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The phytochemistry, traditional uses and pharmacology of Piper Betel. linn (Betel Leaf): A pan-asiatic medicinal plant

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Abstract

Since antiquity, Piper betel. Linn, commonly known as betel vine, has been used as a religious, recreational and medicinal plant in Southeast Asia. The leaves, which are the most commonly used plant part, are pungent with aromatic flavor and are widely consumed as a mouth freshener. It is carminative, stimulant, astringent and is effective against parasitic worms. Experimental studies have shown that it possess diverse biological and pharmacological effects, which includes antibacterial, antifungal, larvicidal, antiprotozal, anticaries, gastroprotective effects, free radical scavenging, antioxidant, anti-inflammatory hepatoprotective, immunomodulatory, antiulcer and chemopreventive activities. The active principles hydroxychavicol, allylpyrocatechol and eugenol with their plethora of pharmacological properties may also have the potential to develop as bioactive lead molecule. In this review, an attempt is made to summarize the religious, traditional uses, phytochemical composition and experimentally validated pharmacological properties of Piper betel. Emphasis is also placed on aspects warranting detail studies for it to be of pharmaceutical/clinical use to humans.

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... The free radical scavenging activity of the P. betle was determined by hydrogen peroxide assay. [25] Hydrogen peroxide (10 mM) solution was prepared using phosphate-buffered saline (0.1 M, pH 7.4). The 1 ml of different concentration of betel extracts (100, 250, 500, 750, and 1000 μg) were rapidly mixed with 2 ml of hydrogen peroxide solution. ...
... In this study, free radical scavenging activities were evaluated by several standard methods using spectrophotometer. Fazal et al. [25] reported that better ability of antioxidant activity of P. betle leaf extract and H 2 O 2 might account for the results. The range of DPPH radical scavenging assay for the P. betle was 69.27% ± 0.92% [ Figure 1d]. ...
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Background: The widespread usage of synthetic chemical drugs often contributes to the development of drug resistance in the clinical pathogens along with hazardous side effects in the human side. Among those clinical pathogens, Candida albicans is a prime consideration to explore. C. albicans is wildly causing a fungal infection of oral cavity well known as candidiasis. This study is prompted to find some novel natural compounds from a medicinal plant, Piper betle against C. albicans. Methods: Bioactive compounds were extracted from the betel leaves using different solvents. The standard drug, fluconazole was used to check anticandidal activity of P. betle against C. albicans. Plant extracts were further characterized by the antioxidant and different scavenging assays. The biocompounds were identified using gas chromatography–mass spectrometry and successfully subjected to molecular docking study. Results: Methanol and ethanol extracts were showed potential antifungal, antioxidant, and scavenging activity against C. albicans, in comparison with control drug. Twenty‑seven bioactive compounds were identified in the methanol extract of P. betle. These active bioactive compounds were docked with candidapepsin‑1, a proteolytic virulent enzyme of C. albicans and compared with a control drug, fluconazole (−7.8 kcal/mol), and the effective interaction was observed with specific bioactive compound, 4‑hydroxy‑5‑imino‑3,4‑dimethyl‑1‑(4‑nitrophenyl)‑2‑imidazolidinone (−7.5 kcal/mol). Conclusion: The present study reveals that methanol and ethanol extract of P. betle is a potential source of natural‑free radical scavenging antioxidants. These findings will be great helpful in the new drug analysis for the determination of antimicrobial biocompounds against candidiasis and other clinically related infections.
... Root and fruits are well known for treating malaria and asthma. It is used to treat diabetes, excessive thirst, fever, loss of appetite, mouth ulcers, nasal inhalation, nausea, and worms (Fazal et al. 2014). It is also used to enhance metabolic functions, reduce inflammation, expel mucus, strengthen the heart muscles, improve appetite, purify the blood, treat ulcers, nosebleeds, acne, bronchitis, halitosis, and bleeding gums, headache and reproductive problems (Fazal et al. 2014). ...
... It is used to treat diabetes, excessive thirst, fever, loss of appetite, mouth ulcers, nasal inhalation, nausea, and worms (Fazal et al. 2014). It is also used to enhance metabolic functions, reduce inflammation, expel mucus, strengthen the heart muscles, improve appetite, purify the blood, treat ulcers, nosebleeds, acne, bronchitis, halitosis, and bleeding gums, headache and reproductive problems (Fazal et al. 2014). The main constituents present are essential oil, amino acids, vitamins and enzymes. ...
Article
Natural products, especially plants and herbs, have always been a common medicament source, either as pure active principles or traditional preparations. Traditional medicine has been used in developing and developed countries for centuries, and still, 80% of the population uses plant-based medicines for their health care needs. The present review discusses all the possible pharmacological activity reported in various literature and active chemical constituents of herbs. A list of various herbs/plants used by Ayurvedacharya Ratiram Sharma (93-year-old and practicing since 1952) and mentioned in Ayurvedic texts. The curated list was prepared by their general availability in the household and local market. This study comprehensively documented the medicinal value of sixty-six dominant plant species used in Ayurveda and local people. In the present review, each herb is discussed with its scientific and common names, geographical distribution, traditional medicinal uses, beneficial plant parts, and active chemical constituents. For each plant, pharmacological activities of different parts of plants are displayed with their chemical constituents and structure. Toxicologists, phytologists, medicinal chemists, and other researchers who are interested in the various therapeutic and related applications of plant materials will be benefited from present review. This information will open new horizons of application for the many novel drugs and drug candidates.
... Its leaves are typically utilized in betel chewing and folkloric uses (Das et al., 2016). Its extracts were previously shown to be non-cytotoxic against human dermal fibroblasts (Valle et al., 2016) but have antifungal, antiprotozoal, antifilarial properties (Fazal et al., 2014), antimicrobial activities against multi-drug resistant pathogens (Valle et al., 2016), and biofilm inhibitory activity against V. harveyi (Srinivasan et al., 2017). However, its mechanism of action, particularly its targets on the QS system of V. harveyi remains unknown. ...
... The presence of alkaloids in CA was confirmed via Dragendorff's test wherein a cloudy orange solution was observed due to the presence of alkaloids (Sharma et al., 2010). Previous reports on the phytochemical composition of P. betle leaves state the presence of phenolic compounds, flavonoids, and alkaloids (Fazal et al., 2014) such as pellitorine, piperidine, and piperine (Lim et al., 2009). ...
Article
Vibriosis, including the luminescent shrimp disease and acute hepatopancreatic necrosis disease (AHPND), with Vibrio harveyi as one of their causative agents, is a major shrimp disease causing huge economic losses in the Philippines, Thailand, Vietnam and other Southeast Asian countries. It is induced through the formation of biofilm as a result of bacterial cell-to-cell communication or quorum sensing (QS). Hence, this mechanism may be used as a target for bioactive compounds in controlling V. harveyi infections in shrimp. In this study, crude ethanolic extract (CE) and crude alkaloids (CA) from Ikmo (Piper betle L.), a plant native to Southeast Asia, were observed to significantly (p < 0.05) inhibit biofilm formation of wild-type strains V. harveyi VH0, VH1 and BAA-1116 in chitosan-coated microtiter plates without inhibiting their growth. Confocal laser scanning microscopy revealed thinner biofilms formed upon treatment with both extracts. Furthermore, both CE and CA significantly (p < 0.05) inhibited bioluminescence in QS reference strain V. harveyi BAA-1116 and was found to interfere with QS by modulating autoinducer (AI) activities as observed in both phenotypic and gene expression analyses. Both extracts also did not negatively affect shrimp growth and pre-infection mortality rate. Despite the in vitro results however, in vivo analysis showed that only P. betle CE, when supplemented to shrimp feed, protected Penaeus vannamei postlarvae against V. harveyi infection after seven days. These suggest the potential supplementation of shrimp feed with P. betle crude extract as protection against Vibriosis.
... Piper betle (PB) or commonly known as "sireh" in Malaysia and Indonesia, belongs to the kingdom Plantae, a family of Piperaceae (Chaveerach et al. 2006;Fazal et al. 2014). The leaves of PB have been commonly used for healing of wounds in many parts of Asian countries. ...
... The leaves of PB have been commonly used for healing of wounds in many parts of Asian countries. Leaf of PB extract is proven to have polyphenols such as hydroxychavicol, chavibetol, chavicol, that have the following properties: anti-microbial, anti-inflammatory, antioxidant, antiseptic, wound healing agent as well as pain relieving properties (Fazal et al. 2014;Arambewela et al. 2005). Moreover, PB has the ability to promote wound contraction and reduction of healing time in Wistar rats by enhancing epithelialization process of the wound (Nilugal et al. 2014). ...
... The leaf is the most widely used and studied part of the betel vine. There are chewing habit practices of betel leaves in many countries which are believed beneficial for avoiding bad breath, strengthening the gum, preserving the teeth, and stimulating the digestive system [1,2]. In traditional medicine practices, betel leaves are used for vaginal douching in Indonesia [3], as a gargle mouthwash in India and Thailand [4], and as a treatment for dental problems, headaches, arthritis, and joint pain in Malaysia [1]. ...
... There are chewing habit practices of betel leaves in many countries which are believed beneficial for avoiding bad breath, strengthening the gum, preserving the teeth, and stimulating the digestive system [1,2]. In traditional medicine practices, betel leaves are used for vaginal douching in Indonesia [3], as a gargle mouthwash in India and Thailand [4], and as a treatment for dental problems, headaches, arthritis, and joint pain in Malaysia [1]. In Srilanka, the betel leaf juice is used to treat skin ailments [5]. ...
