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Koher, G.; Khan, A.; Suarez-Vega, G.; Meesakul, P.; Bacani, A.; Kohno, T.; Zhu, X.; Kim, K.H.; Cao, S.; Jia, Z. Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki. Encyclopedia. Available online: https://encyclopedia.pub/entry/48945 (accessed on 13 June 2024).
Koher G, Khan A, Suarez-Vega G, Meesakul P, Bacani A, Kohno T, et al. Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki. Encyclopedia. Available at: https://encyclopedia.pub/entry/48945. Accessed June 13, 2024.
Koher, Grant, Ajmal Khan, Gabriel Suarez-Vega, Pornphimon Meesakul, Ann-Janin Bacani, Tomomi Kohno, Xuewei Zhu, Ki Hyun Kim, Shugeng Cao, Zhenquan Jia. "Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki" Encyclopedia, https://encyclopedia.pub/entry/48945 (accessed June 13, 2024).
Koher, G., Khan, A., Suarez-Vega, G., Meesakul, P., Bacani, A., Kohno, T., Zhu, X., Kim, K.H., Cao, S., & Jia, Z. (2023, September 08). Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki. In Encyclopedia. https://encyclopedia.pub/entry/48945
Koher, Grant, et al. "Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki." Encyclopedia. Web. 08 September, 2023.
Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki
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In Hawaii, the plants P. albidus, P. forbesii, P. kauaiensis, and P. ruber are collectively known as māmaki in ethnomedicine, where P. albidus predominates. Farmed māmaki is becoming increasingly popular in Hawaii and the United States. Māmaki teas (such as bottled Shaka tea) are the dominant product. Historically, māmaki has been utilized for its medicinal properties, promoting well-being and good health through consuming tea made from its leaves, ingesting its fruit, and incorporating it into ointments.

māmaki Pipturus albidus biological activities therapeutic properties human health phytochemical

1. Introduction

A 1992 report by the United States Fish and Wildlife Service estimated that Hawaii is home to over 1200 vascular plant species, many of which are endemic due to the Hawaiian Islands’ geographical isolation and unique biodiversity [1]. Understanding the anthropological and ecological contexts of life on the Hawaiian Islands necessitates special consideration of the novel plant and animal species, including the native plants that may hold cultural significance among indigenous populations. One such vascular plant species that fits this criterion is Pipturus albidus (Hook & Arn.) A. Gray, also known as Waimea or, most commonly, as māmaki (Figure 1).
Figure 1. Photographic representation of a māmaki (P. albidus) plant specimen, (a) Green māmaki, (b) Red vein coloration of māmaki. Courtesy of Grant.
It is important to acknowledge that historically and presently, the common name māmaki has served as an inclusive term encompassing all four species of the Pipturus genus native to the Hawaiian Islands [2]. Within the Urticaceae family, the Pipturus genus comprises twenty-nine accepted species as of 2023, as documented by the Kew Royal Botanical Gardens online plant database, predominantly inhabiting tropical and subtropical climates across Asia and Pacific Basin islands [3]. Four species of the Pipturus genus, namely P. forbesii, P. kauaiensis, P. ruber, and P. ablidus, are exclusively endemic to Hawaii [2][4]. For the sake of clarity and coherence, this reseach strictly employs the term māmaki to specifically denote P. albidus.
P. albidus holds a significant place in the cultural heritage of indigenous Hawaiian communities, its incorporation predating the era of Western scientific classification, with initial reports dating back to exploratory expeditions conducted by British and French explorers in the late 18th and early 19th centuries [2]. Throughout history, P. albidus has undergone multiple taxonomic revisions, largely driven by inconsistencies in earlier documentation of Hawaiian plant species [2]. In 1854, botanist Hugh Algernon Weddell formally established the Pipturus genus, and the currently accepted species name of P. albidus was subsequently introduced in Alphonse Pyramus de Candolle’s work “Prodromus Systematis Naturalis Regni Vegetabilis” [2]. In 1999, Wagner et al. identified previously recognized Pipturus species as being synonymous with P. albidus and further revised the genus to the currently accepted four members endemic to the Hawaiian Islands, including P. albidus [4].
P. albidus, hereafter referred to as māmaki for the purpose of this reseach, exhibits noteworthy distinction within the Pipturus genus by virtue of its enduring utilization by indigenous Hawaiian communities. Besides its application as a material resource, māmaki enjoys recognition for its traditional medicine applications [5][6][7][8]. The claimed health benefits associated with māmaki are diverse, including potential anti-infectious and anti-inflammatory properties [6][8][9]. Over the past decade, growing public awareness of māmaki’s potential therapeutic benefits has spurred increased consumer demand outside of Hawaii, particularly within the United States [2]. This growth in interest has consequently stimulated the development of industries centered around māmaki, including those involved in agriculture, distribution, and retail operations [2]. As consumer interest in māmaki continues to expand, māmaki has the potential to emerge as a distinctive agricultural resource, further facilitating the growth of the commercial industry in Hawaii. Moreover, māmaki participates in significant ecological relationships, such as its involvement in interspecies interactions with vulnerable avian and insect species [10][11][12][13][14].

