Background: Sleep disturbances and insomnia are highly prevalent among medical students and are associated with adverse physical, psychological, and academic outcomes. Complementary therapies, such as aromatherapy, have been proposed as low-risk approaches for improving sleep quality; however, evidence regarding rose oil aromatherapy in this population remains limited. Objectives: This study aimed to evaluate the effects of topical rose oil aromatherapy on insomnia severity and subjective sleep quality among female medical students living in university dormitories. Methods: This randomized, double-blind, placebo-controlled clinical trial included 80 female medical students with poor sleep quality according to the Pittsburgh Insomnia Rating Scale Short (PIRS-20). Participants were randomly assigned to either the intervention group (rose oil aromatherapy, n = 40) or the control group (placebo oil, n = 40). Both groups applied 3 - 5 drops of the assigned oil topically to the forehead with gentle massage each night before bedtime for seven consecutive days. Sleep quality and insomnia severity were assessed at baseline and after the intervention using the PIRS-20. Each item was scored from 0 to 3, with 3 indicating the greatest negative effect. Total scores ranged from 0 to 60, with higher scores indicating poorer sleep quality. Analyses included independent-samples and paired-samples t tests, chi-square tests, and analysis of covariance (ANCOVA) to adjust for baseline differences and potential confounders. Results: At baseline, the intervention group had significantly poorer sleep quality than the control group (PIRS-20: 52.37 ± 9.45 vs. 45.60 ± 8.86; P = 0.001). After the intervention, the mean PIRS-20 total score decreased significantly in the intervention group (to 37.50 ± 7.35), whereas only a modest reduction was observed in the control group (43.55 ± 9.31). The between-group difference in post-intervention PIRS-20 scores was statistically significant (P = 0.002). Sleep duration increased significantly in the intervention group (mean change = 0.57 ± 0.91 hours; P < 0.001) but not in the control group. Changes in sleep-onset latency were small and not statistically significant. After adjustment for baseline values and confounding variables using ANCOVA, the improvement in overall sleep quality remained significant (β = -6.47, 95% CI, -10.42 to -2.52; P = 0.002), whereas adjusted differences in sleep duration (β = 0.62, 95% CI, -0.05 to 1.31; P = 0.07) and bedtime (β = -0.325, 95% CI, -0.604 to -0.046; P = 0.07) were not statistically significant. Conclusions: Short-term topical rose oil aromatherapy significantly improved subjective sleep quality and reduced insomnia severity among female medical students. Although modest improvements in sleep duration were observed, the effects on sleep-onset latency were limited. Given the short intervention period and the reliance on self-reported measures, further research with longer follow-up and objective sleep assessments is warranted.
Background: The emergence of SARS-CoV-2 has highlighted the need for effective antiviral agents. The viral main protease (Mpro) and the host angiotensin-converting enzyme 2 (ACE2) are attractive therapeutic targets, involved in viral replication and entry, respectively. Objectives: To identify isoflavonoid derivatives with favorable predicted binding to SARS-CoV-2 Mpro and ACE2 using an integrated computational approach. Methods: Eighty-two naturally occurring isoflavonoid derivatives were evaluated using molecular docking, density functional theory (DFT) calculations, and in silico ADMET predictions. Results: Compounds 40, 50, 61, 66, 81, and 82 exhibited the most favorable predicted binding energies toward both Mpro and ACE2. Among these, the Ulexin C derivatives (compounds 81 and 82) achieved the most favorable docking scores under the applied computational protocol. DFT calculations supported their favorable electronic properties, and ADMET predictions indicated acceptable drug-likeness for all selected compounds, with no violations of Lipinski’s rule. Toxicity predictions suggested a medium risk of hERG inhibition for all selected compounds; additionally, compound 82 was predicted to be mutagenic in the Ames test, indicating a potential safety concern. Overall, compounds 50, 61, 66, and 81 were identified as the most promising candidates for further investigation. Conclusions: These findings identify several isoflavonoid derivatives, particularly Ulexin C-related compounds, as computationally prioritized candidates for further experimental evaluation against SARS-CoV-2. However, predicted binding affinities do not necessarily indicate inhibitory activity, and the computationally predicted toxicity profiles, particularly the mutagenicity of compound 82 and potential hERG liability, require experimental confirmation before further development.
