Mezoneuron benthamianum

Mezoneuron benthamianum (Baill.): A Botanical, Phytochemical, and Pharmacological Reference

1. Identity and Botanical Characterization

Scientific Name and Nomenclature

Mezoneuron benthamianum Baill. is the accepted botanical name for this species. It belongs to the family Leguminosae-Caesalpinioideae and was originally described by the French botanist Henri Ernest Baillon. Its principal accepted synonym is Caesalpinia benthamiana (Baill.) Herend. & Zarucchi; the spelling variant Mezonevron benthamianum Baill. is also recorded. Both names appear in the primary scientific literature and are used interchangeably across research publications. The genus Mezoneuron was established by Desfontaines in 1818, and the species was later transferred to Caesalpinia s.l. before being returned to Mezoneuron on the basis of molecular evidence. Molecular evidence now supports Mezoneuron as a distinct genus separate from Caesalpinia s.l.

The genus Mezoneuron is broadly distributed, with its centre of diversity in South East Asia, but with species also in Africa, Australasia, and Hawaii. Mezoneuron benthamianum is one of the African species within this genus. A comprehensive taxonomic revision of Mezoneuron was published in Phytotaxa 274 (2016) by R.P. Clark of the Royal Botanic Gardens, Kew.

Common and Vernacular Names

In The Gambia, the plant is commonly known as "tiger's claw." In the Yoruba region of Nigeria, it is known by the indigenous names "amuranju" or "jenifiran." In South West Nigeria it is called "Jenifinran." Among Senegalese ethnic groups, the plant carries names including némin (Balanta), fu wók (Diola, Fogny), é boñ and fu ngog (Diola), and bu ropoti / bu topot (Banyun), as recorded in Burkill's The Useful Plants of West Tropical Africa (1985).

Morphology and Natural Range

The plant is a shrub or woody climber growing in West Africa. Young leaves are bright fiery red, and as they age, they turn a dark green color. The stem has persistent thorns and is black. The bushes are branching, the root is brown and hard, and the stem is an 8-m-tall woody climber. Flowers are yellow; pods are bright red. Its distribution extends across West Africa, with documented occurrence in Senegal, The Gambia, Guinea-Bissau, Guinea, Sierra Leone, Liberia, Côte d'Ivoire, Ghana, Togo, Benin, and Nigeria, as recorded in the Flora of West Tropical Africa.

Common Forms and Preparations

The plant is used medicinally in several preparations, depending on the plant part and intended use. Traditionally, a paste made from powdered root bark mixed with shea butter, palm oil, or palm kernel oil may be used topically. In Guinea, urethral discharges are treated with a decoction made from the root, bark, and leaves. Senegal uses the dried root's infusion as a bath or beverage to treat general ill health. In scientific studies, preparations have included hydroethanolic extracts (70% v/v), aqueous extracts, methanolic extracts, dichloromethane extracts, ethyl acetate fractions, and hexane fractions, prepared from both leaf and root material.

2. Traditional and Historical Use

West African Ethnomedicinal Context

Mezoneuron benthamianum has a well-documented history of use in the traditional medicine systems of multiple West African nations, spanning at least several centuries of unrecorded practice and documented in ethnobotanical records from the mid-twentieth century onward. The plant is used in traditional medicine for the management of several diseases such as ulcers, wounds, and skin disease in different countries.

Guinea

Decoctions of the leaves of M. benthamianum are used by traditional healers in Guinea to treat malaria, and this use was validated by a preliminary clinical assay. In Guinea, urethral discharges are treated with a decoction made from the root, bark, and leaves.

Ghana

In Ghana, C. benthamiana (=Mezoneuron benthamianum) is found mostly in secondary forest and finds use in the treatment of topical infections and wounds. In Ghana, the powdered roots are used to cure wounds and skin conditions when combined with palm kernel oil or shea butter.

Nigeria

In South West Nigeria, traditional medicine practitioners claim that the plant is effective in the treatment of pain, fever, diarrhoea, and general malaise. The plant is used locally as chewing sticks in southwest Nigeria.

