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It is known that vascular endothelial growth factor receptor (VGFR) is linked with cancer. Therefore, it is of interest to document the molecular binding features of bioactive molecules from Piper longum as potential anti-cancer agents with VGFR2 for further consideration. Thus, we document the binding features of four compounds (sesamin, fargesin, longamide and piperlonguminine) with VGFR2 for further consideration in drug discovery.

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. In view of this 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. Findings of present study reveals that the Ayurveda add-on formulation of Tinospora cordifolia (Guduchi) and Piper 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. It is suggested that 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: 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.

Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.

Graphical abstract, 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.

Graphical abstract, Highlights • Catkin extract of Piper longum was used to optimize and biosynthesize AgNPs. • Biosynthesized AgNPs were characterized using UV, FTIR, TEM, XPS, GC-MS and XRD. • The antibacterial activity of the AgNPs was determined against 7 different food-borne pathogens., 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.

Three new amide alkaloids piperlongumamides A-C (1–3), together with 12 known ones (4–15), were isolated from the fruits of Piper longum. The structures of the new isolates were determined using spectroscopic data analyses. Cytotoxic activity of these amides against HL-60 (human leukemia), A-549 (human lung cancer), MCF-7 (human breast cancer), SMMC-7721 (human liver cancer) and SW480 (human rectal cancer) cell lines were evaluated. Piperchabamide B (11) exhibited weak inhibitory activity against HL-60 (IC50 = 21.32 μM ), A-549 (IC50 = 23.82 μM ) and MCF-7 (IC50 = 16.58 μM ) cell lines. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-013-0073-0 and is accessible for authorized users.

Background: Evidences from ethnopharmacological practices have shown that combination of Abutilon indicum and Piper longum are traditionally used to treat symptoms of the liver disorder. The hypothesis is phytosomes of a combination of both crude drug extract will be more effective and safe as hepatoprotective agent. Aim: Present work is aimed at development and characterization of phytosomes containing ethanolic extract of both drugs to meet the need for better effectiveness and safety. Materials and Methods: Phytosomes were formulated by using Indena's patented process. Characterization involved following parameters: Particle size determination, percentage yield, entrapment efficiency, differential scanning calorimetry, scanning electron microscope, fourier transform infrared spectroscopy, and high performance thin liquid chromatography. Liver damage was induced in adult Charles foster rats (150 ± 10 g) with CCl4 in olive oil (1:1 v/v, i.p) 1 ml/kg once daily for 7 days. LIV 52 (1 ml/kg per oral [p.o]), ethanolic extract of A. indicum and P. longum combination (100, 200, and 400 mg/kg p.o) and phytosomes (100 mg/kg p.o.) was given 3 days prior to CCl4 administration. Estimation of liver marker enzymes and histopathological studies were done. Result was analyzed by using (analysis of variance) followed by Student-Newman–Keuls test. Result: Combined extract has shown hepatoprotective activity but phytosomal formulation has more potent hepatoprotective effect on CCl4 induced liver toxicity at very low dose comparative to a higher dose of combined extract. Conclusion: Novel approach for herbal drug delivery is more prominent than conventional which improves bioavailability of polar extract and also patient compliance. SUMMARY Standardised ethanolic extract of leaves of abutilon indicum and piper longum fruits by microwave assisted extraction was used for phytosomal complex formation and phytosomal complex was characterised by various parameters and finally the hepatoprotective activity of phytosomes and crude extract was evaluated by different biochemical markers and histopathological study. Abbreviations Used: DSC: Differential scanning calorimetry, SEM: Scanning electron microscope, FTIR: Fourier transform infrared spectroscopy, HPTLC: High performance thin liquid chromatography, p.o: Per oral, A. indicum: Abutilon indicum, P. longum: Piper longum.

