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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: 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

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.

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.

Aim: To compare stress resistance increasing and analgesic activities of piperlongumine and a methanolic Piper longum fruit extract (PLE). Methods: Efficacies of a single and repeated daily oral doses (1–256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline against foot shock stress triggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activity in tail suspension test and on pentobarbital induced sedation in male mice were compared. In another experiment, analgesic activities of single and repeated daily 5 mg/kg oral doses of piperlongumine and PLE in mice hot plate test and in acetic acid induced writing tests were compared with those of aspirin and doxycycline. Results: After their single oral doses no effects of piperlongumine or PLE or doxycycline were observed in the footshock stress induced hyperthermia test or in hot plate test. However, significant effects of piperlongumine and PLE in both the tests were observed after their 5 or more daily doses. Both of them also dose dependently suppressed daily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activity in tail suspension test and aspirin like analgesic effects in acetic acid writhing test were observed after their 11 daily 5 mg/kg oral dose. Conclusion: Piperlongumine is another bioactive secondary metabolite of P. longum and other plants of piper species with stress response suppressing, analgesic, and anti-inflammatory activities. Its bactericidal activities can also contribute to its therapeutically interesting bio-activity profile.

Treatment cost is a major concern for modern medicine in developing countries like India and systematic innovative means to reduce these costs are needed. This article reviews the concept of bioenhancers to reduce treatment costs by increasing drug bioavailability. This concept, based on the Ayurvedic system of medicine, works for a wide range of ingested substances, and has been applied to modern drugs, particularly single chemicals. It offers a fine example of the benefit of integrating an ancient system with modern medicine in both theory and practice.

Piper longum extract as a reducing agent in green synthesis method is used to synthesize ZnO nanoparticles (ZnO-NPs). The impact of the reductant on the structural, optical and surface morphological properties of ZnO-NPs can be analyzed. Piper longum extract has delicately tuned the band gap of ZnO-NPs. Increase in energy band gap indicates an increase in the number of capping molecules in the prepared ZnO nanoparticles. The carbohydrates and proteins not only play a fundamental role in ZnO capping, which is important for its stability, determination and biocompatibility. Thus obtained nanosized ZnO particles are confirmed by the surface morphological studies. Because of various surface interface properties might have different physical-chemical, desorption-adsorption abilities in the direction towards microbes, create different antibacterial performances. S.aureus has maximum inhibition zone of 23 mm and Escherichia coli has minimum inhibition zone of 7 mm. To assess the photocatalytic activity of the prepared ZnO-NPs under UV light irradiation, methyl orange, malachite green and methylene blue dyes were utilized as model contaminants. The degradation efficiency of MG, MB and MO dyes solution is found that 96%, 69% and 48% of degradation efficiency respectively under ultraviolet light irradiation. The properties of synthetic nanopowders suggest that they have important potential for a variety of biochemical and environmental applications., (Copyright © 2022. Published by Elsevier Inc.)

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., (© 2021 The Authors.)

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 (C 17 H 11 NO 4 ), Fargesin (C 21 H 22 O 6 ), l-asarinin (C 20 H 18 O 6 ), Lignans Machilin F (C 20 H 22 O 5 ), Piperundecalidine (C 23 H 29 NO 3 ), and Pluviatilol (C 20 H 20 O 6 ). Molecular dynamic (MD) is also performed with the inhibitor-receptor complex which suggest significant inhibition and a stable complex of I-Asarinin with PL pro . Docking scores and simulation results suggest that I-Asarinin can act as a potential drug like candidate against COVID-19., (© 2021 Published by Elsevier B.V.)

Inspired with an increasing environmental awareness, we performed an eco-friendly amenable process for the synthesis of silver nanoparticles (AgNPs) using the catkins of Piper longum as an alternative approach with the existing methods of using plant extracts. The fabrication of nanoparticles occurred within 10 min. This was initially observed by colour change of the solution. UV-visible spectroscopic studies (UV-Vis) were performed for further confirmation. The analysis elucidated that the surface plasmon resonance (SPR) was specifically corresponding to AgNPs. Fourier transform infrared spectrophotometry (FTIR) studies indicated that polyphenols could possibly be the encapsulating agents. The size and shape of the nanoparticles was analysed using Transmission electron microscopy (TEM). The nanoparticles were predominant spheres ranging between 10 and 42 nm at two different scales. The formation of elemental silver was confirmed further by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRD). GC-MS analysis was used to identify the possible encapsulates on the nanoparticles. The antibacterial effect of the biosynthesized AgNPs was tested against two gram-positive (Bacillus cereus and Staphylococcus aureus), and five gram-negative (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhi) bacteria. Outcomes of the study suggest that these pathogens were susceptible to the AgNPs. This is the first ever international report on correlating the antibacterial effect of silver nanoparticles using mathematical modelling with a conventional antimicrobial assay. The results indicate that nanoparticles of silver synthesized using catkin extract of P. longum can be exploited towards the development of potential antibacterial agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

