Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Animals ; Elaeocarpaceae/chemistry* ; Drugs, Chinese Herbal/therapeutic use* ; Hypoglycemic Agents/chemistry* ; Plant Extracts/chemistry*

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A-E (1-5), and three lanostanoids, ganothenoids F-H (6-8), along with 24 known ones (9-32), were isolated from the fruiting bodies of Ganodrma theaecolum. The structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1-32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L^-1, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L^-1. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.
Humans ; Fruiting Bodies, Fungal/chemistry* ; Triterpenes/isolation & purification* ; Neuroprotective Agents/isolation & purification* ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism* ; Ganoderma/chemistry* ; Apoptosis/drug effects* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; alpha-Glucosidases/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Oxidative Stress/drug effects* ; Hydrogen Peroxide/toxicity* ; Molecular Docking Simulation

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

With the rise of incidence, fatality rate, and number of young cases, diabetes mellitus has been one of the seven major diseases threatening human health. Although many antidiabetic drugs(oral or for injection) are available, the majority have serious side effects during the long-term use. Thus, it is of particularly vital to develop new drugs with low risk and definite effect. Psoraleae Fructus, a traditional medicinal widely used in the folk, has hypoglycemic, anti-osteoporosis, antitumor, estrogen-like, and anti-inflammatory effects. Thus, it has great clinical application potential. Chinese medicine and the active ingredients, characterized by multiple targets, multiple pathways, and multiple effects in the treatment of diabetes mellitus, have distinct advantages in clinical application. However, the safety of Chinese medicine remains to be a challenge, and one of keys is to clarifying the mechanism of a single Chinese medicinal and its active ingredients. With the method of literature research, this study summarized and analyzed the hypoglycemic mechanisms of Psoraleae Fructus and its main active ingredients over the last decade: regulating glucose metabolism, improving insulin resistance, and directly acting on pancreatic β-cells. The result is expected to serve as a reference for further research on the effects of Psoraleae Fructus and its main chemical constituents in lowering blood glucose and preventing diabetes mellitus and the clinical application.
Drugs, Chinese Herbal/pharmacology* ; Fruit/chemistry* ; Humans ; Hypoglycemic Agents/pharmacology* ; Osteoporosis/drug therapy* ; Psoralea/chemistry*

Eight terpenoids were isolated from the fruits of Amomum villosum by silica gel, Sephadex LH-20, Rp-C_(18), MCI GEL CHP20 P column chromatography, preparative TLC, and HPLC. Their structures were identified by HR-ESI-MS, ~1H and ~(13)C-NMR, IR, UV, [α]_D, and ECD spectroscopic data as kravanhin A 3-O-β-D-glucopyranoside(1), kravanhin B(2), 6-eudesmene-1β,4β-diol(3), oplodiol(4), vicodiol(5),(1R,2S,4R,7S)-vicodiol 9-O-β-D-glucopyranoside(6),(1R,2S,4S,5R)-angelicoidenol 2-O-β-D-glucopyranoside(7), and(1S,2S,4R,6S)-bornane-2,6-diol 2-O-β-D-glucopyranoside(8). Compound 1 was a new compound, and compounds 2-5 were isolated from A. villosum for the first time. Their hypoglycemic activity was tested based on STC-1 cell model and two enzymatic models(GPa and PTP1 B). The results showed that compounds 1, 7, and 8 could stimulate GLP-1 with the secretion rates of 692.8%, 398.6%, and 483.3% at 25.0 μmol·L~(-1), and compound 6 showed inhibitory activity against GPa with an IC_(50) value of 78.6 μmol·L~(-1).
Fruit/chemistry* ; Terpenes/analysis* ; Amomum ; Hypoglycemic Agents/analysis* ; Chromatography, High Pressure Liquid

BACKGROUND: Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats. METHODS: The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols. RESULTS: HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide. CONCLUSION The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.
1-Butanol/chemistry* ; Administration, Oral ; Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Dose-Response Relationship, Drug ; Hypoglycemic Agents/chemistry* ; Male ; Periploca/chemistry* ; Phytochemicals/chemistry* ; Plant Extracts/chemistry* ; Rats ; Rats, Sprague-Dawley ; Streptozocin/adverse effects*

