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Natural products and traditional ethnomedicines are of great effect in therapeutics. Such types of medicine have been practiced in certain areas of the world to treat different health conditions. This pilot investigation aims to review the cumulative health effect of addendums used in betel quid such as areca nut, lime, and tobacco-associated betel quid chewing and without tobacco-associated chewing. This review shows that betel leaf extract and its essential oil could inhibit growth of microbes and damage different gram-positive and gram-negative bacteria as well as various fungus species. Some studies concluded that the combination of Piper leaves essential oil with antibiotics have potential effect on oral microorganisms. Long-term consumption of betel quid with tobacco is known to cause cancer, chromosomal aberrations, and pharynx tumors. However, consumption of betel leaf without tobacco has health benefits because of ethnomedicinal properties. Its essential is oil utilized as raw material for perfumes and mouth fresheners manufacturing. Scientific researches on this plant revealed that it possesses many beneficial activities to be used for developing novel drugs. However, compounds of betel leaves have beneficial natural antioxidant. Chewing and intake of leaves have effect on moving parts of salivary gland which is the main step of digestion. Its components also act as heartbeat regulators in relaxing the blood vessels to reduce hypertension. So this review discussed the natural compounds of betel leaves which is used as traditional medicine to further develop drug discovery.

Background: Since ancient times, "betel leaf" (Piper betle) has been revered for its reli-gious, cultural, and medicinal properties. Phytochemicals from the Piper betle are effective in a variety of conditions, including cancer. To date, however, no genomic study or evidence has been found to elucidate the regulatory mechanism that underpins its therapeutic properties. This is the first study of its kind to predict Piper betle miRNAs and also the first genomics source representation of Piper betle. According to previous research, miRNAs from the plants we eat can regulate gene expression. In line with this, our in-silico study revealed that Piper betle and human cross-kingdom control occurs. Method: This study demonstrates the prediction and in-silico validation of Piper betle miRNAs from NGS-derived transcript sequences. The cross-kingdom regulation, which can also be understood as in-ter-species RNA regulation, was studied to identify human mRNA targets controlled by Piper betle miRNAs. Functional annotation and gene-disease association of human targets were performed to un-derstand the role of Piper betle miRNAs in human health and disease. The protein-protein interaction and expression study of targets was further carried out to decipher their role in cancer development. Results: Identified six Piper betle miRNAs belonging to miR156, miR164, miR172, and miR535 fami-lies were discovered to target 198 human mRNAs involved in various metabolic and disease processes. Angiogenesis and the cell surface signaling pathway were the most enriched gene ontology correlated with targets, both of which play a critical role in disease mechanisms, especially in the case of carci-noma. In an analysis of gene-disease interactions, 40 genes were found to be related to cancer. Accord-ing to a protein-protein interaction, the CDK6 gene, which is thought to be a central regulator of cell cycle progression, was found as a hub protein, affecting the roles of CBFB, SAMD9, MDM4, AXIN2, and NOTCH2 oncogenes. Further investigation revealed that pbe-miRNA164a can be used as a regula-tor to minimise disease severity in Acute Myeloid Leukemia, where CDK6 expression is highest com-pared to normal cells. Conclusion: The predicted pbe-miRNA164a in this study can be a promising suppressor of CDK6 gene involved in tumour angiogenesis. In vivo validation of the pbe-miRNA164a mimic could pave the way for new opportunities to fight cancer and leverage the potential of Piper betle in the healthcare sector.

Fish is perishable and has the short shelf-life. To maintain its quality, it is necessary to implement the appropriate technology, particularly nonthermal processing along with safe additive, especially from plant origin under the concept of "hurdle technology". The use of potential vesicle including liposome for loading the plant extract could be a means to enhance the stability and activities of the extract. The current study aimed to evaluate the effect of liposomes loaded with betel leaf ethanolic extract (L/BLEEs) or unencapsulated BLEE (U/BLEE) in conjunction with modified atmospheric packaging (MAP) and nonthermal plasma (NTP) on the quality changes and shelf-life of Nile tilapia fillets (TFs) stored under refrigerated condition (4°C). TFs treated with L/BLEE or U/BLEE at 400 ppm, packed under modified atmosphere (CO2 :Ar:O2 = 60:30:10) and subjected to NTP for 300 s (L/BLEE-400/MAP-NTP and U/BLEE-400/MAP-NTP, respectively) had the lowest microbial and chemical changes during storage, while the control showed the highest changes (p 0.05) between all the samples at day 0 of storage. Only L/BLEE-400/MAP-NTP and U/BLEE-400/MAP-NTP were still sensorially acceptable after 12 days at 4°C. Therefore, L/BLEE or U/BLEE combined with MAP/NTP treatment could be adopted as a potent hurdle for shelf-life extension of TFs. PRACTICAL APPLICATION: Natural additives and nonthermal processing technologies have gained increasing interest for preservation of fish. Liposomes loaded with betel leaf ethanolic extract (L/BLEE) rich in polyphenolics could be used together with modified atmospheric packaging (MAP) and nonthermal plasma (NTP) to retard bacterial growth and chemical deterioration in Nile tilapia fillets. These hurdles were proven to be able to maintain the qualities of tilapia fillets stored at 4°C up to 12 days, especially when L/BLEE was used at 400 ppm. Therefore, shelf-life extension of Nile tilapia fillets or other fish can be achieved by using the natural additive and nonthermal processing technologies.

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.

