The favorable impacts of cardamom on related complications of diabetes: A comprehensive literature systematic review.

BACKGROUND AND AIM: Complementary and alternative medicine plays an increasing role in preventing, and regulatory, complications associated with diabetes. There are plenty of polyphenolic compounds found in Elettaria cardamomum (Cardamom) such as luteolin, limonene, pelargonidin, caffeic acid, kaempferol, gallic acid, and quercetin which can be used in many metabolic diseases. METHOD: The objective of this systematic review was to appraise evidence from clinical and in vivo studies on the effects of cardamom on inflammation, blood glucose, oxidative stress and dyslipidemia of diabetes mellitus. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the present study was carried out. Studies were conducted by searching databases such as EMBASE, Scopus, PubMed, Google Scholar, web of sciences, and Cochrane Library from the commencement until April 2022. RESULTS: All available human and animal studies examining the effects of cardamom on diabetes were published in the form of English articles. Finally, only 14 of the 241 articles met the criteria for analysis. Of the 14 articles, 8 were in vivo studies, and 6 were clinical trial studies. Most studies have indicated the beneficial effects of cardamom on insulin resistance, oxidative stress and inflammation. Cardamom also improved dyslipidemia, but had no substantial effect on weight loss. CONCLUSION: According to most studies, cardamom supplementation enhanced antioxidant enzyme production and activity in diabetes mellitus and decreased oxidative stress and inflammatory factors. Despite this, the exact mechanism of the disease needs to be identified through more clinical trials.

Comparing the Effect of Moringa Aqueous Extract and Selenium Nanoparticles Against Complications of Type 2 Diabetes Mellitus.

<b>Background and Objective:</b> Plant extracts were widely used to maintain postprandial levels and minimize diabetes complications. The main goal of this study was to evaluate the therapeutic effect of selenium nanoparticles and aqueous extract of the <i>Moringa</i> plant against diabetes mellitus complications and compare their therapeutic effects. <b>Materials and Methods:</b> Fifty six Wistar male rats were divided randomly into 8 groups (7 rats each): (i) Control, (ii): Received corn oil, (iii): Treated with Se-NPs, (iv): Injected orally with <i>Moringa</i> aqueous extract (MAE), (v): Treated with a single i.p., dose of streptozotocin (STZ), (vi): Single i.p., dose of STZ followed by Se-NPs, (vii): Treated with a single i.p., dose of STZ then MAE orally and (viii): Injected with STZ and then received Se-NPs. After 4 weeks the blood sera were isolated and stored at -20°C for investigation of values of insulin, GSH, MDA, SOD, GSH-PX, triglycerides, T-cholesterol, HDL-cholesterol and LDL-cholesterol. <b>Results:</b> The STZ treatment decreased insulin, HDL cholesterol and body weight values while increasing glucose, total cholesterol, LDL cholesterol and triglycerides and mild degeneration of islets of Langerhans. The single treatment of diabetic rats with either MAE or Se-NPs exhibited a decline in the levels of serum glucose, LDL-cholesterol, triglycerides, MDA and GSH, improving the HDL-cholesterol, insulin level and body weight. <b>Conclusion:</b> The co-administration of diabetic rats with MAE and Se-NPs resulted in a prominent improvement that was revealed by restoring beta-cell function, reducing blood glucose levels and stimulating insulin production rather than their single therapeutic use.

[Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

A Mechanistic Review on Phytomedicine and Natural Products in the Treatment of Diabetes.