2. Physical Characteristics of Māmaki

Māmaki was characterized by the renowned Swedish botanist Carl Skottsberg in 1934, describing māmaki as “a shrub or rarely small tree with somewhat hairy stems. The phenotypic variation in functional leaf traits of the māmaki is ovate in shape, light green on the upper side and almost white, with very fine short hairs on the underside. The māmaki plant possesses three main veins, often characterized as bright red or purple in color”. [15]. Skottsberg’s description, while encompassing a wide range of variable characteristics, can be considered a reliable and overarching general assessment of the physical attributes exhibited by māmaki.
Māmaki, as a species, displays a considerable degree of phenotypic variation [2][7]. This substantial variability and inconsistencies in the documentation have historically resulted in the classification of māmaki as nine distinct species within the Pipturus genus [2]. However, more recent taxonomic revisions have consolidated these variations into a single species, P. albidus [2]. The extensive range of phenotypic variation in māmaki poses challenges in interspecies and intraspecies classification, mainly due to overlapping characteristics with other local plant species [2][7]. These phenotypic differences serve as a basis for categorizing māmaki into its noted variants and subvariants. These distinctions are commonly determined by leaf and vein color, typically reflected by the variant’s common names. Identified māmaki variants include, but are not limited to, green māmaki, panaewa, purple māmaki and associated sub-variants, and additional hybrid varieties [7]. Relatively large variations are seen in height, with mature specimens ranging between 2 and 20+ feet, resulting in māmaki being commonly classified as either a shrub or small tree [2][16]. In line with Skottsberg’s approach, the following description of māmaki’s physical characteristics aims to offer a general portrayal of the species as a whole and does not attempt to go into intricate detail regarding the multiple variants that have been recorded.
In a 1989 report published in the Agricultural Handbook no. 679 by Little & Skolmen, māmaki’s outer bark is described as exhibiting a light brown coloration, accompanied by a surface adorned with randomly distributed raised dots. The inner bark of māmaki is characterized by green-colored streaks, possessing a fibrous and mucilaginous texture [17]. The sapwood exhibits a pale, whitish-brown hue, while the soft heartwood retains a reddish-brown palette [17]. The trunk size of māmaki is largely variable, depending on life stage and environmental conditions; however, larger mature specimens of twenty-plus feet in height are noted as having a trunk size of approximately one foot in diameter [17]. The extension of branches and stems from the trunk occurs at protruding nodes, typically arranged in a zig-zag pattern across the bark [17]. Branches are relatively slender and long with respect to the trunk, giving them a notable drooping appearance [18][19]. New growths in the form of twigs may display fine gray hairs, which are similarly noted on the underside of māmaki’s leaves [17]. The root system of māmaki is fine and fibrous, and the sap is described as having a watery consistency [16][20]. As juveniles, māmaki plants display qualities that are more herbaceous in nature but that transition to more woody phenotypes during maturation [16].
One of the more pertinent identifying features of māmaki leaves (Figure 1) is their oval or elliptical shape, with the margins exhibiting toothed wavy edges [2][17]. The size and shape of the leaves can vary within an individual plant, with alterations in leaf sizes often seen along branches [17]. The green upper surface of māmaki leaves can display a range of hues, ranging from pale to dark greens, that are occasionally accompanied by reddish or purplish undertones [17]. Emerging from the leaf stalk, three prominent veins traverse the blade of each leaf, with the two lateral veins radiating outwards along the side [17]. These veins may exhibit variations in color ranging from light green to greenish shades of red and purple [17]. The underside of the māmaki leaf is layered by fine, pale gray hairs, which are reminiscent of the hairs observed in other nettle species [17]. Unlike certain nettle species, however, māmaki’s hairs do not elicit skin irritation upon contact [21].
Māmaki’s leaf stalks exhibit a range of 2.5–7.5 cm in length, while the leaf blades measure between 6 and 20 cm in length and 3 and 15 cm in width [17]. The leaves are relatively thin, displaying a gentle curvature at the margins that taper into a pointed apex, while a gradual thickening occurs toward the base of the leaf [17]. Close examination reveals the presence of microscopic cystoliths, which are minute carbon-calcium mineral growths dispersed on the leaf surface [17][22]. Cystoliths in other plant species are believed to potentially play a role in regulating physiological calcium concentrations and may serve as reservoirs for releasing CO2 and H2O upon decomposition; whether this is applicable to māmaki has not been clarified [17][22]. In terms of texture, māmaki leaves have been described as ranging from leathery to paper-like, with a subtle roughness to the touch [15][17].
As a monoecious organism, mature individuals of māmaki possess the ability to produce both male and female flowers simultaneously [17]. These flowers, characterized by their greenish-white coloration, are present in clusters that lack stalks and are segregated by sex located on branches in proximity to leaf stems [17]. Māmaki flower clusters exhibit a rounded shape and measure between 6 and 13 mm in diameter, with the sessile female flowers being relatively larger as compared to the males [17]. Māmaki exhibits the ability to continuously fruit throughout the year following maturation [23]. The fruits of māmaki develop as clustered, irregular spheres, displaying a white to translucent appearance, and have an average diameter of approximately 13 mm [17]. Each fruiting body contains individual elliptically shaped seed measuring around 1.5 mm in length [17]. The flavor profile of māmaki’s fruits is commonly described as mild, slightly sweet, or sometimes tasteless [20]. Furthermore, the fruits are adorned with fine hairs that may vary in color, ranging from yellow to pale brown [20].

