Review on antibacterial flavonoids from genus Erythrina: Structure-activity relationship and mode of action

Abstract

The Fabaceae family, particularly genus Erythrina, is renowned for significant medicinal properties. These plants have been used as natural remedies to address various health issues and are rich in flavonoids. Therefore, this review aimed to provide a comprehensive overview of antibacterial activity, structure-activity relationship, especially against drug-resistance Staphylococcus aureus, and mode of action for flavonoids isolated from Erythrina. Data were collected from reputable electronic scholarly resources focusing on publications from 2000 to 2022. The results showed that the evaluated flavonoids include 31 % pterocarpans, 22 % flavanones, 20 % isoflavanones, 18 % isoflavones, 4 % isoflavans, 3 % isoflav-3-enes, 1 % 3-arylcoumarins, and 1 % coumestans. Most of these compounds in Erythrina plants were extracted from the roots and stem bark. Among these group of flavonoids, pterocarpan stands out as the most active class against S. aureus. Structure-activity relationship study emphasized pivotal contribution of the prenyl functional group to enhance antibacterial activity of flavonoids. Increasing the number of prenyl groups enhanced antibacterial effectiveness while modifying the group reduced this activity. The proposed antibacterial mechanisms of these flavonoids include the suppression of nucleic acid synthesis, disruption of cytoplasmic membrane function, and modulation of energy metabolism. Among the potent antibacterial flavonoids from genus Erythrina, compound 3,9-dihyroxy-10-γ,γ-dimethylallyl-6a,11a-dehydropterocarpan was found as the most potent against Methicillin-Resistant Staphylococcus aureus (MRSA) through the inhibition of nucleic acid synthesis. Other common flavonoids such as genistein, daidzein, apigenin, and luteolin exert antibacterial activity through the inhibition of ATP synthase.

1. Introduction

The discovery and development of antibiotics is a significant accomplishment in the dimension of modern technology and knowledge, serving as a means to effectively manage and combat infectious diseases. However, in recent times, the number of infection cases caused by multidrug-resistant bacteria has been increasing due to the improper use of antibiotics [1]. Infections that arise from resistant bacteria can induce severe diseases, extended hospitalizations, increased healthcare costs, and therapeutic inefficacy [2]. Current estimates suggest that annually, around 700,000 lives are lost due to drug-resistant infections, with the potential for this figure to increase to 10 million cases by 2050 in the absence of robust and efficacious efforts to combat antimicrobial resistance [3].

Staphylococcus aureus has been designated as one of the human pathogens capable of inducing a diverse range of clinical diseases, including bloodstream, bone, joint and wound infections, as well as pneumonia, toxin-driven diseases, and life-threatening systemic disorders [[4], [5], [6], [7], [8]]. S. aureus is one of the prominent opportunistic infectious bacteria, significantly affecting morbidity and mortality rate on a global scale [9]. It is also among the primary infections linked to resistance and accounts for 929.000 deaths attributed to antimicrobial resistance (AMR). Moreover, in 2019, 3.57 million people died due to complications related to AMR [10]. Therefore, future studies must focus on the development of novel antimicrobials for combating harmful bacteria. One promising avenue in this pursuit includes the exploration of antimicrobial bioactive compounds derived from natural resources [11,12].

Natural products have a crucial role as valuable reservoirs of novel antibacterial compounds, which are indispensable in combating the growing threat of drug-resistant microorganisms [3,13]. Flavonoids, a class of secondary metabolites that originate from natural products, have a diverse array of pharmacological activity [[14], [15], [16]]. Moreover, flavonoids constitute a fundamental constituent of a phytochemical compound possessing antibacterial properties [[17], [18], [19]]. They are recognized for their diverse bioactive properties, functioning as both phytoanticipins and phytoalexins in regulating bacteria activity. As phytoanticipins, flavonoids are preformed antimicrobial compounds present in healthy plant tissues, providing an initial line of defense against microbial invasion. The compounds also act as phytoalexins which are synthesized as a defense mechanism against pathogens [20].

In nature, flavonoids are mainly isolated from plants [21,22], including genus Erythrina [23,24] which belongs to the Fabaceae family [25]. These plants have garnered considerable recognition due to the medicinal properties and potential therapeutic applications. The genus comprises over 130 species [26] and several species have demonstrated promising potential in combating pathogenic diseases [27]. This has led to their frequent use in traditional medicine to treat various health conditions, including fungal skin diseases, infected wounds, urinary tract, and respiratory infections [[28], [29], [30]].

The plants of genus Erythrina including E. fusca, E. variegata, E. poeppigiana, and E. subumbrans (Fig. 1) have been recognized for their diverse array of secondary metabolites. Among these, flavonoids (including pterocarpans, isoflavones, flavanones, and chalcones) constitute a major group that has been extensively isolated, and are known to have significant role in antibacterial properties [23,24,28,31]. Despite the promising future and flavonoids for the development of antibacterial agents, a comprehensive literature review on antibacterial potential of flavonoids from this genus is currently lacking. Therefore, this literature review aimed to provide an in-depth review of antibacterial activity of flavonoids, as documented in several scientific literature publications available online. Mode of action for flavonoids as antibacterial agents was also evaluated.

Fig. 1.

Several plant species of genus Erythrina; E. fusca (a), E. variegata (b), E. poeppigiana (c), and E. subumbrans (d).

2. Methods

An extensive online literature search was conducted to gather comprehensive information on antibacterial activity of plants from genus Erythrina and flavonoids. The search used specific phrases such as ‘Erythrina plants’ ‘flavonoids from genus Erythrina’ ‘antibacterial activity of Erythrina plants’ ‘antibacterial flavonoids from Erythrina plants’ ‘antibacterial flavonoids’, and ‘flavonoids antibacterial mode of action’. The scientific databases used include Google Scholar, Scopus, Web of Science, Springer, PubMed, and ScienceDirect, focusing on publications from 2000 to 2022. Additional data were obtained by reviewing the references cited in the selected studies. Original studies were included based on the following criteria: (1) reported the isolation of flavonoids, and (2) discussed the biological activity of extracts from genus Erythrina. Studies focused on flavonoids but without information on antibacterial activity were excluded.

