Effects of montmorillonite on the loading and release of Piper betle L. extract applied for wound dressing based on chitosan/polyvinyl alcohol.

In this study, we investigate the influence of montmorillonite (MMT) on the loading and release of Piper betle L. extract (PLE)-a medicinal herb containing active secondary metabolites with antibacterial, antioxidant, and anti-inflammatory effects. MMT (1 %, 3 %, 5 %) was blended into the chitosan/polyvinyl alcohol (CS/PVA) biocomposite film by the solution evaporation method, and then PLE was loaded onto this biocomposite using the immersion method. The tensile strength and the ability to absorb exudates of the CS/PVA film improved with the increase in MMT content. The MMT 3 % film was considered to have the best properties: good mechanical properties with a tensile strength of 27.44 ± 0.27 MPa and elongation at break of 14.57 ± 0.30 %, potential for wound dressing due to its ability to absorb wound exudate (swelling degree 61.70 ± 0.30 %) and a suitable water vapor transmission rate (1999 ± 47 g/m2·d). The presence of MMT (1 %, 3 %, 5 %) in the CS/PVA film led to an increase in the PLE loading efficiency of the films compared to the film without MMT, up to 1.65, 1.73, and 1.87 times, respectively. The MMT 3 % and 5 % films also exhibited a sustained PLE release effect for up to 24 h. MMT increased PLE bioavailability through bioactivity tests: antibacterial activity against both E. coli and S. aureus, antioxidant activity, effective healing of 2nd-degree burn wounds, and biocompatibility with the L929 fibroblasts cell line. The combination of physicochemical properties and biological activities proved that the MMT/PLE drug delivery system based on the CS/PVA biocomposite is promising for wound dressing.

Ultrasound assisted extraction of phytochemicals from Piper betel L.

Piper betel contains phytochemicals with diverse pharmacological effects. The objective of this study was to enhance the extraction efficiency of phytochemicals and the chlorophyll content using ultrasonication. The Box-Behnken design was employed to optimize the time (10, 20, 30 min), temperature (20, 30, and 40 °C), and solid-solvent ratio (1:10, 1:20, 1:30) by utilizing response surface methods with three independent variables. Multiple parameters, including extract yield, total phenol, total flavonoid, antioxidant activity, and chlorophyll content were used to optimize the conditions. The linear relationship between power intensity and responses was determined to be statistically significant, with a p-value less than 0.01. The interaction effect of temperature, time, and ratio of solid solvent was shown to be statistically significant (p < 0.05) for all the obtained results. The optimal parameters for achieving the highest extract yield were as follows: a temperature of 40 °C, a sonication time of 30 min, and a solid solvent ratio of 1:10. These conditions result in an extract yield of 21.99 %, a total flavonoid content of 44.97 mg/GAE, a total phenolic content of 185.05 mg/GAE, a DPPH scavenging activity of 99.1 %, and a chlorophyll content of 49.95 mg/ml. This study highlights the significance of customized extraction methodologies for optimizing the bioactive capacity of phytochemicals derived from betel leaves. The elucidation of extraction parameters and the resultant phytochemical profiles serves as a fundamental framework for the advancement of innovative pharmaceuticals and nutraceuticals, capitalizing on the therapeutic attributes of this traditional medicinal botanical.

Effects of Drying Methods on the Antioxidant Properties of Piper betle Leaves.

Piper betle leaf powder is increasingly utilised as a health supplement. In this study, P. betle leaves were subjected to four different drying methods: convective air-drying, oven-drying, sun-drying, and no drying, with fresh leaves as control. Their antioxidant properties were then evaluated using colourimetric assays and GC-MS. Results showed that the sun-dried leaves had the highest (p < 0.05) total antioxidant capacity (66.23 ± 0.10 mg AAE/g), total polyphenol content (133.93 ± 3.76 mg GAE/g), total flavonoid content (81.25 ± 3.26 mg CE/g) and DPPH radical scavenging activity (56.48 ± 0.11%), and the lowest alkaloid content (45.684 ± 0.265 mg/gm). GC-MS analysis revealed that major constituents of aqueous extracts of fresh and sun-dried P. betle leaves were hydrazine 1,2-dimethyl-; ethyl aminomethylformimidate; glycerin; propanoic acid, 2-hydroxy-, methyl ester, (+/-)-; and 1,2-Cyclopentanedione. In conclusion, sun-dried leaves exhibited overall better antioxidant properties, and their aqueous extracts contained biologically active phytoconstituents that have uses in various fields.

