A Review on the Cytotoxicity and Antibacterial Effect of Marine Organisms of Persian Gulf

Abstract

Marine organisms contain several natural products and bioactive compounds, including hydrolyzed proteins, antioxidant peptides, gelatin, collagen, ω-3 unsaturated fatty acids, vitamin A, vitamin D, calcium phosphate, hydroxyapatite, chitosan, lectin, and various toxins. They can inhibit diverse diseases, be used in pharmaceutical compounds, or as antibiotics and pigments. In this regard, these microorganisms are of crucial medicinal and economical importance. Thanks to new technologies and advanced laboratory methods, bioactive compounds can be extracted from aquatic organisms. In this review study, the cytotoxicity (IC₅₀) and antibacterial effect of various extracts from marine organisms of the Persian Gulf are explored, compiled, and compared. Due to their easy accessibility, most of the studies are green, red, and brown algae.

INTRODUCTION

Water covers about three-quarters of the Earth's surface. The water-covered area is the habitat for various organisms also known as marine organisms.[1] Marine organisms have a very high biological and genetic diversity, and about 300000 species have been identified so far.[2] Due to the biological and genetic diversity of their biomass, these organisms produce various compounds called marine natural products. Marine and ocean environments are a great source of these natural compounds with unique structural features that are far less varied in land-dwelling organisms. These compounds are secondary metabolites produced by marine organisms in their life cycle.[3] Research in this field began in the late 1960s with a rapid development in the 1980s.[4] The last decade witnessed the peak of research in this field and the development of pharmaceutical sciences and organic chemistry. Marine natural products have shown cytotoxicity and antibacterial, antiviral, antifungal, antitumor, and antioxidant effects, suggesting their huge potential for the development of novel natural-based drugs.[3] One of the prerequisites for the availability of these products is to utilize different solvents of different polarities due to the differences in polarities and molecular tensions.[5] Simple organic solvents including methanol, ethanol, and ethyl acetate are mainly used due to the organic structure of these products. Marine plants are an important class of marine organisms among which algae are one of the most abundant and widespread organisms.[6] Algae can be classified based on various parameters. In terms of size, algae are divided into macro and micro-algae. In terms of pigmentation, algae are divided into three categories: brown, red, and green.[7] Algae produce different secondary metabolites depending on the species, age, and the temperature (tropical or cold) and the ecosystem of the habitat.[8]

Algae have been long used as food and medicine. These marine organisms are sustainable sources in the marine ecosystem.[9] Studies have shown the cytotoxicity,[10] antibacterial, antioxidant,[11] antiviral,[12] and antifungal effects of algae-extracted compounds.[13] The Persian Gulf is one of the most prominent marine habitats in the world. With more than 1200 km of coastline, the Persian Gulf is the habitat of more than 250 species of algae.[14] The biological effects of these algae have been widely studied as will be reviewed in this study.

MATERIALS AND METHODS

This systematic review was accomplished following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines checklist (PRISMA). A systematic electronic search was conducted using two databases including Scopus and PubMed from 2010 till now. Duplicated articles were removed. The following keywords were used for investigating cytotoxicity and antibacterial effects: cytotoxic, antibacterial, algae, and Iran.

RESULT

The results of cytotoxicity and antibacterial activities of seaweeds from Persian Gulf was shown in Tables 1 and 2.

Table 1.