3. Discussion

3.1. Antibacterial activity of plant extract from genus Erythrina

The Fabaceae family encompasses various genera, with Erythrina being one of them. The etymology of the name may be traced back to the Greek roots, specifically the word "erythros," which translates to "red." This term is used to describe the vibrant red flowers that are characteristic of trees belonging to genus Erythrina [28]. Furthermore, the genus has gained considerable popularity in the field of medicine, particularly the efficacy against infectious diseases caused by harmful microorganisms [27]. In traditional medicine, these plants are employed to remedy a wide range of human diseases, particularly infections and aiding in wound healing [26]. Wound-healing property of Erythrina plants has also been supported by several previous studies [32,33], indicating their antibacterial potency. Extensive research has been carried out to evaluate the antimicrobial properties of various species within the genus Erythrina, as shown in Table 1.

Table 1.

Antibacterial properties of extract from different species of genus Erythrina.

The plant Erythrina caffra, which is indigenous to the southeastern region of Africa, has historically been used due to the therapeutic attributes. Numerous medicinal uses have been recorded, including the treatment of arthritis, toothache, ulcers, wound infections, tuberculosis, and respiratory infections [34]. Aside from the traditional uses, E. caffra also possesses significant antibacterial activity. A study by O. O. Olajuyigbe and Afolayan, (2012) investigated antibacterial properties of the stem bark acetone extract. The extract showed potent antibacterial activity against K. pneumoniae, P. aeruginosa, and S. aureus. This implies that E. caffra could be a potential source of antibacterial agents [35]. Another study by Olufunmiso Olusola Olajuyigbe and Afolayan, (2012) supported the previous results by demonstrating that the stem bark acetone extract also showed high antibacterial activity against Micrococcus luteus, Proteus vulgaris, Enterococcus faecalis, and S. aureus[[36]. Moreover, the essential oil derived from the bark of E. caffra demonstrated comparable antibacterial activity to amoxicillin against Serratia marcescens, Proteus vulgaris, and Streptococcus pyogenes. This result suggests that essential oil could be a promising alternative to conventional antibiotics [37].

E. stricta is one of the plant species from the Fabaceae/Leguminosae family that commonly found in Asia. Traditionally, the leaves of this plant have been used as a remedy to treat earache, toothache, and eye infections [38]. In addition to the leaves, the stem bark was also used to treat rheumatism, stomachache, asthma, and dysentery by the people of Nagaland, India [39]. The paste from stem bark can also be used topically as a remedy to treat diverse dermatological problems including contact dermatitis, eczema, and skin infections [40]. Antibacterial study of E. stricta stem bark found a substantial inhibitory effect of n-hexane extract against B. cereus, S. aureus, V. mimicus, E. coli, and V. parahemolyticus with inhibitory zones ranging from 16 to 17 mm. Additionally, the ethyl acetate extract showed strong antibacterial activity with inhibitory zones ranging from 14 to 16 mm against B. subtilis, E. coli, S. typhi, and V. parahemolyticus [41]. Another study found that DCM extract from stem bark strongly suppress the bacterial growth of methicillin-sensitive, methicillin-resistant, and multidrug-resistant S. aureus with minimum inhibitory concentration (MIC) lower than 50 mg/L [42].

Antibacterial activity test of chloroform extract from the stem bark of Erythrina burttii showed that on the concentration of 1000 μg/disc, the extract strongly inhibited the growth of Microsporum gypsum (20 mm) and S. aureus ATCC 25923 (20 mm) [43]. These scientific reports support the ethnopharmacological use of genus Erythrina to fight bacterial infection.

3.2. Flavonoids from genus Erythrina

Flavonoids are prominent group of plant-derived secondary metabolites which are characterized by polyphenolic structure [22] specifically, 2-phenyl-benzo-γ-pyrone derivatives [44]. The molecular structure consists of two distinct benzene rings, namely A and B, which are interconnected by a pyrene ring containing oxygen, referred to as C. All flavonoids share a fundamental carbon skeleton based on the flavan system, denoted as C6-C3-C6 [45,46]. There are three distinct classes predicated upon the position of the phenyl group (B ring) to the benzopyrano (chromano) moiety. These classes include bioflavonoids, isoflavonoids, and neoflavonoids [47,48]. In the case of bioflavonoids, the phenyl group is affixed to C2, while in isoflavonoids and neoflavonoids, the prenyl group is located in the C3 and C4 of the benzopyrano moiety, respectively [21] (Fig. 2).

Fig. 2.

Structure of bioflavonoid (1), isoflavonoid (2), and the neoflavonoid (3).

According to previous studies, flavonoids are among the bioactive compounds with a wide array of medicinal properties that can be found in edible plants [49,50]. Genus Erythrina is among medicinal plants that are rich in flavonoids [23,24]. A recent literature review [24] reported that from the genus Erythrina, there are about 409 distinct flavonoids with varied chemical structures have been identified. These include 63 pterocarpans, 4 coumestans, 27 flavones, 127 isoflavones, 109 flavanones, 47 isoflavanones, 11 isoflavans, 7 isoflavens, and 14 chalcones (Fig. 3).

Fig. 3.

Basic skeletons of flavonoids isolated from genus Erythrina.

Plant-derived flavonoids have been reported to exhibit wide array of biological properties [50]. In the case of Erythrina, the bioactive flavonoids have been of particular interest. Studies have shown that compounds from the species had a range of pharmacological activities [23,24] and with great potential as antimicrobial agents. A study revealed that Erythrina species from East Africa contain anti-infective flavonoids [51]. These flavonoids may provide a plant-based alternative to standard antibiotics and could be explored further for the therapeutic potential.

3.3. Antibacterial activity of flavonoids from genus Erythrina

This review found that about 121 flavonoids from genus Erythrina have been evaluated for antibacterial activity including 31 % pterocarpans, 22 % flavanones, 20 % isoflavanone, 18 % isoflavones, 4 % isoflavans, 3 % isoflav-3-enes, 1 % 3-arylcoumarins, and 1 % coumestans (Fig. 4). Furthermore, among the botanical parts of the plants, the roots and stem bark are the most used parts for isolating antibacterial flavonoids.

Fig. 4.

Percentage of flavonoid subclasses from genus Erythrina that have been reported for their antibacterial activity.

The investigation on the stem bark of E. fusca has resulted in the discovery of eight different flavonoids, including 2 pterocarpans, 5 flavanones, and 1 isoflavone. The antibacterial effects of these compounds were tested against B. subtilis, E. faecalis, and S. aureus. Antibacterial assays showed that 3-hydroxy-10-(3-hydroxy-3-methylbutyl)-9-methoxypterocarpan (1) had no activity against any of the tested bacterial strains. Sandwicensin (2) had moderate effects against S. aureus and E. faecalis (MIC = 50 mg/L), but was less effective against B. subtilis (MIC = 100 mg/L). Erythrisenegalone (3) had no activity against S. aureus but showed moderate and weak antibacterial effects against B. subtilis and E. faecalis (MIC = 50 and 100 mg/L respectively). Citflavanone (4) demonstrated no activity against E. faecalis but at the concentration of 12.5 mg/L showed significant inhibition against S. aureus and B. subtilis. Lonchocarpol A (5) showed the strongest antibacterial effects of all the flavonoids, with MIC values of 6.25 mg/L against S. aureus and E. faecalis, and 3.125 mg/L against B. subtilis. Lupinifolin (6) had strong antibacterial effects on S. aureus and B. subtilis (MIC = 6.25 and 12.5 mg/L respectively), and moderate effects on E. faecalis (MIC = 50 mg/L) [52].

