Abstract
Scorodocarpus borneensis, also known as the Kulim tree or Garlic tree, has been consumed by the local communities in Southeast Asia as traditional spice using its old leaves, stem bark, and seeds. The locals also used Kulim tree parts as conventional alternative to treat many diseases such as hemorrhoids, leprosy, diabetes, and diarrhea. However, there was limited scientific evidence to support these traditional claims. Therefore, this systematic review aims to present and evaluate a detailed overview of the phytochemical constituents of S. borneensis from previous existing studies, shedding light on their chemical composition, bioactivity, and potential applications. In addition, current studies regarding S. borneensis are still on a fundamental level. Hence, we aim that this review will reveal the research gap from the previous literature and provide an insight to implement a new research approach in the future. A literature search was conducted using four databases: ScienceDirect, Scopus, Web of Science, and PubMed. The articles were screened and data were extracted based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. 8 studies satisfied the inclusion criteria that focused on the phytochemicals from S. borneensis. The major phytochemical compound reported was phenolic compound. S. borneensis also exhibits several therapeutic outcomes such as antioxidant, antimicrobial, and anticancer but current studies are not enough to support the claims regarding S. borneensis health benefit. In conclusion, this review highlights the current understanding of S. borneensis’ phytochemical composition and its therapeutic applications which are important in preventing human diseases especially non-communicable diseases.
Keywords: Bioactive compound, Phenolic compound, Antidiabetic, Antioxidant, Therapeutic potential
1. Introduction
Scorodocarpus borneensis is a woody and wildlife plant mainly found in Southeast Asia, especially in the lowland tropical forests of Kalimantan, Sumatera, and Peninsular Malaysia. Traditionally, forest villagers used this plant as spice and medicinal plant. The locals consumed the decoctions of the roots to cure hemorrhoids while some boiled the leaves and bark and drank them to treat leprosy, diabetes, and diarrhea.1 It is believed that S. borneensis holds significant promise for human health due to its rich repertoire of phytochemicals.2 However, there was a lack of scientific evidence to support this traditional claim which includes information regarding the phytochemical compounds in S. borneensis and their testing in complex organisms like humans and animals. The classes of phytochemicals are numerous and include phenolic compounds (flavonoids, phenolic acids), alkaloids, carotenoids, glucosinolates, saponins, terpenes, and many others.3
Unfortunately, due to limited evidence regarding the characterisation and quantification of the phytochemicals of S. borneensis, the true compound that is responsible for offering the health benefits mentioned by the locals remains a question. The potential health benefits of phytochemicals derived from plants make them a subject of increasing interest in both traditional and modern medicine. However, current studies regarding the health benefits of S. borneensis were also limited, which revealed a new gap in the literature. Therefore, researchers should fill this literature gap by providing more evidence from the established methodologies regarding the potential of S. borneensis in treating human disease which indirectly supports the traditional claims of the locals. Without a comprehensive overview of the existing literature, new improvements that could be made in the future and the research focus will remain unclear. Therefore, this systematic review aims to present and evaluate a detailed overview of the phytochemical constituents of S. borneensis from previous existing studies, shedding light on their chemical composition, bioactivity, and potential applications. This review also aims to provide valuable insights for interested researchers to explore and prove the true potential of various phytochemicals derived from Scorodocarpus borneensis.
2. Methods
The review was performed based on the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline (Page et al., 2021).
2.1. Search strategy
A systematic literature search was conducted on PubMed (Medline), Science Direct, and Scopus databases, Web of Science in September until December 2023. Search queries were as follows: (“Scorodocarpus borneensis”) AND (“phytochemical” OR “bioactive compound”). The database search was performed by two independent investigators to avoid selection bias. The identified studies were then screened for eligibility and cross-referencing. All related articles published from 2013 to December 2023 were considered for inclusion. To avoid obsolete sources in the included data, the sources must have been published recently, which includes the last 5 up to 10 years.
2.2. Inclusion and exclusion criteria
PICOS (population, intervention, control/comparator, outcome, study type) was used to define the inclusion and exclusion criteria (Table 1). Experimental of in vitro studies related to the phytochemical properties of S. borneensis were eligible for inclusion along with the whole or any part of S. borneensis (bark, leaves, fruit, seeds). Studies using identification, isolation, and characterisation of phytochemical compounds, as well as assessments of their biological activities in vitro were also included. Our inclusion criteria encompass articles, research papers, and studies published up to December 2023. We also considered research published in English and indexed in the chosen databases. Exclusion criteria encompassed non-English language publications, reviews, conference abstracts, book chapters, notes, and articles not directly related to Scorodocarpus borneensis or its phytochemical analysis. Studies that lack clear in vitro experiments or fail to report phytochemical data will also be excluded. In vivo study also accepted, however there was no in vivo study regarding Scorodocarpus borneensis from the search conducted.
Table 1.
Eligibility criteria of the identified studies according to PICOS (Population, Intervention, Control/comparator, Outcomes, and Study type).
| Properties | Eligibility Criteria |
|---|---|
| Population | Plant |
| Intervention | Scorodocarpus borneensis |
| Control/Comparator | Phytochemical and bioactive compound |
| Outcomes |
|
| Study type | -In vitro studies |
2.3. Study selection
Two investigators individually screened the titles and abstracts retrieved from the databases for eligibility. The screening process was performed using Mendeley (version 1.19.8, Mendeley, London, United Kingdom). The number of searches in each database and the number of duplicates were recorded. Duplicates were removed using the built-in function of “check for duplicates” in the Microsoft Excel 16. Abstracts that fulfilled the inclusion criteria were retrieved for further screening before obtaining the full-text articles. Full articles were reviewed based on the inclusion and exclusion criteria. Quality assessment and data extraction were carried out by the two investigators. If there was any discrepancy between the investigators, a consensus was reached by inviting another investigator. Upon confirming the included studies, the corresponding references were searched manually to ensure full inclusion of all articles that fit the pre-defined criteria. The article selection process is presented in Fig. 1.
