A medicinal and edible traditional Chinese medicine composition, a traditional Chinese medicine preparation thereof, a preparation method and an application

Abstract

The present application relates to the field of food or medicine, and particularly relates to a kind of food-medicinal Chinese medicine composition and Chinese medicine preparation, preparation method and application.The raw materials of the food-medicinal Chinese medicine composition of the present application include yam, fuling, radix puerariae, medlar, mulberry leaf, hawthorn, cassia, polygonatum and gardenia.The food-medicinal Chinese medicine composition of the present application takes "clearing heat and drying dampness, benefiting qi and nourishing yin, promoting blood circulation to remove meridian obstruction" as the basic principle, adjusts the function of viscera, improves sugar, lipid and protein metabolism, promotes the recovery of the body environment to normal, and fits the basic pathogenesis of the middle and late stage of type 2 diabetes, and has accurate treatment effect.

Description

Technical Field

[0001] This invention relates to the fields of food or pharmaceuticals, and more particularly to a traditional Chinese medicine composition that is both food and medicine, its preparation method, and its application. Background Technology

[0002] Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disease. The interaction of genetic and environmental factors leads to the heterogeneity and progressive pathology of this disease, including insulin resistance in skeletal muscle, liver, and adipose tissue, dysfunction of pancreatic β-cells and α-cells, and other endocrine disorders. Insulin resistance in muscle and liver, as well as impaired insulin secretion function of pancreatic β-cells, are the core defects in T2DM. Insulin resistance stems from defects in the insulin receptor and its downstream signaling pathways; T2DM occurs when pancreatic β-cells are unable to secrete enough insulin to overcome insulin resistance. Furthermore, persistent hyperglycemia can cause target organ damage by increasing the risk of global vascular disease, including microvascular complications (such as diabetic retinopathy, nephropathy, and neuropathy) and atherosclerotic macrovascular complications (such as cardiovascular disease, cerebrovascular disease, and other peripheral vascular diseases).

[0003] To date, the treatment philosophy for type 2 diabetes mellitus (T2DM) has undergone a fundamental shift in recent years, evolving from a traditional "glycemic control-centered" approach to a personalized treatment strategy prioritizing the protection of cardiovascular and renal organs. While metformin remains the cornerstone of first-line treatment in patients without specific comorbidities, innovative drugs have emerged, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and tirzepatide. However, recent research has revealed risks associated with SGLT2i, including genitourinary tract infections and rare normoglycemic ketoacidosis; the prevalent gastrointestinal side effects and potential pancreatic and thyroid risks associated with GLP-1 RAs; and the marginalization of traditional drugs such as sulfonylureas and thiazolidinediones due to side effects like hypoglycemia and weight gain. Furthermore, the relatively limited time to market for these innovative drugs means that some rare or delayed side effects may take longer to manifest. Safety and efficacy data are often insufficient in special populations such as the elderly, those using multiple medications, and those with severe hepatic impairment, introducing uncertainty into clinical use. The interactions and effects of long-term combination therapy require further investigation.

[0004] The advantages of Traditional Chinese Medicine (TCM) in treating diabetes lie in its holistic approach, synergistic effects, and fewer side effects, emphasizing a comprehensive approach that addresses both the root cause and the symptoms. TCM does not simply aim to lower blood sugar levels, but rather emphasizes overall metabolic balance and regulation of endocrine function. TCM considers diabetes a "wasting and thirsting" disease, primarily caused by an imbalance of Yin and Yang and a deficiency of Qi and blood. Treatment emphasizes nourishing Yin and tonifying the kidneys, strengthening the spleen and replenishing Qi, aiming to restore pancreatic function and enhance insulin sensitivity, rather than merely suppressing blood sugar.

[0005] In view of this, the present invention proposes a novel medicinal and edible herbal composition for the treatment of type 2 diabetes and its application. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a novel medicinal and edible herbal composition for treating type 2 diabetes, its formulation, preparation method, and application.

[0007] This invention addresses the core pathogenesis of type 2 diabetes, which is characterized by "deficiency of both Qi and Yin as the root cause and dryness and heat stagnation as the manifestation," and proposes a combination of medicinal and edible herbs, the raw materials of which include yam, poria cocos, kudzu root, wolfberry, mulberry leaf, hawthorn, cinnamon, polygonatum odoratum, and gardenia.

[0008] The root cause is spleen deficiency, leading to impaired digestion and absorption (resulting in metabolic disorders of essential substances such as blood sugar); liver and kidney yin deficiency, resulting in insufficient body fluids (leading to dry mouth and excessive thirst). The symptoms are internal heat and dryness, as well as blood stasis and dampness caused by insufficient body fluids and impaired peristalsis.

[0009] Therefore, the treatment principle should be "to replenish qi and nourish yin to treat the root cause, and to clear heat and invigorate blood to treat the symptoms".

