STUDY OF CHINESE HONEY LOCUST (GLEDITSIA SINENSIS) AND SHALLOT (ALLIUM ASCALONICUM L.) FOR INTEGRATE TRADITIONAL CHINESE MEDICINE INTO OTHER COUNTRIES' MEDICINE IN ORDER TO IMPROVE PUBLIC HEALTH

STUDY OF CHINESE HONEY LOCUST (GLEDITSIA SINENSIS) AND SHALLOT (ALLIUM ASCALONICUM L.) FOR INTEGRATE TRADITIONAL CHINESE MEDICINE INTO OTHER COUNTRIES' MEDICINE IN ORDER TO IMPROVE PUBLIC HEALTH M. H. Shahrajabian, W. Sun, M. Khoshkharam, H. Shen, Q. Cheng Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran Zhejiang Institute for Food and Drug Control, Hangzhou, China College of Life Sciences, Hebei Agricultural University, Baoding, Hebei, China; Global Alliance of HeBAU-CLS&HeQiS for BioAlManufacturing, Baoding, Hebei, China *Corresponding email: chengqi@caas.cn These authors contributed equally to this paper


Problem statement and analysis of the recent researches and publications.
The population health is an important component of the country development, since the working capacity and workers' safety in the workplace depends on their health status. Very often, the labor process is accompanied by a significant influence of harmful and dangerous factors at the workplace, such as noise, vibration, dust of toxic substances, etc. Toxic substances that are used the manufacturing process often cause allergies, inflammatory processes of the skin and internal organs, sometimes diabetes and cancer. To strengthen immunity and improve the health of workers, traditional Chinese medicine, which has achieved great success at present, can be recommended. Not only natural products, but also traditional medicines have great importance [1-3]. Traditional medicine contains health practices, knowledge, approaches and beliefs incorporating plants, fruits and herbs based on both ancient and modern pharmaceutical science [4][5][6][7]. Traditional Asian and Chinese medicine play a significant role in sustainable food systems, it is also offers a notable approach to prevent diseases while making suitable usage of organic and herbal products [8][9][10][11].
The aim of this manuscript is review of health benefits and pharmaceutical impacts of Chinese honey locust and shallot. It is reported that the fruit of G. sinensis consists of triterpenoids, oligosaccharides and flavonoids and it has been used as a traditional Chinese herbal medicine for the treatment of miscellaneous diseases like epilepsy and parasitic disease [12]. It is called Jo Gak Ja in Korea and also documented in the Chinese Pharmacopoeia as Zao Jiao Ci [13]. In different parts, it is called Da Zao Jiao, Zhu Ya Zao, Zao Jia Zi, Zao Jia Ye, Zao Jiao Ci, and Zao Jia Gen Pi [14]. Values are expressed in g kg -1 of dried fruit mass. Mean ± SD, n = 3.