This study aimed to determine the in vivo effectiveness of the ethanolic extract of Piper betle L. leaves against Staphylococcus aureus-infected wounds in mice and its antimicrobial properties on clinical isolates of multiple drug-resistant bacterial pathogens. Twenty mice were divided into four groups. Wounds were created in all mice under anesthesia by excision from the dorsal skin down to the subcutaneous fat and inoculating with S. aureus. After 24 h, the wound of each mouse was treated once daily by application of the respective cream. Group I was treated with mupirocin antibacterial cream; Group II received a cream base containing no active ingredient; Groups III and IV were treated with 2.5% and 5.0% concentrations of P. betle cream, respectively. Further, an in vitro study was performed by adding undiluted, 1:50 and 1:100 dilutions of the four studied creams in normal saline containing 1.5 × 108 CFU/mL of the following bacteria: antimicrobial-susceptible S. aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus, metallo-βlactamase-producing P. aeruginosa and carbapenem-resistant Klebsiella pneumoniae. The mice in Groups III and IV had significantly faster wound contraction and significantly shorter reepithelialization time than Group II (p 0.05). P. betle creams inhibited all studied bacterial strains at full concentration and at a dilution of 1:50. The inhibitory effect was more significant than Groups I and II (p 0.05) when compared with Group I. Cream formulations derived from P. betle ethanolic extract have great potential as antimicrobial agents for the treatment of wound infection. Further clinical tests are recommended to determine the safety and efficacy of these formulations in other mammalian species.

The aqueous extracts of thirty-four (34) tropical plants were tested in vitro for potential antimarine leech (Zeylanicobdella arugamensis) activity. The anti-leech activity was determined by exposing 8 adult leeches (Z. arugamensis) (9.3 ± 1.5 mm, aged 15 days) to 20 μl of plant extract (0.5 g/ml) for 5 min in a 24-well plate. After 5 min of exposure, the leeches were rinsed and transferred into seawater, to enable them to revive from the effect of the extract. Leech movements were observed from time to time and the numbers of paralyzed or dead leeches were recorded at 5, 20, 30 and 240 min. The efficacy of the plant extract in killing the adult Z. arugamensis during the 5 min exposure is reflected on the anti-leech property of the extract. The anti-leech property of positive plant extracts was also determined at different exposure time (1, 3, 5 min) and dilutions (1/2 (0.25 g/ml), 1/5 (0.1 g/ml) and 1/10 (0.05 g/ml). The extracts of 4 plants (Melastoma malabathricum, Piper betle, Tetracera indica and Etlingera coccinea) demonstrated anti-leech activity. The effects of M. malabathricum, P. betle and E. coccinea extracts on the leeches were very rapid causing death as early as a few seconds upon exposure. However, all four positive plant extracts were found not effective in killing the leeches at 1/10 dilution (0.05 g/ml). A Scanning Electron Microscopy examination on leeches exposed to the positive plant extracts exhibited effects such as protruding proboscis and shrunken or swollen bodies.

Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E

Piper betle leaves possess several ethnomedicinal properties and are immensely used in traditional medicinal practices in regions of Asian and African subcontinents. However, their effects in treating skeletal complications are least known. In this study, we evaluated cellular and molecular effects of betel leaf extract (BLE) and its major phytoconstituent, hydroxychavicol (HCV) in promoting osteogenesis in vitro and alleviating glucocorticoid induced osteoporosis (GIO) in vivo. Both BLE and HCV markedly stimulated osteoblast differentiation of C3H10T1/2 cells with increased expression of RUNX2 and osteopontin through the GSK-3β/β-catenin-signaling pathway. Also, oral administration of BLE and HCV in GIO rats resulted in restoration of bone mass and tissue microarchitecture. Thus, with our findings we conclude that BLE and HCV promote osteogenesis of C3H10T1/2 cells via the GSK-3β/β-catenin pathway and alleviate GIO in rats.

Piper betle (PB), also known as “betel” in Malay language, is a tropical Asian vine. PB leaves are commonly chewed by Asians along with betel quid. It contains phenols such as eugenol and hydroxychavicol along with chlorophyll, β-carotene, and vitamin C (Salehi et al., 2019). Extracts from PB leaves have various medicinal properties including anticancer, antioxidant, anti-inflammatory, and antibacterial effects (Salehi et al., 2019). Previous research has shown that PB induces cell cycle arrest at late S or G2/M phase and causes apoptosis at higher doses (Wu et al., 2014; Guha Majumdar and Subramanian, 2019). A combination of PB leaf extract has also been shown to enhance the cytotoxicity of the anticancer drug, 5-fluorouracil (5-FU), in cancer cells (Ng et al., 2014).

Objectives: Leaves of Piper betle are frequently used in South and Southeast Asia for traditional treatment and as a mouth freshener. Our purpose is to compare the phytochemical and antimicrobial properties of betel leaves from Barguna and Moheshkhali against Bacillus cereus, Staphylococcus aureus, and Escherichia coli. Methods: We extracted the betel leaves with acetone and ethanol according to the standard procedure. The extracts were analyzed for the presence of phytochemical properties by a standard procedure, antibacterial susceptibility by agar well diffusion method, minimum inhibitory concentration (MIC) by broth dilution assay and functional groups were obtained by FT-IR spectroscopic analysis. Results: We found the presence of a good number of phytochemicals in both Barguna and Moheshkhali extracts. Most of the cases, extracts of Moheshkhali leaves showed a greater zone of inhibition than Barguna extracts. Acetonic and ethanolic extracts of Barguna showed the minimum inhibitory concentration (MIC) from 2.12 to 4.25 mg/ml, where Moheshkhali extracts showed between 2.12-8.5 mg/ml. The functional groups obtained by FT-IR spectra analysis were compared for the extracts. Conclusions: Betel leaves can be utilized to augment the shelf life of foods, treatments and boost up immunity following comprehensive studies.

