Reviews in Agricultural Science, 1: 11-30, 2013.
doi: 10.7831/ras.1.11

Irmanida Batubara1 and Tohru Mitsunaga2

1 Department of Chemistry, Faculty of Mathematics and Natural Sciences and Biopharmaca Research Center, Bogor Agricultural University, Jl. Raya Darmaga, Kampus IPB Darmaga, Gedung Fakultas Peternakan lt 4, Darmaga, Bogor, Jawa Barat, Indonesia
2 Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

(Received: Received: February 20, 2013, Accepted: April 4, 2013, Published online: June 19, 2013.)



Indonesia contains a diverse range of cultures and plants. For a long time, Jamu, which is a traditional Indonesian medicine, had been used for beauty and human health in Indonesia. In this study, Indonesian medicinal plants used for skin care were examined, and the relevant information was update to incorporate anti-acne therapies. The anti-acne mechanisms included antibacterial activity against Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus, bacterial lipase inhibition, antioxidant, and anti-inflammatory activities. Most of the Indonesian medicinal plants used in skin care showed anti-acne activity that utilized et least 2 of these mechanisms. The compounds isolated from the Indonesian traditional medicinal plants related to the anti-acne activities are also discussed. In conclusion, more research on Indonesian medicinal plants is needed.
Keywords: Indonesian medicinal plants, Anti-acne, Antibacterial, Propionibacterium acnes lipase inhibition, Antioxidant, Anti-inflammation.



Acne is a very common skin disease affecting almost everyone at some stage and is characterized by pimples on the face, chest, and back (Scheinfeld, 2007). Acne is not a simple disease because it can lead to social phobia, lowered self-image, and depression (Koo and Smith, 1991). Therefore, it is important to develop acne therapies. The most common pathway involved in acne development is excess sebum production, hyperkeratinization of the hair follicle, oxidative stress, and the release of inflammatory mediators (Katzman and Logan, 2007; Nourin and Ballard, 2006) .
    The prevalent bacterium implicated in the clinical course of acne is Propionibacterium acnes, which is a gram-positive anaerobe normally inhabiting the skin and is has been implicated in inflammatory phase of acne (Strauss et al., 2007). This bacterium plays a central role in the current understanding of acne pathogenesis (Zane, 2005), and is the target of oral and topical antibiotic usage. Indeed, reduction in P. acnes numbers is an effective parameter of the therapeutic effectiveness of antibiotic (Burkhart et al., 1999).
    P. acnes secretes several proinflammatory products, which play important roles in the development of inflammation. These include lipases, proteases, hyaluronidase, and chemotactic factors (Heyman, 2006). P. acnes lipase is an important factor in the pathogenesis of acne because free fatty acids (FFA) formed because of the effect of P. acnes lipase on sebaceous triglycerides induce severe inflammation (Higashi, 2003).
    Recently, it was reported that the most chronic medical conditions of acne are characterized by both oxidative stress and inflammation. It is likely that the antioxidants in the blood are readily used up in the presence of acne because there is a greater demand due to the presence of higher levels of free radicals (Katzman and Logan, 2007).
    Therefore, compounds targeting acne, should be able to inhibit P. acnes growth, P. acnes lipase activity, and oxidative stress. In other words, effective compounds or materials for acne control should possess antibacterial, bacterial lipase inhibitor, antioxidant, and anti-inflammatory activities.
    Indonesian traditional medicine known as Jamu is an allnatural medicine involving the use of natural resources including plants, animals, and minerals. Originally, Jamu was a term used for Javanese traditional medicine, but now it is used as a general term pertaining to Indonesian traditional medicine. Indonesia consists of 17,508 islands (Coppola 2008) and each place has its own specific traditional medicine, with Jamu Jawa (traditional medicine from the island of Java) is more widely known than the rest. Other specific and popular Indonesian traditional medicine originates in Bali, Madura, Sumatera, Borneo, Celebes, and Papua.


Traditional use of Indonesian medicinal plants in against acne

The use of plants and other natural resources for medicinal purposes in Indonesia dates back to pre-historic times. Knowledge of Indonesian traditional medicine has been passed down through generations. About 300 distinct native ethnicities live in Indonesia and each ethnic group has used their traditional knowledge to develop medicine based on the availability of materials in their own locality. The geographic variability across Indonesia dictates that different plant species are utilized to cure various diseases by different ethnic communities in different regions of the country. Therefore, there is a complex pattern of traditional medicine across Indonesia.
    Jamu is used to treat a wide variety of ailments ranging from fatigue and headache to malaria. It can also supply the body with vitamin C, cleanse the blood, keep the body in good shape, and nourish the skin. The 3 types of jamu are medicinal, health promoting, and cosmetic. Only limited information exists for Indonesian medicinal plants used as anti-acne treatments. The majority of jamu information relates to skin care, including antisunburn, moisturizers, skin smoothing, and anti-acne treatments.
    We analyzed 27 plants species including 21 families of plants relating to 9 ethnic groups in Indonesia. The scientific, family, and local names of the plant species, as well as the common usage and the ethnic groups that use it are shown in Table 1.
Particular plant species may also be utilized to cure different diseases within different ethnic communities in different regions of Indonesia. For instance, Curcuma longa is used by Sundanese (West Java province) for muscle pain and liver problems, while Javanese (Central Java) use it for skincare and to treat coughs (Sangat et al., 2000). Sometimes, different ethnic groups in different geographic areas use different plant species for the same disease. For example, in Central Kalimantan ethnic Dayak Ngaju use Goniothalamus macrophyllus for skin diseases while Lepisanthes amoena is used by 3 ethnics groups in East Kalimantan, namely, Dayak Tunjung, Kutai, and Punam Lisum. On another island, ethnic Maluk in Sumbawa, West Nusa Tenggara use Caesalpinia sappan. The Indonesian people also make use of plant mixtures, for instance, Javanese from the East Java province treat acne with a mixture of C. longa, C. xanthorrhiza, and Andrographis paniculata (Sangat et al., 2000) .