Eight compounds,(R)-2-[5-(methoxycarbonyl)-4-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl]acetic acid(1),(3S,4R)-3,4-dihydro-3,4-epoxy-5-hydroxynaphthalen-1(2H)-one(2),(-)-mitorubrinol(3),(-)-mitorubrin(4),(±)-asperlone A(5), terreusinone(6), verrucisidinol(7) and cerebroside C(8) were isolated from the endophytic fungus Talaromyces purpurogenus by using various column chromatographic techniques. Their structures were identified by NMR, MS, CD and optical rotation. Compounds 1 and 2 were new compounds. Their anti-diabetic activities in vitro were evaluated, and compound 1 showed moderate inhibitory activity toward XOD at 10 μmol·L~(-1) with the inhibition rate of 69.9%.
Endophytes/chemistry* ; Hypoglycemic Agents/chemistry* ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Secondary Metabolism ; Talaromyces/chemistry* ; Tylophora/microbiology* ; Xanthine Oxidase/antagonists & inhibitors*

The aim of the study was to determine the feasibility of the Vitellaria paradoxa nutshell as a new medicinal resource for treating diabetes. A total of forty-one compounds were identified by HPLC-DAD-Q-TOF-MS and phytochemical methods in V. paradoxa nutshell methanol extract. Based on HPLC fingerprints, four characteristic constituents were quantified and the origin of twenty-eight V. paradoxa nutshells from seven sub-Saharan countries was compared, which were classified into three groups with chemometric method. Twenty-eight samples contained high total phenolic content, and exhibited moderate-higher antioxidant activity and strong α-glucosidase inhibitory activity. Furthermore, all fractions and isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities, and α-glucosidase inhibitory action mechanism of four characteristic constituents including protocatechuic acid, 3, 5, 7-trihydroxycoumarin, (2R, 3R)-(+)-taxifolin and quercetin was investigated via molecular docking method, which were all stabilized by hydrogen bonds with α-glucosidase. The study provided an effective approach to waste utilization of V. paradoxa nutshell, which would help to resolve waste environmental pollution and provide a basis for developing potential herbal resource for treating diabetes.
Africa South of the Sahara ; Chromatography, High Pressure Liquid ; Diabetes Mellitus ; drug therapy ; enzymology ; Glycoside Hydrolase Inhibitors ; chemistry ; pharmacology ; Humans ; Hypoglycemic Agents ; chemistry ; pharmacology ; Molecular Docking Simulation ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Sapotaceae ; chemistry ; alpha-Glucosidases ; metabolism

OBJECTIVES: To investigate the effects of saffron aqueous extract (SE) on blood glucose, lipid and pancreatic tissue in streptozocin-induced diabetes mice. METHODS: Diabetes mellitus mice were established by intraperitoneal injection of streptozocin (60 mg/kg) for two consecutive days. The 30 well-established diabetes mice were randomly divided into three groups(=10):diabetic mellitus (DM) group, SE treated (SE) group and positive control (metformin hydrochloride, MH) group. Another ten normal mice were selected as normal control (NC) group. The mice in SE and MH groups were intragastrically administered with SE 100 mg/kg or MH 100 mg/kg once a day for 6 weeks, mice in DM and NC were given normal saline. The amount of food-intake, water consumption and body weight were measured weekly, the changes of the indicators including fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), glycated serum protein (GSP), insulin (INS) and blood lipid were determined after 6 weeks of continuous administration. The pathologic changes in the pancreas tissues were detected by HE staining. RESULTS: Compared with the normal control group, the amount of food-intake, water consumption, area under the curve, FBG, GSP, and total cholesterol (TC) were significantly increased, while fasting weight, INS and high density lipoprotein cholesterol (HDL-c) were dramatically decreased in DM group. Compared with DM group, the water consumption, FBG, area under the curve and TC in SE group were starkly declined with a notable elevation of HDL-c and INS. In addition, the biopsy from DM mice showed the structure of pancreas islet was destroyed and reduced, and vascular proliferation with irregular shape. The damaged pancreas was obviously repaired by giving SE. CONCLUSIONS The saffron aqueous extract had efficacy on blood glucose and blood lipids reduction, improvement on damaged pancreas in streptozocininduced diabetic mice, which suggested that saffron could be used for the treatment in diabetes.
Animals ; Blood Glucose ; Crocus ; chemistry ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Mice ; Plant Extracts ; pharmacology ; Random Allocation ; Streptozocin