.id
ABSTRACT:
This study aimed to determine the levels of rutin, quercetin, myricetin, and kaempferol in the ethanol extracts of Sauropus androgynus, Moringa oleifera Lam, and Coleus amboinicus Lour leaves, and to evaluate their potential as galactagogue agents to enhance breast milk production in support of sustainable exclusive breastfeeding practices. Extraction of each plant was carried out using percolation method with 70% ethanol as solvent, and analysis of the galactagogue compounds was performed using High-Performance Liquid Chromatography (HPLC). The results showed that the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves contained rutin, quercetin, myricetin, and kaempferol, with myricetin being the most abundant compound among the three extracts. The consumption of rutin, quercetin, myricetin, and kaempferol in the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves may help increase breast milk production and support the continuation of breastfeeding and exclusive breastfeeding. Therefore, the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves have potential to be formulated as nutritional sources for pregnant and breastfeeding women to maintain and enhance the sustainability of breastfeeding and exclusive breastfeeding practices. However, further research is required to confirm safety and efficacy of these ethanol extracts.
KEYWORDS: Galactagogue, HPLC, S. androgynus, M. oleifera Lam, C. amboinicus Lour.
INTRODUCTION:
Breast milk is essential for breastfed babies and breastfeeding mothers. It is the primary and best source of nutrition for a baby's physical growth, cognitive development, and immune system, especially during the first six months of life. Breast milk is rich in proteins, fats, carbohydrates, and essential vitamins for baby's healthy growth. It helps mother's postpartum recovery by releasing oxytocin to reduce bleeding and increase contractions1. Breastfeeding can also boost the immune system, as it contains immunomodulating, antimicrobial, and prebiotic substances that are important for reducing the risk of disease in infants. Meanwhile, for breastfeeding mothers, it is beneficial to reduce cases of postpartum hemorrhage and depression. In the long run, it may contribute to lowering the risk of type 2 diabetes, breast cancer, ovarian cancer, and cardiovascular disease2. The World Health Organization (WHO) recommends exclusive breastfeeding for six months and continued breastfeeding with complementary feeding for up to two years due to its critical benefits for infant health and development2.
Breastfeeding, particularly exclusive breastfeeding, offers substantial health benefits for mothers and infants, contributes significantly to the long-term socio-economic development of nations and to global well-being as well. Improving breastfeeding practices can help achieve the 2030 Sustainable Development Goals (SDGs) and create reliable human resources. Investing in breastfeeding is one of the most effective strategies that a country can adopt to promote a healthy, equitable, and sustainable future. Breastfeeding practices, as emphasized in the health-related SDGs, have the potential to prevent approximately 823,000 deaths in children under the age of two each year. Economically, optimal breastfeeding could save an estimated USD 302 billion annually in healthcare costs and lost productivity3.
Although the benefits of breastfeeding, particularly exclusive breastfeeding, have been well documented in numerous studies, global rates of exclusive breastfeeding remain low, including in Indonesia.
According to the National Health Research data from the Ministry of Health of the Republic of Indonesia in 2018, the number of breastfeeding mothers who provide exclusive breastfeeding in Indonesia is very low, at only 37.8%4. Low breastfeeding rate (hypogalactia) among breastfeeding mothers is mainly due to the risk factors of older age, lower education, heavy physical labor, and certain medical conditions, leading to inadequate milk production5. One public health intervention to support breastfeeding and exclusive breastfeeding among lactating women involves optimizing milk secretion by promoting lactogenesis through galactagogue agents.
Galactagogues, which substantially promote breast milk production, are essential for supporting effective lactation. Recently, increasing attention has been given to natural and herbal galactagogues6. Therefore, the therapeutic efficacy and underlying mechanisms of herbal galactagogues need to be investigated, including the analysis of the active components of galactagogues in treating lactation insufficiency.
Studies on local plants traditionally consumed to enhance breast milk production, such as Torbangun (C. amboinicus Lour.), have shown that their galactagogue properties can effectively increase the milk supply. This increase in milk production can ultimately affect the duration and frequency of breastfeeding7. Katuk (S. androgynus) leaf decoctions and extracts have demonstrated efficacy in promoting sufficient breast milk supply8. Both plants contain flavonoids and exhibit high antioxidant activity, even after processing into flour and food bars. Feeding S. androgynus food bars significantly increased breast milk production (p<0,05)9. Similarly, Moringa Leaf (M. oleifera Lam)10. However, there has been few analysis of flavonoid compounds that are thought to increase milk production (galactagogues) in these three plants, especially rutin, myricetin, quercetin, and kaempferol.