Diabetes mellitus is a metabolic syndrome of excess glucose levels in the blood. It may be due to glucose intolerance by the tissues and inadequate insulin production from pancreatic ß- cells. However, diabetic complication includes cardiovascular and kidney diseases, eye, skin, and foot complications, and neuropathy. The intention behind writing this article was to gather recent information regarding the use of ancient traditional medicinal plants having recent importance in treating diabetes. Several therapies are available for curing the condition based on severity and type of diabetes. Although pharmacological treatments are effective and economical, drugs are associated with unwanted side effects and physiological complications on long-term use. Interestingly, herbs and herbal plants have been used since ancient times against diabetes worldwide. Its importance still exists due to medicinal plants' effectiveness and safety profile in treating various diseases. In this article, we searched online databases, including PUBMED, SCOPUS, MEDLINE, and traditional resources, for collecting information regarding the use of plants against diabetes. We described the pathophysiology of the disease and incorporated plant sources and their chemical constituents responsible for antidiabetic activity with their mechanism in reducing blood glucose levels. The present article may be very helpful for researchers and professionals whose work is inclined towards diabetes and in search of lead compounds for the development of a suitable drug.

Oxygen scavenging, anti-inflammatory, and antiglycation activity of pomegranate flavonoids (Punica granum) against streptozotocin toxicity induced diabetic nephropathy in rats.

Bioactive natural products are essential components for drug development. Protein glycation in diabetic subjects leads to diabetic complications as nephropathy and neuropathy. We investigated the impact of pomegranate hexane extract (PHE) as antioxidant, anti-inflammatory, and antiglycation in diabetic rats. Gas chromatography/mass spectrum (GC/MS) analysis of PHE revealed presence of resorcinol, catechol, tau-cadinol, metacetamol, scopoletin, phytol, and phenol, 3-pentadecyl as the most active ingredients that related to biological activity. Results obtained showed that, PHE increased serum aldose reductase and total antioxidant activity compared with untreated diabetic rats (p < 0.001). In addition, PHE exert antioxidant by enhancing, catalase and SOD (p < 0.001) and decreased MDA (p < 0.001), anti-inflammatory by inhibition production of 1 ß (IL-1ß), tumor necrosis factor (TNF-α) (p < 0.001), and AGEs (p < 0.001) against nephropathy in diabetic rats compared with untreated group. It was concluded that, pomegranate is promising in development a functional biomolecule in treatment and protection against diabetic complications as nephropathy. More study required to investigate the molecular action of these molecules.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Chemical Constituents Based Approach for the Management of Diabetes.

BACKGROUND: A number of complexities in compliance with long-term diabetes have been elicited. It has become a global concern without any convincing medicinal, therapeutical methodology. Both hyperglycaemia and oxidative pressure are major notable parts that play a significant role in the initialization of diabetic inconvenience. Natural medications have gained a lot of attention in recent years as expected restorative specialists in the prevention and treatment of diabetic complications due to their many objectives and less poisonous outcomes. This survey means to evaluate the accessible information on therapeutic spices for constriction and the executives of diabetic complications. MATERIALS AND METHODS: Bibliographic investigation was accomplished by checking old-style course books and papers, directing overall bases of logical information (SCOPUS, PUBMED, SCIELO, Google Scholar, NISCAIR,) to recapture accessible distributed writing. For the assessment of plants with the potential in calming diabetic complications, several inclusion models rely on the numerous medicinal spices as well as their crucial mixes. Furthermore, several models, including plants, have been considered, each of which has a suitable impact on increasing oxidative pressure in diabetes. RESULTS: Different therapeutic plants/plant withdrawals containing alkaloids, terpenoids, phenolic compounds, flavonoids, saponins, and phytosterol-type synthetic constituents were uncovered that are profitable in the administration of diabetic complexities. Results may be attributed to the improvement of oxidative pressure, constant hyperglycemia, and twitch of different metabolic pathways related to the pathogenesis of diabetic confusions. CONCLUSION: An optimistic approach for new medication terminology to treat diabetic confusion is screening compound competitors from homegrown medication. Investigation of the activity of different plant extracts as well as their potency profile and to determine their job in the treatment of diabetic inconveniences must be there. In addition, an ideal rat model which imitates human diabetic complications ought to be created.

