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Study on the relationship between the functional active ingredients in mulberry leaves and human health

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Study on the relationship between the functional active ingredients in mulberry leaves and human health

2025-01-22

Mulberry leaf is a food that can be used as both medicine and food, and is widely grown in China. Mulberry leaf can be used as a supplement and functional food to prevent and alleviate metabolic diseases, and is used in metabolic diseases (obesity, type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease). Mulberry leaf can be consumed as tea, powder, or extract to treat and control health conditions. Exploring the active efficacy and effects of mulberry leaf will help develop high-value utilization of mulberry leaf resources and provide a scientific basis for the active efficacy required for human health.

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01Improvement of hepatic steatosis in db/db mice induced by high-fat diet

Background

Type 2 diabetes has many complications. Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are two complications associated with increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effects of reducing peripheral blood lipid levels, inhibiting the expression of fatty acid synthase (FASN), and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase.

Methods

This study aimed to investigate the effects of MLE and its main component neochlorogenic acid (nCGA) in reducing serum lipids, reducing hepatic lipid accumulation, and improving steatohepatitis levels. The antioxidant activities of glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD) were evaluated, and catalase was tested in mice fed with MLE and nCGA.

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Results

Compared with the db/m and db mouse groups, the serum lipid profile and fatty liver scores in the HFD group were significantly increased, while the liver antioxidant activity in the HFD group was significantly decreased. When fed HFD + MLE or nCGA, the serum lipid profile, hepatic fat deposition status, steatohepatitis level, and liver antioxidant activity were significantly improved compared with the HFD group. Although MLE and nCGA did not directly affect blood glucose levels in db/db mice, they did regulate abnormal lipid metabolism. These results demonstrate the potential of MLE/nCGA in treating glucotoxicity-induced diabetic fatty liver in animal models.

Conclusion

This experiment shows that MLE and nCGA show good prospects in the prevention and treatment of diabetic fatty liver. It is proved that mulberry leaves can effectively enhance the activity of liver antioxidant enzymes, thereby inhibiting lipogenesis, and it is speculated that MLE prevents the formation of diabetic fatty liver by reducing blood cholesterol levels. However, further research is needed in the future to study the molecular mechanism of the inhibitory effects of MLE and nCGA and explore the effectiveness of other potential compounds in preventing and treating diabetic fatty liver.

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02 Mulberry leaf lipid nanoparticles: a natural targeted CRISPR/Cas9 oral delivery platform for alleviating colon diseases

Abstract

The oral treatment of colon diseases using the CRISPR/Cas9 system has been hindered by the lack of a safe and effective delivery platform. Overexpressed CD98 plays a vital role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves were functionalized with Pluronic copolymers and optimized to provide CRISPR/Cas gene editing mechanisms for knockout of CD98. The obtained LNPs had a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporation of Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration of the colonic mucus barrier. The galactose terminal group promoted the internalization of LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency 2.2-fold higher than that of Lipofectamine 6000. LNPs significantly reduced CD98 expression, downregulated pro-inflammatory cytokines (TNF-α and IL-6), upregulated anti-inflammatory factors (IL-10), and polarized macrophages to the M2 phenotype. Oral administration of LNPs alleviated UC and CAC by reducing inflammation, restoring the colonic barrier, and modulating the gut microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system provides a precise and efficient platform for oral treatment of colon diseases.

Conclusion

In this study, an oral CRISPR/Cas9 delivery platform based on edible mulberry lipids and Pluronic F127 was developed. The resulting lipid nanoparticles (P127M@pCD98) maintained stability during passage through the gastrointestinal tract, permeated through the mucus barrier, and penetrated colitis tissue and colorectal tumor tissue. P127M@pCD98s can be specifically internalized by macrophages through galactose receptor-mediated endocytosis and subsequently escape from lysosomes. In vitro experiments showed that P127M@pCD98s alleviated the inflammatory response by downregulating CD 98 expression, polarizing macrophages to the anti-inflammatory M2 phenotype, and reducing the release of TNF-α and IL-6. Oral administration of P127M@pCD98 effectively delayed the progression of ulcerative colitis and colitis-associated colorectal cancer, enriched beneficial bacteria, and reduced the abundance of harmful bacteria. Collectively, these results demonstrate for the first time the feasibility of LNPs (P127Ms) as an oral CRISPR/Cas9 delivery platform for the effective oral treatment of colon diseases.

