Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

Objective: This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Methods: Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. Results: A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. Conclusion: DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

[Role of mitophagy in diabetes mellitus and its complications and traditional Chinese medicine intervention: a review].

Diabetes mellitus(DM) is a chronic endocrine disease characterized by hyperglycemia caused by carbohydrate or lipid metabolism disorders or insulin dysfunction. Hyperglycemia and long-term metabolic disorders in DM can damage tissues and organs throughout the body, leading to serious complications. Mitochondrial autophagy(mitophagy) is an important mitochondrial quality control process in cells and a special autophagy phenomenon, in which damaged or redundant mitochondria can be selectively removed by autophagic lysosome, which is crucial to maintain cell stability and survival under stress. Studies have confirmed that changes in autophagy play a role in the development and control of DM and its complications. Mitophagy has become a research hotspot in recent years and it is closely associated with the pathogenesis of a variety of diseases. Substantial evidence suggests that mitophagy plays a crucial role in regulating the metabolic homeostasis in the case of DM and its complications. Because the destructive great vessel complications and microvascular complications cause increased mortality, blindness, renal failure, and declined quality of life of DM patients, it is urgent to develop targeted therapies to intervene in DM and its complications. Traditional Chinese medicine(TCM), with a multi-component, multi-target, and multi-level action manner, can prevent the development of drug resistance and have significant therapeutic effects in the prevention and treatment of DM and its complications. Therefore, exploring the mechanisms of TCM in regulating mito-phagy may become a new method for treating DM and its complications. With focus on the roles and mechanisms of mitophagy in DM and its complications, this paper summarizes and prospects the research on the treatment of DM and its complications with TCM via re-gulating mitophagy, aiming to provide new ideas for the clinical practice.

Mitigation of lens opacification by a functional food in a diabetic rodent model.

The current study was designed to test a functional food (FF) mixture containing aldose reductase inhibitors and antiglycation bioactive compounds for suppressing the onset and progression of cataracts in a diabetic rat model. Two-month-old Sprague Dawley rats were grouped as control (C), diabetes untreated (D), and diabetic rats treated with FF at two doses (FF1 = 1.35 g and FF2 = 6.25 g/100g of diet). Diabetes was induced by a single injection of streptozotocin. The FF is a mixture of amla, turmeric, black pepper, cinnamon, ginger, and fenugreek added to the rodent diet. The status of cataracts was monitored weekly by a slit lamp examination for 20 weeks, after which animals were sacrificed to collect eye lenses. Feeding FF1 and FF2 to diabetic rats yielded a significant anti-hyperglycaemic effect and marginally prevented body weight loss. FF delayed cataract progression, and FF2 showed better efficacy than FF1. FF prevented the loss of lens crystallins and their insolubilization in diabetic rats. The antioxidant potential of FF was evident with the lowered protein carbonyls, lipid peroxidation, and prevention of altered antioxidant enzyme activities induced by diabetes. These studies demonstrate the efficacy of plant-derived dietary supplements against the onset and progression of cataracts in a well-established rat model of diabetic eye disease.

Targeting ferroptosis: New perspectives of Chinese herbal medicine in the treatment of diabetes and its complications.

Ferroptosis is a non-apoptotic mode of cell death. A large number of studies have confirmed that ferroptosis plays a vital role in the occurrence and development of diabetes and diabetic complications. Previous studies have found that Chinese herbal medicines have very promising results in the prevention and treatment of diabetes and diabetic complications, and some of these herbs or herbal natural compounds may act via the inhibition of ferroptosis. In this review, we summarized the relationship between ferroptosis and diabetes and diabetic complications, and discussed its molecular mechanisms. We also reviewed the published studies of herbal medicines or herbal natural compounds that improved diabetes or diabetic complications via the ferroptosis pathway. In addition, we are trying to provide new insights for better treatment of diabetes and diabetic complications with Chinese herbal medicine and its herbal compounds.