Cytotoxic activities of marine organisms

Marine organism name	Extracting agent	Cell line	IC50 (µg/mL)	Ref.
Gracilaria salicornia	Methanol	HT-29	68.2	[15]
		Hela	125.9
		MCF-7	185.8
	Ethanol	MCF-7	>400	[16]
		T-47D	>400
Gracilaria corticata	Methanol	HT-29	58.6	[14]
		Hela	117.4
		MCF-7	120.6
	n-Hexane	Hela	117.4	[17]
		Huvec	152.7
	Dichloromethane	Hela	291.3
		Huvec	321.6
	n-butanol	Hela	>1000
		Huvec	>1000
	Water	Hela	>1000
		Huvec	>1000
Gracilaria foliifera	Ethanol	MDA-MB-231	74.8	[16]
		T-47D	207.8
		MCF-7	203.2
Gracilariopsis	Ethanol	MDA-MB-231	>400	[16]
		T-47D	>400
		MCF-7	>400
Sargassum oligocystom	Methanol	HT-29	133.9	[15]
		Hela	96.7
		MCF-7	56.9
Sargassum boveanum	Methanol	HT-29	125.6	[15]
		Hela	82.3
		MCF-7	60.4
	n-Hexane	Hela	150.2	[17]
		Huvec	373.0
	Trichloroethane	Hela	473.0
		Huvec	379.2
	Chloroform	Hela	110.3
		Huvec	377.8
	n-butanol	Hela	>1000
		Huvec	456.87
Sargassum swartzii	Methanol	HT-29	>1000	[18]
		Caco-2	>1000
		T-47D	205.2
		N1H-3T3	607.1
	Methanol-water	HT-29	>1000
		Caco-2	>1000
		T-47D	853.8
		N1H-3T3	>1000
	n-Hexane	HT-29	211.5
		Caco-2	99.9
		T-47D	>1000
		N1H-3T3	639.74
	Chloroform	HT-29	446.2
		Caco-2	530.6
		T-47D	>1000
		N1H-3T3	630.9
	Ethyl acetate	HT-29	>1000
		Caco-2	501.1
		T-47D	>1000
		N1H-3T3	697.9
Sargassum acinaciforme	Methanol	MOLT-4	85.6	[19]
	Dichloromethane	MOLT-4	31.6
Sargassum angustifolium	Methanol	HT-29	121.8	[15]
		Hela	87.9
		MCF-7	67.3
	Dichloromethane	MCF-7	36.1	[20]
		Huvec	88.1
		Hela	62.5
	n-Hexane	MCF-7	71.2
		Huvec	122.7
		Hela	134.7
	n-butanol	MCF-7	25.2
		Huvec	23.7
	Methanol-water	T-47D	>1000	[21]
		Caco-2	>1000
		HT-29	>1000
		N1H-3T3	>1000
	n-Hexane	T-47D	166.4
		Caco-2	317.1
		HT-29	190.2
		N1H-3T3	735.4
	Chloroform	T-47D	86.9
		Caco-2	186.6
		HT-29	299.6
		N1H-3T3	162.6
	Ethyl acetate	T-47D	117.8
		Caco-2	101.2
		HT-29	261.6
		N1H-3T3	165.3
Cystoseria myrica	Methanol	HT-29	>1000	[18]
		Caco-2	>1000
		T-47D	99.9
		N1H-3T3	739.6
	Methanol-water	HT-29	473.0
		Caco-2	>1000
		T-47D	381.5
		N1H-3T3	180.7
	n-Hexane	HT-29	>1000
		Caco-2	541.2
		T-47D	>1000
		N1H-3T3	>1000
	Chloroform	HT-29	328.7
		Caco-2	>1000
		T-47D	453.5
		N1H-3T3	>1000
	Ethyl acetate	HT-29	>1000
		Caco-2	254.9
		T-47D	165.4
		N1H-3T3	453.5
	n-Hexane	T-47D	99.9
		T-47D-T.R	143.1
		MDA-MB-468	56.5
	Ethanol	MCF-7	398.1	[16]
		T-47D	>400
Cystoseria indica	Methanol	HT-29	115.8	[22]
		Hela	121.9
		MCF-7	83.3
Cystoseria merica	Methanol	HT-29	145.9	[22]
		Hela	147.7
		MCF-7	69.9