Innok et al. (2010) isolated a total of 17 flavonoids from the stem of Erythrina fusca and subsequently assessed these compounds for antibacterial efficacy against both S. aureus and Methicillin-Resistant Staphylococcus aureus (MRSA). The results showed that S. aureus was significantly sensitive to the inhibitory effects of eryvarin D (7), sandwicensin (2), and scandenone (8), with MIC of 4, 8, and 8 mg/L, respectively. Erythribyssin A (9) and erythrabissin I (10) also demonstrated substantial antibacterial activity against S. aureus, with MIC of 64 mg/L. MRSA showed heightened sensitivity to eryvarin D (7), with a 4 mg/L MIC. Compounds (2), (8), and (9) demonstrated potent antibacterial activity against MRSA, with MIC values of 16, 32, and 32 mg/L, respectively. However, compound (10) had only good antibacterial activity against MRSA, with a MIC of 64 mg/L. Compounds fuscacarpans A (11), fuscacarpans B (12), fuscacarpans C (13), demethylmedicarpin (14), erypoegin I (15), hydroxycristacarpone (16), orientanol A (17), vestitone (18), and 3,7,4′-trihydroxyflavone (19) were found to be inactive against both S. aureus and MRSA at concentrations exceeding 200 mg/L [53]. The chemical structure of compound (1)–(19) is given in Fig. 5.

Fig. 5.

Structure of compounds (1) ˗ (19).

Chukwujekwu et al. (2011) successfully isolated four flavonoids from the bark of Erythrina caffra, specifically identified as abyssioneV 4′-O-methyl ether (20), 6,8-diprenylgenistein (21), alpinumisoflavone (22), and burtinnone (23). Antibacterial properties of these compounds were systematically assessed against four bacteria strains including S. aureus, B. subtilis, E. coli, and K. pneumoniae. Among the compounds examined, 22 had the highest level of activity, demonstrating significant effectiveness against S. aureus, B. subtilis, and E. coli (MIC = 3.9 mg/L), as well as strong activity against K. pneumoniae (MIC = 7.8 mg/L). Compound 21 also showed potent antibacterial activity but with slightly higher MIC values compared to 22. It had MIC of 7.8 mg/L against S. aureus, B. subtilis, and E. coli, as well as strong activity against K. pneumoniae, with MIC of 15.6 mg/L. Compound 20 had very strong antibacterial activity against E. coli and K. pneumoniae, with MIC of 3.9 mg/L, as well as strong activity against S. aureus and B. subtilis, with MIC of 31 and 15.6 mg/L, respectively. Compound 23 demonstrated the lowest level of activity but had strong antibacterial activity against K. pneumoniae, with MIC of 31 mg/L, as well as good activity against B. subtilis and E. coli, with MIC of 62 mg/L, and against S. aureus, with MIC of 125 mg/L [54]. In another study, El-masry et al. (2010) isolated five distinct compounds from the stem bark of E. caffra, three of which were identified as flavonoids. The isolated compounds were evaluated for antibacterial properties against S. aureus ATCC6538P, P. aeruginosa ATCC9027, and E. coli ATCC8739. The results showed that a significant substantial inhibition zone was observed exclusively against S. aureus. Based on antibacterial assay, all three tested flavonoids had significant antibacterial activity against S. aureus. 3R-(−)-Erythbidin A (24) and compound 2 demonstrated the highest activity, with MIC of 62.5 mg/L, as well as minimum bactericidal concentration (MBC) of 250 mg/L and 500 mg/L, respectively. Conversely, 3S-(+)-2′-O-methyl Phaseollidinisoflavan (25) had MIC of 125 mg/L and an MBC of 500 mg/L [55]. The chemical structure of compound (20)–(25) is given in Fig. 6.

Fig. 6.

Structure of compounds (20) ˗ (25).

Rukachaisirikul et al. (2007) successfully isolated 12 flavonoids from the stem of Erythrina subumbrans, comprising 9 pterocarpans, 2 flavanones, and 1 isoflavone. Subsequently, 10 of these isolated compounds were subjected to antibacterial assay against gram-positive bacteria, including S. aureus, four strains of MRSA, and three strains of Vancomycin-Resistant Staphylococcus aureus (VRSA). The growth of S. aureus was found to be significantly inhibited by erybraedin A (26), erythrabyssin II (27), erystagallin A (28), erythrabissin-1 (10), and erycristagallin (29), with MIC ranging from 0.78 to 6.25 mg/L, while glabrol (30) and eryvarin E (31) had strong activity against S. aureus with MICs of 25 mg/L. Eryvarin D (32) showed good activity against S. aureus with MIC of 50 mg/L, while 5-hydroxysophoranone (33) and erysubin F (34) demonstrated no activity against S. aureus even at concentrations exceeding 50 mg/L. The four MRSA strains were also highly susceptible to compounds (26), (27), (28), (10), and (29), with MICs ranging from 0.78 to 12.6 mg/L. Similarly, the three VRSA strains had significant susceptibility to these compounds, with MIC ranging from 0.39 to 12.5 mg/L [56]. The chemical structure of compound (26)–(34) is given in Fig. 7.

Fig. 7.

Structure of compounds (26) ˗ (34).