Senegal

In Senegal, the root is apparently used as a chewing stick with potent anti-dental caries properties, while the leaves are given as a mild laxative to relieve enteralgia (intestinal pain). Senegal also uses the dried root's infusion as a bath or beverage to treat general ill health.

Sexual Health and Vascular Uses

The roots are used in traditional medicine as an aqueous decoction for many purposes, especially for erection impairment. Traditional medicine uses the roots' aqueous decoction as aphrodisiacs, and its vasorelaxant qualities have also been noted.

Summary of Traditional Preparations by Use

• Malaria: Leaf decoction, taken orally (Guinea)
• Wounds and skin infections: Powdered root bark mixed with palm kernel oil or shea butter, applied topically (Ghana)
• Urethral discharge: Decoction of root, bark, and leaves (Guinea)
• Oral hygiene / dental caries prevention: Roots used as chewing sticks (Nigeria, Senegal)
• Laxative / enteralgia: Leaf preparations (Senegal)
• General ill health: Dried root infusion used as bath or beverage (Senegal)
• Erection impairment: Aqueous root decoction (West Africa broadly)
• Pain, fever, diarrhoea: Various preparations (Nigeria)

3. Key Phytochemical Constituents and Active Compounds

Overview of Chemical Classes

Mezoneuron benthamianum is known to contain gallic acid derivatives, cassane diterpenoids, flavonoids, tannins, and anthraquinones. Phytochemical screening of extracts has consistently revealed the presence of anthraquinones, cardiac glycosides, flavonoids, reducing sugars, saponins, steroids, tannins, and terpenoids. M. benthamianum has been shown to include a number of peptides, unsaturated long-chain aldehydes, alkaloidal components, flavonoids, saponins, and tannins.

Gallic Acid Derivatives

The leaves of Mezoneuron benthamianum yielded methyl gallate and gallic acid as the constituents responsible for its antibacterial activity. Additional compounds isolated include (–)-shikimic acid-3-O-gallate, 1-O-methyl-D-chiro-inositol, (–)-epicatechin, (–)-epicatechin-3-gallate, and kaempferol-3-(6′-galloyl)glucoside. Gallic acid and trans-resveratrol were among the predominant phytochemicals found in leaf extracts.

Cassane Diterpenoids

Bioactivity-guided fractionation of the light petroleum extract of Caesalpinia benthamiana (=Mezoneuron benthamianum) root bark led to the isolation of two cassane diterpenoids, designated as benthaminin 1 and benthaminin 2. A subsequent study reported the isolation of a third compound: bioactivity-guided fractionation of the chloroform extract of the root bark of the plant resulted in the isolation of a novel cassane-type furanoditerpenoid, designated as benthaminin 3. Dickson et al. (2012) also reported the isolation of deoxycaesaldekarin C, benthaminin 1, benthaminin 2, and benthaminin 3 from the root of Ghana-grown M. benthamianum.

Novel Diterpenes from Leaves

The phytochemical investigation of leaves further allowed the isolation of three diterpenes, including two new compounds named mezobenthamic acid A and mezobenthamic acid B, and neocaesalpin H, as well as quercetin, kaempferol, resveratrol, gallic acid and its ethyl ester, β-sitosterol glucoside, and 13b-hydroxy-pheophorbide a.

Polyphenols

Polyphenolic compounds including trans-resveratrol, piceatannol, and gallic acid have been isolated from the plant. Trans-resveratrol, piceatannol, and gallic acid are described as potent polyphenols isolated from Mezoneuron benthamianum effective as anticaries, antioxidant, and cytotoxic agents.

Root Phenolic Compounds

Roots of C. benthamiana are rich in phenolic compounds including gallic acid, resveratrol, and tannins.

Essential Oil Constituents

The chemical composition of the essential oil from the aerial part of Mezoneuron benthamianum Baill. was studied using GC and GC-MS. The oil contains fifteen compounds, constituting about 93.4% of the oil, dominated by monoterpenes (36.5%), sesquiterpenes (20.4%), and sesquiterpenoids (19.6%). Five major compounds were 3-carene (14.2%), α-trans-nerolidol (13.3%), α-pinene (11.7%), α-farnesene (11.6%), and α-thujene (6.7%).