Piperine as a Potential Nutraceutical Agent for Managing Diabetes and Its Complications: A Literature Review.

The global prevalence of diabetes and its related complications has increased drastically and is currently a worldwide health challenge. There is still an urgent need for safe and effective natural products and supplements as alternative and/or adjunctive therapeutic interventions. Nowadays, people pay more and more attention to the nutritional and medicinal value of food ingredients. As one of the most widely employed spices in cooking, pepper also has novel medicinal values attributed to its main component, piperine (Pip). Pip is an amide alkaloid with pleiotropic properties such as anti-inflammatory, antioxidant, anti-cancer, and other related activities. Recently, Pip has received increasing scientific attention due to its antidiabetic and related complication properties. However, the values of existing studies are limited due to being scattered and unsystematic. The present study reviewed the therapeutic potential and possible mechanisms of Pip in diabetes and related complications, with the aim of providing promising candidates for the development of novel and effective alternative and/or adjunctive nutraceutical agents for the management of diabetes.

Systematic evaluation of combined herbal adjuvant therapy for proliferative diabetic retinopathy.

Objective: To evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis. Methods: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures. Results: A total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 (CI: 2.18-4.10, I2 = 42.7%, P<0.05); Visual acuity MD=0.10(CI: 0.06-0.13, I2 = 0%, P<0.05); Fundus efficacy OR=5.47 (CI: 1.33-22.51, I2 = 71.4%, P<0.05); Neovascularisation regression rate OR=8 (CI: 3.83-16.71, I2 = 30.1%, P<0.05); Macular foveal thickness MD=-44.24 (CI: -84.55-3.93, I2 = 95.6%, P<0.05); Absorption of vitreous hemorrhage OR=4.7 (CI: 2.26-9.77, I2 = 0%, P<0.05); Fasting blood glucose MD=-0.23, (CI: -0.38-0.07, I2 = 0%, P<0.05); 2h postprandial blood glucose MD=-0.19 (CI: -0.52-0.14, I2 = 0%, P=0.25). From the results, the combined Chinese medicine adjuvant therapy showed better efficacy than the control group. A total of 69 kinds of traditional Chinese medicine were involved in 18 studies, among which the top four applied frequencies were Panax notoginseng, Rehmannia rehmannii, Astragalus membranaceus and Poria cocos. Most of the medicines were sweet and bitter in taste, the qi tended to be slight cold and cold, and the meridian tropism belongs to the liver meridian. Conclusion: The combination of traditional Chinese medicine adjuvant therapy has a good curative effect on PDR patients. However, the relevant clinical trials are few and more high-quality clinical trials are still needed, what's more the attention should be paid to the exploration of its safety.

The protective effects of flavonoids and carotenoids against diabetic complications-A review of in vivo evidence.

Diabetes mellitus is a chronic metabolic disorder caused either by inadequate insulin secretion, impaired insulin function, or both. Uncontrolled diabetes is characterized by hyperglycemia which over time leads to fatal damage to both macro-and microvascular systems, causing complications such as cardiovascular diseases, retinopathy and nephropathy. Diabetes management is conventionally delivered through modifications of diet and lifestyle and pharmacological treatment, using antidiabetic drugs, and ultimately insulin injections. However, the side effects and financial cost of medications often reduce patient compliance to treatment, negatively affecting their health outcomes. Natural phytochemicals from edible plants such as fruits and vegetables (F&V) and medicinal herbs have drawn a growing interest as potential therapeutic agents for treating diabetes and preventing the onset and progression of diabetic complications. Flavonoids, the most abundant polyphenols in the human diet, have shown antidiabetic effects in numerous in vitro and preclinical studies. The underlying mechanisms have been linked to their antioxidant, anti-inflammatory and immunomodulatory activities. Carotenoids, another major group of dietary phytochemicals, have also shown antidiabetic potential in recent in vitro and in vivo experimental models, possibly through a mechanism of action similar to that of flavonoids. However, scientific evidence on the efficacy of these phytochemicals in treating diabetes or preventing the onset and progression of its complications in clinical settings is scarce, which delays the translation of animal study evidence to human applications and also limits the knowledge on their modes of actions in diabetes management. This review is aimed to highlight the potential roles of flavonoids and carotenoids in preventing or ameliorating diabetes-related complications based on in vivo study evidence, i.e., an array of preclinical animal studies and human intervention trials. The current general consensus of the underlying mechanisms of action exerted by both groups of phytochemicals is that their anti-inflammatory action is key. However, other potential mechanisms of action are considered. In total, 50 in vivo studies were selected for a review after a comprehensive database search via PubMed and ScienceDirect from January 2002 to August 2022. The key words used for analysis are type-2 diabetes (T2DM), diabetic complications, flavonoids, carotenoids, antioxidant, anti-inflammatory, mechanisms of prevention and amelioration, animal studies and human interventions.

Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment.

Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.

Garlic (Allium sativum L.) in diabetes and its complications: Recent advances in mechanisms of action.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia and impaired islet secretion that places a heavy burden on the global health care system due to its high incidence rate, long disease course and many complications. Fortunately, garlic (Allium sativum L.), a well-known medicinal plant and functional food without the toxicity and side effects of conventional drugs, has shown positive effects in the treatment of diabetes and its complications. With interdisciplinary development and in-depth exploration, we offer a clear and comprehensive summary of the research from the past ten years, focusing on the mechanisms and development processes of garlic in the treatment of diabetes and its complications, aiming to provide a new perspective for the treatment of diabetes and promote the efficient development of this field.

Common Ayurvedic, Chinese traditional and Unani antidiabetic formulations- a review.

Diabetes mellitus is the most widely recognized endocrine disorder which is influencing a bigger populace on the planet. There are various causes of diabetes, such as physical inactivity, obesity, family history, race, and age. Diabetes mellitus is associated with some life-threatening complications, such as neuropathy, nephropathy, various eye diseases or retinopathy, and cardiovascular disorders. Many synthetic antihyperglycemic agents are available in the market for the treatment of diabetes and its complications. But, due to some serious side effects of these synthetic agents, people are opting for herbal remedies and, therefore, they are now becoming popular. Herbal remedies have lesser side effects and higher affordability and therefore can be preferably used over synthetic agents for a long-term disorder like diabetes mellitus. In the present study, scientific research and review studies on the topic were collected from Science Direct, Scopus, PubMed, Google Scholar, and other relevant sources. The references of all the articles were screened manually for any additional information on popular polyherbal formulations in traditional Ayurvedic, Chinese, and Unani medicinal systems. It is found that these polyherbal formulations are studied for anti-diabetic potential. Furthermore, some are also investigated for mechanism of action of anti-diabetic effects. This review highlights various Ayurvedic, Chinese, and Unani polyherbal formulations commonly utilized in the management of diabetes mellitus along with their pre-clinical and clinical investigations, which will enhance the existing knowledge of the researchers.

Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, which is characterized by hyperglycemia, chronic insulin resistance, progressive decline in ß-cell function, and defect in insulin secretion. It has become one of the leading causes of death worldwide. At present, there is no cure for T2DM, but it can be treated, and blood glucose levels can be controlled. It has been reported that diabetic patients may suffer from the adverse effects of conventional medicine. Therefore, alternative therapy, such as traditional Chinese medicine (TCM), can be used to manage and treat diabetes. In this review, glycyrrhizic acid (GL) and its derivatives are suggested to be promising candidates for the treatment of T2DM and its complications. It is the principal bioactive constituent in licorice, one type of TCM. This review comprehensively summarized the therapeutic effects and related mechanisms of GL and its derivatives in managing blood glucose levels and treating T2DM and its complications. In addition, it also discusses existing clinical trials and highlights the research gap in clinical research. In summary, this review can provide a further understanding of GL and its derivatives in T2DM as well as its complications and recent progress in the development of potential drugs targeting T2DM.

