Search Results (205)

Background: Piperine, an alkaloid from Piper nigrum, modulates oxidative stress, proliferation, and survival pathways in several cancer models; however, its mechanistic effects in colorectal epithelial Caco-2 cells remain insufficiently defined. Objective: This study aimed to investigate the cytotoxic, antiproliferative, oxidative, autophagic, and anti-migratory effects of piperine in Caco-2 cells. Methods: Caco-2 cells were treated with piperine (0.001–0.1 mg/mL) for up to 72 h. Cell viability, proliferation, and migration were assessed using SRB and scratch assays. Oxidative stress, apoptosis, autophagy, and tight junction integrity were evaluated through ROS quantification, Western blotting, gene expression analysis, confocal microscopy, and transmission electron microscopy (TEM). NACET was used to determine the contribution of oxidative stress to piperine-induced cytotoxicity and autophagy. Results: Piperine induced a time- and dose-dependent reduction in viability, with viability decreasing to 53.0 ± 2.88% at 0.1 mg/mL after 72 h. Proliferation decreased to 51% of control levels (p < 0.001), accompanied by p21 upregulation (p < 0.05), indicating G2/M cell cycle arrest. Piperine markedly increased intracellular ROS (p < 0.001), downregulated NRF2 (p < 0.05), and suppressed GSTA1 expression (p < 0.001), while NACET co-treatment restored viability (p < 0.001). No activation of caspase-dependent apoptosis was observed. Piperine significantly enhanced autophagic flux, as shown by the increased LC3B-II/LC3B-I ratio (p < 0.01), elevated LC3B-II/LAMP-1 co-localization (p < 0.01), and chloroquine-induced accumulation of LC3B-II and p62 (p < 0.01), with preserved lysosomal function. TEM analysis confirmed a marked increase in double-membrane autophagosomes in piperine-treated cells compared with controls. NACET reduced LC3B-II/LC3B-I levels, increased p21 expression, and significantly improved cell viability, indicating that piperine-induced autophagy is cytotoxic and driven by oxidative stress. Additionally, piperine upregulated occludin (p < 0.01) and reduced cell migration independently of proliferation (p < 0.01). Conclusions: Piperine exerts antiproliferative effects in Caco-2 cells through ROS-mediated stress, p21-dependent G2/M arrest, and activation of cytotoxic autophagy. Its ability to impair migration and enhance tight junction integrity further supports its potential as a complementary therapeutic agent in colon cancer. Full article

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. Key compounds, including gingerols, shogaols, curcuminoids, and phenylpropanoids, support glucose homeostasis by enhancing insulin sensitivity, promoting Glucose Transporter Type 4 (GLUT4)-mediated glucose uptake, improving β-cell function, and modulating metabolic signaling pathways such as PI3K/Akt, AMPK, PPARγ, and NF-κB. Their potent antioxidant and anti-inflammatory activities further reduce oxidative stress and chronic low-grade inflammation, both central to the progression of type 2 diabetes and its complications. Evidence from selected clinical and experimental studies suggests that dietary supplementation with whole-rhizome preparations or standardized extracts (including formulation-enhanced products) may improve fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid metabolism, and oxidative stress markers. Recent advances in delivery systems, including nanoemulsions, liposomes, and curcumin–piperine complexes, substantially enhance the bioavailability of poorly soluble phytochemicals, strengthening their therapeutic potential. Overall, Zingiberaceae plants emerge as promising natural supplements in nutritional and pharmacological strategies targeting diabetes. Further clinical research is required to refine dosage, confirm long-term efficacy, and support their integration into evidence-based metabolic interventions. Full article

Background: Chronic pain, which affects over 50 million adults in the United States, has stimulated growing interest in natural and nutrition-based remedies as adjuncts to pharmacologic therapies. Evidence suggests that turmeric and related extracts (i.e., curcuminoids) may provide pain relief, albeit often at levels above dietary ranges, while piperine from black pepper exhibits bioenhancer characteristics of relevance with dietary exposures. Objective: To test the effectiveness of dietarily relevant amounts of turmeric with and without black pepper on self-reported pain ratings among adults with chronic pain. Methods: A randomized, crossover clinical trial tested the effectiveness of turmeric only (one of three amounts within culinary ranges) or turmeric with black pepper to influence pain in adults ≥ 40 years of age. Participants (n = 30, with moderate pain: 4–7 on 0–10-point scale) were enrolled in a 21-day trial, and an experience sampling methodology approach was used. Participants were prompted to report current pain using the numeric pain rating scale (NPRS; 0–10) via text message three times per day for the full study period. Data were averaged and analyzed via linear mixed effects models for repeated measurements. Results: Pain ratings from baseline to week 3 were reduced and statistically significant (p < 0.001) but not statistically different between groups. The provided turmeric, both with and without black pepper, and varying amounts of turmeric (300 mg, 1 g, and 3 g, n = 10 participants/amount) did not show statistically significant differences in pain ratings (p = 0.157 and p = 0.338, respectively). Conclusions: Consuming dietarily relevant amounts of turmeric, either alone or with black pepper, appears to improve average pain ratings. This result suggests a feasible dietary option for further study of nutritional interventions for chronic pain management. Full article