Rutin, myricetin, quercetin, and kaempferol are polyphenolic compounds that affect mammary gland function and increase galactagogue activity11. In silico analysis of rutin, quercetin, and kaempferol, as well as quercitrin and afzelin compounds in bowl leaves (Polyscias scutellaria), showed increase of milk production through two main proteins, prolactin and serotonin 5-hydroxytryptamine-2A receptors (5-HT2AR)12. In vitro, quercetin has been shown to promote the proliferation of primary mammary epithelial cells and stimulate prolactin receptor expression. Myricetin effectively inhibits inflammation in the mammary glands and enhances the integrity of the mammary blood barrier in experimental rats13.
There is a lack of comprehensive information regarding the active compounds, particularly rutin, myricetin, quercetin, and kaempferol, in herbal plants traditionally used to enhance breast milk production. Therefore, it is important to quantify the flavonoid compounds in the ethanol extracts of S. androgynus, M. oleifera Lam., and C. amboinicus Lour. This study aimed to determine the levels of rutin, myricetin, quercetin, and kaempferol in the leaf ethanol extracts of these three plants and explore their potential contribution to breastfeeding sustainability.
MATERIALS AND METHODS:
Materials:
Plant preparation and identification:
The plants used in this study were S. androgynus, M. oleifera Lam, and C. amboinicus Lour cultivated in Wonosobo, Central Java. The leaves were used as plant parts for the study. The authenticity of the plant species was confirmed through botanical identification by experts at the Biological Laboratory, Indonesian Institute of Sciences (LIPI), Cibinong, West Java, Indonesia, with identification/determination number 856/IPH.1.01/If.07/VIII/2020.
Leaves from each were cleaned of impurities using distilled water and then oven-dried at 40°C, and finely ground into powder. The powder were stored in airtight containers at ambient temperature until subsequent analysis or processing.
The leaf powders of S. androgynus, M. oleifera Lam, and C. amboinicus Lour were extracted using percolation method with 70% ethanol for 90 min. The percolation yield were extracted using a rotary evaporator until a paste extract was obtained and then concentrated thus the water content below 10%. The moisture content of each extract was determined using a moisture analyzer (Sartorius M150) with the infrared drying method.
Methods:
Preparation of standard solutions and samples:
Stock solutions of 1000ppm rutin, myricetin, quercetin, and kaempferol were prepared by dissolving 10mg each of standard rutin trihydrate Sigma 78095, myricetin Sigma 476275, quercetin dihydrate Sigma 00200595, and kaempferol 3-glucoside Sigma 00550580 in 10ml of methanol followed by sonication for 10min. Calibration curves were constructed using standard solutions at 25, 50, 75, 100, and 150ppm concentrations. Each solution was sonicated for 10min before analysis.
Each 10mg of ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour were dissolved in methanol to the limit of 10ml, sonicated for 10min, and filtered with a 0.20μm PTFE filter and then injected into the HPLC system (Waters 2695) with a PDA detector (Waters 2996). The column used was a Waters C18 Sunfire column (4.6x150mm, 5.0µm). A combination of acetonitrile and 0.1% acetic acid solvents at a ratio of 1:9 was used as the mobile phase to measure the four galactagogue compounds. The flow rate of the mobile phase was 1mL/min. The detection wavelength was set at 272nm, injection volume at 20µL, and column temperature at 30°C14.
Identification and quantification:
The identity and concentration of rutin, myricetin, quercetin, and kaempferol in the samples were determined based on the retention time and by comparing the peak areas of the sample chromatograms with the standards of each compound using HPLC. The types and concentrations of each compound in the three ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves were compared to determine the superiority of each extract.
Plant identification:
Accurate plant identification is a crucial preliminary step before conducting further studies, including those aimed at exploring the plant’s potential benefits and active compounds, as in the present study. Identification can ensure that plants used empirically in the community are the same type and species and are known globally in Latin America. Plant identification is also important to avoid errors between the materials used as samples and the references used for reference. Accurate plant identification can support pharmacological studies and sustainable use of plant resources15.
