Piper Crocatum Research Articles

GARGLING WITH RED BELT LEAF BOILING (PIPER CROCATUM) ON SALIVA pH IN STUDENTS SMP NEGERI 4 PINELENG MINAHASA DISTRICT

Abnormalities in the mouth or dental and oral diseases that occur in a person are usually caused by several factors. The intra-oral and extra-oral environment greatly influences a person's dental and oral health. To maintain healthy teeth and mouth, it is necessary to control saliva, because saliva or saliva in the mouth plays an active role in supporting healthy teeth and mouth. If there is a decrease in saliva pH, it can cause rapid demineralization of tooth elements, while an increase in pH can result in bacterial colonization which deposits and increases the formation of tartar. One way to control the pH of saliva is to gargle with boiled red betel leaves, because they contain compounds that are antibacterial. This study aims to determine the effectiveness of gargling with boiled red betel leaves (piper crocatum) on saliva pH in students at SMP Negeri 4 Pineleng, Minahasa Regency. This research uses a quasi-experimental method with a one group pre and post-test design. This research was carried out by giving treatment to respondents and measuring the pH of saliva before and after gargling with boiled red betel leaves. The sample in this study was 72 students, using random sampling techniques. Data collection was obtained from the results of salivary pH measurements using universal pH test paper with criteria 0-14, the concentration of red betel leaves used in this study was 15%. The data obtained were analyzed using the Wilcoxon test. Based on the results of the Wilcoxon test, it was found that ? value=0.027 (0.027<0.05), so it can be concluded that gargling with boiled red betel leaves is effective in changing saliva pH.

Benefits of Betel Leaves as a Medicine for Postpartum Perineal Wounds

Indonesia is a country rich in natural materials for human health. One of them is red betel. This research was conducted to formulate red betel as a medicine for perineal wounds in mothers after childbirth. Making wound medicine by boiling. Boil 4-5 sheets or 9-11 grams (Piper Crocatum) that have been washed thoroughly, put 500 ml of water into a pot made of clay so as not to damage the substance content of red betel leaf (Piper Crocatum). Wait for it to boil for 15 minutes. Let the boiled water cool for 30 minutes, then strain the water and put the filtered result in the sterile bottle that has been provided. After that, respondents will use boiled water with red betel leaves (Piper Crocatum) after taking a shower in the morning and also in the afternoon. After finishing, the respondent will dry his female intimate organs with a towel until dry. Rinse the boiled water of red betel leaves (Piper Crocatum) once a scoop is given as much as 200 ml for one use.

Formulation of Micellar Based Water from Piper crocatum Leaves Extract Using Various Concentrations of Poloxamer 188

Formulation of Micellar Based Water from Piper crocatum Leaves Extract Using Various Concentrations of Poloxamer 188

Comparison of binahong <em>(Anredera cordifolia) (Ten. Steenis)</em> and red betel <em>(Piper crocatum)</em> leaves ointment formulations toward length of laceration and bleeding time in rats

Laceration is a condition in which the structure of body tissue is damaged as a result of the body being slashed by sharp objects such as knives, razors, or cutters. One plant that can be applied to laceration is binahong leaves (Anredera cordifolia (Ten.) steenis and red betel (Piper crocatum). This plant contains a variety of active compounds, including alkaloids, saponins, and flavonoids. This present study aims to determine the effectiveness comparsion of the formulation and the difference in optimal concentrations of binahong and red betel leaf extract ointment formulation for incision healing with concentrations of 7%, 15%, and 30%. Here, Wistar rats incision were compared with ointment extract. To assesses the healing process with length of laceration and bleeding time. Incision demonstrated the elevated length of laceration and bleeding time. In contrast, animals received ointment extract demonstrated better for length of laceration and reduced the bleeding time. Taken the ointment extract, our results suggest ointment extract binahong and red betel leaves exhibit antioxidant and increase the collagen activity which may contribute to the heal of incision.

