Department of Pharmacognosy & Herbal Medicine

 

 

 

ETHNOBOTANICAL USES

Clausena anisata is commonly utilized by herbalists in the Eastern Cape of South Africa to treat various ailments, including lung ulcers, tuberculosis, and persistent coughs, while traditional healers in Tanzania use it for fungal skin infections and oral candidiasis. In Temeke area of Dar es Salaam, Tanzania, it serves as an anticonvulsant for treating epilepsy, and its new leaf material is burned in some regions of Africa and the Philippines to repel mosquitoes. Clausena anisata is utilized by the Ibibios of the Niger Delta to treat a wide range of health issues, including worm infections, respiratory problems, hypertension, and various pains, with its leaf juice used as ear drops and its roots chewed for stomach aches. In Tanzania, it is employed for oral candidiasis and epilepsy, while in South Africa, it helps manage high blood pressure, and its fresh leaves are burned in some regions of Africa and the Philippines to repel mosquitoes; additionally, it has ethnoveterinary applications for managing maggots and other parasitic infections in cattle. 

PHARMACOLOGICAL ACTIVITIES

ANTIOXIDANT ACTIVITY

Clausena anisata demonstrates significant antioxidant activity, as shown by various methods such as ferric reducing power tests and DPPH assays. Silver nanoparticles synthesized from Clausena anisata root extract exhibited strong scavenging activity of 74.07% at a concentration of 500 μg/mL, with this antioxidant capacity linked to phytochemical components that also aid in the stabilization of the nanoparticles during synthesis. The antioxidant activity of Clausena anisata leaf and stem extracts, evaluated through the DPPH free radical scavenging test, was lower than that of ascorbic acid, which scavenges free radicals and prevents oxidative stress.

 

ANTI-INFLAMMATORY ACTIVITY

The hydroethanolic extracts of Clausena anisata leaf and stem demonstrated anti-inflammatory effects in carrageenan-induced paw edema, comparable to indomethacin, and anti-arthritic activities in the CFA-induced arthritis model in rats, showing a notable reduction in the arthritic index similar to celecoxib, linked to its inhibition of inflammatory mediators and oxidative stress respectively. Likewise, the crude ethanol extract from the roots showed notable activity at 1000 mg/kg, with isolated compounds osthol and an isocoumarin B exhibiting slightly higher efficacy than indomethacin at 9 mg/kg.

ANALGESIC ACTIVITY

Studies showed that the analgesic effect of Clausena anisata leaf and stem extracts was evaluated using hot plate and acetic acid-induced writhing tests, likely due to the presence of opioid receptors. The crude ethanol extract from the roots demonstrated a maximum analgesic effect of 72.1% at 1000 mg/kg. The hydroethanolic leaf extract exhibited notable antinociceptive activity in the formalin-induced pain model, mediated by interactions with multiple pathways, and contained beneficial phytochemicals such cardiac glycosides that may enhance its analgesic effects.

ANTIPLASMODIAL AND ANTI-MALARIAL ACTIVITY

Clausena anisata demonstrated anti-plasmodial activity against chloroquine-sensitive Plasmodium berghei in in vivo mice models with efficacy measured through Leishman-stained thin blood smears.. Clausena anisata's root bark contains bioactive substances with strong anti-malarial activity against Plasmodium falciparum, demonstrating schizonticidal, gametocytocidal, and trophozoite properties, while also showing minimal cytotoxicity and good selectivity; additionally, extracts exhibited significant efficacy against Plasmodium berghei in mice, with a 500 mg/kg/day chloroform extract resulting in a 66.1% reduction in preventive tests and a 73.4% reduction in suppressive tests.

ANTI-DIABETIC ACTIVITY

Silver nanoparticles (SNPs) from Clausena anisata root extract show potential as an anti-diabetic agent. They inhibit α-amylase, postpone carbohydrate digestion, and increase glucose absorption by yeast cells. The study investigated the hypoglycaemic effect of Clausena anisata root methanolic extract on diabetic rats. It found that the extract reduced blood glucose concentrations in both normal and diabetic rats, with the highest dose reducing basal blood glucose by 57.52% and 51.3%, respectively.

ANTIMICROBIAL ACTIVITY

The ethanolic leaf extract of Clausena anisata exhibited strong antibacterial activity against various Gram-positive and Gram-negative bacteria, as well as Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 0.5 to 7.0 mg/mL for Gram-positive bacteria, 2.5 to 10.0 mg/mL for Gram-negative bacteria, and 5.5 mg/mL for the fungal strains evaluated using microdilution and agar well diffusion methods. The study found that hydroethanolic extracts from Clausena anisata stem bark and leaves have antibacterial properties against periodontal disease and cariogenic infections, particularly on Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum.

