harmacologyOnLine August 30, 2012

Archives • 2012 • vol.2 • 1 - 22

A REVIEW OF THE MEDICINAL PROPERTIES AND APPLICATIONS OF Pycnanthus angolensis (WELW) WARB

Daniel Gyingiri Achel*1,2, Miguel Alcaraz1, Robert Kingsford-Adaboh3, Alexander Kwadwo Nyarko4, Yahuza Gomda5 1Department of Radiology and Physical Medicine, University of Murcia. 30100-Campus Espinardo, Murcia 2Applied Radiation Biology Centre, Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, Legon Accra 3Department of Chemistry, University of Ghana, Legon 4Noguchi Memorial Institute for Medical Research, University of Ghana, Legon 5Nuclear Agriculture Centre, Biotechnology and Nuclear Agriculture Research Institute, Ghana Atomic Energy Commission, Kwabenya, Accra-Ghana

Abstract Pycnanthus angolensis (also known as African/false nutmeg) is native to the forest zones of West Central Africa. Its use in folklore for the cure of diseases is well documented. Data collected from several references from various research groups in the literature confirm its wide spread use in folk medicine. Among the ailments purported to be cured or controlled by extracts of the plant include diabetes, cognitive disorders, cancer, osteoarthritis, to assuage inflammation, fight microbial infection and for wound healing. Extensive investigative work conducted on the plant exposing its rich phytochemical profile probably provides clue to its value as an important medicinal plant. Over 50 phytochemicals have been isolated from the plant some of which are potential new drug leads. The current review presents the ethnobotanical uses of Pycnanthus angolensis through some evaluated biological activities of various extracts on different models to the nume- rous chemical compounds isolated from the plant. It concludes by succinctly touching on the current and future perspectives of the plant.

Keywords: Pycnanthus angolensis, medicinal plant, folklore, biological activities, phytochemical profile

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Introduction agent, analgesic, anthelmintic, antidote for poiso- ning, anti-bleeding agent, anti-inflammatory and The Magnonliflorae super-order to which pain soothing agent. At least there exists substan- Pycnanthus angolensis (Myristicaceae) belong tial anecdotal evidence supporting the health comprises 19 genera of trees and shrubs and 380 benefits of the various preparations of the plant species of lowland rainforest trees distributed in either alone or in combination with other agents Asia (four genera), Africa and Madagascar (nine some of which have been summarized in table 1. genera) and America (six genera). Morphologically, Indeed numerous scientific studies seem to suggest the Myristicaceae which are easily recognizable on that some of these claims may be accurate. the fields by their straight trunks, characteristic blood-like sap exudates, few leaves and nutmeg-like fruits are considered one of the most primitive of Major chemical constituents the Angiosperms. They have simple alternate stipules, habitually dark green and leathery leaves In order to evaluate the potential of P. angolensis with tiny male or female petalless flowers on as a source of additional bioactive compounds, different trees [1]. Male flowers have 2 to 20 united various parts of the plant have been investigated stamens while female flowers have a single ovary and important compounds with high therapeutic with one ovule (potential seed). A fleshy covering, potentials reported some of which have been known as an aril, surrounds the fluted seed. The discussed below and summarised in table 2. fruits are yellowish-red, ovoid, drupes, with laciniate seed almost obovoid-globose to base embedded in Flavonoids a fleshy aril. An evergreen tree, P. angolensis may attain a height of 40 m and girth of 150 cm. It P. angolensis is known to elaborate a number of flowers in October and November, at the same time flavonoid compounds including the flavonones as the previous year’s fruits are ripening. The fruits genkwainin [3,4], 8-hydroxykanzakiflavone-2 [4], remain on the tree until about February. Dehiscence liguiritigentin [5] (–)-epicatechin and (+)-catechin takes place on the tree, but many of the fruit [6]. Isoflavonoids established to be present in P. clusters fall unopened [2]. P. angolensis is native to angolensis are biocchanin A [3,5,7,8], formononetin the forest zones of tropical Africa with a geographi- [4,5,7,9-11], 7, 4’-dimethoxy-2’-hydroxyisoflavone cal distribution stretching across western Africa [5,10], prunetin [3,5], calycosin [3], irilone [5,8], from Guinea to Cameroon, including the countries tectorigenine, genistein, and 2’-hydroxybiochanin A of Sierra Leone, Liberia, Cote D'Ivoire, Ghana, Togo, [5]. Mansoor et al, 2011, studied the cytotoxic Benin, Nigeria, Equatorial Guinea, Angola and effects of some nine flavonoid compounds isolated Uganda. from P. angolensis against hepatoma HuH-7 cells (at a concentration 20μM) and reported that genetisin exhibited the highest cytotoxicity of 50% when Folkloric uses compared with the control compound used. The medical importance of the plant has long Furthermore, when screened against a panel human been recognized and at present scientific research hepatoma HuH‐7 cells for apoptosis induction, most is rife on its therapeutic utility because traditional of these isoflavonoids exhibited higher potency healers and ethnobotanists have ascribed nume- than acclaimed control compounds used [5]. Other rous health benefits to the use of the plant. useful bioactivities of some of these flavonoids and Literature is replete with numerous health benefits isoflavonoids have been reported elsewhere [8]. linked to the use of different parts of P. angolensis Flavonoids are polyphenolic compounds posses- including but not limited its role in fighting hypergly- sing 15 carbon atoms; two benzene rings joined by a caemia, sterility in women, as an antimicrobial

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 3 (1 - 22) linear three carbon chain. The six major subgroups musculoskeletal system and other stress related of flavonoids include: chalcones, flavones, flavonols, traumas in animals preferably in equines. In a flavanones, anthocyanins and isoflavonones. randomised controlled double-blind study, myri- Flavonoids are widely valued as nutraceutical and steoleic acid formulated to CMO was compared cosmeceutical phytonutrients, which are based on with phenylbutazone in subjects with rheumatoid their antioxidant activity. Flavonoids have long been arthritis. CMO was found to significantly improve known to exhibit several pharmacological proper- morning stiffness, walking time and joint swelling, ties; acting as anti-allergenic, anti-inflammatory, however, its effects were less than that elicited by antiviral, antiproliferative, anti-cancer, antibacterial, phenylbutazone. A substantial drop in knee pain vasodilatory, and antioxidative properties [12,13]. and disability due to osteoarthritis was observed Flavonoids have also been proven to be good during a randomised, double-blind placebo, control- photo-protective shields against UV and ionizing led crossover study of 42 patients [28,29]. radiations [14]. Circumstantial evidence exist sup- Myristoleic acid, identified as a cytotoxic compo- porting the relationships between the intake of nent in Serenoa repens extracts has been found to flavonoids and reduced risk of coronary heart induce apoptosis and necrosis in human prostate disease [15], neurodegenerative disorders [16] lung cancer LNCaP cells. Treating LNCaP cells with 130 cancer [17,18], stomach and other forms of cancer mg/ml S. repens extract or 100 mg/ml myristoleic [18]. In particular, isoflavonoids have been identified acid for 24 hr produced a proportion of 16.5 and as chemopreventive against various types of cancer 8.8%, apoptotic cells and 46.8 and 81.8% necrotic and cardiovascular diseases [19,20]. We have cells respectively. Thus, the extract from S. repens previously demonstrated that the structure of and myristoleic acid seems to induce both apoptosis flavonoids extracted from citrus and other plants is and necrosis in LNCaP cells at the same time. When related to their antioxidant, anti-proliferative and another prostatic cell line (PC-3 cells) was used in anti-metastatic properties [21-23]. Furthermore, our place of LNCaP cells, apoptotic/necrotic cell death team have shown the antiproliferative action of was also observed after treatment with the extract several phenolic and ployhydroxylated flavonoids [30,31]. Furthermore, myristeoleic acid a by-product on metastatic melanoma B16F10 and melan-a of cheese has been shown to be one of three by- melanocyte cell lines [24-27] products effective at inhibiting in vivo Candida albicans germination with a minimum inhibitory concentration (MIC) of 9µM [32]. Moreover, a Fatty acids massive body of overriding evidence has been Some fatty acids are common plant and animal presented to show CMO can reduce disability constituents and usually exist in vivo as esters. related to migraine headaches, psoriasis broad- Some of these fatty acids are known to have diverse spectrum anti-inflammatory and analgesic applica- and potent biological activities. The fatty acid tions [29]. constituents of P. angolensis have been studied in P. angolensis presents a very important vegetable detail. In addition to medically important myristoleic source of myristoleic acid which was formally acid (9-tetradecenoic acid), lauric, oleic, palmitic largely obtained from ovine and porcine sources. acids and myristic acid (tetradecanoic acid) have The presence of myristoleic acid in commercially been characterized from the seeds of P. angolensis viable amounts in the seed fats of P. angolensis is [9,28]. significant in the sense that it satisfies all classes of Leonard and Simonton, 2010 demonstrated the users; animal sources raises debut in the minds of effectiveness of cetyl myristoleate (CMO), a deriva- some users as to whether the product meets kosher tive of myristeoleic acid, in the treatment of and/or halal requirements. Besides, fatty acids osteoarthritis, joint inflammatory diseases of sourced from land animal or marine animal origins

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are non-vegetarian and when sourced from beef (C20H3002) which demonstrated moderate anti- tallow run the risk, although slight, of inducing plasmodial activity against Dd2-chloroquine resi- bovine spongiform encephalitis (mad-cow disease) stant P. falciparum strain [34]. [28].

