Review Article

Traditional uses, phytochemistry, and pharmacological properties of tomentosa Lam.: A review Sibhatu Gebrehiwot1*, K. Krishna Chaithanya2

ABSTRACT

Capparis tomentosa belongs to the family commonly referred Afrikaans. The species is reported to occur in , , Ethiopia, Lesotho, Namibia, South , Swaziland (which is documented as native), and Kenya (exotic). Conventionally, this has been used for cooking and medicinal purpose and its flower buds are trading in the international market and also its consummation. It is used for medicinal purposes, as food spice, in ritual cleansing, and for decorative purposes in Zimbabwe, , South Africa, and in Kenya where it is native. In herbal and traditional medicine, C. tomentosa is used to treat rheumatism, madness, snakebite, chest pain, jaundice, malaria, headache, coughs, pneumonia, constipation, infertility, and to prevent abortions. It is used to treat leprosy, tuberculosis, and gonorrhea. The phytochemicals that give the plant its unique biological activity are alkaloids, L’stachydrine, saponin glycosides, alkaloids, phytosterols, terpenoids, tannins, sterol, polyphenols, flavonoids, and anthranoids. Two important alkaloids, stachydrine, and 3-hydroxy-4 methoxy-3-methly-oxindole have been isolated from C. tomentosa. In this review, it has been shown that the plant parts (root, leaves, and fruit) have many traditional values, pharmacological uses, and phytochemical constituents that are an excellent source of healing or curing various diseases.

KEY WORDS: Capparis tomentosa, Traditional medicine, Phytochemicals Toxicity, Pharmacological use, Antimalarial Activity

INTRODUCTION thorns at the junction of the stem and leaf base. The white and pink flowers have multiple . The Capparis tomentosa belongs to the family fruit is pink to orange in color, round, and stalked. Capparaceae commonly referred Afrikaans The seeds are surrounded by fleshy and gray fruit (Wollerigekapperbos); Amharic (gumero); Arabic pulp.[1] The Capparaceae composed of 45 genera and (sharube); English (woolly caper-bush); French approximately 1000 species, distributed especially (caprier d΄ Afrique); Shona (khawa); Somali (gomborlik); Swahili (mbadapaka); and Tigrigna in the tropical and subtropical regions, especially (andel).[1,2] Its biophysical limits of altitude range East Africa and South America. Plant of this family [4] from 1200 to 2300 m. The species is reported to occur is annual, perennial some time climbers or tree. in Botswana, Eritrea, Ethiopia, Lesotho, Namibia, Naturally, Capparis grows in various regions and is South Africa, Swaziland (which is documented as distributed in the entire arid region. native), and Kenya (exotic).[2,3] It is a scrambling shrub, sometimes developing into a tree that can There are more than 250 species of the Capparis. grow as high as 10 m tall. The twigs and leaves Conventionally, this plant has been used for cooking are yellow-green in color and are covered in soft, and medicinal purpose, and its flower buds are trading velvety hairs. The oblong leaves are approximately in the international market and also its consummation. 50 mm × 20 mm, with a pair of sharp, hook-like Since this plant has the capacity to grow in arid and semiarid regions that are subject to extreme Access this article online conditions, it is important to consolidate the studies and agriculture of this plant to resolve the problem Website: jprsolutions.info ISSN: 0975-7619 related to its production.[5,6]

1Department of Biology, College of Natural and Computational Science, Raya University, Ethiopia, 2Department of Chemistry, College of Natural and Computational Sciences, Aksum University, Aksum, Ethiopia

*Corresponding author: Sibhatu Gebrehiwot, Department of Biology, College of Natural and Computational Sciences, Raya University, Ethiopia. E-mail: [email protected]