Beneficial effects of ginsenosides on diabetic nephropathy: A systematical review and meta-analysis of preclinical evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is one of the most widely used herbs in the world for the treatment of various diseases, and ginsenoside is the representative bioactive component in ginseng. There have been many in vivo studies on ginsenoside for the treatment of diabetic nephropathy (DN), the most common diabetic microvascular complication and the main cause of diabetic morbidity and mortality. AIM OF THE STUDY: The purpose of this study is to evaluate the efficacy of ginsenosides on DN by preclinical evidence and meta-analysis. Meanwhile, the main possible action mechanisms of ginsenosides against DN were also summarized. MATERIALS AND METHODS: We systematically searched PubMed, WOS, Embase, Cochrane, WanFang, Cqvip, CNKI and CBM databases from January 1, 2000, to November 15, 2021, to evaluate the animal experiments of ginsenosides for the treatment of DN. Finally, 30 animal experiments were included. Twelve outcome measures, including renal function indicators (24-h urine protein, serum creatinine, urea nitrogen, creatinine clearance, uric acid, urinary albumin to creatinine ratio), oxidative stress biomarkers (GPX, MDA, SOD), inflammatory factors (IL-1, IL-6, TNF-α) were obtained by using RevMan 5.4 software for meta-analysis. RESULTS: The results showed that except for no significant difference in CCr, other indicators such as 24h UP, SCr, blood urea nitrogen, uric acid and UACR were significantly decreased. It showed that ginsenoside could improve renal function in diabetes. Meanwhile ginsenoside significantly up-regulated antioxidant enzymes SOD and GPX, down-regulated MDA and inflammatory factors IL-1, IL-6 and TNF-α, indicating that ginsenoside may have antioxidant and anti-inflammatory effects. CONCLUSION: Ginsenoside can protect against the renal failure in diabetes through anti-inflammation, anti-oxidation, anti-renal fibrosis, anti-apoptosis/pyroptosis, regulation of blood glucose/lipid metabolism, etc. Which provides preclinical evidence for the application of ginsenoside in the treatment of DN.

Metabolomics-based evidence of the hypoglycemic effect and alleviation of diabetic complications by Ficus racemosa fruit in diabetic mice.

The hypoglycemic and metabolic effects of Ficus racemosa fruit were studied in diabetic mice, and its potential mechanisms of hypoglycemic activity and its alleviation of diabetic complications were explored using a metabolomics approach. The histopathological effect of Ficus racemosa fruit was characterized by hematoxylin and eosin histological staining. Dynamic fasting blood glucose (FBG), postprandial glucose (PPG), body weight, and biochemical parameters, including hepatic-renal function and lipid levels, were monitored to confirm the hypoglycemic activity and attenuation effect. The metabolomics analysis was performed using the established platform, combining liquid chromatography-tandem mass spectrometry with statistical analysis to identify the metabolites internally regulated by Ficus racemosa fruit. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to explore the presence and spatial distribution patterns of differential molecules further. An inhibition of blood glucose levels and improvements in tissue lesions were observed after Ficus racemosa fruit treatment, especially with high-dose treatment. Ficus racemosa fruit primarily induced metabolomic alterations in amino acids, organic acids and nucleotides, and displayed a systematic effect, which involved the mediation of amino acid metabolism, glucose metabolism, energy metabolism and lipid accumulation. The effect of Ficus racemosa fruit on the liver was primarily discussed in this study, and it regulated purine metabolism, glycolysis/gluconeogenesis, arginine biosynthesis, histidine metabolism, alanine, aspartate and glutamate metabolism, and the citrate cycle. Through the mediation of related pathways or single molecules that could affect insulin resistance, insulin secretion or FBG, e.g., the amino acid histidine or the organic acid uric acid in the liver, Ficus racemosa fruit achieved its hypoglycemic effect and alleviated diabetic complications in the liver. The results of the tissue metabolomic analysis, histopathological analysis, plasma biochemical parameters, plasma metabolite analysis and tissue DESI-MSI analysis were consistent with one another. The present study provides the evidence of the hypoglycemic effect and its alleviation of diabetic complications for Ficus racemosa fruit as well as the scientific support for its traditional use.

Investigations of AGEs' inhibitory and nephroprotective potential of ursolic acid towards reduction of diabetic complications.

