REVIEW OF SOME EUPHORBIACEAE PLANTS IN USADA TARU PRAMANA AND ITS PHARMACOLOGICAL ACTIVITIES

Background: World Health Organization (WHO) states that up to 65% of the world's population uses traditional medicines. Indonesia is one of the countries where most people still use traditional medicine, especially in Bali. The traditional Balinese plant-based medical system that has existed for a long time and is still inherited today is Usada Taru Pramana. One of the many plants found in Usada Taru Pramana is the Euphorbiaceae. Objective: This work aims to review some of the Euphorbiaceae plants written in Usada Taru Pramana, which have a variety of potential pharmacological activities. Method: This article review using a primary and secondary data sources. Results: Some parts of the Euphorbiaceae plants in Usada Taru Pramana contain important phytochemical constituents such as phenols, alkaloids, flavonoids, saponins, tannins and essential oils. Some of the potential pharmacological activities that have been tested are anti-inflammatory, analgesic, and antibacterial. Conclusion: The Euphorbiaceae plants in Usada Taru Pramana have a variety of phytochemical constituents and correlates with its pharmacological activities. Further research needs to be conducted to explore other Euphorbiaceae plants species in Usada Taru Pramana to find compounds and other pharmacological activities to deal with various diseases in the community.


INTRODUCTION
World Health Organization (WHO) states that up to 65% of the world's population uses traditional medicines and medicines from natural ingredients (Kemenkes RI 2007) [1] . Indonesia is one of the countries where most people still use traditional medicine and have a variety of traditional medical systems based on natural ingredients, especially in Bali. The use of plant-based medicines is a popular approach to health care in Indonesia, especially Bali. The traditional Balinese plant-based medical system that has existed for a long time and is still inherited today is Usada Bali. Usada is a term for the Balinese system of treatment written on papyrus with Balinese language and script and compiled into a text of medical knowledge, how to concoct medicine, how to treat or treat traditionally or traditional Balinese medicine [2] . The word Usada comes from the word ausadhi (Sanskrit), which means plants that contain medicinal properties. There are various types of Lontar Usada, one of which is Lontar Usada Taru Pramana. Taru pramana is derived from the word "taru", meaning plant and "premana" means strength or efficacy. Usada Taru Pramana is a papyrus that tells the plants to come to Mpu Kuturan to express their respective properties that can be used as medicines [3] . Usada Taru Pramana contains a description of the method of treatment

METHODS
This primary data source was obtained from the derivation of Usada Taru Pramana papyrus by Putra (1999) [8] . This process of finding secondary data sources is obtained by searching on google, google scholar, and NCBI with the keywords "phytochemical constituents of Acalypha hispida, Antidesma bunius, Ricinus communis, Jatropha curcas, Pedilanthus tithymaloides, Aleurites moluccana, and Sauropus androgynus" and "pharmacological activities of Acalypha hispida, Antidesma bunius, Ricinus communis, Jatropha curcas, Pedilanthus tithymaloides, Aleurites moluccana, and Sauropus androgynus". Secondary data sources used are journals that have been published for the past ten years. The use of data over the last ten years is applied of no last ten years of data is supported.

RESULTS
The result obtained from the primary data source in the form of derivation Usada Taru Pramana is several Euphorbiaceae plants and the plant's parts used. The phytochemical constituents and pharmacological activities were obtained from the various data source in this review. The result obtained from the primary data source is listed in Table 1.
Phytochemical screening of water and methanol extracts of plant leaves showed the presence of phenol compounds, flavonoids, glycosides, steroids, saponins, phlacacin, and hydroxyantraquinones. Isolated compounds from plants include gallic acid, corilagin, triterpenoids, flavonoids such as quercetin and kaempferol derivatives [11] . The leaves of Acalypha hispida are reported to contain several phytochemical compounds and have antibacterial activity. Acalypha hispida leaf extract contains carbohydrates, cardiac glycosides, anthraquinone glycosides, tannins, alkaloids, steroids, saponins, and flavonoids.
