View of A Review on Bioactive Compounds and Pharmacological Properties of Cleome rutidosperma DC

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2023, Vol. 13, No. 3, 615 – 624 http://dx.doi.org/10.11594/jtls.13.03.20

Review Article

A Review on Bioactive Compounds and Pharmacological Properties of Cleome rutidosperma DC.

Trang Nguyen*

Institute of Biotechnology and Food Technology, Industrial University of Ho Chi Minh City, Vietnam

Article history:

Submission April 2022 Revised July 2023 Accepted July 2023

ABSTRACT

Cleome rutidosperma DC., a species of flowering plant in the Cleomaceae family, is commonly known as "fringed spider flower" or "purple cleome". It is distributed in the tropical and subtropical regions of Asia and Africa. The plant species is widely utilized in folk medicinal practices. According to traditional medicinal reports, the plant has been used to alleviate pain, spasms, and skin diseases, as well as to reduce symptoms of deafness, earaches, and convulsions. This study aims to consolidate the available information on traditional medicine, botanical aspects, phytochemistry, and pharmacology of C. rutidosperma. Published articles on this species since 2000 were comprehensively analyzed. Databases, such as Google Scholar, Scopus, ScienceDi- rect, and PubMed, were employed. Pharmacological studies have demonstrated that C. rutidosperma possesses various bioactivities, including analgesic, anti-inflammatory, antidiabetic, and anticancer effects. Multiple phytochemicals have been identified in the plant. These phytoconstituents could contribute to the high antioxidant properties and multiple bioactivities of C. rutidosperma that hold great potential for human health.

Keywords: Anti-inflammatory activity, Antidiabetic activity, Cleome rutidosperma, Fringed spider flower, Phytochemicals

*Corresponding author:

E-mail: nguyenhadieut- [email protected]

Introduction

Cleome rutidosperma DC., widely known as

“fringed spider flower” or “purple cleome”, is a species of flowering plant belonging to the family Cleomaceae (Figure 1). It is commonly found growing in the tropical and subtropical regions of Asia and Africa [1]. The plant is known for its distinctive, spider-like flowers that bloom in shades of pink, purple, and white. In India, Ayurvedic practitioners have utilized various parts of C. ruti- dosperma, such as its leaves, roots, and seeds, for the treatment of pain, spasm, skin diseases [2]. Sap from C. rutidosperma leaves is commonly used in Africa to alleviate symptoms of deafness and earaches while the leaf extract from the plant is ap- plied as a treatment for convulsions [3]. In addi- tion to its ethnomedicinal values, C. rutidosperma has been the subject of numerous studies due to its bioactivities. Research has shown that C. ruti- dosperma possesses anti-inflammatory, antinociceptive, antioxidant, anti-tumor, and antimi-

crobial properties [4]. The plant's bioactive compounds, such as phenolics, alkaloids, tannins, terpenoids, and saponins, are believed to be responsible for its medicinal effects [3, 5].

The previous reviews solely commented on the pharmacological effects of C. rutidosperma, neglecting to provide a comprehensive account of the plant's phytochemical composition. The objec- tive of this review is to provide a summary of the available data on the phytochemical compositions of C. rutidosperma, and to elucidate the relation- ship between the phytochemicals of this species and its bioactivities. In order to achieve this goal, a comprehensive analysis of all published papers focusing on C. rutidosperma from various research databases since 2000 was carried out.

Google Scholar, Scopus, ScienceDirect, and Pub- Med, were used to search for articles using specific keywords. A total of 36 articles related to C.

rutidosperma and other Cleome species, including

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Figure 1. A photo of Cleome rutidosperma those containing chemical analyses, in vitro and in vivo experiments, were found and reviewed. This review will help provide a better understanding of the phytochemical contents of C. rutidosperma and their potential role in the prevention and treatment of diseases.

Botanical aspects

Cleome rutidosperma is an erect, annual plant that can grow up to 2 m tall. It has distinctive, spiny stems and leaves that are covered in sticky hairs. Its flowers are small, pink or white, and are arranged in long, terminal racemes. This species is commonly found in disturbed areas, including roadsides, fields, and waste places. It is known for its ability to tolerate harsh environmental conditions, such as drought, high temperatures, and high levels of salinity, and can grow in a wide range of soils, including sandy, loamy, and clay soils. The plant species is typically found in tropical and subtropical regions, with a preference for warm, hu- mid climates. It is commonly found at elevations ranging from sea level to 1,500 meters.

Phytochemicals

Volatile organic compounds

Volatile constituents of essential oil extracted from plants have attracted much attention due to their bioactivities of importance to human health.

