Jorjani Biomedicine Journal

References	Gram positive	Gram negative	Authors
17	L. monocytogenes	--	Razavi et al.,
18	S.areus	E.coli	Ahmadi et al.,
19	S. aureus	E.coli	Khodaei et al.,
20	S. aureus L. monocytogenes E. faecium E. faecalis B. cereus	--	Azizi Tabrizzad et al.,
21	S. aureus S. pyogenes	--	Nzeako et al.,
22	--	E.coli	Selim
23	S. aureus	--	Carvalho et al.,
24	--	E.coli	Godarzi et al.,
25	B. cereus S. aureus	--	Hanan et al.,
26	Streptococcus spp S. aureus	--	Balkan et al.,
27	L. monocytogenes	--	Mohajerfar et al.,
28	M. tuberculosis	--	Pourazar Dizaji et al

Mentha pulegium
Mentha pulegium is one of the species of Mentha and is a member of the Labiatae family and is a perennial plant (29). Its stems are erect, up to one and a half meters in the final stages of plant maturation. The leaves of this plant are simple and stalk-like (30, 31) and grow wild in the humid regions of central and southern Europe, western Asia and North Africa (31). Mentha pulegium is composed of carvacrol and thymol, which have antibacterial and antifungal properties (32). Carvacrol reduces the concentration of plasma triglycerides. The use of carvacrol stimulates the growth and proliferation of lactobacilli (33). The therapeutic properties of Mentha pulegium are to alleviate gastrointestinal disorders, vomiting, ulcerative colitis, and liver disorders (34). Essential oils due to pulegone groups, Menthone and Neo-menthone has antimicrobial properties because they can cause bacterial lysis by changing the permeability of cell membranes and disrupt the structure of various polysaccharides, fatty acids and phospholipids are the bacterial cell membrane (29, 35). Since essential oils of Mentha pulegium have an important role in preventing the growth, proliferation and spread of several bacterial species, they can be used as anti-spasm and anti-inflammatory (36, 37). Table 2 examines the antimicrobial effect of Mentha pulegium on Gram-positive and Gram-negative bacteria in several different studies.

Table 2. Evaluation of antibacterial properties of Mentha pulegium

References	Gram positive	Gram negative	Authors
38	S.areus	E.coli	Fazeli nasab et al.,
39	--	Citrobacter E.coli S. typhi	Masood  et al.,
40	--	E.coli	Hongbin Si et al.,
41	S.areus	S. typhi	Mahmoudi et al.,
42	S.areus	--	Gholamipour naraki et al.,
43	S.areus	E.coli P.aeruginosa	Rahmani et al.,
44	S.areus	Citrobacter E.coli S. typhi	Ataie et al.,
45	S.areus	E.coli Kelebsiella P.aeruginosa	Nozohor et al.,
46	S.areus	--	Iravani et al.,
47	Streptococccus sp.		Jaber et al.,

Crocus sativus L
Saffron, scientifically named Crocus sativus L. belongs to the family (Iridaceae), mostly grown in arid and semi-arid regions of Iran (48, 49). It is a multi-stemmed plant without stem that has a tubular, spherical shape with a diameter of 5-3 cm (50). The main constituents of saffron, including crocin, crocetin, picrocrocin and safranal, are involved in the prevention of neuronal degradation and memory enhancement (51). The therapeutic value of dried saffron stigma due to the presence of three major secondary metabolites called water-soluble crocin and its derivatives responsible for the red color of saffron, picrocrocin the bitter taste of saffron is safranal, which is responsible for the smell of saffron (52, 53). Fat-soluble safranals and carotenoid pigments are bitter crocin, but the most important cause of bitterness is picrocrocin saffron (54). Saffron has been shown to protect chromosomes from damage and also modulates lipid peroxidation and a potent antioxidant and a rich source of riboflavin (55). The anticancer effects of saffron, including inhibition of tumor formation (56), anti-mutation (57), and inhibition of nucleic acid synthesis in human malignant cells have been demonstrated (54, 58). Some substances derived from saffron stigma have many therapeutic effects due to their hypolipidemic, antipsychotic, antioxidant and antidiabetic the aqueous and alcoholic extracts of saffron are protective of the heart and counteract neurodegenerative disorders. The saffron active ingredient is related to its various components such as crocetin, crocin and carotenoids and monoterpene aldehydes (59, 60). Saffron has anti-cancer properties, decreased blood bilirubin, increased oxygen in various tissues (50). Table 3 examines the antimicrobial effect of Crocus sativus L on Gram-positive and Gram-negative bacteria in several different studies.
 