Screening of growth inhibitors for epithelial-mesenchymal transition-induced cells by TGF-ß from plant-based sources identified the active compound hydroxychavicol from Piper bitle.

Epithelial-mesenchymal transition (EMT) has recently been associated with cancer invasion, metastasis, and resistance. In our previous study, we discovered nanaomycin K, a natural growth inhibitor for EMT-induced Madin Darby canine kidney (MDCK) cells, from the cultured broth of actinomycetes. However, the screening method was undeveloped, because the activity of nanaomycin K was discovered accidentally. In this study, we established a screening method by analyzing the characteristics of nanaomycin K in MDCK cells. Nanaomycin K showed the characteristic growth inhibitory activity on MDCK cells cultured under four conditions: medium containing dimethyl sulfoxide, SB431542, TGF-ß, and a mixture of SB431542 and TGF-ß. The activity was stronger in TGF-ß-treated cells than in DMSO-treated cells. In the mixture of SB431542 and TGF-ß-treated cells, the activity of nanaomycin K was suppressed. The anti-cancer agents, mitomycin C, cisplatin, and staurosporine, lacked the characteristics as that of nanaomycin K for these four treatment conditions. Since these four conditions distinguish between the effects of nanaomycin K and other anti-cancer agents in EMT-induced cells, the screening method was established. Among the 13,427 plant extracts tested, Piper betle leaf extract displayed growth inhibitory activity against EMT-induced cells. Through the purification of the extract via bio-guided fractionation, hydroxychavicol was isolated as an active compound. The cytotoxic activity of hydroxychavicol was stronger in EMT-induced MDCK cells than in control cells. However, its cytotoxic activity was suppressed in EMT-inhibited cells. Furthermore, hydroxychavicol exhibited same activity against SAS cells (human squamous cell carcinoma of the tongue). Thus, we have successfully established a screening method for growth inhibitors of EMT-induced cells and have discovered an inhibitor from plant-based sources.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Development and characterization of edible films based on flaxseed gum incorporated with Piper betle extract.

There has been a shift from use of petroleum-based plastics, causing serious environmental pollution, towards innovative and biodegradable edible packaging. The present study documents the development of composite edible films based on the flaxseed gum (FSG) modified by the incorporation of betel leaf extract (BLE). The films were assessed for physicochemical, mechanical, morphological, thermal, antimicrobial and structural characteristics. Scanning electron microscopy images indicated that the roughness decreased with an increase in BLE concentration. The water vapor permeability of the FSG-BLE films ranged from 4.68 to 1.59 × 10-9 g s- 1 m- 2 Pa- 1, lower than that of the control sample (6.77 × 10-9 g s- 1 m- 2 Pa- 1). The BLE4 (containing 10 % BLE) films had the highest tensile strength of 32.46 MPa compared to the control sample (21.23 MPa). Similarly, EAB and seal strength of the films incorporated with BLE were ameliorated. X-ray diffraction pattern and FTIR illustrated the shift of amorphous to crystalline behavior and a significant interaction among the BLE and FSG functional groups. Furthermore, the thermal stability of the treated films was not affected significantly however, they showed improved antimicrobial activity with the highest diameter of inhibition zone in the BLE4 sample. This study concluded that the FSG-BLE composite films (BLE4 in particular) can be considered as novel packaging material for food conservation coupled with a potential to enhance the shelf life of perishable food products.