Total Phenolics, Flavonoids, and ɑ-Glucosidase Inhibitory Activity of Red Betel (Piper crocatum) Extract in Various Solvents

Alpha-glucosidase enzyme activity needs to be inhibited to avoid increasing blood sugar levels in diabetics. Red betel leaf extract is reported to have active compounds such as phenolics and flavonoids that have alpha-glucosidase enzyme inhibition activity. Previous research showed that 70% betel leaf extract has an ɑ-glucosidase enzyme inhibition activity of 69.84%, but it is not yet known how the effect of extracts with different levels of polarity on the inhibition activity of alpha-glucosidase enzyme. This study aimed to determine extracts that have optimal levels of phenolic and flavonoid content and the highest suppression of α-glucosidase activity. The multistage maceration method was used to extract red betel leaf simplicia using solvents with different levels of polarity (n-hexane, ethyl acetate, methanol). Tests were conducted on overall phenolic concentration, flavonoids, and ɑ-glucosidase inhibition ability. Data were analyzed using one-way ANOVA test with Tukey's further test (p<0.05). The results of the assessment of phenolic concentration, flavonoids, and α-glucosidase inhibitory activity as a whole showed statistically significant differences (p<0.05) in all extracts with the highest total phenolic and flavonoid content found in the n-hexane extract of 25.68 ± 0.29 mg GAE/g and 65.84 ± 0.96 mg QE/g respectively. Meanwhile, methanol extract of red betel leaf became the best extract in this study with the greatest inhibition among all extracts with a percent α-glucosidase inhibition value of 43.87 ± 1.83%.

FORMULATION OF RED BETEL LEAF EXTRACT LOTION (Piper crocatum Ruiz & Pav) AS SUNSCREEN

Betel leaf is a natural ingredient that people use as a traditional medicine. One of the ingredients found in red betel leaves is a phenolic compound in the form of flavonoids, a photoprotective substance that can be used as protection from UV radiation. Sunscreen is a cosmetic preparation that can protect the skin from UV radiation and reduce the amount of radiation harmful to the skin. This study aimed to formulate a lotion preparation from red betel leaf extract that has activity as a sunscreen. Red betel leaf (Piper crocatum Ruiz & Pav) was extracted using the maceration method. Preparation formulations were made with variations of red betel leaf ethanol extract in each formula, namely with concentrations of 0.04% (F1), 0.05% (F2), 0.06% (F3), and base control (F0). The activity of sunscreen lotion extract is based on the Sun Protection Factor (SPF) value using UV-VIS spectrophotometry at wavelengths of 290–320 nm using the Mansur equation. The results of the SPF value of the lotion are F1 of 13.48, F2 of 16.71, and F3 of 18.7. The evaluation of the lotion results obtained a light green lotion with M/A emulsion type that met the requirements, including homogeneity, pH, spreadability, viscosity, centrifugation test, and freeze and thaw test. Research results show that betel leaf extract lotion is physically stable and has a high SPF value, so it has the potential to be a sunscreen.

Effects of Piper crocatum leaf extract-based ointments on bacteria associated with diabetic ulcers: an in vitro study

Effects of Piper crocatum leaf extract-based ointments on bacteria associated with diabetic ulcers: an in vitro study

EFFECTIVENESS OF RED BETEL (PIPER CROCATUM) EXTRACT ON LEUCORRHEA IN WOMEN OF CHILDBEARING AGE

Introduction: Reproductive health problems exist in Asia; 76% of women experience vaginal discharge. Vaginal discharge symptoms are also experienced by women of childbearing age (around 31.8%). Women of childbearing age are more at risk of fluor albus, which can be a trigger for reproductive organ infections. One of the treatments is to use betel leaves, which contain natural antiseptics and antibiotics. Objectives: This study aimed to determine the effectiveness of red betel leaf extract (Piper crocatum) against leucorrhea in women of childbearing age. Method: This research method uses a quasi-experiment design with one pre-and post-test design technique group. The research was conducted at the Independent Midwife Practice in Bandung City. The population in the study were all women of childbearing age in Bandung City. The sample consisted of women of childbearing age, according to the inclusion criteria of 36 people. The data obtained were primary data from the measurement of vaginal pH with Neco test litmus paper. The data analysis used was the Wilcoxon test to test the difference in pH scores before and after the intervention. Result: The results showed a significant difference in the use of 0.5% red betel leaf extract in women of childbearing age before and after the intervention. Conclusion: Red betel leaf extract 0.5% is effective in reducing the incidence of leucorrhea. There is a decrease in vaginal pH before and after the use of red betel leaf extract 0.5% by 1.78 (p <0.05).

