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Abstract Background Numerous insect pests attack stored grains causing both qualitative and quantitative losses. The most damaging pest that infests dry stored produce is the red flour beetle, Tribolium castaneum, a secondary pest of stored goods. This pest, especially in its adult stage, exhibits resistance to chemical insecticides, thereby rendering the traditional pesticides ineffective in controlling it. Phyto-derivatives, which are strong insecticides and also ecologically benign, have gained interest as non-chemical solutions for controlling this pest. Hence, the objective of this study was to investigate the potential of Piper longum leaf extract insecticidal action as an environmentally benign insecticide for the first time against the adults of T. castaneum. In this study, P. longum leaf ethanol extract was tested against the adults of T. castaneum by petri dish bioassay method. Ad hoc studies to verify significant mortality for the initial confirmation of adulticidal activity were conducted for 24 h at different dosages of 62.5, 125, 250, 500 and 1000 mg/L of P. longum leaf ethanol extract. Thereafter, dosages set at 10, 20, 30 and 40 mg/L for the fractions of P. longum leaf ethanol extract were conducted. Prior to this, the leaf extract of this plant was subjected to column chromatography for fractionation. The fractions tested for adulticidal activity were subjected to gas chromatography–mass spectroscopy. Results Significant adulticidal action with 100% adult mortality was observed in ethanol extract of P. longum leaves. Among the fourteen fractions (F0–F13) obtained tested, only fractions, F5, F10 and F13, demonstrated adulticidal activity, and the remaining fractions displayed poor activity. One hundred per cent morality was noted in T. castaneum adults after 96 h at 40 mg/L in F5 and F10, and in F13 at 20 mg/L, and their respective LD50 values were 17.6, 26.6 and 10.0 mg/L. The fractions F5, F10 and F13 contained fatty acids, viz., hexadecanoic acid, dotriacontane and heptacosane in F5; tetradecanoic acid and nonadecanoic acid in F10; and octadecanoic acid, aspartame and tridecanoic acid in F13, revealed through gas chromatography–mass spectroscopy. Conclusions The results of the study showed that P. longum ethanol leaf extract revealed significant adulticidal activity and is a promising toxic agent to the adults of T. castaneum. The fatty acids in the ethanolic leaf extract fractions of P. longum could have caused toxicity to the adults of T. castaneum. According to the current literature survey, this is the first research report on the adulticidal activity of P. longum leaf extracts against the adults of T. castaneum.

Background: Numerous insect pests attack stored grains causing both qualitative and quantitative losses. The most damaging pest that infests dry stored produce is the red flour beetle, Tribolium castaneum, a secondary pest of stored goods. This pest, especially in its adult stage, exhibits resistance to chemical insecticides, thereby rendering the traditional pesticides ineffective in controlling it. Phyto-derivatives, which are strong insecticides and also ecologically benign, have gained interest as non-chemical solutions for controlling this pest. Hence, the objective of this study was to investigate the potential of Piper longum leaf extract insecticidal action as an environmentally benign insecticide for the first time against the adults of T. castaneum. In this study, P. longum leaf ethanol extract was tested against the adults of T. castaneum by petri dish bioassay method. Ad hoc studies to verify significant mortality for the initial confirmation of adulticidal activity were conducted for 24 h at different dosages of 62.5, 125, 250, 500 and 1000 mg/L of P. longum leaf ethanol extract. Thereafter, dosages set at 10, 20, 30 and 40 mg/L for the fractions of P. longum leaf ethanol extract were conducted. Prior to this, the leaf extract of this plant was subjected to column chromatography for fractionation. The fractions tested for adulticidal activity were subjected to gas chromatography–mass spectroscopy. Results: Significant adulticidal action with 100% adult mortality was observed in ethanol extract of P. longum leaves. Among the fourteen fractions (F0–F13) obtained tested, only fractions, F5, F10 and F13, demonstrated adulticidal activity, and the remaining fractions displayed poor activity. One hundred per cent morality was noted in T. castaneum adults after 96 h at 40 mg/L in F5 and F10, and in F13 at 20 mg/L, and their respective LD50 values were 17.6, 26.6 and 10.0 mg/L. The fractions F5, F10 and F13 contained fatty acids, viz., hexadecanoic acid, dotriacontane and heptacosane in F5; tetradecanoic acid and nonadecanoic acid in F10; and octadecanoic acid, aspartame and tridecanoic acid in F13, revealed through gas chromatography–mass spectroscopy. Conclusions: The results of the study showed that P. longum ethanol leaf extract revealed significant adulticidal activity and is a promising toxic agent to the adults of T. castaneum. The fatty acids in the ethanolic leaf extract fractions of P. longum could have caused toxicity to the adults of T. castaneum. According to the current literature survey, this is the first research report on the adulticidal activity of P. longum leaf extracts against the adults of T. castaneum. [ABSTRACT FROM AUTHOR]

This study attempted synthesis and characterization of zinc oxide nanoparticles (ZnO NPs) using the aqueous extract of Piper longum catkin and its in vitro antibacterial efficacy against multi-drug-resistant strains (MDR) of non- typhoidal Salmonella (NTS) spp. (S. enterica Typhimurium and S. Enteritidis). The green synthesized ZnO NPs exhibited an absorbance peak at 340 nm by UV-Vis spectroscopy, which was confirmed by FTIR analysis. The TGA/DTA revealed a progressive thermal degradation of the ZnO NPs between 250 °C and 400 °C; however, good thermal stability was exhibited for annealing temperatures between 900 °C and 1300 °C. The ZnO NPs exhibited hexagonal wurtzite crystalline structure by PXRD analysis, which was further confirmed by electron microscopy. Microbroth dilution technique exhibited an MIC and MBC values of 125 and 250 µg/mL, respectively. Overall, the study demonstrated a facile, eco-friendly method for the synthesis of ZnO NPs, which could be employed as a potential antimicrobial alternative candidate. [ABSTRACT FROM AUTHOR]

