Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis.

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.

Comparative effectiveness of traditional Chinese medicine and angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and sodium glucose cotransporter inhibitors in patients with diabetic kidney disease: A systematic review and network meta-analysis.

Angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and sodium glucose cotransporter inhibitors (SGLT2i) are commonly used to treat diabetic kidney disease (DKD). Currently, increasing evidence also suggests traditional Chinese medicine (TCM) as an effective strategy. We assessed the efficacy of ACEI, ARB, SGLT2i, and TCM on major renal outcomes. We searched the electronic literature published up to March 2021 from CNKI, VIP, WanFang, SinoMed, PubMed, Embase, Cochrane Library, Web of Science, and clinicaltrials.gov; a total of 56 studies and 5464 participants were included. We found that TCM plus ACEI, TCM plus ARB, and TCM alone are very effective treatment methods compared with ACEI, ARB, and the placebo in reducing 24-h urine protein, serum creatinine, and blood urea nitrogen. TCM plus ACEI was the most effective treatment (TCM plus ACEI vs. the placebo in 24-h urine protein [mean difference (MD) - 757.18, 95% confidence interval-1177.41 to - 353.31], serum creatinine [MD - 25.81, 95% confidence interval - 35.51 to - 16.03], and blood urea nitrogen [MD - 3.48, 95% confidence interval - 5.04 to - 1.90]). Although the incidence of end-stage renal disease while receiving an TCM plus ARB compared with a placebo was not statistically significant, the treatment ranking showed this combination therapy to have the greatest probability (72.8%) of reducing end-stage renal disease mortality, followed by SGLT2i (68%). Our analyses showed that combining TCM with conventional treatments for patients with DKD can improve renoprotective effects and superiority, and ACEI plus TCM may be the most effective option for treating DKD.

Efficacy of Mudan Granule (Combined With Methylcobalamin) on Type 2 Diabetic Peripheral Neuropathy: Study Protocol for a Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm, Multi-Center Trial.

Background: Diabetic peripheral neuropathy (DPN) characterized by nerve damage is a common and disabling chronic microvascular complication in patients with type 2 diabetic mellitus (T2DM), affecting at least half of patients diagnosed with T2DM. Unfortunately, the current treatment for DPN is not ideal. Traditional Chinese medicine (TCM), with a unique theoretical system, has made outstanding contributions in the treatment of T2DM and related complications. Mudan granule, a Chinese patent medicine, has been previously validated that could ameliorate the symptoms, promote nerve tissue repair, increase nerve conduction velocity (NCV) in patients with DPN. However, the previous studies are of variable quality, which limits the clinical application of Mudan granule. Therefore, we designed a double-blind, randomized, placebo-controlled, parallel-arm, multi-center trial to estimate the safety and efficacy of Mudan granule in conjunction with methylcobalamin in individuals suffering from type 2 diabetic peripheral neuropathy. Methods: This work is conducted as a 14-center, double-blind, randomized, placebo-controlled, parallel-arm trial. In all, 402 subjects (aged 30-70 years) will be recruited and randomized in a 1:1 ratio to an intervention group (n = 201; Mudan granule + methylcobalamin) and a control group (n = 201; placebo + methylcobalamin). Treatment is administered in 24 weeks cycles without any treatment interruption between cycles. Michigan Diabetic Neuropathy Score (MDNS) as the primary outcome will be evaluated at baseline, 12 weeks during the intervention period, and after 24 weeks of the intervention. Adverse events and safety assessments will be also documented. The analysis of all data will be carried out based on a predefined statistical analysis plan. Discussion: The outcomes from this study will offer important evidence regarding the safety and efficacy that Mudan granule can be used as an alternative and complementary therapeutic intervention in patients with type 2 diabetic peripheral neuropathy. Clinical trial registration: Registered at https://clinicaltrials.gov/. Trial registration number: NCT04711980. Registered January 2021.