Background: Acute sore throat (pharyngitis) is a common condition, and its clinical symptoms, including cough, affect many individuals annually. Dracocephalum kotschyi, a plant endemic to Iran, has a long history of use in traditional medicine. Laboratory studies have confirmed its antibacterial and anti-inflammatory properties, particularly cyclooxygenase enzyme inhibition. Given patient preference for syrups and the need to reduce unnecessary antibiotic use, this study aimed to formulate an herbal cough syrup derived from D. kotschyi. Objectives: This study aimed to develop and evaluate two herbal cough remedies derived from D. kotschyi, including a simple syrup and a formulation suitable for patients with diabetes. Methods: A hydroalcoholic extract of the plant was prepared, and its phenolic compound content was evaluated using the Folin-Ciocalteu reagent. The extract was then standardized. Two syrup formulations were prepared: a sucrose-based simple syrup and a stevia-based sugar-free syrup suitable for patients with diabetes. The syrups were evaluated for stability, pH, specific gravity, viscosity, and microbial limits in accordance with United States Pharmacopeia (USP) standards. Results: The syrups exhibited acceptable pH, specific gravity, and viscosity values of approximately 100 - 120 cP, supporting local efficacy in the throat region. Microbial limit testing was performed in accordance with USP standards, including enumeration of bacteria, yeasts, and molds, expressed as CFU/mL. The results were within normal limits. The absence of Escherichia coli further indicated compliance with the required USP quality-control standards for oral syrups. Conclusions: These findings suggest that the formulated syrups may be promising therapeutic options for managing inflammation and symptoms associated with acute sore throat and cough.
Background: Nanostructured lipid carriers (NLCs) are promising vehicles for the topical delivery of poorly permeable drugs such as methotrexate (MTX). In conventional NLCs, the liquid lipid serves primarily as a structural component, whereas incorporating a bioactive natural liquid lipid may provide additional formulation benefits for the resulting carrier. Objectives: This study aimed to design and physicochemically characterize MTX-loaded NLCs using eicosapentaenoic acid (EPA), a natural omega-3 fatty acid, as a bioactive liquid lipid, and to identify an optimal formulation through a systematic two-level formulation design. Methods: Eight formulations were prepared by hot emulsification followed by sonication, with varying amounts of solid lipid (stearic acid), liquid lipid (EPA), and surfactant (soya lecithin). The MTX assay was validated by reversed-phase high-performance liquid chromatography (HPLC) for linearity, limit of detection (LOD), limit of quantification (LOQ), precision, selectivity, and matrix-matched recovery. The formulations were characterized in terms of particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), drug loading (DL%), and in vitro release. The release kinetics of the optimal formulation were evaluated using four models (zero-order, first-order, Higuchi, and Korsmeyer-Peppas), and physical stability was monitored for three months. Results: The HPLC method was linear over 1 - 20 µg/mL (R2 = 0.9981), with LOD and LOQ of 1.56 and 4.72 µg/mL, respectively, and precision of RSD ≤ 2%. Particle size ranged from 88.92 to 160.7 nm, and PDI ranged from 0.252 to 0.405. The optimal formulation (F5; stearic acid 200 mg, EPA 20 mg, lecithin 40 mg) showed a particle size of 88.92 nm, a PDI of 0.284, a zeta potential of ‒18.5 mV, an EE% of 88.40%, and a DL% of 7.89%. Its 24 h cumulative release reached 88.03%; among the tested models, the release best fit the Korsmeyer-Peppas (R2 = 0.987; n = 1.12) and first-order (R2 = 0.977) models, indicating a coupled diffusion–relaxation mechanism. All formulations remained physically stable over three months. Conclusions: EPA can serve as a bioactive liquid lipid in NLCs, producing nanoscale carriers with high entrapment, adequate drug loading, and sustained release. These findings provide a robust physicochemical basis for topical MTX carriers; however, biological and skin-delivery validation is required before any therapeutic benefit of EPA can be claimed.
