Combretum caffrum is the Eastern Cape South African bushwillow tree.
In C. caffrum, combretastatins A-1, A-4 and B-1 can be found.
- Mike Thompson (2005-09-06). "Combrestatin - Molecule of the month". Bristol University Chemistry Dept Home Page. Bristol University. Retrieved 2006-09-20.
- Pettit GR, Cragg GM, Singh SB (May–June 1987). "Antineoplastic agents, 122. Constituents of Combretum caffrum". Journal of Natural Products. 50 (3): 386–391. doi:10.1021/np50051a008. PMID 3668557.
- ^Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of microtubule assembly, derived from Combretum caffrum. Pettit, G R : Singh, S B : Niven, M L : Hamel, E : Schmidt, J M, J-Nat-Prod. 1987 Jan-Feb; 50(1): 119-31Archived 2009-07-19 at the Wayback Machine.
Medicinal plants have been used since ancient times in virtually all cultures as a source of medicines , and are of great importance to the health of individuals and communities . Traditional medicine is used in all parts of the World and has a rapidly growing economic importance, mainly through the use of medicinal plants, especially in developing countries . The medicinal use of plants of the family Combretaceae is widely described in the scientific literature [4,5,6]. This family is distributed in appoximately 20 genera with 600 species. The largest genera are Combretum and Terminalia, with about 370 and 200 species, respectively . Members of the Combretaceae occur mainly in tropical and subtropical areas, for example, in Africa and Brazil.
Phytochemical Components Isolated from the Active Combretum Species
Phytochemical studies carried out in the genus Combretum have demonstrated the occurrence of many classes of constituents, including triterpenes, flavonoids, lignans and non-protein amino acids, among others . Since the 1970s, several unusual compounds have also been isolated from Combretum species, for example, 9,10-dihydrophenanthrenes and a substituted bibenzyl from C. molle . Bisoli et al. isolated 11 triterpenes and their glycosides from C. laxum, among them, oleanane-, ursane- and lupane-type such as arjunolic acid, arjunglucoside II, bellericoside, chebuloside II, quadranoside IV, asiatic acid and betulinic acid . Cycloartane dienone lactone was isolated from C. quadrangulare , and alkaloids (combretine and betonicine) from the leaves of C. micranthum . Some flavonoids, rhamnoctrin (Figure 1A), quercetin-5,3'-dimetylether (Figure 1B), ramnazin (Figure 1C) and kaempferol were isolated from C. erythrophyllum , as well as quercetrin, kaempferol and pinocembrin (flavanone) from C. apiculatum . Cardamonin (chalcone) was also isolated from C. apiculatum  and ellagic acid derivatives from C. kraussii . Combretastatins, a group of stilbenes, have been isolated from several species of Combretum .
As referenced above, there are several studies describing the phytochemistry of the species of this family, and the medicinal value of plants lies in the chemical substances that produce a physiological change in the human body . Therefore, in continuation of our research on bioactive molecules from the various species of different plant families [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47], the aim of this study was to review the literature on the bioactivity of the genus Combretum.
Figure 1. The molecular structures of compounds isolated from Combretum species.
Figure 1. The molecular structures of compounds isolated from Combretum species.
2. Results and Discussion
In this review, it was possible to list thirty-six species of the genus Combretum. The effectiveness of the plant extracts depended on the type of drug studied and the bioassay models. Thus, it was possible to classify the extracts as active or inactive. In this study, we chose more species referenced in data collected in the NAPRALERT natural products database and the scientific literature databases ScienceDirect and PubMed.
Combretum micranthum is a bushy shrub or creeper found all over Africa. C. micranthum is used in traditional medicine for the treatment of wounds and sores [48,49,50] and of fever (especially malaria fever), cough and bronchitis [49,51]. In studies evaluating its antibacterial activity, the extracts used were obtained with different solvents (ethanol, chloroform, methanol or water). Activity was observed against the following bacterial species: Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella species, Streptococcus species, Proteus vulgaris, Klebsiella species, Sarcina lutea, Micrococcus luteus and Bacillus subtilis [52,53,54,55,56,57]. In addition, antifungal activity against Candida albicans was noted . Antiviral activity of a methanolic extract was reported against Herpes simplex 1 and Herpes simplex 2 . Toxicity studies have reported the activity of an ethanolic extract in the brine shrimp lethality test . Benoit et al.  and Karou et al.  reported anti-Malarial activity against Plasmodium falciparum. However, a methanolic extract did not display cytotoxic activity aganist THP1 cells  (Table 1).
