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Piper retrofractum Vahl contains piperine compounds that, once extracted, have the disadvantages of low solubility and bioavailability. The enhanced solubility will significantly impact the absorption of medications in the body, resulting in rapid and noticeable results. Nanoparticle technology was developed to overcome this problem. The research aims to obtain optimum conditions for synthesizing Javanese long pepper extract nanoparticles under optimal particle size, Polydispersity Index (PDI), and piperine content. The research employed the Response Surface Methodology (RSM) method utilizing Central Composite Design (CCD) with a ratio factor of chitosan:STTP and the stirring speed. The utilization of RSM facilitated the optimization of nanoparticle manufacturing by considering various treatment parameters. RMS was selected due to its relevance as a tool for optimizing the manufacturing process of nanoparticles. The RMS result represents the optimal state of the nanoparticle manufacturing process, effectively addressing the study objectives. The research findings indicated that the most favorable circumstances for producing nanoparticles from Javanese long pepper extract were achieved with a chitosan:STTP ratio of 3,241:1 and a stirring speed of 826,133 rpm. The nanoparticles were obtained under these specific conditions, resulting in an optimal particle size of 33,884 nm, an optimal Polydispersity Index (PDI) of 0.675, and an optimal piperine content of 26,936%. This research provides valuable insights for the community and the pharmaceutical/herbal sector regarding using piperine compounds as therapeutic substances. Specifically, it highlights their potential to enhance bioavailability and absorption in the body.

Antioxidants are considered important in maintaining the balance of free radicals in the body due to exposure to air pollution. Piper retrofractum Vahl which is a traditional Indonesian medicinal herb which is said to have the characteristics of being an antioxidant in preventing free radicals in the body. Therefore, this research aims to investigate possible interactions between new amides of Piper retrofractum Vahl. and Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Molecular docking study, using molecular mechanic calculations with Yasara to investigate binding energy and pkCSM to predict ADMET. Results this study showed that dipiperamides F has binding energy of 9.855 kcal/mol (closest to that of the crystallographic ligands), dipiperamides G (9.543 kcal/mol), piperodione (8.448 kcal/mol), (E)-N-cinnamoyl-2-methoxypiperidine (7.560 kcal/mol), (2E, 12E)-pipertride cadienamid (7.084 kcal/mol), N-isobutyl-(2E, 4E, 10Z)-hexadeca-2, 4, 10-trienamide (6.788 kcal/mol), (R)-1-(2-oxopyrrolidin-3-yl)-5, 6-dihydropyridin-2(1H)-one (6.524 kcal/mol), 2E, 14Z)-N-isobutyleicosa-2, 14-dienamide (5.116 kcal/mol). Visualization of receptors-ligands complex showed data on hydrogen bonds and no-covalen interactions, including hydrogen bond distances. Finally, ADMET (Adsorption, Desorption, Metabolism, Excretion, Toxicity) predictions and drug-likeness properties were performed on the tested compound. Our study indicates that new amides from Piper retrofractum Vahl may behave as potential natural antioxidant agents by targeting the Keap1 inhibitor.

Hard candy was made from the mixture of sucrose, glucose, and water. However, the excessive intake of sucrose can cause serious dental problems such as dental caries. Sucrose in hard candy formula is replaceable, using xylitol with the calory content of 40% lower than sucrose, while it also supresses the bacterial growth of Streptococcus mutans causing dental caries. Hard candy functionality is improved by addition of Javanese long pepper extracts containing various chemicals such as alkaloid, saponin, and piperin found up to 4-6%, and they exert antibacterial activity. This current work characterized the quality (i.e., color, pH, solubility time, sensory) of sucrose-free hard candy supplemented with Javanese long pepper extracts, and evaluated the antibacterial effect against Streptococcus mutans causing dental caries. The experiment followed a non-factorial completely randomized design consisting of different proportions of xylitol and glucose: 0:50, 30:80, 35:85, and 20:90, carried out at triplicates. As a result, the higher concentration of xylitol positively affected the characteristics of sucrose-free hard candy, including color, pH, and sensory properties. In addition, the concentration of xylitol showed positive impact to inhibition of Streptococcus mutans .