Received on: 17-01-2020; Revised on: 12-02-2020; Accepted on: 19-03-2020

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TRADITIONAL USES The oxindole compound has been found to possess weak anti-spasmodic activity, substantiating the traditional Capparis species, as a large spontaneous plant, has a use of Capparis species for their anti-inflammatory wide range of applications in traditional medicine.[8] and anti-convulsive properties. The essential oil from C. tomentosa was composed of a Beta Phellandrene as One of these species is C. tomentosa which is found a major component followed by beta pinene. The other [9] widely in local pharmacopeias throughout Africa. It oils were <6% in the composition. The composition is used for medicinal purposes, as food spice, in ritual of the volatile essential oils may contribute to the cleansing, and for decorative purposes in Zimbabwe, overall repellent activity of the crude essential [10] Senegal, South Africa, and in Kenya where it is native. oil.[29] The fruits of C. tomentosa were examined In herbal and traditional medicine, C. tomentosa is and L’stachydrine (1) was isolated as periodide and used to treat rheumatism, madness, snakebite, chest analyzed as the HCl salt from the ethanol extract of the pain, jaundice, malaria, headache, coughs, pneumonia, seeds pulp.[30] Stachydrine has been widely researched constipation, infertility, and to prevent abortions. It is in the treatment for rheumatism.[3] In another study[31] [11-13] used to treat leprosy, tuberculosis, and gonorrhea. isolated from the roots and oxindole (2) which was The roots are boiled in water and half a cup of this identified as 3-hydroxy-3- methyl-4-methoxyoxindole infusion is drunk three times per day to manage cough from the roots have been reported [Figure 1]. As [2,12] and chest pain. It is traditionally used to cure part of a continuing study of the constituent of this madness, snakebite, headache, impotence, and sterility plant, structural elucidation of a dipeptide derivative [2,14,15] (in women). The roots are boiled in water and (3) and a phytosterol (4) is reported [Figure 1]. The half a cup of this infusion is drunk three times per day phytosterol 24-ethylcholestan-5-en-3-ol and the [3,12,16-18] for coughs, chest pains, and asthma. There had dipeptide derivative N-benzoylphenylalanylaninol been reports of several fatal cases of poisoning from the acetate have also been isolated from the roots.[32] use of this plant as medicine.[19-21] The roots play a key role in sexual and reproductive health. They are used to PHARMACOLOGICAL USE OF cure HIV opportunistic infections, such as tuberculosis, Herpes zoster and Herpes simplex, and chronic diarrhea. C. TOMENTOSA LAM. The roots are also used as an infusion to assist with Anti-repellent threatened abortion, gonorrhea, syphilis, HIV/AIDS, On a study of the plant, the repellent action of the and also to stop bleeding after childbirth.[22,23] In Kenya, essential oil extract of C. tomentosa as anti-maize it is alleged to heal patients suffering from asthma, weevil Sitophilus zeamais was evaluated and the infertility/sterility, high blood pressure, bleeding gums, result showed a dosage-dependent action. Nerolidol gout, arthritis, and diabetes mellitus, as an immune and linalool showed high repellent activity at the booster for HIV/AIDS as it boosts CD4 counts within highest dosage level. The activity of the essential oil a short period of using it.[24,25] It is also used to treat extract from C. tomentosa would be as a result of the psychiatric diseases in Ethiopia.[26] composition of the individual oils. The study also extrapolated that the activity could also be as a result PHYTOCHEMICAL ANALYSIS of synergistic activity between individual essential [29] The phytochemicals that give the plant its unique oils. On another study, C. tomentosa showed good [33] biological activity are alkaloids, L’stachydrine, repellence against the malarial vector, A. arabiensis. saponin glycosides, alkaloids, phytosterols, This could be attributed to the fact that it belongs to terpenoids, tannins, sterol, polyphenols, flavonoids, the family Capparaceae which has a high concentration and anthranoids.[25,27,28] Two important alkaloids, of chemicals such as stachydrine and 3-hydroxy-4- [34] stachydrine, and 3-hydroxy-4 methoxy-3-methly- methoxy-3-methly-oxindole. The methanolic extract oxindole have been isolated from C. tomentosa.[29,30] displayed greater activity because polar solvents extract more volatiles. Volatiles have been reported to have strong repellency and mortality activity.[35] The study also suggested that the repellency and insecticidal potential of C. tomentosa can be recommended as an apparent source of some biologically active compounds valuable in the development of potential options for vector control, in areas where mosquitoes are resistant to conventional insecticides.[33]

Antimicrobial Activity Studies by Steenkamp et al. showed that C. tomentosa Figure. C. tomentosa.[7] has good antimicrobial activity against Staphylococcus

