Ethnomedicinal, Chemical, and Biological Aspects of Lannea Species—A Review

Lannea L. genus belongs to the Anacardiaceae botanical family and has long been used in traditional medicinal systems of many countries to manage several health conditions, but no studies have been conducted regarding its usefulness as a source of herbal medicine for human use. A literature review was conducted on scientific papers indexed on B-On, Pubmed, and Web of Science databases. Our results showed that medicinal plants from this botanical genus, mostly constituted by bark and leaf, are often used to approach a wide variety of disease symptoms, like fever, inflammatory states, pain, and gastrointestinal disorders. Phytochemical profiles of Lannea species revealed that phenolic acid derivatives including hydroquinones, phenolic acids, flavonoids, condensed tannins, and triterpenoids are the main classes of secondary metabolites present. Among the total of 165 identified compounds, 57 (34.5%) are flavonoids, mostly quercetin- and myricetin-derived flavonols and catechin and epicatechin flavan-3-ol derivatives also containing a galloyl group. In vitro and in vivo studies allowed the identification of 12 different biological activities, amongst which antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities were the most frequently cited and observed in in vitro essays. Our review contributes useful information for the scientifical validation of the use of Lannea species in traditional medicinal systems and shows that more research needs to be conducted to better understand the concrete utility of these as herbal medicines.


Introduction
Lannea A. Rich. in Guill. is an important genus of flowering plants in Anacardiaceae, a botanical family comprising 81 genera and 800 species spread across tropical and subtropical regions with warm or temperate climates (tropical and South Africa, Saudi Arabian Peninsula, India, China, and Indochina) [1].In addition to their importance in traditional medicinal systems, some species of Anacardiaceae have high economic value (e.g., Anacardium occidentale L., Mangifera indica L.) due to the use of their fruits and seeds in food and manufacture of beverages, being important to local communities and national economies as renewable forest resources and tradeable products [2,3].The ancestral knowledge of Traditional Medicine Practitioners about the different medicinal proprieties of distinct species of this family has benefited many communities of tropical and sub-tropical countries where access to conventional primary health services is scarce and also in more developed countries as a complementary use to conventional medicine [4].
The Lannea genus was first described by Achille Richard and published in Florae Senegambiae Tentamen 153 in 1831 [5].According to The World Flora Online [6], it includes a total of 36 accepted species (Table 1), of which 14.2% are classified as data deficient (DD), 30.9% as least concern (LC), 4.7% are classified as least concern (NT), and 7.1% as vulnerable (VU).Modern medicine and scientific developments contribute to creating better health conditions in industrialized countries through constant breakthroughs in many areas.However, the global demographic distribution shows us that most of the world's population lives in countries that do not have access to such healthcare.In these countries, people still rely almost exclusively on traditional medical systems, whose practices are based on the use of medicinal plants to treat illness or promote healthy conditions.Research shows that the ethnobotanical uses of Lannea species are well recognized in countries where they are native and includes their use as medicine, food, and ornamental and domestic lumber [12,13].
The use of Lannea species as medicinal plants in traditional medicinal systems is widely accepted, but there is a need for a critical assessment of their potential as a source of effective medicines based on quality, effectiveness, and safety data.A literature review of the available scientific information on Lannea species regarding their ethnomedical uses as well as their chemical, pharmacological, and toxicological data are hereby presented.This work is expected to provide a deep understanding of the potential of this botanical genus as a source of effective medicinal plants.

Selection of Information
Data collection and selection were made according to the scheme presented in Figure 1.Initially, the database search of the scientific literature yielded 438 results.After excluding duplicate results, 82 scientific reports were assessed for relevance.Next, irrelevant reports were eliminated, and finally, 42 scientific publications were considered eligible for detailed analysis.

Vernacular Names
The genus Lannea includes 16 species used in traditional medicinal systems (41.6% of the total number of accepted Lannea species) that are distributed in several countries, most of them in the African continent.Table 2 shows the vernacular names of the various species used in these traditional medicinal systems.

Ethnobotanical and Ethnomedical Data 2.2.1. Vernacular Names
The genus Lannea includes 16 species used in traditional medicinal systems (41.6% of the total number of accepted Lannea species) that are distributed in several countries, most of them in the African continent.Table 2 shows the vernacular names of the various species used in these traditional medicinal systems.(-)-vernacular name or ethnic group not found.

