Research progress on the mechanism of TCM regulating intestinal microbiota in the treatment of DM mellitus.

In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.

Edible wild plants, chicory and purslane, alleviated diabetic testicular dysfunction, and insulin resistance via suppression 8OHdg and oxidative stress in rats.

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties.

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases.

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.

Therapeutic Effects of Amaranth: Analysis of the Antidiabetic Potential of the Plant.

Amaranth is a pseudocereal rich in macronutrients and micronutrients, with about 60 species cultivated worldwide. It is a high nutritional value food because of its many essential amino acids. Recent investigations demonstrate that the phytochemicals and extracts of amaranth have beneficial effects on health, including antidiabetic potential, a decrease in plasmatic cholesterol and blood pressure, and protection from oxidative stress and inflammation. Nowadays, type 2 diabetes has increased worldwide, becoming a problem of public health that makes it necessary to look for alternative strategies for its prevention and treatment. This review aims to summarize the antidiabetic potential of diverse species of the Amaranth genus. A bibliographical review was updated on the plant's therapeutic potential, including stem, leaves, and seeds, to know the benefits and potential as an adjuvant in treating and managing diabetes and associated pathologies (hypertension, dyslipidemia, and heart disease). This analysis contributes to the generation of knowledge about the therapeutic effects of amaranth, promoting the creation of new products, and the opportunity to conduct clinical trials to assess their safety and efficacy.

Effects of Auricularia auricula-judae (Bull.) Quél. polysaccharide acid hydrolysate on glucose metabolism in diabetic mice under oxidative stress.

BACKGROUND: Oxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PURPOSE: Using diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull.) Quél. on improving diabetes. STUDY DESIGN AND METHODS: The structural information of sample polysaccharides was measured by high performance gel permeation chromatography, nuclear magnetic resolution, and high performance liquid chromatography. The diabetic model was established by intraperitoneal injection of streptozotocin. For eight consecutive weeks, the mice were orally administered sample polysaccharides (100, 200, and 300 mg/kg b.w. per day) for intervention. The improvement effect of the samples on diabetes was explored by detecting the changes in biochemical indicators in mice, and the underlying mechanism was studied by transcriptomic and metabolomic analysis. RESULTS: The results showed that acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides consisted mainly of mannose, xylose, glucuronic acid, and glucose; its weight-averaged molecular weight was 6.3842 × 104 Dalton, its number average molecular weight was 2.9594 × 104 Dalton; and the molecule contained α-Glc(1→4)-, ß-Glc(1→3)-, and ß-Man(1→4)-linked glycosidic bonds. A total of 100 mg/kg b.w. per day sample was the best intervention concentration. After eight weeks of intervention, the sample polysaccharides significantly reduced dynamic blood glucose and serum lipids, enhanced antioxidant enzyme activities, promoted glucagon like peptide-1 and insulin secretion, improved insulin sensitivity and alleviated insulin resistance in diabetic mice. Transcriptomic and metabolomic analyses showed that sample polysaccharides was able to ameliorate disorders of glucose metabolism by modulating gene expression such as glucokinase; and modulate the state of oxidative stress in mice in vivo by regulating the glutathione metabolism pathway. CONCLUSION: Acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides improved glucose metabolism disorders by slowing down the oxidative stress injury in mice, thereby alleviating diabetes. This study provided a basis for determining the underlying mechanism of the antidiabetic effect of Auricularia auricula-judae (Bull.) Quél. polysaccharides, which would significantly improve the deep development and application of these materials in diabetes control.

Ethnobotanical assessment of antidiabetic medicinal plants in District Karak, Pakistan.