This study reports the formulation of mupirocin-loaded chitosan microspheres embedded in Piper betle extract containing collagen scaffold as combinational drug delivery for improved wound healing. Selection of chitosan type (molecular weight and degree of deacetylation) was carried out based on their antibacterial efficacy. The low molecular weight chitosan was selected owing to the highest antibacterial action against gram-positive as well as gram-negative bacteria. Low molecular weight chitosan-microspheres showed spherical shape with largely smooth surface morphology, 11.81% of mupirocin loading, and its controlled release profile. The XRD, DSC thermograms, and FT-IR spectral analysis revealed the mupirocin loaded in molecularly dispersed or in amorphous form, and having no chemical interactions with the chitosan matrix, respectively. The in vivo study indicates potential effect of the mupirocin, Piper betle, and chitosan in the collagen scaffold in the wound healing efficiency with approximately 90% wound healing observed at the end of 15 days of study for combinational drug-loaded chitosan microspheres-collagen scaffold-treated group. The histopathology examination further revealed tissue lined by stratified squamous epithelium, collagen deposition, fibroblastic proliferation, and absence of inflammation indicating relatively efficient wound healing once treated with combinational drug-loaded chitosan microspheres containing scaffold.

Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (Piper betle L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC50 value of 41.52 ± 1.02 μg/mL, 45.60 ± 0.56 μg/mL, and 51.42 ± 1.25 μg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC50 = 7.72 ± 0.98 μg/mL, 20.59 ± 0.83 μg/mL and 24.78 ± 0.56 μg/mL, respectively). According to gas chromatography–mass spectrometry, PBL is abundant in caryophyllene, eugenol, O-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent.

Piper betle L. (synonym: Piper betel Blanco), or betel vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as the green gold. The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart-shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes of P. betle are antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application of P. betle did not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety of P. betle. The findings suggest that P. betle represents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure–activity relationships, bioavailability and synergistic interactions with other drugs., This research was funded by projects APOGEO (Cooperation Program INTERREG-MAC 2014–2020, with European Funds for Regional Development-FEDER, ‘Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) del Gobierno de Canarias’ (project ProID2020010134), and CajaCanarias (project 2019SP43).

Betel leaf is consumed as a mouth freshener due to its characteristic flavor, aromaticity, and medicinal values. Abundance of phytochemicals in betel leaf contributes towards unique qualitative features. Screening of metabolites is quintessential for identifying flavoring betel leaves and their origin. Metabolomics presently lays emphasis on the cumulative application of gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopic approaches. Here we adopted different protocols based on the above-mentioned analytical metabolomics platform for untargeted plant metabolite profiling followed by multivariate analysis methods and a phytochemical characterization of Piper betel leaf cultivars endemic to coastal Odisha, India. Based on variation in the solvent composition, concentration of solvent, extraction temperature, and incubation periods, five extraction methods were followed in GC-MS and NMR spectroscopy of betel leaf extracts. Phytochemical similarities and differences among the species were characterized through multivariate analysis approaches. Principal component analysis, based on the relative abundance of phytochemicals, indicated that the betel cultivars could be grouped into three groups. Our results of FTIR-, GC-MS-, and NMR-based profiling combined with multivariate analyses suggest that untargeted metabolomics can play a crucial role in documenting metabolic signatures of endemic betel leaf varieties.

1. The following trial investigated the antigout activity and probable mechanism of

Betel leaf ethanolic extract (BLEE), which was dechlorophyllized by sedimentation process was loaded in liposomes at 1 and 2% (w/v) concentrations using two different methods, namely thin film hydration (TF) and ethanol injection (EI) methods. Liposomes loaded with 1% BLEE and prepared by TF method (BLEE/L-T1) had the smallest particle size and paler color than BLEE/L-E1, BLEE/L-E2, and BLEE/L-T2 (p .05). BLEE/L-T1 also showed strong stability as judged by its lowest zeta potential and polydispersity index. The highest encapsulation efficiency (EE) and lowest releasing efficiency (RE) were also found with BLEE/L-T1. No significant difference (p .05) in the antioxidant activities was detected between the BLEE-loaded liposomes and BLEE solutions, indicating that encapsulation had no adverse effect on BLEE antioxidant potency. BLEE/L-T1 showed higher antioxidant stability than unencapsulated BLEE at the equivalent amount based on EE (BLEE/U-T1) during in vitro gastrointestinal tract digestion system. Therefore, BLEE/L-T1 could be an efficient delivery system for improving stability of antioxidant activities of BLEE. PRACTICAL APPLICATIONS: Despite the many benefits of betel leaf ethanolic extract, it still has some distinctive odor and slightly greenish color as well as instability induced by environment factors, which can limit applications in foods. Encapsulation of the betel extract in liposomes can be a good approach to mask its undesirable color and odor and to augment its antioxidant stability. Liposomal technology can be used to load betel leaf extract. However, different methods have been implemented to prepare liposomes that exhibit varying encapsulation efficacy as well as bioactivities. Thin film hydration method was shown to yield the liposome with better physical characteristics, higher encapsulation efficiency, slower release, and higher antioxidant stability than the ethanol injection method. Therefore, the thin film hydration method could be adopted to prepare stable liposomes loaded with betel leaf extract that possess antioxidant activity suitable for food applications.

The effects of dietary supplementation with phytogenic blend (PB) of Aerva lanata, Piper betle, Cynodon dactylon, and Piper nigrum on growth performance, ileal nutrient digestibility, intestinal morphology, and cecal microflora were determined in a 42-day broiler feeding trial. A total of 192 broilers were assigned to 4 dietary treatments (6 replicates and 8 birds/replicate): basal diet, basal diet supplemented with antibiotic (chlortetracycline), 1% and 2% PB, respectively. The body weight gain (BWG) of starter chicks increased linearly (P = 0.023) as dietary supplementation levels of PB increased. At grower phase, broilers fed diet supplemented with 1% PB had similar BWG with the antibiotic group, but other treatments had reduced (P = 0.0001) BWG. Dietary supplementation with 1% PB resulted in the highest (P < 0.0001) BWG during the study. Feed intake was not affected by the treatments during the starter, finisher, and overall rearing periods. Broilers fed diet supplemented with 1% PB had the best (P < 0.0001) feed conversion ratio during the study. Overall, broilers fed only basal diet had the highest (P = 0.0450) mortality. Ileal organic matter (OM) digestibility increased linearly (P = 0.044) with broilers fed diet supplemented with PB, but reduced with antibiotic group. Dietary supplementation with 1% PB had the highest (P = 0.0402) ileal digestibility of tryptophan. In the duodenum, broilers fed diet supplemented with PB had longer (P = 0.0006) villi heights than the birds fed only basal diet, but similar with antibiotic group. Broilers fed diet supplemented with PB had longer (P = 0.0064) villi height in the jejunum than the antibiotic group. Bifidobacterium concentration of the cecum content showed a slight increase (P = 0.053) with increasing supplementation levels of PB. In conclusion, the current study shows that dietary supplementation with PB improves growth performance, intestinal morphology, and apparent ileal digestibility of OM and tryptophan in a dose-dependent manner with the best response at 1% inclusion level.