The differences in VOCs can affect the flavor and medicinal value of cabya, and the flavor changes that occur in stages as the fruit develops are currently unknown. In order to investigate the influence of the developmental stage on the aroma composition of cabya essential oil, VOCs at each of the four developmental stages were analyzed by steam distillation (SD) extraction combined with GC-MS detection. The similarities and differences in fruit composition among the developmental stages were evaluated using hierarchical cluster analysis (HCA) and principal component analysis (PCA). A total of 60 VOCs, mainly alcohols, alkenes and alkanes, were identified across all of the developmental stages. The most acidic substances were detected in phase A and have a high medicinal value. There was no significant difference between the B and C phases, and the alcohols in those phases mainly promoted terpenoid synthesis in the D phase. Constituents during the D phase were mainly alkenes, at 57.14%, which contributed significantly to the aroma of the essential oil. PCA and HCA both were able to effectively differentiate the cabya fruit developmental stages based on the SD-GC-MS data. In summary, this study investigated the flavor variation characteristics and the diversity of VOCs in cabya fruits at different developmental stages, and its findings can provide a reference for developing essential oil products for different uses and determining appropriate stages for harvesting cabya resources.

Covid-19 is caused by aetiological agent for SARS-CoV-2. The disease has caused pandemic responsible for deaths and economic loss worldwide. Therefore, novel drugs of covid-19 primarily using herbs are urgently needed. Cabya (Piper retrofractum Vahl.) is a popular spice and also traditionally applied for herbal medicines. This study conducted an in silico experiment to screen methanolic active compounds in cabya and test their inhibitory activities against main protease enzyme (M pro ) as receptor of SARS-CoV-2. The in silico approach complied with molecular docking protocols enabling to evaluate performance of the compounds to inhibit M pro . Two common drugs were used as control, i.e. chloroquine and ivermectin. As the results, molecular docking showed a promising inhibition by active compounds in cabya; in this regard, beta-sitosterol demonstrated the strongest inhibition against Mpro with binding affinity -7,5 kcal/mol, which is better than chloroquine (-4.8 kcal/mol) and close to ivermectin (-8,5 kcal/mol). The interaction resulted from two hydrogen bonds with amino acids ARG A131 and ASP A289 at distance of 15Å and 2,49 Å, respectively. The inhibition site of beta-sitosterol was similar to that of ivermectin. This research revealed the potential use of cabya for covid-19 treatment through restriction of molecular binding between virus and receptor.

Bacterial endophytes associated with a Thai medicinal plant, Piper retrofractum Vahl, were investigated. Twenty-one isolates of endophytic bacteria were obtained from three different parts (root, leaf and stem) of P. retrofractum. According to amplified ribosomal DNA restriction analysis patterns and 16S rRNA gene sequence, the endophytic bacteria isolated in this study belong to 11 families, 14 genera and more than 18 species, with one uncultured isolate. Several of the bacteria are in the genera Pseudomonas and Bacillus. Two isolates, S-PR6Y and S-PR1Y, show antagonistic properties against methicillin-resistant Staphylococcus aureus (MRSA). A partially purified antibacterial agent from Lysobacter sp. (isolate S-PR6Y) shows remarkable stability to heat and pH. It has the potential for use as an alternative antibacterial agent for the treatment of infection with MRSA.