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03 Natural lipid nanoparticles extracted from mulberry leaves for targeted treatment of hepatocellular carcinoma via oral route

Abstract

Traditional liver cancer therapeutics are severely limited in their clinical application due to their adverse reactions and unsatisfactory efficacy. Inspired by the concept of "medicine and food are of the same origin", natural exosome-like lipid nanoparticles (LNPs) were extracted and purified from black mulberry leaves. The obtained MLNPs have an ideal hydrodynamic particle size (162.1 nm), uniform size distribution (polydispersity index = 0.025), and negative surface charge (-26.6 mv). These natural LNPs are rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments showed that MLNPs were preferentially internalized by liver tumor cell lines through galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, thereby inhibiting the viability, migration, and invasion of these cells. Importantly, in vivo studies showed that oral MLNPs enter the circulatory system mainly through the jejunum and colon, and have negligible adverse reactions and excellent anti-liver tumor effects by directly killing tumors and regulating intestinal flora. These findings collectively demonstrate the potential of MLNPs as a natural, safe and powerful nanomedicine for oral treatment of hepatocellular carcinoma.

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Conclusion

Natural exosome-like nanovesicles were extracted and purified from fresh leaves of black mulberry. For the treatment of hepatocellular carcinoma. These black mulberry leaf-derived lipid nanoparticles (MLNPs) contain a variety of functional components, including lipids, proteins and flavonoids, among which galactose was identified as a potential target for liver tumor targeting. In addition, they exhibited excellent stability under simulated gastrointestinal conditions and showed excellent biocompatibility, making them very suitable for in vivo applications. In vitro experiments showed that the galactose groups on the surface of MLNPs promoted their specific internalization by Hepa1-6 cells and enhanced their cytotoxicity against liver tumor cells. The results showed that MLNPs could arrest the Hepa1-6 cell cycle at the G0/G1 phase and induce cell apoptosis. They also triggered a surge in intracellular ROS levels and significantly inhibited the proliferation and migration of liver cancer cells. The biosafety of oral MLNPs was superior to that of intravenous administration, and did not cause immunogenicity or toxic side effects. In a mouse model of primary liver cancer, oral MLNPs showed significant liver targeting and enrichment capabilities, significantly inhibited tumor growth and regulated intestinal microbial balance. In conclusion, MLNPs represent a natural, safe and eco-friendly nanomedicine with special liver tumor targeting capabilities, which can be used for oral treatment of hepatocellular carcinoma.

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04 Interaction between mulberry polyphenols and polysaccharides during digestion and colonic fermentation

Abstract

The digestion and absorption characteristics of mulberry polyphenols (MLPP), mulberry polysaccharides (MLPS) and mulberry polyphenol-polysaccharide complexes (PPPS) during fermentation were compared, and the changes in short-chain fatty acids (SCFAs) during fermentation were analyzed. The effect of PPPS on the structural composition of intestinal flora was studied based on 16S rDNA gene sequencing. The digestibility of polyphenols in MLPP and PPPS was 59.48% and 79.95%, respectively, while no free monosaccharides were detected in MLPS and PPPS, indicating that polysaccharides promoted the digestion of polyphenols in PPPS, while the presence of polyphenols had no effect on the digestion of polysaccharides. The production of acetic acid, propionic acid, valeric acid, and butyric acid in the PPPS group increased significantly during the 0-12 h fermentation process, and the pH value dropped sharply, while the MLPS group produced more isobutyric acid and isovaleric acid during the 12-24 h fermentation stage. PPPS significantly increased the relative abundance of Fusobacterium, while significantly reduced the relative abundance of Collinsella aerofaciens, Romboutsia ilealis, and Lachnospiraceae, which may be related to the synergistic regulation of lipid metabolism by polyphenols and polysaccharides.

Conclusion

In this study, a simulation model of human digestion and colonic fermentation was established to study the differences in the composition of mulberry components MLPP, MLPS, and PPPS after digestion, as well as the changes in pH, SCFAs, and intestinal flora during colonic fermentation. The results showed that in the PPPS group, the presence of polysaccharides promoted the digestion of polyphenols, while the digestion of polysaccharides did not change and no monosaccharides were released. During the fermentation process of 0-12 h, the main components of SCFAs were acetic acid, propionic acid, butyric acid and valeric acid; during the fermentation process of 12-24 h, the main components of SCFAs were isobutyric acid and isovaleric acid. PPPS had a significant effect on the pH drop value, the content and composition of SCFAs, and the effect was better than MLPP and MLPS. During the colonic fermentation process, PPPS increased the relative abundance of Fusobacterium and reduced the relative abundance of Collinsella aerofaciens, Romboutsia and Lachnospiraceae, and its effect was the best, which may be the reason for the synergistic regulation of lipid metabolism by polyphenols and polysaccharides. The results of this study will help to reveal the material basis and scientific connotation of the functional activity of mulberry, especially the synergistic effect of polyphenols and polysaccharides in regulating lipid metabolism, and provide guidance for the development of functional foods with active ingredient compatibility.

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