Clusterization of Red Betel Leaves (Piper Crocatum) from Various Regions in Indonesia Based on Secondary Metabolite Fingerprint Analysis and Cytotoxicity Values

Hyperpigmentation is a condition of darkening of the skin which is generally caused by an increase in melanin production. Melanin is produced in melanocytes by the enzyme tyrosinase. Piper crocatum contains flavonoid compounds that are known from previous research to inhibit tyrosinase. The goals of this study were to determine the tyrosinase inhibitory activity and total flavonoid content of seven accessions, as well as look at the Pearson’s correlation and clustering PCA (principal component analysis). The method used was water content analysis, extraction yield measurement, total flavonoids analysis, and in vitro tyrosinase inhibition. Based on the results, P. crocatum from Kendari had the best yield and total flavonoid content of 24.07% and 5.10 mg QE g-1, while P. crocatum from Bogor had the lowest water content with a value of 6.21% and the best in tyrosinase inhibition of 13.77. The correlation between total flavonoid content and percent inhibition showed a very weak correlation. The results of clustering formed four clusters of seven accessions based on total flavonoids and percent inhibition. The cluster was divided into Malang (506mDPL) and Jayapura (287mDPL), Banda Aceh (0.80mDPL) and Bandung (670mDPL), Samarinda (8mDPL) and Bogor (190-350m DPL), and Kendari (14mDPL). In conclusion, the correlation between total flavonoid levels and percent inhibition is very weak and regional diversity had a significant effect on total flavonoids and total inhibition.

Vegetable fungicides are fungicides made from natural ingredients that are widely available in nature. One of the plants that can be used as a vegetable fungicide include several species of betel plants such as forest betel (Piper aduncum L.), red betel (Piper crocatum L.) and green betel (Piper betle L.). The use of several betel extracts can be used as an effective and efficient alternative control. This study aims to obtain the type of betel extract which has the potential as a vegetable fungicide that is able to control the fungus Aspergillus sp. The stages of this study consisted of the isolation of Aspergillus sp., Extraction and inhibition test of several betel extracts against the fungus Aspergillus sp., Seed treatment test with extracts of several types of betel. Based on research results giving green betel leaf extract, forest betel and red betel can inhibit the growth of the fungus Aspergillus sp. With the percentage of inhibition of 32.08%, 37.53% and 33.03% respectively. Giving betel leaf extract green, betel forest and red betel also can reduce the percentage of Aspergillus sp. amounted to 19.60%, 19.20% and 18.80% when compared to controls without administration of betel leaf extract. Application of several types of betel leaf extract and without betel leaf extract both produce a high percentage of normal sprouts (> 80%).

Red betel leaf is a medicinal plant that contains several active ingredients that are beneficial for health. One of the active ingredients in red betelleaves is flavonoids such as quercetin. Quercetin is a flavonoid compound which is found in many plants and has anti-diabetic properties to reduce blood sugar levels in the body. The aim of this research was to determine the effect of administering red betel leaf extract (Piper crocatum) on the blood sugar levels of rats (Rattus novergicus). This research was an analytical experimental research with pretest and posttest. The division of control and treatment groups used Simple Random Sampling sampling techniques. There were 4 groups, namely control, treatment 50 mg/kgBB, 100 mg/kgBB, and 200 mg/kgBB. Treatment was given for 21 days and then blood sugar levels were measured using a Clima MC 15 photometer. Research data was analyzed using the One Way ANOVA Test with SPSS. The results of the Shapiro-Wilk normality test were obtained with a value of sig>0.05; Levene Test homogeneity test with sig. value > 0.05; One Way ANOVA with a sig value <0.05. It can be concluded that there is a real effect on the blood levels of white rats (Rattus norvegicus) after administering ethanol extract of red betel leaves (Piper crocatum) at doses of 50 mg/kgBB, 100 mg/kgBB, and 200 mg/kgBB. kgBB. Key words: Diabetes mellitus, Ethanol Extract of Red Betel Leaves (Piper crocatum), White Rat (Rattus norvegicus)

Abstract. Hartini YS, Nugroho LH. 2020. Short Communication: Antibacterial effect of red betel (Piper crocatum) extract in combination with vancomycin against Staphylococcus aureus. Biodiversitas 21: 3271-3274. The occurrence of bacterial resistance to a single antimicrobial compound has prompted the search for antimicrobials in the form of compound combinations. The current study was performed to show the antibacterial effect of red betel (Piper crocatum Ruiz & Pav.) in combination with vancomycin against Staphylococcus aureus. The combination of the antibacterial compounds from plant with the antibacterial drug was expected to increase antibacterial activity resulted in the reduction of resistance. The interaction effect of extract and antibiotic combination was performed using the microdilution checkerboard method. The combination of red betel extract with vancomycin showed significantly (p < 0.05) greater inhibition growth of S. aureus compared to red betel or vancomycin alone. The addition of red betel extract to vancomycin reduced Minimum Inhibitory Concentration (MIC) vancomycin to be a-4 fold reduction against S. aureus. There was a synergistic effect of the red betel extract in combination with vancomycin against S. aureus. It is the potential result for future research on the infectious treatment of S. aureus resistant to vancomycin.