Ultrasound pretreatment offers a promising approach for improving spice drying efficiency while preserving bioactive compounds. This study explores the optimization of ultrasound pretreatment parameters for black pepper processing, using response surface methodology (RSM) to maximize piperine retention, drying efficiency, and moisture reduction. Compared to traditional one-factor-at-a-time (OFAT) screening, RSM identifies a multi-objective optimal balance that achieves superior results for all three responses. Our optimized conditions (35 kHz, 40 min, 50 °C, 80 W/cm³) achieved 18.64 mg/g DW piperine, a drying time of 444.51 min, and a 9.6% moisture content, demonstrating significant improvements in both bioactive preservation and energy efficiency compared with conventional methods. Compared to control samples requiring 600.69 ± 12.5 min drying time, optimal conditions reduced drying time by 26% to 444.51 min (a net process time reduction of 19%, including a 40 min pretreatment) while achieving the target moisture content (9.6%) and limiting piperine loss to approximately 6% in dried samples. Dual-method validation using UV spectrophotometry and HPLC confirmed model predictions with relative errors below 1%, establishing a consistent UV:HPLC ratio (1:2.12). Multi-analytical characterization revealed that ultrasound-induced cavitation selectively disrupted cellular structures, enhancing mass transfer without significant degradation of piperine’s functional groups. Scanning electron microscopy showed increased porosity and microfractures, while FTIR confirmed preservation of key chemical bonds with minor spectral shifts. The process achieved a five-fold improvement in product consistency (reducing the standard deviation from 0.68 to 0.12 mg/g) compared to conventional drying. These findings demonstrate that optimized ultrasound pretreatment provides a reproducible, scalable, and energy-efficient method for spice processing, supporting industrial adoption where consistent quality and bioactive stability are critical. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder shaped by genetic factors such as LRRK2 and GBA1 mutations, as well as dietary and metabolic influences. Food-derived plasma metabolites—including caffeine, paraxanthine, trigonelline, piperine, and sitosteryl hexoside—have emerged as promising, accessible biomarkers for early detection, progression monitoring, and therapeutic targeting, yet their longitudinal behavior and genetic interactions remain insufficiently characterized. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort (n = 455; 303 PD patients, 152 controls), we quantified plasma levels of these metabolites by quantitative LC-MS/MS with batch correction, examining sporadic PD and genetically defined subgroups (LRRK2-PD [PDL], GBA1-PD [PDG], dual-mutation PD [PDGL], and prodromal equivalents). Baseline one-way ANOVA showed significantly lower caffeine and paraxanthine in PDL (p = 0.0467, p = 0.0178) and PDG (p = 0.0408), reduced piperine in PDL (p = 0.0009), PDG (p = 0.0257), and prodromal LRRK2 (p = 0.0168), and elevated sitosteryl hexoside in PDG (p = 0.0184). Longitudinal regression analyses revealed that in sporadic PD, caffeine negatively correlated with MDS-UPDRS parts I (β = −2, p = 0.0475) and III (β = −7.2, p = 0.007), trigonelline declined over time and was inversely associated with part III (β = −1.7, p = 0.0069), and sitosteryl hexoside negatively correlated with parts II (β = −68.3, p = 0.042) and III (β = −74.1, p = 0.0425). In PDL, sitosteryl hexoside inversely correlated with part I (β = −54.2, p = 0.0049), while in PDGL, paraxanthine showed negative associations with part II (β = −18.5, p = 0.00327). These findings demonstrate subgroup-specific alterations in food-derived metabolites and consistent inverse associations with PD severity, supporting their potential as non-invasive biomarkers, particularly in LRRK2/GBA1 mutation carriers, and highlighting the need for longitudinal validation and dietary intervention trials to advance personalized PD management. Full article

