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REVIEW ARTICLE
Year : 2020  |  Volume : 12  |  Issue : 3  |  Page : 217-222  

Phytochemicals and biological activity of Tetracera scandens Linn. Merr. (Dilleniaceae): A short review


Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), Kuantan, Pahang, Malaysia

Date of Submission27-Aug-2019
Date of Decision13-Oct-2019
Date of Acceptance26-Dec-2019
Date of Web Publication20-Jul-2020

Correspondence Address:
Dr. Mohammad Jamshed Siddiqui
Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), Indera Mahkota, Jalan Istana, Kuantan.
Malaysia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpbs.JPBS_192_19

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   Abstract 

Tetracera scandens is a southeast Asian shrub that belongs to family Dilleniaceae. Over the years, different parts of the plant have been used for the management of different diseases, including diabetes mellitus, hypertension, rheumatism, diarrhea, hepatitis, and inflammation. This variety of medical indications has attracted the attention of many researchers to this plant species, leading to the conduction of many research studies on different parts of the plant. These studies have confirmed some of the aforementioned activities of the plant, whereas other indications remain to be ascertained. This article is an attempt to summarize the studies conducted on T. scandens and to explore the isolated phytochemicals.

Keywords: Diabetes mellitus, hypertension, phytochemicals, Tetracera scandens


How to cite this article:
Nokhala A, Siddiqui MJ. Phytochemicals and biological activity of Tetracera scandens Linn. Merr. (Dilleniaceae): A short review. J Pharm Bioall Sci 2020;12:217-22

How to cite this URL:
Nokhala A, Siddiqui MJ. Phytochemicals and biological activity of Tetracera scandens Linn. Merr. (Dilleniaceae): A short review. J Pharm Bioall Sci [serial online] 2020 [cited 2020 Oct 25];12:217-22. Available from: https://www.jpbsonline.org/text.asp?2020/12/3/217/290114




   Introduction Top


Tetracera scandens Linn. Merr. is a medicinal plant that belongs to family Dilleniaceae. It is native to Malaysia, Vietnam, Indonesia, Philippines, India, Southern China, Thailand, and other Southeast Asian countries. It is usually found in tropical thickets and forest margins. T. scandens has many synonyms including Tetracera sarmentosa, Tragia scandens L., Delima sarmentosa L., Tetracera hebecarpa (DC.) Boerl, Delima hebecarpa DC, and Tetracera monocarpa Blanco. Similarly, it has numerous local names, with the most common is the English name, stone leaf. In Malaysia, it is usually called Mempelas, Akar Mempelas, Mempelas Kasar, Mempelas Putih, Pampan, or Palas.[1],[2] Furthermore, T. scandens is locally known as Akosempalay in Indonesia,[3] as Malakatmon in the Philippines,[4] and as Day Chieu in Vietnam.[5]

T. scandens is an evergreen shrub that grows to 2 m in height. In thickets, the plant usually grows as a woody climber, reaching up to 30 m. It has simple, petiolate leaves that are arranged in opposite pairs along the stem. Moreover, the leaf blade is characterized by its ovate shape, leathery and scabrous texture, serrated margin, and acute apex [Figure 1]. The new leaves are reddish-pink in color before turning green upon maturation.[6]
Figure 1: Tetracera scandens leaves

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   Ethnobotanical Uses Top


Due to their rough texture, the dried leaves of T. scandens are used as sandpaper by local handicrafts for wood-based objects. Sometimes, the young plant stems are used as ropes due to their flexibility and toughness.[7] Moreover, different parts of the plant have been used as folk medicines for the management of a wide range of diseases. Interestingly, different populations have used the same part of T. scandens for different indications. In the Philippines, an infusion of the stem of T. scandens is administered internally for management of hemoptysis in tuberculosis and applied externally to soothe sore throat, due to its high content of tannins. However, Malaysians take the decoction of plant stem orally to overcome the weakness accompanying fever and influenza.[8] Moreover, they administer a decoction of the whole plant after childbirth as a tonic. Young shoots are usually crushed into fine powder, then applied topically in the form of a poultice to treat snake bites in Indonesia.[6] In Vietnam, stem and leaves are used for management of hepatitis, rheumatism, gout, inflammation, and back pain.[8] Furthermore, the pulverized leaves are dispersed in water and administered for treatment of diarrhea, or boiled with water (i.e., decoction) and applied externally to boils. The root of T. scandens has also been used for management of diarrhea, in addition to its use in burn mixtures. The stem’s sap has been administered orally as an antitussive, whereas stem’s infusion has been used as a gargle for treatment of oral candidiasis. The roots are ground and their juice is applied to mouth ulcer.[9] The plant has also been used traditionally for the treatment of diabetes mellitus (DM), hypertension, fever, urinary disorders, internal pains and edema.[2],[8]