Bacterial communication, Quorum Sensing (QS), is a target against virulence and prevention of antibiotic-resistant infections. 16 derivatives of Piperlongumine (PL), an amide alkaloid from Piper longum L., were screened for QS inhibition. PL-18 had the best QSI activity. PL-18 inhibited the lasR-lasI, rhlR-rhlI, and pqs QS systems of Pseudomonas aeruginosa. PL-18 inhibited pyocyanin and rhamnolipids that are QS-controlled virulence elements. Iron is an essential element for pathogenicity, biofilm formation and resilience in harsh environments, its uptake was inhibited by PL-18. Pl-18 significantly reduced the biofilm biovolume including in established biofilms. PL-18-coated silicon tubes significantly inhibited biofilm formation. The transcriptome study of treated P. aeruginosa showed that PL-18 indeed reduced the expression of QS and iron homeostasis related genes, and up regulated sulfur metabolism related genes. Altogether, PL-18 inhibits QS, virulence, iron uptake, and biofilm formation. Thus, PL-18 should be further developed against bacterial infection, antibiotic resistance, and biofilm formation.

Background: There has been an increasing trend for the development of natural formulations for plaque control using medicinal plants as an adjunct, which can be a feasible alternative as these are widely available, cost-effective, and have fewer side effects. Aim: The evaluation of the effects of medicinal plant extracts in chronic periodontitis (CP). Materials and Methods: This study was carried out in two phases; first the antibacterial activity of two medicinal plant extracts was tested on periodontal pathogens, thereafter, a clinical assessment was carried out on subjects with CP. Forty-five individuals suffering from CP were randomized into three different groups; Group A: Scaling and root planing (SRP) along with Piper longum rinse, Group B: SRP along with mixture of Tinospora cordifolia and P. longum rinse, Group C: SRP along with chlorhexidine (CHX) (control group). The clinical parameters (gingival index [GI], plaque index, gingival bleeding index [BI], probing pocket depth [PPD], and clinical attachment level [CAL]) were recorded at baseline and months 1 and 3. The intra- and intergroup comparison of clinical parameters for all groups at different time intervals was performed. Results: At the end of the trial, all the three groups showed a statistically significant reduction when compared to baseline for all the clinical parameters. In intergroup comparison, statistically significant reduction in GI, PPD, and CAL for both Group A and Group C was seen at 3 months as compared to Group B. Comparable reduction was seen between Group A and C for all the clinical parameters. Reduction in plaque and gingival BI was seen to be highest in Group A. Conclusion: P. longum can be effectively utilized as an additive to mechanical periodontal treatment in comparison to CHX mouthwash for CP patients.

Numerous species of beetle attack agricultural storage items, causing significant economic losses in terms of quantity and quality. The most harmful pest infesting dry stored produce is the red flour beetle, Tribolium castaneum, which is a well-known secondary pest of stored products. This insect pest show resistance to chemical insecticides, making it difficult to control this pest species with conventional pesticides. Search for non-chemical alternatives for managing this beetle pest has drawn attention for phyto derivatives, many of which are potent as insecticide and yet environmentally friendly. In this study Piper longum leaf extracts in ethyl acetate and methanol were used against eggs of different age, and fourth and fifth instar larvae of Tribolium castaneum. In petri dish bioassay method, ethyl acetate and methanol extracts showed significant ovicidal action with 100% mortality on '0', '2', and '4' days old eggs at concentrations ranging from 300 to 500 µg/dL after 72 and 96 h. The ethyl acetate extract caused 100% mortality of fourth instar larvae at 10, 9 and 8 µg/dL; and on the fifth instar at 10, 8 and 7 µg/dL after 48, 72 and 96 h, respectively. The methanol extract exhibited a similar pattern to that shown in the ethyl acetate extract on the fourth instar larvae after 48, 72 and 96 h of exposure, while for the fifth instar larvae, 100% mortality was recorded at concentrations of 9, 8 and 7 µg/dL, respectively. The results of the study showed that Piper longum leaf extracts is a promising toxic agent to Tribolium castaneum. According to the existence literature survey, this is the first research report on the ovicidal and larvicidal activity of Piper longum leaf extracts against Tribolium castaneum. [ABSTRACT FROM AUTHOR]

Piper longum, the Indian long pepper, is widely used in Ayurvedic medicine system to cure respiratory and digestive disorders. In a previous study, we reported the isolation and characterization of plant growth promoting (PGP) endophytic bacteria from P. longum. Here, we have tested the effect of two native endophytic bacteria, Acinetobacter soli PlS14 and Enterobacter hormaechei PlR15, on growth attributes, adventitious root development and reactive oxygen species levels in P. longum PlR15. Our results indicate that stem cuttings treated with A. soli PlS14 and E. hormaechei PlR15 exhibited rooting in > 50% of stem cuttings, when none of the Control cuttings did. Further, the endophyte-inoculated plants showed better vegetative growth (in terms of shoot growth and leaf number); higher levels of chlorophyll, proline and phenylalanine ammonia lyase; and lesser accumulation of reactive oxygen species than Control plants. The improved growth performance of endophyte-inoculated plants could be corelated with results of localization studies that indicate higher bacterial population in roots of endophyte-inoculated plants. To our knowledge, this is the first report of use of native endophytic strains as bioinoculants for growth of P. longum. Altogether, our results highlight the (often neglected) role of PGP native endophytes for cultivation of plants including medicinal plant species. [ABSTRACT FROM AUTHOR]