References	Gram positive	Gram negative	Authors
4	S. aureus	--	Talei et al.,
48	B. cereus L. monocytogenes	--	Gandomi Nasrabadi et al.,
61	Lactobacillus S. mutans C. albicans	--	Barani karbasaki et al.,
62	B. subtilis	--	Tayel et al.,
63	S. areus B.subtilis	--	Mohamadian et al.,
64	--	S. typhimurium	Azami et al.,
65	S. areus	E.coli	Vahidi et al.,
66	S. areus	--	Abbasvali et al.,
67	B. cereus S. areus	S. typhimurium S. dysentery	Asgarpanah et al.,
68	S. areus	P. aeruginosa	Parray et al.,
69	S. areus	E.coli Salmonella	Hashemi et al.,
70	--	Salmonella	Pintado et al.,

Salvia officinalis
Salvia officinalis is one of the important genera of the Lamiaceae family (71). With more than 900 varieties of ornamentals, medicines and spices spread worldwide (72-73). It is found in the natural arena, in the Mediterranean, in parts of Europe and Iran (74, 75). About 58 species of this genus are known in Iran, 17 of which (29%) are endemic to Iran (72). Plants of this genus have significant essential oils with more than 100 active compounds, including hydrocarbon monoterpens, oxygenated monoterpens, sesquiterpene hydrocarbons, sesquiterpene oxygenated terpenes and diterpenes which exhibit many biological activities (76, 77). Salvia officinalis contains bitter and diterpene flavonoid substances, phenolic acids and tannins (78, 79). Salvia officinalis essential oil is used in the perfumery, food and pharmaceutical industries (72). Biological activities of this plant such as antibacterial, antioxidant, anti-inflammatory, anti-Alzheimer's, gastric ulcer and lipid-lowering agents have been reported (80, 81). Salvia officinalis has been used in traditional and modern medicine as an effective herbal medicine to heal inflammation and heal skin wounds. Salvia officinalis extract also reduces blood sugar in healthy and diabetic patients but does not affect insulin dependent patients (78). Recent studies have confirmed the plant's antibiotic, antispasmodic, anxiolytic, antifungal, antioxidant, hypoglycemic, tonic, antiperspirant and estrogenic properties (82). It is rich in antioxidants of calcium, potassium, magnesium and zinc and is a vasodilator (78). Salvia officinalis has an effect on the central nervous system. It is calming and hypnotic, skeletal muscle relaxant, analgesic, memory enhancer, anticonvulsant, neuroprotective and anti-infarct protection as well as inhibiting ethanol and morphine withdrawal syndrome (74). Two substances in the extract, including camphor and alpha thujene essence, are used for health benefits (83). Traditional medicine has been used for the treatment of inflammatory bowel disease and wound healing in traditional medicine. Nowadays, a new ointment of salvia officinalis extract is effective in healing wounds (84, 85). Studies have shown that methanol extract of Salvia officinalis is effective for anti-cell growth activity against cervical cancer, skin cancer and post-cancerous cancer. Salvia officinalis extract can play a role in the inhibition of cancer of the large intestine (83). Other studies have shown that Salvia officinalis extract inhibits the growth and proliferation of colorectal cancer cells in cell culture medium (86). Also, in another study it has been shown that some of the compounds extracted from Salvia officinalis have cytotoxic and deleterious effects on the DNA of cancer cells of the colon and liver cultured in cell culture medium (87, 88). Research has shown that the combination of alpha terpineol, which is one of the major compounds in salvia officinalis, can inhibit tumor cell growth and thus inhibit the release of CE, thus inhibiting its effects (89). Salvia officinalis extract, especially alpha-terpineol, Togen monoterpenes, beta-pyrene, synovol and essential fatty acids, prevent the destruction of healthy cells and prevent tumorigenic activity in these cells. The CEA marker is in the blood serum. On the other hand, although the molecular mechanism associated with the metastasis of some cancers is unclear, however, the production of CEA has been both clinically and empirically identified as an effective factor in metastasis (90). Studies have shown that there is a close relationship between serum CEA level and colorectal head metastasis to the liver (91), since salvia officinalis extract has anti-metastatic effects, reducing its effect on CEA. The prospect needs approval (88). Table 4 examines the antimicrobial effect of Salvia officinalis on Gram-positive and Gram-negative bacteria in several different studies.

