Using sumac ( Rhus coriaria L.), as a miraculous spice with outstanding pharmacological activities

Sumac is the wine-colored ground spice, belonging to the cashew family (Anacardiaceae). The most important components of sumac ethanolic extract obtained from sumac are Trans-Caryophyllene, diethyl ester, Butanedioic acid, Cembrene, 1,7-Nonadien-4-ol,4,8-dimethyl, Malate, Palmitate, 9-Octadecenoic acid, Ethyl Linoleic acid, Phytol and Ethyl Linoleate. In the Middle East, sumac is used as a spice and is extensively consumed with Kebabs and grilled meats. It is traditionally used by native Indians of North America in the treatments of bacterial diseases, such as syphilis, gonorrhea, gangrene and dysentery. In traditional medicine of Middle Eastern countries, it has been used for cholesterol reduction and sweating because it has shown antibacterial, hypoglycemic activities and even antioxidant properties due to the presence of tannin fractions in both of their fruits and leaves. The most important health benefits of sumac are reduced cholesterol, balance blood sugar levels, rich in antioxidants, calms muscle aches, reduce the chance of bone depletion, and it can help in the fight against cancer. In this review article all relevant papers of different scholars and researchers were searched in Google Scholar, Science Direct, Scopus and PubMed. Sumac has numerous health benefits and important pharmacological activities, and it can be considered as a valuable source of nutraceuticals, and an efficient natural drug. gallotannins, two subclasses of hydrolysable of typhina of 1,2,3,4,6-penta- -galloyl-β-D-glucopyranose Phytochemical compounds detected and characterized in R. coriaria L. fruits by HPLC-QTOF-MS in positive and negative ionization modes are Malic acid I, Quinic acid I, Malic acid hexoside I, Malic acid hexoside II, Malic acid hexoside III, Oxydisuccinic acid, Malic acid II, Malic acid III, Quinic acid II, O -Succinoyl-di- O caffeoylquinic acid, Malic acid derivative, Caftaric acid, Galloylhexose I, Galloylhexose II, Levoglucosan gallate I, Galloylhexose III, Levoglucosan gallate II, Galloylhexose IV, O -galloylnorbergenin I, Digalloyl-hexoside I, Galloylhexose derivative I, O -galloylnorbergenin II, Digalloyl-hexoside II, Protocatechoic acid, Galloylshikimic acid I, Gallic acid hexose derivative, Syringic acid hexoside, Gallic acid O -malic acid, Galloylshikimic acid II, Digalloyl-hexose malic acid II, Digalloyl-hexoside IV, Trigalloyllevoglucosan I, I, I, I, V, methyl Digallic acid II, Coumaric acid, Myricetin-hexose acid III, Myricetin-3- O -glucuronide, Myricitin derivative, Myricitin derivative, II, Horridin, I,


Introduction
Traditional medicines deal with common principles and methods of education, innovation, prevention, treatment and practical researches which can benefits the society, patients and improvement of sciences (Shahrajabian et al., 2020 a,b,c,d,e). Traditional medicinal plants have notable function for prevention and treatment of diseases by considering their traditional utilizations (Shahrajabian et al., 2021 a,b,c,d,e,f).
Traditional medicine is a collection of written and oral, practical and theoretical knowledge which collected from Iranian, Chinese, Greek, and Indian ancient knowledge and wisdom (Marmitt et al., 2021;Sun et al., 2021 a,b,c,d). Rhus coriaria L. (sumac), belonging to the Anacardiaceae family, is a plant with antioxidant properties whichs grows in Iran, Southern Europe, Mediterranean countries, North Africa, and Afghanistan Yang et al., 2016;Abdel-Mawgoud et al., 2019;Khoshkharam et al., 2021).