Background: There has been an increasing trend for the development of natural formulations for plaque control using medicinal plants as an adjunct, which can be a feasible alternative as these are widely available, cost-effective, and have fewer side effects. Aim: The evaluation of the effects of medicinal plant extracts in chronic periodontitis (CP). Materials and Methods: This study was carried out in two phases; first the antibacterial activity of two medicinal plant extracts was tested on periodontal pathogens, thereafter, a clinical assessment was carried out on subjects with CP. Forty-five individuals suffering from CP were randomized into three different groups; Group A: Scaling and root planing (SRP) along with Piper longum rinse, Group B: SRP along with mixture of Tinospora cordifolia and P. longum rinse, Group C: SRP along with chlorhexidine (CHX) (control group). The clinical parameters (gingival index [GI], plaque index, gingival bleeding index [BI], probing pocket depth [PPD], and clinical attachment level [CAL]) were recorded at baseline and months 1 and 3. The intra- and intergroup comparison of clinical parameters for all groups at different time intervals was performed. Results: At the end of the trial, all the three groups showed a statistically significant reduction when compared to baseline for all the clinical parameters. In intergroup comparison, statistically significant reduction in GI, PPD, and CAL for both Group A and Group C was seen at 3 months as compared to Group B. Comparable reduction was seen between Group A and C for all the clinical parameters. Reduction in plaque and gingival BI was seen to be highest in Group A. Conclusion: P. longum can be effectively utilized as an additive to mechanical periodontal treatment in comparison to CHX mouthwash for CP patients. [ABSTRACT FROM AUTHOR]

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)–bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (Frel = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) has the second highest incidence and fatality rates of any malignancy, at 10.2 and 9.2%, respectively. Plants and plants-based products for thousands of years have been utilized to treat cancer along with other associated health issues. Alkaloids are a valuable class of chemical compounds with great potential as new medicine possibilities. Piper longum Linn contains various types of alkaloids. In this research, the ethanolic root extract of P. longum (EREPL) is the subject of study based on network pharmacology. Two alkaloids were chosen from the gas chromatography mass spectrometry (GC–MS) analysis. However, only piperlonguminine received preference because it adhered to Lipinski's rule and depicted no toxicity. Web tools which are available online, like, Swiss ADME, pkCSMand ProTox-II were used to evaluate the pharmacokinetics and physiochemical properties of piperlonguminine. The database that SwissTargetPrediction and TCMSP maintain contains the targets for piperlonguminine. Using DisGeNET, GeneCards and Open Targets Platform databases, we were able to identify targets of CRC. The top four hub genes identified by Cytoscape are SRC, MTOR, EZH2, and MAPK3. The participation of hub genes in colorectal cancer-related pathways was examined using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The colorectal cancer pathway, the ErbB signaling pathway and the mTOR signaling pathway emerged to be important. Our findings show that the hub genes are involved in the aforementioned pathways for tumor growth, which calls for their downregulation. Additionally, piperlonguminine has the potential to become a successful medicine in the future for the treatment of CRC. [ABSTRACT FROM AUTHOR]

The female spikes (fruits) of Piper longum are widely used in Ayurvedic, Siddha and Unani medicine systems to treat respiratory and digestive disorders. The spikes are rich in piperine, a pharmacologically active amide alkaloid and a potent bioavailability enhancer, which accumulates to the highest level during the dark-green stage of spike development. Plant-associated microbiota influence the plant's fitness, response, and production of economically important metabolites. Considering the economic importance of piperine and other spike-derived alkaloids, understanding microbial community dynamics during spike development would be key to bioprospecting for economically important metabolites. In the present study, the structural diversity of microbial communities associated with early (SI), mid (SII), and late (SIII) stages of spike development in P. longum has been analysed by Illumina-based amplicon sequencing of 16S rRNA gene and ITS region. Results revealed that spike development significantly drives the diversity and abundance of spike-associated microbiota, especially bacterial communities. Cyanobacteria and Ascomycota constituted the most abundant bacterial and fungal phyla, respectively, across all stages of spike development. Interestingly, Halomonas, Kushneria and Haererehalobacter were found to be exclusively associated with SIII (corresponding to economically important) stage of spike development. Sphingomonas, Mortierella, Cladosporium and Vishniacozyma constituted the core microbiome of the spike. Besides, PICRUSt analysis revealed that amino acid metabolism was the most dominant metabolic function attributed to spike-associated bacterial communities. To the best of our knowledge, this is the first study to investigate the endomicrobiome dynamics during spike development in a medicinal plant species. [ABSTRACT FROM AUTHOR]

A selective, simple, and sensitive high-performance thin-layer chromatography (HPTLC) method was developed and validated for identification and quantitative estimation of piperine in different extracts of Piper longum. A developing solvent, acetone‒toluene (3:7, V/V) was employed to attain good separation of bands. Densitometric estimation was performed at 343 nm. Linearity was reckoned to be in the range of 0.2–1.0 μg per spot. Ethanolic extract of P. longum revealed a higher content of piperine than dimethylformamide (DMF), acetone, and dimethyl sulphoxide (DMSO) extract during analysis. The method was further validated for robustness, accuracy, precision, specificity, and linearity. Furthermore, the antioxidant activity of P. longum extracts was scrutinized using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and the ethanolic extract showed the highest antioxidant potential, with 55.26% inhibition. [ABSTRACT FROM AUTHOR]

