Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Identification of novel dimers and chemical profiling of acid amide alkaloids in Piper nigrum.

Peppers (Piper nigrum L.) are distinguished by their pungent flavor and aroma. Piperine is a major acid-amide alkaloid with a piperidine ring that gives pepper its flavor and scent. In plant metabolomics research, the accessibility of the chemical standards is critical for scientific credibility. We isolated and identified 10 novel dimers of acid amide alkaloids (9-15 and 20-22), along with 12 known monomers (1-6) and dimers (7, 8, 16-19) from black pepper. Subsequently, we found the distribution of monomers and dimers of acid amide alkaloids in black and white peppers by twenty-two acid amide alkaloids which we obtained using the molecular networking technique and multivariate analysis to reveal the molecular relationships between the acid amide alkaloids in black and white peppers. Our research delved into the chemical diversity of acid amide alkaloids in black and white peppers, which could help inform future culinary and potential medicinal utilization of pepper.

Network pharmacology and experimental insights into STAT3 inhibition by novel isoxazole derivatives of piperic acid in triple negative breast cancer.

STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications.

Anticancer Potential of the Principal Constituent of Piper nigrum, Piperine: A Comprehensive Review.

Black pepper's main component, piperine, is a phytochemical that gives the spice its distinctively pungent flavor, which has made it a staple in human diets for decades and a widely used food item. In addition to its use as a culinary component and preservation agent, it is also employed in traditional medicine for a diverse range of objectives, a practice that has been substantiated by existing scientific investigations on its physiological impacts in the majority of instances. Piperine contains various bioactive effects, such as antibacterial activity, in addition to several physiological benefits that could help overall human health, such as immunomodulatory, hepatoprotective, antioxidant, antimetastatic, anticancer, and many more properties that have been established. Clinical trials revealed that this phytochemical has exceptional antioxidant, anticancer, and drug availability-enhancing properties, as well as immunomodulatory potential. The different components of evidence indicate the therapeutic potential of piperine and underscore the importance of incorporating it into both broad health-promoting interventions and supplementary treatment pharmaceutical formulations. This inclusion can enhance the bioavailability of other therapeutic medications, including those used in chemotherapy.

Classification of Pepper Seeds by Machine Learning Using Color Filter Array Images.

The purpose of this work is to classify pepper seeds using color filter array (CFA) images. This study focused specifically on Penja pepper, which is found in the Litoral region of Cameroon and is a type of Piper nigrum. India and Brazil are the largest producers of this variety of pepper, although the production of Penja pepper is not as significant in terms of quantity compared to other major producers. However, it is still highly sought after and one of the most expensive types of pepper on the market. It can be difficult for humans to distinguish between different types of peppers based solely on the appearance of their seeds. To address this challenge, we collected 5618 samples of white and black Penja pepper and other varieties for classification using image processing and a supervised machine learning method. We extracted 18 attributes from the images and trained them in four different models. The most successful model was the support vector machine (SVM), which achieved an accuracy of 0.87, a precision of 0.874, a recall of 0.873, and an F1-score of 0.874.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L.

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.

Genetic diversity, mating type and pathogenicity of two Phytophthora species infecting black pepper in India.

Phytophthora capsici and P. tropicalis are the two species of Phytophthora associated with foot rot disease of black pepper in India. High genetic diversity amongst the Phytophthora species contributes to its wide host range and variability in the virulence pattern. In the present study, genetic diversity of Phytophthora species infecting black pepper was analysed using RAMS (Random Amplified Microsatellites) and REP (Repetitive Extragenic Palindromic)-PCR fingerprinting. Forty-eight isolates, 24 each of P. capsici and P. tropicalis collected from major black pepper growing states, such as Karnataka, Kerala, Tamil Nadu and Goa, were used in the study. The analyses revealed a total of 160 loci of which 150 (93.75%) were polymorphic. UPGMA cluster and PCoA analysis based on combined RAMS and REP-PCR data clearly grouped the P. capsici and P. tropicalis isolates into two clusters which were further divided into four sub-clusters viz., I & II (P. capsici) and III & IV (P. tropicalis). The study clearly indicated that all the isolates were genetically unique and the entire population was heterogeneous. REP-PCR primers showed more polymorphic loci than RAMS primers. Further, sixteen isolates were selected for morphological and infectivity analyses under in vitro conditions. The isolates exhibited varied colony morphology, sporangial shapes and belonged to A1 mating type. Under in vitro conditions, all the sixteen black pepper Phytophthora isolates could infect nutmeg, tomato, chilli, pumpkin, and cucumber and few of the isolates could infect cardamom. None of the isolates could infect coconut, areca nut and vanilla. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03843-1.

