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Nanostructured lipid carriers for enhanced oral bioavailability and antibacterial efficacy of curcumin against multidrug-resistant pathogens

Background: Poor solubility and limited oral bioavailability restrict the clinical translation of curcumin despite its well-documented antibacterial and anti-inflammatory activity. Nanostructured lipid carriers (NLCs) offer a promising strategy to overcome these barriers by improving stability, gastrointestinal absorption, and therapeutic delivery.

Methods: Curcumin-loaded NLCs were prepared using hot homogenization and ultrasonication, with glyceryl monostearate as solid lipid and oleic acid as liquid lipid. Particle size, zeta potential, and entrapment efficiency were determined by dynamic light scattering and HPLC. In vitro release was studied under simulated gastric and intestinal conditions. Antibacterial activity was tested against MDR Staphylococcus aureus and Escherichia coli using MIC/MBC assays and biofilm inhibition models. Pharmacokinetic studies were conducted in Wistar rats following oral administration.

Results: Optimized curcumin-NLCs exhibited a mean particle size of 121 ± 8 nm, zeta potential of −32 mV, and entrapment efficiency of 89%. Controlled release demonstrated sustained drug release over 24 h. Antibacterial assays revealed significant improvement in potency, with MIC values reduced fourfold compared to free curcumin. Biofilm inhibition reached 73% at sub-MIC concentrations. Pharmacokinetic analysis showed a 5.2-fold increase in oral bioavailability, with peak plasma concentrations achieved at 3 h post-administration.

Conclusion: Curcumin-loaded NLCs significantly enhance oral bioavailability and antibacterial efficacy, representing a robust drug delivery platform for repositioning natural compounds against multidrug-resistant infections. These findings highlight the potential of lipid nanocarriers in medicinal chemistry and pharmaceutics for developing next-generation therapeutic formulations.

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Nanoparticle Systems for Improved Delivery of Plectranthus-Derived Abietane Diterpenoids in Breast Cancer Therapy

Nanoparticles (NPs) have become key tools in modern drug delivery, especially when used alongside natural compounds. This combination can improve how drugs are absorbed and directed to specific targets in the body. Benefits include higher drug loading, controlled and sustained release, longer presence in the bloodstream, and reduced side effects. These advantages contribute to safer and more efficient therapies.

Among the various nanoparticle types, gold nanoparticles (AuNPs) stand out due to their easy production, strong stability, and unique physical and chemical traits. These properties make them excellent carriers for both drugs and genetic material, especially in cancer-related applications.

One group of natural compounds with promising anticancer activity is the abietane diterpenoids, such as 7α-acetoxy-6β-hydroxyroyleanone (Roy), found in Plectranthus species. Despite their potential, their clinical use is limited by poor water solubility and low bioavailability. To overcome these issues, Roy and one Roy-esterified derivative were incorporated into gold nanoparticle-based systems.

These nanoformulations were evaluated for characteristics like particle size (29.37 nm), polydispersity index (PDI, 0.399), surface charge (zeta potential, −6.84), and drug encapsulation efficiency (79.4%). In vitro experiments using breast cancer cell lines (MDA-MB-231, 4T1, and MCF7) showed that Roy-loaded AuNPs had significantly stronger anticancer effects than Roy alone or unmodified AuNPs. Notably, these systems also demonstrated selectivity, affecting cancer cells while sparing healthy human dermal fibroblasts (HDFs), suggesting strong potential for targeted cancer therapy. These results represent meaningful progress in the development of innovative drug delivery systems for cancer therapy.

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Comparative Assessment of Nigerian and Yemeni Garlic as Phospholipase A2 (PLA2) Inhibitors in Snakebite Envenomation Therapy
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Snakebite envenomation remains a significant medical challenge, particularly in tropical and subtropical regions. This study aimed to evaluate the inhibitory potential of Allium sativum (garlic) from Nigeria and Yemen against Naja nigricollis and Echis ocellatus venoms using both experimental and computational approaches. Fresh garlic samples were collected, authenticated, and extracted using cold methanol maceration to yield Nigerian and Yemeni methanol extracts (NME and YME, respectively). Their antisnake venom activities were assessed in vitro and in silico, with polyvalent antivenin (ASV) serving as the standard control. Comparative qualitative phytochemical screening was performed to identify secondary metabolites in both extracts. The results demonstrated significant (p<0.05), concentration-dependent inhibition of venom phospholipase A2 (PLA2) activity. YME exhibited superior PLA2 inhibitory activity (80.02 to 53.01%) compared to NME (72.51 to 38.20%) across concentrations ranging from 10.0 to 0.625 mg/mL. Furthermore, molecular docking of bioactive compounds identified in YME via HPLC and LC-MS/MS revealed strong binding affinities (−8.5 to −7.2 kcal/mol) to the active site of PLA2, indicating potential inhibitory interactions. The selected compounds also exhibited favorable drug-likeness and pharmacokinetic (ADMET) profiles. In conclusion, the study provides scientific validation for the traditional use of Allium sativum in Nigeria and Yemen as an herbal remedy for snakebite envenomation, highlighting the promising anti-snake venom potential of Yemeni garlic through PLA2 inhibition.