It is considered a reasonable cure in traditional medicine for its analgesic, anorexic, antidiarrhetic, antiseptic, and antihyperglycemic properties (Rayne and Mazza, 2007). The name is originated from "sumaga", meaning red (Wetherilt and Pala, 1994). They have a milky or resinous juice; compound or simple leaves; small flowers, with the parts in fours or sixes; and one-seeded, small dry, usually hairy, sometimes highly colored fruits, generally in dense clusters (Bayram et al., 2005). The name sumac is given also to the commercial preparation of the ground and dried leaves of the Sicilian or tenners sumac (Rhus coriaria) of Southern Europe, long applied in making leather (Bayram et al., 2005). Rhus coriaria, found mostly in the Middle East and Mediterranean basin, has been used in spice blends and in traditional medicines for hundred years (Kirby et al., 2013), while Rhus typhina, the Staghorn sumac, also called Rhus hirta, is a species found throughout North America (Rayne and Mazza, 2007). Sumac can grow in non-agriculturally viable locations, and has a long history of utilized by indigenous people for medicinal and different purposes (Chen and Chen, 2011), and this shows potential for commercializing it without competing for food production land use (Wyk and Wink, 2004). Many compounds have been isolated from different parts of sumac, such as fatty acids, phenolics, organic acids, volatile oils, proteins, fiber, vitamins and minerals (Ozcan and Haciseferogullari, 2004;Anwer et al., 2013). Sumac extract was characterized by both 7-methyl-cyanidin 3-galactoside and gallic acid derivatives (Romeo et al., 2015). In the Middle East, it is also used as the spice, to give sour lemon taste to grilled stews and meats, but in vegetable and rice dishes too (Giovanelli et al., 2017). The red fruits are tightly ranged together into an inverted cone-shaped spike of 5-30 cm, and the fruits are tiny little spheres tightly packed together forming dense clusters of reddish drupes called sumac bobs (Sakhr and El Khatib, 2020). The dimension and physical properties of Rhus coriaria are length (4.72±0.030 mm), width (3.90±0.028 mm), weight (0.018±0.001 g), thickness (2.64±0.025 mm), mean diameter (3.64±0.023 mm), projected area (0.164±0.005 cm 2 ), volume (19.49±0.442 mm 3 ), bulk density (304.25±.364 kg/m 3 ), and porosity (68.52±0.578%) (Ozcan and Haciseferogullari, 2004). In Iran, sumac is grown in Mazandaran, Khorasan, Azadbayegan, Ghazvin, Shiraz, Ghom and Hamedan (Khoshkharam et al., 2020). Syrian sumac (Rhus coriaria L.) is famously used in Mediterranean region and the Middle East as a spice sauce and drink and Chinese sumac (Rhustyphina L.) is indigenous to the Eastern area of North America, is not extensively cultivated in China's North, Northwest and many other regions such as Lanzhou, Beijing, Hebei, Shanxi where it is usually called huojushu (Kossah et al., 2009). Edible sumac varieties consist of smooth sumac (Rhus glabra), dwarf or winged sumac (Rhus copallina), staghorn sumac (Rhus typhina), lemonade berry (Rhus integrifolia), Southwestern sumac (Rhus microphylla), sweet sumac (Rhus aromatic), sugar bush (Rhus ovata), and squaw berry (Rhus trilobata) (Khoshkharam et al., 2020). The aim of this manuscript is introduced and survey the most important pharmaceutical and health benefits of sumac and present chemical constituents of sumac.

Chemical Components and Nutritional Constituents
Rhus coriaria consists of numerous substances including polyphenols such as quercetin, gallic acid, kaempferol, methyl gallate (Shabana et al., 2011), and hydrolysable tannins, which shows a significant strong antioxidant impact (Kosar et al., 2007). The fruit of sumac contains phenolic acids, flavonols, hydrolysable tannins, anthocyans and organic acids such as citric, malic and tartaric acids (Ozcan and Haciseferogullari, 2004;Kossah et al., 2010). The main compound found in Rhus family is hydrolysable gallotannins, and it is the main structural unit in the polyol D-glucose, esterified by gallic acid at its hydroxyl groups to give the βpentagalloyl-D-glucose (Zalacain et al., 2003). Also, gallic acid contains notable anti-obesity (Hsu and Yen, 2007), hepatoprotective (Jadon et al., 2007), antioxidant (Yen et al., 2002) and anticancer  activities. Kosar et al. (2007) also reported that while gallic acid was the principle phenolic acid in the extracts, anthocyanin fraction including cyanidin, pelargonidin, peonidin, petunidin, coumarates and delphinidin glucosides. The antibacterial and antioxidant activities of sumac extract are linked to its phenolic compounds, containing tannins and gallic acid, and different flavonoids (Nimri et al., 1999). R. coriaria methanol extract was determined to contain high amounts of tannins (0.365 mg TAE/mg extract) contents, and total flavonoids (0.177 mg QE/mg extract) (Taskin et al., 2020).