RESULT:
The results of species identification of plant species by botanists from the Biological Laboratory, Indonesian Institute of Sciences (LIPI) in 2020 showed that the leaves used for samples were S. androgynus, M. oleifera Lam, and C. amboinicus Lour species, as shown in (table 1).
|
Plants |
Species |
Family |
|
Katuk |
Breynia androgyna (L.) Chakrab and N.P Balakr |
Phyllanthaceae |
|
Kelor |
Moringa oleifera Lam |
Moringaceae |
|
Torbangun |
Coleus amboinicus Lour |
Lamiaceae |
Figure 1. HPLC chromatograms of rutin, quercetin, myricetin, and kaempferol standards
The diversity and levels of each compound in the test plant extracts are presented in (table 2).
|
Extracts |
Concentration (mg/kg) |
|||
|
Rutin |
Myricetin |
Quercetin |
Kaempferol |
|
|
S. androgynus |
2,000 |
22,300 |
8,300 |
7,100 |
|
M.oleifera |
8,900 |
21,000 |
7,800 |
- |
|
C. amboinicus |
1,300 |
23,000 |
7,900 |
7,100 |
DISCUSSION:
The results of plant determination are presented (table 1). showed that the sampled katuk, kelor, and torbangun plants were correct as desired. The name of the katuk plant species has changed with the development of molecular research. Although the name change was published over ten years since 2012, it is still not widely used. Until now, journal publications naming katuk plants still use Sauropus androgynus, not Breynia androgyna (L.) Chakrab. and N.P. Balakr16.
The HPLC results of the rutin, quercetin, myricetin, and kaempferol standards at a wavelength of 272nm showed good separation. This is indicated by the perfectly separated peaks and the absence of overlapping peaks (figure 1). The first chromatographic peak of the compound to appear was the rutin compound at 11,484 min, followed by the myricetin compound at 16,236min and quercetin at 21,038min. The final chromatographic peak appeared at 26,527min and corresponded to kaempferol (figure 1). For the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves, there was a slight shift in the peaks, as shown in (figure 2).
Rutin compounds, quercetin, myricetin, and kaempferol are found in all leaf extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour, except for kaempferol compounds not found in M. oleifera Lam leaf extracts (figure 2). The content of each compound in each plant leaf extract also differed. The diversity and levels of each compound in the test plant extracts are presented in (table 2).
Myricetin was found to have the highest concentration. This was observed in all three ethanol extracts of the test plants. The highest concentration was observed in the leaf ethanol extract of C. amboinicus Lour. (23,000 mg/kg), followed by S. androgynus (22,200mg/kg), and M. oleifera Lam (21,000mg/kg). Several modern pharmacological studies have shown that myricetin or 3, 5, 7, 3′, 4′, 5′-hexahydroxyflavonol has a wide range of biological activities and has a potent anti-inflammatory agent. Myricetin can provide good protection against various inflammations, including mammary gland inflammation or mastitis17, and also repaired the integrity of the blood-milk barrier to prevent the mixing of blood components in milk. Damaged or dysfunctional blood-milk barrier integrity during mastitis can result in milk mixing with blood or vice versa18. This can be harmful to both the mother and her breastfed baby.
Mastitis, or inflammation of the mammary glands, often occurs in breastfeeding mothers, especially in the first 6-12 weeks after delivery. Mastitis symptoms range from mild symptoms, such as redness, burning, and pain in the breast, to serious symptoms that may require hospitalization, such as fever, abscess, and septicemia (WHO 2020). Recovery from mastitis can take a long time and can cause trauma and reluctance to breastfeed. This condition can decrease milk secretion, as milk production matches or equals the amount of milk secreted from the breast. High levels of the hormone prolactin initially regulate milk production; however, after a few weeks, local autocrine control takes over, allowing the amount of milk produced to equal the amount eliminated19.