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Therapeutic Potential of Mandragora autumnalis: Inflammation Modulation and Antimicrobial Properties

Inflammation is an essential immune defense mechanism that protects the body from infections and tissue injury; however, when dysregulated or persistent, it becomes a pathological driver of chronic diseases. It is an essential immune response; however, its chronic activation contributes to the development of several disorders, including arthritis, cardiovascular diseases, and certain types of cancer. Natural plant extracts, enriched with bioactive compounds, have long been employed in traditional medicine to alleviate inflammation by modulating immune pathways. Mandragora autumnalis (MAE), traditionally recognized for its anticancer, antioxidant, and antimicrobial properties, is rich in phenols, flavonoids, and alkaloids; however, its anti-inflammatory mechanisms remain poorly understood. This study investigated the effects of ethanolic MAE extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Treatment with MAE significantly suppressed the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, MAE reduced macrophage migration and regulated critical inflammatory signaling pathways, notably NF-κB, STAT-3, and MAPKs. Beyond its immunomodulatory activity, MAE exhibited broad-spectrum antimicrobial effects against diverse pathogenic bacterial and fungal strains. Collectively, these findings suggest that MAE possesses dual anti-inflammatory and antimicrobial properties, underscoring its potential as a natural therapeutic agent. Further studies are warranted to elucidate its molecular mechanisms and to explore its possible applications in the prevention and management of inflammation-associated disorders and infectious diseases.

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Phytochemical Profiling and Multi-Target Pharmacological Potential of Peganum harmala Seed Extract

Introduction: Medicinal plants remain a promising reservoir of bioactive compounds with therapeutic potential against chronic and infectious diseases. Peganum harmala L. (Zygophyllaceae), commonly known as Syrian rue, is widely used in traditional medicine for its antitumor, antimicrobial, and anti-inflammatory properties, primarily due to its rich alkaloid profile (harmine, harmaline, and β-carbolines). However, systematic pharmacological validation of its bioactivity against contemporary health challenges is still limited.

Methods: Ethanolic extracts of P. harmala seeds were prepared via Soxhlet extraction and subjected to GC–MS analysis for phytochemical profiling. In vitro antioxidant potential was assessed using DPPH and FRAP assays, while antibacterial efficacy was evaluated against multidrug-resistant (MDR) strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using agar well diffusion and MIC determination. Anti-inflammatory activity was examined via protein denaturation and membrane stabilization assays. Cytotoxicity was analyzed on HepG2 and MCF-7 cell lines using MTT assays.

Results: GC–MS revealed the presence of 22 major phytoconstituents, including harmine, harmaline, vasicine, and quinazoline derivatives. The extract demonstrated strong radical scavenging activity (IC₅₀ = 38.6 µg/mL) and ferric reducing power (420 µmol Fe²⁺/g extract). Potent antibacterial activity was observed with inhibition zones up to 22 mm against MDR S. aureus, with MIC values as low as 125 µg/mL. The extract significantly reduced protein denaturation (67%) and stabilized red blood cell membranes (71%), suggesting robust anti-inflammatory effects. MTT assays revealed selective cytotoxicity, with IC₅₀ values of 48 µg/mL for HepG2 and 62 µg/mL for MCF-7, while sparing normal fibroblast cells.

Conclusion: Peganum harmala seed extract represents a pharmacologically rich candidate for drug discovery pipelines targeting oxidative stress, inflammation, antimicrobial resistance, and cancer. Further in vivo validation and mechanistic studies are warranted to translate its traditional use into modern therapeutic applications.

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Effect of Copaiba Oil on the Thoracic Aorta of Streptozotocin-induced Diabetic Rats
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Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder associated with vascular complications, particularly cardiovascular disease. The use of natural compounds such as copaiba oil (Copaifera spp.) has gained attention due to its antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of copaiba essential oil (OEC) on the thoracic aorta of streptozotocin (STZ)-induced diabetic rats.