[0010] The principal herbs, targeting the main symptoms and establishing the key principles: Chinese yam, kudzu root, and Solomon's seal rhizome work together as the principal herbs to address the root cause of "deficiency of both qi and yin." Chinese yam: It gently tonifies the three jiaos (upper, middle, and lower burners), especially effective in invigorating qi, strengthening the spleen, and consolidating the kidneys and astringing essence. By strengthening the spleen and stomach, the "foundation of acquired constitution," it improves overall metabolic function, forming the cornerstone of stable blood sugar. Kudzu root: It raises yang and generates fluids, distributing body fluids. It can transport body fluids upwards to the mouth and throat, effectively relieving dry mouth and thirst. Its "raising yang" property helps to invigorate spleen yang, and modern research has confirmed that it can improve insulin resistance. Solomon's seal rhizome: It nourishes yin and moistens dryness, clears heat and generates fluids, deeply nourishing the yin of the lungs and stomach, powerfully relieving dryness symptoms. The three herbs work synergistically: Chinese yam addresses "qi" and the "spleen," kudzu root addresses "fluids" and "yang," and Solomon's seal rhizome addresses "yin" and the "lungs and stomach," together forming a solid foundation for invigorating qi, nourishing yin, and generating fluids.

[0011] The assistant herbs, supporting the principal herbs and enhancing their efficacy: Poria cocos, wolfberry, and cinnamon, these three herbs assist the principal herbs from different perspectives, either supplementing their deficiencies or enhancing their effects. Poria cocos: Strengthens the spleen and eliminates dampness. While yam primarily "tonifies," Poria cocos primarily "drains." It helps the spleen to transform and expel "dampness and turbidity" caused by functional disorders, making tonification non-greasy, combining tonification and drainage, restoring the cleanliness and function of the spleen and stomach. Wolfberry: Nourishes the liver and kidneys, benefits essence and improves eyesight. Building upon the principal herbs' nourishment of lung, stomach, and spleen yin, it further nourishes the "liver and kidneys," the innate foundation, achieving simultaneous yin tonification throughout the body, and has preventative significance for long-term eye and kidney complications of diabetes. Cinnamon: Guides fire back to its source, assists yang in transforming qi. Adding a small amount of cinnamon to a large number of yin-nourishing and heat-clearing medicines serves two purposes: firstly, it warms the fire of the gate of life (mingmen), assists yang qi in transforming fluids, and allows body fluids to be generated and distributed normally (i.e., "seeking yin within yang"); secondly, it can draw upward-floating deficiency fire (such as dry mouth and irritability) back to the kidneys, correcting the situation of mixed cold and heat. Modern research shows that cinnamaldehyde can significantly enhance insulin sensitivity.

[0012] The adjuvant herbs, treating secondary symptoms and counteracting the primary herb's bias: Mulberry leaf, gardenia, and hawthorn. These three herbs are responsible for clearing heat, promoting blood circulation, addressing symptoms, and ensuring overall balance. Mulberry leaf and gardenia: This two herbs form a "heat-clearing" combination. Mulberry leaf: Clears heat from the lungs and liver, a recognized key herb for lowering blood sugar, with a relatively mild nature. Gardenia: Clears heat and dampness, drains fire and relieves irritability. Its clearing power is stronger, especially effective at clearing fire from the triple burner, and has a good effect on improving symptoms such as dry mouth, irritability, and dark yellow urine caused by internal heat. Together, they clear the body's dry and hot environment. Hawthorn: Promotes blood circulation, removes blood stasis, and eliminates food stagnation. Its sour and sweet properties can nourish yin and assist in generating fluids; its blood-activating function improves common microcirculatory disorders in diabetes and prevents vascular complications; its digestive function aids digestion, especially in resolving food stagnation and improving lipid metabolism.

[0013] Guiding and harmonizing the other herbs: In this formula, cinnamon and gardenia, to a certain extent, also serve as guiding herbs. Cinnamon: Its pungent, dispersing, and warming properties can guide the other herbs into the blood and nourish the body, and guide the medicinal effects upward and downward, thus having the meaning of "guiding the meridians and acting as a messenger." Gardenia: Its bitter and cold nature can guide heat downward, allowing the heat pathogen to have an outlet through urination, and similarly plays the role of guiding the medicinal effects.

[0014] This formula employs a comprehensive approach, combining tonification and purgation to treat both the root cause and the symptoms: yam, kudzu root, Solomon's seal, and wolfberry are used to tonify deficiency; poria, mulberry leaf, and gardenia are used to purge excess; and hawthorn is used to clear stagnation. It tonifies without retaining pathogens and attacks pathogens without harming the body's vital energy. It uses both warming and cooling herbs for dynamic balance: Among the abundant sweet and cold, bitter and cold herbs (mulberry leaf, gardenia, Solomon's seal), the addition of pungent and warm cinnamon avoids excessive coldness that could damage the spleen and stomach's yang energy, while also stimulating the generation of yin fluids through the principle of "seeking yin within yang." It regulates multiple organs for systemic treatment: This formula does not target a single organ but systematically regulates multiple organs related to diabetes: strengthening the spleen (yam, poria), tonifying the lungs (Solomon's seal, kudzu root), nourishing the liver (wolfberry, mulberry leaf), and warming the kidneys (cinnamon), reflecting the holistic view of traditional Chinese medicine.