Statement
Kuwahara et al. [17] reported that Gleditsia sinensis is extensively used as a medicinal plant in Asian countries, especially in China; triterpenes, alkaloids, and sterols are isolated from Gleditsia species, and among them, triterpenoid saponins are very principal metabolites owing to their numerous pharmacological activities. Wang et al. [18] indicated that arbuscular mycorrhization is advantageous for the growth of young G. sinensis plants. Cai et al. [19] reported that the thorns of Gleditsia sinensis have been historically applied in Chinese medicine and also considered one of the elemental therapeutic herbs. Cai et al. [19] indicated the potential of Gleditsia sinensis extract (GSE) in Hepatocellular carcinoma (HCC) treatment, and expand the understanding of miRNA-related mechanisms in the anticancer effects of GSE. Chow et al. [20] suggested that Gleditsia sinensis fruit extract (GSE) could be potentially used as an angiogenic inhibitor in not only solid tumour, but also leukaemia therapy. Lu et al. [21] found that the saponin fraction isolated from the fruits (SFGS) is considerably able to prevent angiogenesis by interfering with multiple steps. Jian et al. [22] indicated that G. sinensis gum has potential to produce value-added oligosaccharides in food industries. Lee et al. [23] indicated that Gleditsia sinensis ethanolic extract (GSEE) could be a vital novel therapeutic agent for the treatment of allergic asthma. Dai et al. [24] demonstrated that the ethanolic extract from the anomalous fruits of Gleditsia sinensis possesses antiallergic and anti-inflammatory activities, which may mediated by decreasing the release of mediators like histamine from mast cells and also weakening the inflammatory action of all these mediators. Hou et al. [25] stated that the saponin fraction from anomalous fruits of Gleditsia sinensis Lam. (SFGS) should be a candidate important therapeutic agent for rheumatoid arthritis. Moon [26] identified that a novel molecular mechanism for the ethanol extract of Gleditsia sinensis thorns (EEGS) in colon cancer treatment and also provide a theoretical basis for the potential therapeutic use of EEGS in medication of malignancies. Park et al. [27] suggested the application of (EEGS) in both treatment and prevention of vascular proliferative diseases. Lee et al. [28] found that the water extract of Gleditsia sinensis thorns (WEGS) may inhibit proliferation of colon cancer both in vitro and in vivo, and it has proved that WEGS has capablity as an anticancer agent for the treatment of malignancies. Tang et al. [29] found that the anti-cancer effect of fruit extract of Gleditsia sinensis (GSE) on esophageal squamous cell carcinoma (ESCC) inculpate the suppression of oncogenic expression and inhibition of telomerase activity. Choi et al. [30] suggested that fruit hull of Gleditsia sinensis (FGS) effectively vanquish neutrophilic lung inflammation, which can be associate with, at least in part, FGS-activating anti-inflammatory factor of Nrf2. Kim et al. [31] revealed that FGS can be used as a supportive measure to enhance the efficacy of a chemotherapeutic agent like cis-diammine dichloridoplatinum (II) (CDDP). Yi et al. [32] suggested that the ethanolic extract of Gledistia sinensis thorns (EEGS) with its active constituent, cytochalasin H, are possbile candidates for the development of anti-angiogenic cancer drugs. Lee et al. [33] reported that fruits of G. sinensis (GFE) inhibit lipogenesis by negative regulation of adipogenic transcription factors, which is linked with GFE-mediated cell cycle arrest and STAT3 inhibition. Lu et al. [34] revealed that the saponin fraction extracted from the fruits of Gleditsia sinensis (SFGS) is considerably able to prevent angiogenesis by interfering with multiple steps. Yang et al. [35] found that Echinocystic acid (EA), a pentacyclic triterpene extracted from the fruits of Gleditsia sinensis Lam, was considered as an important constituent to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. Yi et al. [36] suggested that EEGS can hinder angiogenesis by down-regulating proangiogenic protein, and therefore it should be considered as a future anticancer drug targeting tumor-derived angiogenesis. Kim et al. [31] indicated that the fruit hull of Gleditsia sinensis (FGS) could enhance the antitumor activity of cis-diammine injury (ALI). They suggested a therapeutic potential of FGS on inflammatory lung diseases. Zhang et al. [37] found that MPF, a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) has a remarkable anti-CPID effect, probably due to inhibition of the inflammation reaction by the promotion, and the induction of the apoptosis of inflammatory