The development of carbon dots via a green synthesis approach from natural products is one of the most researched areas nowadays. Herein, we present the synthesis of Piper longum leaves-derived aqueous carbon dots (PLACDs) via the simplest ecofriendly hydrothermal carbonization method. The PLACDs exhibited excitation-dependent emission behavior with maximum emission at 450 nm at an excitation wavelength of 365 nm. The High-Resolution Transmission Electron Microscopy results showed a quasi-spherical shape with an average size of 4.121 nm. The sharp diffractions of X-ray diffraction revealed its nanocrystalline property. The Energy Dispersive X-ray spectra reflected the presence of carbon, nitrogen, and oxygen. The Fourier-Transform Infrared Spectroscopy disclosed the existence of –OH, –C=C, –C=O, and –C–O–C groups. The PLACDs presented excellent biocompatibility against B16F10 (melanoma) and SiHa (cervical carcinoma) cells lines with concentration-dependent in vitro bioimaging results. It also exhibited antiradical activity with the IC50 value of 0.499 mg/mL and 0.051 mg/mL against DPPH and ABTS.+, respectively. It showed Fe3+ sensing with a lower limit of detection of 0.673 μM. Further, the PLACDs displayed excellent bacterial biocompatibility, pH-dependent fluorescence property, fluorescent ink property, photostability, physical, chemical, and thermal stability. [ABSTRACT FROM AUTHOR]

The recent pandemic due to the COVID-19 virus has caused a global catastrophe. ACE2 and TMPRSS2 are recognized as key targets for viral entry into the host cells. The pandemic has led to the utilization of many synthetic drugs; however, due to various side effects, there is still no effective drug available against the virus. Several natural approaches have been devised, including herbal and ayurvedic medicines, that have proven to be effective against the COVID-19 virus. In the present study, the effect of phytocompounds of Piper longum and Ocimum sanctum on ACE2 and TRMPSS2 proteins has been studied. The in silico study is done using computational tools of networks of protein–protein interaction, molecular docking, and drug assessment in terms of physicochemical properties, drug-likeness, lipophilicity, water solubility, and pharmacokinetics. Out of selected phytoconstituents, vicenin 2, rosmarinic acid, and orientin were found to have the highest efficacy in terms of molecular interaction and drug-likeness properties against ACE2 and TMPRSS2 host receptor proteins. Our in silico study proposes the therapeutic potential of phytocompounds from Piper longum and Ocimum sanctum in modulating ACE2 and TMPRSS2 expression. Targeting ACE2 and TMPRSS2 against the SARS-CoV2 by phytomolecules can serve as a rational approach for designing future anti-COVID drugs. [ABSTRACT FROM AUTHOR]

As India is a heterogeneous country, each region has a distinctive cuisine flavour and taste. This has implications for ethnopharmacology. The spices and condiments, which are the foundation of Indian food, are responsible for these flavours. The foundation of India’s diversified and ethnic cuisine is made up mostly of spices and condiments that are sourced from the country’s many biodiversity hotspots. In addition to having a wide range of scents, flavours, and tastes, these spices and condiments are also recognized to have a number of therapeutic qualities. The majority of these spices are frequently mentioned in Ayurveda, the traditional medical system, as cures for a variety of illnesses. One such spice that has long been known to possess a variety of medicinal effects is pipli, scientifically known as Piper longum (PL), a member of the Piperaceae family. [ABSTRACT FROM AUTHOR]

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

Phytochemical study on the methanolic extract of the aerial parts of this plant led to the isolation of 7 phenolic compounds (1 - 7), including 3 new ones (1 - 3). Their chemical structures were determined to be (7,8- threo)-1 -O-β -D-[6′ -O- syringoylglucopyranosyl]-2-methoxy-7,8,9-trihydroxyphenylpropane (1), (7,8- threo)-8 -O- (2′′-methoxyacetophenone-1′′-yl)-1 -O-β -D-glucopyranosyl-2-methoxy-7,9-dihydroxyphenylpropane (2), 1 -O-β -D-glucopyranosyl-2 -O- (2′′-methoxy-4′′-acetylphenyl)-3-hydroxypropane (3), (−)-isolariciresinol 4 -O-β -D-glucopyranoside (4), (−)-isolarisiresinol 9′ -O-β -D-glucopyranoside (5), (+)-lyoniresinol 9′ -O-β -D-glucopyranoside (6), (+)-isolarisiresinol 9′ -O-β -D-glucopyranoside (7) by the spectroscopic data and in comparison with those reported in the literature. Compounds 3 to 7 significantly inhibited NO production in LPS-activated RAW264.7 cells with IC50 values ranging from 32.09 ± 3.34 to 38.16 ± 1.35 µM, similar to those of the positive control, N G-monomethyl-L-arginine acetate (IC50 32.51 ± 3.70 µM). [ABSTRACT FROM AUTHOR]