[0015] The technical solution provided by the embodiments of the present invention has the following advantages compared with the prior art: The medicinal and edible herbal composition of this invention adheres to the basic principles of "clearing heat and drying dampness, tonifying qi and nourishing yin, and promoting blood circulation and unblocking collaterals," which is highly compatible with the common basic pathogenesis in the middle and late stages of type 2 diabetes (which falls under the category of "Xiao Ke" in Traditional Chinese Medicine): deficiency of both qi and yin as the root cause, and dryness, heat, blood stasis, and dampness as the manifestations. Animal experiments have verified that its therapeutic mechanism is clear and its effects are definite. It can improve blood glucose, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), and total cholesterol (TC) related to glucose and lipid metabolism; improve alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (CHE), and urea levels related to liver and kidney function; improve liver pathological damage; improve lipid metabolism; and improve bile acid metabolism. By regulating the functions of the internal organs (such as strengthening the spleen and stomach and tonifying kidney yin), it improves glucose, lipid, and protein metabolism, promotes the restoration of the internal environment to normal, and systematically regulates multiple organs related to diabetes, reflecting the holistic view of Traditional Chinese Medicine. Attached Figure Description

[0016] Figure 1 shows the results of TCM in improving liver and kidney function and related biochemical indicators of glucose and lipid metabolism in diabetic rats. Figure 2 TCM improves liver pathological damage in diabetic rats; Figure 3 shows the omics analysis of TCM-treated diabetic rats; among them, Figure 3A Results of combined metabolomics and transcriptomics analysis Figure 3B Metabolite and gene interaction network diagram Figure 3C Gut microbiota analysis results, Figure 3D Results of combined analysis of gut microbiota and metabolomics; Figure 4 Evaluation of gene expression in TCM-treated diabetic rats; Figure 5 Immunofluorescence evaluation of TCM-treated diabetic rats. Detailed Implementation

[0017] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0018] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0019] The yam, poria cocos, kudzu root, wolfberry, mulberry leaf, hawthorn, cinnamon, polygonatum odoratum, and gardenia used in the following examples all comply with the relevant provisions of the Chinese Pharmacopoeia (2025 edition) under the respective medicinal materials section. Before adding the materials, each medicinal material was identified and confirmed to be consistent with its name and meet the quality standards.

[0020] Example 1. Preparation of a traditional Chinese medicine composition that is both food and medicine for the prevention and / or treatment of type 2 diabetes. (1) Prescription 30 g of yam, 15 g of poria cocos, 15 g of kudzu root, 12 g of wolfberry, 10 g of mulberry leaf, 10 g of hawthorn, 6 g of cinnamon, 15 g of polygonatum odoratum, and 6 g of gardenia.

[0021] (2) Preparation process Add yam, poria cocos, kudzu root, wolfberry, mulberry leaf, hawthorn, cinnamon, polygonatum odoratum, and gardenia to 10 times the amount of water and soak for 60 minutes. After boiling, continue boiling for another 60 minutes. Filter and collect the filtrate. Repeat the above operation on the residue and combine the filtrates to obtain the medicinal liquid. Concentrate the medicinal liquid under reduced pressure at 60 °C for 2 hours to prepare a traditional Chinese medicine preparation.

[0022] Example 2. Animal Experimental Pharmacodynamics Study 1. Experimental Materials 1.1 Laboratory Animals The experimental animals were 6-week-old male Sprague Dawley rats, with a weight range of 180 ± 20 g. All rats were housed at the Animal Experiment Center of Inner Mongolia Medical University and strictly managed according to the specific pathogen-free (SPF) standard. The experimental environment was controlled within a suitable temperature and humidity range, specifically set at 21-25℃ and relative humidity at 50%-60%, to ensure the health of the animals and the stability of the experimental data.

[0023] 1.2 Experimental Drugs The experimental drug was the traditional Chinese medicine preparation (TCM) prepared in Example 1.

[0024] 2. Experimental Methods 2.1 Animal modeling and grouping Weigh 2.10 g of citric acid and dissolve it in 100 mL of distilled water, stirring thoroughly until completely dissolved. This solution is the citric acid stock solution, referred to as solution A. Weigh 2.94 g of trisodium citrate and dissolve it in 100 mL of distilled water, stirring thoroughly until completely dissolved, to obtain the sodium citrate stock solution, referred to as solution B. Take appropriate amounts of solution A and solution B and mix them in a 1:1 volume ratio to obtain a 0.1 mol / L sodium citrate buffer solution. Measure the pH value of the mixture using a pH meter. Weigh an appropriate amount of streptozotocin using a precision balance and dissolve it in the 0.1 mol / L sodium citrate buffer solution. Finally, adjust the concentration of the streptozotocin solution to 10 mg / mL. Filter the prepared streptozotocin solution through a 0.22 μm sterile filter.

[0025] Rats were fed a 45% high-fat diet for 4 weeks to induce weight gain and fat accumulation, followed by the establishment of a diabetic rat model. A 10 mg / mL streptozotocin solution was prepared. The required volume of streptozotocin solution was calculated based on a dose of 30 mg / kg and the rat's body weight. Rats were fasted for 12 hours before injection. Blood glucose levels were monitored 72 hours after injection using a glucometer. A blood glucose level exceeding 16.7 mmol / L confirmed successful establishment of the diabetic model.