The methanol extract of Acalypha hispida leaves inhibits more bacteria than other extracts of Acalypha hispida solvents such as ethanol, chloroform, and water. In testing the antibacterial activity by the Kirby-Bauer agar diffusion method, the ethanol extract of the leaves of Acalypha hispida with a concentration of 80% has the highest antibacterial activity than the 4 DOI : https://doi.org/10.24843/JPSA.2021.v03.i01.p01 other extracts, producing a diameter of inhibition zone of 18,50 mm in Escherichia coli bacteria and 19,33 mm in Staphylococcus aureus [12,13] . Other studies report that the methanol extract of Acalypha hispida leaves produces a minimum bactericidal concentration (MBC) against Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella typhi with each MBC of 250 mg/mL. All extracts were able to kill Escherichia coli bacteria, but methanol extract produced the lowest MBC of 125 mg/mL while other solvent extracts produced MBC 250 mg/mL. This shows that the methanol extract of Acalypha hispida leaves has stronger antibacterial effectiveness compared to other extract solvents and is more effective against Escherichia coli bacteria compared to other bacteria [14,15] .
Other studies report the presence of antioxidant activity in the extract of Acalypha hispida leaves. The results of antioxidant activity testing using the Water Soluble Tetrazolium Salt-1 (WST-1) reduction method showed that the ethanol extract of Acalypha hispida leaves had antioxidant activity (SOD like activity) with the percentage of inhibition at a concentration of 10 µg/mL, 100 µg/mL, and 1000 µg/mL, which is 11,27%, 15,20% and 22,06%. Ethanol extract fraction of Acalypha hispida leaves which has the best antioxidant activity (SOD-like activity) is ethyl acetate fraction with inhibition percentage at concentrations of 10 µg/mL, 100 µg/mL, and 1000 µg/mL, which is equal to 63,14%, 91,95% and 100% [12] . The antioxidant activity can be related to secondary metabolites found in Acalypha hispida, namely flavonoids and phenols.

Antidesma bunius
Leaf, fruit, root, and bark Antidesma bunius contains polyphenols, terpenoids, glucoside, saponins, tannins, biflavonoids, anthocyanins, luteolin, rutin, resveratrol, quercetin, procyanidin, catechins, amentoflavone, corinagines (1-O-galloyl) 3,6-O-hexahydroxydiphenoyl-βglucopyranoside), gallic acid (3,4,5trihydroxybenzoic), elagic acid, vicinin II, ferulic acid, citric acid, benzoic acid, malic acid, lactic acid, oxalic acid, acetic acid, ascorbic acid, and caffeic acid [16] . The methanol extract of Antidesma bunius leaves contains saponins, tannins, flavonoids, steroids, phlobatin, coumarin, alkaloids, emodin, and anthraquinones [17] . Antidesma bunius leaf extract also has antiinflammatory and antibacterial activity. Anti-inflammatory measurement was carried out by looking at the ability of Antidesma bunius leaf extract to reduce swelling in the legs of experimental animals which were injected with 1% carrageenan solution. After being injected with carrageenan, the rat showed swelling and redness in the legs, and the mouse could not walk nimbly as before injection. The principle in this method is to measure the volume of the swollen sole of a test animal that has been induced by an inflammatory agent. Ethanol extract and ethyl acetate fraction of Buni leaves (Antidesma bunius) have effective antiinflammatory activity at a dose of 200 mg/kg body weight. Antiinflammatory effect of leaf extract Antidesma bunius showed the most effective activity to reduce oedema in rat feet, ethanol extract 200 mg/kg body weight and ethyl acetate fraction 200 mg/kg body weight showed the same value to positive control namely sodium diclofenac. The anti-inflammatory effect is thought to be caused by the activity of secondary metabolites found on the leaves of Antidesma bunius, namely flavonoids, triterpenoid steroids, glycosides, and saponins [18] .