Padina antillarum	Methanol	MCF-7	136.5	[23]
		Hela	65.6
		Vero	134.6
	Ethyl acetate	MCF-7	86.3
		Hela	60.1
		Vero	84.2
Padina boergeseni	Methanol	MCF-7	129.8	[23]
		Hela	198.9
		Vero	123.6
	Ethyl acetate	MCF-7	83.8
		Hela	59.2
		Vero	79.2
J. adhaerens	Methanol	MCF-7	58.3	[24]
		HT-29	72.6
	Chloroform	MCF-7	34.2
		HepG-2	93.6
		A-549	72.2
		HT-29	40.6
		MDBK	46.0
Botryocladia letpada	Ethanol	MDA-MB-231	>400	[16]
		MCF-7	>400
		T-47D	>400
Iyengaria stellata	Dichloromethane	MOLT-4	36.0	[19]
	Methanol	MOLT-4	>100
	Ethanol	MDA-MB-231	>400	[16]
		MCF-7	>400
		T-47D	>400
Sirophysalis trinoids	Methanol	MOLT-4	65.8	[19]
Chondria dasyphylla	Methanol-water	T-47D	522.5	[21]
		Caco-2	>1000
		HT-29	>1000
		N1H-3T3	>1000
	n-Hexane	T-47D	82.2
		Caco-2	421.1
		HT-29	>1000
		N1H-3T3	>1000
	Chloroform	T-47D	33.5
		Caco-2	144.6
		HT-29	114.5
		N1H-3T3	112.3
	Ethyl acetate	T-47D	167.2
		Caco-2	490.6
		HT-29	595.9
		N1H-3T3	505.0
Ulva flexuosa	Methanol-water	T-47D	116.9	[21]
		Caco-2	>1000
	Methanol	MCF-7	107.4	[23]
		Hela	71.9
		Vero	102.8
	Ethyl acetate	MCF-7	60.0
		Hela	59.7
		Vero	55.2
Cladophorosis	Ethanol	MDA-MB-231	66.4	[16]
		MCF-7	150.8
		T-47D	>400
Hypnea flagelliformis	Ethanol	MDA-MB-231	>400	[16]
		MCF-7	>400
		T-47D	>400
	Ethanol	MCF-7	>400	[16]
		T-47D	>400
Holothuria leucospilota	n-Hexane	Hela	301.1	[19]
	Dichloromethane	Hela	210.2
	Butanol	Hela	129.0
	Water	Hela	229.3
Colpomenia sinousa	Methanol	MOLT-4	57.2	[19]
	Dichloromethane	MOLT-4	23.9
	Methanol	HT-29	>1000	[18]
		Caco-2	>1000
		T-47D	494.0
		N1H-3T3	>1000
	Methanol-water	HT-29	>1000
		Caco-2	>1000
		T-47D	>1000
		N1H-3T3	829.4
	n-Hexane	HT-29	771.9
		Caco-2	>1000
		T-47D	>1000
		N1H-3T3	>1000
	Chloroform	HT-29	>1000
		Caco-2	>1000
		T-47D	>1000
		N1H-3T3	>1000
	Ethyl acetate	HT-29	>1000
		Caco-2	>1000
		T-47D	877.8
		N1H-3T3	943.2
	Ethanol	MCF-7	>400	[16]
		T-47D	>400
Junceella juncea	Methanol-ethyl acetate	MCF-7	607.1	[25]
		OVCAR-3	394.7
Cavernularia sp.	Methanol-ethyl acetate	MCF-7	550.1	[25]
		OVCAR-3	315.4
Virgularia sp.	Methanol-ethyl acetate	MCF-7	6364.7	[25]
		OVCAR-3	322.8
White Menella	Methanol-ethyl acetate	MCF-7	607.1	[25]
		OVCAR-3	394.7
Brown Menella	Methanol-ethyl acetate	MCF-7	325.4	[25]
		OVCAR-3	270.3
Sinularia polydactyla	Methanol-ethyl acetate	MCF-7	417.2	[25]
		OVCAR-3	260.9
Sinularia variables	Methanol-ethyl acetate	MCF-7	361.0	[25]
		OVCAR-3	265.9
Sinularia compressa	Methanol-ethyl acetate	MCF-7	413.5	[25]
		OVCAR-3	317.7