[0026] 2.2 Indicator Testing Rats were anesthetized, and serum and liver tissue were collected for further analysis of biochemical indicators and histopathological changes to comprehensively evaluate the degree of metabolic disorder and organ damage in the model. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), high-density lipoprotein (HDL), LDL, triglycerides (TG), and total cholesterol (TC) in serum were measured. The effects of diabetes on liver function and lipid metabolism were assessed by comparing the differences in biochemical indicators between the model group and the control group. Liver tissue was stained with hematoxylin and eosin (HE) to observe morphological changes in hepatocytes and assess the degree of pathological damage to the liver caused by diabetes. Oil Red O staining was performed to detect lipid deposition in the liver and further evaluate the impact of diabetes on hepatic lipid metabolism.

[0027] 2.3 HE and Oil Red O staining.

[0028] 2.4 Omics Analysis 2.4.1 Metabolomics Analysis Sample pretreatment: 100 mg of liquid nitrogen was used to grind liver tissue, and 500 μL of 80% methanol aqueous solution was added. After vortexing and mixing, the protein was precipitated by incubating on ice for 5 min. The mixture was centrifuged at 15000 g for 20 min at 4℃. The supernatant was diluted to a methanol content of 53%, centrifuged again, and the supernatant was used for LC-MS analysis and QC samples were prepared.

[0029] Liquid chromatography conditions: column temperature 40℃, flow rate 0.2 mL / min. Positive ion mode: mobile phase A is 0.1% formic acid in water, and mobile phase B is methanol; negative ion mode: A is 5 mM ammonium acetate buffer (pH 9.0), and mobile phase B is methanol.

[0030] Data processing: Raw data were preprocessed using CD 3.3 software. Metabolites were screened based on retention time and mass-to-charge ratio, and peak area normalization correction was performed using QC samples. Parameters such as a mass deviation of 5 ppm and a signal intensity fluctuation of 30% were set for peak extraction and quantification. Metabolite identification combined ion fragment information, matched using the mzCloud, mzVault, and Masslist databases, and background subtraction was performed. The standardized formula for quantitative data was: peak area of ​​sample metabolites / (peak area of ​​total sample metabolites / peak area of ​​total QC1 metabolites), and metabolites with CV > 30% in QC were removed. Statistical analysis was performed using R and Python on a Linux system. Functional annotation relied on the KEGG, HMDB, and LIPIDMaps databases. Multivariate statistical analysis (PCA, PLS-DA) was performed using metaX, and VIP values ​​were calculated. Univariate analysis used t-tests, and the screening criteria for differential metabolites were VIP > 1 and P < 0.05.

[0031] 2.4.2 Gut microbiota analysis Total microbial DNA was extracted from rat feces using the FastPure Stool DNA Isolation Kit (Magnetic bead, MJYH, Shanghai). After quality control, the V3-V4 region of the 16S rRNA gene was amplified using primers 338F / 806R. The amplified products were recovered, purified, and used to construct libraries using the NEXTFLEX system. Paired-end sequencing was then performed on the Illumina Nextseq 2000 platform. After FastP quality control, sequence assembly, and sample sorting, the raw data were clustered into OTUs using UPARSE with 97% similarity, and chimeras and host sequences were removed. All sample sequences were standardized, species annotation was performed based on the Silva database, and the PICRUSt2 community prediction function was used. Alpha diversity was calculated using Mothur and intergroup comparisons were performed using the Wilcoxon test. PCoA and PERMANOVA analyses were conducted based on Bray-Curtis distance to assess community structure differences. Differential biomarkers were screened using LEfSe, and the correlation between the microbiota and clinical indicators was explored through redundancy analysis and linear regression. A correlation network between the microbiota and metabolites was constructed using Spearman correlation analysis.

[0032] 2.4.3 Transcriptomics Analysis Total RNA was extracted from animal tissues using the Trizol method and its quality was assessed using an Agilent 2100 bioanalyzer. mRNA was isolated using the polyA enrichment method, and sequencing libraries were constructed (fragmentation, double-stranded cDNA synthesis, end repair, adapter ligation, fragment sorting, and PCR amplification). After library quality control, paired-end sequencing was performed on the Illumina platform. Raw sequencing data were filtered through quality control, and clean reads were aligned to a reference genome using HISAT2. New transcripts were predicted using StringTie, and gene reads were calculated using featureCounts and expression levels were normalized using FPKM. Differentially expressed genes were identified using DESeq2 (P ≤ 0.05), and KEGG pathway enrichment analysis was performed using clusterProfiler.