Most bacteria are becoming resistant to almost all of the currently recommended drugs, leading to difficulty in their treatment. The present study focused on evaluating the therapeutic potential of Piper longum fruit extracts in terms of bactericidal, antioxidant and phytochemical evaluation by conducting antibacterial sensitivity tests against four multidrug-resistant Salmonella strains (Salmonella enterica subsp. arizonae, Salmonella Newport, Salmonella enterica ser. Typhi, and Salmonella enterica ser. Paratyphi) obtained from the Institute of Microbial Technology (IMTECH), Chandigarh. The Agar Well Diffusion method and the Minimum Inhibitory concentration (MIC) methods were performed to implement the anti-sensitivity test of crude extracts of the plant. The present study showed that the MIC of the P. longum was between 0.25-0.0625mg/ml, which was lowest in the aqueous extract at 0.5mg/100µl, and the highest in the methanol extract (1mg/100µl). The Minimum Bactericidal Concentration (MBC) was lowest in aqueous (0.5mg/100µl) and highest in methanol plant extract (1mg/100µl). The methanol extract had the maximum antibacterial potency, whereas the aqueous extract had the lowest. The antioxidant capacity of the plant extracts was determined using a DPPH assay. Methanol plant extract revealed the highest antioxidant power (81.92%) and the lowest was found in the aqueous extract (62.84%). The GC-MS approach identified active bioingredients, important botanicals including caryophyllene, eicosane, and piperazine (potent antibacterial agent) as naphthyridine (having antimicrobial, anticancer, and anti -inflammatory activities), among others. The unique aspect of the study was the effectiveness of P. longum against Salmonella strains that are resistant to multiple antibiotics. This suggests that P. longum can be a great source of novel antibacterial compound for the development of herbal formulations. [ABSTRACT FROM AUTHOR]

Piper longum (family Piperaceae), commonly known as "long‐pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo‐Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle‐East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion‐sting and are also used as a contraceptive. Various bioactive‐phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito‐larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro‐pharmacological, antihyperglycaemic, hepato‐protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti‐snake‐venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses. [ABSTRACT FROM AUTHOR]

Antioxidants are compounds that are able to inhibit the negative effects that come from free radicals. The phenomenon of imbalanced antioxidant production and the accumulation of free radicals in cells and tissues can cause oxidative stress. Excessive free radicals that enter the body cannot be warded off by endogenous antioxidant compounds so that the required antioxidant compounds can come from the outside, which helps in the performance of endogenous antioxidants. Antioxidants that come from outside consist of synthetic and natural antioxidants; however, synthetic antioxidants are not an option because they have toxic and carcinogenic effects. Therefore, the use of natural ingredients is an alternative method that is needed to create a new natural antioxidant compound. Piper species are being considered as possible medicinal plants for the development of new sources of antioxidants. Several studies have been carried out starting from the extract levels, fractions, and compounds of the Piper species, which showed good antioxidant activity. Currently, some of these plants are being used as ingredients in traditional medicines to treat allergies, toothaches, and coughs. This review examines the distribution, botanical data, pharmacology, especially antioxidant activity, and the compounds contained in five Piper species, namely Piper amalago L., Piper betle L., Piper hispidum Sw., Piper longum L., and Piper umbellatum L. [ABSTRACT FROM AUTHOR]

Balachaturbhadra Churna (BC), Ayurvedic powder dosage form, has four ingredients (Aconitum heterophyllum Wall. Ex Royle, Pistacia integerrima stew. Ex brandis, Piper longum Linn., and Cyperus rotundus linn.), which is commonly prescribed for treating fever, cough, and diarrhea in a pediatric setting. Aim: The present study evaluates the possible antiviral effect of phytochemicals from the ingredients of BC on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (MPro), Ribose Nucleic Acid (RNA) dependent RNA polymerase (RdRP), and spike-angiotensin-converting enzyme 2 (SA) complex through in silico evaluation. Materials and methods: X-ray crystal structure of MPro and Spike-Ace (SA) complex with Protein Data Bank (PDB) IDs 6LU7 and 6LZG and the SWISS model of RdRP were used as the drug targets. An enhanced docking methodology has been implemented to perform the molecular docking of these phytochemicals against the above-mentioned drug targets of SARS-CoV-2. DOCK6 was used to perform the docking of these phytochemicals. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug likeliness properties for these selected phytochemicals were performed using SWISS ADME. Results: The ensemble docking studies suggest that aconitine, lappaaconitine from Aconitum heterophyllum Wall. Ex Royle, 2'-hydroxyisorientin from Pistacia integerrima stew. Ex brandis, and guineesine, pipercide and piperoic acid from Piper longum Linn. hold the potential to bind favorably with the SARS-CoV-2 drug targets. The drug-likeliness and ADMET properties were calculated for these phytochemicals indicating that all three phytochemicals from Piper longum were observed to have considerate drug-likeliness and ADMET properties. Aconitine has a molecular weight slightly higher than 500 kDA and has more than 10 hydrogen bond acceptors. Conclusion: The in silico study demonstrates that phytochemicals present in BC viz., aconitine, lappaaconitine from Aconitum heterophyllum, 2'-hydroxyisorientin from Pistacia intergerrima and guineesine, pipercide, and piperoic acid from Piper longum hold the potential to bind favourably with the SARS-CoV-2 drug targets. The study also provides evidence for drug likeliness and ADMET properties for these phytochemicals suggesting that BC can be further studied as a potential drug of choice for treating SARS-CoV-2 infection to avert post-infectious disease, characterized by multisystem inflammatory syndrome in children in rare cases and other similar conditions in the pediatric setting. [ABSTRACT FROM AUTHOR]

Alcoholic extract of fruits of Piper longum is reported to have antihypertensive activity, significantly due to presence of alkaloids like piperine, piperlongumine, piperlonguminine and pipernonaline. A sensitive and specific HPTLC method was developed and validated for simultaneous estimation of piperine, piperlongumine and piperlonguminine in fruit extracts with a purpose to provide the analytical support during the development of formulation as well as to serve as a quality control tool for optimised formulation. Developed method was validated with respect to ICH (International Council for Harmonisation) Q2(R1) and found to be accurate, precise, sensitive, specific and robust for estimation of piperine, piperlongumine and piperlonguminine. Method was successfully applied for assay of dry powdered extract and optimised tablet formulation in terms of content of piperine, piperlongumine and piperlonguminine as well as to study the dissolution profiles of formulation batches during development stage.

