Laminaria japonica polysaccharide alleviates type 2 diabetes by regulating the microbiota-gut-liver axis: A multi-omics mechanistic analysis.
International journal of biological macromolecules
The hypoglycemic effects of low-molecular-weight Laminaria japonica polysaccharide (LJO) were investigated in type 2 diabetes mellitus (T2DM) mice, focusing on its effect on the microbiome, metabolome, and transcriptome. The findings demonstrated that LJO significantly reduced fasting blood glucose levels, insulin levels, and inflammatory factors. Additionally, LJO induced changes in gut microbiota composition and increased the concentrations of cecal short-chain fatty acids. Analysis of transcriptomics and metabolomics data revealed that LJO primarily altered the endocrine and digestive systems, signal transduction, and lipid metabolism. It led to a decrease in palmitic acid levels and an increase in glutathione levels. Real-time quantitative polymerase chain reaction assay suggested that LJO upregulated Irs1 expression, consequently reducing insulin resistance. These findings strongly suggest that LJO holds promise in ameliorating T2DM and may serve as a potential dietary supplement for patients with T2DM.
10.1016/j.ijbiomac.2023.128853
Anti-diabetic effects of natural and modified 'Ganzhou' navel orange peel pectin on type 2 diabetic mice gut microbiota.
Food & function
Pectin, a kind of dietary fiber, has attracted much attention owing to its beneficial effect on human health in recent years. In this study, the effects of both 'Ganzhou' navel orange peel pectin (GOP) and modified GOP (MGOP) on type 2 diabetes (T2DM) were investigated. The results indicated that GOP and MGOP intervention had positive effects on T2DM in C57BL/6 mice. After modification, pectin can be changed into low methoxy pectin (LMP) and the content of GalA can increase, which endow MGOP with significant effects on improving lipid metabolism (TC, TG, and LDL-C decreased by 30.46%, 50%, and 37.56%, respectively, and HDL-C increased by 56%) and OGTT, further reducing insulin resistance (insulin decreased by 74.35%). In addition, MGOP was superior to GOP in improving oxidative stress (GSH and GSH-Px increased by 52.05% and 29.08% respectively, and MDA decreased by 84.02%), inhibiting inflammation and promoting SCFA synthesis. 16S rRNA analysis showed that MGOP changed the composition of intestinal microbiota in diabetic mice, decreased the abundance of , and , and increased the relative abundance of , , and . The phenotypes of the gut microbiome also changed accordingly, which showed that MGOP significantly inhibited the growth of Gram-negative bacteria and potential pathogenic bacteria and reversed the related complications. Taken together, our findings revealed that MGOP intake regulated lipid metabolism and oxidative stress and improved the gut health of mice, with promising effects against T2DM and related complications.
10.1039/d3fo04118b
Punicalagin alleviates renal injury the gut-kidney axis in high-fat diet-induced diabetic mice.
Hua Qinglian,Han Yaling,Zhao Haifeng,Zhang Haowen,Yan Bei,Pei Shengjie,He Xin,Li Yue,Meng Xiangyuan,Chen Lei,Zhong Feng,Li Duo
Food & function
Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we hypothesized that PU may improve diabetic renal injury by modulating the gut-kidney axis. The present study evaluated the effect of PU on the gut-kidney axis and kidney function in a diabetic renal injury mouse model induced by a high-fat diet (HFD). Mice were fed a HFD without PU or with at doses of 50 and 100 mg kg d for 8 weeks. Targeted metabolomics by GC-MS and 16S rRNA sequencing were implemented to determine short-chain fatty acids (SCFAs) and microbes. Further RNA sequencing analyses were performed to determine which differentially expressed genes were changed by PU. Compared with the DM model group, PU supplementation improved diabetic renal injury, ameliorated kidney architecture and function, and reshaped gut microbial ecology. Additionally, PU reversed HFD-induced gut barrier dysfunction, promoted cecal SCFA concentrations and inhibited serum lipopolysaccharide (LPS) and diamine oxidase (DAO) levels. Moreover, correlation analysis found that cecal SCFAs were significantly negatively correlated with inflammation-related genes in the kidney. The present results indicated that PU, a promising bioactive polyphenol, successfully improved diabetic renal injury, most likely through the gut-kidney axis.
