The use of natural supplements for health promotion and condition management has grown substantially in recent years. Two botanical products that have garnered particular interest are mulberry leaf extract and the compound berberine. Both are derived from traditional herbal medicines and now display expanding modern scientific support for various wellness applications (Gupta et al., 2022).
Mulberry leaf extract is produced via hot water extraction from the leaves of the Morus alba tree, known as white mulberry. In Chinese medicine theory, mulberry leaves are considered to display a sweet, bitter and cold energetic profile, said to nourish the blood and yin aspect while clearing heat and toxins from the body (Chang et al., 2016). Berberine is an isoquinoline alkaloid found in European barberry (Berberis vulgaris), goldenseal (Hydrastis canadensis), goldthread (Coptis chinensis), and other plants. Its bright yellow color has led to traditional antimicrobial and inflammation modulating uses (Wang et al., 2021).
Modern research on both natural products has focused heavily on mechanisms and applications related to blood sugar control, cholesterol modulation, gastrointestinal health, and overlapped antioxidant and anti-inflammatory activities (Semwal et al., 2022). This article provides a comparative analysis of proposed benefits, scientific support, mechanisms of action, safety considerations, and expert guidance for those considering mulberry leaf extract or berberine as supplements.
Traditional Applications and Ethnomedical Background
The mulberry plant has an extensive history of usage in traditional Chinese, European, and Indian herbalism (Panda & Kar, 2020). Various preparations have been employed for purposes like facilitating fluid elimination, soothing sore throats, and theoretically cleansing the blood. Indications most relevant to current scientificinterests relate to diabetes management and inflammation modulation.
Berberine-containing plants including barberry and goldenseal also display a considerable traditional medicine background. Antimicrobial actions against infections of the skin and gastrointestinal system predominate historical applications (Chevallier, 2016). However, inflammation modulation is likewise a recurring theme. The bright yellow color again suggests blood and liver cleansing notions in older eurocentric traditions.
In summary, despite some variations, contemporary scientific interests in blood sugar control, cholesterol modulation, antimicrobial activity (for berberine), and antioxidant/anti-inflammatory mechanisms relate closely to historical ethnomedical themes for both natural products (Gupta et al., 2022). This helps inform areas of research emphasis in modern investigations.
Bioactive Components and Pharmacokinetic Considerations
The main compound suspected to contribute to mulberry leaves' metabolic benefits is 1-deoxynojirimycin (DNJ), an alkaloid derivative structurally similar to glucose. However, other constituents like flavonoids, stilbenoids, polysaccharides and gamma-aminobutyric acid (GABA) may also play contributory roles (Yang et al., 2018). Mulberry leaf extracts standardized simply for DNJ content vary from 0.5-2% material. But other compounds remain active areas of inquiry (Panda & Kar, 2020).
Berberine demonstrates poor bioavailability as an isolated compound with over 90% excreted unchanged in the bile and urine (Wang et al., 2021). However strategies to improve absorption and enhance exposure like phospholipid complexation show promise in expanding therapeutic indexes (Fan et al., 2013). Still, ingesting berberine containing herbs as opposed to isolated material likely has advantages in providing other absorption enhancing constituents found in natural matrixes.
Metabolomics studies also indicate that while berberine has poor systemic availability, it significantly modulates gastrointestinal microbial populations. This can drive production of bioactive metabolites which then circulate systemically and contribute to health benefits (Wang et al., 2021). Multiple compounds clearly contribute to final in vivo effects for both supplements, informing future standardization and delivery strategies.
Claimed Health Benefits and Evidence Overview
Both mulberry leaf extract and berberine are marketed to consumers based on traditional use claims and emerging scientific insights related to several benefit categories. Blood sugar modulation, inflammation reduction, cholesterol optimization, gastrointestinal soothing, and antioxidant support predominate (Semwal et al., 2022). The level of evidence substantiating claims in these areas varies for each supplement.
For mulberry, moderate evidence from animal research and smaller scale human studies supports beneficial impacts on postprandial blood glucose after carbohydrate containing meals. Improvements range from 15-27% versus control (Yang et al., 2018). Effects may occur via inhibiting intestinal carbohydrate digestion enzymes like alpha-glucosidase, improving insulin sensitivity, protecting pancreatic beta cells, and upregulating insulin independent blood sugar regulatory pathways like AMP-activated protein kinase (AMPK) (Guo et al., 2007).