3. Ecological Characteristics of Māmaki

With the exception of Kaho’olawe and Ni’ihau, māmaki is distributed throughout the Hawaiian Islands, growing at elevations reaching up to 6000 feet above sea level [17]. This plant species displays moderate hardiness and can tolerate diverse environmental conditions [4][17][24]. Māmaki predominantly thrives in coastal mesic, lowland mesic, mixed mesic, and wet forest biomes of the Hawaiian Islands, with the availability of moisture, influenced by rainfall patterns and soil retention, being a primary factor governing its geographical range [4][16][24]. Other factors contributing to its distribution include sunlight exposure, temperature, and intra- and interspecies competition [24]. Exhibiting r-type traits, māmaki demonstrates the capacity to colonize disturbed areas rapidly, facilitated in part by a wide seed dispersal range [25]. Māmaki can also establish itself in volcanic environments, showcasing its resilience in recovering from lava-induced wildfires [26][27].
While tolerating a range of environmental conditions, māmaki prefers well-drained, moist soils [16][24]. In soil with inadequate moisture, māmaki is susceptible to rapid desiccation. In contrast, excessively wet soils with poor drainage can lead to root rot and increased vulnerability to pathogens [24]. Māmaki displays adaptability to different soil types, including clay, organic, and volcanic cinder-dominated soils, with a favorable response to higher soil nitrogen concentrations [24]. Although capable of growth in direct sunlight, māmaki is naturally inclined toward forested understory environments, with partial shade conducive to optimal growth conditions [16][24]. Māmaki seedlings have been observed to exhibit rapid germination in areas with canopy gaps but also display viability regarding other canopy configurations, demonstrating flexibility in response to light availability [28][29].
Regarding interspecies ecological relationships, māmaki has been recognized for attracting diverse insect and bird species [10][11][30]. The entomological papers published by Otto Sweezy in 1904 documented the association of māmaki with over fifty insect species. Notably, māmaki readily attracts the only two native butterfly species endemic to the Hawaiian Islands, namely the Kamehameha butterfly (Vanessa tameamea) and Hawaiian Blue butterfly (Udara blackburni), whose offspring rely on māmaki as a source of shelter and nourishment [14][31]. Moreover, the endemic moth Udea stellata utilizes māmaki as a protective habitat for its larval offspring [13]. Young or weakened māmaki plants are susceptible to infestations by various agricultural pests such as twig borers, multiple ant species, termites, and aphids, in addition to fungal infections by Rhizoctonia, Phytophthora, and Pucciniastrum boehmeriae [24][32]. Invasive species have also been observed to be involved in ecological interactions with māmaki. Invasive gastropod herbivores, such as Cuban slugs (Veronicella cubensis) and Giant African snails (Achatina fulica), pose a threat to māmaki due to their voracious consumption of seedlings [33]. More recently, in 2018, the introduction of the invasive moth species Arcte coerula resulted in the defoliation of māmaki [34]. While māmaki itself is not considered threatened, these examples of invasive species predation underscore the potential risks they pose to Hawaii’s endemic species. Additionally, māmaki serves as a habitat and food source for numerous endemic avian species, including those of high conservation concern, such as the Hawaiian thrush (Myadestes obscurus), Hawaiian Elepaio (Chasiempis sandwichensis), and the endangered Hawaiian crow (Corvus hawaiiensis) [10][12][30].
While the interactions between māmaki and nonnative and native animal species have been more readily documented, interspecies plant interactions and competition involving māmaki remain relatively understudied, particularly in agricultural contexts [16][24]. It has been suggested that Pipturus species exhibit resistance to competition-induced stress, likely attributable to their regular occurrence in densely populated understory environments alongside native and invasive plant species [35]. A study investigating māmaki’s response to competition with breadfruit trees (Artocarpus altilis) in agricultural settings revealed an overall increase in māmaki’s biomass, possibly due to aggressive resource acquisition strategies facilitated by root system expansion [16]. However, the applicability of this aggressive resource allocation model across all māmaki habitats and its implications for agricultural operations are still largely unknown. Further investigations are required to elucidate māmaki’s interspecies interactions, particularly given the predicted future trends of increasing agricultural propagation and the introduction of alien species. It is also essential to recognize that māmaki’s response to anticipated ecological changes resulting from climate change remains understudied.