Table 2.

Extent of cytotoxicity

Effectiveness rate	Area IC50 (µg/mL)
High activity	0–20
Moderate activity	21–200
Weak (low) activity	201–500
Inactive	>501

DISCUSSION

This review study explores, compiles, and compares the cytotoxicity (IC₅₀) effect and antibacterial effect of various extracts from marine organisms of the Persian Gulf. Due to the ease of accessibility and the extent of mist algae, most of the studied algae are green, red, and brown.

The following provides the cytotoxicity and antibacterial effects investigated in the articles.

Cytotoxicity effect

Three variables (the algae type, the solvent used for extraction, and the cell line) should be considered in the study of cytotoxicity. Table 1 shows different cytotoxic potential of all marine organisms.

The extent of cytotoxicity can be classified as given in Table 2:[1]

According to these ranges, the effectiveness of different extracts can be classified based on the impact of available type on different cell lines. The best effect on each cell line studied in all articles will be summarized.

Effect of different extracts on cell lines based on the available type

The methanolic and ethanolic extracts of G. salicornia algae were explored on three cell lines (HT-29, Hela, and MCF-7). The best performance was reported for methanolic extract on HT-29 cell line which was in the average activity range. Ethanolic extract of this alga was also effective on all the mentioned cell lines in the inactive scope.

The order of reported activity of the methanolic extract is as follows:[16]

HT-29 > Hela > MCF-7.

The effect of methanolic extract of G. corticata algae was also studied on HT-29, Hela, and MCF-7 cell lines. The order of effectiveness is reported to be the same as the methanolic extract of the alga G. salicornia but at higher efficacy. Moreover, the influence of hexane, butanol, aqueous, and dichloromethane extracts was examined on the Hela and Huvec cell lines. In general, the impact of aqueous and butanoic extracts lies in the inactive range. The effect of the chloromethane extract is in the weak activity range. The effect of hexane extract was in the average range. The overall effect of the mentioned extracts on the Hela cell line is greater than their effects on the Huvec cell line.[45]

Ethanolic extract of G. foliifera algae moderately affected MDA-MB-231, T-47D, and MCF-7 cell lines. The most effectiveness of this extract was on the MDA-MB-231 cell line. The influence of ethanolic extract of Gracilariopsis algae on the three mentioned cell lines was also reported in the inactive range.[16]

The cytotoxic effect of algae extracts of the Sargassum family and methanolic extract of the S. oligocystom alga on HT-29, Hela, and MCF-7 were high or moderate, and the best effect is the impact of methanolic extract on MCF-7 cell line.[15] The effect of methanolic extract of another species of this family, S. boveanum, was also explored on three cell lines of Hela, HT-29, and MCF-7 whose results were similar to the previous algae, showing moderate influence. It has the best impact on the MCF-7 cell line. Also, another study examined the cytotoxic effect of hexane, trichloroethane, chloroform, and butanol extracts of this algae on Hela and Huvec cell lines. The effect of butanol extract was placed in the inactive range, while the trichloroethane extract had weak effects. Hexane and chloroform extracts showed moderate and poor impacts on the Hela and Huvec cell lines, respectively.[15,17]

The activity of methanolic, methanol-aqueous, hexane, chloroform, and ethyl acetate extracts of S. swartzii was assessed on HT-29, Caco-2, T47D, and N1H 3T3 cell lines. The results of this study showed that the effect of ethyl acetate and methanol-aqueous extracts lied in the inactive range. Except for HT-29 cell line (weak activity), the impact of the chloroform extract on the rest of the cell lines was in the inactive region. The effect of hexane extract on the Caco-2 cell line was in the moderate range; it exhibits poor impact on the HT-29 cell line. For the two other cell lines, its influence was in the inactive range. Furthermore, unlike other algae of the same family, its methanolic extract demonstrated proper cytotoxic effect on different cell lines, moderate for T47D cell line, and in the inactive region for the rest of the cell lines.[18]

Methanolic and dichloromethane extracts of the S. acinaciforme showed moderate effects on the MOLT-4 cell line. The effect of the dichloromethane extract was close to the highly active region, outperforming methanolic extract.[19] Among the Persian Gulf-native brown algae, S. angustifolium is more investigated because of its greater frequency. In general, the effects of methanolic, methanol-aqueous, butanol, hexane, dichloromethane, chloroform, and ethyl acetate extracts of this algae were studied. The overall results of the cytotoxic effect of these extracts on different cell lines lied in the middle area of moderate range. Effect of methanol-aqueous extract of this alga lied in the inactive region for HT-29, Caco-2, T-47D, and N1H-3T3 cell lines. Its ethyl acetate extract showed moderate activity on the mentioned cell lines with the greatest effect on Caco-2. Its chloroform extract also moderately affects all the mentioned cell lines with the best effect on T-47D. The hexane extract of this alga demonstrated poor affects, but moderate influence on Huvec, MCF-7, and Hela cell lines with the greatest impact on the MCF-7. Its methanol, butanol, and dichloromethane extracts moderately affected three cell lines of Huvec, MCF-7, and Hela. The best effect of all three extracts was reported on the MCF-7 cell line.[15,21,46]