Numerous studies have undertaken to investigate the antibacterial flavonoids derived from Erythrina sigmoidea. In a study conducted by Nkengfack et al. (1994), 9 flavonoids were isolated from both the root bark and stem wood. Subsequently, 6 of these isolated flavonoids, namely compound (27), neobavaisoflavone (35), sigmoidin H (36), phaseollin (37), abyssinone IV (38), and abyssinone VI (39) were subjected to antibacterial assay targeting S. aureus 209 P and E. coli RL 65. Based on the results, compounds (35) and (27) demonstrated significant inhibitory effects on the growth of S. aureus, with MIC of 2.5 mg/L and 3.1 mg/L, respectively, while no activity was found against E. coli. Compounds (36), (37), (38), and (39) showed no inhibitory activity against both S. aureus and E. coli. Furthermore, compound (35) also demonstrated antibacterial activity against Cryptococcus neoformans and Aspergillus fumigatus, with a MIC value of 50 mg/L [57]. In an investigation conducted by Biyiti et al. (1988), 2 flavanones, namely sigmoidin A (40) and sigmoidin B (41), were successfully isolated from the bark of E sigmoidea. Both of these flavanones were subjected to antibacterial assay targeting micrococcus luteus and S. aureus. The result showed that compounds (40) and (41) had potent antibacterial activity against micrococcus luteus, with MIC of 25 mg/L and 50 mg/L, respectively. In terms of growth inhibition against S. aureus, both compounds also showed strong antibacterial activity, with MIC of 25 mg/L [58]. In a separate study by Kouam et al. (2008), sigmoidin M (42), extracted from the stem bark of E. sigmoidea, showed significant antibacterial activity against S. aureus, with MIC of 4 mg/L. Furthermore, sigmoidin L (43), isolated from the stem bark of E. sigmoidea, demonstrated potent antibacterial activity against both S. aureus and P. vulgaris, with MIC of 4 mg/L and 7 mg/L, respectively [59]. The chemical structure of compound (35)–(43) is given in Fig. 8.

Fig. 8.

Structure of compounds (35) ˗ (43).

Mitscher et al. (1988) assessed antibacterial properties of compounds isolated from the root of Erythrina mildbraedii, specifically (26), (27), isoneorautenol (44), erybraedin B (45), and erybraedin C (46), against S. aureus ATCC 13709 and Mycobacterium smegmatis. The results showed that compound (27) had exceptional activity against S. aureus with MIC of 3.12 mg/L, while compounds (45), (26), (45), and (46) showed significant activity with MIC values ranging from 12.5 to 25 mg/L. Compound (27) also demonstrated significant efficacy against Mycobacterium smegmatis, with MIC of 0.78 mg/L, while (44), (26), (45), and (46) had substantial inhibition activity with MIC values of 25, 6.25, 12.5, and 12.5 mg/L, respectively [60]. Furthermore, Nakanishi et al. (1981) also isolated 10 flavonoids from the root of Erythrina abyssinica, followed by antibacterial assays against S. aureus, B. subtilis, and M. lysodeikticus. Among these isoflavonoids, compound (27) was found as the most potent, showing significant activity against all tested bacteria, with MIC of 3.13 mg/L. Compound (37) and erythrabyssin I (47) had strong activity against S. aureus, with identical MIC values of 12.5 mg/L, as well as against B. subtilis, with MIC value of 6.25 mg/L. Phaseollidin (48) demonstrated strong activity against B. subtilis, with MIC of 25 mg/L, good activity against S. aureus, with MIC of 50 mg/L, but inactive against M. lysodeikticus. Furthermore, abyssinones I (49) showed strong activity against both S. aureus and B. subtilis, with MIC values of 25 mg/L. Abyssinones II (50) showed good activity against both S. aureus and B. subtilis, with MIC values of 50 mg/L, but had strong activity against M. lysodeikticus, with MIC of 25 mg/L. Abyssinones IV (51) demonstrated strong activity against both S. aureus and B. subtilis, with MIC values of 25 mg/L and 12.5 mg/L, respectively. Abyssinones V (52) had strong activity against both B. subtilis and M. lysodeikticus, with MIC values of 25 mg/L and 12.5 mg/L, respectively, as well as good activity against S. aureus, with MIC of 50 mg/L [61]. The chemical structure of compound (44)–(52) is given in Fig. 9.

Fig. 9.

Structure of compounds (44) ˗ (52).

Bedane et al. (2015) successfully isolated six flavonoid compounds from the stem bark of Erythrina livingstoniana, namely 7,3′-dihydroxy-4′-methoxy-5′-(3-methylbut-2-enyl)flavanone (53), 5,7,3′-trihydroxy-4′-methoxy-5′-(3-methylbut-2-enyl)flavanone (54), erylivingstone C (55), erylivingstone A (56), erylivingstone B (57) and 5,7-dihydroxy-3′,4′-dimethoxy-5′-(3-methylbut-2-enyl)flavanone (58). These compounds were subsequently evaluated for antibacterial efficacy against various bacteria strains, namely E. coli DSM 1116, E. coli DSM 682, B. subtilis DSM 1088, S. pyogenes DSM 11728, and S. aureus DSM 799. Based on the results, compounds (53), (54), and (55) had significant activity against E. coli DSM 1116, E. coli DSM 682, and B. subtilis DSM 1088 with MIC ranging from 5 to 10 mg/L. However, compounds (56), (57), and (58) were found to be inactive against all tested bacteria above the concentration of 10 mg/L [62]. The chemical structure of compound (53)–(58) is given in Fig. 10.

Fig. 10.

Structure of compounds (53) ˗ (58).

Studies on antibacterial flavonoids isolated from the root of E. variegata against 13 strains of MRSA showed that eryvaris W (59) had strong activity with MIC ranging from 1.56 to 3.13 mg/L. Eryvarins V (60) showed strong activity with MIC ranging from 12.5 to 25 mg/L, while eryvarins X (61) had no activity below the concentration of 50 mg/L (MIC >50 mg/L). Eryvarins Y (62) demonstrated strong activity with MIC of 12.5–25 mg/L, while eryvarins Z (63) and 6-demethylvignafuran (64) showed good activity with MIC ranging from 25 to 50 mg/L. Other compounds including 2,3-dihydroauriculatin (65), eryvarins S (67), and eryvarins U (69) showed strong activity with MIC ranging from 6.25 to 25 mg/L. Orientanol E (66) showed very strong activity with MIC ranging from 1.56 to 12.5 mg/L but eryvarins T (68) showed no activity below 25 mg/L (MIC >25 mg/L). Eryvarin Q (70) demonstrated strong activity with MIC of 3.13–6.25 mg/L, while eryvarin M (71), eryvarin N (72), eryvarin O (73), eryvarin P (74), eryvarin R (75) showed no activity below the concentration of 25 mg/L (MIC >25 mg/L) [[63], [64], [65], [66]]. The chemical structure of compound (59)–(75) is given in Fig. 11.

Fig. 11.

Structure of compounds (59) ˗ (75).