One study by McNeil et al. (2018) reported 13 volatile constituents (1 – 13) present in essential oil obtained from C. rutidosperma aerial parts [6]

(Table 1). Among the compound groups, oxygenated diterpenes predominated over the others, ac- counting for 68% of the essential oil. (Z)-phytol was identified as being the most abundant

compound, making up 65% of the oil. This compound was also identified as the main compound (53%) in essential oil of C. serrata [7]. Compared with the other Cleome species, C. rutidosperma volatile profile significantly differs. For instance, essential oils from C. iberica and C. viscosa re- portedly contained monoterpenes and sesquiter- penes as the major groups of compounds [8, 9]. In contrast, diterpenes were typically found to be detected in C. rutidosperma. Acetoxy manool and phyllocladane were present in aerial parts of C.

rutidosperma, which were not detected in the other Cleome species [8-12]. The volatile profile of essential oils is generally affected by various factors, such as origin of the plant samples, growing condition, and distillation method. Therefore, the observed variations in the chemotypes of Cle- ome species could be ascribable to the different environmental and climatic conditions.

Pigments

Pigments, such as chlorophyll and carotenoids, in C. rutidosperma leaves were reported by using a method described by Lichtenthaler and Wellburn (1983) and Arnon (1949) [13, 14]. The study revealed that one gram of the leaves com- prised 1.21 mg of chlorophyll a and 0.43 mg of chlorophyll b [15]. Similarly, a recent study has reported that total chlorophyll content of the aerial parts of the plant is 1.58 mg/g [16]. With respect to carotenoids, research showed total amount of carotenoids in the leaves was about 2.46 mg/g [15].

Phenolics

Phenolics are a group of chemicals that con- tain one or more aromatic rings bearing hydroxyl groups. These compounds are commonly found in fruits and are classified into various subclasses, including tannins, coumarins, stilbenes, flavonoids, and phenolic acids. Information about the phenolic composition of C. rutidosperma is very limited whereas those of the other Cleome species abound in the literature. Previous research into C. ruti- dosperma collected in India showed acetone leaf extracts had about 120 mg GAE/g and 36 mg QE/g dry samples [5]. Aerial parts of the plant were a rich source of tannin as total tannin content of leaf and stem extracts ranged from 6.3 to 10 mg TAE per gram of dry sample [3, 5]. In another study, C. rutidosperma extracts obtained from various solvents (70% ethanol, methanol, chloro-

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Table 1. Phytochemicals in Cleome rutidosperma No. Compounds Chemical

class Structure Analytical

methods Refer- ences

1 Eugenol Phenolics GC-MS

GC-FID [6]

2 n-Tetradecanol Fatty alcohols GC-MS

GC-FID [6]

3 1-Heptadecene Alkenes GC-MS

GC-FID [6]

4 n-Hexadecanol Fatty alcohols GC-MS

GC-FID [6]

5 (3Z)-Cembrene Diterpenes

GC-MS

GC-FID [6]

6 Isopropyl hexadec-

anoate Esters GC-MS

GC-FID [6]

7 Phyllocladene Diterpenes GC-MS

GC-FID [6]

8 n-Octadecanol Fatty alcohols GC-MS

GC-FID [6]

9 (Z)-Phytol Unsaturated alcohols

GC-MS

GC-FID [6]

10 Acetoxy manool Labdane

diterpenes GC-MS

GC-FID [6]

11 (Z,Z)-6,9-cis-3,4- Epoxynonadecadiene

Oxygenated alkadienes

GC-MS

GC-FID [6]

12 2,6,10,14,18-pen-

tamethyl eicosane Alkanes GC-MS

GC-FID [6]

13 Tricosan-1-ol Fatty alcohols GC-MS

GC-FID [6]

14 Syringic acid Phenolics HPLC-

DAD [17]

15 p-Coumaric acid Phenolics HPLC-

DAD [17]

16 Ferulic acid Phenolics HPLC-

DAD [17]

17 Sinapic acid Phenolics HPLC-

DAD [17]

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18 Ellagic acid Phenolics HPLC-

DAD [17]

19 Rutin Phenolics HPLC-

DAD [17]

20 Myricetin Phenolics HPLC-

DAD [17]

21 Quercetin Phenolics HPLC-

DAD [17]

22 Naringenin Phenolics HPLC-

DAD [17]

23 Apigenin Phenolics HPLC-

DAD [17]

24 Kaempferol Phenolics HPLC-

DAD [17]

25

2-ethyl-cyclohex-2- ene-6-hydroxy-meth- ylene-1-carboxylic acid

Esters NMR [21]

26 3-

hydroxy-lup-20(29)-

en-28-oic acid Triterpenes NMR [21]

form, and benzene) contained about 75.3 – 200.9 mg GAE/g dry extract [17]. Among these, the 70%

ethanol extract had the greatest total phenolic content, indicating the strongest extractability on phenolics, followed by methanol. Similarly, total flavonoid contents of the 70% ethanol and methanol extracts were significantly higher compared to those of the two nonpolar solvents. The results in- dicate total phenolic content of C. rutidosperma is equivalent to that of Cleome viscosa [18].