In diabetes, interactions between AGEs (advanced glycation end products) and RAGEs (receptors of AGEs) are responsible for chronic complications and the current work reports the potential of ursolic acid as a RAGE inhibitor. The three-dimensional crystal structure of RAGE was first docked with target molecules by 'AutodockVina' using GROMOS 96 4381 parameters. Druggability and pharmacokinetic properties were calculated from the SwissADME server. In vitro bovine serum albumin (BSA)-glucose fluorescence and BSA-methylglyoxal fluorescence assays were also performed. Finally, alloxan-induced diabetic mice were administered ursolic acid and metformin standards (at 1, 50, 100 mg/kg) for 50 days. Blood glucose levels, several blood parameters, blood lipid profiles, supernatants of homogenized kidney and plasma of mice were examined. In the computational study, ursolic acid showed greater binding affinity (-7.5 kcal/mol) for RAGE with an ADMET profiles and lead-likeness compared to metformin as a standard antidiabetic. In the in vitro fluorescence assays, the IC50 value for ursolic acid was much less than that of metformin standard. During the in vivo study, significant reduction in the levels of blood glucose, HbA1C (glycated hemoglobin), creatinine, uric acid, BUN (blood urea nitrogen), AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase) were observed in the ursolic acid and metformin-treated mice. Substantial inhibition of AGEs' formation in the plasma and kidney were also detected. Finally, the histopathological examinations of the kidney revealed reversal of cellular necrosis. Hence, ursolic acid is proved to be a potent AGE inhibitory agent in managing the diabetic complications.

A Systematic Review of Orthosiphon stamineus Benth. in the Treatment of Diabetes and Its Complications.

(1) Background: Orthosiphon stamineus Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a chronic metabolic disease and the number of diabetic patients in the world is increasing. This review aimed to systematically review the effects of O. stamineus in the treatment of diabetes and its complications and the pharmacodynamic material basis. (2) Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the databases ScienceDirect, PubMed, and Web of Science. (3) Results: Thirty-one articles related to O. stamineus and diabetes were included. The mechanisms of O. stamineus in the treatment of diabetes and its complications mainly included inhibiting α-amylase and α-glucosidase activities, antioxidant and anti-inflammatory activities, regulating lipid metabolism, promoting insulin secretion, ameliorating insulin resistance, increasing glucose uptake, promoting glycolysis, inhibiting gluconeogenesis, promoting glucagon-likepeptide-1 (GLP-1) secretion and antiglycation activity. Phenolic acids, flavonoids and triterpenoids might be the main components for hypoglycemia effects in O. stamineus. (4) Conclusion: O. stamineus could be an antidiabetic agent to treat diabetes and its complications. However, it needs further study on a pharmacodynamic substance basis and the mechanisms of effective constituents.

Curcumin and Its Analogs as Potential Epigenetic Modulators: Prevention of Diabetes and Its Complications.

BACKGROUND: The pathobiology of diabetes and associated complications has been widely researched in various countries, but effective prevention and treatment methods are still insufficient. Diabetes is a metabolic disorder of carbohydrates, fats, and proteins caused by an absence of insulin or insulin resistance, which mediates an increase of oxidative stress, release of inflammatory factors, and macro- or micro-circulation dysfunctions, ultimately developing into diverse complications. SUMMARY: In the last decade through pathogenesis research, epigenetics has been found to affect metabolic diseases. Particularly, DNA methylation, histone acetylation, and miRNAs promote or inhibit diabetes and complications by regulating the expression of related factors. Curcumin has a wide range of beneficial pharmacological activities, including anti-inflammatory, anti-oxidation, anticancer, anti-diabetes, anti-rheumatism, and increased immunity. Key Messages: In this review, we discuss the effects of curcumin and analogs on diabetes and associated complications through epigenetics, and we summarize the preclinical and clinical researches for curcumin and its analogs in terms of management of diabetes and associated complications, which may provide an insight into the development of targeted therapy of endocrine diseases.