Diabetic nephropathy is a complication of diabetes mellitus which results in changes in the structure and function of the kidneys. Red betel leaf (Piper crocatum) can be used as a treatment for diabetic nephropathy, which has antioxidant properties. This study aims to determine the optimal dose of ethanol extract of red betel leaves, the effect of ethanol extract of red betel leaves on blood glucose, improvement of kidney function and kidney histopathology in STZ-NA induced rats. This study used 30 male white rats of the Wistar strain, 5 groups were conditioned to experience hyperglycemia and waited for three weeks after induction of STZ-NA via intra peritoneal 60 mg/kg BW and 120 mg/kg BW. After it was stated that the rats had diabetic nephropathy, they were given an oral test preparation. Parameters measured were blood glucose, BUN, and renal histopathological tests. Data analysis used the ANOVA method followed by the LSD Post Hoc test. The test results of antihyperglycemic activity and improvement of kidney function stated that the ethanol extract of red betel leaves at doses of 125 mg/kg BW and 250 mg/kg BW had a significant difference between the normal group, negative control and positive control, but at a dose of 500 mg/kg BW there was no difference significantly with the positive control where the ethanol extract of red betel leaves has the same effect as the positive control. The results of the renal histopathological test at a dose of 250 mg/kg BW were significantly different from the normal control, negative control, positive control, but at a dose of 500 mg/kg BW there was no difference from the positive group.

The present paper reviews the recent perspectives of end-use studies as a part of urban water crisis mitigation within the past decade in various regions in Indonesia. The paper integrates a critical review of water-end use consumption from five major islands in Indonesia. Comparative methods were used to determine the domestic water consumption behaviour from the collected data from 2013 to 2020. Furthermore, the collected data were classified into two major groups (i.e., regions on Java Island and regions on non-Java Island). At the end, this review reflected a different pattern between domestic water consumption in various socio-economic regions in Indonesia and expected to provide strategies that could be used to mitigate the urban water crisis in the future.

Heavy Equipment business in Indonesia is quite potential considering the Indonesian government is implementing various development programs in various regions of Indonesia such as the construction of the Woosh Jakarta-Bandung fast train line, the Jakarta-Cikampek elevated toll road, the construction of infrastructure in various other regions of Indonesia, and buildings for public facilities. To maintain a sustainable competitive advantage in a situation like this, there is an approach that must be used. If the company has the technological capability and the ability to adapt to resources, the company can achieve this goal. The purpose of this study is to determine how important the concept of Product Life Cycle (PLC) is in marketing strategy. The method used in this paper is a literature study, namely by reviewing reading sources related to the concept of marketing strategy through the Product Life Cycle approach. Based on the results of several literature studies, it states that a company will generally have better capabilities than its competitors' performance if it is able to apply the Product Life Cycle concept. It can be concluded that the Heavy Equipment marketing strategy through the Product Life Cycle approach that needs to be improved is Product, Price, Place and Promotion can be utilized in the context of the product life cycle concept. At the maturity stage, the recommended marketing strategy is to differentiate services to differentiate yourself from competitors. Develop new markets to expand reach. Conduct more aggressive market penetration to maintain market share. Increase effective marketing promotions and communications.

Previous studies had reported antihyperglycemic activity in vitro, in vivo and in silico of red betel (Piper crocatum) extract, which was associated with its polyphenolic, tannins, alkaloids, and flavonoids compounds. This study aimed to determine blood glucose level, Langerhans pancreas, lipid profile and bodyweight of streptozotocin-induced diabetic rats after administrating red betel combination extract. Red betel combination extract is composed of red betel extract that was combined with ginger and cinnamon extracts. 16 male rats (Sprague Dawley) were divided randomly into two controls groups (Normal and diabetic groups; orally administered with 2 mL of aquadest for 14 days) and two extract groups (diabetic groups; orally administered with red betel combination extract 9 mL/kg BW and 13.5 mL/kg BW). Results showed that the administration of red betel combination extract for 14 days (9 mL/kg BW dosage) decreased the rat's blood glucose level up to 55.42%, which was significantly different (p < 0.05) compared to the rat's blood glucose levels on day 3. While the combination extract (dosages 9 mL/kg BW and 13.5 mL/kg BW) increased the numbers of rat Langerhans islets up to 10.9%-30.6%. The level of rat's blood high-density lipoprotein (HDL) and triglyceride levels in the diabetic control group were significantly different (p < 0.05) compared to that of the diabetic with red betel combination extract and normal groups. The treatment orally with red betel combination extract (various dosages) for 14 days suppressed the weight loss of rats by 10%-11%.