The methanolic extract of C. indica and C. merica on Hela cell, HT-29, MCF-7 lied in the middle range with the best effect on the MCF-7.[22]

Order of the efficiency is as follows:

MCF-7 > HT-29 > Hela.

The cytotoxic effect of methanolic, chloroform, and hexane extracts of C. myrica on Caco-2, T-47D, HT-29, and N1H-3T3 lied in the inactive range. The effect of the methanol-aqueous extract of this species on the Caco-2 cell line was in the inactive range, while showing low impact on T-47D and HT-29 cell lines; in case of the N1H-3T3 cell line, this extract showed moderate activity.[16,18,46]

The effect of the methanolic and ethyl acetate extracts of P. antillarum and P. boergeseni on the Hela, MCF-7, and Vero cell lines was in the mid-activity range. P. antillarum showed higher activities on the mentioned cell lines. Among the extraction solvents, the result of ethyl acetate extracts was more desirable.[23] In another study, the methanol and dichloromethane extracts of P. gymnospora showed low activities on the MOLT-4 cell line.[19]

J. Adhaerens red algae were extracted with methanol and chloroform. They showed moderate effect on HT-29, MCF-7, A-549, HEPG-2, and MDBK. Chloroform extract showed the best impact on the MCF-7 cell line.[24]

The effect of ethanolic extract of B. letpada on MDA-MB-231, MCF-7, and T47D located in the inactive area.[16]

The influence of the methanolic and dichloromethane extracts of I. stellata alga on the MOLT-4 cell line was in the moderate range. The activity of chloromethane extract was much higher than that of chloromethane methanolic extract. Furthermore, the effect of the methanolic and dichloromethane extract of S. trinoids was in the moderate range. The effect of methanolic extract was much higher than the dichloromethane one.[19]

Methanol-aqueous, hexane, chloroform, and ethyl acetate extracts of C. dasyphylla were applied on HT-29, T-47D, Caco-2, and N1H-3T3. The effect of methanol-aqueous extract on all 4 lines was in the inactive range, while ethyl acetate extract showed moderate influence on T-47D. The effect of the same extract was in the inactive region for other cell lines. The impact of the hexane extract on the HT-29 and N1H-3T3 cell lines was in the inactive range, while its effect on the Caco-2 cell line was in the low activity region. It showed strong effect on the T-47D cell line in the range of moderate activity. Moreover, chloroform extract of this alga affects all lines in the area of moderate activity, and its greatest effect was on the T-47D cell line in the very active range.[21]

Methanolic and ethyl acetate extracts of U. flexuosa were examined on MCF-7, Hela, and Vero cell lines. The effect of all extracts lied within the scope of moderate activity, and the activity of ethyl acetate extract was much higher than that of the methanolic extract. In another study, methanol-aqueous extract of this alga was examined on Caco-2, T-47D, HT-29, and N1H-3T3 cell lines whose cytotoxic effects are in the inactive region.[21,23]

Ethanolic extract of Cladophorosis was explored on MCF-7, MDA-MB-231, and T-47D cell lines whose effect on MDA-MB-231 and MCF-7 was in the moderate range with a greater influence on MDA-MB-231 cell line. The influence of this extract on T-47D cell line was located in the inactive zone. Moreover, the effects of the ethanolic extracts of H. flagelliformis and L. papillosa on mentioned cell lines were in the inactive range.[16]

Aqueous, butane, dichloromethane, and hexane extracts of the H. leucospilota were applied on the Hela cell line. Among them, butane extract showed moderate activity, while the effect of the rest of the extracts was the inactive range.[47]

Methanolic, hexane, ethyl acetate, methanol-aqueous, and chloroform extracts of C. sinuosa were tested on N1H-3T3, Caco-2, T-47D, and HT-29 cell lines. The effect of all extracts lied in the inactive effect range except for the hexane extract on T-47D and Caco-2 cell lines which was within the weak activity range.[16,18,19]

Methanol-ethyl acetate extracts of J. juncea, Cavernularia sp., Virgularia sp., White Menella, Brown Menella, S. polydactyla, S. variables, and S. compressa were examined on MCF-7 and OVCAR-3 cell. General effects were placed in the inactive range or the area with low activity close to the inactive area.[25]

Evaluating the best effect on each cell line

The greatest impact on each cell line is listed in Table 3:

Table 3.