The signaling pathways of traditional Chinese medicine in promoting diabetic wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: The diabetic wound is one of the common chronic complications of diabetes, which seriously affects patients' quality of life and even causes disability and death. Traditional Chinese medicine (TCM) is a unique and precious resource in China, which has a good curative effect and safety. At present, it has been found that Chinese herbal compounds and effective active ingredients can effectively promote diabetic wound healing, and its mechanism needs to be further studied. Signaling pathways are involved in the pathogenesis and progression of diabetic wounds, which is one of the main targets for the pathologic mechanism of diabetic wounds and the pharmacological research of therapeutic drugs. AIM OF THE REVIEW: This study has been carried out to reveal the classical signaling pathways and potential targets by the action of TCM on diabetic wound healing and provides evidence for its clinical efficacy. MATERIALS AND METHODS: "diabetic wound", "diabetic foot ulcer", "traditional Chinese medicine", "natural plant" and "medicinal plant", were selected as the main keywords, and various online search engines, such as PubMed, Web of Science, CNKI and other publication resources, were used for searching literature. RESULTS: The results showed that TCM could regulate the signaling pathways to promote diabetic wound healing, such as Wnt, Nrf2/ARE, MAPK, PI3K/Akt, NF-κB, Notch, TGF-ß/Smad, HIF-1α/VEGF, which maintaining inflammatory interaction balance, inhibiting oxidative stress and regulating abnormal glucose metabolism. CONCLUSION: The effect of TCM on diabetic wound healing was reflected in multiple levels and multiple pathways. It is envisaged to carry out further research from precision-targeted therapy, provide ideas for screening the core target of TCM in treating diabetic wounds and create modern innovative drugs based on this target.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Recent Insights into the Nutritional Antioxidant Therapy in Prevention and Treatment of Diabetic Vascular Complications: A Comprehensive Review.

Diabetes mellitus (DM) and DM-induced vascular complications are significant global healthcare problems, causing a decrease in patient quality of life. The main reason for the disability and mortality of patients is rapidly progressing micro-and macroangiopathies. Currently, free radical oxidation is recognized as one of the main mechanisms in the development of DM and associated complications. Under normal physiological conditions, the level of free radicals and antioxidant defense capabilities is balanced. However, imbalance occurs between the antioxidant defense system and pro-oxidants during chronic hyperglycemia and may invoke the formation of excess free radicals, leading to activation of lipid peroxidation and accumulation of highly toxic products of free radical oxidation. This is accompanied by varying degrees of insulin deficiency and insulin resistance in DM patients. Simultaneously with the activation of free radical generation, a decrease in the activity of antioxidant defense factors (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamins C and E) and an acceleration of diabetic complications are seen. Therefore, we hypothesize that antioxidants may play a positive role in the treatment of DM patients to prevent DM-induced vascular complications. However, this has not been sufficiently studied. In this review, we discuss recent insights into the potential underlying mechanisms of oxidative stress-induced diabetic complications and the implications of antioxidants in mitigation of DM-induced vascular complications.

The Therapeutic Effect and Mechanism of Qishen Yiqi Dripping Pills on Cardiovascular and Cerebrovascular Diseases and Diabetic Complications.

The alterations in vascular homeostasis are deeply involved in the development of numerous diseases, such as coronary heart disease, stroke, and diabetic complications. Changes in blood flow and endothelial permeability caused by vascular dysfunction are the common mechanisms for these three types of diseases. The disorders of glucose and lipid metabolism can bring changes in the energy production patterns in endothelium and surrounding cells which may consequently cause energy metabolic disorders, oxidative stress, and inflammatory responses. Traditional Chinese medicine (TCM) follows the principle of the "treatment by the syndrome differentiation." TCM considers coronary heart disease, stroke, and diabetes complications all as the type of Qi-deficiency and blood stasis syndrome, which mainly occurs in the vascular system. Therefore, the common pathogenesis of these three types of diseases suggests that the treatment strategy by TCM should be in a close manner and referred to as "treating different diseases by the same treatment." Qishen Yiqi dripping pill is a modern Chinese herbal medicine that has been widely used for the treatment of patients with coronary heart disease characterized as Qi-deficiency and blood stasis in China. Recently, many clinical reports have demonstrated the potential therapeutic effects of Qishen Yiqi dripping pills on ischemic stroke and diabetic nephropathy. Based on these reports, we will summarize the clinical applications of Qishen Yiqi dripping pills on coronary heart disease, ischemic stroke, and diabetic nephropathy, including the involved mechanisms discussed in various research works.