Background: Turmeric (Curcuma longa) and its main bioactive compound curcumin are widely promoted for cardiometabolic health, yet their efficacy on lipid parameters remains uncertain. Piperine, an alkaloid from black pepper, enhances curcumin bioavailability and may potentiate its effects. This systematic review and meta-analysis aimed to assess the impact of turmeric, alone or combined with piperine, on lipid profiles in adults with metabolic disorders. Methods: A systematic search was conducted (2010–2025) in PubMed, Scopus, and Cochrane CENTRAL. Randomized controlled trials (RCTs) evaluating turmeric supplementation (with or without piperine) on lipid outcomes were included. Methodological quality was assessed with Cochrane RoB 2; certainty of evidence was rated using GRADE. Meta-analyses were performed with random-effects models. The protocol followed PRISMA 2020 guidelines. Results: Ten records were identified; six full texts were assessed; three RCTs (n ≈ 250) were included in quantitative synthesis, and three additional RCTs narratively. Pooled analysis demonstrated significant reductions in triglycerides (WMD −25.5 mg/dL, 95% CI −32.5 to −18.4), total cholesterol (−14.1 mg/dL, 95% CI −22.9 to −5.3), and LDL-C (−17.0 mg/dL, 95% CI −25.2 to −8.8), with an increase in HDL-C (+5.7 mg/dL, 95% CI +2.0 to +9.4). Subgroup analysis suggested greater LDL-C reduction with turmeric+piperine (−29.6 mg/dL) compared to turmeric alone (−16.2 mg/dL). Certainty of evidence was moderate for TG, TC, LDL-C, and low for HDL-C. Conclusions: Turmeric supplementation, particularly when combined with piperine, improves lipid profiles in adults with metabolic disorders. These effects are clinically relevant and comparable to other nutraceuticals, although evidence remains limited by short trial duration and small sample sizes. Larger, long-term RCTs are warranted before turmeric can be recommended in evidence-based dyslipidemia guidelines. Full article

The pathogenesis of a bacterial infection is a multistep process typically involving bacterial attachment to the host, toxin production, and/or invasion, followed by inflammation. For many bacteria, the invasion of human cells is a key step in the spread of infection and evasion of host immunity. Fusion of host cell membranes during bacterial penetration is a necessary step in invasion. The aim of this study was to evaluate the plant alkaloids, such as piperine, tabersonine, and lupinine, which have the potential to inhibit membrane fusion, fighting bacterial infection. Despite previous data on lupinine’s inhibition of membrane fusion, it has no effect on invasion or on the synthesis of the proinflammatory cytokines. This was likely due to the synthesis of the surface protein OmpX, which was a virulence factor for S. proteamaculans and can neutralize the effect of lupinine on the host cell membrane. Piperine and tabersonine inhibit invasion and proinflammatory cytokine synthesis in response to bacterial infection. However, tabersonine is toxic to eukaryotic cells. This makes it necessary to select an optimal concentration of tabersonine that suppresses invasion but is nontoxic to human cells. Therefore, piperine holds the greatest prospects for clinical use: it inhibits bacterial invasion while remaining nontoxic to human cells even at higher concentrations. Full article

Background: Piper nigrum L. (PNL) is a rich source of piperine, a bioactive alkaloid with pharmaceutical, cosmetic, nutritional supplement, and agricultural applications, yet efficient and sustainable extraction methods remain underexplored. Methods: This study compared ultrasonic bath extraction (UBE) and ultrasonic probe extraction (UPE) using natural deep eutectic solvents (NADES) for isolating piperine from PNL fruits. Six NADES formulations were screened, with NADES-5 (choline chloride:glycerin:urea, 1:1:1) showing superior performance. Response surface methodology with a Box–Behnken design optimized extraction parameters, including liquid-to-solid ratio, extraction time, temperature, and water content, for both UBE and UPE. Results: Optimized UPE consistently outperformed UBE, yielding 49.97 mg/g of piperine versus 25.67 mg/g under identical NADES conditions. Comprehensive characterization using TLC, HPTLC, UV, FTIR, Raman, HPLC, NMR, XRD, SEM, and EDX confirmed the successful isolation and structural integrity of piperine, with samples obtained via UPE exhibiting higher purity (98.7% vs. 95.2%) and enhanced crystallinity. In vitro cytotoxicity assays demonstrated that piperine extracted by UPE showed stronger activity against C2C12 myoblasts (IC₅₀: 24.3 μg/mL vs. 40.6 μg/mL) and greater anticancer effects in MCF-7 and HT-29 cells compared to piperine extracted by UBE. Antioxidant evaluation via DPPH, ABTS, FRAP, and TAC assays, along with intracellular reactive oxygen and nitrogen species suppression in THP-1 and RAW 264.7 macrophages, further confirmed the superior biological potential of the UPE-derived piperine sample. Conclusions: These findings indicate that UPE using NADES is a sustainable approach for high-yield piperine extraction with enhanced purity and bioactivity, supporting its potential for pharmaceutical applications. Full article