ANTI-HYPERTENSIVE ACTIVITY

The aqueous leaf extract of Clausena anisata effectively lowers aortic blood pressure in a spontaneously hypertensive rat model, particularly at a dosage of 400 mg/kg, through mechanisms involving reduced plasma angiotensin II levels and without significant diuretic or adverse chronotropic effects, likely due to its phytochemical constituents such as terpenoids and flavonoids.

ANTI-CONVULSANT

The ethanolic extracts of Clausena anisata root bark, stem bark, and leaves demonstrated anticonvulsant properties against pentylenetetrazole-induced seizures in mice, with the root bark extract showing a significant delay in convulsion onset and a 33.33% protection rate at an 800 mg/kg dose, likely due to its high levels of tannins and saponins, supporting its traditional use in epilepsy treatment.

ANTI-CANCER ACTIVITY

A comprehensive systematic review meticulously analyzed a myriad of studies investigating the anticancer activity of Clausena species. Collating and synthesizing findings from various authors, their work sheds light on the potential therapeutic benefits of Clausena anisata in combating cancer cells. The table presented herein succinctly summarizes the diverse array of extracts and compounds derived from Clausena anisata, along with their corresponding anticancer activities as reported in the literature.

Extract/Compounds	Cancer Cell Lines Tested	Anticancer Activity
Ethanolic Leaf Extract	Human epidermal melanocyte cell line (PCS-200-013) and cellular tyrosinase	Nontoxic to melanocytes at 15 μg/mL but inhibited cellular tyrosinase with IC50 of 1.56 μg/Ml
Hydroethanolic Root Extract	Jurkat (human acute‐cell leukemia) cells	IC50 = 293.14 μg/mL
Leaves and Stem Bark Ethanol Extracts	HL-60 monocyte lymphoma (U937) cells	Low cytotoxicity with IC50 = 74.46 μg/mL
Leaves Ethanol Extract	Human rhabdomyosarcoma cancer cell line	CC50 of 8.83 μg/mL
Methanolic and DCM Aerial Part Extracts	HL-60 cells	IC50 = 118.50 μg/mL and 225.40 μg/mL
Methanolic Stem Bark Extract	Hoechst 33342, alamar blue, calcein-AM, glutathione depletion and oxygen-consumption assays	Minimal toxic dosage of < 7.81 to 250 μg/mL
Murrayamine-A, 3-(1, 1-dimethyl allyl) xanthyletin, gravelliferone, excavatin D, coumarin, phellopterin, 1-O-methylclausenolide	HeLa cells	For 70, LC50 was > 10 lg/mL. For the other compounds, LC50 = 1.14 to 3.26 lg/mL and selective to normal Vero cells (LC50 = 69.15–434.78 lg/mL)
Roots, Leaves and Bark Extracts	Leukemia CCRF-CEM cells	Inhibited less than 50% of cancer cells at 40 mg/mL
Methanolic and Hexanic Leaves and Stem Bark Extracts	HeLa cells	No anti cancer activity was found
Clausamines B−E, Clausine F, Mukonal, Glycosinine	HL-60 cells	Clausamine E had the highest cytotoxicity (cell viability 47.3%); clausamines B and C had lower cytotoxicity (viability ~80%)
Clausamines A−E, Ekeberginine, Methyl Carbazole-3-carboxylate, Clausine F, O-demethylmurrayanine	Epstein-barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells	All the compounds inhibited Epstein-Barr virus activation at 1 × 10^2 mol ratio

 

TOXICOLOGICAL PROFILE

The acute toxicity of Clausena anisata extracts in hexane and chloroform on mice was investigated. The LD50 of the chloroform extract was 4166.7 mg/kg, but the hexane extract did not exhibit any mortality at dosages up to 5000 mg/kg. These findings imply that whereas the hexane extract seems to have a relatively modest acute toxicity profile, the chloroform extract has a substantial acute toxicity. An exponential association between toxicity and increasing dosages of C. anisata aqueous leaf extracts, spanning from 0 to 10,000 mg/L, was found. The findings showed that the leaf extract was extremely low in toxicity; just 30% of nauplii were killed at a dosage of 10 g/L. Using the fitted line's formulas, the LD50 was determined to be 27172.5 mg/L. Thus, rats administered 400 mg/kg of bw/day should not have any significant harmful effects. Up to the fourteenth day of observation, the extract at up to 5000 mg/kg, p.o. did not cause death; nonetheless, writhing, hyperactivity, tachypnea, and stooling were seen as toxic behaviors. ClDEausena anisata leaf Brine Shrimp Lethality Test findings showed an LC 50 µg/ml of 533± 37.0.