Background: Silymarin is a polyphenol-rich plant extract with antioxidant and UV-absorbing properties. However, its limited solubility and stability present challenges, necessitating further formulation research. Objectives: This study aimed to develop a novel silymarin-loaded nanostructured lipid carrier (NLC) and evaluate its in vitro photoprotective potential. Methods: NLCs were prepared by melt emulsification followed by high-shear homogenization using cetyl palmitate (CP) or beeswax (BW) as the solid lipids, oleic acid as the liquid lipid, and Tween 80 as the surfactant. The NLCs were characterized in terms of particle size, polydispersity index, zeta potential, drug loading, and entrapment efficiency. Their infrared spectra, thermal behavior, crystallinity, in vitro drug release, rheological properties, and in vitro sun protection effects were also evaluated. In addition, a stability study was conducted on the BW-containing NLCs. Results: Formulations containing CP showed mean particle sizes ranging from 102.9 to 140.0 nm and a polydispersity index (PDI) of 0.25 - 0.48, whereas those incorporating BW showed a broader size range (108.8 - 898.8 nm; PDI: 0.28 - 0.88). The developed silymarin-loaded NLCs exhibited high encapsulation efficiency, as confirmed by DSC, XRD, and FTIR analyses. Although silymarin-loaded NLCs, particularly BW-based formulations, exhibited relatively higher UV protection, the achieved SPF values (3.76 - 6.01) indicate that silymarin alone is insufficient for effective clinical photoprotection. Finally, stability assessments revealed notable challenges, with high silymarin loading and elevated surfactant concentrations leading to marked particle aggregation and loss of colloidal stability (PDI reaching 1.0) after three months of storage. Conclusions: This study developed silymarin-loaded NLCs with high loading capacity and biocompatible natural ingredients. However, the formulations showed long-term stability challenges and inadequate sun protection, necessitating the inclusion of UV filters in future research. Their practical application is also limited by the need for comprehensive biocompatibility and safety assessments. Therefore, these formulations should be considered proof-of-concept systems rather than finalized delivery systems.
Background: Concurrent methamphetamine (METH) use among patients receiving methadone maintenance treatment (MMT) is a growing clinical concern associated with cognitive impairment, psychological distress, and an increased risk of relapse. Crocin (CRO), a bioactive constituent of saffron (Crocus sativus L.), has antioxidant, anti-inflammatory, and neuroprotective properties. Objectives: This study aimed to evaluate the effects of CRO supplementation on withdrawal symptoms, craving, sleep quality, cognitive performance, and psychological status in METH users undergoing MMT. Methods: In this trial, 80 male METH users receiving stable MMT were randomly assigned to CRO (n = 40) or placebo (n = 40) for 8 weeks. All analyses were performed according to the intention-to-treat (ITT) principle and included all 80 randomized participants. The primary outcomes were withdrawal symptoms, assessed with the Amphetamine Withdrawal Questionnaire (AWQ), and craving, measured with the Drug Desire Questionnaire (DDQ). Secondary outcomes were sleep quality (PSQI), sexual function (IIEF), cognitive performance (CAQ), and psychological status (DASS-21). Results: In the ITT analysis (n = 80), CRO significantly reduced withdrawal symptoms (P = 0.036, η2p=0.091) and craving (P = 0.024, η2p=0.110) compared with placebo. Significant improvements were also observed in sleep quality (P = 0.025, η2p=0.103), anxiety (P < 0.008, η2p=0.157), and depression (P = 0.014, η2p=0.126). No significant effects were observed for sexual function, cognitive performance, or stress (P > 0.05). Conclusions: The results of this clinical trial indicate that CRO supplementation, administered as a safe and potentially effective adjunct to MMT, may significantly attenuate withdrawal symptoms, reduce craving intensity, improve sleep quality, and alleviate symptoms of anxiety and depression among individuals with METH use disorder. However, the lack of statistically significant improvements in cognitive performance, sexual function, and perceived stress underscores the multifactorial complexity of these clinical domains and highlights the need for further empirical investigation. It is plausible that cognitive deficits resulting from chronic METH exposure, given their putative neurostructural and neurofunctional underpinnings, may require longer treatment durations or integrative therapeutic strategies. Moreover, sexual dysfunction in this patient population is likely mediated by a confluence of physiological, psychological, and psychosocial factors and, as such, may not be readily ameliorated through antioxidant monotherapy alone.
Background: Methamphetamine (METH) is a well-known psychostimulant that induces neurotoxicity and cognitive decline. Resveratrol is a natural phenolic compound found in grapes and berries. Sirtuin-1 (SIRT1) is an important protein involved in neuroprotective pathways. Several microRNAs are dysregulated following METH use, which can affect gene expression. Objectives: This study evaluated the contribution of SIRT1 and its associated microRNAs to resveratrol-mediated neuroprotection against METH-induced neurotoxicity, cognitive decline, and neuronal damage in the prefrontal cortex (PFC). Methods: Rats received METH (5 mg/kg) for 14 days. Resveratrol was administered orally before METH injection. Object-based attention and Y-maze tests were performed to assess attention and working memory, respectively. SIRT1 gene expression and protein levels were assessed using quantitative PCR and immunoblotting. miRNAs related to SIRT1 were predicted, and changes in their levels were examined. Morphological changes in PFC tissue were evaluated using histological analysis. Results: Chronic METH use induced PFC damage and impaired attention and working memory. It also decreased SIRT1 levels and upregulated miR-22 - 3p, miR-9 - 5p, miR-138 - 5p, and miR-133a-3p in the PFC. Administration of resveratrol prevented METH-induced PFC damage and improved cognition. Resveratrol treatment reduced levels of miR-22 - 3p, miR-9 - 5p, and miR-138 - 5p, accompanied by increased SIRT1 levels. Conclusions: Resveratrol treatment exerted protective effects in the PFC against METH toxicity. These effects were associated with increased SIRT1 and altered expression of several SIRT1-related microRNAs, including miR-22 - 3p, miR-9 - 5p, and miR-138 - 5p. However, further research is needed to clarify the roles of SIRT1 and associated microRNAs in resveratrol-mediated neuroprotection.