Authors	Gram negative	Gram positive	References
Salimpour et al.,	E.coli K.pnemuniae	--	5
Moshafi et al.,	Ecoli	B.subtilis S.areus S.epidermidis	73
Batooli et al.,	--	P. vulgaris	92
Ahmady-asbchin et al.,	L.monocytogenes E.coli	S.areus	93
Mitić-ćulafić et al.,	--	B.subtilis S.areus	94
Iravani et al.,	--	B subtilis S.areus S.epidermidis	95
Omidpanah et al.,	E.coli		96
Javidnia et al.,	--	B.subtilis S.areus	97
Gharenaghdeh et al.,	E.faecalis	B.subtilis	98
Rasoli et al.,	--	S.areus	99
Arben et al.,	L.monocytogenes E.coli	S.areus	100
Ghezelbas et al.,	--	B. anthracis S. areus	101

Discussion
Infectious diseases are among the most well-known diseases that have always affected human beings and many efforts have been made to identify the causes, treatment and control of them (102). Due to the drug resistance and side effects of antibacterial chemical drugs, the scientific research approach to natural resources has become very popular in recent decades (103). The discovery of new antimicrobial metabolites from plants is an important alternative to overcome the decrease in the level of drug resistance by human pathogens. Due to the urgent need of the world for new antibiotics, there is a growing interest in the research of the chemistry of medicinal plants (104). Antibacterial herbal medicines inhibit the progression of the disease and in some cases relieve the disease (105). Different parts of medicinal plants such as, roots, stems, flowers, leaves have different antimicrobial properties (106). Antibacterial herbal medicines have various therapeutic properties that have little or no side effects (107). In general, some of the properties of plant essential oils that lead to antibacterial properties are: the hydrophobic property that penetrates the lipids of the bacterial cell membrane, disrupting cellular structure, causing the outflow and saturation of ions and others. Contains cellular contents (108). Phenolic substances in plant essential oils, including carvacrol, eugenol and thymol, which damage the cell's cytoplasmic membrane and coagulate cellular contents (109, 110). Binding of the carbonic group of essential oils to cellular proteins and preventing the role of amine acid and decarboxylase, which is mainly due to the presence of cinnamaldehyde in the essential oils (111). Reactions of aldehydes with -SH groups are effective in fungal growth and prevent the growth of microorganisms (17). Cinnamaldehyde, carvacrol, caron and thymol appear to have no significant or marginal effects in vivo, whereas in vitro they exhibit mild to moderate toxic effects on the cell (112). There appear to be no complications in this regard (113). However, studying and understanding the substances present in these plants and their proper use can overcome many problems, such as the prevalence of antibiotic resistance or the chemical side effects of certain drugs
Conclusion
Proper use of medicinal plants requires accurate scientific information and knowledge of the chemical compounds in them, because the presence of chemical compounds causes the therapeutic effect of the plant. Therefore, it is necessary to study the antimicrobial effects of plant extracts. Oils and compounds isolated from them are of great importance. One of the important reasons for the tendency of medical societies to use herbal compounds is their low side effects to chemical drugs that have been proven over the years in traditional medicine. As the world health organization warns of the overuse of common antibiotics and serious concerns about increased resistance to pathogenic microorganisms, research into the discovery of effective antimicrobial agents on these microorganisms Resistance has begun seriously. The main active ingredients of the essential oils and extracts of these herbs can be potential candidates for use as antibacterial substances. However, confirmation of the antimicrobial efficacy of these plants should be thoroughly investigated.

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