Steroids Terpenes and Sesquiterepene Chemical investigation into the stem, and roots Terpenes represent a large group of compounds resulted in the isolation of stigmast-4-en-6β-ol-3- responsible for the fragrance of plants and com- one, stigmasterol [34], β-sitosterol [7,34] and other prise the so called essential oil fraction. They differ known non-steroidal compounds. These steroids structurally from fatty acids in that they are bran- showed partial in vitro suppression of the growth of ched and cyclized. When additional elements, such Plasmodium falciparum parasites upon evaluation of as oxygen, are added they are called terpenoids. their antimalarial activity [34]. Stigmast-4-en-6β-ol-3- Terpenes particularly triterpenes are known to one has been found elsewhere to possess potent display a wide spectrum of biological activities antitumor-promoting activity [35], while ß-sitosterol including anitumour, antiviral, bactericidal, fungici- has also been implicated in the mitigation of cardio- dal, analgesic, anti-inflammatory spermicidal and vascular diseases through cholesterol reduction cytotoxic activities [33]. Simic et al, (2006) analysed [36]. the volatile oils from the stem bark of P. angolensis and isolated a number of compounds with the major constituents being; α-bergamotene (25.1%), Cerebrosides (pycnangloside) terpinen-4-ol (16.6%), α-terpineol (15.6%), trans β- A biologically uncharacterised novel molecule, bergamotene (12.9%), α--curcumene (6%), piperitone pycnangloside (Fig 1) (C44H85NO10), has been struc- (4.5%) and β-farnesene (4%). Other constituents turally elucidated from the bark of Pycnanthus include borneol (2.8%), bornyl acetate (1.6%), β- angolensis using comprehensive analyses of its 1D santalene (0.6%), acoradene (0.3%), β-bisabolene and 2D NMR spectroscopic, and ESI mass spectro- (3%), δ-cadinene (2.3%), germacrene B (1.0%), cem- metric data [7]. The fact that its biological activities brene A (1.0%) and farnesyl acetone (2.0%). During remain relatively unknown is ostensibly because it screening of the leaf oils, only two compounds, has only recently been reported. spathulenol (82%) a sesquiterepene alcohol and caryophyllene oxide (14%) a sesquiterepene were detected. The authors further demonstrated the antimicrobial effects of these volatile oils against a panel of bacterial and fungal species. Even though the MICs were not reported, the authors found that the leaf essential oils were in general see Table 1. Fig 1: Structure of pycnangloside from Pycnanthus angolensis (adapted from Tsaassi et al, 2010) more potent against the bacterial than fungal strains used. On the other hand, the fungal species Cerebrosides are a family of pharmacologically seemed to succumb more to the essential oils active and important glycosphingolipids, present in obtained from the plant bark. Further purification of a wide variety of tissues and organs in biological the dicholoromethane extracts of the stem bark systems. The cerebrosides are currently receiving afforded the labdane-type diterpene ozic acid

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 5 (1 - 22) attention because of their therapeutic potential methoxylignan (pycnantolol) [34], (−)- including antitumor/cytotoxic and anti-HIV-1 mode- dihydroguaiaretic acid, heliobuphthalmin, talaumi- rating potentials amongst others [37]. Cerebrosides din and hinokinin [9,34,40]. are involved in a very wide range of biological Dihydroguaiaretic acid showed non-selective activities such as cell agglutination, intracellular cytotoxicity to a panel of cancer cell lines with an communication, cellular development, and antitu- ED of 1.63 – 3.10 μg/ml [40] and prevented harmful mor/cytotoxic effects. 50 effects of UV [41] which facilitates skin aging. Furthermore, dihydroguaiaretic acid is important for the treatment of shock, neoplasms [42], sepsis, Allantoin melanoma, and lymphoma [43] and is a promising Allantoin (C4H6N4O3) a diuredide of glyoxylic acid candidate for the treatment of Alzheimer’s disease has been reported to be present in the bark of P. [44,45]. Working on a different plant Moon et al, angolensis [10,38,39]. Allantoin is well known for its (2008) isolated meso-dihydroguaiaretic acid from healing, moisturizing, soothing and anti-irritating, Saururus chinensis and showed that it inhibited the keratolytic and non-toxic effect in dermatological, cyclooxygenase-2 (COX-2)-dependent phase of cosmetic and veterinary preparations. In cosmeto- prostaglandin D generation in bone marrow-derived logy, allantoin is used for sunscreen and skin-care mast cells with an IC50 of 9.8 μM. However, it did products. It has shown clinical potentials for the not inhibit COX-2 protein expression in these cells at treatment of skin ulcers, wounds, scalds, (sun) concentrations up to 30μM, suggesting that the burns, carbuncles, acne, skin eruptions, fissures, lignan directly inhibits COX-2 activity. In addition, impetigo, eczema and psoriasis. It has also been meso-dihydroguaiaretic steadily abrogated the used in various oral hygiene preparations such as production of leukotriene with an IC50 of 1.3 μM toothpaste and mouthwash as well as in eye drops demonstrating that it inhibits both COX-2 and 5- to treat watering eyes and in ear drops to clean the lipoxygenase. Furthermore meso-dihydroguaiaretic ear canal. It is effective at quite low concentrations, was found to strongly inhibit the degranulation 0.1% up to 2%. reaction in bone marrow-derived mast cells with an

IC50 of 11.4μM providing strong basis for novel anti- inflammatory drug development [46]. Again meso- Lignans dihydroguaiaretic acid from the stem bark of P. angolensis is known to produce lignans in its Machilus thunbergii showed significant matrix stems, roots leaves and seed including 3,4- metalloproteinase MMP-9 inhibition in human dimethoxy-3',4'-methylenedioxy-7,7'-epoxylignan keratinocyte cells caused by ultraviolet irradiation. [3] 4,5-dimethoxy-3',4'-methylenedioxy-2,7'- Moon et al, (2005) demonstrated that meso- ycloligna-7,7'-diene, 4'-methoxy-4,5- dihydroguaiaretic acid can prevent the harmful methylenedioxy-2,7-cyclolign-7-ene4,5-dimethoxy- effects of UV that lead to skin aging. The authors 2,7'-cyclolign-7-en-4'-ol (pycnanthulignene A), [3,4], suggests that meso-dihydroguaiaretic acid should 2,7-dimethoxy-3,6 dimethylnaphthalene, 4,5- be viewed as a potential therapeutic agent for dimethoxy-3',4'-methylenedioxy-2,7'-cyclolign-7-ene preventing and/or treating premature skin aging (pycnanthulignene B) 3,6-dimethoxy-4,5- [41]. Li et al., (2004) using bioassay-guided fractiona- methylenedioxy-2,7'-cycloligna-7,7'-dien-4'-ol tion isolated a number of diaryldimethylbutane (pycnanthulignene D), 4'-methoxy-4,5- lignans, of which meso-dihydroguaiaretic acid, methylenedioxy-2,7'-cyclolign-7-ene [4], Calopiptin, inhibited the in vitro enzymatic activity of topoiso- (12 S, 13 S)-12, 13-dihydroxylabda-8, 14-dien-18-oic merase I and II by 93.6 and 82.1% respectively at a acid, (12 R,13 S)-12,13-dihydroxylabda-8 (17),14-dien- concentration of 100 mM [47,48]. Wiart (2006a) 18-oic acid, [8], threo-4,4'-dihydroxy-3- notes that the Myristicaceae abounds in lignans with

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 6 (1 - 22) biological activities against topoisomerases and cases the authors have been silent about the anti- advocates the search for lignans with potent hyperglycemic property of the pycnanthuquinone C. topoisomerase inhibitory activities from amongst Total synthesis of pycnanthuquinone C has since the Laurales–Magnoliales plant group. Nono et al, been achieved in the laboratory via the Diels-Alder 2010, demonstrated that type synthesis [52] however, the absolute configu- ration of the pycnanthuquinones still remain to be see Table 2. established. During the past decade and a half, Fort et al., (2000) have convinced the scientific commu- pycnanthulignenes A and C possess antibacterial nity that the pycnanthuquinones represent a new activity against a panel of drug-resistant bacterial class of anti-diabetic compounds which is structu- and pathogenic fungal strains using gentamicin and rally distinct from the currently available oral type 2 nystatin as references for antibacterial and antifun- diabetes remedies namely sulfonylureas, biguani- gal tests respectively. The MIC values for pycnan- des, disaccharidase inhibitors, and thiazolidinedio- thulignenes A varied from 28.7 μM (against S. nes. Short of clinical data, this could well be the aureus) to 230.9 μM (against K. pneumoniae and P. heralding of a new class of drugs for type -2 anti- aeruginosa) while lowest MIC values of 63.8 μM diabetic therapies and a classic case of a modern observed with pycnanthulignenes A were against S. drug with an origin from ethnopharmacology and aureus, E. coli, and C. albicans. traditional medicine; undeniably, numerous drugs have entered the international pharmacopoeia via the study of ethnopharmacology and traditional Terpene-type quinones: the Pycnathuquinones medicine [53]. Remarkable advances into the study and discovery of these novel class of antidiabetic Quinones constitute a structurally diverse class of principles from P. angolensis has been extensively phenolic compounds with a wide range of pharma- expounded elsewhere [38,49,50]. cological properties. Terepinoid quinones have frequently been isolated from microorganisms and plants to exploit their antimicrobial, antiviral and anticancer properties. Recently attention has been drawn to their anti-mycobacterial properties. P. angolensis is known to elaborate a series of unusual 6, 6, 5-tricyclic geranyltoluquinone terpene-like quinones called pycnanthuquinones (fig 2). A search for physiologically active compounds against Fig 2: Pycnanthuquinones (A, B and C) diabetes using in vitro bioassay-guided fractiona- tions of alcohol extracts of the root and leaves of P. Plastoquinones and Ubiquinones angolensis (Warb.) against ob/ob and db/db mice models for type 2 diabetes led to the discovery of Fractionation of the crude ethanol extracts of the two terepene-type quinones, pycnanthuquinones A seed of P. angolensis yielded a series of medicinally and B [38,49,50]. Further screening of the stem relevant plastoquinones namely kombic acid, bark afforded another novel compound; pycnanthu- sargahydroquinoic and sargaquinoic acids and quinones C [8] which was demonstrated to possess sargachromenol (an ubiquinone) [9,54]. The anti- antifungal properties using Trichophyton souda- inflammatory, antiproliferative, anti-aging, UV- nense as an experimental model. Recently too, Liard protecting and anti-oxidative activities of these and Co-workers have reported the presence of compounds has been established [55-58]. Further in pycnanthuquinone C in the Western Australian vitro and in vivo studies have revealed other bioacti- brown alga Cystophora harveyi [51] however, in both vities inherent in them including cholesterol lowe-