cells and down regulation of the serum levels of inflammation cytokines. Lee et al. [38] recognized a novel molecular mechanism for the ethanol extract of Gleditsia sinensis thorns (EEGS) in the treatment of colon cancer and might provide a theoretical basis for the possible therapeutic use of EEGS in malignancies treatment. Tong et al. [39] indicated that Gleditsioside B (GB), a triterpene saponin isolated from the anomalous fruits of Gleditsia sinensis Lam. was able to abrogate the migration of endothelial cells hrough down-regulating the activation of MMP-2 and FAk via preventing ERK and PI3K/AKT signaling pathways. Park et al. [27] suggested the use of the ethanol extract of Gleditsia sinensis thorns (EEGS) in the treatment and prevention of vascular proliferative diseases. Jin et al. [40] concluded that the addition of Gleditsia sinensis Lam. extract is not effective for improvement of the physical properties compared to chemical additives in sausages, which could be applied to meat products as natural preservatives. Ryu et al. [41] reported that water extract of Gleditsia sinensis thorns (WEGST) inhibit prostate cancer progression in different stages, such as collagen-mediated adhesion and migration, and it might supply further development for the therapeutic use of WEGST in the treatment of prostate cancer progression. Wen et al. [42] found that isolation and identification of the nematode-antagonistic compounds in the fruit of G. sinensis would specify whether these chemicals are potential sources of biologically based nematicides. Zhou et al. [43] revealed that the crude ethanol extract of G. sinensis spines was partitioned sequentially with solvents of increasing polarity. In their experiment, ethyl acetate fraction, which showed the most significant antibacterial activities among the solvent fractions was further isolated by column chromatograph, yielding seven phenolic compounds including gallate (1) and caffeic acid (7), and five flavonoids, dihydrokaempferol (2), eriodictyol (3), quercetin (4), 3,3 / ,5 / ,5,7-pentahydroflavanone (5) and (-)-epicatechin (6).

Shallot (Allium ascalonicum L.)
Shallot is one of the most important vegetable crops in various local cuisines in different part of the world [44]. Greek history and literature mention shallots. They most likely originated in Southeast Asia and from there, spread into India and the Mediterranean region. Shallot is a hardy member of the onion family that is famous for its delicate, meaty, onion-like flavor. Persian shallot is native and endemic of Iran and grows as a wild plant across Zagross mountains at high elevations of different states from Northwestern to Southern of Iran with the climate of very cold to moderate cold [45,46]. The benefit of shallot is as a source of carbohydrate, vitamin A, B, and C. Fasihzadeh et al. [48] noted that 1-Butene,1-(methylthio)-(Z) (18.21 %), Methyl methylthiomethyl disulfide (8.41 %), Dimethyl tetrasulfide (6.47 %), Piperitenone oxide (4.55 %) are the most abundant components of Persian shallot and comprised 37 % of the essential oil. Ebrahimi et al. [47] showed that Iranian shallot landraces are influential in mineral elements and essential fatty acids content and are recommended for human nutrition. Sittisart et al. [48] showed that shallots extracts contained some polyphenols such as apigenin, gallic acid, catechin, quercetin, kaempferol and tannic acid which are famous compounds possessing antifungal activity. Golubkina et al. [49] indicated that shallot is an outstanding candidate for the health-centered strategy of producing functional foods with high levels of Se and antioxidants; and the utilization of arbuscular mycorrhizal fungi and selenium application represent environmentally friendly strategies to increase the overall yield and quality performances of shallot bulbs. Fattorusso et al. [50] reported two new furostanol saponins, named ascalonicoside A1/A2 (1a/1b) and ascalonicoside B(4), respectively, along with compounds 2a and 2b. Phaiphan et al. [51] discovered that heating and shallot supplementation can significantly enhance the quality of apple juice. Yin et al. [52] suggested the use of shallot and scallion oils in food systems which may enhance lipid and microbial stability. Raeisi et al. [53] concluded that the application of 3 % ajwain seed extract gave the best antioxidant and antimicrobial activities, besides sensory, up to 15 days of storage, followed by 3 % shallot fruit extract. Abdelrahman et al. [54] provided evidence for the anticancer from shallot plants and a strong foundation for more investigations to build theoretical bases for cell apoptosis and development of novel anticancer drugs. Seyfi