Eureka Herba Indonesia

Phytotherapeutic Interventions Targeting Microvascular Dysfunction in Early Non-Proliferative Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Effects on Retinal Perfusion and Function

Ramzi Amin, Muhammad Baqir — Tue, 15 Apr 2025 03:12:49 +0000

Microvascular dysfunction, encompassing impaired perfusion and subsequent functional deficits, is a hallmark of early non-proliferative diabetic retinopathy (NPDR). Phytotherapeutic agents, with their potential antioxidant, anti-inflammatory, and vasculoprotective properties, have emerged as candidate interventions. However, synthesized evidence regarding their specific impact on retinal perfusion and function in early NPDR remains limited. This systematic review and meta-analysis aimed to evaluate the efficacy of phytotherapeutic interventions on quantitative measures of retinal perfusion and visual function in patients with early NPDR. A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) published between January 2013 and December 2024. Studies evaluating any phytotherapeutic intervention versus placebo or standard care in patients with early NPDR, reporting outcomes related to retinal perfusion (including Foveal Avascular Zone [FAZ] area, capillary density via Optical Coherence Tomography Angiography [OCT-A]) or retinal function (including Best-Corrected Visual Acuity [BCVA], Contrast Sensitivity [CS], electroretinogram [ERG] parameters) were considered. Data from seven RCTs meeting eligibility criteria were analyzed. Data extraction and risk of bias assessment (Cochrane RoB 2 tool) were performed. Meta-analyses using a random-effects model were conducted for key outcomes, calculating Mean Differences (MD) or Standardized Mean Differences (SMD) with 95% Confidence Intervals (CIs). Heterogeneity was assessed using the I² statistic. Seven RCTs (total N=585 patients) were included. The interventions evaluated included Ginkgo biloba, Bilberry extract, Curcumin, Saffron, Pycnogenol, Mirtogenol, and a standardized Traditional Chinese Medicine (TCM) formula. Risk of bias across the studies varied, with concerns primarily in blinding and outcome measurement domains in some trials. Meta-analysis indicated that phytotherapeutic interventions were associated with a statistically significant improvement in retinal perfusion markers compared to control. This included a reduction in FAZ area (MD: -0.04 mm², 95% CI [-0.06, -0.02], P<0.001; I²=58%) and an increase in parafoveal superficial capillary density (MD: +1.85 %, 95% CI [+1.10, +2.60], P<0.001; I²=65%). Functional improvements were also observed, including BCVA (MD: -0.03 logMAR, 95% CI [-0.05, -0.01], P=0.005; I²=35%) and contrast sensitivity (SMD: 0.35, 95% CI [0.15, 0.55], P<0.001; I²=48%). Safety data suggested no significant increase in major adverse events compared to control groups (Risk Ratio: 1.12, 95% CI [0.75, 1.68], P=0.58; I²=0%). In conclusion, this systematic review and meta-analysis found that phytotherapeutic interventions improve retinal microvascular perfusion and associated visual function in patients with early NPDR, with an acceptable safety profile. These findings support the potential role of specific phytotherapies as adjunctive treatments in managing early diabetic microvascular changes. Further large-scale trials are warranted to confirm these benefits and explore long-term outcomes.

Curcumin Reverses Cisplatin Resistance in NSCLC via Transcriptional Suppression of ABCB1 and Functional Inhibition of P-glycoprotein: A Mechanistic and Synergistic Analysis

Khairiel Anwar, Eduardo Michael Perez, Febria Suryani, Franklin Shane — Tue, 27 Jan 2026 06:01:50 +0000

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality globally. The efficacy of Cisplatin (DDP), a first-line chemotherapeutic, is frequently compromised by multidrug resistance (MDR), primarily driven by the overexpression of the ATP-binding cassette transporter P-glycoprotein (P-gp/ABCB1). Curcumin, a polyphenol with pleiotropic pharmacological effects, has shown potential as a chemosensitizer. This study aimed to rigorously quantify the synergistic interaction between Curcumin and Cisplatin and elucidate whether the reversal of resistance is mediated through functional blockade or genetic suppression of ABCB1. We utilized the human NSCLC cell line A549 and its stable, authenticated DDP-resistant counterpart (A549/DDP). Cytotoxicity was assessed using the CCK-8 assay with strict vehicle controls. Drug synergy was quantified using the Chou-Talalay Combination Index (CI) method. P-gp efflux function was evaluated by Rhodamine 123 (Rh123) accumulation, while apoptosis was analyzed via Annexin V-FITC/PI flow cytometry. The expression levels of P-gp and ABCB1 mRNA were determined by Western blotting and RT-qPCR, adhering to MIQE guidelines. A549/DDP cells exhibited a robust resistance phenotype (Resistance Index: 13.4). Co-treatment with non-toxic concentrations of Curcumin (20 μM) significantly reduced the IC₅₀ of Cisplatin from 56.42 μM to 6.85 μM (p < 0.001), yielding a Reversal Fold of 8.2. The Combination Index was 0.45, indicating strong synergism. Curcumin treatment blocked P-gp-mediated efflux and, critically, downregulated ABCB1 mRNA by 72% and protein expression in a dose-dependent manner. This dual mechanism restored apoptotic sensitivity, increasing rates from 12.5% to 46.8%. In conclusion, curcumin effectively reverses Cisplatin resistance in NSCLC through a dual mechanism: immediate functional inhibition of the P-gp pump and delayed transcriptional repression of ABCB1. These findings support the development of Curcumin-based adjuvant therapies to overcome MDR.

Comparative Efficacy and Acute Tolerability of a Standardized Withania somnifera Root Extract Versus Sertraline in Generalized Anxiety Disorder: A Randomized, Double-Blind, Placebo-Controlled Non-Inferiority Trial

Ni Made Nova Indriani, Suyong Zhou, Riri Arisanty Syafril Lubis, Jason Willmare — Wed, 28 Jan 2026 04:40:24 +0000

Generalized anxiety disorder (GAD) represents a significant psychiatric burden, characterized by chronic hyperarousal and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. While selective serotonin reuptake inhibitors (SSRIs) like Sertraline are the standard of care, their utility is often compromised by delayed onset and adverse effects, specifically sexual dysfunction. Withania somnifera (Ashwagandha) acts as a GABA-mimetic and adaptogen, yet rigorous head-to-head comparisons against pharmaceutical controls are rare. We conducted an 8-week, randomized, double-blind, placebo-controlled trial involving 150 adults with DSM-5 diagnosed GAD. Participants were randomized (1:1:1) to receive High-Concentration Ashwagandha Root Extract (600 mg/day, standardized to >5% withanolides), Sertraline (50 mg/day), or Placebo. Blinding was maintained using mint-scented desiccants to mask the herb's odor. Efficacy was analyzed using Mixed Models for Repeated Measures (MMRM). Of 150 participants, 138 completed the study. Both Ashwagandha (Mean HAM-A reduction -14.2) and Sertraline (-15.1) demonstrated statistical superiority over Placebo (-5.4; p < 0.001). The difference between active arms was not statistically significant, supporting comparable efficacy. Ashwagandha significantly reduced serum cortisol (-24.3%) and improved GAD-7 scores. Crucially, while Sertraline induced significant sexual dysfunction (worsened ASEX scores, p < 0.001) and nausea (28%), Ashwagandha showed a safety profile indistinguishable from placebo. In conclusion, standardized Withania somnifera extract (600 mg/day) offers anxiolytic efficacy comparable to Sertraline (50 mg/day) with a superior safety profile, specifically devoid of sexual and gastrointestinal adverse effects.