Traditional Uses
Table 3 summarises the obtained data on the traditional medicinal uses of the 14 Lannea species.Results showed that for most of them there is little information about the exact methodology and duration of treatment.Bark (29%) and leaf (17%) were the most used plant parts, and the most reported symptoms and illnesses were related to infection symptoms (31%), gastrointestinal discomfort (14%), pain (12%), diarrhoea (9%), and inflammation (7%).Lannea coromandelica and Lannea edulis are the most reported species and are used in traditional medicine systems of 15 and 14 countries, respectively.
Other Lannea species, like L. acida, are employed in tropical Africa to treat and manage bacterial, fungal, and viral infections, fever, and mental and gastrointestinal disorders.For example, L. acida is used to treat dysentery, stomach pain, and other gastrointestinal pathologies [29]; L. microcarpa is used for the treatment of mouth blisters, rheumatism, dysentery, diarrhoea, gastroenteritis, malaria, and bacterial infections [30]; L. schweinfurthii is used for the treatment of diseases related to the reproductive system, circulatory system, and gastrointestinal diseases, headaches, and against opportunistic diseases related to HIV, such as malaria, diarrhoea, tuberculosis, and skin infections [31].
Lannea ambacensis is known to be used in traditional Angolan medicine, particularly in the treatment of diabetes, rheumatism, and symptoms of respiratory, gastrointestinal, and urogenital diseases [32].

Phytochemical Studies
The results of the chemical studies conducted on Lannea species are summarised in Table 4.Most studies focused on leaf and bark plant parts.Polyphenolic compounds, including hydroquinones, phenolic acids, flavonoids, and terpenoids, namely triterpenoids, are the major classes of compounds identified in this botanical genus.Other terpenoid derivatives and fatty acids were also commonly identified.
Among the total 160 compounds identified in Lannea species, 57 (34.5%) are flavonoids (quercetin and myricetin flavonols) and condensed tannins like catechin and epicatechin, also containing a galloyl group.As in other Anacardiaceae species, proanthocyanidins are representative secondary metabolites found in all parts of the plant, mainly in the bark.

Biological Studies
Biological studies were conducted in vitro and in vivo using extracts prepared with different plant parts of Lannea species using, namely, the aerial part, bark, leaf, stem, root, stem and root bark, and the whole plant (Table 5).Most plant extracts were prepared with methanol or ethanol as solvents, and the bark and leaf of Lannea species were the most frequently used plant parts.
L. acida stem bark aqueous extract showed anti-diarrhoeal and anti-inflammatory activity-inhibition of prostaglandin E2 in the paw oedema method [61]; hydroalcoholic extract of the bark and the whole plant showed in vitro antioxidant activity and cytotoxic and anti-Mycobacterium tuberculosis H37Rv activities [62,63]; ethanolic extract of L. acida bark revealed in vitro antibacterial properties against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, and Bacillus subtilis), including against resistant antibiotic strains and also oestrogenic activity and anti-osteoporotic potential in the ovariectomized Wistar rat model [64].
The in vitro antibacterial activity against S. aureus and antioxidant activity exhibited by L. alata were attributed to the presence of prenylated flavonoids, epicatechin gallate, betamidine, and myricetin [47].
Quantitative evaluation of the inhibitory (MIC) and bactericidal (MBC) concentrations of methanolic extracts of the bark, stem, and root of L. barteri, against S. aureus, Staphylococcus epidermidis, Proteus mirabilis, E. faecalis, E. coli, and P. aeruginosa, confirmed that this medicinal plant has significant antibacterial and antifungal activities [65][66][67].
The biological properties of L. coromandelica are numerous (Table 5).A stem bark extract has shown in vitro antimicrobial, hypotensive, and sporicidal activities [68]; studies on the bark revealed in vivo anti-diarrhoeal activity and in vitro antimicrobial activities [69][70][71]; the presence in stem bark of dihydroflavonols and terpenoids, polyphenols, flavonoids, kaempferol, and quercetin provided in vivo hepatoprotective and antioxidant activities to this medicinal plant [72].
According to Sohni et al., 1995, L. edulis whole plant water extract showed low in vitro mutagenic activity against Salmonella typhimurium and antioxidant activity [73].