BACKGROUND: Diabetes is a leading health disorder and is responsible for high mortality rates across the globe. Multiple treatment protocols are being applied to overcome this morbidity and mortality including plant-based traditional medicines. This study was designed to investigate the ethnomedicinal status of plant species used to treat diabetes in District Karak, Pakistan. MATERIALS AND METHODS: A semi-structured survey was created to collect data about traditionally used medicinal plants for diabetes and other ailments. The convenience sampling method was applied for the selection of informants. The collected data was evaluated through quantitative tools like frequency of citation (FC), relative frequency of citation (RFC), informant consensus factor (FIC), fidelity level (FL), and use value (UV). RESULTS: A total of 346 local informants were selected for this research. Out of them, 135 participants were men and 211 participants were women. Overall 38 plant species belonging to 29 plant families were used to treat diabetes. The most dominant plant family was Oleaceae having 11 species. Powder form (19%) was the most recommended mode of preparation for plant-based ethnomedicines. Leaves (68%) were the most frequently used parts followed by fruit (47%). The highest RFC was recorded for Apteranthes tuberculata (0.147). The maximum FL was reported for Apteranthes tuberculata (94.4) and Zygophyllum indicum (94.11) for diabetes, skin, and wounds. Similarly, the highest UV of (1) each was found for Brassica rapa, Melia azedarach, and Calotropis procera. Based on documented data, the reported ailments were grouped into 7 categories. The ICF values range between 0.89 (diabetes) to 0.33 (Cardiovascular disorders). CONCLUSION: The study includes a variety of antidiabetic medicinal plants, which are used by the locals in various herbal preparations. The species Apteranthes tuberculata has been reported to be the most frequently used medicinal plant against diabetes. Therefore, it is recommended that such plants be further investigated in-vitro and in-vivo to determine their anti-diabetic effects.

Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetic medications: a cross-sectional study.

Introduction: type 2 Diabetes mellitus is a chronic metabolic disease with devastating effects on patients and results in numerous healthcare challenges in terms of its management and the cost burden among the affected. Successful management involves maintaining optimal glycemic control to prevent complications, with adherence to antidiabetic medications playing a crucial role in achieving this objective. Additionally, maintaining a healthy electrolyte balance is key for overall well-being and physiological function. However, the correlation between glycated hemoglobin and electrolyte balance remains under investigated, particularly in patients with suboptimal adherence. The aim of this research was to study the relationship between glycated hemoglobin and electrolytes among diabetic patients with poor adherence to antidiabetic medications. Methods: this study was conducted at Samburu County Referral Hospital in Samburu County, Kenya. We employed a descriptive cross-sectional design focusing on adult diabetic patients aged 18 years and above who had visited the diabetic clinic over a three-month period. To evaluate their adherence levels, we employed a Morisky Medication Adherence Scale-8. Seventy-two diabetic patients who got adherence level scores of < 6 were categorized as having low adherence and their blood samples were collected for measuring glycated hemoglobin levels and electrolytes levels particularly potassium, sodium, calcium, magnesium, phosphorus and chloride. Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics was determined using Karl Pearson correlation. Results: among the study participants, the lowest hemoglobin A1C (HbA1c) level recorded was 5.1% while the highest was 15.0% and the majority (41.7%) fell within the HbA1c range of 5-7%. A high proportion of individuals (58.3%) with poor adherence to antidiabetics had elevated HbA1c levels, indicating poor glycemic control. The correlations observed between glycated hemoglobin and electrolytes which included magnesium, sodium, chloride, calcium and phosphorus was r= -0.07, -0.32, -0.05 -0.24 and -0.04 respectively. Conclusion: this study concluded that there is a relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics. A statistically significant negative correlation was observed between glycated hemoglobin and calcium level (r=-0.2398 P ≤0.05) and also sodium (r=-0.31369 P≤0.05). A negative correlation (P≥0.05) was observed between phosphorus, magnesium, chloride and potassium with HbA1c levels though not statistically significant.

"GC-MS profiling, sub-acute toxicity study and total phenolic and flavonoid content analysis of methanolic leaf extract of Schima wallichii (D.C.) Korth-a traditional antidiabetic medicinal plant".