While most of the studies on phenolics of this species have focused on determining total phenolic and flavonoid content, identification and quantification of individual phenolics in the plant are limited. Very recently, one study has reported

the presence of 11 phenolics (14 – 24) in an extract of the plant [17] (Table 1). Syringic acid was shown to be the main phenolic acid while rutin predominated over the other flavonoids. Most of these compounds were also found and quantified in other Cleome species, such as C. droserifolia and C. arabica [19, 20]. Notably, ellagic acid, a hexahydroxydiphenic acid, was often reported to be part of phenolic composition of these species.

Other phytocompounds

One study by Rahman et al. (2008) reported the characterization of two phytochemicals (25, 26) in C. rutidosperma aerial parts using NMR technique [21]. These compounds have never been

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reported in the other Cleome species. Besides, alkaloids, saponins, cyanogenic glycosides and phytates were determined in the plant leaves and/or seeds [22, 23]. The average levels of these phytochemical classes were 0.31 mg, 0.20 mg, 18.50 mg, and 0.38 mg per 100 grams of the seeds, respectively. Moreover, the research indicated that levels of these phytoconstituents tended to de- crease during the boiling process. No information about the presence of these compounds in other plant parts of the species is available in the literature. In general, while data about the other Cleome species, such as C. viscosa, C. arabica and C. dro- serifolia abound in the literature [24, 25], those of C. rutidosperma are limited [26]. Future studies should be focused on exploring the chemical composition of C. rutidosperma and how they contribute to bioactivities of this species.

Pharmacological activities

Considering recent data, it has been demonstrated that extracts obtained from C. ruti- dosperma possess multiple bioactive properties that may have significant implications for human health. This section presents an overview of the available scientific literature pertaining to the bioactive effects of C. rutidosperma extracts and their associated bioactive compounds (Table 2).

Antioxidant activity

Determining the antioxidant activity of plant extracts is crucial because it is a fundamental char- acteristic that contributes to the understanding of biological processes, such as antimutagenicity, an- ticarcinogenicity, and antiaging. Research revealed that raw ethanol extract and its fractions prepared with diethyl ether, petroleum ether, ethyl acetate, butanol) of the C. rutidosperma aerial parts displayed potent antioxidant activities in a dose-dependent manner [27]. Besides, the bioactivities were found to be comparable with those of ascorbic acid and -tocopherol (reference stand- ards). The study also suggested flavonoids, tannins, and terpenoids could account for the antioxidant activities of the plant. In other studies, ethanol and aqueous extracts of aerial parts of C. ruti- dosperma had the capacities to scavenge various types of free radicals, such as ABTS (2,2-diphe- nyl-1-picrylhydrazyl), DPPH (2,2'-azino-bis(3- ethylbenzothiazoline-6-sulfonic acid)), nitric oxide, and hydroxyl, which were equivalent to ascorbic acid [28, 29]. Additionally, the ethanol extracts

possessed significantly stronger activities compared to the aqueous extract for all the assays. The antioxidant activity of this plant was also affected by extraction solvents with different polarity as reported in recent studies[17, 30]. It has been showed that antioxidant activity of the extracts determined by DPPH, ABTS, metal chelating, FRAP (ferric reducing antioxidant power), reducing power, and lipid peroxidation assays all followed the order: 70% aqueous ethanol > methanol >

chloroform > benzene. In general, extracts obtained with more polar solvents appear to have higher antioxidant activity. Essential oil from aerial parts of the plant was also assayed for DPPH antioxidant activity, but it had no scavenging effects on the free radical [6]. In vivo research into aqueous extract of the plant leaves demonstrated aqueous extract of C. rutidosperma leaves orally administrated at different doses (125, 250, and 500 mg/kg) to STZ (streptozotocin)-stimulated diabetic rats for 4 weeks helped remarkably increase activities of SOD (superoxide dismutase), CAT (catalase), GST (glutathione-S-transferase) and GR (glutathione reductase) [31].