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures of the teeth caused by a group of specific microorganisms in dental plaque. Porphyromonas gingivalis (Pg) is a bacterium that causes periodontitis found in subgingival plaque. Antibacterial agents are needed as additional therapy to complete mechanical treatment, the main therapy for periodontitis treatment. Red betel (Piper crocatum) and black betel (Piper betle L. var nigra) are herbal plants with active compounds of flavonoids, alkaloids, saponins, tannins, phenols, and essential oils. These compounds are known to act as antibacterial and anti-inflammatory agents. This study aimed to compare the inhibition of red betel leaf extract and black betel leaf extract on the growth of Pg bacteria. This research method is experimental with an in vitro Post Test Only Control Group design. The study was conducted using the disc diffusion method in 10 groups, namely red betel leaf extract concentrations of 25%, 50%, 75%, 100%, black betel leaf extract concentrations of 25%, 50%, 75%, 100%, metronidazole as a positive control, and sterile distilled water as a negative control. Repetition was done thrice in each group on Mueller-Hinton Agar (MHA) media. The results showed that both types of betel leaf extract at all concentrations had antibacterial effectiveness against Pg bacteria. The higher the extract concentration, the more effective bacteria inhibition is. Betel leaf extract with a concentration of 100% had the highest inhibition zone, which is 25.16 mm for red betel and 19.65 mm for black betel. These results indicate that red betel leaf extract has better effectiveness than black betel leaf extract.

Degenerative diseases occurred due to several risk factors that are directly related to inflammationwhich affected several diseases such as coronary heart disease (CHD) and diabetes. One of theinflammatory causative agents is leukotrienes produced by the lipoxygenase enzyme (LOX) so thatit takes anti-inflammatory drugs made from herbal plants. Red betel leaf (Piper crocatum) potentiallyinhibited the lipoxygenase enzyme because it contains potential phytochemical compounds suchas alkaloids, flavonoids, eugenol, saponins, and tannins. This research aimed to test the inhibitionof active compounds from extract and fractions of red betel leaves that have the best inhibition forlipoxygenase enzymes causing malondialdehyde formed through molecular docking simulations. Thisresearch used lipoxygenase enzyme as receptor (PRB code: 4NRE), C8E as natural ligand and activecompound from extract and fractions of red betel leaves as a ligand. The highest inhibition regarded toNandrolone phenylpropionate and Sofalcone ligand with -10.4 kcal/mol and -9.1 kcal/mol of affinityenergy. Amino acid residues that played a role in ligand and receptor interaction were HIS373 andHIS378. The receptor structure with the best ligands was declared stable based on molecular dynamicssimulations.

Red betel leaf (Piper Crocatum) contains flavonoids, tannins, steroids, and alkaloids, known to act as antioxidants. This study aimed to determine the antioxidant activity of red betel leaf extract. The solvents used for the extraction process are ethanol and n-hexane. The thiobarbituric acid (TBA) method was used to determine antioxidant activity. The results showed that the extract of 200 ppm inhibited fatty acid oxidation by 52.13%. No significant difference (α = 0.05) inhibition of unsaturated fatty acids oxidation between the sample and α-tocopherol at 200 ppm. The ethanol extract of red betel can inhibit the tyrosinase enzyme higher than the n-hexane extract of red betel, as seen from the IC50 value of the ethanol extract of red betel of 1655 ppm, while the IC50 value of n-hexane of red betel is 3090.56 ppm.

This study looks at how red betel (Piper crocatum) extract can help keep women's reproductive health in good condition using natural methods. The research used a descriptive qualitative approach, mainly by looking at existing scientific articles and data from journals and databases between 2015 and 2025. The focus was on finding out which active ingredients are in red betel, how they fight bacteria, and why they might be useful in preventing infections in the female reproductive system. The research shows that red betel has compounds like flavonoids, alkaloids, tannins, and phenolics that work together to stop harmful bacteria from growing, especially Staphylococcus aureus and Pseudomonas aeruginosa. These compounds fight bacteria in several ways, such as breaking down the bacterial cell walls, stopping important enzymes from working, and messing up the bacteria's energy processes. Studies also show that using red betel in the form of a decoction can help reduce symptoms like vaginal discharge while keeping the good bacteria in the vagina balanced. Compared to man-made antiseptics, red betel has similar antibacterial effects but causes less irritation and is less likely to lead to bacteria becoming resistant. This makes it a promising option for a safe and eco-friendly natural alternative in feminine hygiene and women's health care. More research is needed to find the best way to extract these compounds and to test their effectiveness through proper clinical studies.