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ring effects, reduction of elevated plasma levels of BuChE than on AChE; the observed IC50 of 26 nM

Low Density Lipoproteins (LDL) cholesterol, inhibi- was 1000-fold greater than the corresponding IC50 tion of inducible nitric oxide synthase (iNOS) and value for AChE inhibition. BuChE is a new drug Cyclooxygenase-2 (COX-2) protein expression, target for the treatment of Alzheimer’s disease. The inhibition of LPS-induced iNOS and COX-2 mRNA authors remark that sargaquinoic acid represents an expression. effective and selective inhibitor of BuChE with potency similar to or greater than the anticholine- sterases in current clinical use, making it an intere- sting potential drug candidate for AD [60]. These results corroborate the findings of Elufioye et al., (2010) following their attempt to find a scientific rationale for the use of extracts of P. angolensis for the treatment of cognitive problems in Nigerian folklore. Fig 3: Kombic acid (A), Sargaquinoic acid (B), Sargachromenol (C), Sargahydroqunoic acid (D) Only recently, Tchinda et al., (2008) demonstra- ted the promising anti-diabetic potentials of sarga- quinoic acid and sargachromenol sourced from the Activity-guided purification of Sargassum micra- seeds of P. angolensis. While these compounds canthum obtained from the Coast of East Sea in furnished IC50 values of 3 ± 0.123 and 4.6 ± 0.123μM Korea led Park et al., (2008) has yielded to a vasodi- respectively reputed α-glucosidase inhibitors latatiory constituent sargahydroquinoic acid. The deoxynojirimycin and acarbose had IC50 values of compound induced vasodilatation in the basilar and 425 ± 8.14μM and 780 ± 28μM. carotid arteries of rabbits in a concentration- dependent manner. The EC50 values for the basilar and carotid arteries were 11.8 ± 0.28 and 140 ± Glyceryl-1, 3-ditetradecanoate 0.6µM respectively. It selectively dilated the basilar Tcinida et al., (2008) examined in detail the fruits artery more than 10-fold over the carotid artery of P. angolensis and reported for the first time, the without lowering systemic blood pressure. This presence of a diglyceride; glyceryl-1, 3- implies that treatment with sargahydroquinoic acid ditetradecanoate together with two known plasto- may accelerate cerebral blood flow through dilata- quinones. The authors further demonstrated the α- tion of the basilar artery without influencing syste- glucosidase inhibitory tendencies of these com- mic blood pressure. The authors suggests that pounds with glycerol-1, 3-ditetradecanoate registe- compounds that share a similar core structure with ring an IC of 522.0μM. This IC value compared sargahydroquinoic acid, such as plastquinones and 50 50 favourably with deoxynojirimycin a potent α- hydroquinones may be novel lead compounds for glucosidase inhibitor which had an IC of 425 ± selective pharmacological agents for the human 50 8.14μM, and acarbose a popular drug used for type- vascular system [59]. 2 diabetes therapy which had an IC50 of 780 ± 28μM. The acetylcholinesterase (AChE) and butylcholi- As indicated above, the plastoquinones proved to nesterase (BuChE) inhibitory activities of plastoqui- be better glycosidase inhibitors compared with the nones have been amply demonstrated [60] both glycerol derivative. These findings led the authors sargaquinoic acid and sargachromenol isolated to propose the use of extracts from the fruits of P. from Sargassum sagamianum showed AChE inhibi- angolensis for the management of type-2 diabetes tory activity at micromolar concentrations with IC50 and related diseases. In our literature search, the 23.2 and 32.7 μM respectively. However, sargaqui- mention of glycerol-1, 3-ditetradecanoate as a noic acid demonstrated higher inhibitory activity on potential α-glycosidase (protease) inhibitor was

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 8 (1 - 22) rare and this could well be one of the pioneering the compounds are isolated as pure substances as works involving this compound and the moderation experienced by Abrantes et al., (2008). In this light it type-2 diabetes. Apha-glucosidases are key enzymes seems logical to suggest that it may not always be catalyzing the final step in the digestive process of essential to seek pure compounds to develop a carbohydrates. Therefore, α-glucosidase inhibitors therapeutic agent that requires a synergistic action can retard the liberation of D-glucose from dietary of some of the natural components of the plant. As complex carbohydrates and delay glucose absorp- a matter of course the biologically active extracts tion, resulting in reduced postprandial plasma need to be evaluated for general toxicity, since glucose levels and suppression of postprandial there may be unacceptably low distinctions bet- hyperglycemia. An effective way to manage non- ween toxicity towards the test model and that insulin-dependent diabetes mellitus (NIDDM) then shown towards the host. Table 2 highlights some is by inhibiting or reducing the activity of these biological activities of P. angolensis extracts repor- enzymes (e.g. α-glucosidase and α-amylase) in the ted in literature which are discussed in more details digestive organs there by retarding absorption of in the following sections. glucose and decreasing postprandial hyperglyce- mia. Presently, there is renewed interest in plant- based medicines and functional foods modulating Antimicrobial activity physiological effects in the prevention and cure of The antimicrobial properties of different crude diabetes and obesity. The plant kingdom is a wide solvent extracts of P. angolensis have been investi- field to search for natural effective oral hypoglycae- gated and reported by a number of researchers. mic agents that have slight or no side effects. Reasonable to significant anti-microbial, antifungal Therefore, natural alpha-glucosidase and alpha- and anti- mycobacterial activities have been repor- amylase inhibitors from plant sources offer an ted on these phyto-preparations (crude or fractio- attractive strategy for the control of hyperglycae- nated extracts and sometimes individual com- mia [61,62]. pounds) under laboratory conditions. The antimi- crobial activity of crude ethanol leaf extracts of P. angolensis on clinical strains of bacteria and fungi Some biological activities of crude extracts from were investigated by Onocha and Otunla, (2010) P. angolensis using the disc diffusion method. The authors de- Most investigations regarding the bioactivities of monstrated that the leaves possessed the ability to medicinal plants is limited to examination of crude inhibit the growth of two bacterial and three fungal aqueous or organic solvent extracts and in most strains. The mean zones of inhibition produced by cases, the investigators have sought to validate the the crude ethanol extracts of the leaf at 75 mg/ml traditional medicinal use of the plant. Various was found to be around 15 mm for the bacterial workers using different types of extracts in a bid to species and 10-20 mm for the fungai while the assign a scientific rationale for the use of different reference drugs ampicillin and tioconazole at a parts of P. angolensis in folklore have demonstrated concentration of 12.5 μg/ml yielded zones of inhibi- different important biological activities of the tion of 19 mm and 12-16 mm respectively. Similarly extracts thereby adding confidence to the prescrip- Atindehou et al., 2002 have shown that ethanol tions of local herbalist as well as paving the path for extracts of the roots of P. angolensis do possess the effective screening for therapeutically relevant some bactericidal properties against gram positive lead molecules. It is noteworthy to stress that crude strains of bacteria. With regards to the anti- plant extracts could be biologically active against a microbial activity, Oladimeji et al., (2006) showed test model(s); however, the observed activity may that leaf extracts and fractions of P. angolensis be significantly reduced or virtually abolished when abrogated the in vitro survival of Bacillus subtilis,