10.1039/d1fo03343c
A polysaccharide from Tratt fruit attenuates high-fat diet-induced intestinal barrier dysfunction and inflammation in mice by modulating the gut microbiota.
Wang Lei,Zhang Pan,Li Chao,Xu Fei,Chen Jie
Food & function
Obesity-induced colonic inflammation-stimulated colitis is one of the main causes of colorectal cancer. Dietary polysaccharides are considered an effective agent for relieving obesity-induced inflammatory diseases such as diabetes and colitis. In this work, the protective effects of a polysaccharide (RTFP) extracted from Tratt fruit on barrier dysfunction and inflammation were investigated using obesity-induced colitis model mice. RTFP treatment repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (ZO-1, claudin-1, and occludin) and reducing the levels of inflammatory cytokines, intestinal permeability, and colonic oxidative stress in mice fed a high-fat diet. Most significantly, RTFP decreased gut inflammation and ameliorated the metabolic dysbiosis of intestinal microflora by decreasing the Firmicutes/Bacteroidetes ratio, reducing the levels of serum D-lactic acid and lipopolysaccharides, and inhibiting the TLR4/NF-κB signaling pathway. Furthermore, RTFP significantly increased the abundance of beneficial bacteria (Ruminococcaceae, Muribaculaceae, Akkermansiaceae, .) but decreased the abundance of pathogenic bacteria. These findings indicate that RTFP can be used as a natural anti-inflammatory agent to reduce chronic obesity-induced colitis.
10.1039/d1fo03190b
FTZ polysaccharides ameliorate kidney injury in diabetic mice by regulating gut-kidney axis.
Phytomedicine : international journal of phytotherapy and phytopharmacology
BACKGROUND:The Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora. PURPOSE:This study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis. STUDY DESIGN AND METHODS:The DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300 mg/kg daily. Renal histological changes were measured by H&E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles. RESULTS:Treatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage. CONCLUSION:These results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD.
10.1016/j.phymed.2023.154935
Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity.
Nature metabolism
Non-alcoholic fatty liver disease (NAFLD) has emerged pandemically across the globe and particularly affects patients with obesity and type 2 diabetes. NAFLD is a complex systemic disease that is characterised by hepatic lipid accumulation, lipotoxicity, insulin resistance, gut dysbiosis and inflammation. In this review, we discuss how metabolic dysregulation, the gut microbiome, innate and adaptive immunity and their interplay contribute to NAFLD pathology. Lipotoxicity has been shown to instigate liver injury, inflammation and insulin resistance. Synchronous metabolic dysfunction, obesity and related nutritional perturbation may alter the gut microbiome, in turn fuelling hepatic and systemic inflammation by direct activation of innate and adaptive immune responses. We review evidence suggesting that, collectively, these unresolved exogenous and endogenous cues drive liver injury, culminating in liver fibrosis and advanced sequelae of this disorder such as liver cirrhosis and hepatocellular carcinoma. Understanding NAFLD as a complex interplay between metabolism, gut microbiota and the immune response will challenge the clinical perception of NAFLD and open new therapeutic avenues.
10.1038/s42255-021-00501-9
Anthocyanin Extracts Improve Hepatic Structure and Function in High-Fat Diet-/Streptozotocin-Induced T2DM Mice.
Journal of agricultural and food chemistry
Anthocyanins can prevent and ameliorate type 2 diabetes mellitus (T2DM), but its mechanism of action has not been fully established. IKK/NF-κB and JAK/Stat pathways have multiple effects, triggering T2DM. Liver abnormalities in individuals with T2DM are detrimental to glycemic control. We determined whether anthocyanins could improve the liver of individuals with T2DM using IKK/NF-κB and JAK/Stat. We established a T2DM mouse model using a high-fat diet and streptozotocin and then performed anthocyanin extracts' (AMAEs') administration for 5 weeks. AMAEs improved blood glucose and hyperinsulinemia of T2DM mice. In the liver of AMAE-administered T2DM mice, ROS, IKKβ/NF-κB p65, and JAK2/Stat3/5B signalings were down-regulated, thereby reducing the suppressor of cytokine signaling 3 (SOCS3), iNOS, and inflammatory mediators. AMAE-improved hyperinsulinemia also down-regulated SOCS3 by decreasing p-Stat5B in hepatocytes. AMAEs enhanced glucose uptake and conversion and decreased hepatocyte enlargement and inflammatory cells in the liver of T2DM mice. These indicated that AMAEs could alleviate oxidative stress, insulin resistance, inflammation, and tissue damage in the liver of T2DM mice through inhibiting NF-κB p65 and Stat3/5B.