B EtOH
In vitro: antioxidant activity by DPPH Antioxidant activity through DPPH method using quercetin and gallic acid as positive controls.The IC 50 value of each extract was determined and all tests were performed in triplicate.The bark extract of Lannea acida showed IC 50 = 345.72 ± 7.76 µg mL −1 while that of Lannea velutina IC 50 = 478.68 ± 8.55. [40]

R B DCM In vitro: antiproliferative activity
The XTT assay was used to evaluate the antiproliferative activity of the extract, fractions, and compounds on three multiple myeloma cell lines: RPMI 8226, MM.1S, and MM.1R.Fractions were considered active when they inhibited at least 50% of cell growth at 20 µg/mL; two compounds showed activity on all cell lines with IC 50 values < 5 µM.Bortezomib was used as a positive control. [44]

Wp EtOH
In vitro: cytotoxic and anti-Mycobacterium tuberculosis H37Rv activities The rate of monocytes at different stages of mitosis was corrected in the absence and presence of the extract as follows: G0/G1  The extract considerably reduced the number of diarrhoeal episodes compared to control animals.The bark extract of L. coromandelica at a dose of 200 mg/kg showed a significant reduction (p < 0.05) of 68.86% in the number of faecal episodes, compared to the antidiarrheal drug, loperamide which has 89, 14% protection. [69]

L MeOH
In vivo: aspirin-induced antiulcer activity The test was performed on albino rats weighing between 150 and 200 g, using an aqueous suspension of aspirin at a dose of 200 mg/kg orally for 8 days.The result was a significant decrease in the ulcer index, with the percentage of gastric protection of 17.3% (standard), 78.29% (positive control), 30.57% (low dose), and 62.76% (high dose), and a significant reduction in the volume of gastric juice and acidity and increase in pH. [91]

B MeOH
In vitro: antibacterial activity Methanolic extract of L. coromandelica revealed a significant moderate antibacterial activity against Staphylococcus aureus, Salmonella typhi, Shigella dysenteriae, Pseudomonas aeruginosa, and Escherichia coli; there was no activity against Shigella boydii, however, there was a greater zone of inhibition against Escherichia coli (inhibition zone of 15.59 ± 0.22 mm), followed by Staphylococcus aureus and Shigella dysenteriae. [69]

L EtOH
In vivo: antidiabetic activity in rats induced by alloxan The ethanolic extract of L. coromandelica (100 to 200 mg/kg) reduced the glucose level (123 ± 2.2 and 115 ± 2.6, respectively) both in diabetic animals and in those induced with alloxan when compared to normal animals (74 ± 1.7 and 70 ± 1.4). [92]

Wp EtOAc Antimicrobial activity agar diffusion method
The antimicrobial activity demonstrated that the isolated compound was not active against Escherichia coli ATCC25922, Salmonella typhi ATCC 14028, Staphylococcus aureus ATCC25923, and Pseudomonas aeruginosa ATCC 27853 (MIC: 1000 µg/mL).
[93] Daily dosing of L. edulis resulted in significant reductions in blood glucose levels compared to those in the diabetic control from day 3; only the 300 mg/kg and 500 mg/kg L. edulis diabetic positive control groups had significant differences (p < 0.05) in mean blood glucose levels.The 100 mg/kg diabetic positive control group kg of L. edulis showed significant difference (p < 0.05) compared to diabetic control group from day 5. [75] In vitro: cytotoxic activity The cytotoxic effect of aqueous extracts was evaluated on U937, MeWo, and Vero cell lines tested.L. edulis at the highest tested concentration was seen to be significantly toxic (p = 0.007).L. edulis (p < 0.007) showed a similar toxic effect in the MeWo and Vero cell lines. [94]

Wp H 2 O In vitro: anti-inflammatory activity
The anti-inflammatory potential of the extract was evaluated on RAW 264.7 cells, and there was no anti-inflammatory activity observed for the plants tested.However, in the absence of LPS stimulation, there was an increase of NO production, indicating that the extracts might have pro-inflammatory properties. [94] Lannea humilis Lannea rivae