Fresh betel leaves (Piper betle L.), imported into the UK are a traditional ready-to-eat food consumed by Asian populations. We report here the consolidation of routinely collected data to model the public health risks from consumption of this food. Amongst 2110 samples collected at Border Inspection, wholesale, catering or retail, Salmonella was detected in 488 (23%) of samples tested between 2011 and 2017 and was the most commonly Salmonella-contaminated ready-to-eat food examined by Public Health England during this period. Using data from multiple samples (usually 5) tested per consignment sampled at Border Inspection, contamination levels were calculated by most probable number: seasonal, temporal and country specific differences were detected. Quantitative contamination data was used to estimate the levels present at retail, and a β-Poisson dose response model the probability of illness was calculated. Using data for products imported from India, the probability of acquiring infection following a single exposure (comprising of a single leaf) was estimated to be between 0.00003 (January-March) and 0.0001 (July-September). Using British Asian population data for individuals over 30 years of age in England in 2011, two estimates of consumption were modelled as 2.1 and 12.8 million servings per annum. Results from the model estimated 160 cases (range 102 to 242) and 960 cases (range 612 to 1456) per year in England for the two consumption estimates and equated to 34 (range 22 to 51) and 204 (range 130 to 310) salmonellosis cases per year reported to national surveillance. Salmonella from 475 of the contaminated samples were further characterised which showed a heterogeneous population structure with 46 S. enterica subsp. Enterica serovars, together with S. enterica subs diarizonae and salamae identified. Isolates from individual consignments were diverse and close genetic relationships between independent isolates were very rare except from within an individual consignment. There were no outbreaks detected as associated with betel leaf consumption. However analysis by whole genome sequencing of the 2014-17 data identified two cases where the clinical isolate had5 single nucleotide polymorphism differences to isolates from betel leaves which is indicative of a likely epidemiological link and common source of contamination. Due to the diversity of the Salmonella contaminating this product, associations between salmonellosis cases and betel leaf consumption will appear sporadic and unlikely to be detected by current surveillance strategies based on outbreak detection.

Biological methods offer eco-friendly and cost-effective alternatives for the synthesis of silver nanoparticles (AgNPs). The present study highlights a green process where AgNPs were synthesized and optimized by using silver nitrate (AgNO3) and the aqueous extract of Piper betle (Pbet) leaf as the reducing and capping agent. The stable and optimized process for the synthesis of Pbet-AgNPs was exposure of reaction mixture into the sunlight for 40 min, pH 9.0, and 2 mM AgNO3 using 1:4 diluted Pbet leaf aqueous extract. The optimized Pbet-AgNPs were characterized by UV–visible spectroscopy, high-resolution field emission scanning electron microscopy (FE-SEM), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The prepared Pbet-AgNPs were spherical in shape with size in the range of 6–14 nm. These nanoparticles were stable for 6 months in aqueous solution at room temperature under dark conditions. The biogenic synthesized Pbet-AgNPs are found to have significant antifungal activity against plant pathogenic fungi, Alternaria brassicae and Fusarium solani. Synthesized Pbet-AgNPs potentially reduced the fungal growth in a dose-dependent manner. Microscopic observation of treated mycelium showed that Pbet-AgNPs could disrupt the mycelium cell wall and induce cellular permeability. Protein leakage assay supports these findings. Overall, this study revealed the efficacy of green synthesized AgNPs to control the plant fungal pathogens. Pbet leaves are a rich source of phenolic biomolecule(s). It was hypothesized that these biomolecule(s) mediated metal reduction reactions. In this context, the present work investigates the phytobiomolecule(s) of the aqueous extract of Pbet leaves using high-resolution liquid chromatography–mass spectroscopy (HR-LCMS) method. The analysis revealed that eugenol, chavicol, and hydroxychavicol were present in the Pbet aqueous extract.

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

A pure water soluble xylan (PS-I) with an average molecular weight ~1.1 × 10

This study aims to elucidate the antiproliferative mechanism of hydroxychavicol (HC). Its effects on cell cycle, apoptosis, and the expression of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK) in HT-29 colon cancer cells were investigated. HC was isolated from Piper betle leaf (PBL) and verified by high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and gas chromatography-mass spectrometry (GC-MS). The cytotoxic effects of the standard drug 5-fluorouracil (5-FU), PBL water extract, and HC on HT-29 cells were measured after 24, 48, and 72 h of treatment. Cell cycle and apoptosis modulation by 5-FU and HC treatments were investigated up to 30 h. Changes in phosphorylated JNK (pJNK) and P38 (pP38) MAPK expression were observed up to 18 h. The half maximal inhibitory concentration (IC(50)) values of HC (30 μg/mL) and PBL water extract (380 μg/mL) were achieved at 24 h, whereas the IC(50) of 5-FU (50 μmol/L) was obtained at 72 h. Cell cycle arrest at the G(0)/G(1) phase in HC-treated cells was observed from 12 h onwards. Higher apoptotic cell death in HC-treated cells compared to 5-FU-treated cells (P