Fig. 1.
Flow chart of the search and selection process based on the PRISMA guideline.
2.4. Data extraction
The outcome variables were compiled using a standard data collection form. For each of the included studies, the first authors' surname and the study year, the origin of the study, part of the plant, type of extraction, solvent, study design, dosage, compounds, and outcome measures were extracted and synthesised in Table 4.
Table 4.
Summary of the data the included studies.
| Author | Country | Part of Plant | Type of Extraction | Solvent | Study design | Dose Extract | Compound | Outcome |
|---|---|---|---|---|---|---|---|---|
| Dewi et al., 2022 | Indonesia | Leaves | Maceration | 70 % methanol, ethanol, methanol, n-hexane, ethyl acetate | Total phenolic content | 20–140 μg/ml | Phytochemicals:
|
|
| Total flavonoid content | 20–140 μg/ml |
|
||||||
| Total alkaloid content | 20–140 μg/ml |
|
||||||
| Antioxidant (DPPH assay) | 100.24 ± 19.69 to 237.89 ± 2.66 μg/ml. |
|
||||||
| BSLT | 25, 50, 100, 200, 500, 1000 μg/ml |
|
||||||
| Gigante, 2019 | Indonesia | Leaves | Steam distillation 100 °C for 4 h or more | 40 % Ethanol (for dilution of essential oil) | Antimicrobial (Well diffusion method) | 1, 1:10, 1:100 (v/v) | Sulfur-containing compounds
|
|
| Methanol (for dilution of essential oil) | Antioxidant assay (DPPH assay) | 25, 50, 100, 250.500, 1000 μg/ml |
|
|||||
| Helium (carrier gas) | Gas chromatography-mass spectrometry (GC/MS) | _ |
|
|||||
| Harlinda Kuspradini et al., 2016 | Indonesia | Leaves | Steam distillation 100 °C for 2 h | Methanol | Antioxidant (DPPH assay) | 25, 50, and 100 ppm | Sesquiterpene |
|
| Essential oil | Antimicrobial (Well diffusion method) | 25, 50, and 100 ppm |
|
|||||
| Kartika et al., 2015 | Indonesia | Fruit | Maceration | Ethanol, n-hexane, water, ethyl acetate | Antioxidant (DPPH assay) | 25, 50, 100 ppm | Dehydroxy scorodocarpin B and scorodocarpin B |
|
| Anticancer test using Leukemia cell line (L1210) | 25, 50, 100 ppm |
|
||||||
| n-hexane, ethyl acetate | Column chromatography method | The ratio of n-hexane: ethyl acetate is 2:1 |
|
|||||
| Kikue Kubota et al.,2014 | Malaysia | Fruit | Maceration | Ethyl ether | Analytical | 12.5–25 μg/ml | Sulfur-containing compound:
|
|
| Antimirobial (Agar dilution method) | 100 μg/ml |
|
||||||
| Sutiknyawati and Dewi, 2020 | Indonesia | Fruit | Fractionation | Hexane, ethyl acetate, ethanol, methanol, 70 % methanol | Total phenolic content | 52.01–927.36 mg/GAE | Phenolic compounds (flavonoids, tannins, phenols, and terpenoids) |
|
| Antioxidant (DPPH assay) | 14.54–888.60 ppm |
|
||||||
| Sutiknyawati Kusuma Dewi et al., 2020 | Indonesia | Bark | Maceration and fractionation | 70 % Methanol, N-hexane, ethyl acetate, ethanol, methanol, | Total phenolic content | 183.33–2332.64 mg GAE/g | Phenolic compound |
|
| Total flavonoid content | 79.58–273.13 mg QAE/g | Phenolic compound (flavonoid) |
|
|||||
| Total alkaloid content | 13.00 to 19.67 (mg BE/g) | Nitrogen-containing compounds (Alkaloid) |
|
|||||
| Antioxidant (DPPH assay) | 57.88–1288.19 ppm. | Phenolic compound (flavonoid) |
|
|||||
| Dewi et al., 2020 | Indonesia | Stem bark, leaf, and fruit | Maceration | 70 % methanol | Total phenolic content | 100–400 ppm | Phenolic compound |
|
| Antioxidant (DPPH assay) | 15–90 ppm |
|
||||||
| Leaf | Antibacterial (Red Tilapia Fillets) | 5 %–50 % |
|
|||||
| Leaf | Antimicrobial (Well diffusion method) | 5 %–50 % |
|
Abbreviations: TPC, total phenolic content; DPPH, 2,2-diphenyl-1-picrylhydrazyl; BSLT, brine shrimp lethality test; ppm, parts per million; IC50, half maximal inhibitory concentration; mg GAE/g, milligrams Gallic acid equivalent per gram; mg QAE/g, milligrams Quercetin equivalent per gram; mg BE/g, milligrams Berberin equivalent per gram.
2.5. Quality assessment
The quality assessment of the included studies was performed using the Cochrane risk of bias tool. The Cochrane tool was chosen to evaluate the quality of the research and the chosen articles. The Cochrane tool provides a standardised and transparent way to assess the risk of bias. This allows for consistency and comparability across different studies. Key aspects evaluated included randomization, allocation concealment, blinding of assessors, completeness of data, and reporting of measures of variability. Each study was assigned a risk of bias score based on its adherence to these criteria, with higher scores indicating lower risk of bias. Only studies with high methodological quality and a minimized risk of bias were included in the final analysis.