Article
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Piper betle (L) is a popular medicinal plant in Asia. Plant leaves have been used as a traditional medicine to treat various health conditions. It is highly abundant and inexpensive, therefore promoting further research and industrialization development, including in the food and pharmaceutical industries. Articles published from 2010 to 2020 were reviewed in detail to show recent updates on the antibacterial and antifungal properties of betel leaves. This current review showed that betel leaves extract, essential oil, preparations, and isolates could inhibit microbial growth and kill various Gram-negative and Gram-positive bacteria as well as fungal species, including those that are multidrug-resistant and cause serious infectious diseases. P. betle leaves displayed high efficiency on Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram-positive bacteria such as Staphylococcus aureus, and Candida albicans. The ratio of MBC/MIC indicated bactericidal and bacteriostatic effects of P. betle leaves, while MFC/MIC values showed fungicidal and fungistatic effects. This review also provides a list of phytochemical compounds in betel leaves extracts and essential oils, safety profiles, and value-added products of betel leaves. Some studies also showed that the combination of betel leaves extract and essential oil with antibiotics (streptomycin, chloramphenicol and gentamicin) could provide potentiating antibacterial properties. Moreover, this review delivers a scientific resume for researchers in respected areas and manufacturers who want to develop betel leaves-based products.
... is anticaries, antifungal, antioxidant, anti-inflammatory, antiprotozal, antiulcer, chemoprotective, gastroprotective, hepatoprotective, immunomodulatory and larvicidal. 93 Whilst the phytochemical and pharmacological profiling of Piper betel L is well established, and biotechnological interventions have aimed to improve the cash value of this botanical, as yet, no biotechnological interventions have progressed toward the development of a medical product. 94,95 It is vitally important to note that this review is on laboratory studies (in-vitro) only not by choice, but as this is the only evidence available. ...
Research
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Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a growing range of infections and requires immediate intersectoral action. A report into the global burden of AMR estimated that AMR contributed to 700,000 deaths in 2016 and is expected to reach 10 million deaths annually by 2050. Plant-derived antimicrobials (PDAms) have demonstrated the ability to combat multi-drug resistant (MDR) pathogens and hope exists that they may help control AMR. This review investigated and recorded the antimicrobial activity (AMA) of whole plant ethanolic and methanolic extracts in WHO priority pathogens (WHO PPs) reported between 2000 until present. The review collated studies on PDAms tested on WHO PP laboratory isolates, determined efficacious PDAms, and grouped PDAms by WHO PP and antimicrobial susceptibility test (AST).
... A comprehensive library of medicinal plant containing phytochemicals with potential anti-viral activity and traditional medicinal compounds was produced from previously published studies (Supplementary Table 1) [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and screened against the SARS-CoV-2 MPP. The 3-dimensional (3D) structure was obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov/), in .sdf ...
Preprint
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Coronaviruses are endemic in humans and infections normally mild, such as the common cold but cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia and in serious cases even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. For this virus, death toll is increasing in. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. The viral Main Protease controls Coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro. Molecular docking was performed using PyRx-autodock vina to analyze the inhibition probability. MPP (6LU7) was docked with 90 phytochemical compounds and docking was analysed by PyRx-autodock vina, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Furthermore, ADME analysis along with analysis of toxicity was also investigated to check the pharmacokinetics and drug-likeness properties of the antiviral phytochemicals. Remdesivir and lopinavir were used as standards for comparison. Our analyses revealed that the top ten (Azadirachtin,-12.5kcal/mol; Rutin,-9 kcal/mol; Theaflavin,-9 kcal/mol; Astragalin,-8.8 kcal/mol; Isoquercitrin,-8.7 kcal/mol; Hyperoside,-8.6 kcal/mol; Baicalin,-8.4 kcal/mol; Saponin,-8.3 kcal/mol; Sennoside A,-8.3 kcal/mol; Aloin,-8.2 kcal/mol, while Remdesivir and Lopinavir showed-8.2 and-7.9 kcal/mol) hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimization and drug development process to combat COVID-19. Abstract Coronaviruses are endemic in humans and infections normally mild, such as the common cold but cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia and in serious cases even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. For this virus, death toll is increasing in. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. The viral Main Protease controls Coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro. Molecular docking was performed using PyRx-autodock vina to analyze the inhibition probability. MPP (6LU7) was docked with 90 phytochemical compounds and docking was analysed by PyRx-autodock vina, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Furthermore, ADME analysis along with analysis of toxicity was also investigated to check the pharmacokinetics and drug-likeness properties of the antiviral phytochemicals. Remdesivir and lopinavir were used as standards for comparison. Our analyses revealed that the top ten (Azadirachtin,-12.5kcal/mol; Rutin,-9 kcal/mol; Theaflavin,-9 kcal/mol; Astragalin,-8.8 kcal/mol; Isoquercitrin,-8.7 kcal/mol; Hyperoside,-8.6 kcal/mol; Baicalin,-8.4 kcal/mol; Saponin,-8.3 kcal/mol; Sennoside A,-8.3 kcal/mol; Aloin,-8.2 kcal/mol, while Remdesivir and Lopinavir showed-8.2 and-7.9 kcal/mol) hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimization and drug development process to combat COVID-19.
... gondii activity of Artemisia annua L. [5,31,32], Dichroa febrifuga [33], herbal extracts from South Korea (Sophora flavescens, Sinomenium acutum, Pulsatilla koreana, Ulmus macrocarpa and Torilis japonica) [34], and Eurycoma longifolia [29] have been reported. However, piperaceae extracts have not been tested for their potential anti-Toxoplasma effects even though they have many pharmacological properties including activities against fungi [35], insects [8], protozoa [11,17,36], helminthes [37,38] and cancer cells [12]. Only extracts of P. nigrum have been shown to possess in vivo activity, with a reported T. gondii growth inhibition of 78.3% and 86.3% with treatment doses 100 and 200 mg/kg/day, respectively [27], but there is no in vitro information for this extract. ...
Article
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Herbal medicines and natural herb extracts are widely used as alternative treatments for various parasitic diseases, and such extracts may also have potential to decrease the side effects of the standard regimen drugs used to treat toxoplasmosis (sulfadiazine-pyrimethamine combination). We evaluated how effective the Thai piperaceae plants Piper betle, P. nigrum and P. sarmentosum are against Toxoplasma gondii infection in vitro and in vivo. Individually, we extracted the piperaceae plants with ethanol, passed them through a rotary evaporator and then lyophilized them to obtain crude extracts for each one. The in vitro study indicated that the P. betle extract was the most effective extract at inhibiting parasite growth in HFF cells (IC50 on RH-GFP: 23.2 μg/mL, IC50 on PLK-GFP: 21.4 μg/mL). Furthermore, treatment of experimental mice with the P. betle extract for 7 days after infection with 1,000 tachyzoites of the T. gondii PLK strain increased their survival (survival rates: 100% in 400 mg/kg-treated, 83.3% in 100 mg/kg-treated, 33.3% in 25 mg/kg-treated, 33.3% in untreated mice). Furthermore, treatment with 400 mg/kg of the P. betle extract resulted in 100% mouse survival following infection with 100,000 tachyzoites. The present study shows that P. betle extract has the potential to act as a medical plant for the treatment of toxoplasmosis.
... This would be evident from the numerous citations laid down in the ancient literature, particularly the Indian scriptures [1,2] . Betel leaves are very nutritive and contain substantial amount of vitamins and minerals [3] . The leaves also contain the enzymes like diastase and catalase besides a significant amount of several essential amino acids including lysine, histidine and arginine [1,2,[4][5][6] . ...
Article
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The present study aims at finding out the optimum parameters for the extraction of components from Betel leaves possessing medicinal applications using ethanol solvent by Soxhlet apparatus. The optimum conditions for the extract were calculated based on the extract yield by varying four parameters: material quantity (A: 2–4 g), solvent quantity (B: 250–300 ml), mantle temperature (C: 65–75 °C) and extraction time (D: 1–3 hours) and optimized using a four factor three level Box–Behnken response surface design (BBD) coupled with desirability function methodology. Results showed that temperature and extraction time had significant effect on yield of extract. Optimum conditions for highest yield of extract (10.94%) are as follows: material quantity (2 g), solvent quantity (281.4 ml), temperature (72 °C) and time (3 hours). The extract at the maximum yield condition was analyzed for phytocomponents by FTIR and GC–MS. The results indicated the presence of Hydroxy chavicol (69.46%), 4-Chromanol (24%) and Eugenol (4.86%), which possess wide application including as antioxidant, anti-inflammatory, anti-platelet and antithrombotic, antibacterial and antifungal agents.
... Experimental studies have revealed its wide and diverse biological and pharmacological effects. For example, it has conveyed antibacterial, antifungal, antiprotozoal, antioxidant, anti-inflammatory and gastroprotective properties as well as many others (Fazal et al. 2013;Pradhan et al., 2013). This plant contains a broad range of chemical compounds including alkaloids, carbohydrates, amino acids, tannins and steroids (Sugumaran et al., 2011). ...
Article
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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.
... Many of the previous studies have searched for herbs that could kill or inhibit the growth of bacteria and stimulate native immune response in fish through oral administration. Solo garlic, garlic chive and piper betel leaves are common herbs in the Southeast Asian region, which have been used for domestic food preparation (solo garlic, garlic chive) or for chewing together with Betel nut and lime (piper betel leaves) by several groups of ethnic communities throughout Southeast Asia and India (Fazal et al., 2014). Antimicrobial properties of these plants were previously reported, and various natural bioactive compounds have been identified such as alliin, isoallin, methiin, cis and trans isomers of g-glutamyl-S-1-propenylcysteine, g-glutamyl-S-allylcysteine (Charron, Milner, & Novotny, 2016), and phenols (Fratianni et al., 2016) among others from garlic; flavonoids from garlic chive (Knuthsen & Justesen, 1999); and polyphenols and alkaloids from Piper betle leaf (Parmar et al., 1998). ...