ETHNOPHARMACOLOGICAL RELEVANCE: Schima wallichii (D.C.) Korth is traditionally used in Manipur, India for treatment of diabetes and hypertension. However, there is no data reported regarding safety profile of this medicinal plant upon repeated per oral administration over a period of time. AIM OF THE STUDY: In the current study phytochemical profile, toxicological profile and total phenolic and flavonoid compound content of Schima wallichii leaves extract were evaluated. MATERIALS AND METHODS: Gas chromatography coupled to mass spectrometry was performed for chemical profiling by using Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS), Shimadzu, TQ8040 system. A 28 days sub-acute toxicity study was carried out using albino Wistar rats by administering 3 different doses (200, 400 and 800 mg/kg body weight per oral) of methanol leaves extract. Changes in body weights were recorded weekly. Serum biochemical parameters were estimated as well as blood-cell count was done to check the effect of extract on haematopoietic system. Histopathology of vital organs viz. kidney, heart, brain, liver was performed to find any pathological indications. Since, liver is main the site for xenobiotic metabolism, estimation of the level of glutathione, catalase and lipid peroxidation were done. Further, total phenolic and flavonoid compound content estimation was performed for the leaves extract. RESULTS: GC-MS revealed 14 major compounds with area percentage >1% of which quinic acid, n-Hexadecanoic acid, 9,12,15-Octadecatrienoic acid, (Z,Z,Z)-, Octatriacontyl trifluoroacetate, are three major compounds. No mortality was observed after the treatment with extract. Blood-cell count and biochemical parameters didn't show significant deviation as compared to control group. Histopathology study of vital organs viz. (liver, kidney, heart and brain) showed normal cellular construction comparing to control group. There was no sign of membrane lipid peroxidation, depletion of catalase level and glutathione level in liver. The result demonstrates that NOAEL (no-observed-adverse-effect levels) in the sub-acute toxicity was above 800 mg/kg. The leaves extract showed significant total phenol and flavonoid content. CONCLUSION: The present study revealed that Schima wallichii possessed important bioactive compounds with therapeutic values. The plant was safe for consumption after repeated high doses administration in rats and possesses significant amount of total phenol and flavonoid content.

Medicinal plants of Southeast Asia with anti-α-glucosidase activity as potential source for type-2 diabetes mellitus treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus, a widespread chronic illness, affects millions worldwide, and its incidence is increasing alarmingly, especially in developing nations. Current pharmacological treatments can be costly and have undesirable side effects. To address this, medicinal plants with antidiabetic effects, particularly targeting α-glucosidase for controlling hyperglycaemia in type-2 diabetes mellitus (T2DM), hold promise for drug development with reduced toxicity and adverse reactions. AIM OF THIS REVIEW: This review aims to succinctly collect information about medicinal plant extracts that exhibit antidiabetic potential through α-glucosidase inhibition using acarbose as a standard reference in Southeast Asia. The characteristics of this inhibition are based on in vitro studies. MATERIALS AND METHODS: Relevant information on medicinal plants in Southeast Asia, along with α-glucosidase inhibition studies using acarbose as a positive control, was gathered from various scientific databases, including Scopus, PubMed, Web of Science, and Google Scholar. RESULTS: About 49 papers were found from specific counties in Southeast Asia demonstrated notable α-glucosidase inhibitory potential of their medicinal plants, with several plant extracts showcasing activity comparable to or surpassing that of acarbose. Notably, 19 active constituents were identified for their α-glucosidase inhibitory effects. CONCLUSIONS: The findings underscore the antidiabetic potential of the tested medicinal plant extracts, indicating their promise as alternative treatments for T2DM. This review can aid in the development of potent therapeutic medicines with increased effectiveness and safety for the treatment of T2DM.

Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. AIM OF THE STUDY: The objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). MATERIALS AND METHODS: The AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. RESULTS: The acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. CONCLUSION: The phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Phytochemical Profiling and Assessment of Antidiabetic Activity of Curcuma Angustifolia Rhizome Methanolic Extract: An In Vitro and In Silico Analysis.