3. Results
3.1. Search result
Fig. 1 shows flow chart of the search and selection process of included studies. The initial search yielded 114. After the removal of duplicates (n = 3), 111 articles were screened based on the types of articles and out of these, 94 articles were excluded (19 review paper, 9 book chapters, 2 notes and 64 irrelevant articles). The 64 articles were excluded due to the fact that S. borneensis was not the subject of experimentation in the articles. Based on the 17 remaining articles reviewed in full text, additional 4 articles were excluded as they had been published for more than 10 years to avoid outdated resources and publication bias. In addition, 5 articles were excluded as they have not enough information about the phytochemical or bioactive compound of S. borneensis and those 5 studies only focused on the botanical part of S. borneensis such as the characteristics of the soil, climate changes, geographical distributions, and its herbarium.
3.2. Quality assessment and analysis of publication bias
Table 2 shows the designated questions for Cochrane tool risk of bias and the corresponding Table 3 shows an assessment of the methodological quality and potential risk of bias of the included studies. High, unclear, and low risk of bias accounted for 1 and 0 respectively. Results showed that the overall quality of the included studies was relatively high. For all included studies, the total scores of the Cochrane scale were higher than 5 points, indicating high methodological quality.
Table 2.
The questions 1 to 10 from the Cochrane tool risk of bias.
| No | Question |
|---|---|
| 1 | Was a priori design provided? |
| 2 | Was there duplicate study selection and data extraction? |
| 3 | Was a comprehensive literature search performed? |
| 4 | Was the status of publication (i.e., grew literature) used as an inclusion criteria? |
| 5 | Were the characteristics of the included studies provided? |
| 6 | Was the scientific quality of the included studies used appropriately in formulating conclusions? |
| 7 | Were the methods used to combine the findings of studies appropriate? |
| 8 | Was the conflict of interest included? |
| 9 | Was the presence of large-study effects assessed? |
| 10 | Was the study apparently free of other problems that could result in high risk of bias? |
Table 3.
Risk of bias assessment for the included studies.
| Cochrane scale (question based on Table 2) | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Kikue Kubota et al., 2014 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 8 |
| Kartika et al., 2015 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
| Harlinda Kuspradini et al., 2016 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
| Gigante, 2019 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
| Sutiknyawati and Dewi, 2020 (a) | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 10 |
| Sutiknyawati and Dewi, 2020 (b) | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
| Yohana Sutiknyawati Kusuma Dewi et al., 2020 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
| Dewi et al., 2022 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 9 |
1 high; 0 unclear; 0 low.
3.3. Articles included in the study
Table 4 shows the details of the eligible studies included in the final analysis. Protocols for all studies have been ethically approved by their respective institutions. All 8 studies that have been chosen encompassed in vitro studies focusing on the phenolic and bioactive compounds from different parts of S. borneensis. All of the studies have been conducted in Southeast Asia and the majority, (90 %, N = 7) were from Indonesia and 10 %, (N = 1) were conducted in Malaysia. 4 studies obtained their source of S. borneensis from a local forest in Sanggau Regency, Kalimantan Barat Province, Indonesia and 3 studies collected the sources from the Botanical Garden of Mulawarman University, East Kalimantan, Indonesia while one study from Malaysia collected S. borneensis from local forest in Sabah. The majority of the studies (N = 6) performed maceration as their type of extraction while 2 more studies involved the steam distillation method. The solvents used in the maceration were methanol, ethanol, ethyl acetate, and hexane with methanol was used in the majority of studies (N = 6), followed by ethanol (N = 4) and (N = 3) for both ethyl acetate and hexane. For steam distillation, one study was using ethyl ether to extract the volatiles. Active compound reported from the included studies were phenolic compound (N = 5), sulfur containing compound (N = 2), sesquiterpene (N = 1), and Dehydroxy scorodocarpin B and scorodocarpin B (N = 1).
4. Discussion
Kulim tree (Scorodocarpus borneensis) or also known as the Garlic tree, is one of the ancient plants that can be found in grow in tropical forests. S. borneensis belongs to the Oleaceae family of plants, which are known to have phytochemicals consisting of flavonoids, tannins, glycoside cyanogenetic, and polysulfide substances. The locals in Southeast Asia use the leaves, barks, and fruits as seasoning and preservation agents the Kulim tree has a similar polysulfide compound as garlic.4 In addition, S. borneensis has been used in traditional practices to treat several medical problems such as kidney disease, diarrhea, hemorrhoids, leprosy, and diabetes. However, to date, there is still a lack of scientific evidence to support this traditional claim regarding the medicinal usage of S. borneensis. Therefore, this review aims to present a detailed overview of the phytochemical constituents within Scorodocarpus borneensis, shedding light on their chemical composition, bioactivity, and potential applications. Besides, this review is conducted to appraise the data from current researchers into comprehensive insights as well as to suggest potential future studies that can be conducted to support or dispute traditional claims of S. borneensis.
4.1. Source
Based on the 114 records identified from 4 databases, eight studies meet the eligibility and inclusion criteria with the majority of the study from Indonesia. This is not surprising as S. borneensis known locally as “buah kulim,” prospers in Indonesia due to its adaptability to the tropical climate, diverse soil types, and abundant rainfall. Rich biodiversity and traditional agricultural practices in Kalimantan also support its cultivation. The plant's resistance to pests and diseases enhances its suitability. Notably, the Scorodocarpus borneensis tree thrives in humid conditions (51.35 %–73.06 %). Indonesia's equatorial climate and extensive rainforests, as highlighted by5 contribute to its diverse flora, emphasizing the country's abundant natural resources.