Background: Pharmacological intervention plays a critical role in managing cystic echinococcosis, both preoperatively and postoperatively, to reduce the risk of recurrence and treat inoperable cases. Therefore, enhancing therapeutic efficacy against hydatid cysts through novel albendazole (ABZ) formulations is essential. Objectives: This study evaluated the tissue-specific drug absorption profiles of ABZ-loaded solid lipid nanoparticles (ABZ-SLNs) and microemulsions (ABZ-MEs) in a BALB/c mouse model of experimental hydatidosis, with the aim of improving tissue drug uptake through nanoparticle-based delivery systems. Methods: Twenty-five male BALB/c mice were intraperitoneally inoculated with viable Echinococcus granulosus protoscolices isolated from sheep hepatic hydatid cysts. After a 6-month infection establishment period, the animals were stratified into 5 randomized groups (n = 5/group). The study groups received daily oral gavage with albendazole suspension, ABZ-ME, or ABZ-SLN at 20 mg/kg for 30 consecutive days. Subsequently, hepatic and pulmonary tissues were harvested, and the amount of drug extracted from the tissues was measured using high-performance liquid chromatography (HPLC). Results: Both ABZ-SLN and ABZ-ME had particle sizes < 150 nm, drug loading > 60%, and sustained-release profiles. Tissue ABZ levels were significantly higher with ABZ-SLN and ABZ-ME than with the aqueous suspension (P < 0.05), and pulmonary concentrations exceeded hepatic levels for all formulations. Conclusions: ABZ-SLN and ABZ-ME significantly enhanced ABZ distribution and tissue uptake, which were attributed to their lipid nature and nanoscale particle size. Their sustained-release profiles suggest that these formulations act as drug depots and enhance systemic therapeutic delivery.
Background: Varuna (Crataeva nurvala Buch.-Ham.) is a widely used medicinal plant in Ayurveda and is valued for its effectiveness in treating urinary tract and inflammatory conditions. To ensure the authenticity, safety, and therapeutic efficacy of herbal drugs, standardized quality control parameters are essential. Objectives: This study was conducted to assess the pharmacognostical features, physicochemical properties, preliminary phytochemical constituents, and HPTLC fingerprint profile of Varuna leaves, using quercetin as the reference marker. Methods: Authenticated plant material was examined macroscopically and microscopically, followed by physicochemical analysis according to WHO guidelines, including ash values, extractive value, loss on drying, foreign matter, and pH. The methanolic extract was subjected to quantitative phytochemical screening to identify major constituents. HPTLC profiling was performed using toluene:ethyl acetate (7:3) as the mobile phase, with scanning at 254 nm and 366 nm. The fingerprint showed multiple peaks with Rf values similar to those of quercetin, indicating the possible presence of flavonoids. Results: Preliminary microscopy revealed characteristic features such as spiral xylem vessels, fibers, crystals, and trichomes. Physicochemical parameters were within acceptable limits, reflecting the good quality of the plant material. Phytochemical screening confirmed the presence of alkaloids, flavonoids, tannins, glycosides, proteins, steroids, and saponins. Furthermore, HPTLC fingerprinting showed multiple peaks with Rf values comparable to those of the quercetin marker, suggesting the possible presence of flavonoid-like compounds. Conclusions: This study provides preliminary pharmacognostic, physicochemical, and phytochemical reference data for Varuna leaves and presents a qualitative HPTLC fingerprint profile that may support future pharmacognostic and phytochemical research.