Green synthesis of Piper nigrum copper-based nanoparticles: in silico study and ADMET analysis to assess their antioxidant, antibacterial, and cytotoxic effects.

Nanobiotechnology is a popular branch of science that is gaining interest among scientists and researchers as it allows for the green manufacturing of nanoparticles by employing plants as reducing agents. This method is safe, cheap, reproducible, and eco-friendly. In this study, the therapeutic property of Piper nigrum fruit was mixed with the antibacterial activity of metallic copper to produce copper nanoparticles. The synthesis of copper nanoparticles was indicated by a color change from brown to blue. Physical characterization of Piper nigrum copper nanoparticles (PN-CuNPs) was performed using UV-vis spectroscopy, FT-IR, SEM, EDX, XRD, and Zeta analyzer. PN-CuNPs exhibited potential antioxidant, antibacterial, and cytotoxic activities. PN-CuNPs have shown concentration-dependent, enhanced free radical scavenging activity, reaching maximum values of 92%, 90%, and 86% with DPPH, H2O2, and PMA tests, respectively. The antibacterial zone of inhibition of PN-CuNPs was the highest against Staphylococcus aureus (23 mm) and the lowest against Escherichia coli (10 mm). PN-CuNPs showed 80% in vitro cytotoxicity against MCF-7 breast cancer cell lines. Furthermore, more than 50 components of Piper nigrum extract were selected and subjected to in silico molecular docking using the C-Docker protocol in the binding pockets of glutathione reductase, E. coli DNA gyrase topoisomerase II, and epidermal growth factor receptor (EGFR) tyrosine to discover their druggability. Pipercyclobutanamide A (26), pipernigramide F (32), and pipernigramide G (33) scored the highest Gibbs free energy at 50.489, 51.9306, and 58.615 kcal/mol, respectively. The ADMET/TOPKAT analysis confirmed the favorable pharmacokinetics, pharmacodynamics, and toxicity profiles of the three promising compounds. The present in silico analysis helps us to understand the possible mechanisms behind the antioxidant, antibacterial, and cytotoxic activities of CuNPs and recommends them as implicit inhibitors of selected proteins.

Piper nigrum Extract Inhibits the Growth of Human Colorectal Cancer HT-29 Cells by Inducing p53-Mediated Apoptosis.

Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract with the second highest mortality rate globally. Piper nigrum is a widely used traditional medicinal plant, exhibiting antitumor activity against various tumor cells. At present, research on the effect of Piper nigrum on CRC is limited to in vitro cytotoxicity, lacking comprehensive mechanism investigations. This study aimed to explore the inhibitory effect and mechanism of Piper nigrum extract (PNE) on HT-29 cells. Firstly, we identified the chemical components of PNE. Then, MTT assay, colony formation assay, JC-1 staining, and flow cytometry were used to analyze the effect of PNE on HT-29 cells in vitro. A xenograft model, histopathological examination, immunohistochemistry, and western blot were used to evaluate the tumor growth inhibitory activity and mechanism of PNE in vivo. The results indicated that PNE could inhibit cell proliferation and colony formation, reduce mitochondrial membrane potential, induce cell apoptosis in vitro, and inhibit tumor growth in vivo. Furthermore, PNE could regulate p53 and its downstream proteins, and subsequently activate the caspase-3 pathway. In summary, PNE probably induced apoptosis of HT-29 cells through the mitochondrial pathway mediated by p53. All these results suggested that PNE might be a potential natural-origin anti-CRC drug candidate.

Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals.

Background: Spasm of muscle is one of the frequent complaints seen by most of the population worldwide. The present study evaluated the efficacy of some of the commonly used herbal extracts against known spasmogens, such as histamine and 5-hydroxytryptamine (5-HT). Material and methods: The study was conducted on isolated guinea pig ileum and rat uterus preparations using histamine and 5-HT, respectively. Five herbal extracts such as Piper longum (P.L), Piper nigrum (P.N), Terminalia bellerica (T.B), Terminalia chebula (T.C), and Zingiber officinale (Z.O) were tested. Herbal extracts at doses 50, 150, 500, 1500, and 5000 mcg/ml were pretreated to the isolated tissue preparation, and the contractile response of histamine and 5-HT was recorded. The efficacy and the inhibitory concentration (IC50) were calculated and statistically analyzed by one-way ANOVA. Results: The study indicated that all five herbal extracts produced a concentration-dependent suppression of histamine and 5-HT-induced responses. A significant (p < 0.05) non-competitive antagonism was observed against the known spasmogen induced smooth muscle contraction for P.L, P.N, T.B, and Z.O in both guinea pigs and rat uterus preparation. Moreover, P.L and P.N completely abolished (100%) the contractile response induced by histamine and 5-HT. Although, T.C produced a concentration-dependent reduction in known spasmogen-induced contraction but the response was found to be statistically non-significant (p greater than 0.05). Conclusion: The finding suggested that P.L. and P.N. have better activity in terms of reducing the spasmogenic contractions compared to other extracts. Additionally, T.B. and Z.O. can lessen the uterine and intestinal contractions brought on by spasmogens. Although P.L and P.N demonstrated better efficacy against the spasmogenic activity of histamine and 5-HT, more research, particularly on isolated phytochemicals of the extracts and involving different experimental models, is required before establishing the precise safety and efficacy against spasmogenic-induced disorders.