4.2. Traditional claims
Traditionally, all parts of Kulim trees have been used for various purposes. Therefore, researchers from the eight studies performed extraction from the leaves fruit, bark, and seeds. Majority of studies utilised leaves and fruit with limited studies about stem bark and seeds. This is because stem bark is known to have a low concentration of active compounds such as secondary metabolites compared to other plant parts like leaves and fruits.6 Other than that, traditional and cultural practices often influence the choice of plant parts for extraction. In many cases, traditional medicine or local knowledge may specify certain plant parts, and researchers might follow these practices. For example, the locals used the leaves of S. borneensis to treat diarrhea,7 causing the researchers prone to use leaves in their investigation. While seeds may offer chemical composition variation which causes the desired bioactive compounds to be present in lower concentrations compared to other plant parts. Besides, researchers may avoid using seeds due to germination considerations since harvesting seeds may hinder the natural germination and regeneration of the plant.
4.3. Type of extraction
Two types of extraction can be found from the studies recorded, which are maceration and steam distillation with six studies and two studies respectively. Both studies that performed steam distillation used leaves to obtain the essential oil. Fewer studies applied steam distillation compared to maceration might be due to the suitability of maceration to extract heat-sensitive compounds since it involves soaking the plant material in a solvent at room temperature. Plus, maceration is a simple process with low installation and maintenance costs. However, maceration is not suitable for extracting volatile compounds from plant material compared to steam distillation.8 On the other hand, steam distillation still offers another advantage which is a shorter extraction time compared to maceration.9 Moreover, it produces a product free of organic solvents, a larger yield, and inexpensive equipment. Therefore, researchers should carefully decide between these methods which depends on the specific goals of the extraction, emphasizing volatile compounds and efficiency for steam distillation, while maceration greats in providing a comprehensive spectrum of bioactive compounds, making the selection contingent on the nature of the plant material and the intended application of the extracts.
4.4. Solvents
For maceration, there were 4 solvents that have been used in the extraction method which are ethyl acetate, methanol, hexane, and ethanol. Ethanol is polar and versatile solvent and is suitable for both polar and nonpolar compound extraction, including phenolics, flavonoids, and tannins. The ethanol concentration of the extraction solvent was the factor that had the greatest influence on the extraction of different bioactive compounds since different bioactive compounds have varying solubilities in ethanol.10 Besides, different concentration of ethanol in extraction can selectively target different classes of bioactive compounds in which low concentration prone to extract polar compound and higher concentration enhances the extraction of less polar compounds. Ethyl acetate, possessing moderate polarity, is commonly employed for its effectiveness in extracting a diverse range of compounds, including alkaloids, fatty acids, and certain polar pigments. Ethyl acetate was chosen for the extraction because of its ability to dissolve lipophilic and hydrophilic compounds making it useful for extracting compounds from organic and aqueous matrices.11 Majority studies utilised methanol as solvent which are six studies, followed by ethanol with four studies and three studies for both ethyl acetate and hexane. Methanol, a polar solvent, is frequently utilised for extracting polar compounds such as phenols, alkaloids, and flavonoids, making this solvent a common choice in phytochemical studies.1212 stated that ethanol and methanol gave the highest yield for plant extraction since the plant material contains high levels of polar compounds that are soluble in solvents with high polarity. Hexane is a nonpolar solvent, which makes it effective for extracting nonpolar compounds like lipids and hydrocarbons. However, it may not be as efficient for extracting polar compounds making it less suitable to extract phenolic compound and other polar bioactive compounds. In terms of toxicity, hexane is considered more toxic than ethanol and methanol.13 Prolonged exposure to hexane can have adverse health effects, and its use requires careful handling in a well-ventilated environment.
4.5. Beneficial activity of the phytochemicals
Scorodocarpus borneensis claimed for its traditional medicinal usage so far without any concrete evidence to support the claim. From this review, the selected studies focused on three benefits of this plant which are antioxidative effects, antimicrobial, and characterisation of phytochemical compound. The majority of the studies conducted an antioxidant activity assay which is a DPPH scavenging activity assay. Based on the result, all parts of S. borneensis (leaves, stem bark, fruit, and seed) tested showed high antioxidant activity which differs based on the types of solvent used. Studies that used methanol and ethanol showed better antioxidant activities with low IC50 value since both solvents offered better extraction of polar bioactive compounds that are responsible for the antioxidant activity of S. borneensis. Although DPPH scavenging activity assay is a well-established method for measuring antioxidant activity, one disadvantage is that it may not accurately reflect the antioxidant activity in complex biological systems since stable radicals cannot be produced in the normal metabolic processes of a living organism.14 Therefore, other types of antioxidant assays should be carried out to strengthen the confirmation of the antioxidative activity of S. borneensis such as ABTS (2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) assay, FRAP (Ferric Reducing Antioxidant Power) assay, and superoxide radical scavenging assay.
For antimicrobial testing, three studies performed the test using the well diffusion method and one study performed the agar dilution method to measure the inhibition of S. borneensis towards microbial growth. All studies showed high antimicrobial activity of S. borneensis against gram-positive bacteria (Streptococcus aureus, Streptococcus sobrinus, Streptococcus mutans, Bacillus subtilis), gram-negative bacteria (Salmonella typhi), and fungi (Candida albicans, Saccharomyces cerevisiae, Mucor racemosus, Aspergillus niger). A notable investigation conducted an antibacterial test on proteolytic bacteria using red tilapia fillets treated with a methanolic extract of S. borneensis. The extract exhibited significant antibacterial activity, suggesting its potential as an effective preservative agent. However, this study stated an unstable result of inhibition activity of S. borneensis towards proteolytic bacteria due to no fractionation method done. Therefore, it is suggested that fractionation extraction should be done to get pure bioactive compounds and become a more stable inhibitory effect. Maceration is a good choice but it only yields a crude extract that contains many broad-spectrum compounds. Nonetheless, it is advisable to explore alternative solvents such as ethyl acetate, hexane, and ethanol in this assay to further substantiate the efficacy of S. borneensis against proteolytic bacteria since different solvents will produce different yields of bioactive compounds. Additionally, it is suggested to explore other antimicrobial tests, with flow cytometry emerging as a promising choice. This method enables the analysis of individual bacterial cells within a population, providing both quantitative and qualitative data,8 thereby enhancing the reliability of assessing the antimicrobial activity of S. borneensis.