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Figure 1: Compounds isolated from Capparis tomentosa[9]\ aureus, Streptococcus pyogenes, E. coli, and Anti-inflammatory Activity Pseudomonas aeruginosa. The methanolic and aqueous In a study by Van Wyk et al., C. tomentosa is leaf extract of C. tomentosa inhibited P. aeruginosa, S. reported used to treat rheumatism because it contains [13] typhimurium, and Tricoderm sp. Moreover, in studies L’stachydrine and 3-hydroxy-4-methoxy-3-methyl- by Sama and Ajaiyeoba, the antimicrobial activities oxindole, a known anti-inflammatory compound.[40] In of ethanol extracts of aerial part (stem and leaf) of the contrary, another study indicated that the plant had C. tomentosa and learned that the ethanol extract of no significant inflammatory activity.[41] the plant inhibited the growth of S. aureus, Bacillus cereus, Aspergillus flavus, and Candida albicans and Antimalarial Activity A. flavus. The results indicated that the traditional use Much work has not been done on the antiplasmodial of C. tomentosa extract to treat diseases such as coughs activities of the plant. In vitro study of dichloromethane and pneumonia is justified and recommended the extract of C. tomentosa was reported to have activity further identification of the specific active compounds against P. falciparum with respect to its leaf, stem, and from the plant extract.[27] However, the antimicrobial root.[42] activity of the plant could possibly be due to the secondary metabolites present in the plant: Alkaloids, Antioxidant Activity anthranoids, flavonoids, glycosides, polyphenols, The observation that the reducing power of the saponins, and steroids.[34] Flavonoids are known to aqueous roots extracts of C. tomentosa increased with possess antimicrobial properties.[35] C. tomentosa concentration could be explained by the fact that the was found to have antibacterial, anti-Trichomonas, extracts contained chemical substances capable of and antifungal properties.[36] In another study, 70% reacting with potassium ferricyanide (Fe3+) to form EtOH extract of C. tomentosa exhibited moderate potassium ferricyanide (Fe2), which then reacts with to significant (MIC 125 g/mL) activity toward Mycobacterium tuberculosis H37Rv.[37] ferric chloride to form a ferric ferrous complex that has an absorption maximum at 700 nm.[43] The observation Leaf extracts showed pronounced activity against that reducing power was linearly proportional to the Coxsackie virus. Extracts of the aerial parts of the concentration is explained by the fact that the C. tomentosa exhibited significant in-vitro antimicrobial amounts of antioxidants increased with an increase activity against the bacteria S. aureus and B. cereus, in the amount of crude extracts. Reducing power is having stronger activity than the reference drug associated with antioxidant activity and indicates that ampicillin, and against the fungi A. flavus and C. albicans, primary and secondary antioxidants with the ability comparable to griseofulvin.[38] The study demonstrated to donate electrons and reduce oxidized intermediates that L-stachydrin found in C. tomentosa Lamm root of lipid peroxidation processes are present in the barks possessed anti-tuberculosis property in in vivo, and extracts.[43] In the assay, the yellow color of the test this compound was found to increase blood coagulation, solutions changes to various shades of green and blue thus shortening bleeding time and blood loss.[39] and this depends on the reducing power of the extract