A phytochemical investigation of an extract of the leaves of

Journal of Associated Medical Sciences, 54, 2, 42 - 50

Piper betle var. nigra is a tropical plant closely related to the common piper. P. betle has also been dubbed a promising source of natural antioxidants in herbal health products, antibacterial, antifungal, antimalarial, cytotoxic activity against the cancer cell lines K562 and HL-60, and antileishmanial. The aim of this study to observation Antimicrobial activity and isolation of chemical compound. The antimicrobial activity of P. betle extract was performed by well diffusion method against two oral pathogenic bacteria (Streptococcus mutans and Streptococcus sanguinis) and opportunistic pathogenic yeast (Candida albicans). The inoculum (bacterial and yeast suspension) was prepared from a 24-h culture on NB for bacterial suspension and on TSB for yeast suspension. Extraction and isolation using various method of chromatography. Isolated compounds were characterized by spectroscopic means. Our study showed antimicrobial activity from crude ethanol extract of leaves P. betle L. var. nigra against two oral pathogenic bacteria and opportunistic pathogenic yeast with concentration 0.5% and 1%. The first report of two new amides derivatives, piperenamide A (1) and piperenamide B (2) in P. betle L. var. nigra.

Housefly, Musca domestica L. is a pest of public health importance and is responsible for spreading diseases like typhoid, diarrhoea, plague etc. Indiscriminate reliance on synthetic insecticides has led to development of insecticide resistance and ill effect to humans and nontarget animals. This demands an alternative and safer pest control option. This study evaluates the biological effect of Piper betle L essential oil and its constituent eugenol, eugenol acetate, and β - caryophyllene on the housefly. The major components present in P. betel EO were safrole (44.25%), eugenol (5.16%), β -caryophyllene (5.98%), β -selinene (5.93%), α-selinene (5.27%) and eugenol acetate (9.77%). Eugenol caused 4.5fold higher ovicidal activity (EC50 86.99 μg/ml) than P. betle EO (EC50 390.37 μg/ml). Eugenol caused fumigant toxicity to adults (LC50 88.38 mg/dm3). On contact toxicity by topical application, eugenol acetate, eugenol and β-caryophyllene caused higher mortality to larval and adult stages than EO. FESEM (Field Emission Scanning Electron Microscope) images reveal that exposure to P. betle EO causes the shrinkage of the larval cuticle. Both EO and eugenol induced the detoxifying enzymes Carboxyl esterase (Car E) and Glutathione S – transferases (GST) in larvae and adults. EO and eugenol at 0.2% caused effective repellence and oviposition deterrence to M. domestica adults and this merits their use as alternative strategy to manage M. domestica.

Sedimentation process was used to remove chlorophyll from betel leaf ethanolic extracts (BLEE) and chaphlu leaf ethanolic extracts (CLEE). The influence of water quantity on chlorophyll content, total phenolic content (TPC), and antioxidant activity of the extracts was studied. The sedimentation process showed a remarkable reduction in chlorophyll A, chlorophyll B, and total chlorophyll contents of both extracts. Nevertheless, no differences in chlorophyll content, TPC, and antioxidant activities were observed between dechlorophyllized fractions in both extracts (p > .05). Liquid Chromatography-Mass Spectrometry (LC/MS) profiling showed that the BLEE dechlorophyllized using the extract/water ratio of 1:1 (BLEE-DC1) had higher phenolic compounds than CLEE-DC1. Isovitexin was the most abundant compound identified in the BLEE-DC1 while vitexin 4'-O-galactoside was the most prevalent in CLEE-DC1. When thermal and pH stabilities of the dechlorophyllized extracts were tested, BLEE-DC1 exhibited more heat stability (at 60-100°C for 0-60 min) than CLEE-DC1. Both dechlorophyllized extracts showed optimum antioxidant activities at pH 5.0. PRACTICAL APPLICATIONS: Oxidation process is associated with the numerous human diseases as well as it induces the deteriorative changes in foods, especially those rich in fat or lipid containing high polyunsaturated fatty acids. Numerous synthetic antioxidants have been employed but they may not be safe. Natural antioxidants have gained attention, particularly those from several leaves rich in polyphenols. However, due to the green color caused by chlorophylls, the extract is limited for further applications. Betel leaf ethanolic extract possessing high antioxidant activity could be dechlorophyllized using sedimentation process with the appropriate proportion of water. This green process not only showed the effective removal of chlorophyll, but also increased the proportion of polyphenol in the extract. Greenless betel leaf extract with augmented antioxidant activity can be used as natural additive to replace synthetic counterpart.

Malaria disease remains a serious worldwide health problem. In South-East Asia, one of the malaria infection "hot-spots," medicinal plants such as Piper betle have traditionally been used for the treatment of malaria, and allylpyrocatechol (1), a constituent of P. betle, has been shown to exhibit anti-malarial activities. In this study, we verified that 1 showed in vivo anti-malarial activity through not only intraperitoneal (i.p.) but also peroral (p.o.) administration. Additionally, some analogs of 1 were synthesized and the structure-activity relationship was analyzed to disclose the crucial sub-structures for the potent activity.

The purpose of this study was to evaluate anti-candidal activity, gelation time, and surface hardness of a short-term soft lining material incorporated with varying concentrations of Piper betle extract (0.25 to 20% w/w). Agar-diffusion assay was conducted to evaluate an inhibitory effect against Candida albicans. The gelation time was assessed and surface hardness was measured at 2 h and 7 days by Shore AO durometer. A soft liner containing at least 5% w/w of P. betle extract was observed the inhibitory effect against C. albicans. An increasing of P. betle concentrations provided larger inhibition zone. Incorporating 5% w/w of P. betle extract into the soft liner did not significantly alter its gelation time and surface hardness (ANOVA; p0.05). The optimum composition at 5% w/w of P. betle extract can be used as an additive in the soft liner to provide the anti-candidal activity without significantly affect these two main properties.