There was only one study focusing on the anticancer activity of S. borneensis fruit using L1210, a type of leukemia cell line. The data from this study suggests that dehydroxyscorodocarpin b and scorodocarpin b, which have been isolated from the fruits of S. borneensis, hold great potential as an anticancer agent. However, no functional study was conducted regarding the anticancer activity of S. borneensis. Besides, it is not conclusive as the authors stated that a sample is considered as potential for an anticancer agent if the IC50 of the sample is below 20 ppm. The anticancer activity of any product should be assessed further using animal studies which provide a comprehensive overview regarding its efficacy and toxicity. Furthermore, another anticancer assay should be conducted to give rigid support regarding the anticancer effect of Kulim such as the cell cycle analysis using a flow cytometer to evaluate the cell cycle using propidium iodide staining (PI).15 Bioactive compounds from natural products like S. borneensis may arrest the cell cycle at the S phase and specifically induce apoptosis. Unfortunately, cell cycle analysis alone may not distinguish between cells undergoing cell cycle arrest and those undergoing apoptosis. Therefore, future researchers should be concerned about performing additional assays such as apoptosis assays or caspase activity assays to complement cell cycle analysis. Furthermore, there are numerous cancer lines derived from various tissues that can be used by other researchers to study anticancer activity such as MCF-7 (breast adenocarcinoma), HCT-116 (colorectal carcinoma), and A549 (non-small cell lung carcinoma). The use of other cancer cell lines will provide broad supporting details regarding the anticancer activities of natural products specifically on the targeted tissue. It is also worthwhile to observe the effects of S. borneensis on normal cell populations as well to ensure the specificity of this plant towards the disease stage.
4.6. Toxicity
Basic toxicity study was also carried out in one of the chosen studies using Brine Shrimp Lethality test (BSLT). Based on this test, it can be concluded that S. borneensis is non-toxic with only methanol fractions considered as low toxic. It is known that methanol and hexane are more toxic compared to other solvents such as ethyl acetate, ethanol, and water but methanol can be less toxic when diluted into 70 % methanol. Therefore, researchers should choose the solvents by considering factors such as intended application, toxicity concerns, regulatory requirements, and environmental considerations. However, BSLT only provides general toxicity and does not provide information about the specific mechanism of toxicity whether it is cytotoxic, neurotoxic, or other specific types of toxicity. Plus, brine shrimp is a simple organism, and the results may not accurately predict toxicity in more complex mammalian systems like humans. Compounds that are toxic to brine shrimp may or may not be toxic to humans, and vice versa. Other alternative toxicity tests should be carried out to assess the potential toxicity of substances. Mammalian cell viability assay is also known to become one of the toxicity tests such as MTT assay. Besides, in vivo tests using rodents also can be conducted to evaluate acute and chronic toxicity effects by obtaining its lethal dose (LD50) in animals based on the Organisation for Economic Co-operation and Development (OECD) guideline. Thus, future studies should consider conducting more toxicity assays on S. borneensis for human consumption.
4.7. Phytochemical compounds
Based on the eight studies recorded, there were two studies stated that the phytochemical compound from Scorodocarpus borneensis was sulfur-containing compound isolated using steam distillation and maceration techniques. Sulfur-containing compounds have the potential as antimicrobial agent which often exert their antimicrobial effects by disrupting cellular structures, interfering with metabolic pathways, or inducing oxidative stress. However, their effectiveness, safety, and application depend on various factors such as concentration, formulation, and the specific microorganisms involved. Meanwhile, one study recorded that S. borneensis also contains sesquiterpene from the essential oil of the leaves isolated by the steam distillation method. Sesquiterpene showed high antioxidant activity by DPPH scavenging activity assay. Sesquiterpenes can directly scavenge free radicals by donating electrons or hydrogen atoms, interrupting the chain reactions initiated by free radicals and preventing cellular damage.16 The majority of the studies proved that S. borneensis also contains phenolic compounds such as flavonoids, tannins, and terpenoids with the use of methanol as the extracting solvent. Moreover, two studies that performed total flavonoid content assay observed that the ethyl acetate extract of S. borneensis showed the highest content of flavonoids due to its ability to attract polar and nonpolar chemical compounds.17 The total alkaloid content was also performed with methanol yielding the highest content of alkaloid from S. borneensis. Alkaloids are one of the largest phytochemical groups that are present in natural products. It is believed that these compounds have pharmacological effects, including analgesic, antimicrobial, anticancer, and antioxidant activity.
4.8. Phenolic compound
Phenolic compounds were found to be the most abundant in S. borneensis and it is believed to have the potential to attenuate the risk of developing diseases caused by oxidative stress such as cancer, diabetes, and its complications. A general summary of the benefits of phenolic compounds is explained in Fig. 2.
Fig. 2.
Summary of oxidative stress reactions and the beneficial effects of phenolic compounds.