4. Mechanisms of Action

Antibacterial Activity

The leaves of Mezoneuron benthamianum yielded methyl gallate and gallic acid as the constituents responsible for its antibacterial activity. The cassane diterpenoids from the root bark contribute additional antibacterial mechanisms: benthaminin 1 was the more active antibacterial compound with MIC values of 47.8 µM for both Staphylococcus aureus and Micrococcus flavus. In a study examining root bark extracts against multi-resistant clinical strains, the zone of inhibition against Staphylococcus induced by Mezoneuron benthamianum extracts at 100 mg/mL was higher than that of the reference antibiotics oxacillin and cefoxitin.

Antioxidant Activity

Benthaminin 2 was the more active antioxidant compound and showed IC50 values of 42.7 µM and 74.2 µM for the DPPH and TBA assays, respectively. In oral caries-related investigations, the ethyl acetate and aqueous methanol extracts exhibited a higher antioxidant activity (IC50 = 23.70 and 21.30 µg/mL, respectively) than standard ascorbic acid (IC50 = 38.20 µg/mL).

Antiplasmodial Mechanisms

Active compounds from the leaves — belonging to several phytochemical classes — contribute together to the global antiplasmodial activity of the hydroethanolic extract against the P. falciparum parasite. The compounds identified as contributing to this activity include kaempferol, gallic acid ethyl ester, and 13b-hydroxy-pheophorbide a, as identified by bioactivity-guided fractionation.

Vasorelaxant and Nitric Oxide Mechanisms

The aqueous extract of C. benthamiana was tested for vasorelaxing properties using isolated rat aortic rings precontracted by phenylephrine, and the influence of the extract on the production of endothelial isoform of nitric oxide synthase (eNOS) was measured by quantitative polymerase chain reaction (QPCR) analysis. Results showed that the aqueous extract had significant vasorelaxing properties. The extract also had a strong radical activity against reactive oxygen species in cell-free and cellular systems and stimulated eNOS mRNA expression.

Alpha-Amylase Inhibition

The potential antidiabetic mechanism of M. benthamianum has been attributed in part to alpha-amylase inhibition. The α-amylase inhibitory activities showed that the dichloromethane leaf extract (MBLD; IC50 = 27.4 µg/mL), the ethyl acetate root extract (MBRE; IC50 = 72.2 µg/mL), gallic acid (IC50 = 27.4 µg/mL), and methyl gallate (IC50 = 43.9 µg/mL) had higher activity than the standard drug acarbose (IC50 = 378.2 µg/mL). In silico, methyl gallate was docked into the active site of targeted diabetic proteins — human pancreatic alpha-amylase, pig pancreatic alpha-amylase, and tetrameric IIB-HSDI — showing good interactions with binding affinities of −4.8, −4.8, and −6.5 kcal/mol, respectively.

Anti-Candida Mechanisms

M. benthamianum inhibits cell adherence, hyphae formation, and phospholipase production in Candida albicans. The study specifically evaluated antifungal and anti-virulence activities of leaf preparations.

Anti-inflammatory Mechanisms

The topical anti-inflammatory effect of the essential oil was assayed as inhibition of TPA-induced ear edema in mice. The oil at 5.0 and 2.5 mg dose levels exhibited more effect than indomethacin (0.25 mg) in reducing edema.

5. Scientific Evidence by Area of Use

5.1 Antimalarial / Antiplasmodial Activity

Evidence level: Preliminary human evidence (one small clinical trial); supported by multiple in vitro and in vivo studies.

The strongest area of scientific investigation for this plant is its antimalarial activity. Hydroethanolic extracts (70% v/v) of M. benthamianum leaves showed a moderate in vitro activity against P. falciparum 3D7, with IC50 values in the range 22.5–32.6 µg/mL depending on the batch; a dark precipitate formed during ethanol evaporation showed higher activity (IC50 = 6.5 µg/mL).