High levels of myricetin due to the consumption of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaf extracts prevent mastitis in nursing mothers. Breastfeeding mothers who are free of mastitis will avoid breastfeeding trauma and can maintain high milk production for the needs of the baby. Therefore, although myricetin does not directly initiate breast milk production, milk is still released from the mother's breast through the baby's suckling activity. Local autocrine control regulates milk production according to the baby ’sneeds, and breastfeeding and executive breastfeeding can be maintained.
The second most abundant compound in M. oleifera Lam was rutin (8,900mg/kg), but this compound was found in very small amounts in the ethanol extracts of S. androgynus and C. amboinicus Lour. leaves. The levels of rutin in the ethanol extracts of these two plant leaves were only 2,000 and 1,300mg/kg, respectively (table 2). Rutin is a flavonoid of the flavonol type and is a 3, 3', 4', 5,7-pentahydroxyflavone-3-rhamnoglucoside compound20. This compound exhibits several biological and pharmacological activities20. In terms of continued breastfeeding by breastfeeding mothers, Rutin plays an important role in overcoming metabolic stress, especially after childbirth21.
Metabolic stress is a physiological process that occurs when homeostasis is disrupted by abnormal nutrient utilization. Metabolic stress during the transition period, especially after childbirth, can affect mammary gland health in mammals, including human beings. Rutin supplementation in experimental animals (sheep) showed that rutin can inhibit the mRNA expression of inflammatory markers, reducing the ratio of necrosis factor (phosphorylated NF-κB p65) to total NF-κB p65 (p65). Rutin supplementation also plays an important role in maintaining the redox balance of the mammary glands, and anti-apoptotic activity in the mammary glands has a positive effect on preventing inflammation and oxidative stress21.
Although not proven in humans, regular consumption of supplements may prevent breastfeeding mothers from experiencing inflammation, metabolic stress, oxidative stress, and anti-apoptotic mammary glands, as demonstrated in sheep. The preservation of mammary glands from inflammation, metabolic stress, oxidative stress, and anti-apoptotic activity in nursing mothers due to the consumption of M. oleifera Lam leaf extract, which is rich in rutin, can ultimately maintain breast milk production. Smooth and sufficient breast milk production are important for the continuity of breastfeeding and the executive breast milk by nursing mothers for the growth and development of their babies.
Another compound that was found to be quite high was quercetin. The highest concentration of quercetin was found in the ethanol extract of S. androgynus leaves (8,300mg/kg), followed by C. amboinicus Lour (7,900 mg/kg) and M. oleifera Lam (7,800mg/kg) (table 2). Similar to myricetin and rutin, quercetin or 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-on also has many biological activities and strong antioxidant properties that can scavenge free radicals in the body, reduce oxidative stress, and protect against cell damage22. The benefits of breastfeeding mothers consuming quercetin-rich sources will also be passed on to breastfed babies23. Therefore, the benefits of quercetin are not only beneficial for breastfeeding mothers but also for infants to avoid free radicals, oxidative stress, and cell damage. The results of trials and epidemiological studies have found a relationship between the development of diseases after adulthood and conditions that occur in the periconceptional phase, the fetus, and during the newborn period. In addition, quercetin can encourage and stimulate the proliferation of primary mammary epithelial cells and prolactin receptor expression in vitro18. Therefore, quercetin consumption by breastfeeding mothers can increase and maintain the continuity of breast milk production for the health of infants13 and the continuity of breastfeeding and executive breastfeeding by breastfeeding mothers for the growth and development of their infants.
Kaempferol is another compound found in the ethanol extracts of S. androgynus and C. amboinicus Lour leaves. The content of kaempferol compounds in ethanol extracts of S. androgynus and C. amboinicus Lour leaves is the same as in M. oleifera Lam is 7,100mg/kg, this kaempferol compound is not found in ethanol extracts of Moringa oleifera Lam leaves (table 2). This finding differs from those of previous studies, which reported that the main compounds in the ethanol extract of M. oleifera leaves are quercetin and kaempferol24. Kaempferol is a flavonoid found in M. oleifera, as well as in vanilla and quercetin25. Furthermore, Divya et al. stated that the number of compounds in M. oleifera isolates is influenced by several factors, such as temperature, sun exposure, soil composition, and geographical location of the plants grow25. In addition, the absence of kaempferol compounds in the M. oleifera Lam extract in this study may be due to the low levels of kaempferol compounds that were below the detection limit of the tool. The differences in the low levels of kaempferol compounds in this study compared to previous studies24. In addition to environmental factors, where different plants grow, Batmomolin A research used plants from the Batu area, East Java, while in this study, they came from Wonosobo, Central Java. The extraction method can also affect the concentration of the chemical components. Batmomolin A study conducted maceration extraction by dissolving M. oleifera Lam extract powder with 1:10 ethanol solvent, while although both used ethanol solvent, the method used in this study was the percolation method with 70% ethanol for 90 min. Divya stated that the concentration of phytonutrients in M. oleifera leaf extract depends on several things, such as the extraction process, type of solvent, solvent to solid ratio, ambient temperature, stirring rate, and particle size25.