Based on Fig. 2, the phenolic compound in S. borneensis offers various health benefits such as antioxidant effects and reduction of inflammatory cascade as well as reduction of redox-sensitive transcription factors. However, current studies were at a fundamental level which is not enough to prove the traditional health benefits claimed by the locals. Therefore, near future studies should focus on in vivo and clinical studies to support Kulim as an alternative medicine. The protective effects of dietary phenolic against cancer, and infectious and inflammatory diseases are explained in Fig. 3.
Fig. 3.
Protective effects of dietary polyphenols against cancer, infectious illness, and inflammatory diseases.
Traditional claims stated that Scorodocarpus borneensis possesses many health benefits such as antidiabetic and antimicrobial, but the scientific evidence was still limited due to fewer studies focusing on in vivo and clinical studies. Most of the chosen studies in this systematic review utilise S. borneensis at the analytical stage which only emphasizing its phytochemical and in vitro testing. Hence, it is suggested that future studies will apply in vivo and clinical testing to prove the antidiabetic effect of S. borneensis since diabetes is the leading worldwide incidence. Fig. 4 shows the protective role of dietary phenolic compounds against diabetes mellitus.
Fig. 4.
Protective roles of dietary polyphenols against diabetes.
The development of cancer is a multi-stage process that involves initiation, promotion, and progression. Phenolic compounds can affect and modulate multiple diverse biochemical processes and pathways involved in carcinogenesis such as estrogenic and antiestrogenic involvement, antiproliferation, cell cycle arrest or apoptosis activation, oxidation resistance, induction of detoxification enzymes, host immune system regulation, anti-inflammatory activity, and improvements in cellular signaling.18 This was proved by a study from,19 that phenolic compound exhibits anticancer activity by testing the S. borneensis extract on the Leukemia cell lines. They recorded that S. borneensis possesses antioxidative activity by showing a very low value of 50 % inhibitory concentration (IC50) that promises a great anticancer potential.
Phenolic compounds exhibit a broad spectrum of antimicrobial actions through different mechanisms. Upon infection, the host's immune response initiates inflammation through the generation of reactive oxygen species (ROS), causing oxidative stress. Elevated oxidative stress can render the infection more susceptible and induce disruptions in cellular metabolism. Plus, ROS has also been proven to be beneficial to the microorganism for their signaling molecules. Phenolic compounds such as flavonoid from S. borneensis can modulate the effect of oxidative stress in the human body by scavenging free radicals (ROS) and chelating the metallic ions. The capability of the phenolic compound as an antimicrobial agent is also explained by,20 in which the lipophilic character of phenolic compound causes the modification of the cell wall rigidity leading to integrity losses. In addition,21 stated that the antimicrobial effect of phenolic compounds also occurs by inhibiting microorganism virulence factors such as enzymes and toxins, and suppression of bacterial biofilm formation. Based on the eight extracted studies, four studies had proved the capability of phenolic compound in S. borneensis to become a powerful antimicrobial agent that can greatly contribute to human health by inhibiting the formation of oxidative stress agents, avoiding infection, and subsequently lowering the presence of inflammation cascade.
The generation of reactive oxygen species (ROS) triggers inflammatory reactions, leading to the release of cytokines that contribute to immunoregulation and tissue damage. Given the defective natural antioxidant defense mechanism in humans, the utilisation of exogenous antioxidants becomes crucial to combat excessive ROS. In the context of S. borneensis, phenolic compounds extracted from this natural resource emerge as a promising avenue for regulating inflammatory pathways associated with common inflammatory diseases like gout, osteoarthritis, and rheumatoid arthritis. Phenolic compounds function analogously to non-steroidal anti-inflammatory drugs, believed to inhibit pro-inflammatory mediators such as cyclooxygenase (COX) by blocking their activity or gene expression.22 Furthermore, certain phenolic compounds exhibit the ability to modulate transcription factors like nuclear factor-kB or Nrf2 in both inflammatory and antioxidant pathways. Notably, phenolic compounds can effectively inhibit activated immune cells by suppressing inflammatory mediators, including IL-6, IL-1β, and TNF-α. With their multifaceted inhibitory effects, phenolic compounds from S. borneensis play a pivotal role in preventing vascular inflammation, oxidative stress, elevated nitric oxide levels, and platelet aggregation, ultimately reducing the risk of disease development.
4.9. Antidiabetic activity of phenolic compounds
Based on the eight papers, only analytical and in vitro studies were performed by the researchers regarding S. borneensis so far. Analytical studies such as GCMS already proved that S. borneensis is rich in phenolic compounds such as flavonoids, terpenoids, and tannins. However, only few studies provided the information about the specific compounds in S. borneensis. Therefore, further analytical studies should be conducted by the researchers by considering to apply other established methods such as high-performance liquid chromatography (HPLC), high-performace thin layer chromatography (HPTLC), and nuclear magnetic resonance (NMR) to determine and explore more compounds from S. borneensis. The in vitro studies conducted also showed the medicinal benefits of S. borneensis such as antimicrobial, antioxidative, and anticancer activity. Based on the characterisation study, the phenolic compound from S. borneensis is also known to act as antidiabetic which correlates with the traditional claim. However, no current scientific evidence showing the antidiabetic effect of S. borneensis. Therefore, future studies must consider conducting either in vitro antidiabetic assays such as alpha-amylase and alpha-glucosidase inhibition assay, or in vivo studies to strengthen the information about the antidiabetic potential of S. borneensis. As shown in Fig. 4, phenolic compounds found in S. borneensis are believed to possess antidiabetic effects and at the same time bring less adverse health effects. The phenolic compound can maintain the survival and function of pancreatic β-cells, reduce oxidative stress, translocation of pro-inflammatory cytokines in β-cells, increase expression of anti-apoptotic genes, and decrease expression of pro-apoptotic genes. Previous study done by23,24 also showed that phenolic compounds had greatly contribute as a protective agent for high glucose toxicity induced endothelial cells and reduced fasting blood glucose levels in diabetic rats Moreover, phenolic compounds can protect the deoxyribonucleic acid (DNA) from damage caused by free radicals, protecting cells against autophagy and necrosis in hyperglycemia conditions. Phenolic compounds like flavonoids can also block protein glycation and inhibit key enzymes related to carbohydrate metabolism, increase glucose transporter (GLUT4) expression, and reduce glucose uptake.25 Hence, S. borneensis has a promising therapeutic potential to prevent and reduce diabetes mellitus based on the phenolic content reported.