Anti-inflammatory activity

Protein denaturation can occur as a conse- quence of heat stress or exposure to chemicals, leading to significant modifications in their biological, chemical, and physical properties. The denaturation of tissue proteins has the potential to serve as an indicative factor for the presence of inflammatory conditions. In vitro research showed 70% ethanol extract of C. rutidosperma exhibited an inhibitory effect on bovine albumin denaturation (IC50 = 201.58 g/mL), albeit significantly weaker than diclofenac (31.32 g/mL) [17]. It was suggested that several phenolics, including ferulic acid, sinapic acid, ellagic acid, myricetin, and quercetin, could contribute to the protective effect on albumin denaturation. The plant was also studied for an anti-neuroinflammatory activity using LPS (lipopolysaccharide)-induced microglial cell line BV2 [32]. It was shown that treatment of the microglial cells with ethanol extract of C. ruti- dosperma exerted an inhibitory effect on LPS- stimulated NO (nitric oxide) release by inhibiting iNOS (inducible nitric oxide synthase) protein expression. The extract also attenuated COX (cy- clooxygenase)-2 mRNA and protein expression as well as suppressed the release of TNF (tumor ne-

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Table 2. Pharmacological properties of Cleome rutidosperma Pharmacological activityExtractsPlant partsStudyBioassay/treatment Effects References Antioxidant activity Ethanol extract Petroleum ether, diethyl ether, ethyl acetate, n-butanol fractions

Aerial partsin vitroPhosphomolybdate Reducing power Superoxide scavenging Nitric oxide scavenging Thiobarbituric acid [27] Aqueous extract Ethanol extract 70% Ethanol extract

Aerial partsin vitroDPPH ABTS Nitric oxide scavenging Hydroxyl radical scavenging[28, 29] Benzene extract Chloroform extract 70% Methanol extract Ethanol extract Whole plant in vitroDPPH ABTS Metal chelating FRAP Reducing power Lipid peroxidation

[17] Hexane extract Ethyl acetate extract Methanol extract

Leavesin vitroDPPH [23] Essential oil Aerial partsin vitroDPPH [6] Aqueous extract Leavesin vivo: male Wistar albino ratsStreptozotocin-induced diabetes  SOD, CAT, GST, GR [31] Anti-inflammatory activity

70% ethanol extract Whole plant in vitroBovine albumin denaturation [17] Ethanol extract Whole plant in vitro: immortalized mouse microglial cell line BV2

 iNOS, COX-2 expression  NO production  TNF-, IL-6[32] Ethanol extract Petroleum ether, diethyl ether, ethyl acetate, n-butanol fractions

Aerial partsin vivo: male Swiss albino mice, Wistar albino rats, New Zea- land white rabbits Acid acetic-induced writhing Carrageenin-induced rat paw edema Adjuvant-induced polyarthritis Injection of yeast suspension[33]

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90% Ethanol Petroleum ether, diethyl ether, ethyl acetate fractions

Aerial partsin vivo: male albino ratsCotton pellet granuloma method Freund’s adjuvant induced arthritis model [2] Methanol extractWhole plantin vivo: Swiss albino miceAcute toxicity test Hot plate test Tail flick test Acetic acid-induced writhing, formalin-induced licking tests

[34] Antidiabetic activity

70% ethanol extractWhole plantin vitro Inhibition of-amylase and-glucosidase[17] Aqueous extract Leavesin vivo:male Wistar albino rats Streptozotocin-induced diabetes  hepatic glucokinase  glucose-6-phosphatase[31] Methanol extractLeaves in vivo: Wistar albino rats Alloxan-induced diabetes  blood glucose levels [35] Anticancer activityMethanol Leaves in vitro: HepG2 cell line MTT assay [23] Antimicrobial activity

Ethyl acetate extract Methanol extractLeavesin vitro S. aureus, E.coli, B. cereus, S. typhi [23] Aqueous extract Whole plantin vitro B. subtilis, B. laterosporus, S. aureus, M. luteus, P. aeruginosa, V. cholera, E. coli, S. typhi[43] Essential oil Aerial partsin vitroSalmonella spp., B. cereus, B. subtilis, S. pyogenes, S. aureus, E. coli, P. aeruginosa, Shigella spp., C. albicans [6]

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crosis factor)- and IL (interleukin)-6. In an ani- mal study by Bose et al. (2007), extracts of C. ruti- dosperma aerial parts were tested for analgesic effect, antipyretic, and anti-inflammatory activities [33]. In detail, oral administration of ethanol crude extract (200 and 400 mg/kg) and its fractions (200 mg/kg) resulted in significant reduction in the number of writhing stimulated by 0.6% acetic acid in mice. The activity followed the order: petroleum ether > ethyl acetate > n-butanol > diethyl ether fraction. Specific phytochemicals responsible for these bioactivities of C. rutidosperma were unknown. Nevertheless, it was suggested that the presence of phytoconstituents, such as terpenes, triterpenes, and phenolics, in the plant may account for the analgesic, antipyretic, and anti-inflammatory properties.