4. Agricultural Propagation, Challenges, and Commercial Industry

The agricultural propagation of māmaki represents a small-scale commercial industry that has experienced a notable upsurge in consumer interest and demand for māmaki tea in recent years [24][36]. Primarily cultivated for its tea leaves, the māmaki agricultural sector caters to local consumption and export markets [24]. Like all commercial crops, certain considerations must be made to mitigate obstacles in the māmaki cultivation process, such as a high juvenile mortality rate [24]. Once successfully established and reaching maturity, māmaki plants can be harvested for multiple years with minimal maintenance requirements before replacement becomes necessary [24].
Māmaki can be agriculturally propagated through both seed and cutting methodologies [24]. Seed propagation generally yields higher success rates, although it may not produce a parental clone, which may be preferable in certain agricultural scenarios [24]. If retainment of parental characteristics is desired, māmaki clones can be easily generated using leaf and hardwood cuttings [24].
As outlined by Sugano et al. in their 2018 report, māmaki seeds can be planted intact or crushed and sprinkled onto selected soil mediums [24]. Direct-to-ground-soil seed propagation demonstrates limited success, while container-based planting with moist mediums has proven more effective in inducing germination [24]. Germination of seedlings typically occurs within a timeframe of 2 to 4 weeks, after which the young plants are transplanted into individual containers. As the individual māmaki plants grow, they are successfully transplanted into progressively larger containers to prevent growth constriction and development inhibition. Finally, once the propagated māmaki plants attain an adequate size, they will undergo a final transition to ground soils [24].
Best practices for the cutting propagation of māmaki adhere to a similar transitional container-based growth methodology, as Sugano et al. (2018) recommended [24]. Generally, isolated māmaki cuttings are first established in containers with moist mediums to stimulate initial growth. As the cutting continues to develop, it is serially planted into larger containers until a target size is reached, where it will then be deposited in agricultural ground soils for long-term cultivation. Different types of parental plant cuttings are reported to exhibit varying degrees of viability, with hardwood cuttings of māmaki showing higher establishment rates than leaf-tip cuttings [24].
Under optimal environmental conditions, māmaki exhibits a relatively rapid growth rate, allowing for the harvest of mature leaves as early as 2.5 to 4 months following ground soil transplantation [24][36]. Subsequent harvests of māmaki leaves can be conducted at intervals of every 2 to 3 months, extending throughout 2 to 3 years before the need for crop replacement arises [24]. Alternative sources propose that plant productivity can be sustained for up to 5 years, permitting extended harvesting periods [36]. Plant replacement requirements are typically driven by a decline in plant vigor resulting from successive leaf harvests [24]. Once an initial crop of māmaki has been established, agricultural operations hold promise for long-term harvesting potential, benefiting from the species’ vigorous growth and the possibility of both vegetative and reproductive propagation throughout a plant’s agricultural lifespan [24][36].