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 9 (1 - 22) and Staphylococcus aureus, were inactive against activity. Zirihi et al. 2005 confirmed that the ethanol Escherichia coli, Salmonella typhi and Klebsiella extracts of the stem back of this plant possess pneumonia; and exhibited activity against the fungal moderate activity against chloroquine-resistant isolates Aspergilus niger and Candida albicans al- FcB1/Colombia strain of Plasmodium falciparum. In a though the potency in these assays may not have related study, Do Céu de Madureira et al., (2002) been clinically significant. Purified essential oils from previously demonstrated that crude ethanol ex- the stem-bark and leaves have proven to have tracts of the stem bark of P. angolensis cleared measurable antimicrobial activities against various female balb/C mice of parasitemia due to P. berghei fungal and bacterial strains [63,64]. The fact that ANKA infection thereby validating the traditional most crude extracts of the plant demonstrated use of pytopreparations from P. angolensis against antimicrobial activity probably supports its use by malaria fever. traditional healers for the treatment of microbial P. angolensis extracts have shown promising infestations. anthelmintic properties. For instance, the crude chloroformic and methanolic extracts of the leaves and methanolic extracts of the stems were found to Antiprotozoal exhibit in vitro anthelmintic activities using Fasciola Several vector-borne tropical diseases are proto- gigantica, Taenia solium and Pheritima pasthuma as zoal infections, caused by protozoan parasites experimental models consistent with the folkloric which replicate and multiply rapidly inside the host, use of the plant as an anthelminthic [66]. Again, invade the blood stream and lymphatic vessels or measurable activity was recorded when ethanolic tissues. Some of these diseases, including leishma- extracts of the roots were evaluated for potential niasis, trypansosomias, and malaria, persist without anthelminthic activities against the larvae of effective treatment. Although many drugs are Haemonchus contort [67]. Similarly methanolic and available, some have become ineffective due to the chloroformic extracts of stem bark exhibited development drug resistant strains. By far the most anthelmintic activity when tested in vitro against important vector-borne protozoal infection is Eudrilus eugeniae with the methanolic extract malaria caused by Plasmodium parasites which are registering a higher potency [68]. In vitro anti- transmitted through the bite of some species of leishmanial assay using methanolic extracts of the Anopheles mosquitoes. stem against promastigotes of L. major exhibited a Traditional remedies are continually being investi- leishmanicidal action with an IC50 of 70.59µg/ml. On gated as plant derived antimalarial drugs become the other hand, the methanolic extracts of the root more sought after. The anti-plasmodial activities of was not leishmanicidal but cytotoxic while same different extracts of P. angolensis have been investi- solvent extracts of the leaves showed neither gated with promising outcomes. The chloroform leishmanicidal nor cytotoxic activity [39]. When the and ethanol extracts of its stem-back showed nematicidially active crude fractions of P. angolensis activity against chloroquine-sensitive Plasmodium (against C. elegans) were further fractionated, the falciparum strain D6 and the chloroquine-resistant lignan dihydroguaiaretic acid, with an LD50 of 10μg/ml was obtained [40]. strain W2 with both extracts giving an IC50 of less than 25µg/ml [65]. Similarly, Abrantes et al., 2008 showed that the dichloromethane, methanol and Anticancer/antitumor activity aqueous ethanol extracts of the stem bark afforded in vitro anti-plasmodial activity against 3D7 P. Cancer is a disease recognised by seven hall- falciparum strain. While crude CH2Cl2 extracts marks: unlimited growth of abnormal cells, self- produced remarkable activity with an IC50 of 1.6 sufficiency in growth signals, insensitivity to growth μg/ml, the purified fractions lacked anti-plasmodial inhibitors, evasion of apotosis, sustained angioge-

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 10 (1 - 22) nesis, inflammatory microenvironment and even- rating the cholinergic deficit considered to be tually tissue invasion and metastasis [69,70]. It is responsible for the declines in cognitive, behaviou- estimated that without effective measurement, ral and global functioning characteristic of AD [75]. around 84 million people are likely to die of can- AChE and BuChE inhibitors are considered promi- cer between 2005 and 2015. Furthermore, in most sing therapeutic agents for the treatment of AD to developed countries, cancer is the second leading help maintain or elevate the levels of acetylcholine cause of death, falling only behind cardiovascular in the brain [76,77]. Only few synthetic medicines diseases [71] therefore it is important to address exist for treatment of cognitive dysfunction and this ever-increasing burden. Extracts of P. angolensis memory loss associated with these diseases howe- have demonstrated some antitumor activities in ver, they have significant adverse effects. Hence, several cancer cell lines. In vitro assay for anticancer developing potential AChE inhibitors from botani- activity of methanol extracts from the mature stem cals could be helpful. Quiet recently, the bark of P. angolensis have exhibited cytotoxicity and Amaryllidaceae alkaloid, galanthamine was appro- anti-proliferative effects on various cancer cell lines ved in a number of European countries for the [72,73]. When nine flavonoids isolated from the treatment of Alzheimer’s disease [78]. Following ethyl acetate extracts of the plant were screened leads from folklore, Elufioye et al, 2010 screened for apoptosis induction in human hepatoma HCH-7 methanolic extracts of P. angolensis (leaves, root cancer cell lines, the compounds tested showed bark and stem bark) for both AChE and BuChE higher apoptosis induction profiles compared with inhibitory activities. They demonstrated that the the control. The apoptosis inducing activity of these crude stem-bark extracts exhibited the highest in flavonoids was confirmed by caspase activity assays vitro AChE and BuChE inhibitory of 66.52 ± 5.02% [5]. Pure compounds other than flavonoids and and 86.05±8.32% respectively while the leaf extracts belonging to the hydroquinones such as kombic gave nearly equal inhibitory activity of 43.96 ±3.04 acid, sargahydroquinoic acid, sargachromeol, and and 43.59± 1.77% in that order. The root bark sho- hydroquinoic acid isolated from the seeds of P. wed 15.51% inhibition towards AChE but could not angolensis and related compounds have been inhibit the activity of BuChE. Barclay et al, (2010) shown to be efficient at preventing and/or retarding recognised the pro-cognitive properties of extracts the development of cancer [56-58,74]. Results of from the seeds of P. angolensis and traced it to the these studies may be a first step in the verification presence of hydroquinones specifically sargahydro- of the anecdotal claims of the folkloric use of quinoic acid. The authors suggest the use of these Pycnanthus angolensis as an anticancer agent. compounds in Alzheimer disease to enhance cogni- tive function, myasthenia gravis, glaucoma, learning and memory. Earlier studies by Choi et al., 2007, Cognitive disorders demonstrated the effectiveness of sargaquinoic Available records point to a progressive rise in the acid and sargachromenol derived from a marine number of individuals afflicted with neurological plant towards the inhibition of BuChE and AChE disorders including Alzheimer's disease (AD), senile activities which is in consonance with the findings of dementia, ataxia and myasthenia gravis. Special Barclay and others [58]. Substantial amounts of attention is required for researchers to develop these compounds are present in the seed fat of P. better treatment for victims of these ailments. angolensis may be confirming one of the folkloric While butycholinesterase (BuChE) activity is uses of Pycnanthus angolensis. thought to increase progressively in patients with AD, acetylcholinesterase (AChE) activity remains Pain and Anti-inflammatory Activity unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for amelio- Excessive production of some prostaglandins

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(PG) is known to provoke pain and inflammation namely kombo butter, kombo butter acid extract, and enhance blood clotting action. Cyclooxygenase sargaquinoic acid, sargachromenol, and sargahydro- has been implicated in the regulation of prostaglan- quinoic acid on levels NO production, iNOS activity, din synthesis and two isoforms of this enzyme COX-2 proteins and mRNA expression in these cells. (COX-1 and COX-2) have been reported. COX-I is a All test substances suppressed NO production, iNOS constitutive isoform that exists in most tissues and protein and mRNA expression, and COX-2 protein is responsible for the production of prostanoids and mRNA expression in murine macrophages. On involved in homeostasis whilst the inducible isoform substance basis kombo butter was found to inhibit (COX-2) is responsible for the production of prosta- LPS-induced iNOS mRNA expression by approxima- noids involved in inflammation [79]. Enhanced tely 43% at 5μg/ml and 80% at 10μg/ml while sarga- levels of COX-2 have been found in humans during hydroquinoic acid inhibited iNOS mRNA expression the course of numerous inflammatory conditions by 31% at 25μM and 74% at 50μM, these values including rheumatoid arthritis, osteoarthritis and correlated well with the inhibition of iNOS protein acute or chronic inflammatory disease. expression by kombo butter and sargahydroquinoic Conventional Non-Steroidal Anti-inflammatory acid. Even though kombo butter acid extract inhibi- drugs (NSAIDs) non-selectively inhibit both COX ted iNOS mRNA expression it was not dose depen- isoforms. As the induction of COX-2 is responsible dent; inhibiting at approximately 50% at both 5 and for the production of PGs at the site of inflamma- 10μg/ml. Furthermore, sargaquinoic acid and tion, this enzyme represents a possible therapeutic sargachromenol both exhibited inhibitory activity at target. Currently researchers are keenly interested a concentration of 50μM. The inhibitory activity of in finding NSAIDs which selectively inhibit COX-2 compounds from P. angolensis was in many instan- with little or no interference to COX-1. Compounds ces comparable to and in some cases exceeded that that selectively inhibit COX-2 are highly promising of the control compounds (vitamin E and indome- new agents for the treatment of pain and inflamma- thacin). Similarly, the investigation of the extracti- tion, and for the prevention of cancer [79,80]. ves from P. angolensis on COX-2 mRNA expression in LPS-induced RAW 264.7 mouse macrophage cells Herbal therapies present an attractive approach revealed the inhibitory activities of plant extracti- for the treatment of various inflammatory disor- ves. In particular, kombo butter inhibited LPS- ders. The important value of extracts and com- induced COX-2 mRNA expression by nearly 25% at pounds from P. angolensis as anti-inflammatory 10μg/ml, while sargachromenol inhibited COX-2 remedies and treatment of adverse health condi- mRNA expression by 16% at a concentration of tions associated with inflammation and/or the 50μM. Interestingly, sargahydroquinoic acid inhibi- presence of free radicals, joint diseases, arthritis, ted COX-2 mRNA expression by nearly 12% at a and allergies have been documented. Products concentration of 25μM and by almost 19% at 50μM. from the seed of P. angolensis are believed to be As with the experiment regarding iNOS mRNA useful for the prevention and treatment of condi- expression, vitamin E and indomethacin were tions linked to inflammation. included as comparative controls, however, neither Simon et al., (2010) determined that agents in the of these compounds effected any inhibition of COX- fruits of P. angolensis possess anti-inflammatory 2 mRNA expressions within the concentration activities based on in vitro experiments utilizing ranges assayed. Each of the agents demonstrated lipopolysachharide induced murine (RAW 264.7) activity at reducing NO production, iNOS protein macrophage cells. iNOS a pro-inflammatory, en- and mRNA expression, and COX-2 protein and zyme responsible for the generation of NO, has mRNA expression. Thus these agents from P. been implicated in the pathogenesis of inflamma- angolensis have been adjudged to possess beneficial tory diseases. The authors examined the effect of inhibitory activities on the inflammatory response in extractives derived from the seeds of P. angolensis