Three Piper species, Piper longum, P. ribesoides and P. sarmentosum, were selected for investigation of adulticidal potential against Stegomyia aegypti, a main vector of dengue and dengue haemorrhagic fever. Successive extraction by maceration with 95% ethanol showed percentage yields of ethanolic extracts, which derived from P. longum, P. ribesoides and P. sarmentosum, of 8.89, 3.21 and 5.30% (w/w), respectively. All Piper extracts illustrated an impressive adulticidal activity when tested against female mosquitoes by topical application. The susceptibility of St. aegypti females to ethanol-extracted Piper was dose dependent and varied among the plant species. The highest adulticidal effect was established from P. sarmentosum, followed by P. ribesoides and P. longum, with LD50 values of 0.14, 0.15 and 0.26 µg/female, respectively. The potential of these Piper species, as possible mosquitocides, established convincing activity for further researches to develop natural substances for combat against adult mosquitoes. Três espécies de Piper, Piper longum, P. ribesoides e P. sarmentosum, foram selecionadas para investigação da potencialidade contra Stegomyia aegypti adultos, principal vetor de dengue e febre do dengue hemorrágico. Sucessivas extrações por maceração com etanol a 95% mostraram uma porcentagem de extratos etanólicos, derivados de P. longum, P. ribesoides e P. sarmentosum, de 8,89, 3,21 e 5,30% (w/w), respectivamente. Todos os extratos de Piper mostraram atividade adulticida expressiva quando testados contra fêmeas de mosquitos através de aplicação tópica. A suscetibilidade das fêmeas do St. aegypt ao extrato de Piper etanólico foi dose dependente e variou entre as espécies de plantas. O mais elevado efeito adulticida foi demonstrado a partir do P. sarmentosum, seguido pelo P. ribesoides e P. longum, valores LD50 de 0,14, 0,15 e 0,26 µg/fêmea, respectivamente. O potencial destas espécies de Piper, como possíveis mosquiticidas, estabeleceu atividade convincente para futuras pesquisas a fim de desenvolver substâncias naturais para o combate a mosquitos adultos.

Identifying novel therapeutic agents from natural sources and their possible intervention studies has been one of the major areas in biomedical research in recent years. Piper species are highly important - commercially, economically and medicinally. Our groups have been working for more than two decades on the identification and characterization of novel therapeutic lead molecules from Piper species. We have extensively studied the biological activities of various extracts of Piper longum and Piper galeatum, and identified and characterized novel molecules from these species. Using synthetic chemistry, various functional groups of the lead molecules were modified and structure activity relationship (SAR) studies identified synthetic molecules with better efficacy and lower IC50 values. Moreover, the mechanisms of actions of some of these molecules were studied at the molecular level. The objective of this review is to summarize experimental data published from our laboratories and others on antioxidant and anti-inflammatory potentials of Piper species and their chemical constituents. ispartof: Current Topics in Medicinal Chemistry vol:15 issue:9 pages:886-893 ispartof: location:United Arab Emirates status: published

A total of 9 species belonging to 3 genera of keratinophillic fungi were recovered from twelve soil samples collected from different sites in shivamogga using the hair-baiting technique. Most of the fungal species isolated are known to be agents of human and animal infection. The methanolic root extract of Piper longum was evaluated for antifungal activity against the isolated strains to determine the active. It was observed that the extract was effective in inhibiting species with zone of inhibition ranging between 3 mm and 11 mm but the extract showed no zone of inhibition for Chrysosporium keratirophilum. The results indicate that the methanolic root extract of Piper longum might be exploited as natural drug for the treatment of several infection caused by these organisms.

Objective To isolate the larvicidal component from the fruits of Piper longum (P. longum) against the filariasis vector, Culex quinquefasciatus (C. quinquefasciatus). Methods Pulverized fruits of P. longum were subjected to soxhlet extraction using series of organic solvents of increasing polarity. All the solvent extracts were verified for their larvicidal efficacy against 4th instar larvae of C. quinquefasciatus employing standard WHO procedure. Bioassay-guided fractionation through column chromatography lead to the isolation of a bioactive amide, pipyahyine from the petroleum ether extract. Results Petroleum ether extract was found to be the most active fraction among all the extracts tested with LC50 and LC90 being 1.03 and 2.04 ppm respectively. Whereas, pipyahyine, an isolated component of the same fraction was found to be even more effective than the parent extract in terms of LC50 being 0.58 and 1.88 ppm respectively. Conclusions From the results, it is evident that P. longum can be considered as a powerful arsenal for the control of mosquito population.

In the present study, antiinflammatory activity of the Piper longum dried fruit's oil was studied in rats using the carrageenan-induced right hind paw edema method. The activity was compared with that of standard drug ibuprofen. The dried fruit's oil inhibited carrageenan-induced rat paw edema. The results indicated that the dried fruit's oil produced significant (p< 0.001) antiinflammatory activity when compared with the standard and untreated control.

Piper longum Linnaeus, Species Plantarum 1: 29. 1753. "Habitat in India." RCN: 234. Lectotype (Huber in Dassanayake & Fosberg, Revised Handb. Fl. Ceylon 6: 288. 1987): Herb. Hermann 4: 13, No. 30 (BM). Current name: Piper longum L. (Piperaceae). Note: Huber refers to the type as located in vol. 4: 48 of the Hermann herbarium but as the only material is in vol. 4: 13, it seems clear that this was an error, treated here as correctable., Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part P), pp. 718-782 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 745, DOI: 10.5281/zenodo.291971