The present investigation highlights the strong antioxidant, anticancer and larvicidal potential of green synthesized silver nanoparticles (AgNPs) using aqueous leaf extract of Piper longum L. for their diverse therapeutic applications. The optimum conditions for the synthesis of AgNPs were recorded as 1 mM AgNO 3 , 60 ± 2 °C at pH 6 for 120 min. Synthesized AgNPs proved to be highly stable and monodispersed as characterized through various techniques. UV-Vis spectrum of biosynthesized AgNPs showed a maximum absorption peak at 420 nm. Field emission-Scanning electron microscopy (FE-SEM) and High resolution-Transmission electron microscopy (HR-TEM) micrographs showed the spherical shape of AgNPs with mean diameter size of 28.8 nm. Existence of crystallographic AgNPs was proved by X-ray diffraction (XRD) pattern analysis. Presence of phenolics, terpenoids and flavonoids compounds which act as bioreducing agents were confirmed by Fourier-transform infrared spectroscopy (FTIR) analysis. Furthermore, the AgNPs and leaf extracts prepared individually in different solvents such as methanol, ethyl acetate, chloroform, hexane and aqueous were assessed for their bio-efficacies. AgNPs showed the enhanced antioxidant (IC 50 67.56 μg) and radical-scavenging activities (IC 50 196.8 μg) as compared to the crude leaf extracts. Anticancer activity revealed the strong and dose-dependent cytotoxic effect of AgNPs against the HeLa cells showing maximum IC 50 value being 5.27 μg/mL after 24 h and was also found to be non-toxic to normal cells (HEK). The AgNPs induced the fragmentation of DNA in the cells, indicating the occurrence of apoptosis and necrosis. Subsequently, an efficient larvae mortality was also recorded against Anopheles stephensi having LC 50 and LC 90 values being 8.969 and 16.102 ppm, followed by Aedes aegypti (LC 50 ;14.791 and LC 90 ;28.526 ppm) and Culex quinquefasciatus (LC 50 ;18.662 and LC 90 ;40.903 ppm) after 72 h of exposure. Besides, they showed no toxicity against Mesocyclops thermocyclopoides (non-target organism). This is the first report showing strong anti-tumorous and larvicidal activity of AgNPs synthesized using P. longum leaf extract against cervical cancer cell line and mosquito vectors causing dengue, malaria and filariasis. Based on our findings, we suggest that AgNPs derived using P. longum leaf extract possessed excellent anti-cancerous and mosquito larvicidal potential and therefore, can be bioprospected further for the management of these hazardous health diseases. This study has given a new insight for the novel drug designing after conducting experiments on the in vivo models., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Silver nanoparticles synthesized through bio-green method has been reported to have biomedical applications to control pathogenic microbes as it is cost effective compared to commonly used physical and chemical methods. In present study, silver nanoparticles were synthesized using aqueous Piper longum fruit extract (PLFE) and confirmed by UV-visible spectroscopy. The nanoparticles were spherical in shape with an average particle size of 46nm as determined by scanning electronic microscopy (SEM) and dynamic light scattering (DLS) particle size analyzer respectively. FT-IR spectrum revealed the capping of the phytoconstituents, probably polyphenols from P. longum fruit extract and stabilizing the nanoparticles. Further the ferric ion reducing test, confirmed that the capping agents were condensed tannins. The aqueous P. longum fruit extract (PLFE) and the green synthesized silver nanoparticles (PLAgNPs) showed powerful antioxidant properties in in vitro antioxidant assays. The results from the antimicrobial assays suggested that green synthesized silver nanoparticles (PLAgNPs) were more potent against pathogenic bacteria than the P. longum fruit extract (PLFE) alone. The nanoparticles also showed potent cytotoxic effect against MCF-7 breast cancer cell lines with an IC 50 value of 67μg/ml/24h by the MTT assay. These results support the advantages of using bio-green method for synthesizing silver nanoparticles with antioxidant, antimicrobial and cytotoxic activities those are simple and cost effective as well., (© 2013.)

Treatment cost is a major concern for modern medicine in developing countries like India and systematic innovative means to reduce these costs are needed. This article reviews the concept of bioenhancers to reduce treatment costs by increasing drug bioavailability. This concept, based on the Ayurvedic system of medicine, works for a wide range of ingested substances, and has been applied to modern drugs, particularly single chemicals. It offers a fine example of the benefit of integrating an ancient system with modern medicine in both theory and practice.