Curcuma angustifolia Roxb. is a plant with medicinal potential, traditionally used to treat different diseases. The present study aimed to determine the antidiabetic activity of C. angustifolia rhizome in vitro and in silico. The methanolic extract of C. angustifolia rhizome was analyzed by FTIR and GC-MS to determine the phytochemicals present. The antidiabetic potential of the extract was evaluated by different assays in vitro. The extract inhibited both α-amylase and α-glucosidase enzymes and the glucose diffusion through the dialysis membrane in a concentration-dependent manner with IC50 values of 530.39±0.09, 293.75±0.11, and 551.74±0.3 µg/ml respectively. The methanolic extract also improved yeast cell's ability to take up glucose across plasma membranes and the adsorption of glucose. The findings were supported by molecular docking studies. The results showed that the methanol extract of C. angustifolia rhizome has significant antidiabetic activity and thus can be also studied to isolate the potential compound with antidiabetic activities.

Explore the active ingredients and potential mechanism of action on Actinidia arguta leaves against T2DM by integration of serum pharmacochemistry and network pharmacology.

BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.

A fast and efficient method for screening and evaluation of hypoglycemic ingredients of Traditional Chinese Medicine acting on PTP1B by capillary electrophoresis.

As a pivotal enzyme that regulates dephosphorylation in cell activities and participates in the insulin signaling pathway, protein tyrosine phosphatase 1B (PTP1B) is considered to be an important target for the therapy of diabetes. In this work, a rapid and efficient inhibitor screening method of PTP1B was established based on capillary electrophoresis (CE), and used for screening and evaluating the inhibition effect of Traditional Chinese Medicine on PTP1B. Response Surface Methodology was used for optimizing the conditions of analysis. After method validation, the enzyme kinetic study and inhibition test were performed. As a result, the IC50 of PTP1B inhibitors Ⅳ and ⅩⅧ were consistent with reported values measured by a conventional method. It was found that the extracts of Astragalus membranaceus (Fisch) Bunge and Morus alba L. showed prominent inhibition on the activity of PTP1B, which were stronger than the positive controls. Meanwhile, on top of the excellent advantages of CE, the whole analysis time is less than 2 min. Thus, the results demonstrated that a fast and efficient screening method was successfully developed. This method could be a powerful tool for screening inhibitors from complex systems. It can also provide an effective basis for lead compound development in drug discovery.

Chemical Profiling and Biological Activities on Nepalese Medicinal Plant Extracts and Isolation of Active Fraction of Nyctanthes arbor-tristis.