Sato et al. (2006) screened 6 isoflavonoids isolated from the stem bark of E. poeppigiana (Leguminosae) for antibacterial activity against 11 strains of MRSA. Among these compounds, isolupalbigenin (76) and erythrinin B (77) showed very strong activity with MIC ranging from 1.56 to 3.13 and 6.25–12.5 mg/L respectively. Lupiwighteone (78), laburnetin (79), erysubin B (80), and M-Wi-2 (81) showed no activity below the concentration of 25 mg/L (MIC >25 mg/L) [67]. also isolated five flavonoids from the root of E. poeppigiana and screened antibacterial activity against MRSA. Based on the results, compound (2) showed strong activity with MIC ranging from 6.25 to 12.5 mg/L, erypoegin A (82) had good activity with MIC ranging from 25 to 50 mg/L, and (14) showed good activity with MIC of 50 mg/L [68]. In addition, Tanaka et al. (2004), evaluated antibacterial activity of flavonoids isolated from the root of E. poeppigiana against 13 strains of MRSA. Erypoegin F (83) and erypoegin H (84) showed strong activity with MIC of 12.5 mg/L, but erypoegin G (85), erypoegin I (86), erypoegin J (87) had no activity below the concentration of 12.5 mg/L (MIC >12.5 mg/L). A new compound 3,9-dihyroxy-10-γ,γ-dimethylallyl-6a,11a-dehydropterocarpan (88) from the root of E. poeppigiana showed strong antibacterial activity against MRSA with MIC of 12.5 mg/L. Eryvarin D (7) also demonstrated strong activity with MIC ranging from 12.5 to 25 mg/L, while compound (34) and cristacarpin (89) showed good activity with MIC of 100 mg/L [69]. The chemical structure of compound (76)–(89) is given in Fig. 12.

Fig. 12.

Structure of compounds (76) ˗ (89).

Nkengfack et al. (1995) successfully isolated six flavonoids from the root bark of E. eriotricha including (44), (26), (46), eriotrichin B (90), erybraedin D (91), and erybraedin E (92). Antibacterial activity of these isolated compounds was evaluated against two bacteria strains, namely, S. aureus 209 P and E. coli RL65. The results showed that eriotrichin B (90) had significant potent activity against S. aureus, with MIC of 8.3 mg/L. Compounds (46), (26), (92), and (44) demonstrated strong activity, with MIC values of 12.8 mg/L, 13.6 mg/L, 22.1 mg/L, and 28.4 mg/L, respectively. Compound (91) showed good activity, with MIC of 78.3 mg/L. However, none of the isolated compounds exhibited any discernible antibacterial activity against E. coli RL65 [70].

Sadgrove et al. (2020), successfully isolated 7 flavonoids from the stem bark of E. lysestemon, and antibacterial activity was assessed against various bacteria strains, including B. cereus ATCC 1117, S. aureus ATCC 2592, S. epidermidis ATCC 1222, E. coli ATCC 8739, and P. aeruginosa ATCC 27853. Compound (26) had exceptional activity against B. cereus, S. aureus, S. epidermidis, and E. coli, with MIC ranging from 1 to 2 mg/L, as well as strong activity against P. aeruginosa, with MIC of 20 mg/L. Compound (48) demonstrated very strong activity against S. epidermidis, with MIC of 5 mg/L, as well as strong activity against B. cereus, S. aureus, E. coli, and P. aeruginosa, with MIC values of 10 mg/L, 10 mg/L, 20 mg/L, and 20 mg/L, respectively. Abyssinone V-4′ methyl ether (93) had strong activity against B. cereus, with MIC of 26 mg/L, good activity against S. aureus and S. epidermidis, with MIC values of 59 mg/L and 117 mg/L, respectively, as well as moderate activity against E. coli and P. aeruginosa, with MIC of 260 mg/L. Eryzerin C (94) had very strong activity against S. aureus, S. epidermidis, E. coli, and P. aeruginosa, with MIC of 5 mg/L, 2 mg/L, 5 mg/L, and 5 mg/L, respectively, as well as strong activity against B. cereus, with MIC of 10 mg/L. Alpumisoflavone (95) demonstrated strong activity against B. cereus, S. aureus, and P. aeruginosa, with MIC values of 31 mg/L, 31 mg/L, and 20 mg/L, respectively, as well as good activity against S. epidermidis and E. coli, with MIC of 125 mg/L. Cristacarpin (89) showed good activity against P. aeruginosa, with MIC of 78 mg/L, moderate activity against B. cereus, S. aureus, and S. epidermidis, with MIC values of 156 mg/L, 156 mg/L, and 412 mg/L, respectively, but low activity against E. coli, with MIC of 625 mg/L. Lysisteisoflavone (96) had very strong activity against B. cereus and E. coli, with MIC of 2 mg/L and 6 mg/L, respectively, strong activity against S. epidermidis and P. aeruginosa, with MIC of 26 mg/L and 31 mg/L, respectively, as well as good activity against S. aureus, with MIC of 62 mg/L [71]. The chemical structure of compound (90)–(96) is given in Fig. 13.

Fig. 13.

Structure of compounds (90) ˗ (96).

Tanaka et al. (2009) isolated 3 new isoflavones from the stems of E. costaricensis and evaluated antibacterial activity against MRSA. Based on the results, 5,7,3′-trihydroxy-4′-methoxy-6,5′-di(γ,γ-dimethylallyl)isoflavanone (97) showed very strong activity with MIC of 6.25 mg/L, while 5,3′-dihydroxy-4′-methoxy-5′-γ,γ-dimethylallyl-2″,2″-dimethylpyrano[5,6:6,7]-isoflavanone (98), and 5,3′-dihydroxy-2″,2″-dimethylpyrano[5,6:6,7]-2‴,2‴-dimethylpyrano[5,6:5,4]isoflavanone (99) had no activity below the concentration of 50 mg/L (MIC >50 mg/L) [72].

From the root of E. zeyheri, Tanaka et al. (2003) isolated 5 isoflavonoids and evaluated antibacterial activity against MRSA. Eryzerin C (94) showed very strong activity with MIC of 6.25 mg/L. Eryzerin A (100), eryzerin D (101), and eryzerin E (102) demonstrated strong activity with MIC of 25, 12, and 12 mg/L respectively, while eryzerin B (103) had no activity against MRSA below the concentration of 50 mg/L (MIC >50 mg/L) [73]. In another study, eryzerin A-E along with erybraedin A also screened for their antibacterial activity against four strains of VRSA [74]. Based on the results, erybraedin A (26) showed very strong activity with MIC ranging from 1.56 to 3.13 mg/L, and eryzerin C (95) had a very strong activity with MIC of 6.25 mg/L. Eryzerin A (100), eryzerin D (101), and eryzerin E (102) demonstrated strong activity with MIC of 25, 12.5, and 12.5 mg/L, while eryzerin B (103) had no activity below the concentration of 50 mg/L (MIC >50 mg/L). The chemical structure of compound (97)–(103) is given in Fig. 14.