Di Carlo et al.  demonstrated immuno-stimulating activity with a suspension of powdered leaf. Chika and Bello  demonstrated an antidiabetic effect for the aqueous leaf extract of C. micranthum. A dose of 100 mg/kg of the extract was the most effective, among the doses tested. It produced a significant hypoglycemic and antidiabetic activity comparable to the effect of a standard drug (0.6 mg/kg glibenclamide) (Table 1). This study demonstrated the potential antidiabetic properties of aqueous leaf extract of C. micranthum for both type 1 and type 2 diabetes, justifying its traditional use in the treatment of this disease in Northwestern Nigeria. All of the above results contribute to justifying the use of the plant in traditional medicine for treating various conditions, particularly infections and diabetes.
C. molle (soft-leaved Combretum, velvet bush willow) is a tree with a larger, straighter trunk compared to most species of Combretum, further distinguished by its rough bark and dense crown. It occurs throughout tropical Africa and in the Arabian Peninsula in areas where woodlands and wooded grasslands predominate, often forming pure stands on hillsides .
C. molle has been widely used as a medicinal plant to treat various diseases such as parasitic, protozoan and other infectious diseases in East [65,66,67] and West Africa . Antibacterial studies have demonstrated its activity against Staphylococcus aureus and Helicobacter pylori at different extract concentrations [69,70,71]. Antifungal activity was reported in models that used Epidermophyton floccosum, Microsporum gypseum, Trichophyton mentagrophytes, T. rubrum, Candida albicans, C. neoformans, Aspergillus fumigatus, Sporothrix schenckii and Microsporum canis [72,73]. C. molle was also able to inhibit the growth of Mycobacterium tuberculosis . Antitrypansomal and anthelmintic activities of different extracts have also been reported [4,75,76,77] (Table 1).
Toxicity studies have reported the activity of aqueous and acetone extracts against Artemia salina . Furthermore, Asres et al.  and Gansané et al.  reported antimalarial activity of the methanolic extract against Plasmodium falciparum at different concentrations tested. Molluscicidal effect of aqueous extract against Biomphalaria pfeifferi was also observed . Meanwhile, embryotoxic effects have not been reported  (Table 1).
Methanolic extracts of the roots and leaves (25 μg/mL) of C. molle showed strong cytotoxic effects against T-24 bladder cancer cells . In addition, the aqueous and methanol extracts of C. molle were screened for inhibitory effects against HIV-1 reverse transcriptase. These extracts produced relatively strong inhibition of RNA-dependent-DNA polymerase (RDDP) activity. The compounds responsible for these activities in this plant were not sought  (Table 1).
In the case of compounds obtained from C. molle, the analgesic and antiinflammatory properties of mollic acid glucoside (MAG) (Figure 1H), a 1α-hydroxycycloartenoid extracted from Combretum molle leaves, have been investigated in mice and rats . The results of this laboratory animal study indicate that MAG possesses analgesic and antiinflammatory effects in the mammalian models used. The author suggested that MAG possesses both centrally- and peripherally-mediated analgesic effects.
Ojewole also reported on the cardiovascular effects of MAG. The results of this study showed that this compound was capable of causing bradycardia, vasorelaxation and hypotension in the animals evaluated . In addition, hypoglycemic and antidiabetic activity have also been demonstrated .
In vitro anti-HIV activity of two isolated tannins from an acetone fraction, punicalgin (Figure 1F) and CM-A (whose structure has not yet been fully elucidated), was assessed against human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The results displayed selective inhibition of HIV-1 replication with selective indices (ratio of 50% cytotoxic concentration to 50% effective antiviral concentration) of 16 and 25, respectively and afforded complete cell protection against the virus-induced cytopathic effect when compared to control samples. Neither of the tannins was able to inhibit HIV-2 replication .
These results contribute to the validation of the popular use of this plant species in the treatment of bacterial, fungal, protozoan and viral infections and cardiovascular problems, among others.
The plant C. erythrophyllum (Burch.) Sond., commonly known as river Combretum, is a medium-sized, spreading, densely foliaged tree up to 12 m in height, which has been used by traditional healers for a variety of disorders [85,86]. C. erythrophyllum is widely used in traditional medical practice in southern Africa. It has been used for treating abdominal pains and venereal diseases, which suggests the presence of antibacterial compounds in the leaves .
As part of the treatment for venereal diseases, powdered roots of C. erythrophyllum are inserted into the vagina, which has resulted in several fatalities. The same procedure is followed to reduce the size of the vaginal orifice. In addition, the plant has been used to treat sexually transmitted diseases .