This case series presents 10 pediatric patients, aged 4 to 9 years, with leukomelanosis on the chest or forehead. The pigmentary changes developed after the traditional use of Piper betle leaves as a home-based remedy for a cough or cold. Piper betle-induced leukomelanosis in children is a rare dermatosis resulting from cultural practices. It is important to recognize the role of ethnobotany in dermatology.

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B–E (2–5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 μM, respectively, compared with the positive control NG-monomethyl- l -arginine ( l -NMMA, IC50 = 33.84 μM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity.

In this study, phytochemical analyses of the chloroform extract of

Quorum sensing (QS), the communication signaling network, regulates biofilm formation and several virulence factors in Pseudomonas aeruginosa PAO1, a nosocomial opportunistic pathogen. QS is considered to be a challenging target for compounds antagonistic to virulent factors. Biologically synthesized silver nanoparticles (AgNPs) are reported as anti-QS and anti-biofilm drugs against bacterial infections. The present study reports on the synthesis and characterization of Piper betle (Pb) mediated AgNPs (Pb-AgNPs). The anti-QS activity of Pb-AgNPs against Chromobacterium violaceum and the potential effect of Pb-AgNPs on QS-regulated phenotypes in PAO1 were studied. FTIR analysis exhibited that Pb-AgNPs had been capped by phytochemical constituents of Pb. Eugenol is one of the active phenolic phytochemicals in Pb leaves, therefore molecular docking of eugenol-conjugated AgNPs on QS regulator proteins (LasR, LasI and MvfR) was performed. Eugenol-conjugated AgNPs showed considerable binding interactions with QS-associated proteins. These results provide novel insights into the development of phytochemically conjugated nanoparticles as promising anti-infective candidates.

We describe the syntheses of phenolic compounds, 4-[(1

Betel vine is an edible creeper used in folk medicine to aid digestion since time immemorial. It is an ideal candidate deemed for the bioprospection of endophytic microorganisms with valuable attributes. This study aimed at the characterization of potential bacteria from fermented betel leaves. We report the presence of Pediococcus species with probiotic properties from betel. The isolated organisms were subjected to preliminary biochemical analysis and exhibited growth at 37°C and pH 6.7 with fermented glucose, sucrose and lactose without the evolution of CO

Musca domestica can be found easily in the residential area and can be controlled by usingbio-insecticide. Betle leaf contains tannins, terpenoids, flavonoids, and essential oils. Thepurpose of this study was to identify the effectiveness of Piper betle L as a larvicide against Musca domestica larvae. The experiment was a true experimental with a pre-test post-testwith control group design. Feeding assay method was used on 20 third instar larvae ofMusca domestica. Data were analyzed by using descriptive analysis, Kruskal Walls test,and probit analysis. The results showed the p-value for Levene test and Kruskal Walls testwere 0.028 and 0.014 respectively. Moreover, the LC50 was 0.05% and LT50 was 7.7 hours.There was a difference between negative control and all treatment concentrations. Itindicated that the betle leaf extract (Piper betle L) can be used as a bio-insecticide. Abstrak Lalat rumah (Musca domestica) sering terlihat di lingkungan rumah. Upaya yangdilakukan untuk pengendalian lalat rumah yaitu dengan penggunaan insektisida yangramah lingkungan seperti insektisida nabati. Daun sirih mengandung tanin, terpenoid,flavonoid dan minyak atsiri. Tujuan penelitian ini yaitu mengetahui efektivitas ekstrakdaun sirih (Piper betle L) sebagai larvasida larva lalat rumah (M. domestica). Jenis penelitian ini adalah true experimental dengan jenis disain pretest posttest controlgroup. Objek penelitian ini menggunakan 20 ekor larva lalat instar III yang diberiperlakuan dengan metode feeding assay. Analisis data yang digunakan yaitu analisis deskriptif, analisis analitik dengan menggunakan uji Kruskal Walls, serta analisis probit. Penelitian ini dilakukan berdasarkan hasil uji normalitas dengan nilai p value0,002

Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly. Hydroxychavicol (HC) isolated from Piper betle has been reported to possess antibacterial activity. It is currently not clear how the antibacterial activity of HC is manifested. In this investigation we show HC generates superoxide in E. coli cells. Antioxidants protected E. coli against HC induced cell death while gshA mutant was more sensitive to HC than wild type. DNA damage repair deficient mutants are hypersensitive to HC and HC induces the expression of DNA damage repair genes that repair oxidative DNA damage. HC treated E. coli cells are inhibited from growth and undergo DNA condensation. In vitro HC binds to DNA and cleaves it in presence of copper. Our data strongly indicates HC mediates bacterial cell death by ROS generation and DNA damage. Damage to iron sulfur proteins in the cells contribute to amplification of oxidative stress initiated by HC. Further HC is active against a number of Gram negative bacteria isolated from patients with a wide range of clinical symptoms and varied antibiotic resistance profiles.

Piper betle has been used as a medicinal plant in traditional medical systems throughout South and South East Asia. Experimental studies have revealed its wide and diverse biological and pharmacological effects. In this study, antigiardial activity of Piper betle was tested using experimental infections of Giardia intestinalis, the most common cause of protozoal diarrhoea worldwide, in Mongolian gerbils. Plants were extracted in water, methanol and methanol:tetrahydrofuran. Gerbils were treated for ten days intragastrically twice a day, with the dose of 40 mg of the extract per 100 g of body weight. Drug metronidazole was used as a negative control. Gerbils' faeces were taken every day and examined by flotation method, the number of shed cysts were counted using a haemocytometer. After gerbils' sacrifice and dissection, their duodena were then processed for examination using histological sectioning and scanning electron microscopy. The antigiardial activity was evaluated by the course of cyst shedding throughout the entire experiment. A significant decline in cyst shedding, evaluated by linear regression was found in gerbils treated with the aqueous extract. Our results indicate that the aqueous extract of P. betle shows giardicidal effects.