[0033] 2.5 Immunofluorescence The sections were sequentially placed in environmentally friendly dewaxing solutions I, II, and III for 10 min each, followed by immersion in anhydrous ethanol I, II, and III for 5 min each. Finally, they were washed with distilled water to completely dewax the sections to water. The tissue sections were treated using a heat-induced antigen retrieval technique, maintaining the buffer level throughout to prevent tissue drying. After the retrieval process, the sections were allowed to cool at room temperature, then transferred to PBS buffer and rinsed three times in a horizontal shaker for 5 min each time. After gently wiping the edges of the sections with absorbent paper, a blocking area was marked around the tissue periphery using a hydrophobic pen. Non-specific blocking was performed using 3% bovine serum albumin solution for 30 min. The prepared primary antibody working solution was evenly applied to the tissue area and incubated in a humidified chamber at 4 °C for 16 h. The next day, the sections were removed and washed three times with PBS under the same conditions. Fluorescently labeled secondary antibody was added under light-protected conditions and reacted at room temperature for 50 min, followed by another PBS washing procedure. DAPI nuclear staining solution was then applied (incubated in the dark for 10 min), followed by washing with PBS, treatment with autofluorescence quencher B solution for 5 min, and rinsing with running water for 10 min to thoroughly remove residual reagents. Finally, the samples were fixed using mounting media containing an anti-quencher. The fluorescence imaging parameters were set as follows: Nuclear staining (DAPI): excitation at 330-380 nm / emission at 420 nm, showing blue fluorescence; Labeling signal 1 (channel 488): excitation at 465-495 nm / emission at 515-555 nm, showing green fluorescence; Labeling signal 2 (channel CY3): excitation at 510-560 nm / emission at 590 nm, showing red fluorescence.

[0034] 2.6 qPCR After determining the RNA concentration and purity using a NanoDrop 1000 micro-volume spectrophotometer, 1000 ng of total RNA was reverse transcribed using the FastKing cDNA First-Strand Synthesis Kit (Tiangen Biotech, Beijing). First, genomic DNA was removed from a 10 μL system using 5×gDNA Buffer at 42℃ for 3 min. Then, a 10 μL reverse transcription system (containing 2 μL of 10×King RT Buffer, 1 μL of FastKing RT Enzyme Mix, 2 μL of FQ-RT Primer Mix, and 5 μL of RNase-Free ddH2O) was added, and the mixture was reacted at 42℃ for 15 min, followed by inactivation at 95℃ for 3 min, ultimately yielding cDNA. Using the obtained cDNA as a template, a 20 μL RT-qPCR reaction system was prepared using the TB Green® Premix Ex Taq™ II FAST qPCR kit (Takara, Beijing) (containing 10 μL TB Green Premix Ex Taq II, 0.8 μL each of forward and reverse primers, 2 μL cDNA template, and 6.4 μL RNase-Free ddH2O). The reaction program was set as follows: 95℃ pre-denaturation for 30 s; followed by 40 cycles of amplification at 95℃ for 5 s and 60℃ for 30 s; finally, melting curve analysis was performed. Gene expression was relatively quantified using the 2^(-ΔΔCT) method.

[0035] 2.7 Data Statistical Analysis All data were statistically analyzed using GraphPad Prism 9.0. Normally distributed data are expressed as mean ± standard deviation (Mean ± SD). Independent-sample t-tests were used for comparisons between two groups, and one-way ANOVA was used for comparisons among multiple groups. P A value <0.05 is considered statistically significant.

[0036] 3. Experimental Results 3.1 Evaluation of biochemical indicators in TCM-treated T2DM rats The results of this study (Figure 1) indicate that TCM can not only significantly regulate liver and kidney function in diabetic rats, including restoring ALP, AST, ALT, CHE, and UREA, but also intervene in the pathological process of diabetes from multiple aspects by improving glucose and lipid metabolism disorders, including improving blood glucose, LDL, TG, TC, and HDL levels.

[0037] Elevated ALP levels typically indicate hepatobiliary disease, bone metabolism abnormalities, or chronic inflammation. Diabetic patients or experimental animal models often exhibit hepatobiliary dysfunction and elevated ALP levels. Chronic inflammation and insulin resistance can also lead to elevated ALP, which is part of the multi-organ damage caused by diabetes. Serum biochemical markers showed that the TCM group consistently reduced ALP levels, suggesting a potential role in improving hepatobiliary function and reducing inflammatory responses. ALT and AST are enzymes released into the bloodstream when hepatocytes are damaged. ALT is mainly distributed in hepatocytes, while AST is also widely present in the heart, kidneys, and skeletal muscle. Elevated ALT usually indicates hepatocyte damage, while elevated AST may reflect broader tissue damage (such as myocardial or renal injury). Hyperglycemia, hyperlipidemia, and insulin resistance in diabetic states lead to fatty liver, increased inflammation, and oxidative stress, ultimately causing hepatocyte damage and elevated ALT and AST levels. The TCM group significantly reduced ALT and AST, possibly related to its promotion of hepatic lipid metabolism, reduction of fat accumulation, and reduction of oxidative stress. When diabetes leads to impaired liver function, CHE levels may be elevated, indicating abnormal synthetic function. The TCM group showed a reduction in CHE levels, suggesting that it may improve liver protein synthesis capacity, thereby enhancing the body's metabolic capacity. Urea (UREA) is the final product of protein metabolism, mainly synthesized by the liver and excreted by the kidneys. Elevated serum UREA levels usually indicate impaired kidney function, such as diabetic nephropathy. Diabetes can lead to renal tubular damage, glomerular hyperfiltration, and proteinuria under hyperglycemic conditions, ultimately causing kidney dysfunction and elevated UREA levels. A long-term high-glycemic environment can induce oxidative stress and chronic inflammation, further aggravating kidney damage and leading to UREA accumulation. The TCM group reduced urea levels, suggesting that it may alleviate diabetic-induced kidney damage and improve kidney function.