Similar to the other three compounds, kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4 H-chromene-4-on) has many biological activities, including antioxidant, antimicrobial, anti-inflammatory, and anticancer activities, with wide applications26. In terms of the continuity of breastfeeding by nursing mothers to their babies, kaempferol compounds can prevent the development of mastitis (inflammation of the breast) and reduce the expression of myeloperoxidase (MPO), Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and modulate angiopoietin 2 (ANGPTL2) to reduce mastitis in experimental animals27. Kaempferol compounds are both preventive and therapeutic agents in breast cancer. In vitro tests, kaempferol compounds play a role in inhibiting the growth of breast cancer cells (human breast cancer cell lines or MCF-7) by reducing the expression of Bcl2 antibody (Bcl-2 Antibody) and inducing apoptosis27.
The consumption of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves to increase breast milk production has long been empirically used in some communities in Indonesia and Malaysia. Research on the application of the leaves of these herbal plants has also proven to increase breast milk production. The high content of rutin, quercetin, myricetin, and kaempferol in the ethanol extracts of the leaves of S. androgynus, M. oleifera Lam, and C. amboinicus Lour in this study further strengthens the evidence of the importance of these plants in increasing breast milk production and maintaining the continuity of breastfeeding and executive milk in the future. However, direct consumption of herbal plant leaves has many problems, ranging from availability that is not easily accessible to all pregnant and lactating women to the difficulty of standardizing the content of its active components. Extraction of the intended active components is the best solution for overcoming these limitations. The extraction of active components in the leaves of S. androgynus, M. oleifera Lam, and C. amboinicus Lour to obtain rutin, quercetin, myricetin, and kaempferol compounds will be an opportunity for the higher utilization of these herbal plants as one of the efforts to increase breastfeeding by nursing mothers. However, the safety of the extracted products is a concern. The extracts must be free from contamination by residual solvents, heavy metals, and microorganisms, which is the main prerequisite for the further utilization of rutin, quercetin, myricetin, and kaempferol. The availability of rutin, quercetin, myricetin, and kaempferol compounds that have been formulated as therapeutic or functional foods can fulfill the nutritional needs of pregnant and lactating women, so that the continuation of breastfeeding and executive breastfeeding can be carried out. The implementation of increased breastfeeding and executive breastfeeding can ultimately improve the achievement of the Sustainable Development Goals (SDGs) and Indonesia's Golden Generation 2045.
CONCLUSION:
The results of this study indicate that the leaf extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour contain rutin, quercetin, myricetin, and kaempferol, which have the potential to be galactagogues that increase breast milk production. Myricetin had the highest concentration among all of the three plant leaf extracts. The consumption of rutin, quercetin, myricetin, and kaempferol in the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves can help increase breast milk production and maintain the continuity of breastfeeding and executive breastfeeding. Therefore, the ethanol extracts of S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves have the potential to be formulated as a source of nutrition for pregnant and lactating women to maintain and improve the continuity of breastfeeding and executive breastfeeding. However, further research is needed to ensure the safety and effectiveness of the ethanol extracts from S. androgynus, M. oleifera Lam, and C. amboinicus Lour leaves.
CONFLICT OF INTEREST:
The authors declare no competing interests.
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Received on 17.04.2025 Revised on 11.08.2025 Accepted on 18.10.2025 Published on 20.05.2026 Available online from May 25, 2026 Research J. Pharmacy and Technology. 2026;19(5):2052-2058. DOI: 10.52711/0974-360X.2026.00294 © RJPT All right reserved
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