From Traditional Usage to Pharmacological Evidence: Systematic Review of Gunnera perpensa L.

Gunnera perpensa is the only species of the genus Gunnera that has been recorded in Africa. Its leaves, rhizomes, roots, and stems are reported to possess diverse medicinal properties and used to treat or manage various human and animal diseases and ailments. Gunnera perpensa is an ingredient in many herbal concoctions and prescriptions which have been used to induce or augment labour, postnatal medication, to treat parasitic diseases, urinary complaints, kidney problems, general body pains, sexually transmitted infections, and many other diseases. Several classes of phytochemicals including alkaloids, benzoquinones, ellagic acids, flavonoids, phenols, proanthocyanidins, tannins, and minerals have been isolated from G. perpensa. Scientific studies on G. perpensa indicate that it has a wide range of pharmacological activities including acetylcholinesterase, anthelmintic, antibacterial, antifungal, antinociceptive, anti-inflammatory, antioxidant, antitumour, lactogenic, and uterotonic. Gunnera perpensa has a lot of potential as a possible source of pharmaceutical products for the treatment of a wide range of both human and animal diseases and ailments. Some of the chemical compounds isolated from G. perpensa have demonstrated various biological activities when investigated in in vitro assays. Future research should focus on the mechanisms of action of the isolated compounds, their efficacy, toxicity, and clinical relevance.


Introduction
Gunnera perpensa L. is a member of the genus Gunnera L., a single genus of the family Gunneraceae. The genus was named in honour of the Norwegian bishop and botanist Johan Ernst Gunnerus (1718-1773) [1]. According to Qiu et al. [2] and Soltis et al. [3], there is a close relationship between genus Gunnera and Myrothamnus flabellifolia Welw., a morphologically different taxon confined to dry habitats belonging to the monogeneric family Myrothamnaceae. This sister relationship between genera Gunnera and Myrothamnus was inferred by rbcL, atpB, and 18S molecular data with a bootstrap value of 75% [3] and also by rbcL and rps16 introns molecular data [4]. Research by Moore et al. [5] revealed that G. perpensa and M. flabellifolia have similar geographical distribution. Genus Gunnera includes 30-40 herbaceous species, mostly distributed in the southern hemisphere [4]. Gunnera manicata Linden ex Delchev. and G. tinctoria (Molina) Mirb. are among some of the popular Gunnera species in the world [6][7][8]. They are natives of South America but also widely cultivated in temperate, tropical, and subtropical countries as ornamental and medicinal plant species [1,[6][7][8][9][10][11]. Both species have escaped from cultivation in some countries; for example, these species are now naturalized and considered potential invasive aliens in Australia, Ireland, and New Zealand [8,12]. Aqueous and methanolic extracts of G. manicata displayed antioxidant and antimicrobial activities [9] corroborating wide usage of the species as herbal medicines in Brazil. Gunnera tinctoria is widely used as herbal medicine for analgesic, anti-inflammatory, cardiovascular, gastrointestinal, genitor-urinary, obstetricgynaecological, and respiratory diseases in Argentina [13]. In Sub-Saharan Africa, G. perpensa is the most popular Gunnera species. Gunnera perpensa was the first species of the genus to be described by Linnaeus in 1767 and exists in Africa from Sudan, Ethiopia, Democratic Republic of Congo (DRC), Burundi, Madagascar, Rwanda, Uganda, Kenya, Tanzania, Botswana, Namibia, Zimbabwe, Mozambique, Lesotho, South Africa, and Swaziland [14]. Gunnera perpensa is widely known for its high medicinal importance leafy vegetable species [41]. Similarly, in Swaziland, the roots, stalks, and stems are edible and also used as ingredients of traditional beer [42]. In Lesotho, G. perpensa leaves are used as hot poultices for wounds and boils [28,43], decoction of roots is used to regulate menstrual periods and as remedy for menstrual pains [43,44] and as colic in pregnant women [43,44], expulsion of placenta in both women and animals [18], and vermifuge in humans and animals [28], and leaves are burnt, crushed, and smoked for headaches [43].