Quantification of Total Phenol Concentration in Ethanol Extracts of Red and Black Betel Leaves Using UV-Vis Spectrophotometric Method

Red betel (Piper crocatum Ruiz & Pav) and black betel leaves (Piper betle var. nigra) are plant varieties known for their medicinal properties. These plants have various contents including flavonoids, essential oils, tannins and polyphenols. The objective of this research is to ascertain the quantity of phenolic compounds present in ethanol extracts of red and black betel leaves. Determination of the levels of ethanol extracts of red and black betel leaves is done quantitatively by the folin-ciocalteu method. This method relies on the formation of a blue complex compound of of phosphomolybdat-phosphotungstat, generated by the reduction of phenolic compounds in an alkaline environment. The measurement is performed using uv-vis spectrophotometry. Gallic acid, derived from hydroxybenzoic acid and identified as a simple phenolic acid, is employed. This stable and pure polyphenolic compound is commonly found in almost all plants. Drawing conclusions from the study results, it can be affirmed that the average total phenol concentration of red betel was 31.87 GAE per gram extract and the average total phenol concentration of black betel leaves was 39.09 mg GAE per gram extract.

Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper crocatum Ruiz & Pav.

The WHO Global Status Report on Oral Health 2022 reveals that oral diseases caused by infection with oral pathogenic microorganisms affect nearly 3.5 billion people worldwide. Oral health problems are caused by the presence of S. mutans, S. sanguinis, E. faecalis and C. albicans in the oral cavity. Synthetic anti-infective drugs have been widely used to treat oral infections, but have been reported to cause side effects and resistance. Various strategies have been implemented to overcome this problem. Synthetic anti-infective drugs have been widely used to treat oral infections, but they have been reported to cause side effects and resistance. Therefore, it is important to look for safe anti-infective alternatives. Ethnobotanical and ethnopharmacological studies suggest that Red Betel leaf (Piper crocatum Ruiz & Pav) could be a potential source of oral anti-infectives. This review aims to discuss the pathogenesis mechanism of several microorganisms that play an important role in causing health problems, the mechanism of action of synthetic oral anti-infective drugs in inhibiting microbial growth in the oral cavity, and the potential of red betel leaf (Piper crocatum Ruiz & Pav) as an herbal oral anti-infective drug. This study emphasises the importance of researching natural components as an alternative treatment for oral infections that is more effective and can meet global needs.

Formulation and evaluation of antibacterial activity of hand sanitizers containing red betel (Piper crocatum) and white galangal (Alpinia galanga) extract

Background: The COVID-19 outbreak has changed how people live worldwide, making hand hygiene a must, whether it involves hand sanitizer (HS). The majority of HS are made of alcohol. Several side effects of alcohol are dryness and allergies. Alternative natural ingredients and HS are needed. Red betel (Piper crocatum) and white galangal (Alpinia galanga) are familiar and easy to be found. These two plants have the potential to be the composition of HS because of their compounds, such as antioxidants, antibiotics, antifungals, and antivirals. However, there is a need for further research on their formulation and effectiveness in germ-killing.Purpose: To formulate and identify the antibacterial activity of HS containing red betel and white galangal extract.Method: This research was an in vitro laboratory experiment with several steps, including extraction, specific and nonspecific tests, formulation, and antibacterial activity tests.Results: Red betel and white galangal leaves had been extracted at a concentration of 10% and formulated into HS. The HS containing 10% red betel extract produced an inhibition zone of 0 mm against E. coli and 1.05 mm against S. aureus, and the HS containing 10% White galangal extract produced an inhibition zone of 1.47 mm against E. coli and 1.40 mm against S. aureus.Conclusion: The formulation of HS containing 10% of white galangal extract is more effective than the HS containing 10% of Red betel extract.

Phytochemical Analysis of Red Betel (Piper crocatum Ruiz & Pav) Stem Extracts and its Antioxidant and Alpha-Glucosidase Inhibitory Potentials

Phytochemical Analysis of Red Betel (Piper crocatum Ruiz & Pav) Stem Extracts and its Antioxidant and Alpha-Glucosidase Inhibitory Potentials

Formulation and Determination of Tannin and Flavonoid Levels of Anti-Acne Gel Formulation from Red Betel Leaf Extract (Piper crocatum)