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 12 (1 - 22) cells, both in vitro and in vivo. In a related study, trolox as standard. Against DPPH, the respective

Perez-Castorena et al., (2002) evaluated the anti- IC50 values of 17.3 and 9μg/ml for purified sargachro- inflammatory and antioxidant activities of sargahy- menol and sargahydroquinoic acid was ample proof droquinoic acid and sargachromenol isolated from that the compounds are good free radical scaven-

Roldana barba-johannis, alongside their mixtures gers. Also, kombo butter acid extract, with an IC50 and methyl esters and showed their potency as of 25.2μg/ml, was found to be a much better DPPH antioxidants and anti-inflammatory compounds. For free radical scavenger than kombo butter. Results a more elaborate exposition of the anti- of the ABTS free radical scavenging assays corrobo- inflammatory potentials of extracts and compounds rated the outcomes of the DPPH assay. The antioxi- of P. angolensis as well as related compounds the dant components have also been proposed as reader is referred to [58,74]. topical applications in different cosmetic and herbal formulations. In consonance with these reports, Tchnida et al., 2008 demonstrated in nitric oxide

Antioxidant Action scavenging assay that crude CH2Cl2-MeOH extracts Phytochemical antioxidants are touted as free of the fruits of P. angolensis possess 99.0 % compa- radical sinks, effectively neutralizing free radicals, red with 90.3 % Radical Scavenging Activity elicited active atoms or molecules that can damage DNA by n-propyl gallate standard. and corrode cell membranes. Free radicals are known to play a key role in the development of a Anti-atherosclerotic effect (Cholesterol lowe- number of adverse health conditions, including ring) cancer, cardiovascular disease, and cataracts, and have also been implicated in both initiation and Hypercholesterolemia remains to be one of the acceleration of the aging process. Given the wide major risk factors of coronary heart disease, the range and gravity of the adverse health conditions leading cause of death in the world. Atherosclerosis associated with free radicals and other inflamma- is a complex multi-cellular process involving oxida- tory factors, there is a critical need for agents tion of cholesterol and the intracellular accumula- capable of exerting antioxidant and anti- tion of oxidized cholesterol. Currently available inflammatory effects to ameliorate the pharmacolo- hypolipidemic drugs like gemfibrozil, bezafibrate, gical treatment of conditions such as cancer, lovastatin, and nicotinic acid are not totally safe cardiovascular disease, cataracts, rheumatic disea- particularly when used for prolonged periods [36]. ses, fibromyalgia, Alzheimer's disease and nume- Several plant species are known to possess anti- rous other neurodegenerative conditions. In this hypercholesterolemic action and may afford a regard, phyto-preparations could come in handy. suitable alternative to current day cholesterol Studies have shown that extracts of P. angolensis do lowering medicaments. Extractives of P. angolensis possess important liposoluble antioxidant activities have been shown to be efficient at reducing eleva- comparable to or even better than well-known anti- ted plasma levels of total and LDL cholesterol as oxidants like Vitamin E [55,57,58]. Simon et al., well as plasma apolipoprotein B (ApoB) concentra- (2010) studied the antioxidant properties of extrac- tions in humans. ApoB is the dominant protein tives (kombo butter, kombo butter acid extract, and constituent of low-density lipoprotein (LDL) purified sargaquinoic acid, sargachromenol, and thought to stabilize lipid emulsions, serve as a sargahydroquinoic acid) from the seeds of P. cofactor and modulator of enzymatic reactions, angolensis and found them to be strong antioxi- manage export of lipids out of cells and direct lipids dants using both 2,2'-diphenylpicrylydrazyl (DPPH) to target organs. ApoB levels are positively correla- and 2,2'-azinobis- (3-thylbenzothiazoline-6-sulfonic ted with the risk of coronary disease. Studying the acid (ABTS) free radical scavenging assays with effects of extractives from P. angolensis on ApoB

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 13 (1 - 22) concentration, Leonard (2004) exposed confluent these wound healing properties of P. angolensis. HepG2 cells (which have the capacity to secrete and Besides, the plant is known to elaborate allantoin catabolize lipoproteins similar to LDL) to kombic along with other known antimicrobial agents which acid and its derivatives. The cells were incubated in together might have some level of wound healing serum-free medium, which inhibits cell proliferation activity. Allantoin is known to have supportive but stimulates biosynthesis of LDL-like lipoproteins effects on the primary and secondary wound in the presence or absence of kombic acid or its healing process and is known to have bactericidal derivatives at the range of nontoxic concentrations and anti-inflammatory effects [83-85]. (determined by MTT cell viability assay). Changes in medium concentration of ApoB were evaluated by ELISA and compared with changes induced in the Current & future perspectives absence of kombic acid or its derivatives. Kombic From the above review, P. angolensis appears to acid and its derivatives caused a dose dependent be a rich source of phytochemicals that can be used reduction of medium ApoB proving to be useful to design and develop potentially useful therapeutic cholesterol-lowering agents [56]. agents. Some extracts and compounds isolated from P. angolensis have been found to have antitu- mor (cytotoxic), cholesterol lowering, possess Wound healing significant antioxidant and anti-inflammatory Over the years, different herbal products have activities, and iNO inhibitory, anti-ulcerogenic, been used in the management and treatment of antimicrobial and anti-hyperglycaemic. Indeed, wounds particularly in folklore. In Nigerian traditio- some of these promising results are worthy of nal herbal practice, a mixture with ratio 1:1:2 of further investigation. For example, meso- exudates of Anchomones difformis: Cyrtosperma dihydroguaiaretic acid has been ascertained to senegalense and Pycnanthus angolensis respectively, inhibit the enzymatic activity of DNA topoisomerase is used for treatment of corneal ulcers. Similarly [81] I and II. The topoisomerases have recently been there are reports that decoctions of the stem bark identified as molecular targets of a variety of and leaves of P. angolensis are employed to stem pharmaceutical agents. Some of the drugs that haemorrhoids, stomach ulcer and chronic wounds target the topoisomerases are anticancer drugs. in Ghana. Following these folkloric leads Agyare et Thus further investigation into the structure-activity al., using human keratinocytes and dermal fibro- relationship could lead to a better understanding of blasts have confirmed the in vitro wound healing the mechanism of action of these anticancer princi- capability of ethanol and aqueous extracts of the ples. The AchE and BuChE inhibitory activities stem bark of P. angolensis. Moreover, [82] the observed could be the action of different bioactives exudates of P. angolensis exhibited antibacterial expressed in different parts of the plants as crude activity, and healed in vivo corneal ulcers induced in extracts of the stem bark and pure sargaquinoic rabbits even in the absence of prescribed exudates acid (from the seed) both exhibited inhibitory of A. difformis and C. senegalensis. Even though activities. Moreover, mention of a new class of anti- further confirmations and clinical studies are war- diabetic compounds in pycnanthuquinones A and B ranted, these initial findings points to bioactive elaborated by P. angolensis is crucial to say the least. principles present in both the exudates and stem It will be particularly encouraging to see results of bark of P. angolensis that are capable of stimulating the clinical trials on the pycnanthuquinones as well wound healing and may thus justify its traditional as studies on their safety and efficacies either alone use to heal wounds. Therefore, an interesting or in combination with conventional therapies. This development from these reports would be a syste- will go a long way to help control and reduce the matic investigation of compounds responsible for overall burden of diabetes. P. angolensis also ex-