Potential natural antimicrobial and antibiofilm properties of Piper betle L. against Staphylococcus pseudintermedius and methicillin-resistant strains.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper betle L. has potent of antimicrobial activity and is widely used as a traditional remedy to treat skin infections. However, no clear evidence exists concerning antimicrobial and antibiofilm activity against Staphylococcus pseudintermedius and methicillin-resistant S. pseudintermedius (MRSP) opportunistic pathogens that cause wound infections and pyoderma in canines and zoonotic disease. AIM OF THE STUDY: The antimicrobial and antibiofilm activities of P. betle extract were assessed against S. pseudintermedius and MRSP strains. MATERIALS AND METHODS: Ethanol leaf extract of P. betle was investigated for its antibacterial effect on S. pseudintermedius and MRSP by broth microdilution and time-kill assays. Biofilm inhibition and production assays were performed to evaluate antibiofilm and biofilm eradication effects, respectively. Biofilm-associated gene expression was further studied using real-time polymerase chain reaction (PCR). The possible interaction between IcaA and major compounds in P. betle was analyzed by molecular docking. RESULTS: The extract showed minimum inhibitory concentration (MIC) at 250 µg/mL. Growth inhibition of P. betle at 1 MIC against the bacteria was initially observed after treatment for 4 h. All isolates were completely killed after 18 h exposure to the extract. Minimum biofilm inhibitory concentrations (MBICs) of the extract against the tested isolates ranged 1/2 MIC to 1 MIC, while minimum biofilm eradication concentration (MBEC) of P. betle was initialed at 8 MIC. Quantitative inhibition and eradication effects were observed in representative strains. The extract at 1/2 MIC and 1 MIC values inhibited biofilm formation up to 100%, with bacterial biofilm removed at up to 94.21% by 4 MIC of the extract. The extract downregulated the expression of the icaA gene among biofilm-producing isolates. The most abundant compounds, 4-allyl-1,2-diacetoxybenzene and eugenol showed a strong affinity with IcaA protein at -5.65 and -5.31 kcal/mol, respectively. CONCLUSIONS: P. betle extract demonstrated the antibacterial, antibiofilm, and biofilm-removal activity against S. pseudintermedius and MRSP. Downregulation of the icaA gene expression and protein interaction were possible modes of action of the extract that impacted biofilm production. This extract showed promise as an alternative treatment for S. pseudintermedius infection, especially drug-resistant and biofilm-associated cases.

Targeting bone cancer with 4-Allylbenzene-1,2-diol purified from Piper betle L.: an in silico and cytotoxicity scrutiny.

Piper betle L., a well-known medicinal plant with rich source of bioactive compounds, is widely used in several therapeutics. The present study was performed to scrutinize the anti-cancer potential of compounds P. betle petiole by means of in silico studies, purification of 4-Allylbenzene-1,2-diol from petioles and assessing its cytotoxicity on bone cancer metastasis. Subsequent to SwissADME screening, 4-Allylbenzene-1,2-diol and Alpha terpineol were chosen for molecular docking together with eighteen approved drugs against fifteen important bone cancer targets accompanied with molecular dynamics simulation studies. 4-Allylbenzene-1,2-diol was found to be multi-targeting, interacted effectively with all targets, particularly exhibited good stability with MMP9 and MMP2 during molecular dynamics simulations and Molecular Mechanics- Generalized Born and Surface Area (MM-GBSA) analysis using Schrodinger. Later, the compound was isolated, purified and the cytotoxicity studies on MG63 bone cancer cell lines confirmed the cytotoxicity nature (75.98% at 100 µg/ml concentration). The results demonstrated the compound as a matrix metalloproteinase inhibitor, and therefore 4-Allylbenzene-1,2-diol may possibly be prescribed in targeted therapy for alleviating the bone cancer metastasis upon further wet lab experimental validations.Communicated by Ramaswamy H. Sarma.

Utilization of Piper betle L. Extract for Inactivating Foodborne Bacterial Biofilms on Pitted and Smooth Stainless Steel Surfaces.

Biofilms are a significant concern in the food industry. The utilization of plant-derived compounds to inactivate biofilms on food contact surfaces has not been widely reported. Also, the increasing negative perception of consumers against synthetic sanitizers has encouraged the hunt for natural compounds as alternatives. Therefore, in this study we evaluated the antimicrobial activities of ethanol extracts, acetone extracts, and essential oils (EOs) of seven culinary herbs against Salmonella enterica serotype Typhimurium and Listeria innocua using the broth microdilution assay. Among all tested extracts and EOs, the ethanol extract of Piper betle L. exhibited the most efficient antimicrobial activities. To evaluate the biofilm inactivation effect, S. Typhimurium and L. innocua biofilms on pitted and smooth stainless steel (SS) coupons were exposed to P. betle ethanol extract (12.5 mg/ml), sodium hypochlorite (NaClO; 200 ppm), hydrogen peroxide (HP; 1100 ppm), and benzalkonium chloride (BKC; 400 ppm) for 15 min. Results showed that, for the untreated controls, higher sessile cell counts were observed on pitted SS versus smooth SS coupons. Overall, biofilm inactivation efficacies of the tested sanitizers followed the trend of P. betle extract ≥ BKC > NaClO > HP. The surface condition of SS did not affect the biofilm inactivation effect of each tested sanitizer. The contact angle results revealed P. betle ethanol extract could increase the surface wettability of SS coupons. This research suggests P. betle extract might be utilized as an alternative sanitizer in food processing facilities.