Despite the wide range of traditional uses, only a few indications are supported with scientific evidences. Hence, more efforts are still needed to investigate the unexplored potential of T. scandens. The scientifically justified uses will be discussed briefly in the following paragraphs with making highlights on the isolated bioactive compounds.[9] Lima et al.[10] reported that flavonoids and terpenoids constitute the major bioactive constituents amongst plants of family Dilleniaceae. The findings of the following studies are in full agreement with those obtained by Lima et al.[10] as most of the isolated compounds belong to these two classes.[9]


   Medicinal Activities ofTetracera scandens Top


Antidiabetic activity

Lee et al.[5] were the first to investigate the antidiabetic potential of T. scandens and tried to isolate the phytoconstituents responsible for its antihyperglycemic properties. A series of fractionations and purifications of the methanol extract of a branch of T. scandens using various chromatographic techniques led eventually to the isolation of five isoflavones with previously known structures. The isolated flavonoids include genistein, 3′5′-diprenylgenistein 6, 8-diphenylgenistein, derrone, and alpinumisoflavone.[5]

Glucose-uptake stimulant effect was assessed for each of the isolated metabolites. Genistein did not enhance glucose-uptake at all tested concentrations, whereas the other four compounds produced a considerable increase in the basal and insulin-treated glucose uptake. Furthermore, muscle cell toxicity was investigated for each compound. Compounds 3–5 did not show any toxic effect at concentrations up to 60 µM after a 24-h treatment. On the contrary, genistein and 3′,5′-diprenylgenistein showed muscle cell toxicity with half-maximal inhibitory concentration (IC50) values of 34.27 and 18.69 µM, respectively. Results of this study confirmed the antihyperglycemic effect of T. scandens. Moreover, compounds 3–5 were considered the probable lead candidates for antidiabetic drug development without exerting toxicity to muscle cells.[5]

Another study by Umar et al.[2] aimed to evaluate the antidiabetic effect of T. scandens leaf extracts in vivo. Firstly, a separate experiment was performed on normal healthy male rats to investigate the toxicity of both aqueous and methanol extracts of the leaves at different concentrations. No mortality or behavioral changes were observed in the extracts-treated animals, suggesting the safety of both aqueous and methanol extracts.

After the confirmation of safety, the main experiment was carried out in order to investigate the effectiveness of T. scandens leaves as an antidiabetic herb. Healthy and alloxan-induced diabetic rats were fed orally with aqueous and methanol extracts of T. scandens leaves, and blood glucose levels were measured every 2 h (at 0, 2, 4, 6, and 8 h). The results were compared with those of a positive control group treated with the antidiabetic drug glibenclamide at a concentration of 0.25 mg/kg of body weight. Both aqueous and methanol extracts produced a significant fall in the fasting blood glucose levels of diabetic rats (as compared to glibenclamide) without inducing hypoglycemia in healthy nondiabetic rats. Moreover, the aqueous extract showed a more potent antihyperglycemic effect than the methanol extract.[2]

Furthermore, the total contents of phenols and flavonoids were measured spectrophotometrically in both aqueous and methanol extracts and were expressed as gallic acid equivalents (GAE) and quercetin equivalents (QE) mg/g of plant extract, respectively. The chemical characterization of the aqueous extract resulted in 4.75 GAE mg/g of phenolic compounds and 5.77 QE mg/g of flavonoids, whereas the methanol extract was found to contain 7.26 GAE mg/g of phenolic compounds and 6.34 QE mg/g of flavonoids.[2]

Phytochemical investigation of the methanol extract of T. scandens leaves has resulted in the identification of three terpenoids and six flavonoids. The terpenoids were found to be stigmasterol, betulinic acid, and an isomeric mixture of sitosterol (∆5) glycoside and stigmasterol (∆5,22) glycoside, whereas the flavonoids were quercetin, hypolectin, isoscutellarein astragalin, kaempferol, and kaempferol-3-O-(6″-O-p-trans-coumaroyl) glucoside. Further assay of hypoletin showed its adipocyte stimulation and skeletal muscle glucose-uptake stimulation activities, suggesting its usefulness for the management of type 2 DM.[11]

Xanthine oxidase inhibitory activity

Nguyen et al.[12] reported xanthine oxidase (XO) inhibitory activity of the 1:1 methanol:water extract of T. scandens, with an IC50 value of 15.6 µg/mL. Nguyen and Nguyen[13] followed the activity-guided fractionation approach to characterize the metabolites responsible for XO inhibitory activity. Quercetin (IC50 = 1.9 µM), kaempferol (IC50 = 4 µM), tiliroside (13) (IC50 = 10.7 µM), betulinic acid (IC50 = 20.8 µM), platanic acid (IC50 = 42.3 µM), and emodin (IC50 >100 µM) were isolated from the methanol extract of T. scandens’ stem. In addition to these previously known flavonoids, a new nor-lupane triterpene was also isolated. The triterpene was found to be 28-O-ß-D-glucopyranosyl ester of platanic acid (with IC50 of 65.9 µM). It is noteworthy that quercetin was the most potent of the isolated compounds with IC50 of 1.9 µM, even more potent than the prototype XO inhibitor allopurinol (IC50 = 2.5 µM).