Effect of Piper nigrum essential oil in dextran sulfate sodium (DSS)-induced colitis and its potential mechanisms.

BACKGROUND: Piper nigrum essential oil (PnEO) possesses pleasant aroma, unique flavor, and various bioactivities; however, its role against colitis remains unclear. PURPOSE: In this study, we investigated the role of PnEO in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: Initially, we identified and quantified the components of PnEO by gas chromatography-mass spectrometry (GC-MS). Subsequently, we investigated the protective role of PnEO (50 and 200 mg/kg) in DSS-induced colitis in mice by evaluating disease activity index (DAI) scores and colon length, and performing histological analyses. Eyeball blood was collected and cytokines were determined using ELISA kits. The anti-inflammatory mechanisms of PnEO were analyzed by western blot (WB) and immunohistochemistry (IHC). The intestinal barrier function was evaluated according to tight junction (TJ) protein mRNA levels. We used 16S rRNA gene sequencing to analyze the intestinal microflora of mouse cecal contents. RESULTS: Supplementation with PnEO (50 and 200 mg/kg) increased colon length and improved colon histopathology. PnEO regulated inflammatory responses by downregulating TLR4/MAPKs activation, thereby reducing the release of cytokines and mediators. Moreover, it also protected the intestinal barrier through enhancing the expression of claudin-1, claudin-3, occludin, ZO-1, and mucin 2. 16S rRNA gene sequencing revealed that PnEO (200 mg/kg) decreased the abundance of Akkermansia in the gut microbiome. CONCLUSION: PnEO treatment (50 and 200 mg/kg) relieved DSS-induced colitis by inhibiting TLR4/MAPK pathway and protecting intestinal barrier, and high-dose PnEO exhibited better effects. Moreover, PnEO (200 mg/kg) regulated key compositions of the gut microbiome, which indicated that it had therapeutic potential for sustaining gut health to lower the risk of colitis.

Piper nigrum extract suppresses tumor growth and enhances the antitumor immune response in murine models of breast cancer and melanoma.

Although the antitumor effect of P. nigrum has been widely studied, research related to its possible immunomodulatory effects is relatively scarce. Here, the antitumor and immunomodulatory activity of an ethanolic extract of P. nigrum were evaluated in the murine models of 4T1 breast cancer and B16-F10 melanoma. In vitro evaluations showed that the P. nigrum extract has cytotoxic activity, induces apoptotic cell death, and has a pro-oxidant effect in both cell lines, but it regulates glucose uptake differently in both lines, decreasing it in 4T1 but not in B16-F10. P. nigrum extract significantly reduced tumor size in both models and decreased the occurrence of macrometastases in 4T1 model. Evaluation of immune subpopulations by flow cytometry revealed that the P. nigrum extract significantly increases the frequency of dendritic cells and activated CD8+ T cells and decreases the frequency of myeloid-derived suppressor like cells and Tregs in the tumor microenvironment of both models but with different dynamics. Our findings strongly suggest that the P. nigrum extract exerts immunomodulatory functions, slightly related to the modulation of cellular energy metabolism, which could ultimately contribute to the promising antitumor effect of P. nigrum.

Investigation of phytotherapeutic potential of herbal mixtures and their effects on salbutamol induced cardiotoxicity and hyperlipidemia in rabbits.