The importance of medicinal plants for the treatment of different diseases is high from the aspects of the pharmaceutical industry and traditional healers. The present study involves nine different medicinal plants, namely, Neolamarckia cadamba, Nyctanthes arbor-tristis, Pogostemon benghalensis, Equisetum debile, Litsea monopetala, Spilanthes uliginosa, Desmostachya bipinnata, Mallotus philippensis, and Phoenix humilis, collected from Chitwan district of Nepal for biochemical analysis followed by the isolation of active plant fractions from the bioactive plant extract. The methanolic extracts of roots, barks, seeds, seed cover, and the other aerial parts of plants were used for the phytochemical analysis and biological activities. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay was adopted to evaluate the antioxidant activity. Antibacterial activity was evaluated using the agar well diffusion method. The antidiabetic activity was studied by the α-amylase enzyme inhibition assay. The highest antioxidant activity was observed in extracts of Nyctanthes arbor-tristis followed by Mallotus philippensis (seed cover), Pogostemon benghalensis, Litsea monopetala, Phoenix humilis, and Neolamarckia cadamba with IC50 values of 27.38 ± 1.35, 32.08 ± 2.81, 32.75 ± 2.13, 33.82 ± 1.07, 40.14 ± 0.93, and 50.44 ± 3.75 µg/mL, respectively. The highest antidiabetic activity was observed in extracts of Phoenix humilis followed by Desmostachya bipinnata and Pogostemon benghalensis with IC50 values of 95.69 ± 6.97, 99.24 ± 12.6, and 106.3 ± 12.89 µg/mL, respectively. The mild α-amylase enzyme inhibition was found in extracts of Nyctanthes arbor-tristis, Spilanthes uliginosa Swartz, Litsea monopetala, and Equisetum debile showing IC50 values of 110.4 ± 7.78, 115.98 ± 10.24, 149.83 ± 8.3, and 196.45 ± 6.04 µg/mL, whereas Mallotus Philippensis (seed cover), Mallotus philippensis (seed), and Desmostachya bipinnata showed weak α-amylase inhibition with IC50 values of 208.87 ± 1.76, 215.41 ± 2.09, and 238.89 ± 9.27 µg/mL, respectively. The extract of Nyctanthes arbor-tristis showed high zones of inhibition against S. aureus (ATCC 25923) and E. coli (ATCC 25922) of ZOI 26 and 22 mm, respectively. The chemical constituents isolated from the active plant Nyctanthes arbor-tristis were subjected to GCMS analysis where the major chemical compounds were 11,14,17-eicosatrienoic acid and methyl ester. These results support the partial scientific validation for the traditional uses of these medicinal plants in the treatment of diabetes and infectious diseases by the people living in different communities of Chitwan, Nepal.

Effects of Physalis peruviana L. (leaf crude extracts) on blood glucose and functional biomarkers in streptozotocin-nicotinamide-induced diabetic rats.

Promoting antidiabetic phytomedicines necessitates evidence-based preclinical investigations, particularly in animal models. The present study investigated the validity of using the streptozotocin-nicotinamide-induced type 2 diabetic (STZ/NA-induced T2DM) model to evaluate the effects of Physalis peruviana leaf crude extracts on controlling blood glucose levels and regulating physiological biomarkers in rats. Aqueous and methanol extracts dissolved in carboxymethylcellulose 1% (100, 200, mg/kg/day) were administered orally to STZ/NA-induced T2DM rats alongside glibenclamide (5 mg/kg) as the standard drug for four weeks. Blood samples were collected in fasting rats on days 1, 7, 14, 21, and 28 to measure glucose concentration, lipoprotein-cholesterol, and common serum biomarkers. Nutrition characteristics were also monitored, as well as the pancreas histology. Administration of STZ/NA in Wistar rats induced the T2DM significantly lower than did STZ alone (glycaemia 200 vs 400 mg/dL). The significant effects observed with plant extracts compared to untreated diabetic rats were blood glucose reduction (28-52 %), HDL-C increase, LDL-C decrease, ALAT increase, WBC increase, body weight gain (24%), and pancreas protection. The findings confirm the antidiabetic effect of P. peruviana in T2DM animal model.

Nephroprotective and Anti-Diabetic Potential of Beta vulgaris L. Root (Beetroot) Methanolic Extract in a Rat Model of Type 2 Diabetes Mellitus.