Leaf extract of Ricinus communis has an inflammatory activity based on the potential anti-inflammatory test using paw carrageenan oedema for acute inflammation testing in Wistar rats. In the carrageenan-induced paw oedema model, subplantar carrageenan administration resulted in significant paw oedema formation compared to normal paw at consecutive hours of up to 24 hours. The methanol extract of the leaves of Ricinus communis (250 and 500 mg/kg body weight) each showed a cellular protective effect during the formation of oedema and in all stages of acute inflammation. This effect is supported by the protective effect of flavonoids against carrageenan-induced foot oedema in rats [21] .
In addition to anti-inflammatory activity, other studies report that the methanol extract of Ricinus communis leaves has antinociceptive and analgesic activity. The methanol extract of R. communis leaves reduced the writhing of acetic acid-induced rats significantly at doses of 100, 125 and 150 mg/kg body weight. The ethanol extract of the leaves of Ricinus communis showed analgesic effects in phase I and phased II pain that was formalin-induced. Each phase is associated with neurogenic and inflammatory pain. The methanol extract of Ricinus communis leaves inhibits a significant dose-dependent neurogenic and inflammatory phase. The methanol extract of Ricinus communis leaves at a dose of 150 mg/kg body weight showed significant inhibition of neurogenic and inflammatory phases (p < 0,001) which was comparable to standard drugs (diclofenac). The mechanism of the analgesic effect of the methanol extract of Ricinus communis leaves is caused by the inhibitory effect or release of endogenous substances which induce nerve endings of pain similar to NSAIDs [22,23] .

Jatropha curcas
Phytochemical analysis of various parts of Jatropha plant revealed variations in the total content of phenols, tannins, free amino acids and phytic acid. The leaves contain phenols, tannins, and free amino acids [24] . 15% latex of Jatropha curcas has anti-inflammatory activity potential because it can accelerate the healing process of the inflammatory phase of the wound. The results showed that the cream of 10% and 15% latex of Jatropha curcas stimulated a moderate immune reaction against CD68 in wound healing. These extracts show good antioxidant, coagulant and anticoagulant, analgesic, and antiinflammatory properties. Similar results were observed for the effect of n-hexane leaf extract of Jatropha curcas, which showed a hemostatic effect and a significant reduction in bleeding time. Latex from tree branches has been used in healing wounds, refractory lesions, and septic gums and as a barrier to bruising. There are several secondary metabolic compounds extracted from the leaves of Jatropha curcas, which are involved in the wound healing process. Jatropha curcas leaves and sap extracts contain a considerable amount of phenolic compounds and saponins which are responsible for antimicrobial and antioxidant activity. Quercetin and routine flavonoids can enhance the wound healing process in the early phase, that is, regulation of expression of vascular endothelial growth factor (VEGF) for the growth of new blood vessels and the formation of type III collagen. However, flavonoid compounds play a role in the initial phase of wound healing (the inflammatory phase) to increase the activity of the immune system such as interleukin-2, lymphocyte proliferation, and macrophages. In addition, sesquiterpenoids are responsible for antimicrobial and analgesic effects. Meanwhile, proteins such as curcaine are responsible for wound healing. Jatropha curcas leaves and sap contain phenolic compounds and saponins which have antioxidant and anti-inflammatory activity. Flavonoids as antioxidants can reduce free radicals and will bind to free radicals that damage cell membranes. Flavonoids that accumulate in latex Jatropha curcas play an important role in the inflammatory phase by increasing interleukin-2, lymphocyte proliferation, and macrophages. Saponins can increase monocyte proliferation which will ultimately increase the number of macrophages that secrete growth factors that are important for the wound healing process [25] .