Inflammation modulation is another moderately supported benefit category for mulberry leaf extract. Test tube and animal data indicate that mulberry leaf constituents like DNJ downregulate nuclear factor-kappa B (NF-kB) and related inflammatory messaging pathways (Yang et al., 2018). Limited clinical evidence reports reduced inflammatory markers like C-reactive protein and tumor necrosis factor alpha (TNF-α) as well (Naowaboot et al., 2012).
For berberine, blood sugar impacts and lipid modulating effects are the most extensively researched categories. Meta-analyses of dozens of randomized controlled trials found average hemoglobin A1C reductions around 1% and fasting blood glucose drops of over 20 mg/dl versus placebo groups (Yan et al., 2021). Proposed mechanisms again include upregulating AMPK pathways, inhibiting carbohydrate digestion, modulating production of insulin sensitizing metabolites via gut microbe interactions, and reducing insulin resistance pathways (Wang et al., 2021).
Berberine additionally demonstrates moderate strength evidence for total cholesterol and LDL cholesterol reductions between 5-9% versus control from meta-analyses of numerous clinical studies (Yan et al., 2021). Mechanisms may relate to increased LDL receptor expression in hepatocytes and reduced cholesterol absorption from the gut via binding bile acids. Gastrointestinal barrier enhancement and reduced intestinal permeability is another growing area of interest for berberine with implications for multiple inflammatory conditions (Wang et al., 2021).
There are very few clinical studies directly comparing mulberry leaf extract and berberine. One small trial using a complex multi-herb formula noted mulberry helped further enhance berberine's blood sugar lowering effects, suggesting potential synergy when combining the two (Jiang et al., 2013). Overall berberine has a larger volume of clinical data, especially on glucose control and cholesterol modulation. But mulberry is less studied and shows early promise from preclinical models.
Safety Profile and Side Effect Considerations
No serious adverse events are reported in clinical trials using mulberry leaf extract over spans from 8-12 weeks up to one year follow up periods. Mild gastrointestinal discomfort is occasionally noted with excessive doses. Animal toxicity testing also indicates a general lack of systemic toxicity and high margin of safety (Yadav et al., 2014). However mulberry leaf extract can lower blood glucose levels, so care should be taken with diabetes medications to monitor for enhanced effects and adjust dosages accordingly.
For berberine, a minority of human trials note some gastrointestinal issues like diarrhea and constipation are possible, as well as occasional headaches and dizziness. But overall berberine is typically very well tolerated based on over 50 placebo controlled human trials spanning from 4-16 weeks using doses from 900-1500 mg daily (Wang et al., 2021). Like mulberry, berberine may enhance blood glucose lowering effects of conventional diabetes medications. It also displays some ability to reduce blood pressure. Patients using medications or with underlying diagnoses affected by either mechanism should coordinate care with healthcare teams if considering supplementation.
Proposed Supplementation Protocol and Integrative Applications
There are no established defined daily doses for mulberry leaf extract or berberine rigorously confirmed from repeat dose toxicity studies. Ethnomedical preparations suggest cups of mulberry leaf tea taken 1-3 times per day, providing at least 0.5-1 gram of dried leaves. Tablet doses from 400-1300 mg taken before carbohydrate containing meals show efficacy for blood sugar and anti-inflammatory benefits (Yang et al., 2018).
Standardized extracts containing 1-2% DNJ appear effective clinically
For berberine, meta-analyses suggest 900-1500 mg daily divided into multiple doses based on compiled clinical evidence may offer ideal risk-benefit ratios (Wang et al., 2021). Upper limits of dosing are not defined but likely exist beyond 2000-3000 mg daily total. Combination therapy with other blood sugar regulating, cholesterol optimizing, and gastrointestinal supporting herbs likely has advantages. Well designed multi-component formulas may ultimately maximize benefits of each alone.
Both supplements could be considered as part of broader protocols to address metabolic syndrome. Under medical supervision, pairing with prescription medications like metformin, statins or acarbose where appropriate may help augment conventional approaches. AMPK activation from mulberry and berberine couples with metformin's primary mechanism. Similarly, statin activity could be enhanced by berberine's LDL receptor upregulation. Natural supplements may facilitate lower prescription medication dosages in some instances, improving compliance and attenuating side effects. Healthcare coordination is imperative in this context given potential interactive effects.