10.1021/acs.jafc.2c03286
Protective effect of vanillic acid against diabetes and diabetic nephropathy by attenuating oxidative stress and upregulation of NF-κB, TNF-α and COX-2 proteins in rats.
Singh Brahmjot,Kumar Ajay,Singh Hasandeep,Kaur Sarabjit,Arora Saroj,Singh Balbir
Phytotherapy research : PTR
Diabetes is the most prevalent disorder in the world characterized by uncontrolled high blood glucose levels and nephropathy is one of the chief complications allied with hyperglycemia. Vanillic acid; the main bioactive compound derived from natural sources such as vegetables, fruits and plants possesses various pharmacological activities such as antioxidant, anti-inflammatory and anti-proliferative. The current study was designed to investigate the antidiabetic and renoprotective effects of vanillic acid by its various pharmacological activities. Streptozotocin (50 mg/kg)/nicotinamide (110 mg/kg) was used to induce diabetes in rats. Oral administration of vanillic acid once daily for 6 weeks (25, 50 and 100 mg/kg) significantly reduced the hyperglycemia, increased liver enzymes and normalized lipid profile that was altered in diabetic rats. Moreover, vanillic acid attenuated the impaired renal function as evidenced by a reduction in serum creatinine, urea, uric acid and urinary microproteinuria levels with a concomitant increase in urinary creatinine clearance in the nephropathic rats. Diabetic rats showed a marked increase in thiobarbituric acid reactive substances (TBARS) and superoxide anion generation (SAG) along with decreased reduced glutathione (GSH) in the renal tissue which was ameliorated in the vanillic acid-treated rats. Histopathologically, vanillic acid treatment was associated with reduced damage with normalized structural changes in renal tissue. Furthermore, treatment groups showed the suppression of upregulation of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, cyclo-oxygenase (COX)-2 and up-regulation of Nuclear factor-erythroid 2-related factor 2 (Nrf-2) in the renal tissue. In conclusion, vanillic acid's ameliorative impact on diabetic nephropathic rats may be attributed to its powerful free radical scavenging property, down-regulation of NF-κB, TNF-α, COX-2 and up-regulation of Nrf-2 proteins in renal tissue.
10.1002/ptr.7392
Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis.
Yang Junling,Dong Huibin,Wang Ya,Jiang Yun,Zhang Wenna,Lu Yongming,Chen Yan,Chen Lei
International journal of biological macromolecules
Diabetic nephropathy (DN), a complication of diabetes mellitus, has been the leading cause of death in people with chronic kidney disease. This study was conducted to examine the potential health benefits of Cordyceps cicadae polysaccharides (CCP) on kidney injury and renal interstitial fibrosis that occur in DN rats. First, a DN model was established using SD rats fed with a high-fat diet for 8 weeks, then injected with STZ (35 mg/kg) intraperitoneally. The rats were then supplemented with CCP (75, 150 and 300 mg/kg) for 4 weeks. The results indicated that CCP improve insulin resistance and glucose tolerance in DN rats. Furthermore, CCP intervention significantly suppressed the inflammation, renal pathological changes and renal dysfunction, slowing down the progression of renal interstitial fibrosis. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that CCP modulated the dysbiosis of gut microbiota by enhancing the relative abundance and proliferation capacity of probiotics. In vitro, CCP can markedly decrease LPS-induced inflammatory cytokine levels and TGF-β1-induced fibroblast activation. In summary, the results provided evidence that CCP exerted a beneficial effect on tubulointerstitial fibrosis in DN rats by possibly suppressing the inflammatory response and modulating gut microbiota dysbiosis, via blocking the TLR4/NF-κB and TGF-β1/Smad signaling pathway.