Background: Chronic kidney disease (CKD) is a growing global health burden characterized by progressive renal decline, chronic inflammation, oxidative stress, and frequent sleep disturbances. Melatonin, an endogenous regulator of circadian rhythm with antioxidant and anti-inflammatory properties, has been proposed as a potential adjunctive therapy in CKD. Objectives: To evaluate the effects of oral melatonin supplementation on inflammatory markers, oxidative stress, metabolic parameters, blood pressure, and sleep quality in non-dialysis patients with CKD stages 3 - 4. Methods: In this randomized, double-blind, placebo-controlled clinical trial enrolled 73 non-dialysis patients with CKD stages 3 - 4 (glomerular filtration rate < 60 mL/min/1.73 m²). Participants were randomly assigned to receive either oral melatonin (3 mg/day) or matching placebo for 12 weeks. Serum levels of interleukin-1β (IL-1β), malondialdehyde (MDA), blood pressure, sleep quality, and routine biochemical parameters were measured at baseline and post-intervention. Results: After 12 weeks, no significant changes were observed in IL-1β or MDA levels in either group (P > 0.05). The MDA decreased in the melatonin group (-0.39 ± 9.36) and slightly increased in the placebo group (0.69 ± 4.93; between-group P = 0.313). Melatonin supplementation yielded a significant reduction in total cholesterol compared with placebo. Regarding sleep quality, both groups showed slight numerical changes, but the melatonin group exhibited a relatively more favorable trajectory, a smaller mean decline in PSQI score (-0.18 ± 0.84) compared with placebo (-0.69 ± 1.06; P = 0.047). Conclusions: Twelve-week melatonin supplementation did not significantly alter inflammatory or oxidative stress markers in stage 3 - 4 CKD but was well tolerated and demonstrated modest metabolic and sleep-related benefits. Larger and longer studies are warranted to clarify its clinical relevance and mechanistic pathways in this population.
Background: Xantolis cambodiana, a Southeast Asian medicinal plant traditionally used to treat inflammation and infections, has not yet been systematically evaluated for its anticancer potential. Objectives: This study investigated the anticancer effects of 4 X. cambodiana extract fractions, including distilled water, methanol, ethyl acetate, and hexane, on human lung cancer A549 cells and explored the associated molecular mechanisms. Methods: Cells were treated with the extracts, and viability and migration were assessed using sulforhodamine B, colony formation, and wound-healing assays. Apoptosis, autophagy, reactive oxygen species (ROS) production, and mitochondrial membrane potential were analyzed by flow cytometry. Results: All fractions showed dose- and time-dependent cytotoxicity at 72 hours, with hexane being the most potent fraction (IC₅₀, 78.18 ± 1.61 μg/mL), followed by ethyl acetate, methanol, and distilled water. Ethyl acetate suppressed colony formation comparably to hexane. At 250 μg/mL, distilled water, methanol, and hexane significantly inhibited cell migration. The extracts induced late apoptosis, most prominently with methanol, ethyl acetate, and hexane (P < 0.05), and triggered autophagy, with the strongest effect observed in the ethyl acetate fraction. These effects were associated with increased ROS production and mitochondrial dysfunction, suggesting ROS-mediated cell death. Conclusions: Xantolis cambodiana extracts demonstrated potent anticancer activity in A549 cells through apoptosis induction and ROS-mediated mitochondrial dysfunction, highlighting their therapeutic potential for lung cancer.
Background: Methamphetamine-induced psychosis (MIP) is a severe condition for which no approved pharmacotherapy is available. Because of the anti-inflammatory and neuroprotective properties of curcumin (CUR). Objectives: This study examined the potential of nano-curcumin (Nano-CUR) as an adjunctive treatment to reduce craving and psychotic symptoms and modulate inflammatory biomarkers in patients with MIP. Methods: In this double-blind, placebo-controlled trial, 50 patients with MIP were randomized to receive either Nano-CUR (40 mg twice daily; total dose, 80 mg/day) or placebo for 4 weeks, alongside standard antipsychotic treatment. The primary outcomes were craving, assessed using the Desire for Drug Questionnaire (DDQ), and psychotic symptoms, assessed using the Positive and Negative Syndrome Scale (PANSS), at baseline, week 4, and 1-month follow-up. The secondary outcomes were serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), adenosine A2A receptor, and Toll-like receptor 4 (TLR4), measured using enzyme-linked immunosorbent assay (ELISA). Per-protocol analysis was performed on 45 patients who completed the study. Results: Linear mixed models adjusted for baseline scores revealed significant main effects of time [F (2, 84.01) = 71.94, P < 0.001] and group [F (1, 45.09) = 46.78, P < 0.001] on craving, as well as a significant group & times; time interaction [F (2, 84.01) = 38.58, P < 0.001], indicating a greater reduction in the Nano-CUR group. For PANSS symptoms, a significant group & times; time interaction was also observed [F (2, 89.75) = 22.86, P < 0.001], in addition to significant main effects of time [F (2, 89.75) = 63.91, P < 0.001] and group [F (1, 51.03) = 41.91, P < 0.001]. By week 4, Nano-CUR significantly reduced TNF-alpha levels compared with placebo [mean difference (MD)= -18.07 pg/mL; 95% CI, -30.7 to -5.45; P = 0.006]. No significant effects were observed for adenosine A2A receptor, IL-6, or TLR4. Conclusions: Adjunctive Nano-CUR significantly reduced craving and psychotic symptoms and modulated inflammatory pathways by reducing TNF-alpha in patients with MIP. These findings support the potential of Nano-CUR as a novel, safe, and effective adjunctive therapy for the management of MIP.