Māmaki agricultural propagation is accompanied by various challenges that can hinder cultivation efforts. These obstacles encompass several aspects, including the tendency of young plants to exhibit root circularization and constriction, transplantation mortality resulting from physical damage and potential pathogen exposure, susceptibility to root rot in excessively moist and poorly drained soils, the possible loss of vigor due to environmental stressors, and the vulnerability of young or weakened plants to pest infestations [24]. To mitigate issues of root circularization, the utilization of elongated cones or rectangular containers is recommended, as these provide ample space, promoting vertical root growth [24]. While effective in stimulating growth, pruning practices must be executed with caution to minimize the risk of pest infestations [24]. Partial shade is advised to optimize growth conditions for young plants, as reflected in māmaki’s natural inclination to thrive in understory environments [24]. However, this preference for partial shade poses challenges for māmaki agricultural operations in lowland, non-forested areas where little to no natural barriers exist to filter sunlight [24]. As demand for māmaki leaves continues to rise, the expansion of māmaki farming into non-forested or suboptimal environments has become increasingly prevalent [24].
Innovative paired cropping techniques are currently under exploration to address the need for more efficient and cost-effective methods of cultivating māmaki beyond its natural range. In 2018, Sugano et al., in collaboration with the University of Hawaii, aimed to investigate an alternative agroforestry cropping system that would enhance the success rate of commercial māmaki farming in the lowlands of Hawaii while minimizing the over-exploitation of māmaki in forested environments [24]. Their study proposed the paired planting of larger shade-producing native Hawaiian plant species to, in turn, generate a more conducive and naturalistic environment for commercial māmaki growth. Although the long-term results of Sugano et al.’s [24] study are still being evaluated, and no subsequent publications have been released, this report sheds light on the commercial challenges associated with an expanding māmaki agricultural industry, given increases in consumer demand.
Similarly to a combined agroforestry approach, another study explored the paired planting of māmaki and breadfruit trees, a practice currently employed by certain Hawaiian agricultural operations [16][36]. Despite some uncertainties, the presence of competition and shade provided by breadfruit trees demonstrated a positive effect on the overall biomass of māmaki plants when paired together [16][36]. While research on māmaki intercropping is relatively nascent, if successfully implemented, these novel approaches have the potential to facilitate intercrop operations within restricted spaces and contribute to cost and resource reduction by promoting a naturalistic ecological setting for māmaki growth, thereby alleviating the need for potentially costly agricultural infrastructure [24].
Despite market growth over the last 7 years, smaller-scale, family-owned farms employing conventional propagation techniques in forested environments continue to be the predominant method of commercial māmaki production [2]. In recognition of this trend, governmental and private entities have shown increased interest in further developing agricultural operations, as seen by the issuance of small business and research grants to expand existing enterprises [2][16]. As of 2022, over 20 brands selling a range of māmaki products are supported by current operations, with loose-leaf tea mixtures and pre-made bottled beverages being the most popular items [2].