CLINICAL VALIDATED USES

Not reported

DRUG-DRUG INTERACTION

Not reported 

REFERENCE

Agbor, A. M., Fotsing, K. P., Dountio, S. H., Fokunang, N. C., & Naidoo, S. (2020). Phytochemical Investigation and Anti-Microbial Activity of Clausena anisata on Cariogenic and Periodontopathic Bacteria. European Journal of Medicinal Plants, 11–25. https://doi.org/10.9734/ejmp/2020/v31i1930345

Agyepong, N., Agyare, C., Adarkwa-Yiadom, M., & Gbedema, S. (2014a). Phytochemical Investigation and Anti-Microbial Activity of Clausena Anisata (Willd), Hook. African Journal of Traditional, Complementary and Alternative Medicines, 11(3), 200. https://doi.org/10.4314/ajtcam.v11i3.28

Agyepong, N., Agyare, C., Adarkwa-Yiadom, M., & Gbedema, S. (2014b). Phytochemical Investigation and Anti-Microbial Activity of Clausena Anisata (Willd), Hook. African Journal of Traditional, Complementary and Alternative Medicines, 11(3), 200. https://doi.org/10.4314/ajtcam.v11i3.28

Commons, W. (2021). Commons. Wikimedia. Org/wiki/File: Timm, _Vasilii_Fedorovich. _Zashchitniki_Sevastopolia. _ (1851-1862). Jpg.

Hamza, O. J. M., Van Den Bout-van Den Beukel, C. J. P., Matee, M. I. N., Moshi, M. J., Mikx, F. H. M., Selemani, H. O., Mbwambo, Z. H., Van Der Ven, A. J. A. M., & Verweij, P. E. (2006). Antifungal activity of some Tanzanian plants used traditionally for the treatment of fungal infections. Journal of Ethnopharmacology, 108(1), 124–132. https://doi.org/10.1016/j.jep.2006.04.026

Herbal, K. (2020, December 1). TWI NAMES OF SOME PLANTS USED TRADITIONALLY IN GHANA. KENOCH HG HERBAL CLINIC. https://kenochherbal.com/2020/12/01/twi-names-of-some-plants-used-traditionally-in-ghana/

Hyde, M., Wursten, B., Ballings, P., & Coates-Palgrave, M. (2022). Flora of Zimbabwe: Species information: Acmella radicans var. Radicans.

Irungu, B. N., Mbabu, M. J., Kiboi, D. M., Moindi, E., & Romano, M. (2012). In vivo antimalarial and acute toxicity properties of hexane and chloroform extracts from Clausena anisata (Willd.) Benth.

Ishola, I. O., Olayemi, S. O., Oreagba, I. A., Ifeanyi, C. I., & Popoola, T. D. (2015). Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (Willd.) Hook. F. Ex Benth (Rutaceae) in Rodents: Possible mechanism of actions. Niger. J. Physiol. Sci.

Kenechukwu. (2012). Pharmacological justification for the ethnomedical use of Clausena anisata root-bark extract in the management of epilepsy. Journal of Applied Pharmaceutical Science. https://doi.org/10.7324/JAPS.2012.2907

Kumatia, C. K. (2018). Analgesic, Anti-Inflammatory and Anti-Oxidant Activities of Clausena anisata leaf and Stem Extracts and Quantitative and Qualitative Phytochemical Analysis of their Contents.

Kumatia, E. K., Annan, K., Dickson, R. A., Mensah, A. Y., Amponsah, I. K., Appiah, A. A., Tung, N. H., Edoh, D. A., & Habtemariam, S. (2017). Anti-inflammatory and Analgesic Effects in Rodent Models of Ethanol Extract of Clausena anisata Roots and their Chemical Constituents. Natural Product Communications, 12(1), 1934578X1701200. https://doi.org/10.1177/1934578X1701200119

Kumatia, E. K., Zoiku, F. K., Asase, A., & Tung, N. H. (2023). Anti-malarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria parasites: Ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach. Malaria Journal, 22(1), 264. https://doi.org/10.1186/s12936-023-04678-0

Lakshmi, V., Prakash, D., Raj, K., Kapil, R. S., & Popli, S. P. (1984). Monoterpenoid furanocoumarin lactones from clausena anisata. Phytochemistry, 23(11), 2629–2631. https://doi.org/10.1016/S0031-9422(00)84114-X

Lawal, I., Grierson, D., & Afolayan, A. (2015). Phytochemical and antioxidant investigations of a Clausena anisata hook, a South African medicinal plant. African Journal of Traditional, Complementary and Alternative Medicines, 12(1), 28. https://doi.org/10.4314/ajtcam.v12i1.5