Fig. 14.

Structure of compounds (97) ˗ (103).

Iinuma et al. (1992) isolated 5 flavonoids from the root bark of Erythrina x bidwilli, namely erythrabyssin II (27), bidwillon A (104), bidwillon B (105), 8-γ,γ-dimethyl-allyldaidzein (106) and auriculatin (107). These flavonoids were screened for antibacterial activity against oral microorganisms. All four compounds showed no activity at the concentration of 50 mg/L (MIC >50 mg/L) against Lactobacillus casei ATCC 7469, Lactobacillus fermentum YIT 0082, Streptococcus mutans OZI, Streptococcus mutans Ingbritt, S. aureus NIHJ 209P, and E. coli NIHJ K12. Erythrabyssin II (27) demonstrated very strong activity against Fusobacterium nucleatum ATCC 10953 with MIC of 6.25 mg/L, strong activity against Provotella intermedia ATCC 26551 with MIC of 12.5 mg/L, good activity against Porphyromonas gingivaris CTT 33277 and Actinomyces naeslundii ATCC 10953 with MIC of 50 mg/L. However, the compound was inactive below the concentration of 50 mg/L against Actinobacillus actinomycetemcomitans. Bidwillon A (104) showed very strong activity against 7 with MIC of 3.2 mg/L, strong activity against Fusobacterium nucleatum ATCC 10953, and Actinobacillus actinomycetemcomitans with MIC of 25 and 12.5 mg/L respectively, as well as good activity against Porphyromonas gingivaris CTT 33277 with MIC of 50 mg/L. The compound did not show activity below 50 mg/L (MIC >50 mg/L) against Actinomyces naeslundii ATCC 10953. Bidwillon B (105) had no activity below 50 mg/L (MIC >50 mg/L) against all tested microorganisms. Furthermore, 8-γ,γ-dimethyl-allyldaidzein (106), and auriculatin (107) showed very strong activity against Fusobacterium nucleatum ATCC 10953 with MIC of 6.25 and 3.2 mg/L respectively. Both compounds were found to be inactive at 50 mg/L (MIC >50 mg/L) against the rest of the tested microorganisms [75].

Tanaka et al. (2010) evaluated antibacterial activity of 10 flavonoids isolated from the root of E. herbacea against 13 strains of MRSA. Erybacin B (108) and bidwillol A (109) showed very strong activity with MIC ranging from 6.25 to 12.5 mg/L. Eryvariestyrene (110), phaseollidin isoflavan (111), and glabrocoumarone A (112) showed strong activity with MIC of 12.5 mg/L (+)-Glyasperin F (113), erythbidin A (24), eryvarin L (114), and phaseollinisoflavan (115) demonstrated strong activity with MIC ranging from 12.5 to 50 mg/L, 25 mg/L for (114) and 25–50 mg/L for (115). Erybacin A (116) and eryvarin H (117) showed no activity below the concentration of 50 mg/L (MIC >50 mg/L) [76].

From the twig of E. crista-galli infected with Phomopsis sp., Redko et al. (2007) isolated three flavonoids and evaluated antibacterial activity against Bacillus brevis. Coumestrol (118) was found to have very strong activity with MIC of 4.4 mg/L, Genistein (119) showed strong activity with MIC of 17.5 mg/L, while daidzein (120) had good activity with MIC of 35 mg/L [77]. The chemical structure of compound (104)–(120) is given in Fig. 15.

Fig. 15.

Structure of compound (104) ˗ (120).

The majority of antibacterial activity studies involving flavonoids isolated from the genus Erythrina have focused on their effectiveness against Gram-positive bacteria. Among these, S. aureus has been the most frequently evaluated species. Research indicates that various classes of flavonoids exhibit antibacterial properties, but pterocarpan stands out as the most active class against S. aureus. The efficacy of pterocarpan suggests its potential as a promising antibacterial agent. In comparison to other flavonoid classes, pterocarpan consistently demonstrates superior antibacterial activity. This finding emphasizes the importance of further investigating pterocarpan and related compounds. Additionally, the frequent evaluation of S. aureus highlights the significance of this pathogen in antibacterial research. The effectiveness of pterocarpan against S. aureus may lead to the development of new antibacterial treatments. Understanding the mechanisms behind pterocarpan's activity could provide insights into designing more effective antibacterial agents. The genus Erythrina, therefore, represents a valuable source of bioactive flavonoids. Further exploration of this genus may uncover additional antibacterial compounds. This research underscores the potential of natural products in addressing antibiotic resistance. By focusing on Gram-positive bacteria, particularly S. aureus, researchers can better target treatments for infections caused by these pathogens.

In general, flavonoids exhibit differential effects on Gram-positive and Gram-negative bacteria due to structural differences in their cell walls. Gram-positive bacteria, like S. aureus, have a thick peptidoglycan layer that flavonoids can effectively penetrate. In contrast, Gram-negative bacteria possess an outer membrane that serves as an additional barrier, often reducing the efficacy of flavonoids.

3.4. Structure-activity relationship

The chemical structures of flavonoids are characterized by a C6-C3-C6 skeleton, consisting of two aromatic rings (A and B) joined by a three-carbon bridge that may form a third ring (C) [78]. Substitutions in rings A and B, as well as modifications in ring C, contribute significantly to the diversity of flavonoid compounds [44]. For instance, hydroxylation at different positions on rings A and B can lead to the formation of various flavonoid subclasses, such as flavones, flavonols, and flavanones [79]. Additionally, methylation, acetylation, and glycosylation of hydroxyl groups further increase the structural diversity of flavonoids [80]. Oxidation in ring C can also result in different flavonoid derivatives. For example, flavonols are formed when the double bond between positions 2 and 3 in ring C is oxidized, resulting in a saturated ring structure [81]. These structural variations not only contribute to the chemical diversity of flavonoids but also influence their biological activities and functions in plants and their potential health benefits in humans [82].