Gunnera perpensa is a robust, erect, perennial herb which grows up to 1 m tall and always grows in moist habitats, marshy areas, and along river banks. Its roots are 30 cm thick, fleshy, dark brown or blackish on the outside but yellow or pinkish-red inside [1,45]. All the leaves arise from a central tuft near the top of the apex, just above the soil level. The leaves are large, dark bluish-green, and kidney shaped and covered with hairs on both surfaces especially along the veins, in young leaves. The margins of the leaves are irregularly toothed. The veins are very noticeable on the lower surface of the leaf, radiating from the point where the petiole joins the leaf, referred to as palmate radiation [1,45]. The flowers are numerous, small and not very noticeable, pinkish, reddish brown, and borne on a long slender spike, which is taller than the leaves. There will be female flowers at the base, male flowers at the top, and bisexual flowers in the middle of each spike [1,45]. It is unable to tolerate frost and cold conditions [45]. In southern Africa, G. perpensa is often referred to as "river pumpkin" in English, "gobho" in Swati, "iphuzilomlambo" in Xhosa, and "ugobho" in Zulu.
Like most medicinal plants in southern Africa, G. perpensa is collected from the wild. The unsustainable harvesting of G. perpensa as herbal medicine and destruction of its wetland habitat due to development and agriculture are threatening its continued existence. Although G. perpensa is widespread throughout its distributional range, its population is declining due to overexploitation of its rhizomes and roots which are sold in the medicinal (muthi) markets throughout South Africa. According to Dold and Cocks [46], G. perpensa is heavily traded in the Eastern Cape province, South Africa, characterized by a high price on the medicinal (muthi) market with 1 kg fetching R47.80 (US$4.54) with 115.6 kilogrammes as mean quantity traded per trader per annum. In Swaziland, G. perpensa is a dominant medicinal plant harvested from wetlands, with traders generating R150-200 (US$20.49-27.32) monthly from selling the rhizomes or roots of the species [28]. Furthermore, research by Williams [47] revealed that large volumes of this species are traded in medicinal (muthi) markets in South Africa and local extirpations have been noted particularly in the Eastern Cape [46] and KwaZulu Natal provinces [26,48]. Raimondo et al. [49] categorized G. perpensa as declining in South Africa using the modified IUCN Red List Categories and Criteria version 3.1 of threatened species [50][51][52]. According to Victor and Keith [51] and von Staden et al. [52], a species categorized as Least Concern (LC) under the IUCN Red List Categories and Criteria version 3.1 [50] can additionally be categorized either as rare, critically rare, or declining. The observed population decline of G. perpensa in Lesotho and South Africa [49,53] is due to overexploitation as Evidence-Based Complementary and Alternative Medicine 3  Headache Leaves burnt and crushed and smoked, root decoction taken orally Lesotho; South Africa [43,86] Heart diseases Root decoction taken orally Lesotho [33] Hypertension Root decoction taken orally Lesotho [33] Impotence Root decoction taken orally South Africa; Swaziland [16,24,42,85] Indigestion Root decoction taken as tonic South Africa [24,73] Induce or augment labour and as antenatal medication Rhizome decoction taken orally South Africa [22] Infertility in women Root decoction taken orally South Africa [29] Kidney problems Root decoction taken orally South Africa [29] Poor appetite Root decoction taken as tonic South Africa [24] Psoriasis Root infusions applied topically South Africa [22] Pulmonary ailments Rhizome decoction taken orally South Africa [73] Rheumatic fever Root decoction taken as tonic South Africa [22,24] Scabies Root decoction taken as tonic South Africa [24] Stimulate milk production Root decoction taken orally South Africa [35] Stomachache Leaves, rhizome decoction taken orally Lesotho; South Africa [22,53,86] Syphilis Root decoction taken orally South Africa [32] Swelling Rhizome decoction applied topically South Africa [22] Ticks and other parasites Leaves and