To reduce population growth, the Indonesian government promotes a Family Planning Program for fertile couples. Depot-medroxyprogesterone acetate (DMPA) combined with testosterone or herbal androgens as testosterone substitute is intended for hormonal male contraception because it is expected that these combinations can suppress gonadotropin and inhibit spermatogenesis. Various medicinal herbs contain androgens, e.g., Javanese long pepper (JLP) ( Piper retrofractum Vahl). Traditionally, JLP chili extract (JCE) is used to cure impotency and was proven to increase blood testosterone levels in hypogonad men. The aim of this study is to combine increasing amounts of JCE (0.94 – 3.76 mg) with DMPA (1.25 mg) and to study the effects on testicular parameters using male Sprague-Dawley rats: testis weight, seminiferous tubule diameter, the subpopulations of spermatogenic cells, and Leydig cells. Our randomized study design used six equally sized groups with 6 animals, each. Testis weight only decreased vs. controls in two groups, DMPA + placebo and DMPA + 3.76 mg JCE. Significant decrease occurred in the diameter of seminiferous tubules and at 3.76 mg JCE, in Leydig cell population. Within spermatogenic cell population spermatogonia A, spermatocyte-I preleptotene, spermatocyte-I pachiten, and spermatid population decreased. The combination of 1.25 mg DMPA and 3.76 mg JCE appears to be the minimal dose and a potent candidate for male contraception in our rat model.

Long Pepper ( Piper retrofractum Vahl ) is a leading agricultural commodity on Madura Island that contributes significantly to national and export demand. Despite its great potential, long pepper farming faces challenges threatening its sustainability, such as price fluctuations, limited access to capital, water availability problems, and pest attacks. This study aims to analyze the sustainability of long pepper farming in Madura by paying attention to economic, social, and ecological dimensions. The research methodology uses a quantitative and qualitative approach (mixed method) through an explanatory sequential design. Data was collected from interviews involving 46 farmers in Sumenep Regency. The result showed that the long pepper’s sustainability status for the ecological dimension is less sustainable (46.9), the economic dimension is less sustainable (43.1), and the social dimension is quite sustainable (51.3). The recommendation is to strengthen farmer institutions through the intensiveness of farmer groups and extension, which is also the most significant value of the attribute that affects the dimension.

This research aimed to determine the effectiveness of Piper retrofractum extract on Spodoptera frugiperda , including larval mortality, feeding inhibition, and ovicidal activities. The study was designed using a completely randomized design (CRD). The test used the dipping method with 5 concentration levels (0.0, 0.03, 0.05, 0.08, 0.12, and 0.25%) which were repeated 5 times. The feeding inhibition test was carried out using a choice method with concentrations equivalent to LC 15 , LC 35 , and LC 55. The ovicidal test was carried out by spraying the extract solution on the egg group using concentrations equivalent to LC 95 and 2 x LC 95 . The results showed that P. retrofractum extract caused a high mortality rate to the second instar larvae of S. frugiperda with LC 50 and LC 95 values of 0.06% and 0.26%, respectively. In addition, the ovicidal activity at LC 95 and 2 x LC 95 concentrations also showed a high inhibition percentage of 81.38% and 94.67%, respectively. Meanwhile, the feeding inhibition activity of P. retrofractum extract was categorized as weak, with a maximum inhibition of 51.04% observed at LC 55 .

Ferrisia virgata is one of the mealybugs that are often found on black pepper and other horticultural and state crop plantations. This mealybugs is a piper yellow mottle virus (PYMoV) vector. Botanical pesticides can be used as an alternative to control this insect vector. One of the plant materials that can be used to control F. virgata is Javanese long pepper ( Piper retrofractum ). This study aimed to investigate the insecticidal activity of ethyl acetate extract of P. retrofractum fruits (Ea-Pr) against female adults of F. virgata using insect spray and leaf dipping methods. The results showed that the Ea-Pr extract tested using the insect spray method was more effective than leaf dipping as indicated by a lower lethal concentration (LC) value. The LC 50 and LC 95 values of the Ea-Pr extract with the insect spray method against female adults of F. virgata were 0.23% and 1.74%, respectively. Meanwhile, the LC 50 and LC 95 values of Ea-Pr extract with leaf dipping method were respectively 2.23 and 5.90 times higher than the insect spray. Therefore, Ea-Pr extract can be further developed as an effective botanical insecticide against F. virgata .