Use of Indonesian medicinal plants in antibacterial therapies

The human skin is densely populated with resident microbiota, which is mainly commensal microorganisms, such as Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus (Thiboutot, 2002; Gollnick et al., 2003; Nagy et al., 2006). The bacteria P. acnes and S. epidermidis have been recognized as the major cause of acne comedos (Leyden and Klingman, 1976). In addition, large numbers of P. acnes occur in all stages of the acne process (Zane, 2005). Antibacterial therapy in the treatment of acne suggests that microbial components play an important role in acne progression and reducing the population numbers of bacteria such as P. acnes, S epidermidis, and S. aureus is an appropriate parameter of the therapeutic effectiveness of an antibiotic (Burkhart et al., 1999) .
    Data pertaining to the antibacterial activity of 27 Indonesian medicinal plants are shown in Table 2. The antibacterial data are reported as minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ). MIC refers to the minimum concentration that can inhibit the bacterial growth, whereas MBC denotes the minimum concentration that can kill the bacteria. The lower the values of MIC and MBC mean the more active the samples. The IZ refers to the area around the bacterial growth where other organisms cannot grow. The larger the IZ value the more active the sample.
    Only 3 species had been reported to have antibacterial activity against 3 skin bacteria, namely, P. acnes, S. epidermidis, and S. aureus. These are Andrographis paniculata, Psidium guajava, and Terminalia catappa. The other promising antibacterial plant species are Caesapinia sappan (Xu and Lee, 2004), which has been specifically reported as anti-P. acnes, and Curcuma xanthorrhiza, Goniothalamus macrophyllus, Helminthostachys zeylanica, and Hibiscus tiliaceus (Batubara et al., 2009). In addition, Gynura pseudochina, Koompassia malaccensis, Lepisanthes amoena, Piper cf. fragile, Talinum sp., Vitex pubescens, and Usnea misaminensis have potential antibacterial activity for acne treatment; however, the studies are still limited.




Indonesian medicinal plants as bacterial lipase inhibitors

P. acnes secretes several proinflammatory products that play important roles in the development of inflammation. These include lipases, proteases, hyaluronidases, and chemotactic factors (Heymann, 2006). FFA produced by lipase (glycerolester hydrolase, EC on sebaceous triglycerides has been implicated an irritant and a comedogenic agent that induces severe inflammation (Higashi, 2003; Lee et al., 1982) .
    In addition, lipases of P. acnes are thought to degrade human skin lipids such as sebum, which might be an important process in the colonization of human skin sites. Sebum and sweat are nutrient sources for the microorganisms. Specifically, sweat contains vitamins, amino acids, and lactate; whereas sebum contains lipids and amino acids (Bojar and Holland, 2012). It was also proposed that FFA, produced by P. acnes lipase activity on the sebum assist bacterial adherence and colonization of the sebaceous follicle (Bruggemann, 2005; Nagy et al., 2006).
    S. epidermidis and S. aureus also have the ability to synthesize lipases that degrade sebum triglycerides into FFA (Leyden and Kligman 1976; Armold et al., 1990). Analysis of the research by Batubara et al., (2009) on selected Indonesian medicinal plants revealed that only P. acnes possesses lipase inhibition activity (Table 3). The data is reported as IC50, which is the concentration that can inhibit 50% of the lipase activity.
    Intsia palembanica is the most promising plant with P. acnes lipase inhibition activity. Other active plants are C. longa, Rhizophora sp, Psidium guajava, and Helminthostachys zeylanica. In total only 15 plants are able to inhibit P. acnes lipase activity out of the 27 plants analyzed.