10.1016/j.ijbiomac.2020.06.153
Licorice extract ameliorates hyperglycemia through reshaping gut microbiota structure and inhibiting TLR4/NF-κB signaling pathway in type 2 diabetic mice.
Zhang Yongli,Xu Yanni,Zhang Ling,Chen Yijun,Wu Tao,Liu Rui,Sui Wenjie,Zhu Qiaomei,Zhang Min
Food research international (Ottawa, Ont.)
Previous studies suggested that licorice possessed hypoglycemic activity, but its anti-diabetic mechanism has not been clearly illustrated. Herein, we aimed to investigate the hypoglycemic activity and underlying hypoglycemic mechanisms of licorice extract (20, 40, and 80 mg kgday) in type 2 diabetes mice. The results showed that licorice extract could improve the levels of fasting blood glucose, insulin resistance, serum lipids, and endotoxemia-related colonic inflammation in diabetic mice in a dose-dependent manner. Western blots also suggested that a high-dose licorice extract could effectively decrease the levels of nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), and tumor necrosis factor-α (TNF-α) in colon of diabetic mice. More importantly, all the doses of licorice extract reshaped the gut microbiota by decreasing the contents of Lachnospiraceae_NK4A136_group at the genus level and increasing the contents of Alloprevotella, Bacteroides, and Akkermansia, especially for the high-dose of licorice extract. These results indicated that the anti-diabetic effect of licorice extract might be attributed to the regulation of the gut microbiota and the colon TLR4/NF-κB signaling pathway in diabetic mice. Thus, licorice extract can be a promising dietary agent to improve type 2 diabetes.
10.1016/j.foodres.2022.110945
Cordyceps militaris polysaccharide alleviates diabetic symptoms by regulating gut microbiota against TLR4/NF-κB pathway.
International journal of biological macromolecules
The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has attracted increasing attention. In our work, one purified fraction a (AEPSa) was obtained from Cordyceps militaris polysaccharides, and its hypoglycemic activity and underlying mechanisms were investigated in high-fat diet (HFD)- and streptozotocin (STZ)-induced T2DM mice. The results revealed that AEPSa reshaped gut microbiota by increasing Allobaculum, Alistipes, Lachnospiraceae_NK4A136_group and norank_f_Muribaculaceae and decreasing Enterococcus and Ruminococcus_torques_group to inhibit the colonic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and upregulate intestinal tight junction protein expression, thereby improving glucose and serum lipid metabolism, hormone secretion and complications. Fecal microbiota transplantation (FMT) also confirmed these findings. These results indicated that symptomatic relief of T2DM might be related to AEPSa regulating the gut microbiota against the TLR4/NF-κB pathway to protect the intestinal barrier. Therefore, AEPSa might be developed as a prebiotic agent against T2DM by regulating gut microbiota.
10.1016/j.ijbiomac.2023.123241
Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Regulating of Intestinal Flora and the TLR4/NF-κB Signaling Pathway in C57BL/6 Mice.
Chen Hongwei,Yang Haixia,Deng Jianjun,Fan Daidi
Journal of agricultural and food chemistry
Obesity-induced colonic inflammation-stimulated colitis is one of the main causes of colorectal cancer. Dietary phytochemicals are considered to be an effective strategy for relieving obesity-induced inflammatory diseases such as diabetes and colitis. Ginsenoside Rk3 (Rk3) is the main bioactive component of ginseng. Our previous study has demonstrated that Rk3 can effectively alleviate obesity-induced type 2 diabetes, but whether it plays a beneficial role in obesity-induced colitis remains poorly understood. Here, we found that Rk3 intervention repaired the intestinal barrier dysfunction by increasing the expression of the tight junction proteins (zonula occludens-1, claudin, and occludin), and reduced colonic inflammatory cytokine levels, oxidative stress, and macrophage infiltration in high-fat diet-induced mice. Importantly, Rk3 effectively ameliorated the metabolic dysbiosis of intestinal flora with significantly decreased / ratios and suppressed the inflammatory cascade by inhibiting the TLR4/NF-κB signaling pathway. Taken together, our findings indicate that Rk3 can be used as a potential natural anti-inflammatory agent to reduce chronic obesity-induced colitis.