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

In the present study, the extracted volatiles from dried leaf and fruit of Piper longum were analysed by gas chromatography-mass spectrometry (GC-MS) and each detected 53 constituents having 92.41% and 96.31% of the total volatiles respectively. E-nerolidol (19.56%), β-pinene (17.07%) and α-pinene (6.8%) were main constituents in leaf volatiles whereas the fruit volatiles dominated by germacrene-D (23.38%), 8-heptadecene (8.95%) and β-caryophyllene (8.20%). Antioxidant potential of the volatiles were assessed by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The fruit volatiles revealed higher radical scavenging activities as compared to leaf. The samples were also evaluated against multidrug resistant (MDR) isolates including one non MDR fungal strain. The fruit volatiles showed a very strong activity against Acinetobacter baumannii than others whereas leaf volatiles possessed strong activity against Klebsiella pneumoniae as compared to other strains. Thus, the dried fruits can be exploited for drug development towards therapeutic purpose. [ABSTRACT FROM AUTHOR]

Medicinal plants are rich source of pharmacologically active secondary metabolites, which find wide applications in food, medicine and cosmetic industries. Besides, medicinal plants have been reported to harbour a rich diversity of microbiota with plant growth promoting potential, and source of novel and economically important compounds. In this study, we have investigated the endophytic microbiota of Piper longum, an ethnomedicinal plant of Indian subcontinent, which is widely used in Ayurvedic formulations for curing respiratory and digestive disorders. Here, we report the isolation of 67 bacterial endophytes from different plant parts, namely roots (18), shoots (25), and spikes (24). Interestingly, most of the isolated bacterial endophytes produced varying concentrations of indole-3-acetic acid (some producing > 20 µg/ml), ammonia and siderophores. Next, 16 endophytic isolates that exhibited high plant growth promoting (PGP) trait(s) under in vitro conditions were identified by 16S rRNA gene sequencing. Further, the individual inoculation of four endophytes with multiple (and high) PGP potential, namely Acinetobacter soli S14, Pseudomonas khazarica S34, Bacillus paramycoides S9, and Enterobacter hormaechei R15, was found to enhance seed germination percentage and seedling growth in tomato and wheat. Altogether, our results provide substantial clues for further investigation of P. longum endophytic microbiome for sustainable agriculture and bioprospecting for novel traits. [ABSTRACT FROM AUTHOR]

Piper nigrum and Piper longum are the most popular and economically essential spice crops globally valued for their aromatic alkaloids, especially Piperine. However, Piperine synthesis pathway mechanisms are not yet well known. This work was aimed to generate the full-length comparative berry transcriptome analysis dataset of P. nigrum and P. longum by Illumina and Nanopore sequencing platforms. While short-read sequencing technology is widely using to capture transcriptome profiles, there are still some limitations due to the read length. We used Oxford Nanopore technology for long reads and the Illumina sequencing platform for short reads to generate a hybrid transcriptome assembly from half matured and fully matured berries of P. nigrum and P. longum. From P. nigrum and P. longum 37.3 million and 38.1 million raw reads were generated respectively. A total of 308369 contigs from P. nigrum and 267715 contigs from P. longum were obtained and successfully annotated. The transcriptome data revealed gene families involved in piperine and other secondary metabolite biosynthetic pathways. The raw data were uploaded to NCBI database. This dataset shed light on the further exploration of the piperine biosynthetic pathway, its transcriptomic changes, and evolution. Data generated has been submitted to SRA of NCBI with Bio samples accession: (SAMN13981803, SAMN22826456).

Background: After declaration of COVID- 19 as pandemic by WHO, countries adopted several measures to contain the spread as well as test and treat the patients. Further, as no effective management protocols to address this pandemic were available, a need was felt to explore the integration of modern and traditional medicines to treat COVID- 19 cases. Objective: To undertake a study with Ayurveda formulation as add on to existing standard of care (SOC) and to compare the outcomes in terms of patient acceptability, the time to clinical recovery, hospital stay as well as any signs of drug-herb interaction between the Ayurveda formulation and the SOC. Material and methods: An exploratory nonrandomized prospective study has been undertaken for comparing the outcomes of traditional Ayurvedic classical formulation of Tinospora cordifolia (Guduchi) and Piper longum (Pippali) as an add on to standard of care (SOC) using modern medicine with SOC alone. This has been done in mild and moderate COVID- 19 cases, at a tertiary care integrative Medicine hospital in the National Capital Region, Gurgaon, India. The outcomes have been evaluated in terms of the duration of hospital stay, the time to clinical recovery, safety and non- interference/interaction of Ayurvedic and Further, long term impact of COVID- 19 treatment has been evaluated using quality of life questionnaire after 3 months of discharge. Results: Findings of present study reveals that the Ayurveda add-on formulation of T. cordifolia (Guduchi) and P. longum (Pippali) has reduced the length of hospital stay and improve the recovery time. General feeling of wellbeing and activity levels were better in the 3 month follow-up post discharge in the Ayurveda add-on group. Conclusion: Addition of Ayurveda formulation has reduced the time of recovery and duration of hospital stay. However, this formulation needs further investigated to provide more information on effective and safe herbal add-on to SOC for better outcomes to treatment of COVID-19 disease.

