Explore the vast range of titles available.

A new hydroxychavicol dimer, 2-(g'-hydroxychavicol)-hydroxychavicol (1), was isolated from the roots of Piper betle Linn. along with five known compounds, hydroxychavicol (2), aristololactam A II (3), aristololactam B II (4), piperolactam A (5) and cepharadione A (6). The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

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

Alzheimer’s disease (AD) is a commonly occurring neurodegenerative disease in elderly and it is a leading cause of dementia worldwide. Hydroxychavicol (HC), a major phenolic component of Piper betle, has prominent anti‐inflammatory and antioxidant properties, and studies have found its role in cognition improvement. Here is a systematic approach to deciphering the potential protein targets of HC in AD through network pharmacology and validation from molecular docking and dynamics simulation study. First, the druglikeliness of HC was predicted using the SwissADME analysis, which showed significant druglikeliness. A total of 88 possible target genes between HC and AD were obtained from the Swiss Target Prediction, HIT Version 2, DisGeNET, and GeneCards database. The pathway analysis was carried out using the STRING database which showed several genes including COMT, HSP90AA1, and GAPDH as the top hub genes on the basis of degree. GO and KEGG analyses demonstrated that the core targets were mainly involved in cAMP, PI3K/AkT, HIF1, Rap1, and Calcium signaling pathways. The molecular docking of HC with top hub genes resulted in the highest binding of HC with COMT (−8.9 kcal/mol), GAPDH (−6.7 kcal/mol), and HSP90AA1 (−6.5 kcal/mol) that showed stable binding in the molecular dynamics simulation study. COMT regulates the dopamine levels in the prefrontal cortex and impairment of the COMT is associated with the rapid progression of AD. HSP90, a ubiquitous molecular chaperone, is involved in regulating tau metabolism and Aβ processing and found to be downregulated in AD. GAPDH has been reported as the disease‐susceptible gene in AD and its interaction with amyloid precursor protein and NFTs has also been reported. These findings suggest that HC is a promising therapeutic candidate, targeting multiple AD‐related pathways, warranting further investigation into its molecular mechanisms and potential for clinical application.

Plant-based insecticides are getting attention as an alternative mosquito control strategy because of the emergence of insect resistance to currently used synthetic chemicals. Further, their high safety profile makes them ideal candidates for environmental applications. The current study evaluated the insecticidal potential of Psidium guajava and Piper betle leaf extracts against Aedes aegypti through in vitro and in silico approaches . In laboratory studies, the LC 50 of n-hexane extract of P. guajava and ethyl acetate extract of P. betle were 95.21 ppm and 217.7 ppm after 24-h exposure, respectively. The gas chromatography-mass spectrometry analysis identified important bioactive compounds, including caryophyllene (21.2%), globulol (19.9%), squalene (8.3%), and γ-muurolene (6.6%) in P. guajava and hydroxychavicol (57%), 5-allyl-2-hydroxyphenyl acetate (5.6%), phytol (2.3%), and safrole (1.8%) in P. betle extract. In silico analysis of these compounds with target proteins acetylcholinesterase (AChE), S-adenosylhomocysteine hydrolase (SAHH), and sterol carrier protein-2 (SCP-2) in Ae. aegypti larvae showed that squalene from P. guajava had a higher binding affinity with AChE (–8.4 kcal/mol) compared to globulol (–7.3 kcal/mol). However, conventional hydrogen bonding, which is stronger and more stable, was observed in the globulol-AChE complex. The in silico analysis of P. betle phytochemicals demonstrated that hydroxychavicol, phytol, and safrole had binding affinities of –6.1 kcal/mol, –6.0 kcal/mol, and –6.0 kcal/mol with SAHH, respectively. A minor increase in binding affinity was observed in the safrole-SAHH complex (–6.1 kcal/mol), whereas no change was observed in the 5-allyl-2-hydroxyphenyl acetate-AChE complex (–5.9 kcal/mol) in 2-ligand binding mode. Since these bioactive compounds target the important proteins in the developmental processes of mosquito larvae, they can further be evaluated to design natural and organic insecticides against Ae. aegypti.