Leaves of staghorn sumac (Rhus typhina) present several galloyltransferases that catalyze the βglucogallin dependent transformation of 1,2,3,4,6-pentagalloylglucose to gallotannins (Niemetz and Gross, 2001). It has been also reported that ellagitannins and gallotannins, the two subclasses of hydrolysable tannins of Rhus typhina, are derivatives of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (Niemetz and Gross, 2005). . It has rich mineral compounds such as aluminum, bromine, barium, calcium, chlorine, chrome, copper, iron, manganese, magnesium, potassium, lithium, nitrogen, nitrate, phosphorus, zinc, strontium, titanium and vanadium, of which, calcium, magnesium, phosphorous, and potassium are main elements found in sumac fruits (Anwar et al., 2018;).Egyptian sumac was more enriched in o-cymene, limonene, and β-ocimene, while Jordanian and Palestinian specimens showed more close volatile profile being enriched in naphthalene and α-pinene (Farag et al., 2018). The most important isolated essential oil of sumac fruit in Iranian populations were (E)-Caryophyllene (5.9-50.3%), n-nonanal (1.8-23.3%), cembrene (1.9-21.7%), α-pinene (0.0-19.7%), (2E,4E)-decadienal (2.4-16.5%), and nonanoic acid (0.0-15.8%) (Morshedloo et al., 2018). In one experiment, on the basis of NMR and mass spectral data, the fruit extract of winged sumac contained a new galloyl derivative, (R)-galloyl malic acid dimethyl ester, and eleven known compounds, gallic acid, glucogallin, methyl gallate, methyl m-digallate, quercetin, methyl p-digallate, rhamnazin, myricetin, betulinic acid, kaempferol, and oleanolic acid (Ma et al., 2012). Structures of the most important phenolic compounds from Rhus coriaria fruit is shown in Figure 1. Structures of the most notable anthocyanins from Rhus coriaria are presented in Figure 2. In Iran, sumac is used as a spice and is extensively consumed with Kebabs and grilled meats (Fereidoonfar et al., 2018;Langroodi et al., 2018). Rhus glabra L. is traditionally used by native Indians of North America in the treatments of bacterial diseases, such as gonorrhea, syphilis, gangrene and dysentery (Erichsen-Brown, 1989). Sumac is often used as a spice by grinding the dried fruits with salt for salads and Kebabs, and is also broadly utilized as a medicinal herb in Iran and Turkey, particularly for skin problems and wound healing (Sezik et al., 1991). In traditional Chinese medicine, all parts of it have been used for treating diseases; for example, the leaves are used for treating diarrhea and inflammations; the root is used for treating jaundice and malaria; the fruits and seeds are commonly used for treating dysentery and hepatitis (Djakpo and Yao, 2010;Zhang et al., 2018). In traditional Arabic Palestinian herbal medicine, this plant has been applied in the treatment of cancer, diarrhea, stroke, dysentery, hypertension, ophthalmia, haematemesis, stomach ache, diuresis, liver disease, diabetes, measles, atherosclerosis, headaches, small-pox, aconuresis, teeth and gum ailments, animal bites, liver disease and dermatitis (Shafiei et al., 2011;Abu-Reidah et al., 2015). Sumac fruit has also been introduced in Iranian traditional medicine as a herb with some therapeutic activities, and traditionally the powdered fruits have been prescribed as astringent, anti-trachoma, anti-diarrhea, and anti-pus in infectious wounds (Ahmadian-Attari et al., 2017). Sumac is utilized in the Iranian traditional medicine as an astringent and stancher agent, and it is also used to eye trachoma, and to suppress the incidence of pox in eye (Mazaheri et al., 2017). This plant is used in traditional medicine of Jordan for cholesterol reduction and sweating that sumac indicated antibacterial, hypoglycemic properties and even antioxidant activities because of the presence of tannin fractions in both of their fruits and leaves (Adwan et al., 2009;Aliakbarlu et al., 2013).
In some Eastern Mediterranean regions powdered sumac is applied in the composition of Za , atar, a mixture of a homemade earthy and herby savory blend of dried thyme-like herbs such as Thymbra spicata and Origanium syriacum, used for a numerous of dishes specially for the Lebanese flatbread "Mankouche" (Alwafa et al., 2021).