Background : The environmental hazards posed by microplastics have drawn considerable concern due to their buildup in ecosystems. Microplastics accumulate in human saliva, skin, and hair. Developing effective technology for managing and degrading microplastics remains a substantial challenge. In a concerted attempt to save the ecology, this study explores the photocatalytic breakdown of common microplastics like polystyrene (PS) microspheres and polyethylene (PE) using green-synthesized zinc oxide nanoparticles (ZnO NPs) under UV light exposure. Aim : To synthesize and characterize zinc oxide nanoparticles prepared using the extract of the leaves of Piper longum  and qualitatively assess the photocatalytic degradation potential of the nanoparticles under light microscopy. Material and Methods : A fresh extract of P. longum leaves was used as a reducing agent to synthesize zinc oxide nanoparticles. Fourier transform infrared (FTIR) analysis, X-ray diffraction (XRD) analysis, UV-Vis spectra analysis, and scanning electron microscopy (SEM) analysis were performed to characterize the nanoparticles. Microplastics were isolated from the saliva of 50 healthy patients and were purified and filtered. In a six-well microtiter plate, 0.5 μg of varying concentrations of nanoparticles were added. After fixing with 15% formaldehyde, microplastics were subjected to UV irradiation for 2 hours with different concentrations of ZnO nanoparticles (25, 50, 75, and 100 µg). Custom photoreactors activated the photocatalysts to degrade the microplastic pollutants. The six-well microtiter plate was viewed under 40x magnification in a light microscope to observe microplastic morphology after 24 hours of degradation. Results : The FTIR spectrum showed distinct peaks at 890.51 cm⁻¹, indicating the involvement of C-N in-plane vibrations of amino acids. XRD analysis revealed three distinct diffraction peaks at 31.68°, 34.39°, and 36.33°, corresponding to the hexagonal wurtzite structure of ZnO nanoparticles. The synthesized ZnO nanoparticles ranged from 50 to 90 nm in size, viewed at 100x magnification on SEM. The highest degradation of microplastics was observed at a ZnO NP concentration of 100 µL, with the ZnO NPs 50-90 nm in size. Conclusion : Zinc oxide nanoparticles synthesized using Piper longum leaf extract effectively degrade microplastics, with the highest degradation observed at a 100 µL concentration of ZnO nanoparticles and optimal degradation occurring at a concentration of 75 µL., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Saveetha Dental College - Institutional Human Ethical Committee issued approval IHEC/SDC/ORTHO-2102/24/176. Saveetha Dental College - Institutional Human Ethical Committee number for the study entitled "Degradation of Microplastics by Zinc Oxide Nanoparticle Synthesized using Piper longum Leaf Extract" is IHEC/SDC/ORTHO-2102/24/176. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vas et al.)

Piper longum L. (PL) is considered one of the most important species traditionally used for treating various ailments and has indicated the presence of alkaloids, flavonoids, and steroids. In this study, we isolated the chemical compounds of PL leaves, and measured NO, IL-6, iNOS, as well as COX-2 protein levels. In addition, molecular docking analysis was used to further understand the anti-inflammation effect of the compounds. We identified one new alkaloid named piperlongumine A (1) with ten known compounds (2-11). The new compound (1) and two other alkaloids 2E)-3-(4-hydroxy-3-methoxyphenyl)-1-(pyrrol-1-yl) propanone (7) and piperchabamide A (8) significantly reduced NO production in LPS-stimulated RAW 264.7 cells with the IC 50 values of 0.97±0.05 μM, 0.91±0.07 μM, 1.63±0.14 μM, respectively. Moreover, at concentration of 2 μM, compound 1 inhibited approximately 98±0.64 % of IL-6 secretion, and decreased iNOS and COX-2 protein level by about 96 and 19 folds compared to LPS treatment alone, respectively. Furthermore, compounds 1, 7, and 8 were predicted to bind and inhibit IL-6, TNF-α, and iNOS, with compound 1 showing the highest binding energy of -7.09 kcal/mol. This study provides new insights for potential anti-inflammatory drug design and warrants further investigation., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Bacterial communication, Quorum Sensing (QS), is a target against virulence and prevention of antibiotic-resistant infections. 16 derivatives of Piperlongumine (PL), an amide alkaloid from Piper longum L., were screened for QS inhibition. PL-18 had the best QSI activity. PL-18 inhibited the lasR-lasI, rhlR-rhlI, and pqs QS systems of Pseudomonas aeruginosa . PL-18 inhibited pyocyanin and rhamnolipids that are QS-controlled virulence elements. Iron is an essential element for pathogenicity, biofilm formation and resilience in harsh environments, its uptake was inhibited by PL-18. Pl-18 significantly reduced the biofilm biovolume including in established biofilms. PL-18-coated silicon tubes significantly inhibited biofilm formation. The transcriptome study of treated P. aeruginosa showed that PL-18 indeed reduced the expression of QS and iron homeostasis related genes, and up regulated sulfur metabolism related genes. Altogether, PL-18 inhibits QS, virulence, iron uptake, and biofilm formation. Thus, PL-18 should be further developed against bacterial infection, antibiotic resistance, and biofilm formation., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Mosquito-borne diseases are major public health-associated diseases. The chemical insecticides are used for several decades to control vector mosquitoes. The large-scale application of chemical insecticides caused several problems like insecticide resistance, the resurgence of pest species, environmental pollution, toxic hazards to humans and other nontarget organisms. Mosquito control with botanicals proved to be a good alternative to chemical insecticide. The essential point of this investigation was to screen non-poisonous and effectively accessible mosquito control of natural origin. The current investigation evaluated the role of larvicidal activity of crude hexane, petroleum ether, chloroform, and ethanol leaf extracts of Piper longum L. tested against the third instar of Aedes aegypti larvae at 24h exposure. Among the crude extracts, the highest larval mortality crude extract was undergone the GC-MS analysis for the identification of active phytocompouds. The highest larval mortality was observed in ethanolic extract followed by chloroform, petroleum ether, and hexane. The corresponding LC50 and LC90 values of hexane, petroleum ether, chloroform, and ethanol were 46.90 and 82.30; 39.82 and 75.22; 30.00 and 63.33; 22.55 and 52.63µg/dl respectively. Twenty-four compounds were identified by GC-MS analysis. Results of this study revealed that the ethanolic leaf extract of P. longum may be considered a potent source of mosquito larvicidal agents. [ABSTRACT FROM AUTHOR]