rhizome used as repellent South Africa [79] Ulcers Leaf decoction taken orally South Africa [73] Urinary infections Root decoction taken orally South Africa [32] Urinary stones Root tinctures South Africa [22] Uterine bleeding Root bark decoction taken orally Swaziland [87,88] Wound dressing Leaves used as poultices, rhizome decoction applied as a dressing Lesotho; South Africa [16,22,24,36,43,73] Evidence-Based Complementary and Alternative Medicine 5 herbal medicine, destruction of its habitat, medicinal plant trade, and popularity of the species in the medicinal (muthi) markets. It is within this context that the current study was carried out, aimed at discussing how G. perpensa is used as a single agent or in complex herbal mixtures, and assesses the phytochemistry and pharmacology of the species. The review is also aimed at assessing whether there is correlation between the ethnomedicinal uses of G. perpensa with its chemical and bioactive properties. Figure 1 shows structures of some of the secondary metabolites isolated from the leaves, rhizomes, roots, and stems of G. perpensa. These are the plant parts that are used to prepare G. perpensa herbal decoctions or infusions that are widely used in different traditional medicine systems in southern Africa. The reported compounds were identified and characterized by various criteria including UV, 1 H NMR, 13 C NMR, and mass spectroscopy. The phytochemical screening of methanolic extract of G. perpensa rhizomes carried out by Simelane et al. [54] revealed the presence of steroids, saponins, and glycosides in addition to secondary compounds shown in Figure 1. Mtunzi et al. [55] quantified inorganic elements in G. perpensa roots, with manganese showing the highest concentration of 1.46 ± 0.001 ppm, followed by iron (1.12 ± 0.003 ppm), nickel (0.239± 0.006 ppm), zinc (0.201 ± 0.0002 ppm), lead (0.153± 0.003 ppm), and copper (0.124 ± 0.002 ppm). According to Mtunzi et al. [55], the use of G. perpensa roots as herbal medicine will not cause heavy metal toxicity but can be of good use to the users in cases of micronutrient deficiency. Similarly, Chigor [56] isolated alkaloids, flavonoids, flavonols, phenols, proanthocyanidins, and tannins from aqueous, acetone, and methanol leaf and rhizome extracts of G. perpensa. Brookes and Dutton [57] isolated 3,3 ,4 -tri-Omethyl ellagic acid lactone 1, ellagic acid lactone 2, Z-methyl lespedezate 4, p-hydroxy-benzaldehyde 6, 1,1 -biphenyl-4,4 -diacetic acid 10, and glucose from methanol extracts of G. perpensa roots. Drewes et al. [58] isolated 2-methyl-6-(-3-methyl-2-butenyl)benzo-1,4-quinone 7, 3-hydroxy-2methyl-5-(3-methyl-2-butenyl)benzo-1,4-quinone 8, and 6hydroxy-8-methyl-2,2-dimethyl-2H-benzopyran 9 from dichloromethane extract of the leaves and stems of G. perpensa while rans-phyt-2-enol 13 was isolated from methanol extracts of the aerial parts of the species. Khan et al. [59] isolated trimethyl ether of ellagic acid glucoside 3,

Acetylcholinesterase (AChE) Enzyme Inhibition
Ndhlala et al. [60] investigated the acetylcholinesterase enzyme inhibitory activity of aqueous, petroleum ether, dichloromethane, and 80% ethanol rhizome extracts of G. perpensa using the enzyme isolated from electric eels. Gunnera perpensa water extracts showed good AChE inhibitory activity (>90%) with IC 50 value of 3.249 ± 0.56 g/mL which is considered potent inhibitor of AChE. Similarly, Simelane et al. [35] estimated the acetylcholinesterase activity of an aqueous extract of Gunnera perpensa rhizome using acetylthiocholine iodide and found the extract to inhibit 23% of AChE activity. Ozturk Sarikaya [68] evaluated the compound pyrogallol 14 as a potential inhibitor for AChE enzyme and the results showed that the compound exhibited potent AChE enzyme inhibitory activity with IC 50 and inhibitory constant (K i ) values 10.2 and 8.6 M, respectively. These findings call for detailed research on acetylcholinesterase (AChE) enzyme inhibition activities of G. perpensa as the mechanisms of action of the species during muscle contraction when used as herbal medicine to induce labour or expel placenta after birth [15,18,22,[24][25][26]35] are through the inhibition of AChE enzyme.