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 14 (1 - 22) presses the α-glycosidase inhibitors, glyceryl-1, 3- very vital aspect of the genetic safety evaluation of ditetradecanoate, sargaquinoic acid and sargachro- herbal extracts in a bid to uncover lead molecules menol. It seems likely that more than one anti- with therapeutic utility. Previous pharmacological diabetic therapy could be derived from the plant. As screening and toxicology assays on plants used noted earlier the butter extracted from the seeds of medically showed that several plants used for Pycnanthus angolensis could become the much- medicinal purposes cause damage to the genetic needed vegetable substitute for animal-fat based material and, therefore, should be used with cau- cetyl myristoleate employed in arthritis manage- tion [87]. ment. Plants over exploitation have become a global Most of the characterized compounds are only concern, but even so, most developing countries poorly understood biologically since many reports are still involved in plant over-exploitation and the are limited to isolation and structure elucidation for trend is anticipated to continue if adequate control unascribed reasons. Howbeit, many of these com- measures are not put in place. Notable examples of pounds are found in low concentrations in the plant over exploited plants are Okoubaka aubrevillei, as part of complex mixtures which makes their Garcinia afzelii, G. epunctata, and G. kola in Ghana, isolation and purification highly expensive. Côte d’Ivoire and Nigeria. What is highly significant Nonetheless, these could serve as important tem- from a resource management viewpoint is that so plates for future synthesis. far, most of the items of commerce in P. angolensis seem to be elaborated in the seed (i.e myristeoleic The current paradigm is to evaluate antioxidants acid, sargahydroquinoic acid, kombic acid, sarga- from flora (for obvious reasons) for their radiopro- chromenol and sargahydroquinone) and the leaves tective potential in order to exploit them for the (the pycnanthuquinones), thus unsustainably high development of countermeasure agents for radia- levels of exploitation may not pose too much tion exposure [86]. The in vitro and in vivo antioxi- challenge since these parts are renewable. The fact dant potential of P. angolensis has been amply that the stem bark and roots also contain consti- demonstrated. In particular the plastoquino- tuents with important biologic activities like flavo- nes/ubiquinones kombic acid, sargahydroquinoic noids but also lower levels (compared with the acid, sargachromenol and sargahydroquinone and leaves) of pycnanthuquinones could lead to de- the flavonoid compounds if evaluated could lead to structive harvesting when demand for these com- promising radioprotective compounds. Literature pounds are triggered. At any rate, local threat of search for the radioprotective evaluation of these over-exploitation of P. angolensis is more likely to compounds or other phytochemicals elaborated by arise due to demand for its timber than the herbal P. angolensis did not yield results probably due to medicine trade. [Amanor, 1997] notes that in Ghana, the fact that there is no place in folklore for radio- P. angolensis is one of the forest trees that is popu- protection to offer research leads in this direction. It larly preserved by farmers and recognized as having will be interesting to investigate this property of the favourable interactions with crops, however, in plant extracts and if confirmed, this might increase recent years, with growing shortage of timber in the economic potential and prospects for the plant. off-reserve areas it has been increasingly exploited Further work on this topic should be encouraged, by timber contractors. According to the author, in and one can reasonably expect interesting results the past P. angolensis was hardly exploited and to radioprotective leads. Again, through the litera- considered an inferior timber species. In 1994, with ture search, it has been noted that the potential increasing shortages of prime timber species P. genotoxic effects that may follow usage of the angolensis together with three other previously less preparations from P. angolensis have not been exploited species accounted for 80% of export investigated even though there is extensive cove- volume. Probably in bid to maintain sustainability rage on cytotoxicity. In our view this constitutes a

http://pharmacologyonline.silae.it ISSN: 1827-8620 PhOL 15 (1 - 22) and for continual generation of income for indige- Pycnanthus angolensis (Myristicaceae). Nat Prod Res 2011;25:432-443. nes who ply their trade in this plant, 4. Nono EC, Mkounga P, Kuete V, Marat K, Hultin PG, Mapongmetsem, (2007) recommends that new Nkengfack AE: Pycnanthulignenes A-D, antimicrobial cyclolignene derivatives from the roots of Pycnanthus opportunities for exploiting the oil and medicinal angolensis. J Nat Prod;73:213-216. properties should be investigated. 5. Mansoor TA, Ramalho RM, Luo X, Ramalhete C, Rodrigues CM, Ferreira MJ: Isoflavones as Apoptosis Inducers in Human In conclusion, the phytochemistry of P. angolensis Hepatoma HuH-7 Cells. Phytother Res 2011. 6. Yazaki Y, Bauch J, Endeward R: Extractive components reported in current literature is probably not quiet responsible for the discoloration of Ilomba wood exhaustive. Most of the phytochemical investiga- (Pycnanthus angolensis Exell). Eur J Wood Prod 1985;43:359- 363. tions have centred on the above phytochemicals; 7. Tsaassi VB, Hussain H, Tamboue H, Dongo E, Kouam SF, however, the Myristeacea may have become Krohn K: Pycnangloside: a new cerebroside from bark of Pycnanthus angolensis. Nat Prod Commun 2010;5:1795-1798. important due to their ability to elaborate therapeu- 8. Wabo HK, Tatsimo SN, Tane P, Connolly JD: tically relevant compounds like indole alkaloids Pycnanthuquinone C: a new terpenoid-quinone from Pycnanthus angolensis. Planta Med 2007;73:187-189. (with potential for anti-depression), phenylacylphe- 9. Mapongmetsem P-M: Pycnanthus angolensis (Welw.) Warb. nols and phenylpropanoids [1]. No report about in Vossen HAMvd, Mkamilo GS (eds): PROTA 14: Vegetable oils/Oléagineux. Wageningen, Netherlands: [CD-Rom]. these compounds exists for P. angolensis. It is quite PROTA, 2007. obvious that P. angolensis requires thorough phyto- 10. Omobuwajo OR, Martin MT, Perromat G, Sevenet T, Awang K, Pais M: Cytotoxic cycloartanes from Aglaia argentea. chemical and pharmacological investigations to Phytochemistry 1996;41:1325-1328. unearth more useful phytochemicals. 11. Adesanya SA: From nature to drugs: theories and realities. Nigeria, Obafemi Awolowo University Press, Ile-Ife 2005. 12. Yao LH, Jiang YM, Shi J, Tomás-Barberán FA, Datta N, Singanusong R, Chen SS: Flavonoids in Food and Their Health Benefits. Plant Foods for Human Nutrition (Formerly Acknowledgements Qualitas Plantarum) 2004;59:113-122. 13. Sandhar HK, Kumar B, Prasher S, Tiwari P, Salhan M, Sharma The authors acknowledge the International P: A Review of Phytochemistry and Pharmacology of Atomic Energy Agency (IAEA) for sandwich PhD Flavonoids. Intle Pharma Sci 2011;1:25-41. 14. Sanchez-Campillo M, Gabaldon JA, Castillo J, Benavente- fellowship GHA/10021 and a National Spanish Garcia O, Del Bano MJ, Alcaraz M, Vicente V, Alvarez N, Research and Development CENiT programme Lozano JA: Rosmarinic acid, a photo-protective agent against UV and other ionizing radiations. Food Chem Toxicol grant from the Spanish Ministry of Science and 2009;47:386-392. Technology (SENIFOOD). The authors are also 15. Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I: Green tea consumption and grateful to Dr. Mahmoud Magdy Abdallah Awad of mortality due to cardiovascular disease, cancer, and all the Department of Botany, University of Murcia for causes in Japan: the Ohsaki study. JAMA 2006;296:1255-1265. 16. Checkoway H, Powers K, Smith-Weller T, Franklin GM, helping in the formatting and revision of this script. Longstreth WT, Jr., Swanson PD: Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155:732-738. 17. Cui Y, Morgenstern H, Greenland S, Tashkin DP, Mao JT, Cai Conflict of interest statement L, Cozen W, Mack TM, Lu QY, Zhang ZF: Dietary flavonoid intake and lung cancer-a population-based case-control The authors certify that there is no conflict of study. Cancer 2008;112:2241-2248. 18. Neuhouser ML: Dietary flavonoids and cancer risk: evidence interest concerning the contents of the study. from human population studies. Nutr Cancer 2004;50:1-7. 19. Watanabe S, Uesugi S, Kikuchi Y: Isoflavones for prevention of cancer, cardiovascular diseases, gynecological problems and possible immune potentiation. Biomed Pharmacother References 2002;56:302-312. 20. Widyarini S: The Phyto-Oestrogens: Its Anticarcinogenic and 1. Wiart C: Family Myristicaceae. In Medicinal plants of the Asia- Antioxidant Activity - A Review. Indonesian Food Nutr Prog Pacific: Drugs for the future?. in Wiart C (ed): Singapore: 2005;12:27-36. World Scientific Publishing Co. Pte. Ltd, 2006a, 27-31. 21. Yanez J, Vicente V, Alcaraz M, Castillo J, Benavente-Garcia 2. Orwa C, Mutua A, Kindt R, Jamnadass R, A. Simons: O, Canteras M, Teruel JA: Cytotoxicity and antiproliferative Agroforestree Database: a tree reference and selection activities of several phenolic compounds against three guide version 4.0 In, World Agroforestry Centre ICRAF 2009. melanocytes cell lines: relationship between structure and 3. Kuete V, Nono EC, Mkounga P, Marat K, Hultin PG, activity. Nutr Cancer 2004;49:191-199. Nkengfack AE: Antimicrobial activities of the CH2Cl2-CH3OH 22. Rodriguez J, Yanez J, Vicente V, Alcaraz M, Benavente- (1:1) extracts and compounds from the roots and fruits of Garcia O, Castillo J, Lorente J, Lozano JA: Effects of several