Methods: Forty male Wistar rats were randomly assigned to five groups: non-diabetic control (CT), non-diabetic + OEC 200 mg/kg (C200), diabetic control (DC), diabetic + OEC 100 mg/kg (D100), and diabetic + OEC 200 mg/kg (D200). Diabetes was induced using STZ (65 mg/kg, i.v.). OEC was administered orally for 20 days. Body weight, glycemia, heart weight, and thoracic aorta morphology were analyzed. Histological sections were stained and assessed for intima-media thickness and volume density (Vv%) of smooth muscle and collagen. ANOVA followed by Tukey’s test was used for statistical analysis (p<0.05).

Results: Diabetic groups showed significant weight loss and hyperglycemia compared to controls (p<0.0001). Treatment with OEC did not reverse these metabolic changes. No significant differences were found in intima-media thickness or Vv% of collagen and smooth muscle between diabetic groups. However, OEC-treated diabetic groups showed a non-significant trend toward preserved intima-media thickness.

Conclusions: OEC (100 and 200 mg/kg) did not significantly improve glycemic control or vascular morphology in diabetic rats within 20 days. Nevertheless, its safety in normoglycemic animals and possible protective trend on vascular structure support further long-term studies at higher doses.

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Effects of Copaiba Oil on Myocardial Morphology in Streptozotocin-Induced Diabetic Rats

Introduction: Diabetes mellitus is associated with cardiovascular complications, including structural and functional alterations of the myocardium. Copaiba oil (Copaifera spp.) has been traditionally used for its anti-inflammatory, antioxidant, and wound-healing properties. This study aimed to evaluate the potential cardioprotective effects of copaiba essential oil (OEC) on the myocardial morphology of diabetic rats.

Methods: Male Wistar rats (70 days old, n=40) were divided into five groups (n=8 each): control (CT), control treated with OEC 200 mg/kg (C200), diabetic control (DC), diabetic treated with OEC 100 mg/kg (D100), and diabetic treated with OEC 200 mg/kg (D200). Diabetes was induced by intravenous streptozotocin (65 mg/kg). OEC was administered daily by gavage for 18 days. After euthanasia, the hearts were collected, weighed, and processed for histological and stereological analyses. Parameters included cardiosomatic index and volume densities (Vv) of cardiomyocytes, collagen, and blood vessels. Statistical analysis was performed using ANOVA with Tukey’s post-test (p<0.05).

Results: Diabetic animals showed significantly reduced body and heart weights compared to controls (p<0.001). However, no significant differences were observed among groups in cardiosomatic index or stereological parameters of cardiomyocytes, collagen, and vessels. Interestingly, OEC administration in diabetic rats was associated with worsened hyperglycemia, with final blood glucose levels exceeding those of untreated diabetic controls. No morphological evidence of cardioprotection or reduction of inflammatory infiltrates was detected.

Conclusion: Copaiba oil did not promote cardioprotective effects in this model of type 1 diabetes. On the contrary, it aggravated hyperglycemia in diabetic rats, while producing only mild hypoglycemic effects in controls. These findings highlight the need for caution regarding indiscriminate use of copaiba oil in diabetic patients and underscore the importance of further studies addressing dosage, administration, and chemical composition standardization to better clarify its cardiovascular effects.

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Parmeliaceae Lichens as Sources of Antioxidant Metabolites with Pharmacological Value

Lichens are a valuable source of secondary metabolites with high antioxidant and therapeutic potential. This study evaluated the antioxidant activity of methanolic extracts from three species of the Parmeliaceae family—Parmelia discordans, Parmelia saxatilis, and Xanthoparmelia tinctina—. Antioxidant activity was determined using ORAC, FRAP and DPPH assays. The phenolic compound content was also evaluated, using the Folin-Ciocalteu assay.

Parmelia discordans showed the highest ORAC value (24.94 µmol TE/mg) and a considerable phenolic content (106.49 µg AG/mg), indicating strong radical scavenging capacity associated with phenolic metabolites. Parmelia saxatilis exhibited a balanced profile, with high ORAC activity (19.03 µmol TE/mg), relevant reducing power (FRAP = 1.029 Eq Fe²⁺/g), and strong DPPH activity (IC₅₀ = 814.42 µg/mL), together with high phenolic content (97.86 µg AG/mg). Xanthoparmelia tinctina displayed the highest reducing capacity (FRAP = 2.295 Eq Fe²⁺/g) and the most potent DPPH activity (IC₅₀ = 642.93 µg/mL), despite its low phenolic content (20.13 µg AG/mg). This finding suggests that non-phenolic compounds may play a central role in its antioxidant potential.