In the context of phytochemical diversity in genus Erythrina, prenylated flavonoids, represent a significant portion of secondary metabolites with pterocarpans being the largest sub-class. The results suggest that the prenyl group attached to the basic flavonoid skeleton acts as a common pharmacophore in Erythrina flavonoids, enhancing antibacterial activity. An increase in hydrophobicity due to prenyl groups enhance the efficacy of pterocarpans against S. aureus and MRSA. Specifically, compounds with one or more prenyl groups tends to have a lower MIC, demonstrating increased antibacterial efficacy. For instance, MIC of compound 14 (>200 mg/L) is significantly higher than that of 48 (12.5 mg/L), and further decreased in compound 26 (1.56 mg/L) with additional prenylation. However, modifications to these prenyl groups or cyclization tend to reduce antibacterial activity, as observed in comparisons between compound 48 (12.5 mg/L) and 45 (25 mg/L). The hydrophobicity imparted by prenyl groups is crucial for the potency of pterocarpans in Erythrina. The prenyl group is known to introduce hydrophobicity to flavonoids, thus enables flavonoids to better penetrate bacterial cell membranes and enhances their activity at the active site [83]. In addition, the conversion of -OH group at C9 into -OCH₃ appeared to decrease antibacterial activity of prenylated pterocarpan, which can be observed by comparing the MIC of compound 48 (12.5 mg/L) and 2 (50 mg/L) (Fig. 16). The antibacterial properties of prenylated flavonoids significantly influenced by the presence of the hydroxyl group (-OH). The hydroxyl groups improve the solubility and interaction of flavonoids with bacteria cell membranes. Hydrogen bonds are formed with components of the bacteria cell wall, disrupting membrane integrity and causing cell death [84].

Fig. 16.

Structure-activity relationship of pterocarpans from genus Erythrina against S. aureus.

As observed for pterocarpan, the prenyl group also seemed to affect antibacterial activity of flavanones against S. aureus. By comparing the MIC of compound 5 (MIC: 6.25 mg/L), compound 6 (MIC: 12.5 mg/L), and compound 3 (MIC >100 mg/L), it seemed that modification of prenyl group decrease their antibacterial activity, but what′s interesting is that the position of prenyl group in ring A that undergoes modification also affect their antibacterial activity, where modification of prenyl group at C8 position on compound 3 show significant decrease of antibacterial activity compared to modification of prenyl group at C6 position on compound 6. The importance of prenyl group position attached to flavonoids also supported by Osorio et al. (2021) which stated that prenylation at C6 or C8 are the key to antibacterial activity of flavonoids [85]. In addition, the position of prenyl group also play important role on flavanones antibacterial activity. When both the prenyl groups are present on ring A as in compound 5 (MIC: 6.25 mg/L), the compound showed strong antibacterial activity, on the other hand, when one of the prenyl group present on ring A and the other one present on ring B, as in compound 31 (MIC: 25 mg/L), the antibacterial activity decreased. The same thing also observed when both of the prenyl groups are present on ring B of the flavanone, as in compound 53 (MIC: 50 mg/L). Despite compound 34 have three prenyl groups, but since both the prenyl group are attached to the ring B, this compound showed lower antibacterial activity compared to those with prenyl group attached to ring A. This demonstrate that the presence of prenyl group on ring B of flavanones, seemed unfavorable for their antibacterial activity against S. aureus. In addition to prenyl group, the presence of hydroxyl group also plays important role on antibacterial activity of flavanone, this can be observed by comparing the antibacterial activity of compound 53 (MIC: 50 mg/L) and compound 39 (inactive) (Fig. 17).

Fig. 17.

Structure-activity relationship of flavanones from genus Erythrina against S. aureus.

3.5. Flavonoid antibacterial mode of action

Mode of action can be defined as the process of how pharmacologically active molecules produce pharmacological effects through interaction with molecular targets [86]. The study is considered important because it provides knowledge and understanding of how drugs act on the body, offering insights into the appropriate use, possible side effects, and contradictions [87]. Flavonoids are polyphenolic compounds with the ability to fight against bacterial through multiple mechanisms [88], including suppressing the synthesis of nucleic acid, disruption of cytoplasmic membrane integrity, interference with metabolic energy pathways, as well as suppression of bacteria attachment and biofilm formation. Other modes of action include inhibition of porin function on the cell membrane, which disrupt the transport of molecules across the bacterial cell wall [89]; and attenuation of bacteria pathogenicity, reducing the ability of bacteria to cause disease [90]. Among many identified flavonoids evaluated for antibacterial activity, only a few have clearly delineated modes of action (Table 2).

Table 2.

Antibacterial mode of action of flavonoids identified in genus Erythrina.

Compound	Flavonoid sub-class	Source in genus Erythrina	Antibacterial Mode of Action	Reference
3,9-dihyroxy-10-γ,γ-dimethylallyl-6a,11a-dehydropterocarpan (88)	Pterocarpan	E. poeppigiana	Interfering with incorporation of metabolites and nutrients into bacterial cells or affects the nucleic acids in MRSA cells	[69]
Genistein (120)	Isoflavone	E. abyssinica; E. brucei; E. crista-galli; E. droogmansiana; E. fusca; E. indica	Inhibition of nucleic acid synthesis	[91]
			Partial inhibition of ATP synthase	[92]
Daidzein (121)	Isoflavone	E. brucei; E. crista-galli; E. droogmansiana; E. indica; E. orientalis	Significant inhibition of ATP synthase	[92]
Apigenin (122)	Flavone	E. crista-galli	Inhibition of DNA gyrase	[91]
			Partial inhibition of ATP synthase	[92]
Luteolin (123)	Flavone	E. crista-galli	Destroyed the cell membrane integrity	[93]
			Significant inhibition of ATP synthase	[92]

3.6. Flavonoids disrupt bacterial cell membrane integrity

Flavonoids have been shown to disrupt bacteria cell membrane integrity, leading to potent antibacterial properties. Luteolin (123) is among flavonoids found in different plants such as vegetables and fruits [94]. It was first identified in Erythrina crista-galli [95], and reportedly has significant antibacterial activity against S. aureus, B. careus, E. coli, and S. infatis [96]. The antibacterial mechanism of action of (123) was first studied by Qian et al. (2020). According to his research group study, (123) was found to have MIC and MBC of 16 and 32 mg/L respectively against S. aureus, making this compound considered bactericidal against S. aureus [97]. FESEM results showed that S. aureus cells treated with MIC or 2 MIC of (123) had deformed shapes. TEM images also revealed damage to the cell membranes, with visible dents and hollows. This suggests that the cell membranes' integrity was compromised [93]. The ability of flavonoids to disrupt cell membranes are attributed to their lipophilic nature, which allows them to integrate into the lipid bilayer of bacterial membranes [98]. This integration can lead to the formation of pores or other structural alterations, disrupting the membrane's integrity and function [99].