The aim of the present study is carried out to purify the medicinally potent Hydroxychavicol from methanolic extract of Betel leaf (Piper betle L.) and evaluation of its antimicrobial activity against some of the selected food poison causing pathogens. Hydroxychavicol was successfully purified by silica gel assisted column chromatography. Authenticity of purified Hydroxychavicol was confirmed by Reverse Phase High Performance Liquid Chromatography (RP-HPLC). Minimal Inhibitory Concentration (MIC) and Minimal Bacterial Concentration (MBC) of E.coli and Salmonella were found to be in the range between 20-50 µg. Furthermore, hydroxychavicol was also tested for Time-kill curve and its potential to inhibit the formation of biofilm against E.coli and Salmonella respectively. In summary, antimicrobial study strongly suggests that the hydroxychavicol possess potent antimicrobial activity against E.coli and Salmonella.

The present study was conducted to evaluate the methanolic extracts from several plant leaves widely used in traditional medicine to cure digestive tract disorders and in the self-medication of wild animals such as non-human primates, namely Archidendron fagifolium , Diospyros sumatrana , Shorea sumatrana, and Piper betle leaves, with regard to their antimicrosporidial activity against Encephalitozoon cuniculi in immunocompetent BALB/c mice determined using molecular detection of microsporidial DNA (qPCR) in various tissues and body fluids of infected, treated mice. Of the plant extracts tested, Diospyros sumatrana provided the most promising results, reducing spore shedding by 88% compared to untreated controls. Moreover, total burden per 1 g of tissue in the D. sumatrana extract-treated group reached 87% reduction compared to untreated controls, which was comparable to the effect of the standard drug, Albendazole. This data represents the baseline necessary for further research focused on determining the structure, activity and modes of action of the active compounds, mainly of D. sumatrana , enabling subsequent development of antimicrosporidial remedies.

Vibrio harveyi is a potent biofilm former, which confers resistance to multiple antimicrobials, disinfectants, chemicals and biocides. The prevalence of biofilm mediated antibiotic resistance among aquatic bacterial pathogens stresses the search for novel alternative approach to treat vibriosis in aquaculture. Exploring suitable therapeutics from natural resources could be a novel area of research. Therefore, this work was executed to evaluate the inhibitory effect of Piper betle ethyl acetate extract (PBE) on bioluminescence production and biofilm formation of V. harveyi. Minimal inhibitory concentration (MIC) of PBE against planktonic V. harveyi was found to be 1600 μg ml−1; furthermore, PBE inhibited the quorum sensing (QS) mediated bioluminescence production and biofilm formation in V. harveyi upto 98 and 74% respectively, at its sub-MIC concentration of 400 μg ml−1 without affecting their cell viability. Similar results were obtained for exopolysaccharides production and swimming motility related to biofilm formation of V. harveyi, where PBE reduced EPS production upto 64%. Light and confocal laser scanning microscopic analyses further confirmed that the PBE effectively prevented the initial attachment as well as microcolonies formation of V. harveyi biofilm, when compared to their untreated controls. This study demonstrates the promising antibiofilm activity of PBE and confirms the ethnopharmacological potential of this plant against V. harveyi infections.

We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case–control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34–14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70–575.73). The synergy index was 16.58 (95% CI, 2.27–70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355–62. ©2017 AACR.

Resistance to treatments with Temephos or plant derived oil, Pb-CVO, between a field collected Wild Strain (WS) and a susceptible Laboratory Strain (LS) of Ae. aegypti were measured. The Temephos (0.1mg/L) showed the greatest percentage of mosquito mortality compared to Pb-CVO (1.5mg/L) in LS Ae. aegypti. However, WS Ae. aegypti was not significantly affected by Temephos (0.1mg/L) treatment compare to the Pb-CVO (1.5mg/L). However, both strains (LS and WS) when treated with Pb-CVO (1.5mg/L) displayed steady larval mortality rate across all instars. The LC50 of Temephos was 0.027mg in LS, but increased in WS to 0.081mg/L. The LC50 of Pb-CVO treatment was observed at concentrations of 0.72 and 0.64mg/L for LS and WS strains respectively. The enzyme level of α- and β-carboxylesterase was reduced significantly in both mosquito strains treated with Pb-CVO. Whereas, there was a prominent deviation in the enzyme ratio observed between LS and WS treated with Temephos. The GST and CYP450 levels were upregulated in the LS, but decreased in WS, after treatment with Temephos. However, treatment with Pb-CVO caused both enzyme levels to increase significantly in both the strains. Visual observations of the midgut revealed cytotoxicity from sub-lethal concentrations of Temephos (0.04mg/L) and Pb-CVO (1.0mg/L) in both strains of Ae. aegypti compared to the control. The damage caused by Temephos was slightly less in WS compared to LS mosquito strains.

Background: Oral candidiasis is a common fungal infection caused by Candida albicans. In recent years, Candida species have shown resistance against many synthetic drugs, which has highlighted the need for novel antifungal drugs with fewer side effects for effective management of candidiasis. Several studies have suggested that some plant species possess promising antimicrobial compounds. Piper betle and Ocimum sanctum Linn are such common medicinal plants that show strong antimicrobial activity by the release of secondary metabolites. However, the effect of these plants on oral candidiasis has not been studied and hence, the present study aimed to evaluate the antifungal activity of these plant extracts on the subcultures of C. albicans and compared with a standard drug, fluconazole. Materials and Methods: Subcultures of C. albicans obtained from oral thrush patients were used in the present study. Ethanolic and ethyl acetate extracts of P. betle (betel) and O. sanctum L. (tulsi) leaves were prepared by cold extraction method. The anticandidal activity and minimum inhibitory concentration (MIC) were evaluated using disc diffusion method and microbroth dilution method, respectively. Values were compared with the standard drug fluconazole. Results: Both the extracts exhibited anticandidal activity on the subcultures of C. albicans. The ethyl acetate extract of mature betel leaf showed a maximum zone of inhibition (26 mm) when compared with tulsi and fluconazole (13 mm). Betel leaf extract showed better MIC values (125 μg/ml) than tulsi (2000 μg/ml). However, these values were high when compared with those of fluconazole (62.5 μg/ml). Conclusion: Ethyl acetate extract of mature betel leaf exhibited good anticandidal activity than that of tulsi and fluconazole.