5. Cultural and Medicinal Use of Māmaki

In the Hawaiian Islands, māmaki has deep cultural significance and has been traditionally utilized by native Hawaiian populations in several applications, including woodworking, textile, and medicinal practices [7][19][20][37]. With its reputation for being easily workable, māmaki hardwood has been employed in tool production [17][38]. A notable tool crafted from māmaki hardwood is the “i’e kuku”, a club used to beat and process bark cloth [5][18]. Bark cloth, which can be partially or entirely derived from the fibrous inner bark of māmaki, is a fundamental material in the historical production of textiles, including clothing, cordage, and paper, by indigenous communities [19][37].
Bark cloth, also referred to as “kapa” in the Hawaiian Islands, is a general term encompassing nonwoven textiles made from various barks, including that of māmaki [39]. Different types of bark cloth exhibit distinct characteristics and applications based on their composition, with māmaki-based bark cloths noted for their strength and durability [37][40]. The prevalence of different types of bark cloth varies by location, with māmaki bark cloths being unique to Hawaii [37][39][40][41]. Hawaiian kapa is incorporated in many products, including clothing such as loin cloths or skirts, netting, cordage, blankets, and artistic creations [39]. Producing bark cloth typically involves peeling the inner bark, moistening it, and flattening it using clubs [39]. Once the desired thickness and shape are achieved, the bark cloth is dried before use [37][39].
Māmaki, as a medicinal resource, was widely consumed by native Hawaiian populations for the treatment of various ailments [7][8][9][15]. Both the leaves and fruits were utilized, with the fruits being consumed directly or applied as poultices, and the leaves brewed into tea [7][18]. Traditional tea preparation involves mixing fresh māmaki leaves into the ground with spring water and hot stones [15][20]. Depending on the specific condition being treated or desired medicinal effects, māmaki could be consumed individually or in combination with other therapeutic substances to achieve desired outcomes [7].
Numerous health benefits have been associated with the consumption of māmaki, and these claims continue to be promoted in contemporary times. The purported health benefits include cholesterol reduction, blood sugar regulation, reductions in blood pressure, cardiovascular benefits, anti-inflammatory effects, stress relief, digestive aid, anti-infectious properties (anti-viral, anti-fungal, and anti-microbial), promotion of liver health, action as a laxative, use as a pregnancy aid, and treatment for thrush and general debility [7][9][15][18][20]. While promising, it is important to note that the majority, if not all, of these health claims lack significant scientific characterization, and the specific active compounds and underlying mechanisms associated remain relatively unknown.
More contemporarily, māmaki is typically consumed as brewed tea produced from dried leaves [20]. One Hawaiian-based retailer, Big Island Coffee Roasters, characterizes māmaki tea as having an earthy and nutty flavor, with a natural sweetness and a lack of bitterness. The steeping time for dried māmaki leaves can vary according to personal preference, with longer steeping resulting in more pronounced flavors. Māmaki tea is often marketed for its perceived health benefits, being advertised as a supplemental treatment for a range of conditions such as diabetes mellitus, depression, rat-lungworm disease, fatigue, and anxiety (Big Island Coffee Roasters, Bee Boys, 2020). Moreover, advertisers often highlight the antioxidant profile of māmaki tea as a selling point (Big Island Coffee Roasters). Given the significance of these claims, it becomes important to conduct investigations to verify the scientific basis for such statements. While preliminary studies indicate potential therapeutic properties, more comprehensive investigations are necessary to validate and fully understand the contexts of māmaki’s medical capabilities.