R, St
Hx, DCM, EtOAc, MeOH In vitro: antibacterial activity of selected compounds The hexane extracts of L. rivae exhibited intermediate antibacterial activity against E. faecalis, while the DCM extracts showed intermediate activity against both Gram-positive bacteria E. faecalis and S. aureus, but no activity against Gram-negative bacteria.The EtOAc and MeOH extracts demonstrated a broader spectrum of activity, with better activity being observed with the Gram-positive bacteria. [46]

Ap EtOH
In vivo: effect of ethanolic extract on ethanol/HCl-induced gastric ulcers in rats Doses of ethanolic extract of 100, 200, 400, and 800 mg/kg were tested in rats against gastric ulcer induced by ethanol-HCl and the effects were compared to those of pantoprazole 40 mg; after removal and analysis of the stomach, it was found that the ethanolic extract of L. schimperi showed an average protection of 81.7% compared to 87.5% for the drug pantoprazole. [55]

L MeOH
In vitro: anticoccidial activity in Eimeria tenella oocysts This activity was carried out using oocysts isolated from infected chicks, and three doses of methanolic extract of L. schimperi leaves were used, 25 mg/mL, 50 mg/mL, and 100 mg/mL.Anticoccidial activity was determined by counting lysed and non-sporulated oocysts and sporulated oocysts.The extract dose at 100 mg/mL exhibited 98% higher anticoccidial activity and an inhibition of 97.92%.Doses 25 and 50 mg/mL of extract showed activities and inhibitions against non-sporulated oocysts of E. tenella of 68% and 89% and 66.65 and 88.5, respectively. [37] In vitro: cytotoxic activity colorimetric test MTT was used to measure all growth and cellular chemosensitivity.The samples were prepared for a stock solution of 20 mg/mL in 100% DMSO, and emetine was used as a positive control.The 5-[alkenyl]-4,5-dihydroxycyclohex-2-enone mixture (1a-d) exhibited good in vitro cytotoxicity against the Chinese Hamster Ovarian mammalian cell line. [97]

MeOH
In vivo: anti-inflammatory activity The test was carried out using the egg albumin induction method in rats.Tested doses were 12 and 24 mg/kg, and acetylsalicylic acid 80 mg was used as standard.The anti-inflammatory response was significant (p< 0.05); however, there was no significant difference (p > 0.05) between the extract-treated groups and the standard drug-treated group (positive control).

R EtOAc
In vitro: ACHE inhibitory activity The ethyl acetate extract of L. schweinfurthii showed an IC 50 value higher than that of galanthamine (standard) 0.00053 mg/mL.The extract has ACHE inhibitory activity with an IC 50 of 0.0030 ± 0.000 mg/mL.[ The methanolic extract of the stem bark of L. Schweinfurthii was active against HIV type 2, with IC50 values < 10 µg/mL and 9.9 µg/mL against HIV-1, respectively. [99] Lannea velutina
[74] R B EtOH:H 2 O In vitro: antioxidant activity DPPH method 50% radical scavenging, at concentrations of 5-7 micrograms/mL, and 15-lipoxygenase inhibitors (50% inhibition at 10-18 micrograms/mL).L. velutina extract possessed a weak DPPH radical scavenging action. [ In vitro.Antimicrobial activity tested on mosquito larvae; molluscicidal activity with molluscs Positive results were obtained for antioxidant activity (methanolic extracts of bark and roots), antifungal activity (dichloromethane extract active against Candida albicans and Cladosporium cucumerinum); larvicidal activity against the malarial mosquito Anopheles gambiae (dichloromethane extract of bark and methanolic extract of leaves); and molluscicidal activity directed at the snail Biomphalaria pfeifferi, transmitter of schistosiasis.The ethanol extract of the bark showed greater antibacterial activity against Bacillus subtilis, Staphylococcus aureus (Gram-positive), Pseudomonas aeruginosa, and Salmonella typhimurium (Gram-negative). [ In vitro: antioxidant activity by DPPH method Petroleum ether, chloroform, and dichloromethane extracts are inactive as DPPH radical scavengers; the aqueous extract had moderate activity while the methanolic and hydroalcoholic extracts of root bark and stem bark were very active. [57]

B EtOH In vitro: antioxidant activity by DPPH method
For the test on the free radical potential on the radical DPPH, o L. velutina, which showed a percentage inhibition of 52.8125 ± 2.16% lower than that of the gallic acid, was used as reference substance. [79]