This research was carried out in order to find out the potential for utilizing wind energy as a source of electrical energy in Indonesia. Where this research is to fulfill the final assignment of the environmental physics course. This research is a literature study which aims to analyze several results of articles, journals and previous research. The purpose of this analysis refers to the application and development of the potential use of wind energy as a source of electrical energy in various regions of Indonesia. Like in the rice fields of Blang Krueng Village, Baitussalam District. This research is a qualitative descriptive design method through analysis, identification and exploration of previous findings. The subject targeted for this research is the use of wind energy as a source of electrical energy in various regions of Indonesia. The objects of this research are journals and articles. Briefly, the results of this research show two categories. first analysis of the categories of application of wind energy as a source of electrical energy in various regions of Indonesia. Analysis of the two categories of authentic development from several researchers who developed hydropower as a source of electrical energy.

Indonesian people prefer to eat fast food which is generally rich in flavorings. The most common ingredient found in fast food is MSG (monosodium glutamate). MSG consumption that exceeds the limit will produce free glutamate which is excitotoxic in various organs, one of which is the neurological system. Red betel has a fairly high antioxidant content which can inhibit excitotoxicity by inhibiting the occurrence of free radicals. The aim of this research was to determine the neuroprotective effect of red betel extract (Piper crocatum) on the brains of rats (Rattus norvegicus) given monosodium glutamate (MSG). This research is a laboratory experimental study with a completely randomized design method using 5 treatment levels, namely negative control (NC), positive control (PC), treatment 1 (T1), treatment 2 (T2), treatment 3 (T3). The NC treatment level was given 2 mL of distilled water. The PC treatment level was given 7gr/KgBB MSG. Levels T1, T2, T3 were each given MSG 7gr/KgBW in the morning, then after 8 hours, level P1 was given 200mg/KgBW of red betel extract, P2 was given 400mg/KgBW of red betel extract, and P3 was given 600mg/KgBW of red betel extract. Examination of the number of neurons in the dentate gyrus of the hippocampus using the ImageJ application and examination of calcium ion levels using the RAPIDLab 348X tool. Data analysis used the One Way Anova test with the SPSS 24 program. The results showed that there was a significant difference (p&lt;0.05) between PC and NC. The results of the calcium ion parameters showed that only the 600mg dose treatment group functioned as a protector in the occurrence of hypocalcemia, while the histopathology parameters showed that the 400mg and 600mg dose treatment groups functioned significantly as a neuroprotector.

Potential plants found in Indonesia that can be used for the treatment of urinary tract infections include: Manjakani seeds (Quercus infectoria) and red betel leaves (Piper crocatum). Manjakani seeds are pharmacologically claimed to have biological activities such as anti-inflammatory, antibacterial and antifungal. Red betel leaf has the potential as an antibacterial in the treatment of infectious diseases. The purpose of this study was to determine the antibacterial activity of the combination of manjakani seed extract and red betel leaf in inhibiting the growth of Klebsiella pneumoniae bacteria. The type of research used istrue experiment study with a completely randomized design (CRD) with three factors, namely the type of solvent n-hexane, ethyl acetate, ethanol 96%, ratio (1:1,1:2,2:1) and concentration (75%,100%) with each treatment being repeated twice. This research was conducted in the microbiology laboratory, Labkes, East Kalimantan. The population in this study is the manjakani plant and red betel plant and tested using the agar diffusion technique method Kirby Bauer with positive control (Ciprofloxacin) and negative control (aquadest). Data analysis used is One Way ANOVA and advanced test methods Duncan with a significance level of 0,05. The results obtained showed that there was an effect of antibacterial activity of Manjakani seed extract and red betel leaf on growth K. pneumoniae. The most effective concentration was found in ethanol 96% extract, (2:1 combination of 100% concentration) of 13,97 mm and an effectiveness of 55,74% with a positive control ciprofloxacin 5µg of 25,06 mm. It can be concluded that the combined extract of manjakani seeds and red betel leaves has antibacterial activity against bacteria Klebsiella pneumoniae,but the potential is still low of ciprofloxacin.