Greatest impact on each cell line

Range	Cell line	Solvent	Existing name
1	HT-29	Chloroform	J. adhaerens
2	Hela	Ethyl acetate	U. flexuosa
3	MCF-7	Butanol	S. angustifolium
4	T47D	Chloroform	C. dasyphylla
5	Huvec	Butanol	S. angustifolium
6	MDA-MB-231	Ethanol	Cladophrosis
7	CACO-2	Hexane	S. swartzii
8	NIH 3T3	Chloroform	C. dasyphylla
9	MOLT-4	Dichloromethane	C. sinuosa
10	Vero	ethyl acetate	U. flexuosa
11	OVCAR-3	Methanol - ethyl acetate	S. polydactyla

Table 4 shows the cell lines that were examined in only one study.

Table 4.

Cell lines that were examined in only one study

Range	Cell Line	Solvent	Existing name	IC50
1	HEPG-2	Chloroform	J. adhaerens	94
2	A-549	Chloroform	J. adhaerens	72
3	MDBK	Chloroform	J. adhaerens	46

Antibacterial effect

The antibacterial activity of sea cucumber muscle wall and S. horrens extracts was assessed against L. garvieae, S. iniae, A. hydrophila, and Y. ruckeri using the disk-diffusion and well-diffusion methods [Table 5]. Muscle walls were extracted with ethyl acetate, methanol, and acetone solvents. Only ethyl acetate extract of S. horrens showed an antibacterial effect on all the mentioned bacteria. A. hydrophila was also sensitive to acetone extract. Methanol extracts were only effective on Y. ruckeri.[28]

Table 5.

Antibacterial activities of marine organisms

This research investigated the antibacterial activity of ethanolic, methanolic, and Estonian H. parva sea cucumber extracts. Fisher LSD test results showed that methanol had the highest effect on inhibiting bacterial growth, but acetone and ethanol had the least inhibitory effect. All the studied extracts showed the most inhibitory and bactericidal activity on P. aeruginosa, while E. faecalis was the most resistant species.[26]

Bioactive compounds of H. leucospilota sea cucumber were extracted with water and organic solvents (chloroform and methanol). Their antimicrobial activity was examined by disk-diffusion tests against SEA, MRSA, and SEB. This study showed that antibacterial assays and methanol extracts have significant activity against SEA and MRSA. On the other hand, the highest antibacterial activity in the disk-diffusion method was for the methanolic extract against MRSA. This review showed the highest antibacterial activity was for methanolic extract.[30]

Methanol, ethanol, and acetone extracts of S. hermanni sea cucumber were assessed against five human pathogenic microorganisms. The results showed that none of the concentrations of the tested extracts (methanol, water-methanol, ethyl acetate) had antibacterial activity.[31]

Antimicrobial activity of gonads, body walls, intestine tract, and the respiratory tree of three species of Holothuria sea cucumbers in the Persian Gulf (scabra, H. parva, and H. leucospilota) was evaluated against S. aureus using ethyl acetate and methanol 99.99% extracts through disk-diffusion method. The results showed the highest activity of this cucumber's methanolic extracts of the intestine tract compared to the methanol and ethyl acetate extracts of its other organs. The most effective and highest antimicrobial activity of intestine tract methanolic extract was for H. Parva, H. scabra, and H. lecuospilota.[32]

Bioactive compounds of H. leucospilota sea cucumbers were extracted using different organs and various solvents (ethyl acetate, methanol, and methanol-water (50:50)). The antibacterial and antifungal activities of these extracts were investigated against C. albicans and A. niger based on the disk-diffusion method. The results show at all concentrations of the three extracts produced from gonads, the respiratory tree, the cuvierian limb, and the body wall of this sea cucumber had no antibacterial activity against S. aureus.[33]

Methanolic extracts from sea cucumber generally have more antibacterial properties than ethanol and ethyl acetate extracts. Among all the studied bacteria, the methanol extract of this sea cucumber showed the greatest effect on P. aeruginosa and the least impact on E. faecalis.