Jatropha curcas leaf extract has the potential for antibacterial activity. The result of methanol extract of J. curcas leaves which use maceration method has inhibitory against Staphylococcus epidermidis at a concentration of 50 ppm (6,67 mm) and is increasing at a concentration of 100 ppm (19,33 mm). Inhibition zone diameters in reflux Jatropha curcas leaves extracts showed inhibition in all concentration series. The smallest inhibition zone is shown at a concentration of 3,125 ppm (9,33 mm) and has positive colleration with increasing concentration. The biggest inhibition zone at a concentration of 100 ppm was 22,67 mm. Reflux extracts provide greater resistance than methanol maceration extracts against Staphylococcus. epidermidis and Staphylococcus aureus. The methanol extract of Jatropha curcas leaves resulting from maceration and reflux has strong antibacterial activity against both Staphylococcus epidermidis and Staphylococcus aureus but still below the standard antibiotic drug, such as clindamycin [26] .

Pedilanthus tithymaloides
Phytochemical screening reveals the presence of alkaloids, flavonoids, terpenoids, phenols, tannins, saponins, glycosides, sterols, amino acids, kaempferol 3-O-β-D-glucopyranoside, quercitrin, isoquercitrin, and scopoletin. The relevant phytochemical groups are identified as steroids in hexane and ethyl acetate, triterpenes in hexane, tannins in ethyl acetate, coumarin in ethyl acetate and saponins in hexane and ethyl acetate extract [27] . Methanol and chloroform extracts of Pedilanthus tithymaloides leaves have antiinflammatory activity based on the results of inflammatory induction test of swollen feet with carrageenan. Methanol extract significantly reduced carrageenan-induced foot oedema after three hours of injection at all doses tested compared to the positive control group indomethacin (p < 0,001). Significant reduction in feet oedema was also given by chloroform extract at doses of 200 and 400 mg/kg body weight compared to the positive control group indomethacin (p < 0,05). Methanol extract dose of 400 mg/kg body weight showed inhibition of oedema paw that was almost the same (62,28%) as observed with the indomethacin group (65,80%) whereas in chloroform extract with the same dose showed inhibition of 49,29% after five hours carrageenan injection. It is known that carrageenan-induced inflammatory reactions occur in two phases: the initial phase (0-2,5 hours after injection) resulting from the release of serotonin, bradykinin, and histamine, then the advanced phase is associated with the release of prostaglandins. Methanol and chloroform extracts of Pedilanthus tithymaloides leaves produced inhibition after the third hour of carrageenan-induced inflammation, showing a selective inhibitory effect on prostaglandin synthesis. The mechanism of anti-inflammatory activity of leaves of Pedilanthus tithymaloides is thought to originate from the blocking of synthesis and release of prostaglandins, which correlate naturally with therapeutic doses of most clinically effective antiinflammatory agents [28] .
Methanol and chloroform extracts also showed peripheral antinociceptive activity in the inflammatory pain model induced by acetic acid. Oral administration of methanol and chloroform extracts (100, 200, and 400 mg/kg body weight) resulted in a reduction in the amount of writhing (p < 0,001) of 22%, 39,3%, and 48,48%, respectively and 36,36%, 66,67%, and 79,17% compared to the inhibition (90,9%) produced by diclofenac sodium (10 mg/kg body weight). This nociceptive activity is associated with an increase in PGE2 and PGF2a levels in peritoneal fluid and inhibits synthesis of prostaglandin and cyclooxygenase [29] .
The disk diffusion test results showed significant Aleurites moluccana extract activity against Gram-positive (Staphylococcus aureus and Streptococcus pyrogenes) and Gram-negative bacteria (Pseudomonas aeruginosa and Klebsiella pneumoniae). Results for MIC and MBC against Staphylococcus aureus showed the lowest MIC in acetonitrile bark extract (195 μg/mL) whereas Streptococcus pyogenes had the lowest MIC in methanol extract from the same bark (781 μg/mL). Pseudomonas aeruginosa showed very low MIC shown in methanol extracts of bark (98 μg/mL). Finally, for Klebsiella pneumoniae all extracts showed high MIC, but the lowest in the group was shown in cutaneous acetonitrile extract [31,32] .