[0038] Elevated blood glucose is the core pathological feature of diabetes mellitus, primarily attributed to insulin resistance and impaired pancreatic β-cell function. Insulin resistance reduces the uptake and utilization of glucose by peripheral tissues (such as muscle and adipose tissue), while impaired pancreatic β-cell function leads to reduced insulin secretion. This results in the body's inability to effectively regulate blood glucose levels, ultimately leading to chronically high blood glucose levels. Furthermore, diabetic patients often exhibit enhanced hepatic gluconeogenesis (the process of glucose synthesis in the liver), mainly due to the weakened inhibitory effect of insulin on hepatic gluconeogenesis, leading to continuous synthesis and release of glucose by the liver, further elevating blood glucose. Experimental results showed that transcatheter glucose mediators (TCMs) significantly reduced blood glucose levels in diabetic rats, with a statistically significant difference compared to the model group. This suggests that TCMs may exert their hypoglycemic effect by promoting glucose uptake and utilization by peripheral tissues while inhibiting hepatic gluconeogenesis.

[0039] Diabetes also causes lipid metabolism disorders, with elevated LDL levels being a typical manifestation. LDL is primarily responsible for transporting cholesterol from the liver to peripheral tissues. In diabetes, insulin resistance affects not only glucose metabolism but also lipid metabolism. Insulin resistance leads to reduced LDL uptake and metabolism in the liver, causing LDL to accumulate in the blood and increasing the risk of atherosclerosis. This study found that TCM significantly reduced LDL levels in diabetic rats, suggesting that TCM may reduce LDL accumulation in the blood and improve lipid metabolism disorders caused by diabetes by inhibiting hepatic cholesterol synthesis or enhancing LDL receptor-mediated clearance pathways.

[0040] Elevated triglyceride (TG) levels are associated with lipid metabolism abnormalities caused by insulin resistance. Under normal circumstances, insulin inhibits hepatic lipogenesis. However, in diabetes, impaired insulin function leads to increased hepatic lipogenesis and enhanced lipolysis of adipose tissue, releasing large amounts of free fatty acids into the liver, further promoting TG synthesis and accumulation. Excessive TG accumulation in the blood not only increases insulin resistance but may also lead to non-alcoholic fatty liver disease and cardiovascular disease. Experimental results showed that transcatheter arteriosclerosis (TCM) significantly reduced TG levels, suggesting that TCM may improve diabetes-induced hypertriglyceridemia by downregulating the expression of genes related to hepatic lipid synthesis, inhibiting TG synthesis, and promoting TG breakdown and clearance.

[0041] Elevated total cholesterol (TC) levels are another common metabolic abnormality in diabetic patients, primarily attributed to a decline in insulin's ability to regulate cholesterol metabolism. Normally, insulin inhibits cholesterol synthesis in the liver and promotes cholesterol transport and clearance. However, in diabetes, impaired insulin function leads to increased cholesterol production and decreased clearance, resulting in elevated TC levels. Experimental results show that total cholesterol molecule-mediated metabolism (TCM) significantly reduces TC levels, suggesting that TCM may lower serum TC levels and improve diabetes-related cholesterol metabolism abnormalities by enhancing cholesterol transport, promoting bile acid metabolism, or accelerating cholesterol excretion.

[0042] Furthermore, decreased HDL levels are another important lipid metabolism abnormality caused by diabetes. The main function of HDL is to mediate the reverse transport of cholesterol, that is, to transport cholesterol from peripheral tissues (such as arterial walls) back to the liver for bile excretion or reuse, thereby playing an anti-atherosclerotic role. In diabetes, insulin resistance affects HDL synthesis and function, leading to decreased HDL levels, reduced cholesterol clearance capacity, and increased risk of atherosclerosis and cardiovascular disease. This study found that TCM significantly increased HDL levels, suggesting that TCM may enhance HDL-mediated cholesterol clearance capacity by regulating hepatic cholesterol transport and bile acid metabolism, thereby increasing HDL levels and reducing the risk of cardiovascular disease caused by diabetes.