Additionally, methanolic extracts were tested on human neuroblastoma SH-SY5Y cells to assess their effects on cell viability, resistance to oxidative stress, and intracellular generation of reactive oxygen species (ROS). The combined biochemical and cellular data highlight complementary antioxidant strategies: phenolic-driven activity in P. discordans, a robust and balanced profile in P. saxatilis, and non-phenolic but highly effective mechanisms in X. tinctina.

These findings support lichens as promising candidates for further phytochemical and pharmacological research focused on natural antioxidant agents. Nevertheless, it is necessary to continue researching.

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Phytochemical Analysis, Quantification of Flavonoids and Phenols, and Assessment of Anti-Tubercular Activity of Citrus jambhiri Fruit Peel Extract
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Introduction:
Tuberculosis (TB) remains a global health concern, prompting the exploration of natural products for novel therapeutics. Citrus fruit peels, often discarded as waste, are rich in bioactive compounds with potential antimicrobial and antioxidant properties.

Methods:
This study investigated the extraction, phytochemical profiling, and anti-tubercular potential of Citrus jambhiri fruit peel. The dried and powdered peel was extracted by maceration with 95% ethanol for 72 hours at room temperature with intermittent shaking. The extract was filtered and concentrated under reduced pressure to yield a semi-solid residue. Phytochemical screening was performed using standard qualitative tests. Total phenolic content (TPC) was determined by the Folin–Ciocalteu method, where 1 mL of extract (1 mg/mL) was mixed with 5 mL of 10% Folin–Ciocalteu reagent and 4 mL of 7.5% sodium carbonate. After 30 minutes, absorbance was measured at 765 nm, using gallic acid as a standard. Total flavonoid content (TFC) was determined by the aluminium chloride colorimetric assay, mixing 1 mL of extract with 4 mL of distilled water, 0.3 mL of 5% sodium nitrite, 0.3 mL of 10% aluminium chloride, and 2 mL of 1 M sodium hydroxide. Absorbance was measured at 510 nm with quercetin as standard. Anti-tubercular activity was evaluated against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA), with results expressed as minimum inhibitory concentration (MIC).

Results:
The extract showed the presence of alkaloids, flavonoids, tannins, phenols, terpenoids, and saponins. Quantitative analysis revealed TPC of 7.66 mg GAE/g and TFC of 10.76 mg RE/g. The extract exhibited potent anti-tubercular activity with an MIC of 25 μg/mL.

Conclusion:
Citrus jambhiri fruit peel, rich in polyphenols and flavonoids, demonstrates promising anti-tubercular potential, supporting its use as a natural source for lead molecule development in TB therapy.

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From Hive to Health: Propolis Bioactives for Integrated Management of Trypanosomatid Infections

Trypanosomatid parasites—particularly Trypanosoma and Leishmania species—are causative agents of several Neglected Tropical Diseases (NTDs) that impose substantial health and economic burdens on both humans and livestock across endemic regions. With no vaccines available and current chemotherapy is limited by toxicity, and widespread resistance. The need for sustainable, cross-species therapeutics is urgent. Guided by the One Health approach, which integrates human, animal, and environmental health, we investigated the antiparasitic potential of propolis-derived natural products.

Propolis is a complex resinous material produced by bees from local vegetation. It varies in composition depending on geographical and botanical sources. Using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS), followed by principal component analysis (PCA), we profiled propolis samples collected from diverse geographical regions. This analysis revealed significant chemical diversity among samples. Orthogonal partial least squares (OPLS) regression analysis further identified bioactivity-associated markers: a butyrate ester of pinobanksin was linked to strong activity against T. brucei, while methyl ethers of chrysin and pinobanksin were associated with activity against T. congolense.

Our results indicate that the principal bioactive constituents across these samples are flavonoids—particularly phenolic compounds—which appear responsible for the observed broad-spectrum antiparasitic activity. Both crude and fractionated propolis extracts exhibited potent in vitro efficacy against Trypanosoma and Leishmania species, with low half-maximal effective concentrations (EC₅₀) and no detectable cytotoxicity to mammalian cells. Moreover, these compounds retained activity against drug-resistant strains, including diamidine-, arsenical-, and phenanthridine-resistant T. brucei, as well as miltefosine-resistant L. mexicana.

Altogether, these findings highlight propolis as a promising reservoir of flavonoid-based compounds for the rational development of safe, sustainable, and cross-species drugs targeting trypanosomatid diseases. This work supports a One Health-aligned strategy for integrated disease control and natural product drug discovery.

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