A separate investigation tested the methanolic extract against multiple protozoan parasites. The methanolic extract showed the strongest antiprotozoal activity against P. falciparum (IC50 4 µg/mL), a good activity against T. brucei (IC50 13 µg/mL), and a moderate activity against T. cruzi (IC50 31 µg/mL), along with an IC50 on human MRC-5 cells of 32 µg/mL.

Clinical / human evidence: A prospective, placebo-controlled ethnotherapeutic trial assessed the antimalarial effectiveness and tolerability of C. benthamiana syrup administered orally to children with uncomplicated malaria as compared with chloroquine syrup. Evaluated on two groups of 21 children (5–15 years, versus chloroquine), a hydroethanolic leaves extract showed promising results regarding efficacy (92% reduction of parasitic load in the treatment group at day 28, versus 91% for chloroquine) as well as its tolerance. This pilot clinical result is encouraging; however, the trial was small (21 children per group), and these findings require confirmation in larger, adequately powered randomized controlled trials. No regulatory approval or systematic review currently exists for this indication.

This study provides some concrete evidence to support the ethnopharmacological use of Mezoneuron benthamianum leaves extract in the management of malaria, and the active compounds can be further studied for their antiplasmodial potential.

5.2 Antibacterial Activity

Evidence level: In vitro only; no human clinical studies.

Multiple independent laboratory investigations have confirmed antibacterial activity of M. benthamianum extracts and isolated compounds. The leaves yielded methyl gallate and gallic acid as the constituents responsible for antibacterial activity; additional isolates — (–)-shikimic acid-3-O-gallate, (–)-epicatechin, (–)-epicatechin-3-gallate, and kaempferol-3-(6′-galloyl)glucoside — were also isolated, and minimum inhibitory concentrations of these compounds against Gram-positive and Gram-negative microorganisms and a fungus were determined.

From root bark, the lowest MIC (63 µg/mL) of benthaminin 3 was recorded against Staphylococcus aureus and Bacillus subtilis. However, this compound was observed to have only a mild inhibitory effect against resistant strains of bacteria including methicillin-resistant S. aureus, tetracycline-resistant S. aureus, and erythromycin-resistant S. aureus, with MIC values greater than 1000 µg/mL. All antibacterial evidence is from in vitro models; no human clinical data are available.

5.3 Oral Health / Anticaries Activity

Evidence level: In vitro only; no human clinical studies.

A study investigated the anticaries activities of crude extracts of M. benthamianum root against four clinical oral pathogens (S. aureus, E. coli, Pseudomonas aeruginosa, and Streptococcus mutans); the ethyl acetate extract had the highest anticaries activity, with MIC values of 78 and 156 µg/mL, while the hexane extract had the least activity (MIC 2500 µg/mL against S. mutans and E. coli). The traditional use of the plant root as a chewing stick in Nigeria is thus supported at the in vitro level, but no clinical oral health trials have been conducted.

5.4 Anticandidal / Antifungal Activity

Evidence level: In vitro only; no human clinical studies.

Studies evaluated the phytochemical constituents, antioxidant, antifungal, and anti-virulence activities of traditionally used Mezoneuron benthamianum leaves; extracts were prepared using acetone and methanol, antioxidant activity was studied using the DPPH method, anti-Candida albicans activity was established, and the effects on germ tube and phospholipase production, as well as on host cell adherence, were assessed.

5.5 Analgesic, Antipyretic, and Anti-inflammatory Activity

Evidence level: Animal studies (rodent models) only; no human clinical studies.

The analgesic, antipyretic, and anti-inflammatory effects of the aqueous extract of Mezoneuron benthamianum were evaluated in mice, rats, and rabbits using the mouse writhing, tail flick, hot plate, and formalin-induced pain tests; 2,4-dinitrophenol-, D-amphetamine-, and E. coli lipopolysaccharide-induced pyrexia; and carrageenan-, egg albumin-, and xylene-induced oedema models. The extract (400–1600 mg/kg) and acetylsalicylic acid (100 mg/kg) produced a significant (p < 0.05) inhibition of the second-phase response in the formalin pain model, while only the highest dose (1600 mg/kg) of the extract showed a comparable antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid–induced abdominal writhing, and the tail flick latency and hot-plate pain threshold were dose-dependently enhanced by the extract, though these were significantly lower than those produced by morphine (2 mg/kg).