Article
An in vitro assessment of antimicrobial properties of aqueous and ethanol extracts from solo garlic (Allium sativum), garlic chive (Allium tuberosum) and betel leaves (Piper betle) on six bacterial pathogens in aquaculture, and a challenge of Nile tilapia, Oreochromis niloticus with Streptococcus agalactiae were performed. Generally, minimum inhibitory concentrations (MIC) ranged from 26.63 to 53.25 mg mL-1 for aqueous solo garlic (G) and 14.60 to 29.20 mg mL-1 for garlic chive extracts for all pathogens tested. Ethanol extract of betel leaves (P) exhibited the strongest antibacterial activity (0.15 – 0.60 mg mL-1). P and G incorporated in feed at high and low doses as multiples of MIC [High; H (10X for PH and 3X for GH) and Low; L (3X for PL and 1X for GL)] were fed to tilapia followed by in vivo challenge against S. agalactiae (1 x 108 CFU mL-1). Ethanol extract of P. betle significantly improved survival (P<0.05; PH=100%, PL =77%). White blood cells (WBC), lymphocytes and monocytes differed significantly (P<0.05) among treatments and the highest WBC value (1.175 × 103) was for PH. Use of ethanol extract of Piper betle seems promising for sustainable disease management in aquaculture.
... ound the world. The traditional communities in Brazil used decoction of Piper spp. against rheumatism, bronchitis, and sexually transmitted diseases (Agra et al. 2007). The Piper was used as fold medicine in India (Atal et. al., 1974, Nakatani, 1986. Piper betel. Linn has been used as a religious, recreational and medicinal plant in Southeast Asia (Fazal et. al., 2013). ...
Conference Paper
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Pisang Raja is well-known banana cultivars in Indonesia. Particularly in Java, there are not less than 40 local cultivars of Pisang Raja were recorded which needs to be clearly classified and identified. Genomic group identifications were conducted both morphology and molecular to thirteen local cultivars of Pisang Raja originated from Yogyakarta, Central Java and East Java collection of Purwodadi Botanic Garden – Indonesian Institute of Sciences. Morphological identification was using taxonomic scoring of fifteen dianogstic characters between M. acuminata and M. balbisiana wild species as their ancestral parents, whereas molecular identification was using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism/PCR-RFLP of Internal Transcribed Spacer/ITS method. Result showed that genomic group of 13 Pisang Raja local cultivars based on morphology consists of 8 AAB, 3 ABB, and 2 AAA; whereas molecular result consists of 4 AAB, 3 ABB, and 6 AAA. About 4 out of 8 banana cultivars which identified as AAB morphologically were revealed as AAA molecularly. Molecular approach using PCR-RFLP of ITS to identify genomic group of Pisang Raja local cultivars provide more objective, consistent and reliable result, also less time-consuming than morphology. Nonetheles morphological description of bananas is still necessary to conduct as part of a longer-term systematic evaluation and selection basis for further utilization and development. Genomic group result of Pisang Raja local cultivars examined are as follows: Raja Bandung (ABB), Raja Siem (ABB), Raja Prentel (ABB), Raja Gintung (AAB), Raja Temen (AAB), Raja Lingi (AAB), Raja Marto (AAB), Raja Kenanga (AAA), Raja Ketan (AAA), Raja Nangka (AAA), Raja Pendek (AAA), Raja Talun (AAA) and Raja Warangan (AAA).
... The isolated compound from betel leaf was identified as allylpyrocatechol with a molecular formula, C 9 H 10 O 2 , deduced on the basis of its spectroscopic analyses (IR, 1 H, 13 C NMR and GC-MS). Although, this compound was isolated earlier from piper betel plant, investigation on its biological effects were primarily done with respect to antioxidative, gastro-protective and anti-inflammatory properties only 11,12,14 and practically nothing was studied in relation to the regulation of thyroid dysfunction. Findings of this in vivo study clearly indicated the ameliorative nature of the test compound, APC in T 4 -induced hyperthyroid rats, suggesting its therapeutic use in thyrotoxicosis. ...
Article
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Allylpyrocatechol (APC) was isolated from betel leaf and its possible role in L-thyroxin (L-T4)-induced thyrotoxic rats was evaluated. The disease condition, thyrotoxicosis was confirmed by higher levels of thyroid hormones and low thyrotropin (TSH) in serum. Increased hepatic activities of 5′-mono-deiodinase(5′D1), glucose-6-phospatase (G-6-Pase); serum concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase(LDH) and tumour necrosis factor-alpha(TNF-α) were observed in thyrotoxic rats. Hepatic lipid peroxidation(LPO) was also increased and the endogenous antioxidants were depleted in these rats. In western blot analysis thyroid peroxidase expression was found to be reduced, whereas thyrotropin receptor(TSHR) expression was enhanced in thyroid gland of these animals. On the other hand, APC treatment in thyrotoxic rats decreased the levels of serum thyroid hormones, ALT, AST, TNF-α and LDH, as well as hepatic 5′ D1 and G-6-Pase activities. However, it increased the serum TSH levels. APC also reduced the hepatic LPO and increased the cellular antioxidants in thyrotoxic rats. However, expression of TSHR was inhibited and TPO was increased by APC. The test compound also improved histological features in both liver and thyroid. Present report appears to be the first one that indicates the positive role of APC in ameliorating T4-induced thyrotoxicosis.
... The major components of P. betle leaves/oil are polyphenols, terpenes, alkaloids, steroids, saponins, tannins, and flavonoids out of which allyl pyrocatechol, eugenol, and chavibetol are the major active phytoconstituents. P. betle leaves are also rich in vitamins, minerals, and essential amino acids, particularly tyrosine [12,13] . ...
... The leaves of Piper betle (betel vine) is used in south Asia for traditional and religious ceremonies, and as medicine (Fazal et al., 2014). The leaf extract of Piper betle has been used to test for its antimicrobial activities against bacterial and fungal pathogens. ...
... A comprehensive library of medicinal plant containing phytochemicals with potential anti-viral activity and traditional medicinal compounds was produced from previously published studies (Supplementary Table 1) [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and screened against the SARS-CoV-2 MPP. The 3-dimensional (3D) structure was obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov/), in .sdf ...
Preprint
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div> <sup>Coronaviruses are endemic in humans and infections normally mild, such as the common cold but cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia and in serious cases even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. For this virus, death toll is increasing in. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. The viral Main Protease controls Coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro. Molecular docking was performed using PyRx-autodock vina to analyze the inhibition probability. MPP (6LU7) was docked with 90 phytochemical compounds and docking was analysed by PyRx-autodock vina, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Furthermore, ADME analysis along with analysis of toxicity was also investigated to check the pharmacokinetics and drug-likeness properties of the antiviral phytochemicals. Remdesivir and lopinavir were used as standards for comparison. Our analyses revealed that the top ten (Azadirachtin, -12.5kcal/mol; Rutin, -9 kcal/mol; Theaflavin, -9 kcal/mol; Astragalin, -8.8 kcal/mol; Isoquercitrin, -8.7 kcal/mol; Hyperoside, -8.6 kcal/mol; Baicalin, -8.4 kcal/mol; Saponin, -8.3 kcal/mol; Sennoside A, -8.3 kcal/mol; Aloin, -8.2 kcal/mol, while Remdesivir and Lopinavir showed -8.2 and -7.9 kcal/mol) hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimization and drug development process to combat COVID-19. </sup> <sup> </sup></div
... It is a traditional herb that has been used as mouthwash, dental medicine, cough medicine, astringent, tonic, and others. The extract of betel leaves has been reported to demonstrate antioxidative, antiinflammatory, antibacterial, and antifungal activities (7)(8)(9). Another plant is Syzygium aromaticum (clove) which is one of the interesting plants with antifungal activity. The clove oil from S. aromaticum and eugenol are wildly used in dental medicine because they exhibit useful antiseptic, analgesic, and anaesthetic effects (10,11). ...
Article
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This work aims to develop the herbal oil-incorporated nanostructure mats with antifungal activity for the prevention and treatment of Candida-associated denture stomatitis. The nanofiber mats loaded with betel oil or clove oil were fabricated via electrospinning process. The morphologies and physicochemical properties of the herbal oil loaded nanofiber mats were examined using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and mechanical testing. The release characteristic, antifungal activity, and cytotoxicity were also investigated. The SEM images confirmed the homogeneous and smooth nanoscale fibers. The addition of the herbal oil into the nanofiber mats reduced the fiber diameters. The DSC and FT-IR results confirmed the presence of the oil in the nanofiber mats. The herbal oils can be released from the mats in a very fast manner and inhibit the growth of candida cells within only few minutes after contact. These nanofiber mats may be beneficial for the prevention and treatment of denture stomatitis.
... 22] ...
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The present review was aimed to find out the best natural remedies from medicinal plants like Piper betle that offer potential efficacy against inflammation. Several phytoconstituents classes such as flavonoids, triterpenoids, alkaloids, steroids, polyphenols etc. have been documented to possess interesting anti-inflammatory properties. Many of them exhibit potent bioactivities in minute concentrations against well-established biomarkers of inflammation. Natural plant metabolites extracted from medicinal herbs can act by modulating the expression of pro-inflammatory signals thus helps to manage arthritic conditions. Other than inflammation Piper betle is also reported to possess other bioactivities like antimicrobial, antibacterial, gastroprotective, wound healing, hepatoprotective, antioxidant, anti-fertility & antimotility activities etc. The review indicated that Piper betle is very useful medicinal herb to treat inflammation naturally with better safety and efficacy.
... Biovia Discovery Studio 4.5 was utilized to predict the interaction between the mentioned ligands and the MPP of SARS-CoV-2. List of phytochemicals that showed good results in docking with their medicinal activities are represented (Table 2) [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. Table 4. ...
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... Aegle marmelos Food [95] Influenza A virus [96] Aqueous leaf extract/ polysaccharide [96] Inhibits viral attachment to host cell [96] 7 Areca nut L./Arecaceae Supari, Betelnut Arecoline, guvacine [97] Mouth fresher [98] Human ...