Piper betle leaves are widely cultivated in Malaysia, India, Indonesia and Thailand. They have been used as a traditional medicine for centuries due to their medicinal properties, including antioxidant, antiproliferative, antibacterial, antifungal and anti-inflammatory properties, which are attributable to their high phenolic contents. Hydroxychavicol (HC), a primary constituent of P. betle leaves, is known to possess antiproliferative activity at micromolar doses on various cancer cell lines of different origins while leaving normal cells unharmed. The present review summarises the mechanisms of action of HC reported in the literature, reviews the scope of work done thus far and outlines the direction of future research on the potential of HC as an anticancer agent. PubMed, Scopus and Web of Science were searched using the keywords (hydroxychavicol OR 4-allylpyrocatechol OR 4-allylcatechol) AND (cancer OR carcinogenesis OR tumour OR carcinoma) to acquire research articles. In vitro studies reported several possible mechanisms for the chemopreventive effects of HC against cancer cell lines, including chronic myelogenous leukaemia (CML), prostate, glioma, breast and colorectal cancers, while in vivo studies encompassed investigations on Ehrlich ascites carcinoma cells in Swiss albino mice and a CML mouse model. These studies suggest that HC exerts its anticancer effect via the modulation of mitochondrial membrane potential and the c-Jun N-terminal kinase, mitogen-activated protein kinase and endoplasmic reticulum-unfolded protein responses pathways and the generation of reactive oxygen species. In summary, future research should focus on combinations of HC with other anticancer drugs and testing in animal models to evaluate its bioavailability, potency and tissue and dose selectivity.

Emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolated from dogs with cutaneous and wound infections has significantly impacted veterinary medicine. This study aimed to isolate S. pseudintermedius from canine pyoderma and investigate the effects of ethanolic extracts of Piper betle (PB), P. sarmentosum (PS), and P. nigrum (PN) on the bacterial growth and biofilm formation of S. pseudintermedius and MRSP. Of the isolated 152 isolates, 53 were identified as S. pseudintermedius using polymerase chain reaction, and 10 isolates (6.58%) were identified as MRSP based on the presence of mecA. Based on phenotype, 90% of MRSPs were multidrug-resistant. All MRSP had moderate (10%, 1/10) and strong (90%, 9/10) biofilm production ability. PB extracts were the most effective in inhibiting planktonic cells, and the minimum inhibitory concentration at which ≥50% of the isolates were inhibited (MIC50) was 256 µg/mL (256–1024 µg/mL) for S. pseudintermedius isolates and 512 µg/mL (256–1024 µg/mL) for MRSP isolates. The MIC90 for S. pseudintermedius and MRSP was 512 µg/mL. In XTT assay, PB at 4× MIC showed an inhibition rate of 39.66–68.90% and 45.58–59.13% for S. pseudintermedius and MRSP, respectively, in inhibiting biofilm formation. For PB at 8× MIC, the inhibition rates for S. pseudintermedius and MRSP were 50.74–81.66% and 59.57–78.33%, respectively. Further, 18 compounds were identified in PB using gas chromatography–mass spectrometry, and hydroxychavicol (36.02%) was the major constituent. These results indicated that PB could inhibit bacteria growth of and biofilm formation by S. pseudintermedius and MRSP isolated from canine pyoderma in a concentration-dependent manner. Therefore, PB is a potential candidate for the treatment of MRSP infection and biofilm formation in veterinary medicine.

Emerging reports have shown therapeutic potential of hydroxychavicol (HC) and epigallocatechin-3-gallate (EGCG) against cancer cells, however high concentrations are required to achieve the anticancer activity. We reported the synergy of low combination doses of EGCG+HC in glioma cell lines 1321N1, SW1783, and LN18 by assessing the effects of EGCG+HC through functional assays. Using high throughput RNA sequencing, the molecular mechanisms of EGCG+HC against glioma cell lines were revealed. EGCG/HC alone inhibited the proliferation of glioma cell lines, with IC50 values ranging from 82 to 302 µg/ml and 75 to 119 µg/ml, respectively. Sub-effective concentrations of combined EGCG+HC enhanced the suppression of glioma cell growth, with SW1783 showing strong synergism with a combination index (CI) of 0.55 and LN18 showing a CI of 0.51. A moderate synergistic interaction of EGCG+HC was detected in 1321N1 cells, with a CI value of 0.88. Exposure of 1321N1, SW1783, and LN18 cells to EGCG+HC for 24 h induces cell death, with caspase-3 activation rates of 52%, 57%, and 9.4%, respectively. However, the dose for SW1783 is cytotoxic to normal cells, thus this dose was excluded from other tests. EGCG+HC induced cell cycle arrest at S phase and reduced 1321N1 and LN18 cell migration and invasion. Combined EGCG+HC amplified its anticancer effect by downregulating the axon guidance process and metabolic pathways, while simultaneously interfering with endoplasmic reticulum unfolded protein response pathway. Furthermore, EGCG+HC exerted its apoptotic effect through the alteration of mitochondrial genes such as MT-CO3 and MT-RNR2 in 1321N1 and LN18 cells respectively. EGCG+HC dynamically altered DYNLL1 alternative splicing expression in 1321N1 and DLD splicing expression in LN18 cell lines. Our work indicated the pleiotropic effects of EGCG+HC treatment, as well as particular target genes that might be investigated for future glioma cancer therapeutic development.