Antioxidant and hepatoprotective activity

The leaves of T. scandens have been traditionally used in folk medicine for the treatment of hepatitis. Thanh et al.[14] proposed that the hepatoprotective effect of T. scandens is due to the antioxidant properties of the plant metabolites. To explore the hepatoprotective potential of T. scandens and to prove their hypothesis, Thanh et al.[14] conducted an in vivo study using a model of acute hepatitis based on the well-known hepatotoxin “carbon tetrachloride” (CCl4). Metabolism of CCl4 results in the production of reactive oxygen species (ROS), including trichloromethyl free radical (CCl3) and trichloromethyl peroxy radical (CCl3OO). Hepatotoxicity caused by CCl4 is mediated by the induction of oxidative stress in the hepatic tissue, leading eventually to hepatic necrosis and fibrosis.

Animals were divided into three groups each of 10 rats. In one group, no pretreatment was performed (control group). In the second group, a single intraperitoneal injection of the hepatotoxin CCl4 was performed (CCl4-treated group). In the last group, rats were pretreated with a once-daily dose of the ethanol extract of T. scandens leaves (orally as aqueous suspension) for seven consecutive days. After that, all animals were intraperitoneally injected with a single dose of CCl4 and were killed 24 h later. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured to give an indication about the hepatic function. Moreover, malondialdehyde levels (indicative of lipid peroxidation), protein carbonyl groups (marker of protein oxidation) and the antioxidant enzymes activities were measured in the liver homogenate of the killed animals to assess the damage caused by CCl4 and the protective effects of the ethanol extract on liver tissues.[14]

Serum levels of AST and ALT were considerably higher in the CCl4-treated group as compared to the control group (proves the hepatotoxic effect of CCl4) and were significantly lowered in the extract-pretreated group as compared to the CCl4-treated group (indicates the hepatoprotective effect of T. scandens leaves in the prevention of hepatotoxin-induced acute liver injury). Similarly, levels of the biomarkers that denote lipid peroxidation and protein oxidation were much higher in the CCl4-treated group than in the control group. Furthermore, pretreatment with T. scandens ethanol extract had significantly reduced their levels in the extract-treated group. On the contrary, activities of the antioxidant enzymes were significantly reduced in the CCl4-treated group but were of normal levels for the extract pretreated animals. These findings proved that T. scandens extract has a significant protective effect against CCl4-induced hepatotoxicity in rats, which may be due to its antioxidant properties.[14]

Antibacterial activity

Muliyah et al.[3] conducted an in vitro study to evaluate the antibacterial potential of the methanol extract of T. scandens’ stem as a proposed mechanism for its antidiarrheal activity. Antibacterial activity was assayed on the Gram-negative bacilli Escherichia coli and the Gram-positive cocci Staphylococcus aureus following the well diffusion approach. Samples of different concentrations (25, 50, 75, and 100 mg/mL) were tested, using the solvent 10% dimethyl sulfoxide as the control and the antibiotic tetracycline as a positive control. All concentrations of T. scandens’ stem extracts showed antibacterial activity against both E. coli and S. aureus, with the later more sensitive than the former (i.e., has larger inhibition zone).[3] Moreover, Guzman and Padilla[4] have reported the quorum sensing inhibitory activity to the methanol extract of T. scandens leaves against the Gram-negative bacteria Chromobacterium violaceum, with minimum quorum sensing inhibitory concentration (MQSIC) of 500 mg/mL as compared to the positive control (Psidium guajava extract), which have shown MQSIC of 125 mg/mL.

Anti-human immunodeficiency virus activity

Kwon et al.[15] were the first to report the human immunodeficiency virus (HIV)-1 reverse transcriptase (RTase) inhibition activity of the ethanol extract of T. scandens. Treatment of HIV-1-infected MT-4 cells with T. scandens extract has resulted in a dose-dependent inhibition of virus production with IC50 values in the range of 2.0–2.5 µg/mL, suggesting a significant anti-HIV activity of the plant extract. An in vitro test was further performed using a RTase inhibition assay kit in order to evaluate the potential of T. scandens extract to inhibit viral RTase as a possible underlying mechanism of its anti-HIV effect. The extract inhibited HIV-1 RTase in a concentration-dependent manner, with an estimated IC50 value of 0.7 µg/mL.