Why is Nicotiana tabacum leaf extract more effective than Piper betle leaf extract on mortality of Aedes aegypty larvae ?

The control of the dengue vector is an important step in preventing dengue fever. The use of synthetic pesticides has been proven to cause environmental pollution, death of various living things and resistance. Therefore, research on innovative vegetable insecticides such as nicotiana tabacum leaf extract and piper betel leaf extract is urgently needed. This true experimental research to compare the effectiveness of nicotiana tabacum leaf extract and piper betle leaf extract on the Aedes aegypti larva using a post-test only design with a controlled-group design. The nicotiana tabacum leaf and piper betle leaf were extracted with 96% ethanol to be tested on the 600 third instar larvae. Then, the test was done with three concentrations of nicotiana tabacum leaf extract and piper betel leaf extract, including 0.1%, 0.2%, and 0.4%, with three repetitions in each concentration. The most effective concentration and time of nicotiana tabacum leaf extract and piper betel leaf extract on the larvae mortality were analyzed using the Freadman test as the alternative test since the data were not normally distributed. LC 50 and LC 90 of nicotiana tabacum leaf extract and piper betel leaf extract were tested using probit analysis. The results showed that the treatments of nicotiana tabacum leaf extract and piper betel leaf extract affected larvas mortality. The average mortality of larvae in nicotiana tabacum leaf extract was at concentrations of 0.1% (6 larvae), 0.2% (12 larvae), 0.4% (24 larvae) and occurred after 1 h exposure, whereas in piper betle leaf extract, only occurred after 4 h of exposure, with an average death ratio at a concentration of 0.1% in nicotiana tabacum leaf extract (29.33 larvae) and piper betle leaf extract (1.33 larvae). The results of the Probit analysis of nicotiana tabacum leaf extract and piper betle leaf extract at 8 h of exposure obtained LC50 results of 1.2% nicotiana tabacum leaf extract and 9.036% piper betle leaf extract. The LC90 yield of nicotiana tabacum leaf extract was 3.086% and piper betle leaf extract was 14.81%. The results of this study indicated that there were differences in the mortality rates of the two extracts, and that nicotiana tabacum leaf extract had a higher mortality rate than piper betle leaf extract. LC50 and LC90 of piper betle leaf extract had lower values than nicotiana tabacum leaf extract. Piper betle leaf extract requires a higher extract concentration to kill 50% and 90% of test larvae compared to nicotiana tabacum leaf extract.

Technique for order preference by similarity to ideal solution (TOPSIS): a MCDM approach for selecting suitable solvent considering biochemical profiles and in vitro antibacterial efficacy of petioles of betel leaf (Piper betle L.).

Petioles of betel leaf (BLP) are the major industrial by-products of betel leaf industries sold at throwaway prices or used as cattle feed. The present work was taken up to evaluate suitable solvent based on yield, antioxidant, and antimicrobial properties to isolate extract of BLP using the Shannon entropy-TOPSIS method. Four solvents were chosen for the extraction process: hexane, toluene + ethanol (2:1), acetone, and ethanol. The findings showed that ethanol-based BLP extract had the highest TPC value, measuring 2193.71 ± 0.17 mg of gallic acid equivalence/g of dry extract, while acetone-based extracts had the highest TFC value, measuring 8.03 mg of quercetin equivalent/g of dry extract. Radical scavenging activities like DPPH (IC50 = 52.44 µg/mL), ABTS (IC50 = 62.41 µg/mL), and FRAP (8.03 mg QE/g of dry extract) were found best for acetone extract. The antibacterial study of the extracts revealed that acetone extract was more sensitive to Gram-positive and Gram-negative bacterial strains followed by ethanol, toluene + ethanol, and hexane extracts. Among five foodborne bacteria, B. subtilis showed the highest susceptibility against all extracts. GC-MS analysis showed that acetoxychavicol acetate (31.27%) (PubChem ID: 119,104), germacrene D (7.24%) (PubChem Id: 531,750), isoxylic acid (22.56%) (PubChem ID: 11,892), and cis-1,2-indandiol (43.92%) (PubChem ID: 20,758) are four major compounds among 22 components. TOPSIS analysis revealed that acetone extract had the highest relative closeness value (0.71) followed by ethanol (0.65), toluene + ethanol (0.53), and hexane (0.32). These results indicate that acetone extract of BLP can be considered an alternative to synthetic active ingredients in the future. These results indicated that TOPSIS method has computational robustness for selecting a solvent comparing yield, antioxidant, and antimicrobial activities of extract of a plant part.