The antimicrobial activity of diethyl ether extract of Haliclona sp. sponge was tested against E. coli, P. aeruginosa, S. aureus, and B. subtilis. The tested marine sponge extract was effective against B. subtilis.

Antimicrobial activity of diethyl ether, methanol, and aqueous extracts of marine sponges I. mutans was surveyed against E. coli, S. aureus (ATCC 1764), P. aeruginosa (ATCC 25619), and B. subtilis spizizenii (ATCC 6633) using bacterial broth dilution methods. The methanolic extract was effective on B. subtili, S. aureus, and spizizeni bacteria, while it did not affect E. coli and P. aeruginosa. Furthermore, diethyl ether extract was only effective on P. aeruginosa. The aqueous extract did not affect any of the studied bacteria, as well as no inhibitory activity against microorganisms.[34]

The antibacterial activity of diethyl ether, methanolic, and aqueous extracts of Haliclona sp. sponge was examined by the broth dilution method. The methanolic extract showed better activity against C. albicans and A. fumigatus than the diethyl ether extract, while the aqueous extract does not show any antibacterial activity. Based on the results of this study, Haliclona sp. could be considered a new source of antibiotics.[36]

Antibacterial activities of methanol, diethyl ether, and aqueous extracts of marine D. pallescens extracted by the Bligh and Dyer method were examined on S. aureus aureus-ATCC1764, B. subtilis spizizenii-ATCC6333, E. coli-ATCC, and P. aeruginosa-ATCC 25619. The results showed that the bacteria were highly resistant to aqueous extract. Diethyl extract also had antibacterial activity against S. aureus-ATCC1764 and B. subtilis spizizenii. The methanolic sponge extract showed weaker antibacterial activity than its diethyl ether extract. It should be noted that both extracts were not effective against P. aeruginosa.[37]

Antibacterial effects of dichloromethane and methanolic extracts of five species of sponge (Callyspongia siphonella, N. furcata, Pseudosuberites clavatu s, C. clavatus, and Fascaplysinopsis) were assessed against S. aureus as well as three hospital species of S. aureus resistant to Methicillin, Streptococcus pyogenes, E. faecalis, B. cereus, S. mutans, and three hospital samples resistant to Enterococcus, E. coli, Salmonella paratyphoid A, K. pneumoniae, and P. aeruginosa. In this review, F. reticulata sponge had a good antimicrobial effect, and its dichloromethane extract was effective against S. aureus. Methanolic extract of F. reticulata sponge had a weaker effect on S. aureus, but it generally had more effective activity than other sponges. This review also stated that other studied sponges had moderate to inactive effects and were not good candidates for more advanced studies.[38]

The antimicrobial activity of G. carnosa sponge was examined as crude and soluble extracts in ethanol, methanol, acetone, ethyl acetate, chloroform, ethanol: ethyl acetate: methanol (1:2:1) mixture, and distilled water based on the disk-diffusion method. These activities were evaluated on two groups of bacteria (gram-positive and gram-negative). Among the tested bacteria, S. marcescens and P. aeruginosa showed the highest and lowest resistance against all extracts.[39]

Methanolic extracts of sponges exhibited higher antibacterial properties compared with aqueous and diethyl ether extracts. Among all the studied bacteria, the methanolic extract has the greatest effect on S. aureus and E. coli while exhibiting the least impact on P. aeruginosa.