Betel leaf ( Piper betle ) contains an essential oil that has extreme antiseptic power (bactericidal and fungicidal). Betel leaf ( Piper betle ) can be used in the treatment of Tinea versicolor or known in the community as panu . However, its use in the form of leaves is considered impractical by the public and also difficult to obtain. This research formulated betel leaf ( Piper betle ) into lotion preparations, so its use in the community can be more practical. This study aims to determine the type and concentration of the suspending agent used to produce lotion preparations from betel leaf extract ( Piper betle ), which has optimal physical quality. This research was an experimental study. The distillation of betel leaf ( Piper betle ) was carried out to get essential oils. The essential oils of betel leaf ( Piper betle ), which was used as an active substance in formulations, was 5%. Suspending agents that were used in this study were Arabic gum with concentrations of 10%, 15%, 20%, and CMC Na, with concentrations of 0.25%, 0.5%, and 1%. The formulation of lotion preparations included organoleptic observation, pH test, homogeneity test, and adhesion test. Based on the physical quality test of the lotion preparations that had been conducted, it can be concluded that the lotion preparations of betel leaf extract with 20% concentration of Arabic Gum suspending agent had physical qualities in accordance with lotion dosage criteria.

Streptococcus intermedius, Streptococcus mutans, and Candida albicans are harmful oral pathogens and prone to resist chemical antimicrobial agents. Active ingredients from plants are of increasing interest as an alternative. This study aims to compare antimicrobial effects of 4-allylpyrocatechol (APC) extracted from Piper betle on these oral pathogens. Minimum concentration of APC against the tested pathogens was determined using a broth microdilution assay. Killing kinetic study of APC was carried out within 24 h. Morphology of the pathogenic cells was assessed using scanning electron microscopy (SEM). Anti-biofilm was investigated using crystal violet assay and confocal laser scanning microscopy (CLSM). The results showed that the mechanism of inhibition of APC was bactericidal and fungicidal effects. APC at minimum concentration of 400 μg/mL could completely kill Streptococcus and Candida spp., however, the killing rate on S. intermedius and C. albicans was significantly faster than on S. mutans. APC inhibited biofilm formation of C. albicans more efficiently than that of the bacterial cells. Cell morphology from SEM indicated that APC caused bacterial cell membrane destruction and inhibited fungal budding or tubing formation. CLSM images confirmed the killing potential of APC and suggested that bacterial dead cells could be easier washed out than the fungal dead cells. It is concluded that APC potentially inhibits growth and biofilms of oral Streptococcus and Candida spp. in different mechanism of action and killing rate. APC can be considered as a promising agent for preventing and treating dental disorders caused by S. intermedius, S. mutans, and C. albicans.

Rationale Piper betle leaf, used as masticatory in South Asia, is also medicinally important. Objective This work was done to analyze phytochemical composition of two solvent fractions (chloroform and ethyl acetate) of the aqueous extracts obtained from eight varieties of P. betle leaves and to identify the active components against β-glucuronidase by chemometric analysis. Results Twenty-four phenolic compounds, in addition to different organic acids, fatty acids, amino acids, sugars, and polyols, were identified from the solvent fractions. The extracts inhibited the enzyme β-glucuronidase. Piceatannol was the most active constituent against the enzyme (activity 12 times higher than that of silymarin), Chlorogenic acid also inhibited β-glucuronidase (activity 4.4 times higher when compared to silymarin). 2,2'-Diphenyl-1-picrylhydrazyl and superoxide free radical scavenging activities of both the fractions of eight varieties of P. betle leaf extracts showed very strong antioxidant potentiality. Conclusion The findings validated some medicinal properties of the said leaves. Practical applications Edible leaves of Piper betle are medicinally and economically important. Leaves of different local varieties are reported to be used for the treatment of different diseases. The leaves have many biological properties, hepatoprotection being one of them. A large number of rural population is economically dependent on the cultivation of betel vine. But with a rapid change in lifestyle, the chewing habit of P. betle is decreasing ultimately affecting the livelihood of farmers dependent on betel cultivation. Knowledge on β-glucuronidase inhibitory activity and the mechanism for hepatoprotection of different P. betle varieties may validate the medicinal properties of betel, which would increase consumption of these leaves.

Piper betle L., belonging to Piperaceae family, known as a traditional herbal medicinal plant and used for several health benefits in Asian countries. Currently, demand for its products such as herbal drugs, medicines, and natural herbal formulations has increased. The beneficial effects of betel leaves and its products have traditionally exploited for the treatment of several diseases like bad breath, cuts, injuries, inflammations, cold cough, indigestion, etc. Till now, a broad range of bioactive compounds including polyphenols, terpenes, etc., has been identified from the extracts and essential oil (EO) of betel leaves. The structural and functional characterization of the extract and EO bio-actives has been derived by various advanced standard methods. Most of the health-related benefits of betel leaves have been associated with their bioactive phenolic compounds. The extract of this highly perishable product can be used in organic synthesis, food, and beverage industry, pharmaceuticals, etc., to the environmental issues. The present review provides information on extraction techniques, identification of bioactive compounds, and their biological activities. That apart, information on processing, preservation, and health benefits along with their mechanisms has also been added.