5. Study strengths and limitations
This study exhibits strengths in its systematic and comprehensive approach to reviewing the literature on S. borneensis. By focusing specifically on the therapeutic potential of its phytochemical compounds, the research addresses a critical gap in the literature. The inclusion of diverse data sources enhances the reliability and depth of the findings. However, the study faces challenges such as potential data heterogeneity due to varied methodologies and geographic influences of raw materials. Limited clinical evidence and the possibility of publication bias may restrict the direct translation of phytochemicals to clinical outcomes. Thus, only papers being published within 10 years had been chosen to avoid outdated data and publication bias. Additionally, the in vivo study of Scorodocarpus borneensis is limited and non-existent. Despite these limitations, the methodology and the focus on therapeutic potential contribute valuable insights to the current understanding of S. borneensis, its phytochemical compounds, and the potential therapeutic values.
6. Recommendations for future research
The research about S. borneensis is still scarce and introductory. So far, most of the studies are focussed on the phytochemical compounds and lack fundamental and translational research. In order to achieve a comprehensive finding and support traditional claimed, future studies should focus on the mechanistic elucidation to understand the pathways underlying their therapeutic effects. Animal studies should be conducted first followed by human studies and clinical trials to assess the efficacy and safety of these compounds in human populations, strengthening translational applications. Exploring potential geographic influences on phytochemical composition and conducting longitudinal studies can provide a more comprehensive understanding of S. borneensis bioactivity and sustained therapeutic effects. These recommendations aim to guide future research, building upon the current foundation and advancing our understanding of S. borneensis for potential healthcare applications.
7. Conclusion
In conclusion, based on the previous selected studies, this review concludes that S. borneensis contains several types of phytochemicals such as phenolic compounds (flavonoid, terpenoid, tannins), sulfur-containing compounds, sesquiterpene and nitrogen-containing compounds which possess several health benefits such as antioxidant, antimicrobial and anticancer. Different phytochemical compounds can be obtained by different types of extraction methods using different types of solvents with different polarity. Future researchers who want to dig deeper into the potential of phytochemicals from natural products like S. borneensis or other traditional plants are encouraged to carefully consider the best methodologies to be applied in their studies. Besides, this review also provides the research gap regarding the application of S. borneensis in previous studies. Existing studies only focused on the in vitro studies which were not enough to provide rigid support for the traditional claims for S. borneensis. No in vivo or human studies were involved before, hence next researchers should initiate a new study to evaluate the true activity of S. borneensis in complex organisms through its efficacy dose and toxicity. With a comprehensive literature from this review and new insights for new research will surely contribute to the development of innovative and effective health interventions.
Author contributions
Muhammad Hamizan performed database search identified relevant articles and contributed to the writing of the manuscript. Siti Azhani performed extraction and analysis of data assessed articles for methodological quality and risk of bias. Sabreena Safuan and Zuraidah Abdullah provides guidance and feedback on the manuscript.
Funding
This work is supported by Fundamental Research Grant Scheme, Ministry of Higher Education, Malaysia (Ref: FRGS/1/2020/STG03/USM/03/2).
Data availability statement
The dataset generated during and analysed for the present review is available from the corresponding author on request.
Declaration of competing interest
The authors declare that the systematic review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgement
Sincere gratitude to the authors of the systematic review for their thorough and comprehensive synthesis of existing evidence, which significantly contributes to our understanding of the research topics.