B EtOH
In vitro: antimicrobial activity by inhibition method Shigella dysenteria, S. aureus were sensitive to Lannea velutina extracts with inhibition diameters of 10 mm; Bacillus cereus and Escherichia coli were also sensitive to the extract with 8 mm and Salmonella thyphi with 7 millimetres.[

Discussion
Our analysis found that 14 Lannea species are reportedly used in traditional medicinal systems of over 35 countries to treat a variety of disease signals and symptoms.Among these, fever, inflammation, diabetes-related symptoms, gastrointestinal disorders, and sexually transmitted diseases are the most common diseases treated with various extracts of Lannea species.Although not all Lannea species have been studied for their biological activity, those that have been showed antimicrobial, antioxidant, and anti-inflammatory properties, mainly observed in vitro.These results support the use of Lannea medicinal plants in traditional medicinal systems, as most of their applications are in the treatment of disease symptoms related to the activities observed in vitro.
In the genus Lannea, some characteristic Anacardiaceae compounds such as anacardic acid, as well as common natural products such as gallic acid and derivatives, flavonol derivatives such as quercetin and rutin, kaempferol, myricetin, and flavones like luteolin, have been identified [49,58,97,101].
Twelve different biological activities have been reported in vitro and/or in vivo for Lannea species, with antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities being the most common.In many cases, the observed activity was considered significant when compared to the positive controls used in the studies.Most extracts were prepared with methanol, ethanol, and water, suggesting that most extracted compounds have a relatively high polarity.
Previous research on anacardic acid showed that this natural compound can exhibit a wide variety of other biological activities.For instance, antibacterial activity was observed against bacteria species like Bacilus subtilis, Helycobacter pylori, Propionibacterium acnes, and Staphylococcus aureus.Antimicrobial activity exhibited by L. velutina ethanolic leaf extracts, in which this compound has previously been identified, thus may be related to anacardic acid [100,101].
In an in vivo mouse model of inflammation induced by carrageenan, prostaglandin E2, dextran, and histamine, the effects of pretreatment with anacardic acid (administered at doses of 10, 25, and 50 mg/kg intraperitoneally) were investigated.The study revealed that anacardic acid exhibited inhibitory effects on carrageenan-induced oedema, with a significant efficacy observed at a dose of 25 mg/kg, surpassing that of the positive control, indomethacin.Histological examination of tissue specimens from the anacardic acid-treated group indicated reduced neutrophil infiltration compared to the carrageenantreated group.Furthermore, anacardic acid demonstrated inhibitory properties against carrageenan-induced depletion of glutathione and reduced levels of malondialdehyde, a pivotal marker of oxidative stress.Taken together, these results suggest that the antiinflammatory effect of anacardic acid is due to its ability to inhibit inflammatory mediators, mitigate chemotaxis, and alleviate oxidative stress.In addition, the assessment of antinociceptive activity showed a reduction in pain symptoms in the anacardic acid-treated group.Mechanistic insights into this activity revealed a link to opioid receptors, as demonstrated using the nonselective opioid receptor antagonist naloxone as a control [102].
Anacardic acid also exhibited modulatory activity in gene expression, cell death, and cell proliferation; selective cytotoxicity against human cancer cell lines was also observed, indicating that this compound may be a useful focus of study for the development of new therapeutic anticancer agents [101].
Quercetin, a common flavonol abundantly present in numerous plant species, has a significant antioxidant activity and has been described to prevent diseases like osteoporosis, cancer, tumours, and lung and cardiovascular diseases.In vivo studies have shown that this antioxidant activity is mainly exerted through the effect on gluthathione reactive oxygen species, enzymatic activity (namely acetylcholinesterase), and signal transduction pathways.Quercetin has also shown to be able to prevent lipopolysaccharide (LPS)-induced heart damage by clearing oxygen-free radicals and consequently preventing myocardium damage.Its activity is also exerted in several steps of signal transduction pathways, decreasing the impact of oxidative stress.In a LPS-induced acute liver injury in vivo mouse model, quercetin inhibited NF-κB and MAPK signalling pathways and inhibited the expression of apoptosis-related proteins, which led to decreased oxidative stress and tissue damage.Antioxidant and anti-inflammatory properties have been demonstrated for L. acida and L. coromandelica, from which quercetin has previously been identified [103].This natural product demonstrated selective in vitro antibacterial efficacy against various infectious strains of both Gram-positive and Gram-negative bacteria.Notably, Staphylococcus aureus, Staphylococcus epidermidis, and clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) exhibited significant susceptibility to quercetin.Furthermore, when administered concomitantly with antibiotics such as ampicillin, erythromycin, gentamycin, oxacillin, and vancomycin, quercetin significantly potentiated the antibacterial activity of these drugs against clinical MRSA strains, implying a synergistic interaction between quercetin and antibiotics.This observed phenomenon underscores the potential of quercetin as a promising therapeutic agent for the treatment of infectious diseases [104].