Kidney disease (KD) is a major health challenge, affecting millions of people worldwide, highlighting the need for improved prevention and management strategies. The pathophysiological mechanisms converged on a common pathway characterized by inflammation, oxidative stress, fibrosis, nephron loss and failure. Curcumin, the active compound derived from turmeric (Curcuma longa), attracts considerable interest as a potential therapy for KD due to its anti-inflammatory, antioxidant and anti-fibrotic properties. Despite the benefits of curcumin, co-administration with kidney medications may cause drug interactions. Here, we systematically reviewed the efficacy of curcumin in alleviating KD and its safety when used with conventional treatments. Search terms included: curcumin AND (“diabetic nephropathy” OR “renal disease” OR “kidney disease”). Data on mechanisms of action, redox status, clinical benefits, side effects, and drug interactions were extracted and analyzed. Curcumin reduces oxidative stress, inflammation, apoptosis, fibrosis, ER stress, and lipid and glucose metabolism. Curcumin has multifaceted nephroprotective effects, while it is safe and well-tolerated. The curcumin–drug interactions reviewed were: -piperine, -epigallocatechin gallate, -losartan, -ginkgolide B, -rosuvastatin, -insulin, -cilostazol, and -ginger. These interactions improve curcumin bioavailability, and synergistic anti-inflammatory/antioxidant/antifibrotic and renoprotective effects. Future research should prioritize large-scale clinical trials to evaluate the efficacy and safety of curcumin in diverse KD populations. Full article

Human adenovirus infections are typically self-limiting but can become life-threatening in pediatric populations and immunocompromised individuals. Despite this clinical importance, efforts to develop antiviral drugs against adenoviruses remain limited. A promising strategy is to target the adenovirus protease (AVP), an enzyme essential for viral maturation and infectivity. Yet, research on AVP has lagged far behind that on other viral proteases. In this work, we aimed to reposition AVP as a viable target for antiviral therapy. We first discuss why AVP research has fallen behind and emphasize the need to redirect attention toward this protease. Building on advances in SARS-CoV-2 drug discovery, we evaluated the potential of repurposing inhibitors of the main protease (M^pro) and papain-like protease (PL^pro) as modulators of AVP. Additionally, we examined the untapped potential of phytochemicals as novel scaffolds. These analyses were supported by original molecular docking studies. Our results revealed that previously reported SARS-CoV-2 inhibitors, such as the M^pro inhibitor ensitrelvir and the PL^pro inhibitor (compound) 19, engage the catalytic site of AVP and may serve as starting scaffolds for inhibitor design. Screening of phytochemicals further identified promising candidates, including apigenin, camptothecin, kaempferol, and piperine. Together, these findings highlight AVP’s druggability and suggest that both repurposed antivirals and natural products provide complementary avenues for inhibitor development. Finally, we provide some recommendations to facilitate efforts in the discovery of novel AVP inhibitors. Full article

This study examined the characteristics of essential oils and ethanolic extracts from nine pepper species’ fruits to determine their chemical compositions and assess their biological activity. Ethanolic extracts and essential oils were analyzed using HPLC, GC-MS, FTIR, and ¹H NMR spectroscopy. The total phenolic content, total flavonoid content, antioxidant activity (DPPH assay), and antibacterial efficacy against five bacterial strains were assessed. Additionally, multielement analysis was performed using the TXRF method. The results demonstrated that the yields and chemical compositions differed markedly according to the pepper origin and extraction method. Ethanolic extracts consistently demonstrated greater total phenolic content and total flavonoid content and enhanced antioxidant and antibacterial properties relative to their respective essential oils. The increased bioactivity is due to the presence of non-volatile, polar compounds, which are not effectively transferred via hydrodistillation. Piperine was solely detected in extracts from black, green, white, Bengali, and Voatsiperifery peppers. This study emphasizes the necessity of optimizing extraction techniques to enhance the bioactivity of pepper extracts, highlighting their potential as sources of natural antioxidants and antibacterial agents. Full article