In traditional Iranian medicine, sumac has been consumed as an anti-diarrhea, hemostasis factor, anti-pus, and trachea treatment (Tohma et al., 2019).

Potential Health Benefits in Modern Pharmaceutical Science
Rhus coriaria contains significant antimicrobial and antioxidant activities (Kossah et al., 2009;Rima et al., 2011;Wu et al., 2013). Rhus coriaria-fortified yogurt indicated a significant boost in total phenolic constituents and antioxidant activity in comparison with plain yogurt (Perna et al., 2018). Former studies have shown the positive antimicrobial effects of sumac extracts on Bacillus spp., Listeria monocytogenes, Citrobacter freundii, Staphylococcus aureus, Escherichia coli, Hafniaalveri, Proteus vulgaris, Salmonella typhi, Salmonella enteritidis, and Shigella flexneriin vitro conditions (Nasar- Fazeli et al., 2007). The methanolic extract of Rhus coriaria may be considered as an efficacious natural scolicidal agent (Moazeni and Mohseni, 2012). The application of sumac extracts as a potential natural preservative have been used in food industry, for the control of natural microflora of broiler meat has been found in raw broiler wings (Gulmez et al., 2006), and raw broiler drumsticks (Vatansever et al., 2008). Sumac supplementation revealed to have a potential weight-reduction impact, along with a positive influence on insulin resistance in patients who were obese or overweight (Heydari et al., 2019). The analgesic impacts for the hydro alcoholic leaf extract of Rhus coriaria (HRCLE) in a rat model may be mediated through both central and peripheral mechanisms, and the presence of flavonoids might be accountable for the antinociceptive characteristic of this plant (Mohammadi et al., 2015). In one experiment, sumac indicated better activity against the tested bacteria compared to avishan-e shirazi suppressing Bacillus cereus and Staphylococcus aureus at concentrations of 0.05% and 0.1%, respectively, and this common Iranian spice which is traditionally used as astringent agent has promising inhibitory impacts on food-borne bacteria and could be considered as natural food preservatives (Fazeli et al., 2007).
Its extract recently underwent evaluation as a potent biocontrol candidate that works against human pathogens . Its extract can be judged as an affordable and eco-friendly replacement to chemical fungicides in the management of tomato anthracnose disease caused by Colletotrichum acutatum, and it can also cause significant improvement of the shoot height, dry shoot height, dry root length, root length, chlorophyll content and leaf surface area of treated plants (Rashid et al., 2018).  (Kossah et al., 2009). Sumac with a fatty diet effectively decreased blood cholesterol and may possibly help in both prevention and treatment of hyperlipidemia in a small sample of white Wistar rats (Soltani et al., 2017). Clinical studies using sumac or its major constituents, proposed that this herbal product may represent an appropriate therapeutic tool in the management of metabolic-related conditions such as liver-atherosclerosis disorders (Khalil et al., 2021a). It has been reported that some active bio-active constituents of sumac have impacts against metabolic syndrome, such as Gallic acid on diabetes, obesity, NAFLD, oxidative-inflammatory damage; Methyl gallate on oxidative-inflammatory damage, cancer and obesity; Quercetin on obesity and hypertension, Myricetin on obesity and NAFLD; and Cyanidin, delphinidin on obesity, NAFLD, diabetes, and inflammation (Khalil et al., 2021a). Sumac fruit powder improved intestinal morphology of rainbow trout, and it may boost antioxidant status in rainbow trout, but dietary sumac fruit powder did not influence the serum biochemistry in rainbow trout (Diler et al., 2021). Sakhr and El Khatib (2020) reported that sumac can be applied as an effective food preservative and harmless, natural food additive. Sumac, as an adjuvant therapy, may reduce serum levels of insulin, fasting blood sugar (FBS), and HOMA-IR (Ghafouri et al., 2021). The free phenolics fraction of Rhus family fruits has an effective lipase inhibitory activity, and can potentially treat obesity-related problems; quercetin and myricetin were the principle phenolics in all fractions with good dosedependent lipase inhibitory impacts, and myricetin had a positive inhibitory effect (Zhang et al., 2018;Wu et al., 2019). Increase in the body weight gain, feed conversion ration because of increased antibody level, intestinal morphology, and some notable microbial population in female broiler chicks receiving the sumac and dried when power (Kheiri et al., 2015). The most important pharmaceutical and health benefits of sumac are shown in Table 1. Ahmadian-Attari et al. (2016) El-Khatib and Salame (2019) Sumac leaf extract is a novel green reducing and stabilizing factor for the biosynthesis of silver nanoparticles (Ag NPs), and both Ag NPs and sumac leaf extract additively contribute to the antimicrobial and UV protection of cotton. Stular et al. (2021) Anti-cancer activity It has growth inhibitory impacts on cervical cancer cells in a time-and a concentration-dependent manner, which can be utilized as a therapeutic drug agent for uterus cervix cancer.