3.7. Flavonoids disrupt bacterial nucleic acid synthesis

Flavonoids have been shown to disrupt bacterial nucleic acid synthesis, contributing to their potent antibacterial properties. These compounds interfere with the processes involved in the replication and transcription of bacterial DNA and RNA, leading to the inhibition of bacterial growth and proliferation [100]. For example, compound 3,9-dihyroxy-10-γ,γ-dimethylallyl-6a,11a-dehydropterocarpan (88) which is a prenilated pterocarpan, a new compound from the root of E. poeppigiana showed strong antibacterial and bactericidal activity against MRSA. The antibacterial mechanism of action study showed that though (88) does not affect the cellular membrane permeability, (88) completely blocked the incorporation of thymidine, uridine, and leucine, and greatly reduced glucose uptake. These results suggest that (88) might work through two mechanisms: interfering with metabolite and nutrient uptake, and affecting nucleic acid synthesis in MRSA cells [69].

Ulanowska et al. (2006) studied the possible mechanism of action of genistein (120). (120) is a natural isoflavonoid found in Leguminosae [101]. This compound was found to strongly inhibit the growth of Gram-negative bacterium, V. harveyi at concentration of 0.1 μM. From the observation of bacterial cell morphology, V. harveyi cell becomes significantly longer after treatment with (120) for 3 h, indicating that (120) might interfere with bacterial cell division and/or completion of chromosome replication. (120) was also found to strongly inhibited DNA and RNA synthesis of V. harveyi 15 min after addition of genistein (120). Kinetics of incorporation of labeled thymidine and uridine into TCA-precipitable material in genistein-treated V. harveyi further support that inhibition of nucleic acid synthesis may be the primary cause of the antibacterial activity of (120). In another study, Chinnam et al. (2010) evaluated the effect of (120) along with another 16 flavonoids including daidzein (121), apigenin (122), and luteolin (123) on the inhibition of ATP synthase. Genistein (120) and apigenin (122) showed partial inhibition of ATP synthase in the range of 40–60 %, whereas daidzein (121) and luteolin showed significant inhibition of ATP synthase.

Morito et al. (2015) screened 104 commercially available flavones for their antibacterial activity against 36 S. aureus strains, including quinolone-resistant mutants and found that among these flavones, apigenin (122) was found to be the most potent in reverse antibiotic (RA) activity, meaning that this compound poses stronger activity against quinolone-resistant strains than quinolone-sensitive strains. Apigenin (122) was also tested against 17 clinically isolated strains S. aureus with QRDR mutation. The result showed that apigenin (122) inhibited the growth of 14 tested S. aureus strains having gyrA (Ser84Leu, Glu88Gly) mutation with MIC of 0.5 mg/L, suggesting that this compound might exert its antibacterial activity through inhibition of DNA gyrase subunit A. To further confirm that apigenin (122) act on GyrA with Ser84Leu mutation, this compound was subjected to a topoisomerase DNA cleavage assay system using wild-type as well as mutated DNA gyrase subunit A. When the mutated form of GyrA was used, apigenin (122) particularly accumulated cleaved form of the substrate DNA, indicating direct inhibition of the mutated DNA gyrase in the presence of apigenin (122) [102].

3.8. Toxicological evaluation of extract from genus Erythrina

Toxicological evaluation is an essential step in the drug development process, particularly when it comes to plant extracts [103]. Plants have been used for medicinal purposes for thousands of years, but not all plant compounds are safe for human consumption [104]. Toxicological studies help to identify any potential adverse effects that plant extracts may have on human health, ensuring that only safe and effective compounds are considered for further development into drugs [105]. One of the primary reasons for conducting toxicological evaluations is to assess the safety profile of plant extracts. This involves determining the toxic dose levels and identifying any toxic effects on different organs and systems in the body. Without this crucial information, there is a significant risk of developing drugs that could cause harm to patients, which could lead to serious health consequences and legal liabilities for pharmaceutical companies [106]. The extract of several plant species from genus Erythrina have been evaluated for their toxicological potency (Table 3). The toxicological data for these Erythrina species indicate that while some extracts exhibit moderate toxicity, others are relatively non-toxic. The choice of solvent and plant part significantly influences the LD₅₀ values, highlighting the need for careful selection in the extraction process. These findings are crucial for the safe development of Erythrina-based therapeutics, ensuring that only extracts with acceptable toxicity levels proceed to clinical testing.

Table 3.

Toxicological evaluation of several plant species of genus Erythrina.

No	Plant Species	Botanical Part	Solvent	LD50 (mg/kg body weight)	References
1	E. senegalensis	Stem bark	Aqueous	450	[107]
		Stem bark	DCM/Methanol	>1200	[108]
		Stem bark	40 % Ethanol	16,000	[109]
		Leaves	Ethanol	>5000	[110]
		Leaves	Aqueous	>4000	[111]
2	E. variegata	Leaves	Methanol	>1000	[112]
3	E. veluntina	Leaves	Aqueous	>5000	[113,114]
4	E. sacleuxii	Root	Ethanol	>2400	[115]
5	E. fusca	Fruit	Ethanol	>5000	[116]
6	E. abyssinica	Leaves and bark	50 % Aqueous methanol	>300	[32]
		Root	Methanol	776.2	[117]

4. Conclusions

Our findings suggest that the ethnobotanical use of genus Erythrina for infection treatment have been supported by numerous research. Among the phytochemicals responsible for the reported antibacterial activity of genus Erythrina are flavonoids. Among the flavonoids that have been evaluated for their antibacterial activity, 31 % are pterocarpans, 22 % are flavanones, 20 % isoflavanone, 18 % isoflavones, 4 % isoflavans, 3 % isoflav-3-enes, 1 % 3-arylcoumarins, and 1 % coumestans. Most of these flavonoids are reported to be isolated from the roots and stem bark. The structure-activity relationship study emphasizes the crucial role of the prenyl functional group in enhancing the antibacterial activity of flavonoids. Increasing the number of prenyl groups in the flavonoid structure boosts their antibacterial effectiveness, whereas modifying the phenyl group reduces this activity. The antibacterial mechanism of action suggested that flavonoids from genus Erythrina exert their antibacterial activity through suppressing nucleic acid synthesis, disrupting cytoplasmic membrane function and energy metabolism.

CRediT authorship contribution statement

Tati Herlina: Writing – original draft, Supervision, Project administration, Conceptualization. Abd Wahid Rizaldi Akili: Writing – original draft. Vicki Nishinarizki: Writing – review & editing. Ari Hardianto: Writing – review & editing, Visualization. Jalifah Binti Latip: Writing – review & editing.

Data and code availability statement

Data will be made available on request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.