6. Anti-Microbial, Anti-Viral, and Anti-Fungal Activity of Māmaki

Prior data have indicated that māmaki may possess anti-microbial, anti-viral, and anti-fungal properties, as initially demonstrated by Locher et al. in a 1995 report published in the Journal of Ethnopharmacology [6]. This study assessed different fractional extracts of māmaki and other Hawaiian medicinal plants for their inhibitory activity against select bacterial, viral, and fungal infectious agents in vitro [6].
Extract-treated disk diffusion assays conducted on Trypticase Soy Agar (TSA) bacterial cultures revealed that māmaki inhibited the growth of two out of the four tested bacterial strains [6]. Specifically, water- and methanol-based extracts derived from the bark and leaves of māmaki, respectively, exhibited growth inhibition against the pathogenic Gram-positive strains Staphylococcus aureus and Streptococcus pyogenes at a treatment concentration of 100 µg/mL [6]. However, the two Gram-negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa, demonstrated no discernible response upon exposure to māmaki extracts. Differential inhibitory activity between the bark H2O extracts and the leaf methanol māmaki extracts may suggest that the inhibitory active compounds responsible are solvent-specific and distinct. Moreover, differential anti-microbial compositions may be present in the leaves of māmaki as compared to the bark, this being reflected by māmaki leaf H2O extracts not exhibiting inhibitory activity against S. aureus and S. pyogenes, unlike the H2O extracts derived from māmaki bark [6]. In the same study, māmaki extracts were also analyzed for their ability to inhibit the growth of three fungal species over a 24 h incubation period at body temperature [6]. In this assessment, māmaki leaf acetonitrile extracts inhibited the growth of Microsporum canis and Trichophyton rubrum at treatment concentrations of 1000 µg/mL and Epidermophyton floccosum at a treatment concentration of 125 µg/mL. These fungal species, known as dermatophytes, have a global distribution and are commonly associated with low-risk dermal infections in humans and other mammals [42][43][44]. While the acetonitrile māmaki leaf extract displayed fungal inhibition, it did not display inhibition against the previously mentioned bacterial strains, suggesting that māmaki leaf’s anti-fungal compounds are distinct from its anti-microbial compounds.
Currently, Locher et al.’s 1995 study represents the first and only published literature investigating the anti-microbial and anti-fungal properties of māmaki [6]. The inhibitory properties demonstrated by māmaki extracts do offer preliminary insight giving initial support to medicinal claims of māmaki’s potential in combating fungal and bacterial infections. Still, the efficacy of these therapies as they relate to established clinical treatments requires further expansion. The possible mechanisms of action and the associated active compounds responsible for the observed growth inhibition in the Gram-positive bacterial strains remain unknown. It remains unclear whether the displayed anti-microbial activity indicates selective inhibition specific toward Gram-positive strains. Similarly, it is unknown whether māmaki would show anti-fungal inhibition of fungal strains outside dermatophytes. This uncertainty highlights a need for follow-up assessments to investigate the broader spectrum of māmaki’s anti-fungal and anti-microbial activity.