Abdallah et al. (2019)
Anti-diabetic activity The favorite influence of sumac consumption on apolipoprotein (apo) B, serum glycemic status, apoA-I and total antioxidant capacity (TAC) levels in type 2 diabetic patients were reported. Shidfar et al. (2014) Rhus coriaria L. lyophilized extract has a healing impact on diabetes and diabetes-related complications. Dogan and Celik (2016) Anti-inflammation activity The potential impacts of R. coriaria fruit extracts, commonly mERC, as preventive candidate in the treatment of keratinocyte inflammation through their inhibitory impacts on the production of skin proinflammatory mediators. Khalilpour et al. (2019) Sumac powder increased significantly hepatic fibrosis and glycemic status. Kazemi et al. (2020) Supplementation with sumac lead to a significant decline in inflammation and oxidative stress. The neuro-inflammation inhibitory activity of R. coriaria extracts consists of the inhibition of NF-κB signaling pathway, and it might carry therapeutic potential against neurodegenerative diseases.

Conclusions
The sumac group Rhus L. belongs to Anacardiaceae family, is considered the largest and the most heterogeneous taxon and is commonly connected to as the Rhus complex in the sumac. Sumac is a prominent spice in the Middle East, which is made from berries from a bush of the same name. In order to produce the spice from the plant, its fruit is dried and then crushed into a thin red-purple powder. The red berries are delicious and tangy, containing malic acid which is originated in apples. As a spice, it is delicious on meat, in salad dressing, and makes the tasty infused vinegar if you macerate it in apple cider vinegar. The most important phenolic acids and flavonoids are catechin, gallic acid, ferulic acid, apigenin, gentisic acid, P-coumaric acid, chlorogenic acid, isorhamnetin, caffeic acid, quercetin, cinnamic acid, taxifolin, kaempferol, epicatechin, vanillic acid, P-hydroxybenzoic acid, vanillin, anisic acid, pyrogallol, syringaldehyde, sinapic acid, syringic acid and benzoic acid. Organic acids of sumac are citric acid, malic acid, fumaric acid and tartaric acid. The fatty constituents of sumac fruits are palmitic acid, oleic acid, myristic acid, stearic acid, palmitoleic acid, linoleic acid and linolenic acid. The vitamin contents of sumac fruits are riboflavin, thiamin, pyridoxine, cyanocobalamin, biotin, nicotinamide, and ascorbic acid. The principal health advantages of sumac are 1) anti-inflammatory: inflammation is believed to be the main cause of many diseases and Sumac is an anti-inflammatory medicinal herb that assists fight numerous disorders, colds, and the Flu, 2) anti-cancer: it is packed with vitamin C and a great anti-oxidant which means it can promote ward off diseases like cancers, diabetes, and cardiovascular diseases, 3) anti-microbial and anti-fungal: Sumac is anti-microbial and anti-fungal spice which can increase treatment of skin disorders and inflammation, it has also been studies to be effectual in fighting bacteria like Salmonella and can be applied to safely disinfect vegetables and fruits, 4) It has been considered as a potent in regulating cholesterol levels and treating diabetes by decreasing blood sugar, 5) it can boost breast milk production and decrease menstrual cramps, 6) Sumac is a diuretic which means it assists remove toxins from the body via urine and had been utilized traditionally to treat urine digestive and infections disorders. Due to wonderful pharmacological characteristics, sumac is considered as a high potent natural and organic spice with effective pharmacological activities.

Authors' Contributions
Both authors read and approved the final manuscript.
Ethical approval (for researches involving animals or humans) Not applicable.