Diabetes and zinc dyshomeostasis: Can zinc supplementation mitigate diabetic complications?

Zinc present in the islet cells of the pancreas is crucial for the synthesis, storage, and secretion of insulin. The excretion of large amounts of zinc from the body is reported in diabetic situations. Zinc depletion and increased oxidative stress have a major impact on the pathogenesis of diabetic complications. It would be most relevant to ascertain if intervention with supplemental zinc compensating for its depletion would beneficially mitigate hyperglycemia and the attendant metabolic abnormalities, and secondary complications in diabetes. An exhaustive literature search on this issue indicates: (1) Concurrent hypozincemia and decreased tissue zinc stores in diabetes as a result of its increased urinary excretion and/or decreased intestinal absorption, (2) Several recent experimental studies have documented that supplemental zinc has a potential hypoglycemic effect in the diabetic situation, and also beneficially modulate the attendant metabolic abnormalities and compromised antioxidant status, and (3) Supplemental zinc also alleviates renal lesions, cataract and the risk of cardiovascular disease accompanying diabetes mellitus, and help restore gastrointestinal health in experimental diabetes. These studies have also attempted to identify the precise mechanisms responsible for zinc-mediated beneficial effects in diabetic situation. The evidence discussed in this review highlights that supplemental zinc may significantly contribute to its clinical application in the management of diabetic hyperglycemia and related metabolic abnormalities, and in the alleviation of secondary complications resulting from diabetic oxidative stress.

The Potential Role of Curcumin in Modulating the Master Antioxidant Pathway in Diabetic Hypoxia-Induced Complications.

Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells' redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.

Efficacy Evaluation of Plant Products in the Treatment of Erectile Dysfunction Related to Diabetes.

Erectile dysfunction affects more than 50% of diabetic male patients, with a higher prevalence compared with the general population. Age, clinical factors, and lifestyle habits have been suggested to contribute to the pathophysiology and worsening of erectile dysfunction in diabetic patients. First- and second-line standard treatments are represented by phosphodiesterase type 5 (PDE5) inhibitors and alprostadil, respectively. However, natural compounds have been suggested to ameliorate this clinical condition. This study aims to preclinically characterize the potential synergism among plant-derived products for the improvement of erectile dysfunction in the diabetic condition. The effects of a nutritional supplement composed of Panax ginseng, Moringa oleifera and rutin, as single agents or as a mixture, were evaluated in a streptozotocin (STZ)-induced diabetic rat model with erectile dysfunction. The treatment efficacy was evaluated by measuring sexual-related parameters (i.e., mount and intromission latencies, the mount and intromission frequencies and the ejaculation latency). Results showed that only the mixture was able to significantly reduce the diabetes-related delay in mount latency (p < 0.01). Substantial similar effects were observed by measuring the intromission latency and the mean number of mounts was very similar between rats treated with the mixture and controls. Single agent treatments showed very low effects in terms of intromission frequency, whereas the mixture was able to increase this parameter. Additionally, a statistically significant reduced ejaculation latency was observed in rats treated with the mixture compared with the STZ control. These results are in agreement with the available literature and suggest that the study mixture may ameliorate sexual behavior compared with the administration of the study natural compounds as single agents in diabetic rats. Further preclinical and clinical studies are needed to perform a more comprehensive evaluation of the efficacy and safety of the study mixture.

11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes.

Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day intravitally up to wound closure. Wounds were stained for VEGF, CD31, TGF-ß, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-ß level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.