Stroke is a major cause of mortality and disability globally, with ischemic stroke (IS) accounting for over 80% of all stroke cases. The pathological process of IS involves numerous signal molecules, among which are the highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known as sirtuins (SIRTs). SIRTs modulate various biological processes, including cell differentiation, energy metabolism, DNA repair, inflammation, and oxidative stress. Importantly, several studies have reported a correlation between SIRTs and IS. This review introduces the general aspects of SIRTs, including their distribution, subcellular location, enzyme activity, and substrate. We also discuss their regulatory roles and potential mechanisms in IS. Finally, we describe the current therapeutic methods based on SIRTs, such as pharmacotherapy, non-pharmacological therapeutic/rehabilitative interventions, epigenetic regulators, potential molecules, and stem cell-derived exosome therapy. The data collected in this study will potentially contribute to both clinical and fundamental research on SIRTs, geared towards developing effective therapeutic candidates for future treatment of IS.
1 January 2025 in The American Journal of Chinese Medicine
Importance. Panax Notoginseng Saponins (PNS) are proven to have antiplatelet effects in patients with acute ischemic stroke (AIS). Objective. To assess the efficacy and safety of PNS on antiplatelet therapy in the treatment of AIS. Methods. We searched 7 literature databases and 2 clinical studies databases for randomized controlled studies (RCTs) evaluating PNS as an adjuvant therapy for AIS. Relevant studies were retrieved and screened, and data were extracted independently by two reviewers. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was carried out with the Rev Man 5.4 software. Results. Of 8267 records identified, 43 RCTs met our inclusion criteria (n = 4170 patients). Patients assigned to PNS with conventional treatments (CTs) had improved functional independence at 90 days compared with those assigned to CTs alone (RR = 1.87, 95% CI = 1.37, to 2.55, ). Patients who received PNS combined with CTs showed significantly high improvements in neurological function among individuals with AIS on the neurologic deficit score (NDS) (MDCSS = −5.71, 95% CI = −9.55 to −1.87, ; MDNIHSS = −3.94, 95% CI = −5.65 to −2.23, ). The results also showed PNS contributed to a betterment in activities of daily living (ADL) on the Barthel index (MDday10 BI = 4.86, 95% CI = 2.18, to 7.54, ; MDday 14 BI = 13.92, 95% CI = 11.46 to 16.38, ; MDday 28 BI = 7.16, 95% CI = 0.60, to 13.72, ). In addition, PNS, compared with CTs alone, could significantly improve overall response rate (ORR) (RRNIHSS = 1.20, 95% CI = 1.16, to 1.24, ; RRCSS = 1.15, 95% CI = 1.08, to 1.24, ), hemorheological parameters, maximum platelet aggregation rate (MPAR) (MD = −6.82, 95% CI = −9.62 to −4.02, ), platelet parameters (MDPLT = 4.85, 95% CI = 1.82 to 7.84, ; MDMPV = −0.79, 95% CI = −1.09 to −0.48, ), and serum CD62P (MD = −0.21, 95% CI = −0.29 to −0.13, ). The incidence of adverse reactions in PNS was lower than that in the control group (RR = 0.62, 95% CI = 0.39 to 0.97, ). Adverse reactions in the PNS were mild adverse reactions. Conclusion. PNS may be effective and safe in treating AIS on ameliorating neurological deficit, improving activities of daily living function, and enhancing antiplatelet effects. However, more high-quality evidence is needed before it can be recommended for routine antiplatelet therapy in patients with AIS.
To date, Nao-an capsules are the only Chinese patent medicine primarily prescribed for the primary prevention of stroke. To evaluate the efficacy and safety of Nao-an capsules in the primary prevention of stroke in high-risk patients. A systematic review and meta-analysis of randomized controlled trials. We searched 7 electronic databases and 2 registries from inception to January 13, 2022 for relevant randomized controlled trials. Two independent investigators selected trials, collected data, and judged the risk of bias. We performed a meta-analysis using the Review Manager software. Nine randomized controlled trials involving 14 744 patients at high risk of stroke were included. Nao-an capsules reduced the risk of first stroke compared with no intervention (risk ratio [RR] = 0.49, 95 % confidence interval [CI] 0.29 to 0.82, p = 0.006) or aspirin (RR50 mg qd = 0.47, 95 % CI 0.25 to 0.91, p = 0.03; RR100 mg qd = 0.46, 95 % CI 0.22 to 0.99, p = 0.05), without increased bleeding risks. The certainty of evidence was evaluated as moderate to very low. In addition to controlling specific risk factors, Nao-an capsules might provide additional preventive effects on first stroke with an acceptable safety profile for populations at high risk of stroke. However, as current evidence is too weak, a firm recommendation depends on further confirmation from more studies with more rigorous methodology.