References
- 1.Gigante D. Chemical composition and bioactivity of essential oil from the leaves of Scorodocarpus borneensis Becc. (Olacaceae) grown in Indonesia. William Blake Context. 2019:270–276. doi: 10.1017/9781316534946.031. [DOI] [Google Scholar]
- 2.Kustiawan P.M., Siregar K.A.A.K., Saleh L.O., Batistuta M.A., Setiawan I.M. A review of botanical characteristics, chemical composition, pharmacological activity and use of scorodocarpus borneensis. Biointerface Res. Appl. Chem. Dec. 2021;12(6):8324–8334. doi: 10.33263/BRIAC126.83248334. [DOI] [Google Scholar]
- 3.Altemimi A., Lakhssassi N., Baharlouei A., Watson D.G., Lightfoot D.A. Phytochemicals: extraction, isolation, and identification of bioactive compounds from plant extracts. Plants. 2017;6(4) doi: 10.3390/plants6040042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Dewi Y.S.K., Lestari O.A., Fadly D. Identification phytochemicals and antioxidant activities of various fractions of methanol extracts from bark of kulim tree (Scorodocarpus borneensis Becc.) Sys Rev Pharm. 2020;11(8):217–221. doi: 10.31838/srp.2020.8.32. [DOI] [Google Scholar]
- 5.Dewi Y.S.K., Purwayantie S., Christian F., Fadly D., Simamora C.J.K. PHYTOCHEMICALS, antioxidant activities, and toxicity evaluation of several fractions of scorodocarpus borneensis becc. Leaves. Rasayan J. Chem. 2022;15(1):705–710. doi: 10.31788/RJC.2022.1516580. [DOI] [Google Scholar]
- 6.Oladeji O.S., Adelowo F.E., Oluyori A.P., Bankole D.T. Ethnobotanical description and biological activities of Senna alata. Evid base Compl Alternative Med. 2020;2020 doi: 10.1155/2020/2580259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Sudrajat S., Kartika R., Kustiawan W. Analysis phytochemical compounds of ethyl acetate extract garlic tree, scorodocarpus borneensis becc as a source of bioactive ingredients. Int. J. Sci. Technol. Res. 2019;8(6):183–186. [Google Scholar]
- 8.Zand E., Froehling A., Schoenher C., Zunabovic-Pichler M., Schlueter O., Jaeger H. Potential of flow cytometric approaches for rapid microbial detection and chracterization in the food Industry—a review. Foods. 2021;10(12):1–43. doi: 10.3390/foods10123112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Kapadia P., Newell A.S., Cunningham J., Roberts M.R., Hardy J.G. Extraction of high-value chemicals from plants for technical and medical applications. Int J Mol Sci. 2022;23(18) doi: 10.3390/ijms231810334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Jiménez-Moreno N., Volpe F., Moler J.A., Esparza I., Ancín-Azpilicueta C. Impact of extraction conditions on the phenolic composition and antioxidant capacity of grape stem extracts. Antioxidants. 2019;8(12) doi: 10.3390/antiox8120597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Vásquez-Villanueva R., Plaza M., García M.C., Turner C., Marina M.L. A sustainable approach for the extraction of cholesterol-lowering compounds from an olive by-product based on CO2-expanded ethyl acetate. Anal Bioanal Chem. 2019;411(22):5885–5896. doi: 10.1007/s00216-019-01970-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Truong D.H., Nguyen D.H., Ta N.T.A., Bui A.V., Do T.H., Nguyen H.C. Evaluation of the use of different solvents for phytochemical constituents, antioxidants, and in vitro anti-inflammatory activities of severinia buxifolia. J Food Qual. 2019;2019 doi: 10.1155/2019/8178294. [DOI] [Google Scholar]
- 13.Malaysiana S., Etanol K., Fenolik J.K., Antioksidan K., Chia B. Effect of ethanol and methanol on the total phenolic content and antioxidant capacity of chia seeds (salvia hispanica L .) Sains Malays. 2020;49(6):1283–1292. [Google Scholar]
- 14.Csicsor A., Tombácz E. Screening of humic substances extracted from leonardite for free radical scavenging activity using DPPH method. Molecules. 2022;27(19):1–15. doi: 10.3390/molecules27196334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Elasbali A.M., Al-Soud W.A., Al-Oanzi Z.H., et al. Cytotoxic activity, cell cycle inhibition, and apoptosis-inducing potential of athyrium hohenackerianum (lady fern) with its phytochemical profiling. Evid base Compl Alternative Med. 2022:2022. doi: 10.1155/2022/2055773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Farombi E.O., Owoeye O. Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid. Int J Environ Res Publ Health. 2011;8(6):2533–2555. doi: 10.3390/ijerph8062533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Nurcahyo H., Sumiwi S.A., Halimah E., Wilar G. Total flavonoid levels of ethanol extract and ethyl acetate fraction dry shallots (Allium cepa L. Var. Garden onion of brebes) with maceration methods using UV-vis spectrophotometry. Sys Rev Pharm. 2020;11(10):286–289. doi: 10.31838/srp.2020.10.48. [DOI] [Google Scholar]
- 18.Rudrapal M., Khairnar S.J., Khan J., et al. Dietary polyphenols and their role in oxidative stress-induced human diseases: insights into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 2022;13(February):1–15. doi: 10.3389/fphar.2022.806470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Kartika R., Barus T., Surbakti R., Simanjuntak P. Anticancer activity of bioactive compounds from fruits of Bawang hutan (Scorodocarpus borneensis Becc) Asian J Chem. 2015;27(12):4663–4665. doi: 10.14233/ajchem.2015.19309. [DOI] [Google Scholar]
- 20.Bouarab-Chibane L., Forquet V., Lantéri P., et al. Antibacterial properties of polyphenols: characterization and QSAR (Quantitative structure-activity relationship) models. Front Microbiol. 2019;10(APR) doi: 10.3389/fmicb.2019.00829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Miklasińska-Majdanik M., Kępa M., Wojtyczka R.D., Idzik D., Wąsik T.J. Phenolic compounds diminish antibiotic resistance of staphylococcus aureus clinical strains. Int J Environ Res Publ Health. 2018;15(10) doi: 10.3390/ijerph15102321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Rahman M., Rahaman S., Islam R., et al. Role of phenolic compounds in human disease : current. Molecules. 2022;27(233):1–36. doi: 10.3390/molecules27010233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Hamzah N., Safuan S., Wan Ishak W.R. Potential effect of polyphenolic-rich fractions of corn silk on protecting endothelial cells against high glucose damage using in vitro and in vivo approaches. Molecules. Jun. 2021;26(12) doi: 10.3390/MOLECULES26123665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Hamzah N., Safuan S., Wan Ishak W.R. Protective effects of the polyphenolic-rich fraction of cornsilk against oxidative stress in streptozotocin-induced diabetic rats. J. Gizi dan Pangan. 2023;18(1):41–50. doi: 10.25182/jgp.2023.18.1.41-50. [DOI] [Google Scholar]
- 25.Praparatana R., Maliyam P., Barrows L.R., Puttarak P. Flavonoids and phenols, the potential anti-diabetic compounds from Bauhinia strychnifolia craib. Stem. Molecules. 2022;27(8):1–16. doi: 10.3390/molecules27082393. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The dataset generated during and analysed for the present review is available from the corresponding author on request.