Anthelmintic
Victor and Keith [51]    orally administered with G. perpensa 50, 100, and 400 mg/kg doses and haemoglobin was out of the range on day 0 and improved to be within the range on days 7 and 14. The observation that haemoglobin and haematocrit were within the expected range signifies that G. perpensa could influence the replenishment of lost blood thereby curbing anaemia that may be caused by Heterakis gallinarum [71]. According to Brookes and Dutton [57]

Antinociceptive and Anti-Inflammatory
Nkomo et al. [66] evaluated the antinociceptive and antiinflammatory activities of aqueous and methanolic extracts of G. perpensa rhizome using the abdominal constriction, hotplate, formalin, hyperalgesia, and fresh egg albumininduced inflammation. According to Nkomo et al. [66], both aqueous and methanolic extracts of G. perpensa demonstrated analgesic activities which were not dose dependent. In the acetic acid-induced writhing test, both doses of methanolic extracts of G. perpensa significantly reduced abdominal contortions. Nkomo et al. [66] used the hotplate test to assess the central antinociceptive properties of G. perpensa with both doses of aqueous and methanolic extracts significantly increasing the reaction time to thermal stimulation. The formalin test induced a biphasic response in all animals, and during the inflammatory phase both the aqueous and methanolic extracts significantly reduced pain. These findings suggest that G. perpensa possesses both antinociceptive and anti-inflammatory activities supporting its traditional use for pain management. Ndhlala et al. [60] investigated the anti-inflammatory effects of aqueous rhizome extracts of Gunnera perpensa using Cyclooxygenase (COX-1 and COX-2) inhibitory bioassays. The water extracts of G. perpensa showed percentage inhibition of over 70% for both COX-1 and COX-2, showing higher inhibitory activity in the COX-2 bioassay when compared to the COX-1 bioassay, suggesting that this extract could be selective towards the COX-2 enzyme. The high COX-2 inhibitory activity of G. perpensa makes the species a better product when treating because the COX-2 enzyme is specific in treating inflamed tissue, resulting in less gastric irritation as compared to COX-1 inhibitors and hence decreased risk of gastric ulceration [60]. Similarly, Muleya et al. [72] evaluated anti-inflammatory activity of G. perpensa using the in vitro lipoxygenase inhibition assay determined by the Evidence-Based Complementary and Alternative Medicine 9 soybean derived 15-lipoxygenase type I-B (15-LOX). Gunnera perpensa exhibited some soya bean 15-LOX inhibitory activity with EC 50 value of 81.18 g/ml [72]. Lim et al. [74] evaluated anti-inflammatory and antinociceptive activities of p-hydroxy-benzaldehyde 6 isolated from Gastrodia elata Blume using the acetic acid-induced vascular permeability test and acetic acid-induced writhing test in male ICR mice. The compound, p-hydroxy-benzaldehyde 6, suppressed the production of nitric oxide and induction of inducible nitric oxide synthase COX-2 in the lipopolysaccharide-(LPS-) activated RAW264.7 macrophages [74]. The compound, phydroxy-benzaldehyde 6, also diminished the reactive oxygen species level elevated in the LPS-activated macrophages [74]. Gunnera perpensa can therefore be used for treating inflammation related conditions including abdominal pain, swelling of the body, menstrual pains, kidney inflammation and problems, sores, general body pain, and wounds (see Tables 1 and 2).
The compound pyrogallol 14 inhibited 78.0% lipid peroxidation of linoleic acid emulsion at 30 g/mL concentration; and BHA, BHT, -tocopherol, and trolox exhibited inhibitions of at least 83.8% against peroxidation of linoleic acid emulsion at the same concentration [68]. In addition to this, pyrogallol 14 was effective of all the scavenging and reducing power results [68]. Previous researchers argued that the antioxidant properties of G. perpensa are probably due to the presence of flavonoids and phenolics [56] as these compounds, for example, flavonoids, are known to have free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, antioxidative, anticancer, and antiviral activities [76].

Antitumour
Mathibe et al. [67] evaluated the in vitro antitumour effects of Z-venusol 5 isolated from the roots of G. perpensa as well as Re-Joovena6, a commercial concoction containing G. perpensa (0.3 mg/ml), Ocotea bullata (Burch.) E. Meyer (0.3 mg/ml), and unspecified quantities of Vitamin E using human breast (MCF-7) cancer cells and human mammary epithelial cells (HMECs) with cisplatin and camptothecin drugs as positive controls. Z-venusol 5 showed a statistically significant, concentration dependent, apoptotic inhibitory effect on proliferation of MCF-7 cells, with an IC 50 of 53.7 g/ml after 72-hour exposure and the highest concentration (250 g/ml) used resulted in 69% inhibition [67]. There was insignificant inhibition (of 20%) of HMECs proliferation which was observed when concentration of Z-venusol 5 was increased beyond 16.6 g/ml and the highest concentration used resulted in only 27% inhibition of proliferation of HMECs [67]. The fluorescein isothiocyanate Annexin V and the lactate dehydrogenase activity assays suggested that Z-venusol 5 induced apoptotic cell death in the breast cancer cells. None of the Re-Joovena concentrations tested showed any significant effect. These findings suggest that Z-venusol 5 is cytotoxic to human breast tumour cells in vitro, and cell death follows an apoptotic pathway. Khan et al. [77] evaluated the in vitro antiproliferative activity of pyrogallol 14 towards human tumour cell lines, including human erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, and erythroleukemic HEL cell lines. In this study, inhibition of cell proliferation was consistently observed with IC 50 values of pyrogallol 14 on K562, Jurkat, HEL, and Raji cell lines within the range of 10-30 M [77]. These documented antitumour properties of G. perpensa justify the use of gently warmed aqueous rhizome decoctions and infusions administered orally for three to four weeks as remedy for cancer in the Eastern Cape province, South Africa [78].