Regarding topical anti-inflammatory effects, the essential oil was assayed for inhibition of TPA-induced ear edema in mice, and the oil at 5.0 and 2.5 mg dose levels showed more effect than indomethacin (0.25 mg) in reducing edema, supporting its use as an anti-inflammatory agent in folk medicine.

5.6 Anti-diarrhoeal Activity

Evidence level: Animal studies only; no human clinical studies.

The effect of the aqueous extract of Mezoneuron benthamianum on experimentally induced diarrhoea, intestinal propulsive movement, and intestinal fluid accumulation (enteropooling) were investigated in rats and mice; the extract (400, 800, and 1600 mg/kg, orally) produced a significant (p < 0.05) and dose-dependent reduction in propulsion in castor oil–induced intestinal transit in mice. In a dose-dependent manner, the extract delayed the onset of diarrhoea, produced a significant decrease in the frequency of defaecation and severity of diarrhoea, and protected the mice treated with castor oil.

5.7 Vasorelaxant and Aphrodisiac / Sexual Health Activity

Evidence level: Animal studies and in vitro models only; no human clinical studies.

The roots of Caesalpinia benthamiana (=Mezoneuron benthamianum) are used in traditional medicine as an aqueous decoction for many purposes, especially for erection impairment, and studies investigated the action of the plant on sexual behaviour and assays on potential modes of action. The aphrodisiac properties of the aqueous extract administered orally by gavage (50 mg/kg body weight) to male rats were evaluated by observing the sexual behaviour of animals. A short-term toxicity study was undertaken to establish the therapeutic index of the extract administered orally to rats at high dose (2 g/kg body weight). The results showed that the aqueous extract had significant vasorelaxing properties; the extract also had strong radical activity against reactive oxygen species in cell-free and cellular systems and stimulated eNOS mRNA expression.

5.8 Antidiabetic Activity

Evidence level: In vitro and in silico only; no human clinical studies.

Research has revealed detailed chemical and biological studies on Mezoneuron benthamianum and its isolated compound as an antioxidant and antidiabetic. The α-amylase inhibitory activities showed that the dichloromethane leaf extract (IC50 = 27.4 µg/mL), the ethyl acetate root extract (IC50 = 72.2 µg/mL), gallic acid (IC50 = 27.4 µg/mL), and methyl gallate (IC50 = 43.9 µg/mL) had higher activity than the standard drug acarbose (IC50 = 378.2 µg/mL). Furthermore, in silico pharmacokinetic and toxicology properties of methyl gallate using the AdmetSAR and SwissADME software showed that the compound has good pharmacokinetic properties and is generally non-toxic. These results are entirely preclinical; translation to human therapeutic use has not been demonstrated.

5.9 Antiprotozoal Activity Beyond Malaria

Evidence level: In vitro only.

Leaf extracts were tested for their in vitro antiprotozoal activity against Trypanosoma brucei brucei and T. cruzi and the chloroquine-sensitive Ghana strain of Plasmodium falciparum; the methanolic extract showed the strongest antiprotozoal activity against P. falciparum (IC50 4 µg/mL), a good activity against T. brucei (IC50 13 µg/mL), and a moderate activity against T. cruzi (IC50 31 µg/mL), along with an IC50 on human MRC-5 cells of 32 µg/mL. This selectivity index (SI >8 for P. falciparum) was considered favorable in the context of screening studies.