[Table 1] summarizes the studies conducted on various parts of T. scandens, emphasizing the part investigated, the objective of the study as well as the isolated metabolites [Figure 2].
Table 1: Summary of the potential studies conducted on Tetracera scandens

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Figure 2: Phytochemicals isolated from Tetracera scandens

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   Conclusion Top


T. scandens is a traditional medicinal shrub that is widely used in Southeast Asia. Numerous indications have been reported to be managed by different parts of the plant, including DM, rheumatism, hypertension, hepatitis, urinary disorders, gout, snake bites, and diarrhea. Only few activities have been scientifically ascertained, including glucose-uptake stimulant activity, XO inhibitory activity, anti-quorum sensing activity, anti-HIV, antioxidant, and hepatoprotective activities. Flavonoids and terpenoids are the major phytochemical classes isolated from the plant.

Acknowledgement

We would like to thank the Kulliyyah of Pharmacy, Research Management Centre, International Islamic University Malaysia (IIUM), Kuantan, for support and providing the research facilities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Tawan CS Tetracera scandens (L.) Merr. In: van Valkenburg JLCH, Bunyapraphatsara N, editors. Plant resources of South-East Asia No. 12 (2): Medicinaland poisonous plants 2. Leiden, The Netherlands: Backhuys Publisher; 2001. p. 543.  Back to cited text no. 1
    
2.
Umar A, Ahmed QU, Muhammad BY, Dogarai BB, Soad SZ Anti-hyperglycemic activity of the leaves of Tetracera scandens Linn. Merr. (Dilleniaceae) in alloxan induced diabetic rats. J Ethnopharmacol 2010;131:140-5.  Back to cited text no. 2
    
3.
Muliyah E, Sulistijorini S, Sulistyaningsih YC, Rafi M Tetracera scandens as a medicinal plant: secretory structures, histochemistry, and antibacterial activity. J Trop Life Sci 2018;8:68-74.  Back to cited text no. 3
    
4.
Guzman JP, Padilla LV Anti-quorum sensing activity of Tetracera scandens and Aleurites moluccana leaf extracts against Chromobacterium violaceum. Microbiol Res J Int 2017;22:1-10.  Back to cited text no. 4
    
5.
Lee MS, Kim CH, Hoang DM, Kim BY, Sohn CB, Kim MR, et al. Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes. Biol Pharm Bull 2009;32:504-8.  Back to cited text no. 5
    
6.
NParks Flora & Fauna Web. (n.d.). Available from: https://florafaunaweb.nparks.gov.sg/special-pages/plant-detail.aspx?id=5821. [Last accessed on 2018 Dec 10].  Back to cited text no. 6
    
7.
Flickr. (n.d.). Available from: https://www.flickr.com/photos/adaduitokla/5912765188/. [Last accessed on 2018 Dec 10].  Back to cited text no. 7
    
8.
Stuartxchange.org. (n.d.). Available from: http://www.stuartxchange.org/Malakatmon.html. [Last accessed on 2019 Aug 5].  Back to cited text no. 8
    
9.
Useful Tropical Plants. (n.d.). Available from: http://tropical.theferns.info/viewtropical.php?id=Tetracera+scandens. [Last accessed on 2019 Aug 6].  Back to cited text no. 9
    
10.
Lima CC, Lemos RPL, Conserva LM Dilleniaceae family: An overview of its ethnomedicinal uses, biological and phytochemical profile. J Pharmacog Phytochem 2014;3: 181-204.  Back to cited text no. 10
    
11.
Ahmed QU, Umar A, Taher M, Susanti D, Amiroudine MZAM, Latip J Phytochemical investigation of the leaves of Tetracera scandens Linn. and in vitro antidiabetic activity of hypoletin. In: Proceedings of the International Conference on Science, Technology and Social Sciences (ICSTSS) 2012. Singapore: Springer; 2014. p. 591-608.  Back to cited text no. 11
    
12.
Nguyen MT, Awale S, Tezuka Y, Tran QL, Watanabe H, Kadota S Xanthine oxidase inhibitory activity of Vietnamese medicinal plants. Biol Pharm Bull 2004;27: 1414-21.  Back to cited text no. 12
    
13.
Nguyen MTT, Nguyen NT A new lupane triterpene from Tetracera scandens L., xanthine oxidase inhibitor. Nat Prod Res 2013;27:61-7.  Back to cited text no. 13
    
14.
Thanh TB, Thanh HN, Minh HPT, Le-Thi-Thu H, Ly HDT, Duc LV Protective effect of Tetracera scandens L. leaf extract against CCl4-induced acute liver injury in rats. Asian Pac J Trop Biomed 2015;5:221-7.  Back to cited text no. 14
    
15.
Kwon HS, Park JA, Kim JH, You JC Identification of anti-HIV and anti-reverse transcriptase activity from Tetracera scandens. BMB Rep 2012;45:165-70.  Back to cited text no. 15
    


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