Lactogenic
Simelane et al. [35] evaluated the effect of an aqueous extract of G. perpensa rhizome on milk production in rats. Female lactating rats that received oral doses of the extract of G. perpensa significantly produced more milk than controls. The mammary glands of rats treated with G. perpensa extract showed lobuloalveolar development and 0.8 g/ml of the extract was also found to stimulate the contraction of the uterus [35]. It is inferred that the plant extract exerted its activity on milk production and secretion by stimulating lobuloalveolar cell development and the contraction of myoepithelial cells in the alveoli. It is concluded that G. perpensa contains constituents with lactogenic activity mediated through binding to acetylcholine receptors that apparently contribute to its effectiveness in folk medicine. The reported lactogenic properties of G. perpensa corroborate the traditional use of the species to stimulate milk production in KwaZulu Natal province, South Africa [35].

Uterotonic
Kaido et al. [21] investigated the uterotonic activity of the crude decoction of G. perpensa on the isolated rat uterus and ileum preparation. Aqueous extract of G. perpensa initiated contractions in the isolated rat uterus, showed direct smooth muscle activity on the uterus, and potentiated the initial response of the uterus to oxytocin. Khan et al. [59] evaluated the effect of aqueous G. perpensa extract, ethyl acetate, ethyl acetate-methanol extract, and pure Z-venusol 5 on rat uterine and ileal muscles. Gunnera perpensa extract stimulated direct contractile response on isolated uterine smooth muscle and induced a state of continuous contractility of the uterus once all physiological buffer had been removed from the organ bath. By contrast, Z-venusol 5 did not trigger the direct contractile response but induced the state of continuous contractility once the organ bath was flushed [59]. These uterotonic properties of G. perpensa which promote uterine contractions were identified by traditional healers in southern Africa several years ago, and the species is now widely used to induce or augment labour, as an antenatal medication to tone the uterus and to assist in the expulsion of the placenta [15, 16, 18-22, 24-26, 35, 79].

Toxicity and Mutagenic
McGaw et al. [27] evaluated the possible toxicity of G. perpensa rhizome extracts using the brine shrimp microwell cytotoxicity bioassay [80]. All the extracts were lethal to the brine shrimp larvae at a concentration of 5 mg/ml. The acetone extract was extremely toxic at 1 mg/ml, with some toxicity evident at 0.1 mg/ml with the dichloromethane, ethanol, water, hexane, and methanol extracts displaying little activity at concentrations lower than 5 mg/ml [27]. Simelane et al. [54] evaluated the toxicity of G. perpensa rhizome methanol extract using the brine shrimp lethality test. The degree of the brine shrimp lethality was found to be directly proportional to the different concentrations of the extract, with lethal concentration (LC 50 ) of 137.62 mg/100 ml [54]. Mwale and Masika [81] evaluated the potential toxicity of G. perpensa leaf aqueous extract through the acute, subacute, and chronic toxicity tests using Wistar rats. Neither rat mortality nor changes in behaviour were noted for acute test and rat mortality for 400 mg/kg dose of subacute and 200 mg/kg of chronic test was 20% [81]. The authors observed mild splenic siderosis and renal inflammation in the subacute test and therefore G. perpensa is potentially toxic when used consecutively for a long period. Simelane et al. [35] determined the cytotoxicity activity of aqueous rhizome extract of G. perpensa using the MTT cell proliferation assay via the human embryonic kidney (HEK293) and human hepatocellular carcinoma (HepG2) cells. The cytotoxicity of the extract (LC 50 ) to two human cell lines (HEK293 and HepG2) was 279.43 g/ml and 222.33 g/ml, respectively [35].