6. Body Systems and Health Areas Associated with the Plant

• Immune / Infectious Disease: Antimalarial, antiprotozoal (trypanosomiasis models), antibacterial (Gram-positive and Gram-negative organisms)
• Integumentary (Skin): Wound healing, treatment of skin infections
• Oral Health: Anti-dental caries (chewing stick use), antifungal against oral Candida species
• Gastrointestinal: Anti-diarrhoeal, laxative (leaf preparations), anti-ulcer (referenced in animal work)
• Cardiovascular / Vascular: Vasorelaxation via eNOS stimulation, antioxidant activity against ROS
• Reproductive / Sexual Health: Aphrodisiac use (traditional), animal aphrodisiac models
• Endocrine / Metabolic (Potential): Alpha-amylase inhibition relevant to blood glucose management (in vitro/in silico only)
• Pain and Inflammation: Analgesic, antipyretic, and anti-inflammatory (animal models)

7. Dosage Forms and Dosages Reported in Studies

No standardized dosage has been established for any application of Mezoneuron benthamianum. The following dosages appear in cited research literature exactly as reported:

• Anti-diarrhoeal (rodent): 400, 800, and 1600 mg/kg, given orally, in castor oil–induced intestinal transit studies in mice.
• Analgesic / antipyretic / anti-inflammatory (rodent): 400–1600 mg/kg in analgesic and anti-inflammatory rodent models.
• Aphrodisiac (rodent): 50 mg/kg body weight, administered orally by gavage to male rats.
• Short-term toxicity (rodent): 2 g/kg body weight, given orally, to establish therapeutic index.
• Antiplasmodial in vitro: Hydroethanolic extracts tested at concentrations yielding IC50 values of 22.5–32.6 µg/mL (moderate fraction) and 6.5 µg/mL (most active fraction) against P. falciparum 3D7.
• Anticaries (in vitro): MIC values of 78 and 156 µg/mL for the most active (ethyl acetate) extract against cariogenic pathogens.
• Alpha-amylase inhibition (in vitro): IC50 values of 27.4 µg/mL (dichloromethane leaf extract and gallic acid) and 43.9 µg/mL (methyl gallate), compared to acarbose at 378.2 µg/mL.
• Clinical antimalarial (pediatric): Syrup form administered orally to two groups of 21 children aged 5–15 years in a clinical comparison with chloroquine syrup. Exact dosage/concentration of the syrup was not specified in the available abstract data.

8. Safety Considerations

Short-Term Toxicity in Animal Models

The aphrodisiac properties of the aqueous root extract were evaluated at 50 mg/kg body weight in male rats, and a short-term toxicity study was undertaken at 2 g/kg body weight orally to establish the therapeutic index. Systematic long-term toxicity studies specific to M. benthamianum are not available in the published literature accessed for this article.

In Silico Safety Data for Isolated Compounds

In silico pharmacokinetic and toxicology properties of the isolated compound methyl gallate, evaluated using AdmetSAR and SwissADME software, showed that the compound has good pharmacokinetic properties and is generally non-toxic. These are computational predictions only and do not constitute clinical safety data.

Resistance-Modifying Activity

Research on M. benthamianum has explored the concept of antimicrobial resistance modification. Benthaminin 3 was observed to have only a mild inhibitory effect against resistant strains of bacteria including methicillin-resistant S. aureus, tetracycline-resistant S. aureus, and erythromycin-resistant S. aureus, with MIC values greater than 1000 µg/mL.

Presence of Cardiac Glycosides

Phytochemical screening of extracts has revealed the presence of cardiac glycosides alongside other compound classes. The toxicological implications of cardiac glycoside content in preparations prepared from this plant have not been formally characterized in human safety studies.

Clinical Tolerability

In the one available human study, a hydroethanolic leaves extract showed promising results regarding tolerability in two groups of 21 children (5–15 years) in a clinical antimalarial trial compared with chloroquine syrup. No serious adverse events were specifically reported in the available data from this trial, but the small sample size limits definitive safety conclusions.

Absence of Regulatory Assessments

As of the most recent research identified, Mezoneuron benthamianum has not been evaluated by any major regulatory body or pharmacopeial authority, including the NIH Office of Dietary Supplements, NCCIH, WHO, EMA, EFSA, or any national pharmacopeia. No monograph, safety limit, or authorized therapeutic indication exists at the international level. All scientific data remain at the level of ethnobotanical documentation, in vitro experimentation, animal models, or a single small clinical pilot.

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