Acne is a common skin condition that often occurs among teenagers and adults aged 18-23 years. Acne can be triggered by several factors, genetic, psychological, weather, stress, cosmetics, and bacterial infections. In addressing the problem of acne, a good dosage form to use is a gel preparation. Acne skin care by utilizing natural ingredients, one of which is red betel leaf. Red betel leaf contains phytochemical compounds, namely tannins and flavonoids, which function as antibacterial agents. The formulation of anti-acne gel is designed by varying the concentration extract, F0 (0%), F1 (10%), F2 (15%), and F3 (20%), with the aim of determining the best anti-acne gel formulation. Red betel leaf extract is tested for tannin and flavonoid levels using the UV-Vis Spectrophotometer test method. The gel preparation is examined, including organoleptic testing, pH testing, homogeneity testing, and spreading testing. The research results show that red betel leaf extract has a tannin content of 4.7056% and a flavonoid content of 0.0934%. The results of the anti-acne gel preparation study meet the requirements for organoleptic properties, pH, homogeneity, and spreading. Based on the results of various concentrations of extract, satisfactory results are obtained, with formulations F2 and F3 meeting the requirements.Acne; Gel; Extract; Piper crocatum

In Vivo Uricosuric Effect of Red Betel Leaves (Piper crocatum RUIZ & PAV) Ethanol Extract

Hyperuricemia a condition where a person has high levels of uric acid in the blood. Red betel (Piper crocatum RUIZ & PAV) is a plant empirically used to reduce uric acid levels. This study aimed to determine the effective dose of red betel plant in reducing urinary uric acid levels in male Wistar rats with hyperuricemia. Hyperuricemia condition was obtained by giving chicken liver juice 25 mL/kg orally and potassium oxonate 250 mg/kg intraperitoneally. Red betel extract (RBE) is made by maceration using 50% ethanol. Male Wistar rats were divided into five groups: negative control (CMC-Na 0.5%), Positive control (Probenecid 4, 5 mg/kg), and extract at doses 11.5, 23 and 46 mg/kg. The results showed that the RBE increased uric acid secretion through urine (uricosuric) compared to controls. The optimal dose for the uricosuric effect of the extract is 46 mg/kg, although this effect is lower than probenecid. Keywords: Red betel, uric acid, potassium oxonate, uricosuric

Secondary Metabolite Profile in Mature and Old Leaves of Four Piper Species: Forest Betel (Piper aduncum L.), Red Betel (Piper crocatum Ruiz & Pav.), Javanese Chili Betel (Piper retrofractum Vahl.), and Green Betel (Piper betle L.)

Piper species is a potential medicinal plant, empirically known for its effectiveness in curing various diseases, particularly in Indonesia. Therefore, this research aimed to evaluate the similarities and differences in the profile of secondary metabolite compounds in mature and old leaves of four Piper species using Gas Chromatography-Mass Spectrometry (GC-MS). The analysis was also carried out to identify the specific compounds found in each species at different leaf development stages. Samples used were mature and old leaves from four species of Piper, namely forest betel (Piper aduncum L.) (PA), red betel (Piper crocatum Ruiz & Pav.) (PC), Javanese chili betel (Piper retrofractum Vahl.) (PR), and green betel (Piper betle L.) (PB). Subsequently, samples were extracted using ethanol solvent and secondary metabolite profile was detected through GC-MS. A total of 40 secondary metabolite compounds were found in mature and old leaves of four species. The results showed that alkaloid content contributed 25% of the total compounds detected, while fatty acids yielded the largest portion (27.5%). Based on PCA score plot analysis, a significant grouping of secondary metabolite compounds was observed in all species, where PC was categorized separately on the right, and the other species were on the left. Several specific compounds were also found only in one species and not in others. Similar to mature and old leaves, some compounds were discovered in one of the developmental phases. Dillapiole and hexadecane were only found in PA, both in mature and old leaves; germacrene A, eugenol, and chavicol were found in mature and old leaves of PB, but beta-selinene, delta-guaiene, and linolelaidic acid were only found in mature leaves. In PC, there were specific compounds namely benzofuran, myrcene, and 1,6,10-dodecatrien that were found in mature and old leaves. Besides that, trans-ocimene and alpha-bisabolol were only found in old leaves of PC. In PR, only tetracosane was found in mature leaves, while piperidine, octanodecanoic acid, and benzylmalonic acid were found in old leaves.