A phenylpropanoid dimer from the leaves of Piper betle.

Phytochemical analyses of the chloroform extract of Piper betle L. var. Sanchi, Piperaceae, leaves led to the isolation of a new phenylpropanoid analogue for the first time: hydroxychavicol dimer, 2-(γ'-hydroxychavicol)-hydroxychavicol (S1), on the basis of spectroscopic data 1 D (1H and 13C) and 2 D (1H-1H COSY and HMBC) NMR, as well as ESI-MS, FT-IR, HR-ESI-MS and LC-ESI-MS. Compound S1 exhibited excellent antioxidant DPPH radical scavenging activity with IC50 values of 9.07 µg/mL, compared to ascorbic acid as a standard antioxidant drug with IC50 value of 3.41 µg/mL. Evaluation of cytotoxic activity against two human colon cancer cell lines (HT 29 and COLO-205) showed significant effect with GI50 values of 73.81 and 64.02 µmol/L, compared to Doxorubicin® as a standard cytotoxic drug with GI50 value of <10 µmol/L.

Four new N-phenethylbenzamide derivatives from the stems of piper betle and their antimicrobial activity.

Four new N-phenethylbenzamide derivatives, named piperbetamides A-D (1-4), and six allylbenzene derivatives (5-10) were isolated from the stems of Piper betle L. Their structures were determined by HR-ESI-MS and NMR spectroscopic methods. Compounds 1-10 were evaluated for their inhibitory effects on the growth of nine microorganisms including five Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, Shigella flexneri, Pseudomonas aeruginosa, and Extended-spectrum beta-lactam resistant Klebsiella pneumoniae), three Gram-positive (Listeria monocytogenes, Methicilin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis), and one yeast (Candida albicans) strains. Compounds 1, 3, 4, 6 and 10 exhibited potential antimicrobial activity against S. flexneri, L. monocytogenes, methicillin-resistant S. aureus and vancomycin-resistant E. faecalis with minimum inhibitory concentration (MIC) values in the range of 16-32 µg/mL.

In vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract on staphylococcus aureus ATCC 29213

Background and Objective@#Staphylococcus aureus is the leading cause of skin and soft tissue infections such as abscesses, furuncles, and cellulitis. Biofilm forming strains of S. aureus have higher incidence of antimicrobial resistance to at least three or more antibiotics and are considered as multidrug resistant. Since S. aureus biofilm-producing strains have higher rates of multidrug and methicillin resistance compared to non-biofilm-producing strains, the need for alternative therapeutic option is important. Furthermore, rates of methicillin-resistant Staphylococcus aureus (MRSA) in Asia remain high. Results of the study may provide support for the clinical uses of P. betle as a topical antibacterial and antiseptic in the treatment and prevention of infections involving the skin, mouth, throat, and indwelling medical devices. Thus, this study aimed to evaluate the in vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract (PBE) against a biofilm-forming methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).@*Methods@#The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PBE against MSSA were determined using the agar dilution assay. The biofilm inhibition and eradication assays using crystal violet were done to quantify the antibiofilm activities of PBE on MSSA biofilm.@*Results@#PBE showed activity against MSSA in agar dilution assay with MIC and MBC values of 2500 μg/mL and 5000 μg/mL, respectively. At subinhibitory concentrations, PBE showed biofilm inhibition activity at 1250 μg/mL but a lower percent eradication of biofilms as compared to oxacillin was noted.@*Conclusion@#PBE showed antibacterial activities including biofilm inhibition against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA).

A Review of Bioactive Compounds and Antioxidant Activity Properties of Piper Species.

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

Anti-inflammatory and antioxidant activities of methanol extract of Piper betle Linn. (Piper betle L.) leaves and stems by inhibiting NF-κB/MAPK/Nrf2 signaling pathways in RAW 264.7 macrophages.

Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E2 by reducing the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages without affecting cell viability. Furthermore, our findings suggested that the inhibitory effects of MPBLLS on pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were due to the inhibition of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-treated RAW 264.7 macrophages. MPBLLS and hydroxychavicol, a major constituent of MPBLLS, suppressed LPS-induced translocation of NF-κB p65 from cytoplasm to nucleus. Interestingly, MPBLLS increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and transcription levels of Nrf2 target genes in a dose-dependent manner. Collectively, our findings suggest that MPBLLS could serve as a basis for the development of novel orally-administered therapies due to its inhibitory effects on oxidative and inflammatory stress. DATA AVAILABILITY: The data presented in this study are available on request from the corresponding author.

Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (Piper betle L.) for Investigating the Potential Inhibition of Alpha-Amylase and Alpha-Glucosidase of Type 2 Diabetes.

Piper betle L. is widely distributed and commonly used medicinally important herb. It can also be used as a medication for type 2 diabetes patients. In this study, compounds of P. betle were screened to investigate the inhibitory action of alpha-amylase and alpha-glucosidase against type 2 diabetes through molecular docking, molecular dynamics simulation, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The molecule apigenin-7-O-glucoside showed the highest binding affinity among 123 (one hundred twenty-three) tested compounds. This compound simultaneously bound with the two-target proteins alpha-amylase and alpha-glucosidase, with high molecular mechanics-generalized born surface area (MM/GBSA) values (ΔG Bind = -45.02 kcal mol-1 for alpha-amylase and -38.288 for alpha-glucosidase) compared with control inhibitor acarbose, which had binding affinities of -36.796 kcal mol-1 for alpha-amylase and -29.622 kcal mol-1 for alpha-glucosidase. The apigenin-7-O-glucoside was revealed to be the most stable molecule with the highest binding free energy through molecular dynamics simulation, indicating that it could compete with the inhibitors' native ligand. Based on ADMET analysis, this phytochemical exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities and had no significant side effects, making them prospective drug candidates for type 2 diabetes. Additional in vitro, in vivo, and clinical investigations are needed to determine the precise efficacy of drugs.

A xylan from the fresh leaves of Piper betle: Structural characterization and studies of bioactive properties.

A pure water soluble xylan (PS-I) with an average molecular weight ~1.1 × 105 Da was isolated from the hot water extraction of fresh leaves of Piper betle (paan). The xylan was found to be composed of xylose, galactose and methyl galacturonate in a molar ratio of nearly 3:1:1. The repeating unit was composed of a backbone containing three (1 â†’ 4)-α-D-Xylp residues, one of which was branched at O-2 position with the side chain consisting of (1 â†’ 4)-α-D-GalpA6Me and terminal ß-D-Galp residues. This xylan exhibited macrophage, splenocyte, and thymocyte stimulatory activities. In vitro antioxidant studies demonstrated that the xylan has DPPH radical scavenging potential (EC50 = 148 µg/mL), ABTS radical quenching activity (EC50 = 188 µg/mL) and ferrous ions chelating activity (EC50 = 370 µg/mL). These findings elicit the need for further exploration of the xylan as a natural antioxidant and a potent immunostimulating agent.

Anticancer Potential of Hydroxychavicol Derived from Piper betle L: An in Silico and Cytotoxicity Study.

Piper betle L. is a popular medicinal plant in Asia, and extracts of the plant leaf are used for several therapeutics. It is known for its rich source of phenolic compounds, including hydroxychavicol. Hydroxychavicol is an allylbenzene that has gained much attention due to its anticancer properties. The current study quantified and purified hydroxychavicol from P. betle L. and predicted its anticancer competence through in silico and cytotoxicity studies. Leaf samples of 22 P. betle L. accessions from different locations of Tamil Nadu, India, were analyzed using reverse phase-high performance liquid chromatography for quantification of hydroxychavicol. The highest quantity of hydroxychavicol was obtained from the accession BV22 (89.2%). Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of hydroxychavicol using SwissADME satisfied the physicochemical property guidelines of Lipinski's Rule of Five, ensuring its drug-likeness behavior. Molecular docking studies confirmed the interaction of hydroxychavicol with all 16 tested cancer targets. In Vitro MTT assay of hydroxychavicol in bone cancer cell lines (MG63) also demonstrated the anticancer competency, indicating the requirement to formulate the molecule as a drug in treating various types of cancers.