Antioxidants are compounds that are able to inhibit the negative effects that come from free radicals. The phenomenon of imbalanced antioxidant production and the accumulation of free radicals in cells and tissues can cause oxidative stress. Excessive free radicals that enter the body cannot be warded off by endogenous antioxidant compounds so that the required antioxidant compounds can come from the outside, which helps in the performance of endogenous antioxidants. Antioxidants that come from outside consist of synthetic and natural antioxidants; however, synthetic antioxidants are not an option because they have toxic and carcinogenic effects. Therefore, the use of natural ingredients is an alternative method that is needed to create a new natural antioxidant compound. Piper species are being considered as possible medicinal plants for the development of new sources of antioxidants. Several studies have been carried out starting from the extract levels, fractions, and compounds of the Piper species, which showed good antioxidant activity. Currently, some of these plants are being used as ingredients in traditional medicines to treat allergies, toothaches, and coughs. This review examines the distribution, botanical data, pharmacology, especially antioxidant activity, and the compounds contained in five Piper species, namely Piper amalago L., Piper betle L., Piper hispidum Sw., Piper longum L., and Piper umbellatum L.

Unavailability of treatment for the SARS-CoV-2 virus has raised concern among the population worldwide. This has led to many attempts to find alternative options to prevent the infection of the disease, including focusing on vaccines and drugs. The use of natural products and herbal extracts can be a better option in beating the virus and boosting up immunity. In the present paper, we have done a systematic in silico study of papain-like protease of COVID-19 virus with the chemical constituents of herbal plant Piper Longum. Screening of the pharmacokinetic properties is done with thirty-two phytoconstituents of Piper Longum which help us in selecting the most active components of the plant. After selection molecular docking is performed with Aristololactam (C17H11NO4), Fargesin (C21H22O6), l-asarinin (C20H18O6), Lignans Machilin F (C20H22O5), Piperundecalidine (C23H29NO3), and Pluviatilol (C20H20O6). Molecular dynamic (MD) is also performed with the inhibitor-receptor complex which suggest significant inhibition and a stable complex of I-Asarinin with PLpro. Docking scores and simulation results suggest that I-Asarinin can act as a potential drug like candidate against COVID-19.

Cardimap tablet is a polyherbal formulation manufactured by Maharishi Ayurveda and used as an antihypertensive. The Ayurvedic formulation contains Rauwolfia serpentina, Nardostachys jatamansi, Convolvulus pluricaulis, Bacopa monnieri, Piper longum, and hence contains five markers, namely, reserpine, lupeol, scopoletine, bacoside A and piperine. This paper reports the standardization of Cardimap tablet according to World Health Organization (WHO) guideline and also by high-performance thin-layer chromatography method for the presence of the markers reserpine, lupeol, scopoletine, bacoside A and piperine. Both marketed and lab preparation complied all parameters according to WHO guideline and each marker compound showed a linear relationship in the concentration range 1‒2 µg per spot for reserpine, 2.5‒4.5 µg per spot for scopoletine, 10–50 µg per spot for piperine, 12–24 µg per spot for bacoside A and 1‒5 µg per spot lupeol. The proposed method was found to be precise, specific, and accurate, with a recovery of 98‒102%, and hence can be used for the routine analysis of this formulation. [ABSTRACT FROM AUTHOR]

Piperine, the well known alkaloid, is frequently used for preparation of several drug formulations in medicament industries. It is a medicinally potent bio-molecular compound having enormous biological and pharmacological activities. Piperine is frequently extracted from the spikes and root parts of the plants of Piperaceae family. But with a little deviation to that of general fact, in this case experimentation was carried out to evaluate Piperine from leaves of Piper longum plant of Piperaceae family. Comparative assessment of extraction methods used for yielding Piperine along with their quantitative estimation through spectrophotometric and high performance liquid chromatography methods is the prior agenda. Two types of extraction processes were selected along with use of two types of solvent systems. Piperine content was estimated to be within range of 0.096-0.194% dry weight spectrophotometrically and 0.087-0.157% dry weight through HPLC analysis. From this experiment it could be opined that leaf parts of P. longum also contains piperine. This validated new result would be helpful in finding suitable alternate non-destructive source of piperine, which will lessen the threat status of the concerned species in their natural habitat. [ABSTRACT FROM AUTHOR]