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The pandemic of Serious Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) that produces corona virus disease (COVID-19) has challenged the entire mankind by rapidly spreading globally in 210 countries affecting over 25 million people and about 1 million deaths worldwide. It continues to spread, afflicting the health system globally. So far there is no remedy for the ailment and the available antiviral regimens have been unsatisfactory for the clinical outcomes and the mode of treatment has been mainly supportive for the prevention of COVID-19-induced morbidity and mortality. From the time immortal the traditional plant-based ethno-medicines have provided the leads for the treatment of infectious diseases. Phytopharmaceuticals have provided potential and less toxic antiviral drugs as compared to conventional modern therapeutics which are associated with severe toxicities. The ethnopharmacological knowledge about plants has provided food supplements and nutraceuticals as a promise for prevention and treatment of the current pandemic. In this review article, we have attempted to comprehend the information about the edible medicinal plant materials with potential antiviral activity specifically against RNA virus which additionally possess property to improve immunity along with external and internal respiration and exhibit anti-inflammatory properties for the prevention and treatment of the disease. This will open an arena for the development of novel nutraceutical herbal formulations as an alternative therapy that can be used for the prevention and treatment of COVID-19.
... The Piper species have been reported to be rich in phytochemicals and essential oils, which showed strong antioxidant, antibacterial and antifungal activities [1]. Besides being used as a wrapper for the chewing of areca nut, P. betle leaves are also used as an ingredient in stimulant, antiseptic, tonic, and other ayurvedic formulations thanks to its bioactivity components such as hydroxychavicol, allylpyrocatechol, and eugenol [2,3]. The other Piper species, P. sarmentosum, has been reported to possess many potential bioactivities due to its bioactive compounds such as Vitamin E, carotenoids, xanthophylls, tannins, flavanoid, and phenolics [4][5][6]. ...
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Piper betle (P. betle) and Piper sarmentosum (P. sarmentosum) are the two members of the Piper genus, have been reported to be rich in phytochemicals and essential oils, which showed strong reducing power, antibacterial, and antifungal activities. P. betle recently has been studied and applied in several commercial products in the antimicrobial respect, meanwhile its relatives, P. sarmentosum has been lesser-known in this field. In this study, the two Piper species—P. betle and P. sarmentosum were studied to compare their ability in silver nanoparticle synthesis and efficacy in antibacterial activity. P. betle and P. sarmentosum were extracted by distilled water at different temperatures and times. Subsequently, their total reducing capacity was determined by DPPH scavenging and Folin-Ciocalteu assays to choose the appropriate extraction conditions. The silver nanoparticle solutions prepared by the extracts of P. betle (Pb.ext) and P. sarmentosum (Ps.ext) were characterized by Dynamic light scattering (DLS), Zeta potential, UV-vis, and Fourier-transform infrared (FTIR) measurements. Finally, the antibacterial activity of the synthesized silver nanoparticle solutions was tested against Escherichia coli using the agar diffusion well–variant method. The Pb.ext showed stronger reducing power with higher total polyphenol content (~125 mg GAE/mL extract) and better DPPH activity (IC50~1.45%). Both the green synthesized silver nanoparticle solutions (Pb.AgNP and Ps.AgNP) performed significantly stronger antibacterial activity on Escherichia coli compared to their initial extracts. Antibacterial tests revealed that Ps.AgNP showed remarkably better growth inhibition activity as compared to Pb.AgNP. This study would contribute useful and important information to the development of antibacterial products based on green synthesized silver nanoparticles fabricated by the extracts of P. betle and P. sarmentosum.
... Interestingly, the plant has given different names in different languages. In colloquial terms the plant is known as Betel vine in English), in Urdu/Hindi it is called as Paan, Tanbol in Arabic, Bulung samat (Kapampangan), Vettila, Vettilakkoti (Malayalam), Plu (Mon), Malus (Tetum), Maluu (Khmer), Plue (Thai), Malu (Tokodede), Vetrilai (Tamil), Tanbol, Burg-e-Tanbol in Persian, Daun sirih (Malay), Papulu (Chamorro) and Tråu (Vietnamese) [3]. The names of beetle vine in various Southeast Asian languages can be found enlisted in Table 1 [1]. ...
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Herbal medicines are widely used as alternative treatments for various chronic diseases. They have proved to be of immense importance in treating many diseases and conditions. These medicines have potential to decrease the side effects of other drugs. In this regard Betel vine (Piper betel) leaves are known for its medicinal properties since long. It is a cash crop for many under developed Southeast Asian countries and therefore also known as “Green Gold and Green Heart" in those countries, as many people cultivate this crop to meet their both ends. The contemporary world approves its several medicinal properties as the growth of knowledge in this regard is unprecedented. The objective here is to reveal the potential effect of this plant against different diseases. Along with its traditionalism uses which signify its tremendous potential, it is also used towards cure of many antimicrobial ailments of great concern. The leaf extract and purified compounds are found to play a vital role and are of immense benefits in oral hygiene, anti-diabetic, cardiovascular, anti-inflammatory, and anti-ulcer. The active compounds isolated from leaf and other parts have great therapeutic role. This paper basically focus on emphasizing the varied pharmacological properties of Piper betel Linn along with its traditional uses and a cursory view of its active constituents.
... Experimental studies have shown that it possess diverse biological and pharmacological effects, which includes antibacterial, antifungal, larvicidal, antiprotozal, anticaries, gastroprotective effects, free radical scavenging, antioxidant, anti-inflammatory hepatoprotective, immunomodulatory, antiulcer and chemopreventive activities. [22] Distribution: The tree is found in the Eastern Himalayas, Northeast India and Western ghats. It is also cultivated in greater parts of India for its foliage and fragrant flowers. ...
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The dependence of man on his environment is well understood since the beginning of our civilization. Early man's inquisitiveness about plants was necessitated by his inherent desire and instinct to seek food and medicine for his survival. Thus, plants played a vital role in the progress and evolution of civilization. In India, all the religions adore plants or make use of their parts in several ways to fulfil their socio-religious ceremonies. The traditional worship practices exhibit the symbiotic connection of human beings and nature. Ancient scriptures like Rigveda, Yajurveda, Samaveda and Atharvaveda also implicates the importance of worshipping of plants and trees as a part of Indian tradition since 1500 BC. Sacred trees establish a principal portion of the ecological heritage of India. Apart from, there is credence that the plants which are holy or being worshipped have medicinal potential too. The scientific documentation of these sacred plant species having ethnomedicinal importance is essential for widening the horizon of research in this field. The present review is an attempt to give a brief description on the importance of certain plants mainly seen in India, which are having a significant role in rites and rituals dealing with cultural heritage, festivals and religious ceremonies standing from birth till death in Indian tradition along with a small enlightenment on their medicinal importance. The study attempts to bring out the rationale of their cultivation enlightening on the important role these plants in human life for their well-known ethnomedicinal values, rather than seeing their cultivation as a mere ritual practice. The study concludes that, the pinnacle of religious pursuit linked with plants having ethnomedicinal importance can upraise the conservation of biological resources and their sustainable use.
... Biting betel quid causes malignant growth of the oral depression and throat, and when blended in with tobacco, likewise causes disease in pharynx [46]. Head and neck malignant growth in betel quid chewing zone were investigated by Chen et al. 2008 [47]. The predominance of oral precancerous sores (leukoplakia, submucosal fibrosis, and verrucous sores) has been related with various ways of life identified by quid chewing. ...
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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.
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Rheumatoid Arthritis is a chronic, inflammatory, and systemic autoimmune disease, it affects elders worldwide. Herbal medicines have been used for the treatment of various ailments from ancient times. Betelvine (Piper betle L.) leaves have long been used in Asian countries as a medicine to relieve pain and some metabolic diseases. The present study of methanolic extract of phytochemical analysis confirms the presence of alkaloids, tannins, terpenoids, saponins, steroids, total flavonoids and total phenols. GC-MS analysis of MeOH extract of Piper betle (PBME) revealed the presence of 40 bioactive compounds. In vitro antioxidant and anti-inflammatory assays showed greater inhibitory effect. The anti-arthritic effects of PBME at 250 and 500 mg/kg concentration showed recovery from joint damage in in vivo rat model. Among the 40 GC-MS derived bioactives, 4-Allyl-1,2-Diacetoxybenzene exhibited the higher interactions with minimized binding energy to the RA targets of MMP 1 (-6.4 kcal/mol), TGF-β (-6.9 kcal/mol), IL-1β (-5.9 kcal/mol). Further, the effect of PBME extract against RA molecular disease targets (IL-1β, MMP1 and TGF- β) were studied using Real-time PCR. These results substantiate that P. betle leaves could be a source of therapeutics for the treatment of rheumatoid arthritis.
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Antibiotic resistance has emerged as a threat to global health, food security, and development today. Antibiotic resistance can occur naturally but mainly due to misuse or overuse of antibiotics, which results in recalcitrant infections and Antimicrobial Resistance (AMR) among bacterial pathogens. These mainly include the MDR strains (multi-drug resistant) of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). These bacterial pathogens have the potential to “escape” antibiotics and other traditional therapies. These bacterial pathogens are responsible for the major cases of Hospital-Acquired Infections (HAI) globally. ESKAPE Pathogens have been placed in the list of 12 bacteria by World Health Organisation (WHO), against which development of new antibiotics is vital. It not only results in prolonged hospital stays but also higher medical costs and higher mortality. Therefore, new antimicrobials need to be developed to battle the rapidly evolving pathogens. Plants are known to synthesize an array of secondary metabolites referred as phytochemicals that have disease prevention properties. Potential efficacy and minimum to no side effects are the key advantages of plant-derived products, making them suitable choices for medical treatments. Hence, this review attempts to highlight and discuss the application of plant-derived compounds and extracts against ESKAPE Pathogens.