Lunyera, J., Wang, D., Maro, V., Karia, F., Boyd, D., Omolo, J., Patel, U. D., & Stanifer, J. W. (2016). Traditional medicine practices among community members with diabetes mellitus in Northern Tanzania: An ethnomedical survey. BMC Complementary and Alternative Medicine, 16(1), 282. https://doi.org/10.1186/s12906-016-1262-2

Mbah, C., & Kenechukwu, F. (2010). Preliminary Screening of Ethanolic Extracts of Clausena anisata for Anticonvulsant Activity. Bio-Research, 7(2). https://doi.org/10.4314/br.v7i2.56601

Moshi, M. J., Kagashe, G. A. B., & Mbwambo, Z. H. (2005). Plants used to treat epilepsy by Tanzanian traditional healers. Journal of Ethnopharmacology, 97(2), 327–336. https://doi.org/10.1016/j.jep.2004.11.015

Ngadjui, B. T., Ayafor, J. F., Sondengam, B. L., & Connolly, J. D. (1989). Quinolone and carbazole alkaloids from Clausena anisata. Phytochemistry, 28(5), 1517–1519. https://doi.org/10.1016/S0031-9422(00)97778-1

Ntamo, M. T. L., Paul, J. S., Leon, H., Linde, B. O. H., & Melvin, M. G. (2016). The effects of an aqueous leaf extract of Clausena anisata (Willd.) Hook.f.ex Benth. On blood pressure, urine output, angiotensin II levels and cardiac parameters in spontaneously hypertensive rats. Journal of Medicinal Plants Research, 10(28), 425–434. https://doi.org/10.5897/JMPR2016.6135

Ojewole, J. A. O. (2002). Hypoglycaemic effect of Clausena anisata (Willd) Hook methanolic root extract in rats. Journal of Ethnopharmacology, 81(2), 231–237. https://doi.org/10.1016/S0378-8741(02)00085-5

Okokon, J. E., Etebong, E. O., Udobang, J. A., & Essien, G. E. (2012). Antiplasmodial and analgesic activities of Clausena anisata. Asian Pacific Journal of Tropical Medicine, 5(3), 214–219. https://doi.org/10.1016/S1995-7645(12)60027-3

Okokon, J. E., Udoh, A. E., Andrew, U. E., & Uchechukwu, L. (2012). Antiinflammatory and antipyretic activities of Clausena anisata. Clinical Pharmacology.

Omara, T., K., A., J., V., & Kagoya, S. (2022a). Clausena anisata (Willd.) Hook.f. ex Benth. (Rutaceae): Ethnomedicinal uses, phytochemistry, pharmacological activities, toxicity, and clinical application. Traditional Medicine Research, 7(6), 51. https://doi.org/10.53388/TMR20220417001

Omara, T., K., A., J., V., & Kagoya, S. (2022b). Clausena anisata (Willd.) Hook.f. ex Benth. (Rutaceae): Ethnomedicinal uses, phytochemistry, pharmacological activities, toxicity, and clinical application. Traditional Medicine Research, 7(6), 51. https://doi.org/10.53388/TMR20220417001

Omara, T., K., A., J., V., & Kagoya, S. (2022c). Clausena anisata (willd.) hook.f. ex benth. (rutaceae): Ethnomedicinal uses, phytochemistry, pharmacological activities, toxicity, and clinical application. Traditional Medicine Research, 7(6), 51. https://doi.org/10.53388/TMR20220417001

Songue, J., Kouam, Dongo, E., Mpondo, T., & White, R. (2012). Chemical Constituents from Stem Bark and Roots of Clausena anisata. Molecules, 17(11), 13673–13686. https://doi.org/10.3390/molecules171113673

Tafadzwa, M., Chagonda, L. S., & Moyo, R. S. (2005). Screening of some Traditional Medicinal Plants from Zimbabwe for Biological and Anti-microbial Activity.

Teklehaymanot, T., & Giday, M. (2007). Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia. Journal of Ethnobiology and Ethnomedicine, 3(1), 12. https://doi.org/10.1186/1746-4269-3-12

Uwaifo, A. O. (1984). The mutagenicities of seven coumarin derivatives and a furan derivative (nimbolide) isolated from three medicinal plants. Journal of Toxicology and Environmental Health, 13(4–6), 521–530. https://doi.org/10.1080/15287398409530517

Yakoob, A. T., Tajuddin, N. B., Mohammed Hussain, M. I., Mathew, S., Qadri, I., & Govindaraju, A. (2016). Antioxidant and Hypoglycemic Activities of Clausena anisata (Willd.) Hook F. Ex Benth. Root Mediated Synthesized Silver Nanoparticles. Pharmacognosy Journal, 8(6), 579–586. https://doi.org/10.5530/pj.2016.6.10

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