1008 Drug Invention Today | Vol 13 • Issue 7 • 2020 Sibhatu Gebrehiwot and K. Krishna Chaithanya concentrations. Similarly, the radical scavenging test of 1000 mg/kg body weight of aqueous roots activity by DPPH and phosphomolybdate assay extracts of C. tomentosa was found to allow normal indicates that the roots extracts contain antioxidant growth of mice compared to the normal control over compounds. In the body, free radicals are constantly 30-day toxicity experiment.[48] This could be explained generated and they can cause extensive damage to by the fact that the extracts did not contain any toxic tissues and biomolecules, leading to various disease chemical compound or mineral element.[33] The root conditions, especially degenerative diseases and extract of C. tomentosa did not cause any mortality extensive lyses. Many synthetic drugs protect against up to a dose of 5000 mg/kg in acute toxicity study oxidative damage but they have adverse side effects. and did not show any sub-acute toxicity properties on An alternative solution to the problem is to consume the given doses.[52] A similar result was also reported natural antioxidants from food supplements and by Hurinanthan in which C. tomentosa displayed traditional medicines.[44] These vitamins are involved in no toxic effects on the brine shrimp.[33] Moreover, the synthesis of enzymes that are essential to metabolic Mlambo et al. reported that the leaves and fruit do not cell activity, synthesize of hormones, repairing genetic need to be detoxified to be fed to goats.[53] However, materials, and maintain the normal functioning of contradictory to report made by Ahmed et al. in which the nervous system, processes critical in alleviating C. tomentosa had a toxic effect on goats fed with the the effects of diabetes mellitus.[45] Furthermore, the leave.[21] Moreover, Getahun reported that both goats extracts of C. tomentosa demonstrated excellent and camels die instantly if consumed.[54] On another scavenging capability. This result indicates that the report compiled by Melaku and Getachew, the rise extract can be used for the prevention of degenerative of unknown Camel diseases, namely, camel hind leg diseases such as Parkinson’s, Alzheimer’s, cancer, paralysis which is believed to be due to the ingestion diabetes, heart disease, arthritis, and osteoporosis.[46] of the plant C. tomentosa.[55] A report from West They also provide important health benefits in the African Dry Zones revealed that C. tomentosa Lam. form of antioxidant activity by preventing aging.[47] (root and fruit) was found to toxic to humans and even other animals.[56] Similarity, poisoning of donkeys Antidiabetic Activity after browsing C. tomentosa have been reported Antidiabetic activity of the aqueous root extracts of in northern Kenya and poisoning of cattle, sheep, C. tomentosa was investigated in alloxanized mice. goats, and camels in Sudan, resulting in hydrothorax, Extracts at a dose of 50, 100, and 200 mg/kg body hydropericardium, and ascites.[57] However, toxicity weight were given orally. This study demonstrated studies conducted by Tefera demonstrated that this that the aqueous roots extracts of C. tomentosa plant is harmless.[58] From this, it can be extrapolated exhibited dose-dependent hypoglycemic activity that observational studies have been implied that that is significantly higher than that of the reference the plant is toxic to the given animals, whereas drug glibenclamide.[48] The observed hypoglycemic experimental studies confirmed that the plant is activity of C. tomentosa could apparently be due innocuous. As suggested by Bahru et al.[59] concrete to its strong antioxidant activity and antidiabetic and detailed evidence on nutritional values and the chemical compounds or possibly due to the alkaloids’ possible toxic effects of this plant are not confirmed presence in this plant.[33,34] These antioxidants may despite its positive/negative perception for its edibility. contribute by balancing free radical production at the On the other hand, the plant is accessible and may cell or even mitochondrial level by scavenging free contribute to new bioactive compounds that are safe [49] radicals produced in the cells. The hypoglycemic and effective.[60] Therefore, such discrepancies may activity could also be due to increased glucose plant urge further research works on the area. transport and uptake, increased glycogen storage, and modulation of insulin secretion. In a study by CONCULSION Sharma et al.[50] demonstrated the action of alkaloids from Capparis on various targets for the treatment of The plant C. tomentosa has various medicinal values diabetes and their multiple therapeutic effects. These in folk medicine. In this review, it has been shown facts explain the use of a caper by old people to treat that the plant parts (root, leaves, and fruit) have diabetic disease.[51] many traditional values, pharmacological uses, and phytochemical constituents that are an excellent source SAFETY AND TOXICITY OF of healing or curing various diseases. To mention few, C. TOMENTOSA it has been used traditionally to treat is used to treat rheumatism, madness, snakebite, chest pain, jaundice, Some medicinal has been found to cause abnormal malaria, headache, coughs, pneumonia, constipation, laboratory results in the form of alteration in liver infertility, and to prevent abortions. It is used to function tests, electrolyte disturbances, blood sugar treat leprosy, tuberculosis, gonorrhea, and cough level changes, heavy metal poisoning, and alteration and chest pain. Moreover, it is traditionally used to in thyroid profiles. However, the single-dose toxicity cure madness, snakebite, headache, impotence, and

Drug Invention Today | Vol 13 • Issue 7 • 2020 1009 Sibhatu Gebrehiwot and K. Krishna Chaithanya sterility (in women). It is also used to treat fever; 2014. Available from: http://www.worldbotanical.com/african_ mixed with dried hyena and antelope blood and ox plants.html. [Last accessed on 2019 Mar 07]. 8. Nizar T, Walid E, Ezzeddine S, Abdelhamid K, Saida T, Nizar N. fat, it is used in the ritual treatment of pneumonia The caper (Capparis L.): Ethnopharmacology, phytochemical antioxidants play a key role in preventing the risk of and pharmacological properties. Fitoterapia 2011;82:93-101. so many diseases by interacting with free radicals. 9. Akoto O, Oppong IV, Addae-Mensah I, Waibel R, Achenbach H. The plant has variety pharmacological activities. Isolation and characterization of dipeptide derivative and phytosterol from Capparis tomentosa Lam. Sci Res Essays These activities are present due to the presence of a 2008;3:355-8. variety of phytochemicals present in the plant. The 10. Kokwaro JO. Medicinal Plants of East Africa. 3rd ed. Nairobi: plant parts have medicinal value and used for the University of Nairobi Press; 2009. same traditionally throughout the world, especially 11. Expert Committee on the Diagnosis and Clasification of Diabetes Mellitus. American diabetes association: Clinical in African countries. Ethnopharmacological studies practice recommendations 2002. Diabetes Care 2002;25 Suppl of the plant strengthen the concept of utilizing the 1:S1-147. plant as a source to facilitate safe and effective 12. Van Wyk B, Gericke N. Peoples Plants-A Guide to Useful herbal treatments for biological problems. Despite, Plants of South Africa. Pretoria: Briza Publications; 2003. 13. Steenkamp V, Mathivha E, Gouws MC, Van Rensburg CE. its biological action has been approved by various Studies on antibacterial, antioxidant and fibroblast growth researchers, only a few biologically active compounds stimulation of wound healing remedies from South Africa. 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