Use of Ferulic Acid in the Management of Diabetes Mellitus and Its Complications.

Diabetes mellitus, a metabolic disease mainly characterized by hyperglycemia, is becoming a serious social health problem worldwide with growing prevalence. Many natural compounds have been found to be effective in the prevention and treatment of diabetes, with negligible toxic effects. Ferulic acid (FA), a phenolic compound commonly found in medicinal herbs and the daily diet, was proved to have several pharmacological effects such as antihyperglycemic, antihyperlipidemic and antioxidant actions, which are beneficial to the management of diabetes and its complications. Data from PubMed, EM-BASE, Web of Science and CNKI were searched with the keywords ferulic acid and diabetes mellitus. Finally, 28 articles were identified after literature screening, and the research progress of FA for the management of DM and its complications was summarized in the review, in order to provide references for further research and medical applications of FA.

A randomized placebo-compared study on the efficacy of classical ayurvedic pharmaceutical form versus aqueous alcoholic extracts of Phyllanthus niruri Linn. Plus Sida cordifolia Linn. in patients of diabetic sensory polyneuropathy.

BACKGROUND: In routine, Ayurveda practitioners prefer classical pharmaceutical form of herbal medicines in compare to modern extracts. OBJECTIVE: To explore the difference of efficiency between whole drug powder of Phyllanthus niruri plus root decoction of Sida cordifolia and modern extracts of the same in compared to placebo in patients of diabetic poly-neuropathy. MATERIAL AND METHODS: A randomized, partly-double-blinded, placebo-controlled trial evaluated the efficacy of two different pharmaceutical forms of herbal medicines over placebo in 90 patients (30 in each group) of diabetic sensory polyneuropathy for first three weeks period. After three weeks, active herbal medication groups were continued with their assigned medicaments for next 5 weeks period and all placebo-patients were randomized again into 2 groups of active medication and treated for next 8 weeks. Patients were assessed with Neuropathy Total Symptom Score 6 and sensation thresholds. RESULTS: Significant effect of both form of herbal medicines over placebo was found in aching pain [F (2, 49) = 6.79, p = 0.002], allodynia [F (2, 59) = 6.74, p = 0.002], burning pain [F (2, 82) = 14.66, p < 0.0001], numbness [F (2, 77) = 16.37, p < 0.0001] and pricking pain [F (2, 50) = 14.23, p < 0.0001]. After the 8 weeks period, no significant difference was identified between the effect of both the herbal treatment on aching pain (U = 220, p = 0.03), allodynia (U = 421.5, p = 0.29), burning pain (U = 881.5, p = 0.846), numbness (U = 778, p = 0.92) and pricking pain (U = 260, p = 0.15). CONCLUSION: Both herbal groups have significant effect to reduce NTSS-6 score in compare to placebo. No significant difference found between the effect of two different pharmaceutical forms of Phyllanthus niruri and S. cordifolia.

Impact of Dietitian-Led Nutrition Therapy of Food Order on 5-Year Glycemic Control in Outpatients with Type 2 Diabetes at Primary Care Clinic: Retrospective Cohort Study.