In another investigation, 90%-ethanol extract of C. rutidosperma aerial parts displayed potent anti-arthritic activity compared to other extracts (i.e., petroleum ether, diethyl ether, ethyl acetate fractions) [2]. In the chronic model of granuloma pouch in rats, the ethanol extract at the dose of 200 mg/kg inhibited 48% while the figure for the arthritis model was 44%. For prednisolone (5 mg/kg), the percentages of inhibition were 58.5%

and 59%. Methanol extract of C. rutidosperma was shown to possess significant anti-nociceptive activity assessed by analgesic and anti inflammatory assays, as evidenced by its ability to reduce nociception in a mouse model [34]. In hot-plate and tail-flick assays, the extract exerted a significant dose-dependent increase in the time taken to respond to thermal stimuli (at doses of 100 and 200 mg/kg), with a marked latency increase occur- ring at 90 and 120 minutes. Notably, in acetic acid- stimulated writhing and formalin-stimulated licking tests for anti-inflammatory potential, the extract at doses of 100 and 200 mg/kg demonstrated a remarkable reduction in writhing and licking re- sponses.

Antidiabetic activity

When diabetic patients consume carbohy- drates, the enzymes -amylase and -glucosidase break these molecules down and cause an increase in postprandial glucose levels. To reduce the risk of developing diabetes, it is important to control postprandial hyperglycemia by inhibiting the activity of these enzymes. Previous research reported the inhibitory efficacy of 70% ethanol C.

rutidosperma extract towards -amylase was comparable with that of diclofenac [17]. One in vivo study found that administration of aqueous leaf extract of the plant to streptozotocin-diabetic rats enhanced the activity of hepatic glucokinase and inhibited glucose-6-phosphatase (gluconeo- genesis enzymatic activity) [31]. The hypoglycae- mic and antihyperglycaemic activities of the plant were studied in alloxan diabetic rats [35]. In the model, methanol extract of the plant’s leaves at the dose of 200 mg/kg presented stronger glycemic control in comparison with glibenclamide.

Anticancer activity

Methanolic extracts of C. rutidosperma leaves were screened for anticancer activity against HepG2 cancer cell line [23]. The cytotoxicity analysis revealed a concentration-dependent manner. At the level of 100 g/mL, the methanol extract showed the considerable cytotoxicity against HepG2 cells.

Antimicrobial activity

Research has shown that multiple phenolics including sinapic acid, myricetin, ellagic acid, ferulic acid, and kaempferol detected in C. ruti- dosperma may exert powerful antimicrobial activities [36-40]. There is also evidence that eugenol and phytol found in C. rutidosperma essential oil have the ability to suppress the growth of bacteria and fungi [41, 42]. This suggests that C. ruti- dosperma could have inhibitory eﬀects on microbial growth. In fact, one study reported that ethyl acetate and methanol extracts of C. rutidosperma leaves (150 g/mL) exhibited inhibitory effects on the growth Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Bacillus cereus with inhibition zone ranging between 10 and 12 mm [23] while those of streptomycin were 14 – 16 mm. Aqueous extract of the plant was shown to have moderate antibacterial activity against Bacil- lus laterosporus, Staphylococcus aureus and Escherichia coli [43]. Besides, essential oil of the plant has demonstrated strong inhibition of the growth of Bacillus cereus, Streptococcus py- ogenes and Candida albicans, with inhibition zone approximate to those of ampicillin and gentamicin [6].

Conclusion

C. rutidosperma has a widespread distribution

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across multiple tropical and subtropical countries in Asia and Africa. The plant contains a diverse mixture of phytochemicals, such as carotenoids, chlorophylls, alkaloids, saponins, phenolic acids, flavonoids, and diterpenoids. The presence of these phytochemicals could be responsible for the high antioxidant properties and numerous bioactivities of C. rutidosperma important to human health. Future research endeavors and clinical studies should be focused on comprehensively in- vestigating the health-promoting properties of isolated phytochemicals obtained from the plant.

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