Antibacterial activity of methanolic extract of red algae (H. flagelliform) and brown algae (C. myrica and S. boveanum) collected on the shores of the Persian Gulf was assessed against B. subtilis, P. aeruginosa, S. aureus, and E. coli. The agar disk-diffusion bioassay (ADD) method was also investigated. Results showed that C. myrica has no antibacterial properties, while the methanolic extract of H. flagelliform alga has antibacterial properties only against S. aureus and B. subtilis. Other research results revealed the bactericidal properties of methanol/water and distilled water extracts of S. boveanum against S. aureus. Methanol and dichloromethane extracts also showed bacterial properties against B. subtilis.[40]

Antibacterial activity of methanolic extract of S. haddoni sea anemone was examined against P. aeruginosa, Klebsiella, B. cereus, A. baumannii, S. aureus, E. coli, and pneumoniae using agar disk-diffusion (ADA) method. The results showed that the methanolic extracts are effective against all studied bacteria, and the maximum effect was related to the anemone tentacles.[41]

Antibacterial properties of hexane, ethyl acetate, and methanolic extracts of V. juncea sea pen (pennatulacean) were investigated against S. aureus and E. coli. The studies showed the significant growth inhibition activity of ethyl acetate extract on S. aureus. The purified composition of this sea pen had the highest antibacterial properties against S. aureus.[44]

The antibacterial properties of three species of sea coral were examined against five human pathogenicity microorganisms. The results showed the significant activity of corals extracts only against S. aureus. The highest antibacterial activity was seen in the case of aqueous methanolic extract equal to Porites compress against S. aureus.[43]

Methanolic, acetone, and methanol/water extracts of T. savigni were tested on E. coli, K. pneumoniae, P. aeruginosa, B. cereus, and S. aureus using the overall agar method. This sea creature has good bacterial properties against pneumoniae, E. coli, Klebsiella, P. aeruginosa, B. cereus, and S. aureus. Moreover, the inhibition activity of the methanolic extract is better than the Estonian extract, while the methanol/water extract of this creature has no antibacterial properties.[44]

The maximum impact on each bacterium is listed in Table 6:

Table 6.

Maximum impact on each bacterium

Range	Bacterium	Solvent	Existing name
1	P. aeruginosa	Methanol	Sea cucumber H. parva
2	K. pneumoniae	Methanol	S. haddoni (Haddon’s sea anemone)
3	B. cereus	Ethyl acetate	G. carnosa sponge
4	A. baumannii	Methanol	S. haddoni (Haddon’s sea anemone)
5	S. aureus	Methanol dichloromethane	N. furcata
6	E. coli	Methanol dichloromethane	N. furcata
7	S. marcescens	Mixed (ethanol: ethyl acetate: methanol1:2:1)	G. carnosa sponge
8	E. faecalis	Ethyl acetate	Sea cucumber H. leucospilota

CONCLUSION

The study of the marine aquatic microbiome could be a successful strategy for finding new natural compounds. The Persian Gulf ecosystem is a pristine resource with a high potential for natural marine compounds. Various studies have been performed on the isolation and evaluation of antimicrobial and cytotoxic activity in organisms living in the Persian Gulf. This article reviews the studies conducted on this field.

The results showed the following:

• In general, the cytotoxic findings showed that the chloroform extracts of J. Adhaerens, C. dasyphylla, and C. dasyphylla had the greatest effect on HT-29, T47D and N1H 3T3 cell lines, respectively.

• Also, ethyl acetate extract of U. flexuosa affected Hela cell line. The butanolic extract of S. Angustifolium was effective on MCF-7 and Huvec cell lines. The ethanolic extract of Cladophrosis influenced MDA-MB-231 cell line. The hexane extract of S. swartzii was influential on CACO-2 cell line, The dichloromethane extract of C. sinuosa was effective on MOLT-4 cell line, and U. flexuosa ethyl acetate extract had the highest effect on Vero cell line. The methanol-ethyl acetate extract of S. polydactyla had the greatest effect on OVCAR-3 cell line.

• In general, methanolic extracts of sea cucumber have more antibacterial properties compared to ethanolic and ethyl acetate extracts. Among all the studied bacteria, methanolic extract of sea cucumber showed the highest and lowest effects against P. aeruginosa and E. faecalis, respectively.

• Methanolic extracts extracted from sponges have more antibacterial properties against aqueous extracts and diethyl ether rather than bacteria. Among all the studied bacteria, methanolic extract has the highest and lowest effects on S. aureus, E. coli, and P. aeruginosa, respectively.

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Conflicts of interest

There are no conflicts of interest.