10.1021/acs.jafc.0c07805
Compound Danshen Dripping Pills moderate intestinal flora and the TLR4/MyD88/NF-κB signaling pathway in alleviating cognitive dysfunction in type 2 diabetic KK-Ay mice.
Phytomedicine : international journal of phytotherapy and phytopharmacology
BACKGROUD:Bidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown. PURPOSE:An extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction. METHODS:For 12 weeks, KK-Ay mice, a spontaneous T2DM model, were intragastrically administered various doses of CDDP solution or an equivalent volume of water, and the nootropic drug piracetam was orally administered as a positive control. At the 12th week, cognition was assessed using Morris water maze tests and brain magnetic resonance imaging (MRI). Furthermore, transcriptomics, metabolomics, and network pharmacology analyses were applied to reveal novel molecular mechanisms of CDDP-treatment in diabetic cognitive dysfunction of KK-Ay mice, which were then validated using quantitative real-time polymerase chain reaction and Western blot. RESULTS:Here we verified that CDDP can suppress inflammatory response and alleviate the cognitive dysfunction in KK-Ay mice. Also, as demonstrated by 16S rRNA sequencing and short-chain fatty acids (SCFAs) analysis, CDDP attenuated intestinal flora disorder as well as increases of metabolites including butyric acid, hexanoic acid, and isohexic acid. Given the integrated analyses of network pharmacology, transcriptomic, metabolomic data, and molecular biology, the TLR4/MyD88/NF-κB signaling pathway was activated in diabetes, which could be reversed by CDDP. CONCLUSIONS:Our findings demonstrate that CDDP restructures the gut microbiota composition and increased the intestinal SCFAs in KK-Ay mice, which might inhibit neuroinflammation, and thus improve diabetic mice cognitive disorder.
10.1016/j.phymed.2023.154656
PKCβ/NF-κB pathway in diabetic atrial remodeling.
Wang Haili,Xu Yuanyuan,Xu Aiqing,Wang Xinghua,Cheng Lijun,Lee Sharen,Tse Gary,Li Guangping,Liu Tong,Fu Huaying
Journal of physiology and biochemistry
Atrial remodeling in diabetes is partially attributed to NF-κB/TGF-β signal transduction pathway activation. We examined whether the hyperglycemia-induced increased expression of NF-κB/TGF-β was dependent upon protein kinase C-β (PKCβ) and tested the hypothesis that selective inhibition of PKCβ using ruboxistaurin (RBX) can reduce NF-κB/TGF-β expression and inhibit abnormal atrial remodeling in streptozotocin (STZ)-induced diabetic rats. The effects of PKCβ inhibition on NF-κB/TGF-β signal transduction pathway-mediated atrial remodeling were investigated in STZ-induced diabetic rats. Mouse atrial cardiomyocytes (HL-1 cells) were cultured in low- or high-glucose or mannitol conditions in the presence or absence of small interference RNA that targeted PKCβ. PKCβ inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-κBp65, p-IκB, P38MARK, TNF-α, TGF-β, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats. Exposure of cardiomyocytes to high-glucose condition activated PKCβ and increased NF-κB/TGF-β expression. Suppression of PKCβ expression by small interference RNA decreased high-glucose-induced NF-κB and extracellular signal-related kinase activation in HL-1 cells. Pharmacological inhibition of PKCβ is an effective method to reduce AF incidence in diabetic rat models by preventing NF-κB/TGF-β-mediated atrial remodeling.
10.1007/s13105-020-00769-7
Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications.
Bhattamisra Subrat Kumar,Koh Hui Min,Lim Shin Yean,Choudhury Hira,Pandey Manisha
Biomolecules
Catalpol isolated from is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords "Catalpol", "Type 1 diabetes mellitus", "Type 2 diabetes mellitus", and "diabetic complications". Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.
10.3390/biom11020323