H Hepatoprotective Activity of Piper crocatum (Ruiz &Pav.) Leaves Against Monosodium Glutamate -Induced Hepatotoxicity in Rats

Monosodium glutamate (MSG) is widely used as additive in food. Excess consumption of MSG was reported to cause oxidative stress on liver resulted increased production of reactive oxygen species (ROS). Without proper treatment, it can induce liver injury and fatal hepatic diseases, including cirrhosis. Red betel (Piper crocatum Ruis and Pav.) is one of Indonesia’s medicinal plants that has been known to exhibit antioxidant activity. The current study evaluated hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury. Animals (n=5 per group) were randomly divided into five groups as follows: Group 1, control (distilled water); group 2, negative control, receive 7 mg/kg bw of MSG; group 3, receive oral 7g/kg b.w of MSG plus 200 mg/kg bw RBLE; group 4, receive oral 7g/kg b.w of MSG plus 400 mg/kg b.w RBLE and group 5, receive oral 7g/kg b.w of MSG plus 600 mg/kg b.w RBLE. The rats were sacrificed on twenty-ninth day of the experiment. Measuring serum levels of aspartate aminotransferase (AST) and alanin aminotransferase (ALT) was done. Histopathological examination of liver was performed by calculated necrosis cell percentage. RBLE treatment (200 mg/kg b.w) decrease alanin aminotransferase and aspartate aminotransferase demonstrated increased compare to negative control. The histological findings revealed RBLE treatment were also able to decrease necrosis cells percentage. The study was able to demonstrate that RBLE treatment could decrease necrotic cell percentage. Low concentration of RBLE (200 mg/kg b.w) exhibit best anti-inflammatory properties and had the lowest ALT enzyme and increased live cell percentage by shifting cell death pathway from necrosis to apoptosis, and these indicating its antioxidant properties. These results could be used as a baseline in the purification of red betel bioactive components to be used for liver injury medication.
 Key words: Antioxidant, hepatoprotective, histopathology, liver enzymes, MSG, red betel.

Matrix Metalloproteinase-9 Testing of Golden Rice Cookies With Piper Crocatum Active Extract for Preventing Foot Ulcers in Patients With Diabetes: Protocol for a Randomized Controlled Trial.

Diabetic foot ulcers (DFUs) present a formidable challenge to both patients and health care systems. DFUs significantly reduce the quality of life for patients, prolong hospital stays, and are the cause of approximately 70,000 lower limb amputations across the globe annually. Prevention of DFUs primarily involves the optimization of blood sugar levels and the effective management of complications, particularly peripheral neuropathy. Golden Rice has been proven to lower blood sugar levels due to its beta-carotene content, and Piper crocatum (P. crocatum) has been found to be effective in reducing the risk factors of DFUs through biomolecular regulation because of its polyphenol content. The principal objective of this study is to identify the efficacy of P. crocatum-enriched cookies, with Golden Rice as their primary ingredient, in preventing DFUs. The evaluation will center on their impact on the expression of matrix metalloproteinase-9 (MMP-9), a pivotal factor in the development of DFUs. This study is an experimental clinical research that follows the randomized controlled trial method and uses a single-blind design. The participants in the study are outpatients from primary health centers in Makassar, Indonesia, who have been diagnosed with diabetes mellitus. The sample for the study will be randomly selected and subsequently categorized into 2 groups: the intervention group and the control group. The intervention group consumes P. crocatum-enriched Golden Rice cookies, while the control group receives cookies without these additives. The participants from both groups will consume their respective cookies (packaged identically) twice a day for 14 days. The cookies will be prepared according to a modified recipe with an emphasis on low glucose content, resulting in 51 calories per cookie, comprising 1% carbohydrates, 6% fat, 4% cholesterol, and 4% fiber, excluding gluten, sugar, and salt. They will be baked at 158°C for 20 minutes. The process involves the addition of 20% Golden Rice and 10% P. crocatum ethanol extract, both prepared via maceration with 96% ethanol. The dependent variable in this study is the expression of gelatinases matrix metalloproteinase, to be assessed at 2 distinct time points-preintervention (pretest) and postintervention (posttest)-with the evaluation conducted through the western blotting method. The recruitment and testing phase started in January 2024. The study is scheduled to be completed by the end of March 2024. Data analysis will commence in April 2024, and the publication of the results is anticipated in the same year (2024). The study will report on the changes in primary data, encompassing gelatinases matrix metalloproteinase, as well as secondary data, including the ankle-brachial index, neuropathy score, and random blood glucose level. The findings of this trial are expected to significantly impact the selection of strategies by health care practitioners to enhance diabetes self-management, particularly in the domain of therapeutic snacking, for patients diagnosed with diabetes mellitus. Thai Clinical Trials Registry TCTR20230502001; https://www.thaiclinicaltrials.org/show/TCTR20230502001. PRR1-10.2196/49940.