Malaria is one of the diseases that is a serious threat to global health, with millions of cases reported worldwide in recent years. The treatment of malaria is still a challenge due to its complex pathogenesis, resistance to many of the antimalarial drugs, and adverse toxicity. Nowadays, the possibilities of applying new natural molecules alone or in combination is being researched. However, many of these substances possess low aqueous solubility, which limits their bioavailability. The solubility of such substances could be improved by applying various techniques for their nanoencapsulation, e.g., incorporation in nanocapsules, liposomes, lipid nanoparticles, etc. The current review emphasizes studies on the nanoencapsulation of some of the well-known natural antimalarial agents (quinine, artemisinin) as well as substances with newly demonstrated antimalarial potential (piperine, quercetin, etc.). The review also discusses the opportunity to simultaneously load two natural agents in nanoparticles. Special focus is given to the metal nanoparticles (e.g., silver, gold, etc.) obtained by green synthesis from plants. Full article

Piperine is an alkaloid found in plants of the genus Piper, and particularly in P. nigrum. This compound has been under extensive research lately for its antimicrobial, antiviral, and also anti-inflammatory, anti-oxidant, anticancer, and positive metabolic properties. Regarding its antibacterial applications, current data show that piperine is effective against Bacillus sphaericus, Bacterioides fragilis, Escherichia coli, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus mutans, Pseudomonas aeruginosa, and Vibrio cholerae; its antifungal potency is exerted against Candida albicans and members of the Aspergillus family; antiviral activity has been documented against MERS-CoV, SARS-CoV2, EBOV, DENV, HCV, ZKV, and HPIV; and antiparasitic activity against Leishmania spp., Plasmodium spp., Trichomonas vaginalis, and Trypanosoma spp. While such applications are promising, more research is required to elucidate the mechanisms of action and to discover new ways of administration. Full article

Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits and cognitive decline. Cuprizone (CPZ)-induced demyelination is a well-established model for studying multiple sclerosis-like neurotoxicity. This study investigated the neuroprotective and immunomodulatory effects of self-nanoemulsifying drug delivery systems (SNEDDSs) incorporating curcumin, piperine, and Zanthoxylum rhetsa seed oil. Methods: Male mice were divided into five groups: control, CPZ-only, and CPZ co-treated with three nanoformulations BFZ (blank SNEDDS), CFZ (curcumin-SNEDDS), and PFZ (curcumin–piperine SNEDDS). CPZ was administered for 5 weeks, followed by a 2-week recovery or treatment phase. Key neuroinflammatory markers like CD4, CD8, cholinergic (acetylcholinesterase, AChE), myelin integrity (MBP), BDNF, CREB, TNFα, Il-1β were assessed at weeks 5 and 7 using ELISA. Alterations in antioxidant enzymes, brain histology, and behavioral outcomes were also investigated. Results: At week 5, CPZ significantly increased CD4 and CD8 expression and reduced AChE and MBP levels, indicating neuroinflammation, cholinergic impairment, and demyelination. Nanoformulation treatments (both prophylactic and therapeutic) markedly reduced CD4 and CD8 levels, with PFZ showing the most pronounced effect. AChE activity was significantly restored in all treatment groups, with PFZ and CFZ exceeding baseline levels, suggesting enhanced cholinergic function. MBP levels were highest in PFZ-treated mice, surpassing control values and indicating strong remyelination potential. These improvements persisted and further advanced at week 7, especially in PFZ and CFZ groups. Conclusions: Curcumin-based SNEDDS, particularly PFZ, significantly mitigated CPZ-induced neuroinflammation, promoted remyelination, and restored cholinergic activity in the frontal cortex. These findings highlight the therapeutic potential of bioenhanced curcumin nanoformulations for treating demyelinating and neuroinflammatory disorders. Full article

The phytochemical profiles, antioxidant capacities, mineral composition, and antibacterial activities of Zingiber officinale (Z. officinal) and Piper nigrum (P. nigrum) were explored through aqueous, ethanolic, and methanolic extractions. The extracts were analyzed for polyphenols, flavonoids, and tannins, and their antioxidant potential was assessed using the DPPH assay. UPLC-HRMS identified major bioactive compounds, including 6-gingerol and shogaol in Z. officinale, and piperine and piperlonguminine in P. nigrum. Mineral analysis showed that P. nigrum was particularly rich in essential elements, including calcium (Ca), magnesium (Mg), and iron (Fe). In antibacterial testing, P. nigrum demonstrated wider zones of inhibition against E. coli, whereas Z. officinale was more active at lower concentrations, showing MICs as low as 3.91 µg/mL against Salmonella and S. aureus. PCA analysis revealed strong correlations between phenolic content and biological effects. These results underscore the potential of both spices as effective natural agents for use in food preservation and health-promoting applications. Full article