Background: Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality worldwide. Tumor development is strongly influenced by the tumor microenvironment, including mechanisms such as antitumor cellular immunity, angiogenesis, and chronic inflammation. This study aimed to evaluate the effects of Phyllanthus niruri L. extract on colorectal cancer through immunological, angiogenic, and inflammatory pathways. Methods: This in vivo laboratory-based experimental study employed a post-test-only control group design. Fifty male Sprague-Dawley rats were randomly allocated into three groups: (1) healthy control, (2) colorectal cancer without treatment, and (3) colorectal cancer treated with P. niruri L. extract. Colorectal carcinogenesis was induced using 1,2-dimethylhydrazine (DMH) for 12 consecutive weeks. The extract was administered orally at a dose of 13.5 mg/kg body weight once daily from weeks 13 to 16, indicating a therapeutic post-induction model rather than a preventive concurrent-induction model. Biomarker analysis included cytotoxic T lymphocytes (CTLs) to assess cellular immunity, vascular endothelial growth factor (VEGF) as an angiogenesis marker, and cyclooxygenase-2 (COX-2) as an inflammatory marker. Pairwise p-values reported in the Results correspond to adjusted post hoc comparisons, and effect sizes were estimated to reflect the magnitude of between-group differences. Results: Administration of P. niruri L. extract significantly increased CTL expression compared with the untreated colorectal cancer group (P < 0.01), indicating enhanced adaptive cellular immune response. In contrast, VEGF expression was significantly reduced (P < 0.01), suggesting suppression of angiogenesis. Similarly, COX-2 expression decreased significantly (P < 0.01), reflecting reduced inflammatory activity within the tumor microenvironment. Conclusions: Phyllanthus niruri L. demonstrated multiple anticancer effects by enhancing cellular immunity, inhibiting angiogenesis, and attenuating inflammatory responses. These findings support its potential role as a complementary therapeutic agent in colorectal cancer management.
Context: Oxidative stress, resulting from an imbalance between reactive oxygen species and antioxidant defenses, is a key driver of chronic diseases such as cardiovascular disorders, diabetes, and neurodegenerative conditions. Objectives: This systematic review and meta-analysis aimed to evaluate the dose-dependent effects of ginseng supplementation on superoxide dismutase (SOD) and malondialdehyde (MDA) levels in randomized controlled trials (RCTs), and to explore sources of heterogeneity to guide clinical applications Methods: According to PRISMA guidelines, we searched PubMed/MEDLINE, Scopus, Google Scholar, and trial registries up to July 2025 for RCTs assessing ginseng’s effects on MDA and/or SOD. Nine studies (366 participants) were included after eligibility screening. Data were pooled using a random-effects model and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity was assessed via Cochran’s Q and I² statistics, and subgroup analyses explored dose effects based on estimated ginsenoside content (approximately 0.5 - 6 mg), derived from reported extract doses. Results: Ginseng supplementation was associated with a statistically significant increase in SOD activity (SMD = 0.220, 95% CI: 0.095-0.344, P = 0.001) and showed a borderline reduction in MDA levels (SMD = -0.291, 95% CI: -0.585-0.004, P = 0.053). Subgroup analysis indicated the strongest SOD effect in studies corresponding to an estimated ginsenoside exposure of approximately 3 mg (SMD = 0.336, P = 0.005), with variable MDA effects. High heterogeneity (I² = 96.7% for MDA, 60.5% for SOD) was associated with differences in ginseng formulations, study durations, and participant demographics. Conclusions: Ginseng supplementation is thought to increase SOD activity and may reduce MDA levels, particularly at a 3 mg dose, suggesting a possible antioxidant role, which should be interpreted with caution given the observed heterogeneity.