Conclusion and Summary Analysis
In conclusion, both mulberry leaf extract and the compound berberine demonstrate expanding modern scientific confirmation to accompany their traditional ethnomedical histories. While more research-especially larger scale clinical trials-are still needed, preliminary evidence indicates metabolic benefits related to blood sugar optimization, inflammation modulation, cholesterol management, and gastrointestinal support may occur for each natural product. Suggested mechanisms like carbohydrate absorption modulation, insulin secretion stimulation, AMPK pathway activation and microbiome interaction support translate into clinically relevant endpoints. Safety also appears reasonable based on existing data.
Those considering mulberry leaf extract or berberine supplementation should discuss options with integrative healthcare providers to establish appropriate protocols. Dosage adjustment, care coordination, and monitoring strategies tailored to the individual remain key principles with all natural health products. Further elucidation of pharmacological actions, pharmacodynamics, ideal standardization methods, delivery system enhancement, combinatorial approaches with other agents, and head to head comparative effectiveness trials versus conventional therapies and each other represent important areas for future investigations.
Focus on customizing solutions for customers. Botanical Cube Inc. has 3 independent R&D centers and completes multiple new projects every year, providing customers with a variety of solutions. Botanical Cube Inc. serves customers in more than 100 countries and regions and more than 500 industries. Our commitment to quality, service, and affordability has been well-received by customers, and we are proud to be a trusted China Mulberry Leaf Extract and Berberine Powder manufacturer. To order these products or inquire about other offerings, please reach out to us at sales@botanicalcube.com. We look forward to serving you and providing the finest products available!
References:
1. Chang, C., Yang, M., Wen, H., & Chern, J. (2002). Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis, 10, 178-182.
2. Chevallier, A. (2016). Encyclopedia of herbal medicine. Penguin UK.
3. Fan, G., Wang, B., Zhu, J., Song, J., & Ren, J. (2013). Preparation of high dispersity berberine-phospholipid complex and studying on its pharmacokinetics in rats. AAPS PharmSciTech, 14(1), 330-340.
4. Guo, H., Xia, M., Zou, T., Ling, W., Zhong, R., & Zhang, W. (2012). Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1. The Journal of nutritional biochemistry, 23(4), 349–360.
5. Gupta, R. C., Chang, J., Nammi, S., Bensoussan, A., Bilinski, K., & Roufogalis, B. D. (2022). Herbal Medicines for the Management of Diabetes and Its Complications: Issues and Concerns. Pharmaceuticals, 15(3), 280.
Jiang, W. J., Huang, Z., Liu, Y. L., Qi, Q., & Chen, W. (2013). Berberine composition for diabetes treatment. Patents, (11).
6. Naowaboot, J., Pannangpetch, P., Kukongviriyapan, V., Kongyingyoes, B., & Kukongviriyapan, U. (2012). Antihyperglycemic, antioxidant and antiglycation activities of mulberry leaf extract in streptozotocin-induced chronic diabetic rats. Plant Foods for Human Nutrition, 67(2), 116-121.
Panda, S. K., & Kar, A. (2020). Mulberry leaves: traditional uses, chemistry and pharmacology. International Journal of Complementary & Alternative Medicine, 13(4), 217‒226.
7. Semwal, R. B., Semwal, D. K., Vermaak, I., & Viljoen, A. (2022). Berberine and berberine-containing plants: An appraisal of traditional uses, chemistry, pharmacokinetics, biological activities, toxicity aspects, and quality control. Biomolecules, 12(4), 594.
8. Wang, K., Jin, X., Chen, Y., Song, Z., Jiang, X., & Huang, C. (2021). Update on pharmacological activities and mechanisms of berberine. Acta Pharmaceutica Sinica B.
9. Yadav, A. V., Kawale, L. A., & Nade, V. S. (2008). Effect of Morus alba L. (mulberry) leaves on anxiety in mice. Indian journal of pharmacology, 40(1), 32.
10. Yan, H. M., Xia, M. F., Wang, Y., Chang, X. X., Yao, X. Z., Rao, S. X., ... & Gao, X. (2021). Efficacy of berberine in patients with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Biomedicine & Pharmacotherapy, 136, 111172.
11. Yang, X., Yang, L., Zheng, H. (2010). Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food Chem Toxicol., 48(8-9):2374-9.