The results of the isolation and identification of the methanol extract of Aleurites moluccana leaf showed two main flavones of C-glycosida, namely swertisin and 2-O-rhamnosylswertisin, which have Aleurites moluccana extract, dose 125 to 500 mg/kg body weight, has been proven effective in preventing mechanical hypnosis from being induced by PGE2 for up to one hour after irritant injection. The reduction percentages are 26 ± 10% and 33 ± 3%, for 250 and 500 mg/kg body weight. Swerticin isolate compound and 2-Orhamnosylswertisin dose of 30 mg/kg body weight was effective in inhibiting the hypernociceptive response, when compared to the control group, with inhibitions of 70 ± 2% and 50 ± 5%, respectively.
The methanol, ethanol, and water extracts of Sauropus androgynus leaves contain bioactive compounds which have pharmacological properties and are responsible for anti-inflammatory activities such as tannins, flavonoids, alkaloids, phenols, and steroids. Leaves extract in doses of 200 mg/kg body weight and 400 mg/kg body weight has resulted in a significant increase in heat plate reaction time in doses depending from 0 to 90 minutes compared to 100 mg/kg body weight. Leaf extract in both doses of 100 mg/kg body weight also produced significant inhibition with average plate reaction time. Extracts of 100, 200 and 400 mg/kg body weight and 100 mg/kg Papaverine and 100 mg/kg Phenylbutazone (positive control) significantly reduce the volume of paw oedema that is not dosedependent. There is also substantial inhibition of oedema of feet volume induced in extracts and in animals treated with medication. The results of this study indicate that Sauropus androgynus leaf extracts show activity in varying degrees of inflammation, pain and fever by activating cyclooxygenase, prostaglandin levels, especially PGE2, significantly increasing and their production triggers inflammation, pain and fever. The significant reduction, as well as the inhibitory effect of extracts on carrageenan-induced oedema foot volume, is an indication of the plant's antiinflammatory potential [35] .
Sauropus androgynus leaves extract at a concentration of 5 mg/mL is the lowest concentration that can inhibit the growth of bacterial strains after incubation when compared to controls. Chloramphenicol and gentamicin are used as standard antibiotics for Gram-positive and Gramnegative bacteria. The Kirby-Bauer disk 9 DOI : https://doi.org/10.24843/JPSA.2021.v03.i01.p01 diffusion method is used to determine the inhibition of bacterial growth by plant extracts. Six bacterial strains were used to test the antimicrobial activity of Sauropus androgynus. Among the six organisms investigated, three were Gram-positive, namely Bacillus cereus, Bacillus subtilis, Staphylococcus aureus and the other three were Gram-negative organisms, namely Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium. Sauropus androgynous methanol leaf extract showed more inhibitory effect on Gram-positive bacteria when compared with ethanol extract. Methanol leaf extract also shows the best inhibitory effect on Gram-negative bacteria when compared with ethanol and water extracts [36,37] .
Sauropus androgynus leaf extract has anti-obesity activity. The extract can reduce body weight and eating index, increase stool weight and consistency comparable to orlistat, decrease retroperitoneal fat index, affect organ index by increasing the weight of the liver and testes. The best dose of Sauropus androgynus leaf extract in reducing body weight is 400 mg/kg body weight. Sauropus androgynus leaf extract with a dose of 400 mg/kg body weight has a bodyweight reduction activity of mice closer to the comparison (orlistat) than extract dose of 100 mg/kg body weight and 200 mg/kg body weight. S. androgynus leaf extract group 100, 200, and 400 mg/kg body weight had significant differences compared to the negative control group (p < 0,05). The content of flavonoids in the leaves of Sauropus androgynus can reduce body weight through the mechanism of action to reduce food intake and reduce lipid accumulation in the liver [38] .

CONCLUSION
The