The nontoxic nature of aqueous G. perpensa extracts has also been demonstrated at a cellular level using human fibroblast and monkey vero cell lines by Brookes and Smith [82]. Brookes and Smith [82] investigated whether G. perpensa exhibited any significant toxic effects on monkey vero cells and human fibroblasts. These cells were exposed for 24 hours to aqueous extracts of G. perpensa at concentrations ranging from 500 g/ml to 8 g/ml. The threshold for zero cell deaths occurred for monkey vero cells at 250 g/ml, and at this concentration it was found that 100% of human fibroblast cells survived [82]. The authors estimated the concentrations of G. perpensa in the bloodstream to be 4.6 g/ml, and based on this dilution that takes place in the bloodstream, the extract of this species is regarded as nontoxic.
Ndhlala et al. [60] investigated the mutagenic activity of aqueous rhizome extract of G. perpensa using the Salmonella microsome assay based on the plate-incorporation procedure with Salmonella typhimurium tester strain TA98, with and without metabolic activation. The results revealed that all the extracts were nonmutagenic towards the Salmonella typhimurium strain TA98 for the assay with and without S9 metabolic activation. The results obtained in this study offer supporting evidence for the safe use of these water extracts. However, animals or in vivo studies followed by human clinical trials are needed before G. perpensa herbal decoctions and infusions are recommended to induce labour, easy childbirth, and labour pains and expel the placenta.

Conclusion
Biological and pharmacological studies of various extracts and isolated compounds from G. perpensa confirmed acetylcholinesterase (AChE) enzyme inhibition, anthelmintic, antibacterial, antifungal, antinociceptive, anti-inflammatory, antioxidant, antitumour, lactogenic, and uterotonic activities. There is need to assess if G. perpensa has other chemical compounds such as anthocyanins, caffeic acid, ellagitannin, and quercetin that have been isolated from other Gunnera species and related genera [83]. A large number of the isolated compounds shown in Figure 1 have not been biologically tested; therefore, these compounds must be evaluated biologically in more detail. Further investigations should focus on the bioactive properties of these isolated compounds and their mechanisms of action aimed at illustrating the correlation between ethnomedicinal uses and pharmacological activities of various extracts of the species. Thus, more systematic research is required on G. perpensa compounds; their effects need to be further proved through additional animal experiments. Future research should combine the pharmacological effects, mechanisms of action, and clinical applications in assessing the efficacy of G. perpensa compounds and/or their extracts. Continued research on G. perpensa compounds, development, and discovery of pharmaceutical products and drugs from this species in the future will require more detailed studies in both the preclinical and clinical trials.
Future research should also focus on assessing toxicological aspects of the leaves, rhizomes, roots, and stems of G. perpensa as at present there is not enough systematic data about the pharmacokinetics and toxicity of this species, especially target-organ toxicity. More rigorous investigations should be done in the future investigating dosage range that is safe for humans and evaluations of target-organ toxicity. Such research work should be extended to focus on aspects of quality control to ensure safety and the fact that potentially toxic components of G. perpensa in herbal decoctions and infusions are kept below tolerance levels. Future research should also investigate any side effects that are associated with intake of G. perpensa herbal decoctions and infusions as a monotherapeutic agent or as an ingredient of complex herbal concoctions. Future research should also evaluate the combinational, additive, and synergetic effects associated with complex herbal concoctions that have G. perpensa as an ingredient.
The traditional usage of G. perpensa as herbal medicine to induce or augment labour, as an antenatal medication to tone the uterus and assist in the expulsion of the placenta and other ethnomedicinal uses as detailed in Tables 1 and 2, resulted in increased collection of its rhizomes and roots from the wild. The widespread usage of G. perpensa in southern Africa calls for conservation strategies and mechanisms for sustainable utilization of the species. McGaw et al. [27] obtained highest antibacterial activity from the leaf extracts followed by the stems, with the least activity noted for the root extracts. These findings provide a strong motivation for comparing the phytochemistry and biological activities of the leaves, stems, flowering stalks, flowers, and fruits with those of the rhizomes and the roots so as to justify the plant part substitution as a means of sustainable utilization of the species. Harvesting of G. perpensa rhizomes and roots means that the whole plant is removed resulting in reductions in the population size of the species.