In other antibacterial studies, quercetin has showed inhibitory activity on pathogenic bacteria growth, namely E. coli, P. mirabilis, Aspergillus flavus, P. aeruginosa, Salmonella enteritidis, and S. aureus.Synthetic derivatives of this compound also showed growth inhibitory activity against E. coli, S. aureus, and P. aeruginosa.The current research proposes that the antibacterial mechanism is related to cell wall destruction and cell permeability deregulation, compromising metabolic pathways crucial for bacterial survival, like protein synthesis and expression, enzyme activity, and nucleic acid synthesis.This mechanism may justify the synergistic effect observed when quercetin was administered in combination with antibiotics [105].
Myricetin is a flavonol with a wide distribution in many plants and is highly recognised for its nutritional value.Previously conducted studies on this compound showed that it can display different biological activities, such as antioxidant activity, being able to reduce oxidative stress through mechanisms like radical scavenging, decreasing production of pro-inflammatory agents, and disrupting inflammatory pathways.Similar activities have also been observed for L. welwitschii and L. rivae, where this compound was previously identified.Anticancer activity has also been reported, with myricetin exhibiting selective cytotoxic activity against human hepatic, pancreatic, skin, colon, and leukaemia cancer cell lines with clinical relevance.Research showed that myricetin can also interfere with different mechanisms related to tumour proliferation, namely modulating gene expression and inhibiting enzymes and other agents that directly promote cell division.Other studies showed that myricetin can act as an anti-platelet aggregation agent, supressing thromboxane formation and inhibiting specific receptor binding of platelet activating factor, and as an antihypertensive agent, reducing systolic blood pressure and vascular reactivity; immunomodulatory activity has been described in vivo and in vitro, with myricetin acting on stimulating antibody formation and regulating TNF-α, IL-2, IL-6, and IL-12 expression and lymphocyte proliferation [106].
Flavonoid compounds like catechins and its derivatives, found in L. alata, and terpenoid compounds like b-sitosterol, found in L. coromoandelica, have previously been studied for their biological activities.While catechins have shown antioxidant activity in in vitro essays, b-sitosterol has exhibited several in vitro biological activities like antimicrobial, anti-inflammatory, antioxidant, and antidiabetic activities [96,107].
Understanding the biological activities of plant extracts represents a significant challenge due to their complex composition, which includes a variety of natural products derived from the secondary metabolism of plants.It is often believed that the observed activities of plant extracts are associated with the presence of the most common occurring compounds or classes of compounds; however, this association often occurs based on an equilibrium between concentrations of compounds belonging to different classes.In particular, synergistic and other complex interactions may play a role, and numerous reports documented in the literature indicate that the biological activities of isolated major compounds can be inferior to those of all extracts.
Our research showed that different plant parts of Lannea species are used as medicinal plants for the preparation of traditional herbal preparations through decoction and maceration.Phytochemical studies on this genus have shown that phenolic compounds are the chemical class with higher representativity, and that Lannea species have in vitro/in vivo biological activities (antibacterial, antidiabetic, antifungal, antimicrobial, anti-inflammatory, antioxidant, antipyretic).Since these activities reported in the literature are aligned with their use in traditional medicine, we can thus consider that this use is totally or partially scientifically valid.
Given that a significant proportion of the identified secondary metabolites in Lannea species belong to the chemical class of polyphenols, it is plausible to correlate the observed biological activities with phenolic compounds in general.Nevertheless, this hypothesis requires empirical validation through specific studies aimed at a comprehensive characterization of these activities.