The Effect of Boiled Water Concentration of Red Betel Leaf (Piper crocatum) on the Kidney and Pancreas Histopathology of Diabetic Mice (Mus musculus)

The Effect of Boiled Water Concentration of Red Betel Leaf (Piper crocatum) on the Kidney and Pancreas Histopathology of Diabetic Mice (Mus musculus)

Subchronic Toxicity Testing of Ethanol Extract of Red Betel Vine (Piper crocatum) Leaves in DDY Strain Mice

Background: The red betel vine (Piper crocatum) is a plant that has potential as a medicinal plant. The use of medicinal plants should be tested for safety. Acute toxicity testing has been performed with safe results for consumption, but there is no known long-term effect on various organs.Objective: To determine whether an ethanol extract of the red betel vine could be used safely on different parts of DDY mice.Methods: The treatment of ethanol extract was performed orally every day by using a feeding tube with different doses in mice within 3 months. Those were divided into several groups, each consisting of 5 male and 5 female mice. The dosages used consisted of 50 mg/kgBW, 100 mg/kgBW, 200 mg/kgBW, and 400 mg/kgBW, with aquadest and solvent as controls. The treatment was done every day for 3 months. At the end of the study, the mice were terminated, and their organs were collected, which included the spleen, liver, kidney, heart, lungs, brain, testes, and ovaries.Results: The results of this study show no significant difference compared to controls in all organs. There are liver changes from cloudy swelling degeneration and reversible hydropic degeneration, but the effect is reversible.Conclusion: To conclude, long-term use of the red betel vine as a medicinal plant can be recommended for healthy people but not for people with a history of hepatic disorders.International Journal of Human and Health Sciences Vol. 08 No. 01 Jan’24 Page: 69-74

Molecular Dynamics Simulation of Various Bioactive Compounds of Red Betel (Piper crocatum) as Anti-Inflammatory Drug-Like Candidates in Rheumatoid Arthritis Treatment

Joint inflammation and damage can be caused by rheumatoid arthritis (RA), a systemic autoimmune disorder. Long-term RA affects the joints, causing pain, edema, and stiffness. Several studies have revealed that the exact origin of RA is still unidentified, but inherited disorder and external factors may contribute to the inflammatory condition. The incidence of RA is mostly caused by uncontrolled-production of pro-inflammatory cytokines under nuclear factor-kappa B (NF-κB) overexpression condition. The nuclear factor-kappa B plays an important role in inflammatory T cell activation, differentiation, and effector function. Therefore, the inhibition of NF-κB can be a strategy to reduce the adverse effects or incidence of RA. Red betel is a perennial herb native to Indonesia that is widely used by conventional healers. Many reports show that red betel leaf extracts contain several critical bioactive compounds such as Apigenin, Luteolin, Hydroxychavicol, Eugenol, and Chavibetol. This present study aims to evaluate and predict the therapeutic potential of those compounds as medication that reduce inflammation against RA by disturbing and inactivating the NF-κB molecular interaction. The LC-MS chromatography was used to evaluate the chemical contents of red betel leaves. Furthermore, in silico study, the 3D structure of the active compounds of red betel leaves is obtained from PubChem web server, while NF-κB is obtained from Protein Data Bank (PDB) website. Molecular docking was used to screen the potential compounds compared to aspirin as control. As a result, 2 compounds including Apigenin and Luteolin have smaller bond affinity values, −6.3 and −6.0 kcal/mol, respectively compared to aspirin. Based on molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) value of protein-ligand complexes have the similar pattern over 1000/ps except the NF-κB-Chavibetol complex which has an unstable pattern. On the other hand, the total energy of the protein-ligand complexes have similar average number of −1.69 kJ/mol. The simulation indicates the ligands have constant binding energy to the protein. Furthermore, numerous pharmacokinetic properties of compounds including absorption, distribution, metabolism, excretion and toxicity are exponentially greater than the control drugs. Finally, red betel active compounds can be used as alternative candidates of RA therapy medication. HIGHLIGHTS Rheumatoid arthritis, a systemic autoimmune condition, damages joints. Long-term RA causes joint discomfort, swelling, and stiffness. The identified flavonoids from red betel leaf extract include flavonone, isoflavone, auron, catechin, anthocyanidin, and chalcone. Apigenin, chavibetol, eugenol, hydroxychavicol, and luteolin, the active chemicals found in red betel, have the potential to serve as NF-B inhibitors, making them potentially useful in the treatment of rheumatoid arthritis. GRAPHICAL ABSTRACT