Locher et al. (1995) also evaluated the in vitro effects of māmaki extracts on various viruses, including Herpes simplex virus 1 and 2 (HSV 1 and 2), vesicular stomatitis virus (VSV), poliovirus, Semliki Forest virus, and coxsackie B3 virus [6]. The researchers employed a 50% endpoint viral titration technique to compare virus-induced cytopathy between māmaki extract-treated and non-extract-treated cell lines. While not displaying inhibition of poliovirus, Semliki Forest virus, and coxsackie B3, māmaki did exhibit a high degree of anti-viral activity against HSV 1 and 2 and VSV relative to 16 other medicinal plants evaluated in the study. Expressed as the minimal concentration of plant extract needed for the prevention of virus-induced cytopathic effect, the water-based extracts derived from māmaki stems demonstrated inhibition of HSV 1 and 2 at an extract concentration of 250 µg/mL (virus titer of 10−4) and VSV at a concentration of 500 µg/mL (virus titer of 10−4) [6]. A subsequent 1996 study by Locher et al. further assessed māmaki’s in vitro anti-viral properties by examining its inhibitory activity against human immunodeficiency virus-1 (HIV-1) [8]. By comparing māmaki extract-induced cytotoxicity and HIV-1-induced cytopathy, researchers observed that methanol and water extracts produced from the leaves and bark of māmaki inhibited HIV-1 cytopathy in MT-4 cultured cell lines [8]. In both of Locher et al.’s 1995 and 1996 studies, māmaki extracts demonstrated a relatively low degree of cytotoxicity and a high degree of viral protection, suggesting selectivity toward the viral agents [6][8].
Like māmaki’s anti-fungal and anti-microbial properties, the specific active compounds responsible for the observed anti-viral activity have not been explicitly elucidated in Locher et al.’s 1995 [6] and 1996 [8] studies. Nonetheless, certain assumptions regarding māmaki’s anti-viral compounds can still be inferred from their findings. In Locher et al. (1996), extracts separated māmaki’s compounds based on their polarity [8]. The differential degrees of HIV-1 anti-viral inhibition observed between water and methanol māmaki extracts thus implies the existence of distinct anti-viral components occurring within each respective extract. Additionally, the variances in anti-viral activity observed among extracts derived from different parts of the māmaki plant suggest localized discrepancies in the anti-viral compound composition throughout the plant. This is reflected by the superior levels of anti-viral activity against HIV-1 exhibited by the methanol and water māmaki leaf extracts compared to their stem extract counterparts. Among the many questions raised by Locher et al.’s 1995 and 1996 reports [6][8], the reasons why māmaki extracts’ anti-viral compounds displayed selectivity toward only HSV 1 and 2, VSV, and HIV-1 and not the other viruses evaluated is unclear. Whether this specificity of māmaki’s anti-viral activity towards these viruses is due to similarities in mechanisms of anti-viral action or other factors is unknown.
Overall, little to no additional data exploring the potential anti-infectious activity of māmaki have been published since Locher et al.’s 1995 and 1996 reports [6][8]. Although the results from these studies show promising preliminary evidence, further extensive research is required to understand the scope and capabilities of māmaki as an anti-infectious therapeutic, especially in comparison to other, better understood clinical treatments. Given the growing concern of antibiotic resistance and the continuous evolution of viral strains, there is an increasing need to identify future pharmaceutical compounds that may hold potential as novel or alternative drug therapies against infectious agents. Underrepresented plants used in traditional medicine, such as māmaki, may serve as valuable sources for discovering such compounds. Given the current data, comprehensive investigations are necessary to explore māmaki further and unveil its anti-infectious active compounds and mechanisms of action.

References

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