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flavonoids on the growth of B16F10 and SK-MEL-1 melanoma Phyto and Cytotoxicity of Pycnanthus angolensis Methanolic cell lines: relationship between structure and activity. Extracts. Res J Med Sci 2008;2 178-181. Melanoma Res 2002;12:99-107. 40. Njoku JC, Hopp CD, Alali F, Asuzu UI, McLaughlin LJ: 23. Benavente-García O, Castillo J, Alcaraz M, Vicente V, Rio Dihydroguaiaretic Acid: A Bioactive Component of the Stem JAD, Ortuno A: Beneficial action of Citrus flavonoids on Bark of Pycnanthus angolensis Planta Medica 1997;63 580- multiple cancer-related biological pathways. Curr Cancer 581. Drug Targets 2007;7:795-809. 41. Moon HI, Chung JH: Meso-dihydroguaiaretic acid from 24. Martinez C, Yanez J, Vicente V, Alcaraz M, Benavente-Garcia Machilus thunbergii SIEB et ZUCC., and its effects on the O, Castillo J, Lorente J, Lozano JA: Effects of several expression of matrix metalloproteinase-2, 9 cause by polyhydroxylated flavonoids on the growth of B16F10 ultraviolet irradiated cultured human keratinocyte cells melanoma and Melan-a melanocyte cell lines: influence of (HaCaT). Biol Pharm Bull 2005;28:2176-2179. the sequential oxidation state of the flavonoid skeleton. 42. Davis RA, Barnes EC, Longden J, Avery VM, Healy PC: Melanoma Res 2003;13:3-9. Isolation, structure elucidation and cytotoxic evaluation of 25. Martínez C, Castillo J, Alcaraz M, Martínez C, Benavente- endiandrin B from the Australian rainforest plant Endiandra García O, Yáñez J, Castells MT, Ortega VV: The effect of the anthropophagorum. Bioorg Med Chem 2009;17:1387-1392. flavonoid diosmin, grape seed extract and red wine on the 43. Anonymous: Dihydroguaiaretic acid Summary. In, pulmonary metastatic B16F10 melanoma Histology and CureHunter Inc., 2003. histopathology: cellular and molecular biology 2005;20:1121- 44. Sandson TA, Felician O: The potential application of cyclo- 1129 oxygenase type 2 inhibitors to Alzheimer's disease. Exp Opin 26. Martinez Conesa C, Vicente Ortega V, Yanez Gascon MJ, Invest Drugs 1998;7:519-526. Alcaraz Banos M, Canteras Jordana M, Benavente-Garcia O, 45. Ríos JL, Giner RM, Prieto JM, Atta ur R: New findings on the Castillo J: Treatment of metastatic melanoma B16F10 by the bioactivity of lignans. in Studies in Natural Products flavonoids tangeretin, rutin, and diosmin. J Agric Food Chem Chemistry. Elsevier, 2002, vol 26, 183-292. 2005;53:6791-6797. 46. Moon TC, Seo CS, Haa K, Kim JC, Hwang NK, Hong TG, Kim 27. Benavente-García O, Castillo J, Lorente J, Alcaraz M, Yañez JH, Kim do H, Son JK, Chang HW: Meso-dihydroguaiaretic J, Martinez C, Vicente V, Lozano JA: Antiproliferative activity acid isolated from Saururus chinensis inhibits of several phenolic compounds against melanoma cell lines: cyclooxygenase-2 and 5-lipoxygenase in mouse bone Relationship between structure and activity. Agro Food Ind. marrow-derived mast cells. Arch Pharm Res 2008;31:606-610. Hi-Tech 2005;4:30–34. 47. Li G, Lee CS, Woo MH, Lee SH, Chang HW, Son JK: Lignans 28. Leonard EC, Simonton D: Uses of vegetable butter-based from the bark of Machilus thunbergii and their DNA cetyl myristoleate for treating osteoarthritis and other topoisomerases I and II inhibition and cytotoxicity. Biol musculoskeletal disease conditions and injuries. InUSA, 2010. Pharm Bull 2004;27:1147-1150. 29. Brill K, Eckes D, Weiler E, Lord G: Chronic inflammatory pain 48. Wiart C: Ethnopharmacology of medicinal plants: Asia and control with omega-5. In, Sierra Life Sciences INC, 2004. the Pacific. Totowa, N.J, Humana Press, 2006b. 30. Iguchi K, Okumura N, Usui S, Sajiki H, Hirota K, Hirano K: 49. Ubillas RP, Shivanand JD, Mendez DD, Fort DM, Evans JL, Myristoleic acid, a cytotoxic component in the extract from Luo J: Terpenoid-type quinones for treatment of diabetes. Serenoa repens, induces apoptosis and necrosis in human InUSA, 1997. prostatic LNCaP cells. Prostate 2001;47:59-65. 50. Luo J, Cheung J, Yevich EM, Clark JP, Tsai J, Lapresca P, 31. Vacherot F, Azzouz M, Gil-Diez-De-Medina S, Colombel M, Ubillas RP, Fort DM, Carlson TJ, Hector RF, King SR, Mendez De La Taille A, Lefrere Belda MA, Abbou CC, Raynaud JP, CD, Jolad SD, Reaven GM: Novel terpenoid-type quinones Chopin DK: Induction of apoptosis and inhibition of cell isolated from Pycnanthus angolensis of potential utility in proliferation by the lipido-sterolic extract of Serenoa repens the treatment of type 2 diabetes. J Pharmacol Exp Ther (LSESr, Permixon in benign prostatic hyperplasia. Prostate 1999;288:529-534. 2000;45:259-266. 51. Laird DW, Poole R, Wikstrom M, Altena IA: 32. Clément M, Tremblay J, Lange M, Thibodeau J, Belhumeur Pycnanthuquinone C, an unusual 6,6,5-tricyclic P: Whey-derived free fatty acids suppress the germination of Geranyltoluquinone from the Western Australian brown alga Candida albicans in vitro. FEMS Yeast Res 2007;7:276-285. Cystophora harveyi. J Nat Prod 2007;70:671-674. 33. Patoèka J: Biologically active pentacyclic triterpenes and 52. Löbermann F, Mayer P, D.Trauner: Biomimetic Synthesis of their current medicine signification. J Appl Biomed 2003;1:7- (−'2d)-Pycnanthuquinone C through the Diels–Alder 12. Reaction of a Vinyl Quinone. Angew. Chem. Int. Ed. 34. Abrantes M, Mil-Homens T, Duarte N, Lopes D, Cravo P, 2010;49:6199–6202. Madureira M, Ferreira MJ: Antiplasmodial activity of lignans 53. Fabricant DS, Farnsworth NR: The value of plants used in and extracts from Pycnanthus angolensis. Planta Med traditional medicine for drug discovery. Environ Health 2008;74:1408-1412. Perspect 2001;109 Suppl 1:69-75. 35. Habsah M, Ali AM, Lajis NH, Sukari MA, Yap YH, Kikuzaki H, 54. Lok CM, Groenewegen A, Stroink JBA, Ward JP: Kombic Nakatani N: Antitumour-promoting and cytotoxic acid, a hydroquinone polyisoprenoic carboxylic acid from constituents of etlingera elatior. Malaysian J Med Sci Pycnanthus kombo seed fat. Phytochemistry 1983;22:1973- 2005;12:6-12. 1976. 36. Mukherjee PK: Plant products with hypocholesterolemic 55. Leonard EC: Uses of kombic acid as an antioxidant. InUSA, potentials. Adv Food Nutr Res 2003;47:277-338. 2002:9. 37. Tan RX, Chen JH: The cerebrosides. Nat Prod Rep 56. Leonard EC: Uses of kombic acid as an anticancer and 2003;20:509-534. cholestrol lowering agent. InUSA, 2004. 38. Fort DM, Ubillas RP, Mendez CD, Jolad SD, Inman WD, 57. Leonard EC: Uses of hydroquinone substituted Carney JR, Chen JL, Ianiro TT, Hasbun C, Bruening RC, Luo J, polyunsaturated fatty acids as antioxidants. InUSA, 2004. Reed MJ, Iwu M, Carlson TJ, King SR, Bierer DE, Cooper R: 58. Barclay SS, Bosley JA, Cain FW, Koenen C, Rogers JS, Ulrike Novel antihyperglycemic terpenoid-quinones from S: Patent application title: Blends Comprising a Substituted Pycnanthus angolensis. J Org Chem 2000;65:6534-6539. Fatty Acid or a Derivative Thereof. InUSA, Loders Croklaan 39. Onocha PA, Ajaiyeoba EO, Ali MS: In vitro Antileishmaniasis, USA LLC, 2010:25.