Use of Indonesian medicinal plants in anti-inflammatory therapies

Since acne is an inflammatory skin disease, it is important to assess the anti-inflammatory activity of Indonesian medicinal plants. After phagocytosis of the bacteria in the skin keratinocytes, the attracted neutrophils produce reactive oxygen species (ROS) in a dose-dependent manner (Grange et al., 2009). This phenomenon requires the activation of inducible nitric oxide synthase (iNOS). After that, P. acnes induces human keratinocytes to produce interleukin-1α (IL-1α), tumor necrosis factor (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Farrar and Ingham, 2004).
    The summarized data (Table 3) based on the decrease in cytokines such as TNF-α, superoxide production, nitric oxide production, or the number of iNOS. Among the 27 plants species, only 11 plants possess as anti-inflammatory activity. These plants are A. paniculata, Avicennia sp. C. sappan, C. longa, C. xanthorrhiza, Goniothalamus macrophyllus, Guazuma ulmifolia, Phaleria papuana, Rhizophora sp, Swietenia sp, and Tinospora tuberculata. The data collected are not specific to the inflammation caused by P. acnes since the effects of medicinal plants on the inflammation caused by P.acnes are still limited.


Indonesian medicinal plants as antioxidant sources

The numerous bacterial biotas on the skin produce low molecular weight chemotactic factors that release ROS (Jain and Basal, 2003). Recently, it was reported that the most chronic medical conditions of acne are characterized by both oxidative stress and inflammation. To alleviate oxidative stress, antioxidants are essential.
    ROS include many chemical species such as superoxide anion (O2), nitric oxide and peroxide. Any material that could decrease the number of these species could be considered as an antioxidant agent. These species are also radical species, which means that the antioxidant activity could be measured by the anti-radical scavenging activities such as the trolox equivalent antioxidant capacity (TEAC) based on radical cations, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) , ABTS and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) method (Prior and Cao, 1999; Koleva et al., 2002). In addition, in vivo analysis of antioxidant potential could be measured on plasma and serum. The antioxidant capacity assays involving oxidants that are not necessarily pro-oxidant such as ferric reducing/antioxidant power (FRAP) could also be used for screening purposes.
    All plant species mentioned in this paper possess antioxidant activity. They could potentially be used in anti-ROS therapies. Based on the summarized data in Table 3, there are 8 plants species that are reported to have antioxidant activity according to 1 assay method,these species are G. macrophyllus, Gynura pseudochina, H. zeylanica, I.palembanica, Koompassia malaccensis, Litsea spp. Melaleuca cajuputi, Piper cf. fragile, T. tuberculata, Usnea pubescens, and Xylocarpus granatum. Among them, T. tuberculata has the lowest antioxidant activity on DPPH (Arung et al., 2009; Batubara et al., 2009). The other plants species still need to be analyzed using other assay procedures.


Compounds isolated from Indonesian medicinal plants for use in anti-acne treatment

On searching the responsible compounds with anti-acne activity, some compounds isolated from medicinal plants were characterized and published. The data collected are based on 4 activities, namely antibacterial, bacterial lipase inhibition, antiinflammation, and antioxidant. The compound found to be a good bacterial lipase inhibitor was isolated from C. sappan and C. xanthorrhiza.
    The summarized data relating to the compounds isolated for anti-acne activity is shown in Table 4. Isolated compounds related to anti-acne activities are reported from 13 plants species. The antioxidant activity is reported for 5 compounds from H.zeylanica (Huang et al., 2003), 2 compounds from P. papuana (Susilawati et al., 2011 & 2012), 3 compounds from P. guajava (Tachakittirungrod et al., 2007), 7 compounds from Rhizophora sp (Takara et al., 2008), 1 compound from Swietenia sp (Falah et al., 2008), and 2 compounds from Talinum sp (Kinoshita et al., 2007). Two antibacterial compounds were characterized from G.macrophyllus (Humeirah et al., 2010), and anti-inflammatory compounds from 4 plants species, 1 compound from A.paniculata (Chiou et al., 2000), 2 compounds from T. catappa (Fan et al., 2004), 1 compound from T. tuberculata (Yokozawa et al., 2004), and 6 compounds from Xylocarpus granatum (Ravangpai et al., 2011) .
    There are numerous compounds related to anti-acne found in C. sappan and Curcuma genus, C. longa and C. xanthorrhiza. Seven compounds isolated from C. sappan have anti-acne activity. Four compounds from C sappan show anti-inflammatory activities (Washiyama et al., 2009), one has antibacterial and antioxidant activities and two have all the properties (Batubara et al., 2010). The 2 compounds that have antibacterial, lipase inhibition, anti-inflammation, and antioxidant properties are brazilin and protosappanin A (Xu and Lee, 2004, Washiyama et al., 2009, Batubara et al., 2010) .
    About 7 compounds were isolated from the Curcuma genus. Three curcuminoid compounds were reported to have antiinflammatory and antioxidant activities (Ramsewak et al,. 2000; Jantan et al., 2012). Xanthorizol, a compound isolated only from C. xanthorrhiza was also reported to have anti-inflammatory and antioxidant activities. Two compounds from Curcuma essential oils, ar-turmerone and zerumbone, have antioxidant activity (Jantan et al., 2012); and s-elemenon and γ-elemenene have antibacterial and lipase inhibitory activities (Batubara et al., 2008).










Prospects of Indonesian medicinal plant product against acne

The activities and isolated compounds reported for C. sappan wood and Curcuma genus imply these are the most promising Indonesian medicinal plants for development anti-acne products. However, further research is required to identify other effective plant species.



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