Aim: To compare doxycycline like oral efficacies of piperlongumine and a Piper longum fruits extract (PLE) as stress resistance inducers. Methods: Efficacies of oral pretreatments with 5 mg/kg piperlongumine or PLE or of 50 mg/kg doxycycline for 10 consecutive days in inducing stress resistance against alteration in body weights, core temperatures, gastric ulcers, and other pathologies in male mice triggered by occasional exposures to less than 1 min durations of unavoidable foot shocks were compared. Results: Doxycycline like long lasting protective effects of piperlongumine and PLE against gradual alterations in body weights, basal core temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed one day after the last foot shock exposures and gastric ulcers and other pathologies quantified one day after the test were also suppressed in piperlongumine or PLE or doxycycline pretreated groups. Conclusion: Piperlongumine and crude Piper longum fruit extracts are doxycycline like long acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of piper longum and other plants of the Piperaceae family, and reveal that piperlongumine is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant derived products enriched in piperlongumine or piperine like amide alkaloids in volunteers and patients can be warranted. [J Intercult Ethnopharmacol 2015; 4(4.000): 277-283]

Piper hispidinervum e Piper aduncum apresentam compostos metabolitos secundarios como safrol e dilapiol de interesse comercial em seus oleos essenciais. O trabalho teve como objetivo comparar aspectos anatomicos, relacionados a respostas fisiologicas das folhas de P. hispidinervum e P. aduncum propagadas in vitro, in vivo e durante a aclimatizacao. Seccoes paradermicas e transversais da lâmina foliar do cultivo in vitro, ex vitro e in vivo, feitas a mao-livre foram realizadas para a medicao das estruturas anatomicas em microscopio de luz. A espessura da epiderme e hipoderme de P. hispidinervum e P. aduncum sofrem alteracoes na transicao de cultivo in vitro para o ex vitro. Os tecidos do mesofilo e a abertura do poro estomatico de ambas as especies sao influenciados pelo ambiente in vitro. Diferentes ambientes de cultivo promovem a plasticidade das estruturas celulares da lâmina foliar e fundamentam o sucesso da micropropagacao de ambas as especies.

Objectives. Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and Pacific islands, which has been reported to exhibit a wide spectrum of activity, including antioxidant activity. In this study, we evaluated the effect of hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced hair cell loss in basal, middle and apical regions in a neonatal cochlea cultures. Methods. The protective effects of SPL extract were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. The anti-apoptosis activity of SPL extract was measured using double labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myosin-7a staining. The radical-scavenging activity of SPL extract was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Results. SPL extract at a concentration of 1 mu g/mL significantly inhibited GM-induced hair cell loss at basal and middle region of cochlea, while 5 mu g/mL was effective against apical region hair cell loss. The protective effect of SPL extract was concentration dependent and hair cells retained their stereocilia in explants treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair and inner hair counts were not decreased in SPL extract treated groups in compare to GM treated explants. Additionally, SPL extract showed concentration dependent radical scavenging activity in a DPPH assay. Conclusion. An anti-apoptosis effect and potent radical scavenger activity of SPL extract protects from GM-induced hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.

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.

Objective: To investigate the effects of alcoholic extract of Allium sativum and Piper longum on the muscular activity of a parasitic amphistome, Gigantocotyle explanatum. Materials and Methods: Amphistomes were isometrically mounted to record the spontaneous muscular activity by using Chart 4 software program (Power Lab, AD Instruments, Australia) and to examine the effects of cumulative doses (100, 300, 1000, and 3000 µg/ml) of the plant extracts on the amplitude (g), frequency (per 10 min), and baseline tension (g) of the spontaneous muscular activity of the amphistome. Results: Alcoholic extract of A. sativum produced significant reduction in the frequency and amplitude of contractile activity of the amphistome at 1000 and 3000 µg/ml bath concentrations. Complete paralysis of the amphistome was observed after 15 min of addition of 3000 µg/ml concentration. Alcoholic extract of P. longum also caused paralysis following 15-20 min exposure of the amphistome to 3000 µg/ml concentration. In both the cases the amphistomes did not recover from paralysis following 2-3 washes. Conclusion: The observations demonstrate the paralytic effect of alcoholic extract of A. sativum and P. longum on G. explanatum.

Piper longum, spec. nov. 5. Piper foliis cordatis petiolatis sessilibusque. Fl. zeyl. 30. * Mat. med.20. Piper longum orientale. Bauh. pin. 412. Piper longum, pistolochiae foliis absque pediculis, maderaspatanum. Pluk. alm. 297. t.104. f.4. Cattu-tirpali. Rheed. mal.7. p.27. t.14. Habitat in India ., Published as part of Linnaeus, Carolus, 1753, Species plantarum: exhibentes plantas rite cognitas, ad genera relatas, cum differentiis specificis, nominibus trivialibus, synonymis selectis, locis natalibus, secundum systema sexuale digestas, Stockholm :Laurentius Salvius on page 29, DOI: 10.5281/zenodo.3931989