Background and Objectives: Diabetes mellitus is a chronic metabolic disease associated with several complications, including that of kidney disease. Plant-based dietary products have shown promise in mitigating these effects to improve kidney function and prevent tissue damage. This study assessed the possible favorable effects of beetroot extract (BE) in improving kidney function and preventing tissue damage in diabetic rats. Materials and Methods: Type 2 diabetes mellitus (T2DM) was induced using a low dose of streptozotocin (STZ). Both control and rats with pre-established T2DM were divided into six groups (each consisting of eight rats). All treatments were given by gavage and continued for 12 weeks. Fasting blood glucose levels, serum fasting insulin levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum triglycerides, cholesterol, low-density lipoprotein-cholesterol, serum and urinary albumin, and creatinine and urea levels were measured. Apart from this, glutathione, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, and interleukine-6 in the kidney homogenates of all groups of rats were measured, and the histopathological evaluation of the kidney was also performed. Results: It was observed that treatment with BE increased body weight significantly (p ≤ 0.05) to be similar to that of control groups. Fasting glucose, insulin, HOMA-IR levels, and lipid profile in the plasma of the pre-established T2DM rats groups decreased to p ≤ 0.05 in the BE-treated rats as the BE concentration increased. Treatment with BE also improved the renal levels of oxidative stress and inflammatory markers, urinary albumin, and serum creatinine and urea levels. Unlike all other groups, only the kidney tissues of the T2DM + BE (500 mg/kg) rats group showed normal kidney tissue structure, which appears to be similar to those found in the kidney tissues of the control rats groups. Conclusion: we found that streptozotocin administration disturbed markers of kidney dysfunction. However, Beta vulgaris L. root extract reversed these changes through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Antioxidant, Anti-Diabetic, and Anti-Inflammation Activity of Garcinia livingstonei Aqueous Leaf Extract: A Preliminary Study.

Diabetes mellitus (DM) is the second leading cause of mortality globally. The increased concern for DM is due to the underlying complications accompanying hyperglycaemia, associated with oxidative stress and consequent inflammation. The investigation of safe and effective treatments for DM is necessary. In the present study, the cytotoxicity, phytochemical analysis, antioxidant capacity, anti-inflammatory, and antidiabetic effects in an aqueous extract of Garcinia livingstonei leaves were assessed. All tested extract concentrations showed no toxicity against C3A hepatocytes. Several phenolic compounds were identified using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). The total polyphenol content was 100.9741 mg GAE/g, 16.7712 mg CE/g flavanols, and 2.3548 mg QE/g flavonols. The antioxidant capacity values were 253.4268 mg AAE/g, 192.232 mg TE/g, and 167.8724 mg TE/g for ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH), respectively. The plant extract significantly (p < 0.05) demonstrated anti-inflammatory and hypoglycaemic effects in a dose-dependent manner, with the α-glucosidase inhibition of the extract being higher (p < 0.05) than in the standard conventional drug (acarbose). The findings of this study revealed the potential of the constituents of G. livingstonei aqueous leaf extract in DM treatment. Further studies on the preparation and mechanisms of action of the plant in DM treatment are recommended.

Yunvjian decoction mitigates hyperglycemia in rats induced by a high-fat diet and streptozotocin via reducing oxidative stress in pancreatic beta cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Yunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by which YNJ affects T2DM remains unclear. AIM OF THE STUDY: This study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels. RESULTS: Five major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1. CONCLUSION: YNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.

Extraction, purification, structural modification, activities and application of polysaccharides from different parts of mulberry.

The mulberry plant is a member of the Moraceae family and belongs to the Morus genus. Its entire body is a treasure, with mulberries, mulberry leaves, and mulberry branches all suitable for medicinal use. The main active ingredient in mulberries is mulberry polysaccharide. Studies have shown that polysaccharides from different parts of mulberry exhibit antioxidant, antidiabetic, antibacterial, anti-inflammatory, and blood pressure-lowering properties. There are more studies on the biological activities, extraction methods, and structural characterization of polysaccharides from different parts of mulberry. However, the structural characterization of mulberry polysaccharides is mostly confined to the types and proportions of monosaccharides and the molecular weights of polysaccharides, and there are fewer systematic studies on polysaccharides from different parts of mulberry. In order to better understand the bioactive structure of mulberry polysaccharides, this article discusses the recent research progress in the extraction, separation, purification, bioactivity, structural modification, and application of polysaccharides from different parts of mulberry (mulberry leaves, mulberry fruits, and mulberry branches). It also delves into the pharmacological mechanisms of action of mulberry polysaccharides to provide a theoretical basis for further research on mulberry polysaccharides with a view to their deeper application in the fields of feed and nutraceuticals.