The aim of this retrospective cohort study was to evaluate the effect of 5-year follow-up of dietitian-led medical nutrition therapy (eating vegetables before carbohydrates) on glycemic control in outpatients with type 2 diabetes (T2DM) at a primary care clinic. A total of 138 patients with dietitian-led medical nutrition therapy (intervention group) and 104 patients without dietitian-led nutrition therapy (control group) were compared for glycemic control, serum lipid, blood pressure, and diabetic complications for 5 years. Each patient in the intervention group received dietary education focused on food order (eating vegetables before carbohydrates) by dietitians. A significant improvement in HbA1c after 5 years in the intervention group [8.5 ± 1.7% (69 mmol/mol) to 7.6 ± 1.1% (59 mmol/mol), p < 0.001] was observed, whereas no change was observed in the control group [7.9 ± 1.2% (62 mmol/mol) to 8.0 ± 1.2% (63 mmol/mol)]. Dietary intake of protein, fat, carbohydrates, cholesterol, and salt in the intervention group demonstrated significant reduction, while the intake of dietary fiber significantly increased after the dietary education. Simple dietary education of 'eating vegetables before carbohydrates' presented by dietitians achieved good glycemic control after a 5-year period in outpatients with T2DM at primary care clinic.

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review.

The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications. Hesperetin (Hst), a citrus flavonoid, is of increasing interest in scientific studies recently due to its properties in combating diabetes and its complications, whereas existing studies are scattered and unsystematic. Here, we summarized the literature studies over the last 10 years to review the potential therapeutic role of Hst in the prevention and mitigation of diabetes and its complications, intending to provide promising strategies for the clinical management of diabetes and its complications.

Hyperbaric oxygen therapy as an adjunct to the standard wound care for the treatment of diabetic foot ulcers in Indian patients: a cost utility analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is a common complication of diabetes. Hyperbaric oxygen therapy (HBOT) is an adjunct treatment that expedites the healing of DFU. AIM: To evaluate the cost-utility of using standard wound care (SWC) plus HBOT as compared to SWC alone for the treatment of DFU from a societal perspective in the Indian context. METHOD: A Markov decision analysis model comparing SWC with and without HBOT was developed. Data for the model were derived from relevant literature and secondary data from India. The main outcome measures were minor and major lower extremity amputations (LEA) averted, incremental quality-adjusted-life-years (QALY) gained, incremental costs, incremental cost-effectiveness ratio (ICER) per amputation averted and ICER per QALY gained. Sensitivity and threshold analyses were also done. RESULT: HBOT, when added to SWC, lowered the proportion of minor LEA and major LEA among patients with DFU by 6.1% and 4.2%, respectively. The discounted ICER was INR 193,939 [95% CI: 186,745-203,753] or US$ 2,621 [95% CI: 2,524-2,753] per QALY gained. CONCLUSION: SWC plus HBOT is not cost-effective in India. Additional information is required on patient experiences with adjunctive HBOT, if it were to be adopted as the standard of care in India.

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.

Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis.

BACKGROUND: Aberrant angiogenesis plays a fateful role in the development of diabetes and diabetic complications. Lipids, as a diverse group of biomacromolecules, are able to relieve diabetes through the modulation of angiogenesis. OBJECTIVES: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis. METHODS: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane. RESULTS: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) with neovasculogenesis dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol- α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema. CONCLUSION: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

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.

Azadirachta indica A. Juss (neem) against diabetes mellitus: a critical review on its phytochemistry, pharmacology, and toxicology.

OBJECTIVE: We aim to provide a critical review focused on the various pharmacological activities of Azadirachta indica A. Juss related to diabetes management. We also emphasise on phytochemistry and toxicology of A. indica, which could provide a comprehensive approach for plant-based drug development in future. KEY FINDINGS: From 2784 identified studies, only 83 were considered after double screening based on the inclusion criteria. Further, 63 pharmacological investigations were considered for review. Resultant studies deliberated on using different extracts and phytochemicals of A. indica on blood glucose level, lipid profile, oxidative stress, carbohydrate digestion enzymes, diabetic complications, glucose tolerance, and uptake of glucose. SUMMARY: In the end, one can know the efficacy of A. indica as a potent antidiabetic herbal medicine. However, based on gaps in research, recommendations have been provided to evaluate A. indica. in a systematic manner to develop plant-based drugs, nutraceuticals, and to evaluate their clinical efficiency and safety against diabetes mellitus.