[0043] 3.2 Pathological evaluation of TCM-induced liver damage in T2DM rats HE staining is mainly used to observe cell morphology, degree of inflammation, and fibrosis in liver tissue to assess the extent of liver damage and pathological changes. Figure 2 As shown, in normal rats, hepatocytes are neatly and tightly arranged, with regular cell morphology, abundant cytoplasm, uniform nuclear staining, and intact tissue structure, without obvious pathological changes. However, in the diabetic model group, hepatocytes are disordered, significantly swollen, with loose cytoplasm exhibiting vacuolar appearance, dilated central veins, and extensive inflammatory cell infiltration, resulting in loose tissue structure. This suggests that diabetes may lead to significant liver damage, including cell edema, enhanced inflammatory response, and tissue structure destruction. After TCM intervention, compared with the model group, the hepatocyte arrangement in diabetic rats tended to be more regular, inflammatory cell infiltration was significantly reduced, cell swelling was decreased, and liver tissue structure was relatively restored, indicating that TCM has a certain protective effect against liver damage caused by diabetes. Among them, the improvement effect of high-dose TCM (TCM-H group) was particularly significant, suggesting that it has a stronger anti-inflammatory effect and tissue repair capacity, which helps to alleviate liver damage caused by diabetes. Oil Red O staining is mainly used to detect lipid deposition in the liver, where the red area represents the degree of fat accumulation. In liver tissue sections from normal rats, minimal red staining was observed, indicating minimal lipid deposition in the liver under normal conditions. However, in the diabetic model group, abundant red lipid deposits were observed in the hepatocyte cytoplasm and intercellular spaces, suggesting that diabetes may cause abnormal lipid metabolism, leading to hepatic steatosis and fat accumulation, thus exacerbating liver damage. After TCM intervention, the area of ​​red lipid deposition in the livers of diabetic rats was significantly reduced, the distribution of fat droplets was more dispersed, and the staining intensity was reduced, indicating effective improvement in hepatic lipid accumulation. The high-dose TCM (TCM-H group) showed the most significant improvement, suggesting that it may effectively alleviate the symptoms of fatty liver caused by diabetes by regulating hepatic lipid metabolism and reducing fat accumulation. In summary, both HE staining and Oil Red O staining results indicate that TCM can alleviate liver damage caused by diabetes to a certain extent, and its mechanism of action may involve anti-inflammatory, cell repair, and lipid metabolism regulation. The high-dose TCM (TCM-H group) exhibited superior protective effects, further supporting the potential value of TCM in the prevention and treatment of diabetes-related liver injury.

[0044] 3.3 Omics analysis of TCM treatment in T2DM rats KEGG enrichment analysis of liver metabolomics and liver transcriptomics in TCM showed interactions among pathways such as cholesterol metabolism, AMPK signaling pathway, and bile secretion. Figure 3A -B). The TCM-H group showed significant changes in gut microbiota structure, specifically manifested as follows: Allobaculum , Faecalibaculum , Lactobacillus , Clostridium Increased abundance of probiotics was observed. These changes may be closely related to the regulatory role of TCM, involving improving gut microbiota balance, promoting beneficial bacteria proliferation, inhibiting potentially pathogenic bacteria, and regulating energy metabolism and immune function. Association analysis between gut microbiota and metabolomics showed… Faecalibaculum It showed a significant positive correlation with various bile acids, including Glycochenodeoxycholic acid and Glycodeoxycholic acid. Lactobacillus It showed a significant positive correlation with various bile acids, including taurodeoxycholic acid, glycochenodeoxycholic acid, and tauroursodeoxycholic acid. In summary, TCM may improve the gut microbiota structure and hepatobiliary bile acid circulation, thereby correcting glucose and lipid metabolism disorders in type 2 diabetes, providing mechanistic support for its clinical application.

[0045] 3.4 Evaluation of gene expression in T2DM rats treated with TCM Compared with the control group ( Figure 4 ), in the liver of the model group rats Ppara , Fxr and Cpt1 Gene expression levels were significantly reduced, while Scd-1 as well as Cyp8b1 The expression levels of these genes were significantly upregulated. These gene changes indicate that the model group rats exhibited significant abnormalities in the regulation of glucose and lipid metabolism and bile acid synthesis, potentially leading to lipid metabolism disorders and bile acid metabolism imbalances, thereby exacerbating liver function damage. After TCM intervention, the expression trends of these abnormal genes were significantly reversed. Ppara , Fxr , Cpt1 The level of expression is increased, while Scd-1 , Cyp8b1The overexpression of Scd-1 was inhibited. This result indicates that TCM may restore the Ppara-mediated fatty acid oxidation pathway by activating the AMPK signaling pathway, thereby enhancing Cpt1-dependent fatty acid breakdown and reducing lipid deposition. Simultaneously, TCM may promote Fxr activity through AMPK, enhancing the negative feedback regulation of bile acid synthesis, thereby restoring bile acid metabolic homeostasis, reducing excessive cholesterol conversion to bile acids, and alleviating the metabolic burden on the liver. Furthermore, the inhibitory effect of TCM on Scd-1 may be achieved through the AMPK pathway, thereby reducing hepatic fat accumulation and improving insulin resistance. In summary, TCM may play an important role in improving glucose and lipid metabolism disorders and liver function damage by simultaneously regulating lipid metabolism and bile acid homeostasis through the AMPK-mediated Ppara-Fxr axis. In addition, in the diabetic model group... Acc1 , Acc2 and Srebp1c The expression of all genes was significantly upregulated, indicating that the fatty acid synthesis pathway in the liver was overactivated, which may lead to hepatic lipid deposition, insulin resistance, and metabolic disorders. However, after TCM intervention, the abnormal expression of these genes was significantly reversed, suggesting that TCM may reduce fatty acid synthesis and enhance fatty acid oxidation by promoting AMPK-mediated phosphorylation inactivation of Acc1 / Acc2, while downregulating Srebp1c activity and reducing its transcriptional activation of downstream genes such as Acc1, ultimately reducing the rate of hepatic fatty acid synthesis and alleviating lipid metabolism imbalance.