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Methanol extract of Piper betle leaves exhibited an inhibitory effect on grape downy mildew. This extract might contain more than two compounds which have different polarities that suppress grape downy mildew. Gas chromatograph-tandem mass spectrometry analysis identified 4-allylpyrocatechol, eugenol, α-pinene, and β-pinene in the methanol extract. Neither of the compounds suppressed grape downy mildew by single treatment. On the other hand, treatment with a combination of 4-allylpyrocatechol with eugenol, α-pinene or β-pinene enhanced the inhibitory effects on grape downy mildew and perfectly suppressed it. The complex extracted from P. betle leaves may be used in organic agriculture as an alternative to chemical fungicides in viticulture.
Chapter
Since time immemorial, Piper betle Linn. (betel vine or paan) has been an integral part of various traditional and folk medicines of Southeast Asian countries. The betel leaves are the most valued plant parts routinely used as chewing agent and known to prevent halitosis. Betel vine leaves possess numerous medicinal benefits, such as relieving indigestion, bronchitis, constipation, congestion, and cough. Betel vine leaves are mostly consumed as a part of betel quid, which consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum Linn.), and slaked lime, a concoction with potent carcinogenic properties. Routine consumption of betel quid is associated with oral cancer, and scientific analyses have attributed that both tobacco and areca nut as carcinogenic, while slaked lime as a promoter of carcinogenesis. Conversely, betel vine leaves are devoid of carcinogenic effects and in turn known to possess cancer preventive effects that can negate carcinogens present in the quid. The aim of the chapter is to provide the information on betel vine’s cancer preventive effects and the mechanisms involved. Moreover, it also highlighted the various phytoconstituents that promote beneficial role of betel vine leaves against different cancers.
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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.
Article
Purpose A case of new onset bradycardia and hypotension following betel leaf consumption in combination with verapamil and metoprolol in an atrial fibrillation (AF) patient. Summary A 66-year-old Nigerian woman presented to the emergency department for evaluation of multiple near syncope episodes with underlying AF and slow ventricular response. After initial evaluation, the patient disclosed she had ingested several betel leaves that morning. She was admitted for observation of severe, progressive hypotension and symptomatic bradycardia. Her past medical history included AF, type 2 diabetes, asthma, obesity, hypertension and hypothyroidism. Her home medications consisted of spironolactone, metoprolol succinate, and verapamil ER. Upon admission, her home medications were held. She received IV fluids and atropine .4 mg IV as needed for symptomatic bradycardia. Approximately 18 h following admission, her vital signs stabilized and her labs returned to baseline. She remained stable and was discharged with a recommendation to continue her home medications at prescribed doses with reduced doses of verapamil and metoprolol and to follow-up with her primary care provider. Conclusion A patient with a history of AF developed significant hypotension and symptomatic bradycardia after betel leaf consumption resulting in an overnight critical care unit admission. The use of betel leaf is not common in the United States; however, practitioners should be cognizant of the use of complementary and alternative medications like betel leaf and incorporate this knowledge in patient evaluation. Patients consuming betel leaf or betel nut should be evaluated for cardiovascular effects as well as laboratory evaluation for organ damage.
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The plant extracts of 17 commonly used Indian medicinal plants were examined for their possible regulatory effect on nitric oxide (NO) levels using sodium nitroprusside as an NO donor in vitro. Most of the plant extracts tested demonstrated direct scavenging of NO and exhibited significant activity. The potency of scavenging activity was in the following order: Alstonia scholaris > Cynodon dactylon > Morinda citrifolia > Tylophora indica > Tectona grandis > Aegle marmelos (leaf) > Momordica charantia > Phyllanthus niruri > Ocimum sanctum > Tinospora cordifolia (hexane extract) = Coleus ambonicus > Vitex negundo (alcoholic) > T cordifolia (dichloromethane extract) > T. cord folia (methanol extract) > Ipomoea digitata > V negundo (aqueous) > Boerhaavia diffusa > Eugenia jambolana (seed) > T. cord folia (aqueous extract) > V. negundo (dichloromethane/methanol extract) > Gingko biloba > Picrorrhiza kurroa > A. marmelos (fruit) > Santalum album > E. jambolana (leaf). All the extracts evaluated exhibited a dose-dependent NO scavenging activity. The A. scholaris bark showed its greatest NO scavenging effect of 81.86% at 250 mug/mL, as compared with G. biloba, where 54.9% scavenging was observed at a similar concentration. The present results suggest that these medicinal plants might be potent and novel therapeutic agents for scavenging of NO and the regulation of pathological conditions caused by excessive generation of NO and its oxidation product, peroxynitrite.
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The heart shaped betel leaves are found in ancient Sanskrit texts, including Charaka, Sushruta Samhita and Astanga Hradayam. Piper betle L. have been used in chinese, Indian folk medicine for centuries. In this review, different research works related to Ayurvedic consequence, geographical distribution and cultivation, morphoanatomy, phytochemistry, biological activities, along with tradomedicinal uses which signify the tremendous potential of “Piper betle L.” to come out as Green medicine. The objective of it is to revels the potential effect of this plant in the development of therapeutically active herbal drugs against different microbial infections especially for oral cavity, which also gives the opportunity to pharmaceutical companies interested in formulation and production of natural product based drugs targeted towards specific aliments.
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The fresh leaves of betel vine are popularly known as Paan in India, which are consumed by about 15-20 million people in the country. It is cultivated following the traditional methods in India on about 55,000 ha with an annual production worth about Rs 9000 million. On an average about 66% of such production is contributed by the state of West Bengal where it is cultivated on about 20,000 ha encompassing about 4-5 lakh Boroj employing about the same number of agricultural families. There is a menacing wastage of the leaves during storage, transportation and the glut season. Moreover, the surplus leaves, if not disposed off properly may cause environmental pollution and health hazards. Such wastage may be minimized by various ways and means including extraction of essential oil from the surplus betel leaves. This oil may be used as an industrial raw material for manufacturing medicines, perfumes, mouth fresheners, tonics, food additives etc. The leaves are nutritive and contain anticarcinogens showing promise for manufacturing of a blood cancer drug. Some disputed reports also claim that chewing betel leaves excessively may cause oral cancer. The agricultural, industrial, economic, medicinal and allied potentialities of the crop are discussed.
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Piper betle L. is one of the important plants in the Asiatic region which ranks second to coffee and tea in terms of daily consumption. Though the plant is known for abuse, in recent years several reports have been published on the effects of the plant extract and chemical constituents on different biological activities in vitro and in vivo. The leaf extract, fractions and purified compounds are found to play a role in oral hygiene, anti-diabetic, cardiovascular, anti-inflammatory/ immunomodulatory, anti-ulcer, hepato-protective and anti-infective, etc. Patents were also awarded for some of the biological activities like anti-inflammatory, anti-cancer and immunomodulatory associated with leaf extracts and purified compounds. The active compounds isolated from leaf and other parts are hydroxychavicol, hydroxylchavicol acetate, allypyrocatechol, chavibetol, piperbetol, methylpiperbetol, piperol A and piperol B. Phenol-rich leaves of P. betle show high antioxidant activities. A number of biologically active compounds from P. betle have potential for use as medicines, neutraceuticals and industrial compounds. Since the traditional use of P. betle involves chewing, it offers possibilities of use in drug delivery through buccal mucosa bypassing the gastric route.
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Since antiquity, Piper betel Linn (betel vine; family Piperaceae) has been an important medicinal agent in the various traditional and folk systems of medicine in Southeast Asia countries. The leaves are the most valued plant part and in the past were routinely used as a chewing agent to prevent halitosis. The leaves are also supposed to harden the gum, conserve the teeth and to prevent indigestion, bronchitis, constipation, congestion, coughs and asthma. Innumerable scientific studies have validated the ethnomedicinal claims. Betel leaves are an integral component of the betel quid that consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum L) and slaked lime; a highly abused agent with carcinogenic properties. Regular chewing of betel quid is associated mainly with oral cancer and detail studies with individual constituents of the quid have shown that both tobacco and areca nut are carcinogenic, while slaked lime is shown to promote the process of carcinogenesis. However unlike other constituents of the betel quid, the betel leaves devoid carcinogenic effects and on the contrary possesses cancer preventive effects including against the carcinogens present in tobacco. This review for the first time provides information on cancer preventive effects and also addresses the various mechanisms which might be involved.
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Previous studies have shown that Piper betle L. leaves extract inhibits the adherence of Streptococcus mutans to glass surface, suggesting its potential role in controlling dental plaque development. In this study, the effect of the Piper betle L. extract towards S. mutans (with/without sucrose) using scanning electron microscopy (SEM) and on partially purified cell-associated glucosyltransferase activity were determined. S. mutans were allowed to adhere to glass beads suspended in 6 different Brain Heart Infusion broths [without sucrose; with sucrose; without sucrose containing the extract (2 mg mL(-1) and 4 mg mL(-1)); with sucrose containing the extract (2 mg mL(-1) and 4 mg mL(-1))]. Positive control was 0.12% chlorhexidine. The glass beads were later processed for SEM viewing. Cell surface area and appearance and, cell population of S. mutans adhering to the glass beads were determined upon viewing using the SEM. The glucosyltransferase activity (with/without extract) was also determined. One- and two-way ANOVA were used accordingly. It was found that sucrose increased adherence and cell surface area of S. mutans (p<0.001). S. mutans adhering to 100 µm² glass surfaces (with/without sucrose) exhibited reduced cell surface area, fluffy extracellular appearance and cell population in the presence of the Piper betle L. leaves extract. It was also found that the extract inhibited glucosyltransferase activity and its inhibition at 2.5 mg mL(-1) corresponded to that of 0.12% chlorhexidine. At 4 mg mL(-1) of the extract, the glucosyltransferase activity was undetectable and despite that, bacterial cells still demonstrated adherence capacity. The SEM analysis confirmed the inhibitory effects of the Piper betle L. leaves extract towards cell adherence, cell growth and extracellular polysaccharide formation of S. mutans visually. In bacterial cell adherence, other factors besides glucosyltransferase are involved.