Background: Amphetamine and methamphetamine use disorders are associated with significant psychiatric and social consequences, and effective pharmacological treatments remain limited. Objectives: This study was conducted in male participants in Iran to evaluate the efficacy of mirtazapine in reducing stimulant use, depressive symptoms, and craving intensity among individuals with stimulant use disorder. Methods: In a 12-week, double-blind, randomized controlled trial, 84 male participants diagnosed with amphetamine or methamphetamine use disorder were assigned to receive either mirtazapine (30 mg/day) or placebo. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Participants were excluded only based on the clinical diagnosis of severe major depressive disorder, not solely on the BDI-II score. Urine drug screens were conducted biweekly (Session 1-6, with Session 6 corresponding to Week 12), and craving was measured using the Persian Stimulant Craving Questionnaire (14 items; score range 14 -140). Adverse events were actively monitored at each visit and categorized by severity and duration. Results: By Week 12, 52.4% of participants in the mirtazapine group tested negative for amphetamines, compared to 9.5% in the placebo group (P = 0.007). BDI-II scores decreased from 44.44 +/- 1337 to 34.78 +/- 10.06 in the mirtazapine group, while the placebo group showed minimal change. Craving scores declined from 83.83 +/- 17.48 to 70.77 +/- 12.75 in the mirtazapine group versus 84.94 +/- 9.70 to 80.25 +/- 12.57 in the placebo group. Mirtazapine was well tolerated, with no serious adverse events reported. Conclusions: Mirtazapine demonstrated potential effectiveness in reducing stimulant use, alleviating depressive symptoms, and decreasing craving in male participants with amphetamine or methamphetamine use disorder. These findings are limited to men over 12 weeks, and further studies are required to evaluate long-term safety, functional outcomes, and effectiveness in diverse populations. While the results support its possible role as an adjunctive treatment in addiction care, caution is advised due to the short-term nature of the trial and the absence of functional outcome measures.
Background: Type 1 diabetes (T1D) is an autoimmune disease primarily caused by inflammation and oxidative stress. The treatment of this condition has encountered numerous challenges and limitations to date. Astaxanthin (AST) is a carotenoid known for its antioxidant properties. Gamma-aminobutyric acid (GABA) is a vital neurotransmitter that regulates the activity of beta cells in pancreatic islets. Objectives: The present study aimed to investigate the effects of AST and GABA alone and in combination on beta cell regeneration, fasting blood sugar (FBS), and oxidative stress in streptozotocin (STZ)-induced T1D in rats. Methods: In this experimental in vivo study, 30 male Wistar rats were used. Diabetes was induced with intraperitoneal injection of STZ (55 mg/kg). We randomly divided the rats into five groups (n = 6): control, diabetic, AST (20 mg/kg), GABA (100 mg/kg), and combination therapy (GABA + AST). Following 21 days of treatment, we measured serum FBS, C-peptide, insulin, nitric oxide (NO), and total antioxidant capacity (TAC). We removed the rats’ pancreases to examine gene expression (PDX1, NEUROG3) and histological changes. Results: The FBS and NO levels of treated diabetic rats with GABA, AST, and their combination decreased significantly (P < 0.05). The amount of C-peptide, insulin, TAC, and expression of PDX1 and NEUROG3 genes increased significantly. Conclusions: AST and GABA reduce FBS and improve serum and histology factors of the pancreas in diabetic rats.
Context: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, largely attributable to the limited selectivity and cumulative toxicity of conventional anticancer therapies. Despite advances in chemotherapy and targeted agents, treatment-associated adverse effects and therapeutic resistance continue to hinder clinical outcomes. In this context, natural and naturally derived peptides have emerged as promising anticancer candidates due to their inherent biocompatibility, structural diversity, and capacity to selectively target cancer-associated molecular and cellular pathways. Objectives: A comprehensive evaluation of in vivo evidence is essential to clarify their therapeutic potential and mechanistic relevance in lung cancer. Data Sources: A structured systematic literature search was conducted exclusively in the PubMed database to identify original in vivo studies published between 2015 and 2025. Study Selection: Eligible studies were selected using predefined inclusion criteria emphasizing lung cancer animal models and peptide-based interventions derived from natural sources/natural scaffolds or operationally defined peptide-inspired designs. Studies limited to in vitro experiments, review articles, duplicates, and publications lacking quantifiable antitumor outcomes were excluded. Reporting followed PRISMA 2020, and 29 eligible in vivo studies were included in a qualitative synthesis. Data Extraction: Because the search was restricted to a single database, studies indexed exclusively in Embase, Scopus, or Web of Science may have been missed, and findings should be interpreted as a structured qualitative synthesis rather than an exhaustive evidence capture. Results: Analysis of eligible in vivo studies indicates that natural, naturally derived, and peptide-inspired strategies can inhibit lung tumor growth through convergent biological mechanisms. For synthesis, studies were grouped into four principal mechanistic clusters based on the primary mechanism most directly linked to in vivo outcomes: (1) inhibition of oncogenic kinases and dysregulated signaling pathways; (2) modulation of NF-κB-associated inflammatory responses; (3) induction of mitochondrial and lysosomal dysfunction culminating in tumor cell death; and (4) suppression of angiogenesis and metastatic progression. Multi-modal peptides were discussed as such, but were not double-counted across clusters. Several platforms also incorporated rational optimization to improve stability, tumor targeting, and delivery efficiency. Conclusions: The in vivo literature supports natural, naturally derived, and peptide-inspired approaches as experimental preclinical platforms with antitumor activity in lung cancer models. However, the evidence base is dominated by immunocompromised xenograft studies, pharmacokinetic and safety reporting is inconsistent, chronic toxicity and immunogenicity are rarely evaluated, and none of the peptides discussed have entered lung cancer clinical trials. Accordingly, these findings should be viewed as proof-of-concept platforms requiring extensive translational validation in clinically relevant models before inferences about clinical viability can be made.