[0046] In normal rat liver tissue, the fluorescence signals of AMPK and its phosphorylated form p-AMPK were clearly visible, with AMPK mainly exhibiting red fluorescence and p-AMPK mainly exhibiting green fluorescence, indicating that AMPK and its activated state maintain stable expression levels and functions under normal physiological conditions. However, in the liver of diabetic rats, the fluorescence signals of AMPK and p-AMPK were significantly weakened, suggesting a decrease in the overall expression level of AMPK and a severe inhibition of its activity. Since p-AMPK represents the activated state of AMPK, its reduced fluorescence intensity further indicates that the activation capacity of the AMPK pathway is significantly impaired in diabetic conditions, which may lead to reduced fatty acid β-oxidation, glucose metabolism disorders, and increased insulin resistance. After TCM intervention, the fluorescence signals of AMPK and p-AMPK in the liver of diabetic rats were significantly enhanced, indicating that TCM can effectively promote the recovery of AMPK and its phosphorylation levels, thereby partially reversing the AMPK inactivation state caused by diabetes. In addition, the degree of recovery of green fluorescence of p-AMPK was significantly higher than that of red fluorescence of AMPK, suggesting that TCM may not only increase the overall expression level of AMPK, but more importantly, enhance its activation, i.e., promote AMPK phosphorylation (…). Figure 5 ).

[0047] These results systematically reveal that TCM improves insulin resistance and regulates lipid and bile acid metabolism by activating the AMPK-PPARα signaling pathway. Furthermore, TCM further improves glucose and lipid metabolism disorders by modulating the interaction between gut microbiota and bile acids.

[0048] The above description is merely a specific embodiment of the present invention, enabling those skilled in the art to understand or implement the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A composition of traditional Chinese medicine that is both food and medicine, characterized in that, The raw materials of the medicinal and edible herbal composition include yam, poria cocos, kudzu root, wolfberry, mulberry leaf, hawthorn, cinnamon, polygonatum odoratum and gardenia.

2. The medicinal and edible herbal composition according to claim 1, characterized in that, The raw materials in the medicinal and edible herbal composition include: 15-30 parts by weight of yam, 10-15 parts by weight of poria cocos, 10-15 parts by weight of kudzu root, 6-12 parts by weight of wolfberry, 5-10 parts by weight of mulberry leaf, 5-10 parts by weight of hawthorn, 3-6 parts by weight of cinnamon, 10-15 parts by weight of polygonatum odoratum and 3-6 parts by weight of gardenia. Optionally, the raw materials in the medicinal and edible herbal composition are composed of the following raw materials: 30 parts by weight of yam, 15 parts by weight of poria cocos, 15 parts by weight of kudzu root, 12 parts by weight of wolfberry, 10 parts by weight of mulberry leaf, 10 parts by weight of hawthorn, 6 parts by weight of cinnamon, 15 parts by weight of Solomon's seal and 6 parts by weight of gardenia.

3. A method for preparing a medicinal and edible herbal composition as described in claim 1 or 2, comprising the following steps: S1. Soak the raw material in 5-12 times its weight of water for 30-60 minutes, decoct, filter, and collect the filtrate; Repeat the decoction process 2 to 5 times with added water, combine the filtrates, and obtain the medicinal liquid. S2. The medicinal liquid is concentrated under reduced pressure to obtain the medicinal and edible herbal composition.

4. The preparation method according to claim 3, characterized in that, In S1, the weight of water added is 10 times the total weight of the active pharmaceutical ingredient; Optionally, the soaking time is 40 to 60 minutes; Optionally, the simmering time is 30 to 80 minutes after boiling; Optionally, the simmering time is 40 to 60 minutes after boiling.

5. The preparation method according to claim 3, characterized in that, In S2, the temperature for vacuum concentration is 55 ~ 60℃; Optionally, the pressure for vacuum concentration is 0.05 ~ 0.07 MPa, and the vacuum concentration time is 2-3 h.

6. A traditional Chinese medicine preparation prepared by the method described in claim 3.

7. The use of a traditional Chinese medicine composition that is both food and medicine as described in claim 1 or 2, or a traditional Chinese medicine preparation as described in claim 6, in the preparation of a medicament for treating type 2 diabetes.

8. The application according to claim 7, wherein the medicinal and edible herbal composition and / or herbal preparation is used in the preparation of a drug having any one or more of the following effects (1)-(5): (1) Foods or medicines used to improve blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and total cholesterol related to glucose and lipid metabolism; (2) Foods or medicines used to improve liver and kidney function related indicators such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, cholinesterase, and urea. (3) Foods or medicines used to improve pathological liver damage; (4) Foods or medicines used to improve lipid metabolism; (5) Foods or medicines used to improve bile acid metabolism.

9. The application according to claim 8, characterized in that, Among the foods or medicines used to improve pathological liver damage are those used to improve cellular edema and cytoplasmic vacuolation as well as extensive lipid droplet accumulation.

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