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The need for new compounds active against malaria parasites is made more urgent by the rapid spread of drug-resistance to available antimalarial drugs. The crude methanol extract of Piper betle leaves (50-400 mg/kg) was investigated for its antimalarial activity against Plasmodium berghei (NK65) during early and established infections. The phytochemical and antioxidant potentials of the crude extract were evaluated to elucidate the possibilities of its antimalarial effects. The safety of the extract was also investigated in ICR mice of both sexes by the acute oral toxicity limit test. The leaf extract demonstrated significant (P < 0.05) schizonticidal activity in all three antimalarial evaluation models. Phytochemical screening showed that the leaf extract contains some vital antiplasmodial chemical constituents. The extract also exhibited a potent ability to scavenge the free radicals. The results of acute toxicity showed that the methanol extract of Piper betle leaves is toxicologically safe by oral administration. The results suggest that the Malaysian folklorical medicinal application of the extract of Piper betle leaf has a pharmacological basis.
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The present study was designed to investigate the cardioprotective potential of Piper betle (P. betle) against isoproterenol (ISP)-induced myocardial infarction in rats. Rats were randomly divided into eight groups viz. control, ISP, P. betle (75, 150, and 300 mg/kg) and P. betle (75, 150, and 300 mg/kg) + ISP treated group. P. betle leaf extract (75, 150, or 300 mg/kg) or saline was orally administered for 30 days. ISP (85 mg/kg, s.c.) was administered at an interval of 24 h on the 28(th) and 29(th) day and on day 30 the functional and biochemical parameters were measured. ISP administration showed a significant decrease in systolic, diastolic, mean arterial pressure (SAP, DAP, MAP), heart rate (HR), contractility (+LVdP/dt), and relaxation (-LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP). ISP also caused significant decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and myocyte injury marker enzymes; creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; thiobarbituric acid reacting species (TBARS) in heart. Pre-treatment with P. betle favorably modulated hemodynamic (SAP, DAP, and MAP) and ventricular function parameters (-LVdP/dt and LVEDP). P. betle pre-treatment also restored SOD, CAT, GSH, and GPx, reduced the leakage of CK-MB isoenzyme and LDH along with decreased lipid peroxidation in the heart. Taken together, the biochemical and functional parameters indicate that P. betle 150 and 300 mg/kg has a significant cardioprotective effect against ISP-induced myocardial infarction. Results of the present study suggest the cardioprotective potential of P. betle.
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In this study the effect of crude aqueous extract of the leaves of Piper betle L. on the virulence properties of Streptococcus mutans ATCC 25175 was investigated. It was carried out based on the effect of the extract towards growth, cell surface hydrophobicity, adhering property and glucosyltransferase activity of the S. mutans. The concentration of crude aqueous extract of Piper betle L . used in the experiments above was between 0 to 20 mg mL<sup>-1</sup>. Chlorhexidine (0.12%) and sterile deionised water was used as positive and blank control, respectively. The results obtained showed that the crude extract at a concentration as low as 2.5 mg mL<sup>-1</sup> exhibited reduced effect towards the growth (p<0.01), adhering ability (p<0.01), glucosyltransferase activity (p<0.05) and cell surface hydrophobicity (p<0.05) of S. mutans when compared with the blank control. This implies that the Piper betle L . extract may have anti-virulence property towards S. mutans .
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The study was planned to evaluate modulatory effect of aqueous extract of Piper betle leaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 microg/ml) and superoxide radicals (up to 95% at 80 microg/ml), chelated metal ions (up to 83% at 50 microg/ml) and inhibited lipid peroxidation (up to 55.65% at 500 microg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of radiation during unplanned exposures.
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Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of hydroxychavicol were determined by using broth microdilution method following CLSI guidelines. Time kill curve studies, post-antifungal effects and mutation prevention concentrations were determined against Candida species and Aspergillus species "respectively". Hydroxychavicol was also tested for its potential to inhibit and reduce the formation of Candida albicans biofilms. The membrane permeability was measured by the uptake of propidium iodide. Hydroxychavicol exhibited inhibitory effect on fungal species of clinical significance, with the MICs ranging from 15.62 to 500 μg/ml for yeasts, 125 to 500 μg/ml for Aspergillus species, and 7.81 to 62.5 μg/ml for dermatophytes where as the MFCs were found to be similar or two fold greater than the MICs. There was concentration-dependent killing of Candida albicans and Candida glabrata up to 8 × MIC. Hydroxychavicol also exhibited an extended post antifungal effect of 6.25 to 8.70 h at 4 × MIC for Candida species and suppressed the emergence of mutants of the fungal species tested at 2 × to 8 × MIC concentration. Furthermore, it also inhibited the growth of biofilm generated by C. albicans and reduced the preformed biofilms. There was increased uptake of propidium iodide by C. albicans cells when exposed to hydroxychavicol thus indicating that the membrane disruption could be the probable mode of action of hydroxychavicol. The antifungal activity exhibited by this compound warrants its use as an antifungal agent particularly for treating topical infections, as well as gargle mouthwash against oral Candida infections.
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Aqueous and methanol extract of the leaves of Terminalia catappa L., Manilkara zapota L. and Piper betel L. were evaluated for antibacterial activity against 10 Gram positive, 12 Gram negative bacteria and one fungal strain, Candida tropicalis. Piperacillin and gentamicin were used as standards for antibacterial assay, while fluconazole was used as standard for antifungal assay. The three plants showed different degree of activity against the microorganisms investigated. The methanolic extract was considerably more effective than aqueous extract in inhibiting the investigated microbial strains. The most active antimicrobial plant was Piper betel.
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In this study, the bacteriostatic effect of Piper betle and Psidium guajava extracts on selected early dental plaque bacteria was investigated based on changes in the doubling time (g) and specific growth rates (micro). Streptococcus sanguinis, Streptococcus mitis and Actinomyces sp. were cultured in Brain Heart Infusion (BHI) in the presence and absence of the extracts. The growth of bacteria was monitored periodically every 15 min over a period of 9 h to allow for a complete growth cycle. Growth profiles of the bacteria in the presence of the extracts were compared to those in the absence and deviation in the g and micro were determined and analyzed. It was found that the g and mu were affected by both extracts. At 4 mg mL(-1) of P. betle the g-values for S. sanguinis and S. mitis were increased by 12.0- and 10.4-fold, respectively (p < 0.05). At similar concentration P. guajava increased the g-value by 1.8- and 2.6 -fold, respectively (p < 0.05). The effect on Actinomyces sp. was observed at a much lower magnitude. It appears that P. betle and P. guajava extracts have bacteriostatic effect on the plaque bacteria by creating a stressed environment that had suppressed the growth and propagation of the cells. Within the context of the dental plaque, this would ensure the attainment of thin and healthy plaque. Thus, decoctions of these plants would be suitable if used in the control of dental plaque.
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In this study, the antimicrobial influence of crude aqueous extract of Piper betle L. on Streptococcus mutans (S. mutans) was investigated. The focus of the antimicrobial effects includes the ultrastructure and acid producing properties of S. mutans. Transmission electron microscopy (TEM) was used to determine the effect of the extract on the ultrastructure of S. mutans. Analysis of the effect on the acid producing properties was analyzed by pH drop assay. The investigation was further carried out to determine the possible chemical components of the extract using thin layer chromatography (TLC), bioautography and gas chromatography mass spectrometry (GCMS). From the micrographs of the transmission electron, it was found that the crude extract of Piper betle L. leaves causes plasma cell membrane damage and coagulation of the nucleoid. The extract was found to significantly reduce acid producing properties of the bacteria. Chemical analysis of the extract showed that hydroxychavicol, fatty acids (stearic and palmitic) and hydroxy fatty acid esters (stearic, palmitic and myristic) as the main components. It was suggested from the results obtained that the crude extract of Piper betle L. leaves may exert anticariogenic activities that are related to decrease in acid production and changes to the ultrastructure of S. mutans. Further study will be carried out to determine if the effect observed is attributed to the presence of hydroxychavicol, fatty acids and hydroxy fatty acid esters in the extract.
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Larvae of Chrysomya bezziana are the commonest cause of wound myiasis in some parts of the world. This obligatory parasite is important in humans and in commercial livestock. Kumarasinghe et al have reported that essential oil of betel leaf (EOBL) is larvicidal to C. megacephala but there are no publications on its effect on C. bezziana . This study was done to evaluate the efficacy of essential oil of betel leaf ( Piper betle ) against the larvae of C. bezziana in vitro . EOBL was prepared at the Industrial Technology Institute Colombo, Sri Lanka, according to a standard protocol. The experiment on larvae was carried out at the Research Institute for Veterinary Sciences in Bogor, Indonesia. EOBL concentrations of 2%, 3% and 4% were prepared with Tween 80. Two ml of 4%, 3% and 2% EOBL in 1% Tween 80 (v/v/aq) were poured into separate Petri dishes. Ten 1st and 2nd instar larvae were placed in each Petri dish. Asuntol (Chaumaphos) 1% was used as positive control and distilled water with 1% tween 80 was the negative control. Larval mortality was assessed half-hourly. The experiment was repeated five times and averages were compared. Sustained immobility of the larvae, after exposure to the relevant substances was considered as death. The efficacy of EOBL depended on, the stages of C. bezziana larvae and the concentration. With 4% EOBL, all first instar larvae were killed within two hours and the second instar larvae were killed by four hours. The positive control showed no mortality until four hours but all larvae were weak, from the first 30 minutes. In the negative control, larvae were mobile and active. EOBL 3% killed all the first instar larvae by 150 minutes and 74% of the second instar at four hours. By 210 minutes, 2% preparation had killed 100% of the first instars. EOBL is an effective larvicidal for C. bezziana first and second instar larvae in vitro . This natural product has a great potential to be developed as a novel larvicide against this parasite.