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59. Park B-G, Shin W-S, Um Y, Cho S, Park G-M, Yeon D-S, Kwon Int J Geriatr Psychiatry 2001;16:852-857. S-C, Ham J, Choi BW, Lee S: Selective vasodilatation effect of 79. Dannhardt G, Kiefer W: Cyclooxygenase inhibitors-current sargahydroquinoic acid, an active constituent of Sargassum status and future prospects. Eur J Med Chem 2001;36:109- micracanthum, on the basilar arteries of rabbits. Bioorg Med 126. Chem Lett 2008;18:2624-2627. 80. Marnett LJ, Kalgutkar AS: Design of selective inhibitors of 60. Choi BW, Ryu G, Park SH, Kim ES, Shin J, Roh SS, Shin HC, cyclooxygenase-2 as nonulcerogenic anti-inflammatory Lee BH: Anticholinesterase activity of plastoquinones from agents. Curr Opin Chem Biol 1998;2:482-490. Sargassum sagamianum: lead compounds for Alzheimer's 81. Asase A, Oppong-Mensah G: Traditional antimalarial disease therapy. Phytother Res 2007;21:423-426. phytotherapy remedies in herbal markets in southern Ghana. 61. Tundis R, Loizzo MR, Menichini F: Natural products as alpha- J Ethnopharmacol 2009;126:492-499. amylase and alpha-glucosidase inhibitors and their 82. Onwukaeme DN, Ikuegbvweha TB, Asonye CC: Evaluation hypoglycaemic potential in the treatment of diabetes: an of Phytochemical Constituents, Antibacterial Activities and update. Mini Rev Med Chem 2010;10:315-331. Effect of Exudate of Pycanthus Angolensis Weld Warb 62. Subramanian R, Asmawi MZ, Sadikun A: In vitro á- (Myristicaceae) on Corneal Ulcers in Rabbits. Trop J Pharm glucosidase and á-amylase enzyme inhibitory effects of Res 2007;6:725-730. Andrographis paniculata extract and andrographolid. Acta 83. Beuth J, Hunzelmann N, Van Leendert R, Basten R, Noehle Biochim Pol 2008;55:391-398. M, Schneider B: Safety and efficacy of local administration of 63. Simic A, Kroepfl D, Simic N, Ogunwande IA: Pycnanthus contractubex to hypertrophic scars in comparison to angolensis (Welw) Excell: Volatile oil constituents and corticosteroid treatment. Results of a multicenter, antimicrobial activity. Nat Pro Comm 2006;1:651 -654 comparative epidemiological cohort study in Germany. In 64. Ogunwande IA, Walker TM, Setzer WN: A Review of Vivo 2006;20:277-283. Aromatic Herbal Plants of Medicinal Importance from 84. Maragakis M, Willital GH, Michel G, Gortelmeyer R: Nigeria. Nat Prod Comm 2007;2:1311-1316. Possibilities of scar treatment after thoracic surgery. Drugs 65. Ancolio C, Azas N, Mahiou V, Ollivier E, Di Giorgio C, Keita A, Exp Clin Res 1995;21:199-206. Timon-David P, Balansard G: Antimalarial activity of extracts 85. Willital GH, Heine H: Efficacy of Contractubex gel in the and alkaloids isolated from six plants used in traditional treatment of fresh scars after thoracic surgery in children medicine in Mali and Sao Tome. Phytother Res 2002;16:646- and adolescents. Int J Clin Pharmacol Res 1994;14:193-202. 649. 86. Alcaraz M, Acevedo C, Castillo J, Benavente-Garcia O, 66. Onocha PA, Otunla EO: Biological activities of extracts of Armero D, Vicente V, Canteras M: Liposoluble antioxidants Pycnanthus angolensis (Welw.) Warb. Afr J Trad provide an effective radioprotective barrier. Br J Radiol Complement Altern med 2010;2:186-190. 2009;82:605-609. 67. Diehl MS, Atindehou KK, Tere H, Betschart B: Prospect for 87. Fennell CW, Lindsey KL, McGaw LJ, Sparg SG, Stafford GI, anthelminthic plants in the Ivory Coast using ethnobotanical Elgorashi EE, Grace OM, van Staden J: Assessing African criteria. J Ethnopharmacol 2004;95:277-284. medicinal plants for efficacy and safety: pharmacological 68. Gbolade AA, Adeyemi AA: Investigation of in vitro screening and toxicology. J Ethnopharmacol 2004;94:205- anthelmintic activities of Pycnanthus angolensis and 217. Sphenocentrum jollyanum. Fitoterapia 2008;79:220-222. 88. Amanor KS: Collaborative forest management, forest 69. Mantovani A: Cancer: Inflaming metastasis. Nature resource tenure and the domestic economy in Ghana. 2009;457:36-37. IRDCurrents. 1997;15:10-16. 70. Gallo MB, Sarachine MJ: Biological Activities of Lupeol. Intl J 89. Agyare C, Asase A, Lechtenberg M, Niehues M, Deters A, Biom Pharm Sci 2009;3:44-66. Hensel A: An ethnopharmacological survey and in vitro 71. WHO: Diabetes. In Fact sheet N°312. WHO Media centre, confirmation of ethnopharmacological use of medicinal 2011. plants used for wound healing in Bosomtwi-Atwima- 72. Ashidi JS, Houghton PJ, Hylands PJ, Efferth T: Kwanwoma area, Ghana. J Ethnopharmacol 2009;125:393- Ethnobotanical survey and cytotoxicity testing of plants of 403. South-western Nigeria used to treat cancer, with isolation of 90. Abbiw D: Useful plants of Ghana. London, Intermediate cytotoxic constituents from Cajanus cajan Millsp. leaves. J Technology Publications & The Royal Botanic Gardens, Kew, Ethnopharmacol 2010;128:501-512. 1990. 73. Kuete V, Krusche B, Youns M, Voukeng I, Fankam AG, 91. Zirihi GN, Mambu L, Guede-Guina F, Bodo B, Grellier P: In Tankeo S, Lacmata S, Efferth T: Cytotoxicity of some vitro antiplasmodial activity and cytotoxicity of 33 West Cameroonian spices and selected medicinal plant extracts. J African plants used for treatment of malaria. J Ethnopharmacol 2011;134:803-812. Ethnopharmacol 2005;98:281-285. 74. Simon JE, Wang M, Gbewonyo K, Rafi MM, Acquaye DF, 92. Odugbemi TO, Akinsulire OR, Aibinu IE, Fabeku PO: Asianowa Y: Antioxidant and anti-inflammatory activity of Medicinal plants useful for malaria therapy in Okeigbo, Ondo compounds and preparations from African nutmeg seeds. State, Southwest Nigeria. Afr J Tradit Complement Altern InUSA, 2010. Med 2006;4:191-198. 75. Greig NH, Lahiri DK, Sambamurti K: Butyrylcholinesterase: 93. Do Céu de Madureira M, Paula Martins A, Gomes M, Paiva J, an important new target in Alzheimer's disease therapy. Int Proença da Cunha A, do Rosário V: Antimalarial activity of Psychogeriatr 2002;14 S 1:77-91. medicinal plants used in traditional medicine in S. Tomé and 76. Sramek JJ, Frackiewicz EJ, Cutler NR: Review of the Príncipe islands. J Ethnopharmacol 2002;81:23-29. acetylcholinesterase inhibitor galanthamine. Expert Opin 94. Jiofack T, Ayissi L, Fokunang C, Guedje N, Kemeuze V: Investig Drugs 2000;9:2393-2402. Ethnobotany and phytomedicine of the upper Nyong valley 77. Sramek JJ, Zarotsky V, Cutler NR: Review of drug forest in Cameroon. Afr J Pharm Pharmacol 2009;3:144-150. development and therapeutic role of cholinesterase 95. Irvine FR: Woody plants of Ghana. London:, Oxford inhibitors in Alzheimer's disease. Drug Develop Res University Press, 1961. 2002;56:347-353. 96. Betti JL: Medicinal plants sold in yaoundé markets, 78. Wilkinson D, Murray J: Galantamine: a randomised, double- Cameroon. Afr Stud Monogr 2002;23:47-64. blind, dose-finding trial in patients with Alzheimer's disease. 97. Betti JL, Lejoly J: Contribution to the knowledge of

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medicinal plants of the Dja Biosphere Reserve, Cameroon: studies from Ghana and Rwanda. in Janick J, Whipkey A Plants used for treating jaundice. J Med Plant Res (eds): Issues in New Crops and New Uses. Virginia: ASHP, 2009;3:1056-1065. 2007, 332-337. 98. Ogbole OO, Ajaiyeoba EO: Traditional management of 106. Atindehou KK, Kone M, Terreaux C, Traore D, Hostettmann tuberculosis in Ogun State of Nigeria: the practice and K, Dosso M: Evaluation of the antimicrobial potential of ethnobotanical survey. Afr J Tradit Complement Altern medicinal plants from the Ivory Coast. Phytother Res Med;7:79-84. 2002;16:497-502. 99. Olowokudejo JD, Kadir AB, Travih VA: An Ethnobotanical 107. Elufioye TO, Obuotor EM, Sennuga AT, Agbedahunsi JM, Survey of Herbal Markets and Medicinal Plants in Lagos Adesanya SA: Acetylcholinesterase and State of Nigeria. Ethnobot Leaf 2008;2008. butyrylcholinesterase inhibitory activity of some selected 100. Onocha PA, E. O. Otunla: Biological activities of extracts of Nigerian medicinal plants. Rev Bras Farmacogn 2010;20:472- Pycnanthus angolensis (Welw.)Warb. 2010;2:186-190. 477. 101. Betti JL: An ethnobotanical study of medicinal plants among the Baka pygmies in the Dja biosphere reserve, Cameroon. African Study Monographs 2004;25:1-27. Figures 102. Kayode J, Jose RA, Ige OE: Conservation and Biodiversity Fig 1: Structure of pycnangloside from Pycnanthus angolensis Erosion in Ondo State, Nigeria:Assessing Botanicals Used in (adapted from Tsaassi et al, 2010) the Cure of Sexually Transmitted Diseases in Owo Region. Fig 2: Pycnanthuquinones (A, B and C) Ethnobot Leaf 2009;13:734-738. Fig 3: Kombic acid (A), Sargaquinoic acid (B), Sargachromenol 103. Tchinda AT, Tchuendem MH, Khan SN, Omar I, Ngandeu F, (C), Sargahydroqunoic acid (D) Nkeng PEA, Choudhary IM: Antioxidant activity of the crude extract of the fruits of Pycnanthus angolensis and á- glucosidase inhibitory activity of its constituents. Tables Pharmacologyonline 2008;1:422-431. Table 1. Documented Ethnomedical Information for Pycnanthus 104. Akendengué B: Medicinal plants used by the Fang angolensis traditional healers in Equatorial Guinea. J Ethnopharmacol Table 2. Documented Biological Activities for Extracts of 1992;37:165-173. Pycnanthus angolensis 105. Govindasamy R, Simon J, Puduri VS, Juliani HR, Asante- Dartney J, H. Arthur, Diawuo B, Acquaye D: Retailers and wholesalers of african herbal and natural products: case

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