BACKGROUND: Cardiovascular diseases (CVDs) are the major cause of deaths all over the world. The high level of blood cholesterol and oxidative stress are major risk factors for heart diseases. The phytotherapeutics have attracted attention as potential agents for preventing and treating oxidative stress associated diseases. The objective of present study was to evaluate the synergetic cardio-protective and antilipidemic potential of medicinal plants viz. Coriandrum sativum, Piper nigrum and Cactus grandiflorus. Cardio-protective and anti-lipidemic potential of herbal mixture was evaluated against salbutamol induced cardiotoxicity in rabbits. For this purpose, rabbits were divided into six groups as normal control, salbutamol control, curative and standard drug curative. RESULTS: Salbutamol significantly (p < 0.05) increased the level of serum cardiac biomarkers (ALT, CK-MB, AST and LDH) and lipids (LDL, triglycerides, cholesterol) in rabbits. The prior and post administration of herbal mixture significantly (p < 0.05) lowered the elevated level of serum cardiac biomarkers and lipids equal to normal control. Gross pathological examination revealed that heart of salbutamol control animals became hardened, congested and were enlarged than preventive and curative groups. The phytotherapeutic analysis of medicinal plants revealed the presence of phenols, tannins, alkaloids and steroids. CONCLUSION: The results showed that this herbal mixture has strong cardio-protective and anti-lipidemic potential.

Identification and screening of fungicides against Piper nigrum basal Fusarium wilt disease in Hainan, China.

Fusarium wilt has occurred in the main Piper nigrum cultivation regions, which seriously affects the yield and quality of P. nigrum. To identify the pathogen of this disease, the diseased roots were collected from a demonstration base in Hainan Province. The pathogen was obtained by tissue isolation method and confirmed by pathogenicity test. Based on the morphological observation, sequence analyses of TEF1-α nuclear gene, Fusarium solani was identified as the pathogen causing P. nigrum Fusarium wilt and induced symptoms on inoculated plants, including chlorosis, necrotic spots, wilt, drying, and root rot. The experiments for the antifungal activity showed that all the 11 fungicides selected in this study showed certain inhibitory effects on the colony growth of F. solani, where 2% kasugamycin AS, 45% prochloraz EW, 25 g·L-1 fludioxonil SC and 430 g·L-1 tebuconazole SC exhibited relative higher inhibitory effects with EC50 as 0.065, 0.205, 0.395, and 0.483 mg·L-1 , respectively, and were selected to perform SEM analysis and test in seeds in vitro. The SEM analysis showed that kasugamycin, prochloraz, fludioxonil, and tebuconazole might have exerted their antifungal effect by damaging F. solani mycelia or microconidia. These preparations were applied as a seed coating of P. nigrum Reyin-1. The kasugamycin treatment was most effective in reducing the harmful impact of F. solani on the seed germination. These results presented herein provide useful guidance for the effective control of P. nigrum Fusarium wilt.

Piper nigrum Extract: Dietary Supplement for Reducing Mammary Tumor Incidence and Chemotherapy-Induced Toxicity.

A low piperine fractional Piper nigrum extract (PFPE) was prepared by mixing cold-pressed coconut oil and honey in distilled water, namely, PFPE-CH. In this study, PFPE-CH was orally administered as a dietary supplement to decrease the risk of tumor formation and reduce the side effects of chemotherapeutic drugs during breast cancer treatment. The toxicity study demonstrated no mortality or adverse effects after administrating PFPE-CH at 5000 mg/kg during a 14-day observation period. Additionally, PFPE-CH at 86 mg/kg BW/day did not cause any harm to the kidney or liver function of the rats for six months. In a cancer prevention study, treatment with PFPE-CH at 100 mg/kg BW for 101 days induced oxidative stress and increased the immune response by altering the levels of cancer-associated cytokines (IL-4, IL-6, and IFN-g), leading to a reduction in the tumor incidence of up to 71.4% without any adverse effects. In combination with doxorubicin, PFPE-CH did not disrupt the anticancer effects of the drug in rats with mammary tumors. Surprisingly, PFPE-CH reduced chemotherapy-induced toxicity by improving some hematological and biochemical parameters. Therefore, our results suggest that PFPE-CH is safe and effective in reducing breast tumor incidence and toxicity of chemotherapeutic drugs during cancer treatment in mammary tumor rats.

Effects of Piper betle Extracts against Biofilm Formation by Methicillin-Resistant Staphylococcus pseudintermedius Isolated from Dogs.

Emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolated from dogs with cutaneous and wound infections has significantly impacted veterinary medicine. This study aimed to isolate S. pseudintermedius from canine pyoderma and investigate the effects of ethanolic extracts of Piper betle (PB), P. sarmentosum (PS), and P. nigrum (PN) on the bacterial growth and biofilm formation of S. pseudintermedius and MRSP. Of the isolated 152 isolates, 53 were identified as S. pseudintermedius using polymerase chain reaction, and 10 isolates (6.58%) were identified as MRSP based on the presence of mecA. Based on phenotype, 90% of MRSPs were multidrug-resistant. All MRSP had moderate (10%, 1/10) and strong (90%, 9/10) biofilm production ability. PB extracts were the most effective in inhibiting planktonic cells, and the minimum inhibitory concentration at which ≥50% of the isolates were inhibited (MIC50) was 256 µg/mL (256-1024 µg/mL) for S. pseudintermedius isolates and 512 µg/mL (256-1024 µg/mL) for MRSP isolates. The MIC90 for S. pseudintermedius and MRSP was 512 µg/mL. In XTT assay, PB at 4× MIC showed an inhibition rate of 39.66-68.90% and 45.58-59.13% for S. pseudintermedius and MRSP, respectively, in inhibiting biofilm formation. For PB at 8× MIC, the inhibition rates for S. pseudintermedius and MRSP were 50.74-81.66% and 59.57-78.33%, respectively. Further, 18 compounds were identified in PB using gas chromatography-mass spectrometry, and hydroxychavicol (36.02%) was the major constituent. These results indicated that PB could inhibit bacteria growth of and biofilm formation by S. pseudintermedius and MRSP isolated from canine pyoderma in a concentration-dependent manner. Therefore, PB is a potential candidate for the treatment of MRSP infection and biofilm formation in veterinary medicine.

Black Pepper (Piper nigrum) Alleviates Oxidative Stress, Exerts Potential Anti-Glycation and Anti-AChE Activity: A Multitargeting Neuroprotective Agent against Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are a family of disorders that cause progressive structural and functional degeneration of neurons. Among all the organs in the body, the brain is the one that is the most affected by the production and accumulation of ROS. Various studies have shown that an increase in oxidative stress is a common pathophysiology for almost all NDs, which further affects various other pathways. The available drugs lack the wide spectrum necessary to confront these complexities altogether. Hence, a safe therapeutic approach to target multiple pathways is highly desirable. In the present study, the hexane and ethyl acetate extracts of Piper nigrum (black pepper), an important spice, were evaluated for their neuroprotective potential in hydrogen peroxide-induced oxidative stress in human neuroblastoma cells (SH-SY5Y). The extracts were also subjected to GC/MS to identify the important bioactives present. The extracts exhibited neuroprotection by significantly decreasing the oxidative stress and restoring the mitochondrial membrane potential in the cells. Additionally, the extracts displayed potent anti-glycation and significant anti-Aß fibrilization activities. The extracts were competitive inhibitors of AChE. The multitarget neuroprotective mechanism displayed by Piper nigrum indicates it as a potential candidate in the treatment of NDs.

Effects of Piper nigrum L. Fruit Essential Oil Toxicity against Stable Fly (Diptera: Muscidae).

The efficacy of Piper nigrum L. fruit essential oil (EO) against Stomoxys calcitrans (stable fly), a blood-feeding fly distributed worldwide, was investigated. This study aimed to evaluate the insecticidal activity of EO based on contact and fumigant toxicity tests. Chemical analysis of the EO using gas chromatography-mass spectrometry revealed that sabinene (24.41%), limonene (23.80%), ß-caryophyllene (18.52%), and α-pinene (10.59%) were the major components. The results demonstrated that fly mortality increased with increasing EO concentration and time during the first 24 h of exposure. The median lethal dose was 78.37 µg/fly for contact toxicity, while the 90% lethal dose was 556.28 µg/fly. The median lethal concentration during fumigant toxicity testing was 13.72 mg/L air, and the 90% lethal concentration was 45.63 mg/L air. Our findings suggested that essential oil extracted from P. nigrum fruit could be a potential natural insecticidal agent for control of stable fly. To examine the insecticidal properties of P. nigrum fruit EO, further field trials and investigation into the efficacy of nano-formulations are required.

A review on multi-therapeutic potential of (-)-cubebin: experimental evidences.

Lignans are a large category of polyphenolic compounds that have low molecular weight and are widely distributed in the plant kingdom. They have been recognized for their potential antioxidizing and antiproliferative action. One of the most important lignans is cubebin which is abundantly isolated from the leaves and seeds of Piper cubeba and Piper nigrum. Cubebin possesses numerous biological actions such as antileukemic, trypanocidal, antimycobacterial, analgesic, anti-inflammatory, histamine antagonist, antifungal, and antispasmodic. This review discusses the in vitro and in vivo pharmacological studies on cubebin related to biochemistry and pharmacological applications and it ensures that it widely shows therapeutic potential. We expect that these therapeutic actions will set a new track in the formation of novel biological agents by the derivatization of cubebin. This review will assuredly fascinate countless researchers to begin further experimentation that might lead to novel agents for the treatment and prevention of diseases.