Ethanol crude extract of Piper betel Linn. (Piperaceae) leaves were tested under in vitro for antifungal activity against plant pathogenic fungi in economic crops. It exhibited 100 percent inhibition against all tested plant pathogenic fungi at a concentration of 1 % using the dilution method whereas inhibition was evident at 10% when tested by the diffusion method. The results suggested that crude extract exhibited fungistasis activity by inhibiting mycelial growth, and fungicidal activity by inhibiting spore germination. Fractionation of crude extract by column chromatography eluted with 51 solvent combination systems of increased polarity yielded 51 micro fractions which were tested for inhibition activity against plant pathogenic fungi in vitro. The micro fractions F4, F5, F7 and F8 showed antifungal activity and the TLC chromatogram indicated the common compounds were contained in these four fractions. Further re-fractionation of the most active fractions, F7 and F8 were eluted with mixture of petroleum ether and chloroform and tested for antifungal activity. The 21 submicro fractions of PE: CHCl3 at ratio of 40:60 to 32:68 exhibited antifungal activity with the same results as in the former experiment. The TLC chromatograms indicated the presence of the like compounds and it is suggested that the active compounds might be contained in these sub micro fractions of PE: CHCl3. The dosage response curve indicated a positive linear relationship between concentrations and the level of antifungal activity. NMR (Nuclear Magnetic Resonance) spectroscopy was conducted to elucidate the chemical structure of the active compound contained in the fractions F7 and F8 which was identified as hydroxychavicol. The study concluded that hydroxychavicol in the crude extract from P. betel leaves is an active constituent against plant pathogenic fungi.

Background: Avian pathogenic Escherichia coli (APEC) is a leading cause of colibacillosis in poultry. Piper betle L. is a medicinal plant rich in bioactive compounds including hydroxychavicol that possess potent antibacterial activity. This study aimed to investigate the efficacy of a P. betle L. leaf nanoemulsion (NEPE) and hydroxychavicol against multidrug-resistant APEC isolates. Methods: In vitro and in silico analysis of NEPE and hydroxychavicol against APEC were determined. Results: The nanoemulsion exhibited potent antibacterial activity, with MIC and MBC values of 0.06–0.25% v/v and 0.125–0.25% v/v, respectively. The MIC and MBC values of hydroxychavicol against isolates ranged from 0.25 to 1.0 mg/mL. A time–kill assays revealed rapid bactericidal effects of both compounds, achieving a ≥3-log reduction within 4 h at 4 × MIC. Scanning electron microscopy demonstrated that APEC cells treated with hydroxychavicol exhibited filamentous cells with incomplete septa. Molecular docking and dynamics simulations of hydroxychavicol against APEC cell division proteins were investigated. According to the binding energy, hydroxychavicol exhibited the highest affinity with ZapE, FtsW, FtsX, FtsZ, and FtsA, respectively. However, the FtsA protein showed the least protein conformational change throughout the 5000 ns simulation, reflecting a highly stable conformation. Conclusions: These confirm the potential stability of protein and ligand, as supported by molecular dynamics simulation. The results suggested the potential of NEPE and hydroxychavicol, which may have promising antibacterial potential that can be used to inhibit APEC growth.

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-β, and a mixture of SB431542 and TGF-β. The activity was stronger in TGF-β-treated cells than in DMSO-treated cells. In the mixture of SB431542 and TGF-β-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. Graphical abstract