et al. [55] proved that shallot is a useful herb with therapeutic or preventive activity against angiogenesis related disorders. Chen et al. [56] have shown the potential of shallots for use in treating adenoviral infection activities. Krejcova et al. [57] found that the important usage of Persian shallot for the treatment of inflammatory disorders. They have introduced 2-[(Methylthio) methyldithio] pyridine N-oxide with high anti-inflammatory effects. Hajian et al. [58] showed that shallot extract can dose dependently lessen the factors related to lead induced renal damages. Falahati et al. [59] indicated that crude juice of shallot has anti-candidal activity and might be promising in treatment of candidiasis. Kongkaew and Phichai [60] found that dried shallot powder, which was practical at inhibiting the growth of Trichoderma spp. isolated from Yanagi mushroom. Amin et al. [61] noticed that based on the antimicrobial compounds, shallot can be effective medicine for treatment of dermatomycosis and other infectious diseases. Jalal et al. [62] found that Iranian shallot extracts appear to improve learning and memory impairments in fructose-fed rats. Sadat Hosseini et al. [63] found that the Persian shallot extract can be considered as a potential candidate as a natural drug for both prevention and treatment of human hepatoma. Iranian shallot extracts appear to enhance learning and memory impairments in fructose-fed rats [64]. Farajii et al. [65] stated that the shallot extract was preferred in both terms of reducing microbial growth and suitable sensory properties. Kazemian et al. [66] noted that hydroalcoholic shallot extract increases the number of germ cells in mice tested and helps amplify the sexual ability of male mice. Shallot as traditional herbal medicine are for febrifuge, diabetes, blood sugar and blood cholesterol, prevents thickening and hardening of the blood vessels and also ulcers [67]. Setyadjit and Sukasih [67] also reported that its powder is generally used as industrial raw materials such as in snacks production, seasoning in cooking, and medicine. Persian shallot has been reported to have a range of health benefits which include anticarcinogenic, hypoglycemic, hypolipidemic, antioxidant, antibiotic properties, kidney and liver protective impacts [45]. Some important components found in Persian shallot [45] ( Table 2). The most important medicinal properties of Persian shallot [45] ( Table 2). The most important health benefits of shallots (Table 2). Traditional Asian medicinal plants can consider as an important key in the treatment and prevention of many diseases [68][69][70][71][72].

Conclusion and recommendations.
Gleditsia sinensis Lam. (G. sinensis) is a perennial arbour spread in most parts of the world, especially in China. It is a classical traditional Chinese medical herb. Its different parts named Da Zao Jiao (fruit), Zhu Ya Zao (anomalous fruit), Zao Jia Zi (seed), Zao Jia Ye (leave), Zao Jiao Ci (thorn), and Zao Jiao Gen Pi (radix cortexes), have long been used in traditional herbal Chinese medicine (TCM).The most important components of Gleditsia sinensis are triterpenoid saponins, triterpenes, flavonoids, alkaloids, phenolics, sterols, and their derivatives are responsible for great pharmacological effects which is they it has been considered as a medicinal treasure. It has been reported that Gleditsia sinensis Lam thorn (GST) possesses a wide spectrum of pharmacological activities such as antioxidant, anti-inflammatory, anti-microbial, antiangiogenic and also anti-tumor effects. Its fruit is antibacterial, antifungal, antitussive, astringent, emetic, expectorant, haemostatic and stimulant. The seed is emetic, expectorant, decongestant and purgative, and the root bark is anthelmintic and antifebrile. Shallot is an important part of diet of many countries, especially in Asian countries and its fantastic medicinal effects have been proved. Historically, the shallot has been used for both its nutritional and aromatic properties in Iranian, Indian, Chinese, Asian, French and Mediterranean cooking. Like onions, shallots are a member of the allium family, but their flavor is richer, sweeter, yet more potent. The most important benefits of shallots are high source of antioxidants, improve heart health, cancer prevention, and diabetes, antiinflammatory, antimicrobial, might help fight obesity, and help to prevent or treat allergies. The demand for shallot products is increasing every year with increase population growth and food industries. More clinical studies may necessary to uncover the numerous substances and their effects in Chinese honey locust and shallot that contribute to public health.