Materials and Methods
This review was performed following the criteria described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 2020 (https:// prisma-statement.org/prismastatement/flowdiagram.aspx;accessed on 1 February 2023).
A literature search covering articles published between January 1995 and June 2023 was conducted using databases from, B-on, Google Schoolar, Prelude Medicinal Plants database, Pubmed, Web of science, and primary bibliographic sources.These bibliographic sources were searched using different key words: "Lannea"; "Ethnomedicinal"; "Chemical"; "Biological activity", and the Boolean connectors AND/OR.
The studies that were related to plants belonging to the Lannea genus and were concerned with their medicinal importance were selected and included in this review.

Conclusions
Lannea species may represent an important source of natural products with relevant biological activities that can contribute to the development of new drugs.This study of this genus highlights its importance for traditional medicine in developing countries where access to primary health care is still poor.Despite this wide utilization, more multidisciplinary (taxonomic, conservational, ethnopharmacological) studies are needed to validate their concrete use as herbal medicines for the specific treatment of pathologies to which they are traditionally indicated.

Figure 1 .
Figure 1.Data screening based on the PRISMA methodology.

Figure 1 .
Figure 1.Data screening based on the PRISMA methodology.

Table 2 .
Lannea species used in traditional medicine and their vernacular names, countries, and ethnic groups.

Table 2 .
Lannea species used in traditional medicine and their vernacular names, countries, and ethnic groups.

Table 3 .
Traditional uses of Lannea species by geographical region.

Table 5 .
In vitro and in vivo biological studies on Lannea species.Potential source of new antibacterial agents against Gram-negative (Escherichia coli and Pseudomonas aeruginosas) and Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Bacillus subtilis); crude extract showed bactericidal and bacteriostatic activity (IC 50 values between 12 and 94 µg/mL).Treatment with L. acida extracts was significant (p ≤ 0.05-0.001)because it reversed the reproductive system-induced damage, especially after 28 days of treatment with aqueous solution (340 mg/kg) and methanol extracts (170 mg/kg).Selective antibacterial activity against Gram-negative (E. coli and P. aeruginosa) and Gram-positive (S. aureus, E. faecalis, S. pyogenes, and B. subtilis), including against resistant strains, with MICs/MBCs ranging from 7.80 to 125 µg/mL.The highest sensitivity was seen against Bacillus subtilis and Pseudomonas aeruginosa.Determination of total phenolic compounds and flavonoids by the Folin Ciocalteu method, expressed in mg of gallic acid equivalents and quercetin equivalents, respectively (total phenols vary between 34.4 to 40.55; total flavonoids vary between 6.4 and 11.02).L. acida bark extract induced proliferation of MCF-7 cells.At 200 mg/kg, prolonged treatment with the extract prevented ovariectomy-induced body weight gain and loss of bone mass and/or density.The ethanol extract induced a significant increase in MCF-7 cell production at concentrations of 10 (p < 0.05), 100 (p < 0.05), and 200 (p < 0.01)/g/mL compared to control DMSO.
The antimicrobial test result showed that stem bark extracts exhibited antimicrobial activity against several microorganisms (Bacillus cereus, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes), with clear zones of inhibition ranging from 6 mm to 21 mm.

Table 5 .
Cont.Rats received doses of 100, 150, and 200 mg/kg of body weight in an elevated plus maze and motor coordination; 100 and 200 mg/kg of body weight in sleep time, hole crossing, hole plate, and open field testing; and 200 and 400 mg/kg body weight in the antidiabetic activity test.The results obtained were all significant and dose dependent.L. coromandelica extracts possess significant neuromodulatory properties, had no significant effect on normal blood sugar levels, but corrected alloxan-induced changes in blood sugar and pancreas.The percentage of free radical scavenging by the DPPH, with IC 50 12.12 ± 0.48 µg/mL compared to the ascorbic acid standard 8.66 ± 0.11 µg.
L EtOHIn vitro: antidiabetic activity in rats Blood glucose levels in normal rats reached high levels 60 min after oral glucose administration (3 g/kg) and gradually decreased to 125 mg/dL in 2 h.Groups pretreated with ethanolic extract of L. coromandelica (100 and 200 mg/kg) and metformin (250 mg/kg) had induced decreased blood glucose levels significantly (p < 0.05) compared with that of the control group.