Background: This study investigated the antimicrobial and antioxidant properties of Citrus reticulata (mandarin) peel essential oil against multidrug-resistant bacteria, specifically Staphylococcus aureus and Pseudomonas aeruginosa. Given the global health threat posed by antibiotic resistance, this research aimed to explore plant-derived alternatives. Objectives: This study aimed to evaluate the antimicrobial activity of Citrus reticulata peel essential oil against multidrugresistant isolates of Staphylococcus aureus and Pseudomonas aeruginosa and to assess the oil's antioxidant capacity. Methods: The essential oil was extracted by steam distillation and analyzed using gas chromatography-mass spectrometry (GC-MS), which identified D-limonene as the primary component (88.45%), along with minor constituents. Results: The essential oil's primary component was D-limonene (88.45%). The oil exhibited potent antibacterial activity against all tested multidrug-resistant S. aureus (n = 6) and P. aeruginosa (n = 5) isolates, with a minimum inhibitory concentration (MIC) of 40,000 ppm. Furthermore, in the DPPH assay, the oil showed superior antioxidant capacity, with a 1OO% oil concentration achieving 60% radical scavenging activity, exceeding the 54.08% activity of the ascorbic acid control. Conclusions: Mandarin peel essential oil exhibits significant antimicrobial and antioxidant properties, suggesting its potential as a source of bioactive compounds against multidrug-resistant infections. Its dual antibacterial and antioxidant activities highlight its promise in combating antimicrobial resistance. Future research should focus on optimizing formulations, conducting in vivo studies, and evaluating potential clinical applications.
Background: Triple-negative breast cancer (TNBC) lacks hormone- or HER2-targeted therapies and remains associated with early relapse and therapeutic resistance. Targeting metabolic pathways has emerged as a complementary approach to conventional cytotoxic therapy. The mevalonate pathway supports oncogenic signaling through prenylation-dependent activation of small GTPases, whereas arsenic trioxide (As2O3) induces oxidative stress-mediated apoptosis, thereby reducing cell viability. Objectives: This study investigated whether pharmacologic inhibition of HMG-CoA reductase with lovastatin (Lov) enhances the cytotoxic efficacy of As2O3 in TNBC cells. Methods: The human TNBC cell line MDA-MB-231 was treated with Lov and As2O3 as monotherapies and in combination. Cell viability was assessed using MTT assays and morphological evaluation. Long-term proliferative capacity was evaluated using clonogenic survival analysis. Drug interactions were quantified using the Chou-Talalay method, including combination index (CI) calculations and isobologram modeling. Results: Lov and As2O3 each reduced cell viability in a concentration-dependent manner, with IC50 values of approximately 2 & micro;M and 7.5 & micro;M, respectively. Combined treatment produced synergistic growth inhibition across multiple concentration ratios (CI < 1), enabling significant cytotoxicity at lower drug concentrations. Clonogenic assays showed marked suppression of colony formation after combination exposure compared with single-agent treatment, indicating an impaired long-term proliferative potential. Conclusions: Lov enhances the in vitro antitumor activity of As2O3 in MDA-MB-231 TNBC cells, supporting the potential for metabolic sensitization by targeting the mevalonate pathway. Although these findings are limited to a single cell line and require mechanistic and in vivo validation, they support further preclinical investigation of statin-based combination therapies in TNBC.