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The association between the oral microbiota and oral diseases is well established. Various antimicrobial agents including antibiotics are commercially available against oral pathogenic bacteria. For the reasons of antibiotic resistance, their adverse effects and financial considerations in the developing countries, there is a need for alternate preventive and curative treatment options that are also safe, effective and economical. Traditional medicines have been used since ancient times for the treatment of oral diseases including dental caries, periodontal diseases that affect the majority of the population and can affect a person's overall health. Natural phytochemicals are certain organic components isolated from plants and some of these extracts are considered to be beneficial to health. They serve as antioxidants, enhance immune response, provide protection against oral cancer and other diseases and also repair DNA damage caused by smoking and other toxic exposure, and detoxify carcinogens. The natural products derived from medicinal plants have proven to be an abundant source of biologically active compounds, many of which have been the basis for the development of new lead chemicals for pharmaceuticals. They are considered to be good alternatives to synthetic chemicals. This article presents a review of natural alternatives derived from plants and plant products that can serve as a prevention and treatment option against cariogenic bacteria.
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Scientists are constantly searching for phytochemical compounds with anti-cancer activity. In this study, activity of plant extract NPB001-05 from Piper betle was tested on human chronic myelogenous leukemia (CML) xenograft models. NPB001-05 was active when dosed orally (500 mg/kg) once or twice a day in xenograft tumor models. NPB001-05 showed activity to T315I tumor xenograft, where imatinib failed to show antitumor activity. NPB001-05 showed no relevant toxicity in animal models during 2 weeks exposure to drug. Responsive tumor showed inhibition of tyrosine kinase activity with lowered Bcr-Abl protein levels and increased apoptosis. Microarray based transcription profiling studies demonstrated that both imatinib and NPB001-05 dysregulated imatinib- responsive genes. NPB001-05 showed additional genes selectively dysregulated from ER stress, PI3K/AKT, MAPK pathways. Additionally, we tested gene expression of PI3K, AKT1, JUN, CASP3 and DDIT3 in K562, BaF3P210(BCR-ABL) and BaF3 P210(BCR-ABLT315I) cell line treated for 6- and 12- hours with NPB001-05 and imatinib. The data indicates that NPB001-05 mediated cell death in K562 affects the function of ER stress. NPB001-05 shows antitumor activity with favorable toxicity profile.
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Alkaloids and lignans from the stems of Piper betle were studied. Compounds were isolated and purified by repeated silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography and preparative thin layer chromatography. The structures were elucidated on the basis of spectral analysis. From the ethyl acetate soluble fractions of the 70% acetone extract, ten compounds were isolated and identified as piperine (1), pellitorine (2), N-isobutyl-2E,4E-dodecadienamide (3), dehydropipernonaline (4), piperdardine (5), piperolein-B (6), guineensine (7), (2E,4E)-N-isobutyl-7-(3',4'-methylenedioxyphenyl)-2,4-heptadienamide (8), syringaresinol-O-beta-D-glucopyranoside (9),pinoresinol (10). All Compounds were isolated from the plant for the first time, and compounds 9 and 10 were isolated firstly from the genus.
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The study investigates fungal contamination in some dry fruits, spices and areca nut and evaluation of the essential oil (EO) of Piper betle var. magahi for its antifungal, antiaflatoxigenic and antioxidant properties. A total of 1651 fungal isolates belonging to 14 species were isolated from the samples and Aspergillus was recorded as the dominant genus with 6 species. Eleven aflatoxin B(1) (AFB(1)) producing strains of A. flavus were recorded from the samples. Eugenol (63.39%) and acetyleugenol (14.05%) were the major components of 32 constituents identified from the Piper betle EO through GC and GC-MS analysis. The minimum inhibitory concentration (MIC) of P. betle EO was found 0.7 microl/ml against A.flavus. The EO reduced AFB(1) production in a dose dependent manner and completely inhibited at 0.6 microl/ml. This is the first report on efficacy of P. betle EO as aflatoxin suppressor. EO also exhibited strong antioxidant potential as its IC(50) value (3.6 microg/ml) was close to that of ascorbic acid (3.2 microg/ml) and lower than that of the synthetic antioxidants such as butylated hydroxytouene (BHT) (7.4 microg/ml) and butylated hydroxyanisole (BHA) (4.5 microg/ml). P. betle EO thus exhibited special merits possessing antifungal, aflatoxin suppressive and antioxidant characters which are desirable for an ideal preservative. Hence, its application as a plant based food additive in protection and enhancement of shelf life of edible commodities during storage and processing is strongly recommended in view of the toxicological implications by synthetic preservatives.
Article
The present study was undertaken to investigate the anti-arthritic activity of hydroxychavicol (HC) a major phenolic compound isolated from the aqueous extract leaves of plant Piper betle (Piperaceae). The compound showed significant lowering of pro-inflammatory (Th1) cytokine levels in arthritic paw tissue homogenate supernatant viz. IL-2, IFN-gamma, and TNF-alpha with maximum inhibition at higher dose levels of 2 and 4 mg/kg p.o. and enhanced the production of anti-inflammatory (Th2) cytokines IL-4 and IL-5 estimated by cytometric bead array immunoassay. Cytometric bead array uses the sensitivity of amplified fluorescence detection by flowcytometer to measure soluble analytes in a particle based immune assay. This assay can accurately quantitate five cytokines in a 50-microl sample volume. The T-helper (Th1) deviated cells produce detectable level of tumor necrosis factor (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma), while the Th2 deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin-5 (IL-5). HC at graded doses also significantly decreased the expression of IL-1beta, PGE(2), LTB(4), and nitric oxide levels showing significant inhibition of these parameters. Elevated levels of CD4(+) T cell specific interferon-gamma (IFN-gamma) in splenocytes of arthritic animals was also inhibited in treated animals. The oral LD(0) in both mice and rats was more than 1000 mg/kg.
Article
To study the chemical constituents from the stems of Piper betle. Various chromatographic techniques were used to isolate and purify the constituents. The structures of these compounds were elucidated on the basis of spectral analysis. Nine compounds were isolated from the petroleum ester and ethyl acetate soluble fractions of the 70% acetone extract and their structures were identified as 6beta-hydroxystigmast-4-en-3-one (1), beta-sitosterol (2), stigmasterol (3), oleanolic acid (4), 23-hydroxyursan-12-en-28-oic acid (5), beta-sitosterol-3-O-beta-D-glucoside-6'-O-palmitate (6), beta-daucosterol (7), (2S) -4'-hydroxy- 2,3-dihydroflavonone-7-O-beta-D-glucoside (8) and alpha-ethyl glucoside (9). Among these compounds, 1, 3 -9 are isolated from this plant for the first time.
Article
The screening of Piperaceous plants for xanthine oxidase inhibitory activity revealed that the extract of the leaves of Piper betle possesses potent activity. Activity-guided purification led us to obtain hydroxychavicol as an active principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than allopurinol, which is clinically used for the treatment of hyperuricemia.
Article
Modulation of immune functions by using herbal plants and their products has become fundamental regime of therapeutic approach. Piper betle Linn. (Piperaceae) is a widely distributed plant in the tropical and subtropical regions of the world and has been attributed as traditional herbal remedy for many diseases. We have recently reported the antifilarial and antileishmanial efficacy in the leaf extract of Bangla Mahoba landrace of P. betle which is a female plant. The present report describes the in vivo immunomodulatory efficacy of the crude methanolic extract and its n-hexane, chloroform, n-butanol fractions of the female plant at various dose levels ranging between 0.3 and 500 mg/kg in BALB/c. Attempts were also made to observe antifilarial activity of the active extracts and correlate it with the antigen specific immune responses in another rodent Mastomys coucha infected with human lymphatic filarial parasite Brugia malayi. The crude methanol extract and n-hexane fraction were found to potentiate significant (p<0.001) enhancement of both humoral (plaque forming cells, hemagglutination titre) as well as cell-mediated (lymphoproliferation, macrophage activation, delayed type hypersensitivity) immune responses in mice. The flow cytometric analysis of splenocytes of treated mice indicated enhanced population of T-cells (CD4(+), CD8(+)) and B-cells (CD19(+)). The n-hexane fraction (3 mg/kg) was found to induce biased type 2 cytokine response as revealed by increased IL-4(+) and decreased IFN-gamma(+) T-cell population while the chloroform fraction (10 mg/kg) produced a predominant type 1 cytokines. Crude methanolic extract (100 mg/kg) demonstrated a mixed type 1 and type 2 cytokine responses thus suggesting a remarkable immunomodulatory property in this plant. The induction of differential T-helper cell immune response appears ideal to overcome immunosuppression as observed in case of lymphatic, filarial Brugia malayi infection which may also be extended to other infections as well.
Article
Betle leaf chewing is an old traditional practice in India and other countries of East Asia. We have investigated the antioxidant and antihyperlipidaemic potential of an alcoholic leaf-extract of Piper betle against D-galactosamine (D-GalN; 400 mg/kg body weight, i.p. single dose) intoxication in male albino Wistar rats. Rats were treated with leaf-extract (200 mg/kg body weight) by intragastric intubations daily for 20 days. The animals were divided randomly into five groups of six animals each as control, control plus extract, D-GalN control, D-GalN-rats on treatment with extract or silymarin, a standard drug. We observed an increase in the plasma levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and a decrease in vitamin C, vitamin E and reduced glutathione concentrations. Very low density lipoprotein cholesterol and low density lipoprotein cholesterol increased significantly while high density lipoprotein cholesterol decreased. Further, increase in the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney were observed in D-GalN-treated rats. Administration of P. betle leaf-extract prevented the increase or decrease of these parameters and brought towards normality. These results suggest that P. betle could afford a significant antioxidant and antihyperlipidaemic effect against D-GalN-intoxication.
Article
D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.
Article
The effect of betel leaf extract and some of its constituents, eugenol, hydroxychavicol, beta-carotene and alpha-tocopherol, on benzo[a]pyrene-induced forestomach neoplasia in male Swiss mice was examined. Betel leaf and its constituents decreased the number of papillomas per animal with the maximum protection, considering molar dosage, exhibited by beta-carotene and alpha-tocopherol. Except for beta-carotene, eugenol, hydroxychavicol and alpha-tocopherol increased the levels of reduced glutathione in the liver while glutathione S-transferase activity was enhanced by all except eugenol. Of seven sources, Banarasi betel leaves showed the maximum amounts of beta-carotene and alpha-tocopherol.
Article
Earlier studies showed that betel leaf inhibits the mutagenic action of standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since tobacco-specific nitrosamines are the major carcinogens present in unburnt forms of tobacco, we studied the effect of an extract of betel leaf on the mutagenic and carcinogenic actions of one of the most potent, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). Betel-leaf extract and hydroxychavicol suppressed the mutagenicity of NNK in both the Ames and the micronucleus test. In studies in mice, betel-leaf extract reduced the tumorigenic effects of NNK by 25%. Concurrent treatment with the extract also inhibited the decreases in levels of vitamin A in liver and plasma induced by NNK. Betel leaf thus has protective effects against the mutagenic, carcinogenic and adverse metabolic effects of NNK in mice.
Article
Effects of topically applied betel leaf extract (BLE) and its constituents. beta-carotene, alpha-tocopherol, eugenol and hydroxychavicol on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumors were evaluated in two strains of mice. BLE, beta-carotene and alpha-tocopherol, significantly inhibited the tumor formation by 83, 86, 86% in Swiss mice and 92, 94 and 89% in male Swiss bare mice respectively. Hydroxychavicol showed 90% inhibition in Swiss bare mice at 24 weeks of treatment. Eugenol showed minimal protection in both strains of mice. The mean latency period and survivors in BLE, beta-carotene, alpha-tocopherol and hydroxychavicol treated groups were remarkably high as compared to DMBA alone treated group. Intraperitoneal injection of betal leaf constituents showed a significant effect on both glutathione and glutathione S-transferase levels in the Swiss mouse skin.
Article
Chronic administration (sc) of the extract of the stalk of P. betle at 30 mg/kg body weight daily for 21 days produced significant decrease in oestrogen and androgen dependent target organ weights along with increase in cholesterol in adrenal, ovary and testis. Acid and alkaline phosphatase activities in serum, liver and kidney did not exhibit any toxic effect. There was marked change in morphology of testis and ovary. Vaginal smear showed prolonged dioestrus in treated female. The treated male showed decreased number and motility of sperm. Both male and female remained infertile after treatment suggesting antifertility activity of the extract on both sexes of albino rats.
Article
Hydroxychavicol and eugenol are the phenolic compounds isolated from betel leaf (piper betel). The modulation of nitrosation of methylurea by sodium nitrite at pH 3.6 and 30°C was studied. The formation of mutagenic N-nitroso-methylurea was monitored by checking the mutagenicity of reaction mixture in Salmonella typhimurium strain TA100 and TA1535 without S9 mix. Hydroxychavicol and eugenol exhibit dose-dependent suppression of nitrosation in vitro without affecting the survival of the bacteria. Pre-or post-treatment of bacterial cells from S.typhimurium strains TA100 and TA1535 with phenolics did not modify the mutagenicity of nitrosomethylurea. The blocking of hydroxy group(s) in the benzene ring by acetylation abolishes the anti-nitrosating activity of the molecule(s). The nitrosation inhibition by hydroxychavicol is through scavenging of nitrite ions in the media, thus making them non-available for the nitrosation of methylurea.
Article
Epidemiological studies have implicated chewing tobacco alone to be more hazardous than chewing tobacco with betel quid. Experimental studies have shown that betel leaf is antimutagenic against standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since the tobacco-specific N-nitrosamines (TSNA) are the only carcinogens present in unburnt forms of tobacco, including chewing tobacco, we tested the effect of an extract of betel leaf against the mutagenicity of the two important TSNA, viz., N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, using the Ames Salmonella/microsome assay with TA100 +S9 and the in vivo micronucleus test. In both the test systems it was observed that betel leaf extract suppressed the mutagenic effects of both the nitrosamines to a significant extent.
Article
The anti-inflammatory effects of phenolic dental medicaments were evaluated by mouse ear edema assay. p-Chlorophenol (PCP) inhibited edema when applied topically in dosages of 0.2 and 0.5 mg per site at 15 min before or 1.0 and 2.0 mg per site at 60 min after the application of croton oil. The inhibitory effects were also noted with eugenol, guaiacol, o-cresol, phenol and orally administered indomethacin (10 mg/kg). The involvement of the effects on prostaglandin biosynthesis in the anti-inflammatory effects of these compounds is discussed.
Article
Epidemiological studies have implicated that betel quid offers some protection to tobacco induced carcinogenesis. Earlier studies in our laboratory have shown betel leaf extract (BLE) to be antimutagenic against standard mutagens and tobacco-specific N'-nitrosamines (TSNA), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the present study, we have tested the anticarcinogenic effect of BLE using Swiss male mice. Two protocols of study were used to test this effect. In the first protocol, the effect of BLE was tested against the standard carcinogen benzo[a]pyrene (BP) using Wattenberg's stomach tumor model, Cancer Res., 41 (1981) 2820-2823. In this protocol, BLE inhibited the tumorigenicity of BP to a significant extent. In the second protocol, the effect of BLE against the two tobacco-specific nitrosamines, NNN and NNK was studied using long-term studies on Swiss male mice. The nitrosamines were administered on the tongues of the mice, while the BLE was supplied in drinking water. Two doses of NNN (22 mg and 72 mg) and one dose of NNK (22 mg) were used. In this study, it was observed that the number of tumor bearing animals decreased, but the difference was significant only in the group treated with the low dose of NNN in combination with BLE. However, in all the BLE treated animals, irrespective of the dose of nitrosamine, the hepatic vitamin A and C levels were elevated significantly as compared to the corresponding nitrosamine-treated controls. These results indicate that BLE has a promising anticarcinogenic role to play in tobacco induced cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The phenolic compounds eugenol and hydroxychavicol were separated from betel leaf extract using C18 phase bonded Hiflosil silica gel. The structures of the two compounds were confirmed by nuclear magnetic resonance data. Neither eugenol nor hydroxychavicol was mutagenic when tested in various strains of Salmonella typhimurium with or without metabolic activation. Both compounds exhibited dose-dependent suppression of dimethylbenzanthracene-induced mutagenesis in S. typhimurium strain TA98 with metabolic activation. Hydroxychavicol was more potent than eugenol in this respect.
Article
Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.
Article
When an aqueous extract of the leaves of Piper betle, a medicinal plant, was given orally at different dose levels during the initiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in rats, higher doses of the extract inhibited the emergence of tumors. However, when the extract was fed to the rats bearing DMBA-induced mammary tumors for 8 weeks, no appreciable degree of inhibition of tumor growth was noticed. Betel leaf extract at the dose levels used in the present study did not affect the body weight gain among rats.
Article
The present study evaluates the incidence of tumors in hamster buccal pouches following short-term (10 days) and long-term (6 months) topical exposures to graded doses of benzo(a)pyrene, B(a)P (25 micrograms, 50 micrograms and 100 micrograms per pouch either daily for 10 days or thrice weekly for 6 months) alone or in combination with extract of tobacco (1 mg/pouch, twice daily), betel nut (1 mg/pouch, twice daily) or betel leaf (5 mg/pouch, twice daily). Given alone, the three doses of B(a)P respectively yielded, 6 months after the last treatment, 4%, 8.7% and 16.7% tumors in the short-term study, and 20%, 35% and 61% tumors in the long-term study. Short-term treatments with individual ingredients of betel quid did not produce any tumors while long-term treatments produced tumors only with tobacco (17.6%) and betel nut (10.5%). When B(a)P, and betel quid ingredients were painted concomitantly for 10 days, there was, depending upon the dose of B(a)P, complete or partial suppression of tumor production. But when B(a)P-plus-tobacco or B(a)P-plus-betel nut treatments were given for 6 months, there was a considerable increase in tumor incidence. Betel leaf extract, in both short-term and long-term studies, expressed its inhibitory influence on B(a)P-induced tumorigenesis.
Ground powder of the leaf and fruit of Piper betle L., a tropical spice plant grown in Southeast Asia, was prepared and extracted by chloroform, ethanol and water with one solvent only or with 3 solvents in sequence. The betel powder and various extracts were added to YES broth to determine their effects on the growth and aflatoxin production by Aspergillus parasiticus. Results showed that betel leaf powder exhibited higher antimycotic activity than fruit. One half percent of ground leaf powder completely inhibited the growth and aflatoxin production by A. parasiticus. Among the solvent extracts, chloroform and ethanol extracts of betel leaf prepared from a single solvent extraction showed more antimycotic activity. The ethanol extract of betel leaf at the level of 450 micrograms/ml would eliminate A. parasiticus growth and aflatoxin production. The antimycotic activity of this ethanol extract was most pronounced at pH 4.
Article
The mutagenic activity of betel quid and its ingredients was determined using Salmonella typhimurium tester strains TA 100, TA 1535, TA 98, and TA 1538, both in the presence and absence of S9 mixture. Aqueous extracts of betel quid (BQ), betel quid with tobacco (BQT), and betel nut (BN) were mutagenic in strain TA 100. Aqueous extract of betel leaf (BL) was not mutagenic in any of the four strains. Arecoline and arecaidine, which are major alkaloids present in BN, were mutagenic in all four tester strains. Tumorigenicity studies in Swiss mice given the above constituents showed that BN and BQ induced lung tumors (47% and 26%, respectively). However, when BN was fed with BL, tumorigenicity was lowered to 38%. BL alone was not tumorigenic. Thus, the mutagenicity of betel quid and its ingredients is correlated with tumorigenicity.